Document zzkyoQNoqeKjOkZ9DrGBNnGM7

-1- Final Report Volume 1 of 6 (Text, Figures and Tables 1-51) Study Title An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats Study Number WIL-180017 Data Requirement EPA OPPTS Guideline 870.6300; OECD Draft Guideline 426 Study Director Donald G. Stump, PhD, DABT Study Initiation Date 21 April 2006 Study Completion Date 10 January 2008 Performing Laboratory WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-9281 Sponsor Study Number 06-128 Sponsor 3M Corporation 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 WIL-180017 -2- 3M Corporation MTDID 208 06-128 Compliance Statement This study, designated WIL-180017, was conducted in compliance with the United States Environmental Protection Agency (EPA) Good Laboratory Practice (GLP) Standards (40 CFR Part 792); the standard operating procedures of WIL Research Laboratories, LLC and the protocol as approved by the sponsor, with the following exceptions. Analyses of the test article in the dosing formulations, plasma samples and tissue samples for toxicokinetic analysis and transcriptional analyses using rtPCR were conducted under non-GLP conditions. The protocol was designed to be in general accordance with the United States EPA Health Effects Test Guideline OPPTS 870.6300 Developmental Neurotoxicity Study, August 1998 and the Organisation for Economic Cooperation and Development (OECD) Revised Draft Guideline No. 426,2003. Donald G. Stump, PhD, DABT Date Associate Director, Developmental and Reproductive Toxicology Study Director WIL-180017 -3- 3M Corporation MTDID 208 06-128 Table Of Contents Volume 1 Page Compliance Statement.......................................................................................................2 Table Of Contents ..............................................................................................................3 Index Of Figures ................................................................................................................9 Index Of Tables ................................................................................................................12 Index Of Appendices........................................................................................................16 1 1.1 1.2 TT 1. TT 2. 1.3 1.4 2 2.1 2.2 Summary...................................................................................................21 Objective ....................................................................................................21 Study Design..............................................................................................21 Maternal Tissue Collection ........................................................................23 Offspring Tissue Collection.......................................................................23 Results........................................................................................................24 Conclusions................................................................................................26 Introduction..............................................................................................27 General Study Information ........................................................................27 Key Study Dates ........................................................................................29 WIL-180017 -4- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 3 Study Design .............................................................................................30 4 4.1 4.1.1 TT 3. 4.1.2 4.1.3 TT 4. 4.1.4 4.2 4.3 TT 5. TT 6. 4.4 4.4.1 4.4.2 4.4.3 4.4.4 4.4.5 5 5.1 5.1.1 5.1.2 Experimental Procedures - Materials And Methods ...........................32 Test Article And Vehicle ...........................................................................32 Test Article Identification ..........................................................................32 Test Article Characterization .....................................................................32 Vehicle Identification.................................................................................33 Preparation .................................................................................................33 Test Article Dosage Levels and Concentration .........................................34 Sampling And Analysis .............................................................................35 Test System................................................................................................35 Organization Of Test Groups, Dosage Levels And Treatment Regimen....................................................................................36 Group Assignments - Main Study Phase (WIL-180017) ..........................36 Group Assignments - Toxicokinetic Phase (WIL-180017T) ....................36 F0 Maternal Generation..............................................................................38 Animal Receipt And Acclimation..............................................................38 Animal Housing .........................................................................................38 Diet, Drinking Water And Maintenance....................................................39 Environmental Conditions .........................................................................40 Assignment Of Animals To Treatment Groups And Breeding Procedures ..................................................................................40 Parameters Evaluated .............................................................................41 F0 Observations ..........................................................................................41 Clinical Observations And Survival ..........................................................41 Body Weights.............................................................................................42 WIL-180017 -5- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 5.1.3 5.1.4 5.1.5 5.2 5.2.1 5.2.2 5.2.3 5.2.4 5.2.5 5.2.6 5.2.7 TT 7. 5.2.8 5.2.8.1 5.2.8.2 5.2.8.3 5.2.8.4 5.2.8.5 5.2.8.6 5.2.9 5.2.9.1 5.2.9.2 5.2.9.3 5.2.10 5.2.10.1 Food Consumption.....................................................................................42 Parturition ..................................................................................................43 Macroscopic Examinations........................................................................43 F1 Litter Parameters ...................................................................................44 Litter Viability And Deaths .......................................................................44 Litter Reduction .........................................................................................44 Clinical Observations.................................................................................45 Body Weights.............................................................................................45 Sex Determination .....................................................................................46 Calculation Of Litter Parameters ...............................................................46 Weaning And Selection .............................................................................46 Allocation Of Pups For Behavioral Tests And Brain Weights ......................................................................................................47 Developmental Landmarks, Sensory Function And Neurobehavioral Testing............................................................................48 Balanopreputial Separation - Subset A ......................................................48 Vaginal Patency - Subset A .......................................................................48 Functional Observational Battery (FOB) - Subset A.................................48 Acoustic Startle Response - Subset A........................................................49 Locomotor Activity - Subset A..................................................................50 Biel Maze Swimming Trials - Subset A ....................................................51 Macroscopic Examinations........................................................................52 Offspring Not Selected For Behavioral Evaluations Or Brain Weight Measurements......................................................................52 Offspring Euthanized At Study Termination (Not Selected For Brain Weight Measurements)..............................................................53 Offspring Selected For Brain Weight Measurements Subsets A and B .........................................................................................53 Microscopic Examinations.........................................................................54 Neuropathology..........................................................................................54 WIL-180017 -6- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 5.2.10.2 5.2.10.3 5.3 5.3.1 5.3.1.1 5.3.1.2 5.3.1.3 5.3.1.4 5.3.2 5.4 5.5 Thyroid Evaluations...................................................................................54 Thyroid Cell Proliferation Assay ...............................................................55 Toxicokinetic Analysis And Thyroid Function Assessment .....................55 Sample Collection......................................................................................55 Gestation Day 20 (Toxicokinetic Phase) ...................................................55 Lactation Day/PND 4 (Main Study Phase)................................................56 PND 21 (Main Study Phase)......................................................................56 PND 72 (Main Study Phase)......................................................................57 Sample Processing And Analysis ..............................................................57 Statistical Methods.....................................................................................58 Data Retention ...........................................................................................60 6 6.1 6.2 6.2.1 6.2.2 6.2.3 6.2.3.1 6.2.3.2 6.2.4 6.2.4.1 6.2.4.2 6.2.5 6.2.6 6.3 6.3.1 Results .......................................................................................................61 Analytical Chemistry .................................................................................61 F0 Maternal Generation..............................................................................61 Clinical Observations And Survival ..........................................................61 Pregnancy Status........................................................................................62 Gestation Period.........................................................................................62 Body Weights.............................................................................................62 Food Consumption.....................................................................................63 Lactation Period .........................................................................................64 Body Weights.............................................................................................64 Food Consumption.....................................................................................64 Gestation Length and Parturition ...............................................................65 F0 Macroscopic Examinations ...................................................................65 F1 Litter Data..............................................................................................66 PND 0 Litter Data And Postnatal Survival ................................................66 WIL-180017 -7- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 6.3.2 6.3.3 6.3.4 6.3.4.1 6.3.4.2 6.4 6.4.1 6.4.2 6.5 6.5.1 6.5.2 6.5.3 6.5.3.1 6.5.3.2 6.5.3.3 6.5.3.4 6.5.4 6.6 6.6.1 6.6.1.1 6.6.1.2 6.6.2 6.6.2.1 6.6.2.2 6.7 6.7.1 General Physical Condition And Mortalities.............................................66 Offspring Body Weights - Pre-weaning....................................................67 Macroscopic Examinations - Pre-weaning................................................67 Offspring Found Dead ...............................................................................67 Offspring Not Selected For Behavioral Evaluations Or Brain Weight Measurements (PND 21).....................................................68 Developmental Landmarks ........................................................................68 Balanopreputial Separation - Subset A ......................................................68 Vaginal Patency - Subset A .......................................................................69 F1 Generation .............................................................................................69 Clinical Observations and Survival ...........................................................69 Offspring Body Weights - Post-weaning ..................................................70 Sensory Function And Behavioral Testing ................................................70 Functional Observational Battery - Subset A............................................70 Locomotor Activity - Subset A .................................................................71 Acoustic Startle Response- Subset A ........................................................73 Biel Maze Swimming Trials - Subset A....................................................74 Macroscopic Examinations - Post-weaning (Not Selected For Brain Weight Measurements on PND 72)...........................................74 Animals Selected For Perfusion And Brain Weight Measurements ............................................................................................75 PND 21.......................................................................................................75 Macroscopic Examinations........................................................................75 Brain Weights/Brain Measurements ..........................................................75 PND 72.......................................................................................................76 Macroscopic Examinations........................................................................76 Brain Weights/Brain Measurements ..........................................................76 Thyroid Function Assessment....................................................................76 Thyroid Stimulating Hormone...................................................................76 WIL-180017 -8- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 6.7.2 6.7.3 TT 8. TT 9. TT 10. TT 11. 6.8 TT 12. 6.9 TT 13. Thyroid Histopathology .............................................................................78 Thyroid Morphometry ...............................................................................78 Thyroid Follicular Epithelial Cell Height, PND 4 .....................................79 Thyroid Follicular Epithelial Cell Height, PND 21 ...................................79 Thyroid Follicular Colloid Area, PND 4 ...................................................80 Thyroid Follicular Colloid Area, PND 21 .................................................80 Toxicokinetics and rtPCR ..........................................................................80 rtPCR Results For F0 Dams And F1 Fetuses On Gestation Day 20 And F1 Male Pups Group On PND 21 ..........................................83 Thyroid Cell Proliferation Assay ...............................................................83 Ki-67-Positive Follicular Epithelial Cells in Thyroid Gland, Gestation Day 20........................................................................................84 7 Discussion .................................................................................................84 8 Conclusions ...............................................................................................87 9 Key Study Personnel and Report Submission.......................................88 10 Quality Assurance Unit Statement .........................................................90 10.1 Phases Inspected ........................................................................................90 10.2 Approval ....................................................................................................93 11 References .................................................................................................94 12 Deviations From The Protocol................................................................96 WIL-180017 -9- 3M Corporation MTDID 208 06-128 Index Of Figures Volume 1 (continued) Page 1. Summary Of Body Weights During Gestation [G] (F0 Females)............................100 2. Summary Of Body Weights During Lactation [G] (F0 Females)............................101 3. Summary Of Offspring Weights [G] (F1 Males - PND 1-21) .................................102 4. Summary Of Offspring Weights [G] (F1 Females - PND 1-21)..............................103 5. Summary Of Body Weights [G] (F1 Males - PND 28-72) ......................................104 6. Summary Of Body Weights [G] (F1 Females - PND 28-72)...................................105 7. Summary Of Mean Forelimb Grip Strength [G] (F1 Males) ...................................106 8. Summary Of Mean Hindlimb Grip Strength [G] (F1 Males)...................................107 9. Summary Of Mean Forelimb Grip Strength [G] (F1 Females)................................108 10. Summary Of Mean Hindlimb Grip Strength [G] (F1 Females) ...............................109 11. Summary Of Motor Activity Total Counts By Session (F1 Males - PND 13, 17 And 21)..............................................................................110 12. Summary Of Motor Activity Ambulatory Counts By Session (F1 Males - PND 13, 17 And 21)..............................................................................111 13. Summary Of Motor Activity Total Counts By Session (F1 Males - PND 61).................................................................................................112 14. Summary Of Motor Activity Ambulatory Counts By Session (F1 Males - PND 61).................................................................................................113 15. Summary Of Motor Activity Total Counts (F1 Males - PND 13) ...........................114 16. Summary Of Motor Activity Ambulatory Counts (F1 Males - PND 13) ................115 17. Summary Of Motor Activity Total Counts (F1 Males - PND 17) ...........................116 18. Summary Of Motor Activity Ambulatory Counts (F1 Males - PND 17) ................117 WIL-180017 -10- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 19. Summary Of Motor Activity Total Counts (F1 Males - PND 21) ...........................118 20. Summary Of Motor Activity Ambulatory Counts (F1 Males - PND 21) ................119 21. Summary Of Motor Activity Total Counts (F1 Males - PND 61) ...........................120 22. Summary Of Motor Activity Ambulatory Counts (F1 Males - PND 61) ................121 23. Summary Of Motor Activity Total Counts By Session (F1 Females - PND 13, 17 And 21) ..........................................................................122 24. Summary Of Motor Activity Ambulatory Counts By Session (F1 Females - PND 13, 17 And 21) ..........................................................................123 25. Summary Of Motor Activity Total Counts By Session (F1 Females - PND 61) .............................................................................................124 26. Summary Of Motor Activity Ambulatory Counts By Session (F1 Females - PND 61) .............................................................................................125 27. Summary Of Motor Activity Total Counts (F1 Females - PND 13)........................126 28. Summary Of Motor Activity Ambulatory Counts (F1 Females - PND 13).............127 29. Summary Of Motor Activity Total Counts (F1 Females - PND 17)........................128 30. Summary Of Motor Activity Ambulatory Counts (F1 Females - PND 17).............129 31. Summary Of Motor Activity Total Counts (F1 Females - PND 21)........................130 32. Summary Of Motor Activity Ambulatory Counts (F1 Females - PND 21).............131 33. Summary Of Motor Activity Total Counts (F1 Females - PND 61)........................132 34. Summary Of Motor Activity Ambulatory Counts (F1 Females - PND 61).............133 35. Summary Of Startle Response Data [Vmax] (F1 Males - PND 20) ........................134 36. Summary Of Startle Response Data [Tmax] (F1 Males - PND 20).........................135 37. Summary Of Startle Response Data [Vmax] (F1 Females - PND 20).....................136 WIL-180017 -11- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 38. Summary Of Startle Response Data [Tmax] (F1 Females - PND 20) .....................137 39. Summary Of Startle Response Data [Vmax] (F1 Males - PND 60) ........................138 40. Summary Of Startle Response Data [Tmax] (F1 Males - PND 60).........................139 41. Summary Of Startle Response Data [Vmax] (F1 Females - PND 60).....................140 42. Summary Of Startle Response Data [Tmax] (F1 Females - PND 60) .....................141 43. Summary Of Biel Maze Data (F1 Males - Time To Escape - PND 22) ..................142 44. Summary Of Biel Maze Data (F1 Males - Mean No. Of Errors - PND 22).............................................................143 45. Summary Of Biel Maze Data (F1 Females - Time To Escape - PND 22)...............144 46. Summary Of Biel Maze Data (F1 Females - Mean No. Of Errors - PND 22) .........................................................145 WIL-180017 -12- 3M Corporation MTDID 208 06-128 Index Of Tables Note: Some table titles have been shortened due to software spacing constraints. Volume 1 (continued) Page Summary Data - F0 Generation 1. Summary Of Maternal Survival And Pregnancy Status (F0)...................................147 2. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (F0 - Daily Examinations).........................................................................................148 3. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (F0 - 1 Hour Post-Dosing).........................................................................................151 4. Summary Of Body Weights During Gestation [G] (F0) ..........................................152 5. Summary Of Body Weight Changes During Gestation [G] (F0).............................154 6. Summary Of Food Consumption During Gestation [G/Animal/Day] (F0) ............................................................................................................................156 7. Summary Of Food Consumption During Gestation [G/Kg/Day] (F0) ............................................................................................................................158 8. Summary Of Body Weights During Lactation [G] (F0) ..........................................160 9. Summary Of Body Weight Changes During Lactation [G] (F0).............................162 10. Summary Of Food Consumption During Lactation [G/Animal/Day] (F0) .............163 11. Summary Of Food Consumption During Lactation [G/Kg/Day] (F0) ............................................................................................................................165 12. Summary Of Gestation Lengths [Days] (F0)............................................................167 13. Summary Of Macroscopic Findings (F0 - Failed To Deliver).................................168 14. Summary Of Macroscopic Findings (F0 - Lactation Day 21)..................................169 15. Summary Of Implantation Sites (F0)........................................................................170 WIL-180017 -13- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page Summary Data - F1 Litters 16. Summary Of PND 0 Litter Data (F1) .......................................................................171 17. Summary Of Postnatal Survival [% Per Litter] (F1) ................................................172 18. Summary Of Pup Clinical Observations (F1 - Pre-Weaning)..................................174 19. Summary Of Offspring Weights [G] (F1 - Pre-Weaning)........................................175 20. Summary Of Offspring Weight Changes [G] (F1 - Pre-Weaning) ..........................178 21. Summary Of Pup Necropsy Findings (F1 - Found Dead Pups)...............................180 22. Summary Of Pup Necropsy Findings (F1 - PND 21 Scheduled Necropsy) .........................................................................181 Summary Data - F1 Developmental Landmarks/F1 Generation 23. Summary Of Animal Developmental Parameters Balanopreputial Separation (F1) ...............................................................................182 24. Summary Of Animal Developmental Parameters - Vaginal Patency (F1) ..............183 25. Summary Of Clinical Findings: Total Occurrence/No. Of Animals (F1)...............184 26. Summary Of Body Weights [G] (F1 - Post-Weaning).............................................187 27. Summary Of Body Weight Changes [G] (F1 - Post-Weaning) ...............................191 Summary Data - F1 Neurobehavioral Testing And Brain Weights 28. Summary Of Detailed Clinical Observations (F1 Functional Observational Battery - Handling Observations).............................195 29. Summary Of Detailed Clinical Observations (F1 Functional Observational Battery - Open Field Observations)..........................227 30. Summary Of Motor Activity Counts (F1) ................................................................257 31. Summary Of Startle Response Data (F1) .................................................................273 WIL-180017 -14- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 32. Summary Of Biel Maze Data (F1 - PND 22)............................................................................................................283 33. Summary Of Biel Maze Swim Trials (F1 - PND 22)...............................................285 34. Summary Of Macroscopic Findings (F1 - PND 72 Pups Not Selected For Brain Weights)..............................................301 35. Summary Of Macroscopic Findings (F1 - PND 21 Pups Selected For Brain Weights).....................................................303 36. Summary Of Brain Weights And Brain Measurements (F1 - PND 21 Pups Selected For Brain Weights).....................................................305 37. Summary Of Brain Weights Relative To Final Body Weights (F1 - PND 21 Pups Selected For Brain Weights).....................................................307 38. Summary Of Macroscopic Findings (F1 - PND 72 Pups Selected For Brain Weights).....................................................309 39. Summary Of Brain Weights And Brain Measurements (F1 - PND 72 Pups Selected For Brain Weights).....................................................311 40. Summary Of Brain Weights Relative To Final Body Weights (F1 - PND 72 Pups Selected For Brain Weights).....................................................313 Summary Data - Thyroid Function Assessment 41. Summary Of TSH Values (F0 Dams - Gestation Day 20) .......................................315 42. Summary Of TSH Values (F1 Fetuses - Gestation Day 20) ....................................316 43. Summary Of TSH Values (F0 Dams - Lactation Days 4 and 21)............................317 44. Summary Of TSH Values (F1 Pups - PND 4)..........................................................318 45. Summary Of TSH Values (F1 Pups - PND 21)........................................................319 46. Summary Of Microscopic Findings (F1 Fetuses - Gestation Day 20) ...............................................................................321 47. Summary Of Microscopic Findings (F1 Pups - PND 4) ..........................................323 WIL-180017 -15- 3M Corporation MTDID 208 06-128 Volume 1 (continued) Page 48. Summary Of Microscopic Findings (F1 Pups - PND 21) ........................................325 49. Summary Of Thyroid Morphometry (F1 Pups - PND 4).....................................................................................................327 50. Summary Of Thyroid Morphometry (F1 Pups - PND 21)...................................................................................................329 51. Summary Of Ki-67 Cell Counts (F1) ............................................................................................................................331 WIL-180017 -16- 3M Corporation MTDID 208 06-128 Index Of Appendices Volume 2 Page Individual Data - F0 Generation 1. Individual Clinical Observations [Positive Findings Only] (F0 - Daily Examinations).........................................................................................334 2. Individual Body Weights During Gestation [G] (F0)...............................................402 3. Individual Body Weight Changes During Gestation [G] (F0) .................................406 4. Individual Food Consumption During Gestation [G/Animal/Day] (F0)..................410 5. Individual Food Consumption During Gestation [G/Kg/Day] (F0).........................414 6. Individual Body Weights During Lactation [G] (F0)...............................................418 7. Individual Body Weight Changes During Lactation [G] (F0)..................................422 8. Individual Food Consumption During Lactation [G/Animal/Day] (F0)..................426 9. Individual Food Consumption During Lactation [G/Kg/Day] (F0) .........................430 10. Individual Gestation Lengths [Days] (F0) ................................................................434 11. Individual Macroscopic Findings (F0 - Failed To Deliver) .....................................435 12. Individual Macroscopic Findings (F0 - Lactation Day 21) ......................................438 13. Individual Implantation Sites (F0) ............................................................................535 Individual Data - F1 Litter Data 14. Individual Litter Viability (F1) .................................................................................539 15. Individual Pup Viability (F1) ....................................................................................543 16. Individual Pup Clinical Observations (F1 - Pre-Weaning) .....................................555 17. Individual Offspring Weights [G] (F1 - Pre-Weaning) ............................................613 WIL-180017 -17- 3M Corporation MTDID 208 06-128 Volume 3 Page 18. Individual Offspring Weight Changes [G] (F1 - Pre-Weaning)...............................691 19. Individual Pup Necropsy Findings (F1 - Found Dead Pups) ...................................766 20. Individual Pup Necropsy Findings (F1 - PND 21 Scheduled Necropsy) .........................................................................770 Individual Data - F1 Developmental Landmarks/F1 Generation 21. Individual Animal Developmental Parameters Balanopreputial Separation (F1) ...............................................................................789 22. Individual Animal Developmental Parameters - Vaginal Patency (F1)...................793 23. Individual Clinical Observations [Positive Findings Only] (F1)..............................797 24. Individual Body Weights [G] (F1 - Post-Weaning) .................................................807 25. Individual Body Weight Changes [G] (F1 - Post-Weaning)....................................815 Individual Data - F1 Neurobehavioral Testing and Brain Weights 26. Individual Detailed Clinical Observations (F1 - Functional Observational Battery - Handling Observations) ............................................................................823 27. Individual Detailed Clinical Observations (F1 - Functional Observational Battery - Open Field Observations) .......................922 28. Individual Motor Activity Counts (F1)...................................................................1021 29. Individual Startle Response Data (F1)....................................................................1053 30. Individual Biel Maze Straight Channel Swim Trials (F1 - PND 22)..........................................................................................................1069 31. Individual Biel Maze Swim Trials (F1 - PND 22) .................................................1077 Volume 4 32. Individual Macroscopic Findings (F1 - PND 72 Pups Not Selected For Brain Weights)............................................1095 WIL-180017 -18- 3M Corporation MTDID 208 06-128 Volume 4 (continued) Page 33. Individual Macroscopic Findings (F1 - PND 21 Pups Selected For Brain Weights)...................................................1135 34. Individual Final Body And Brain Weights And Brain Measurements (F1 - PND 21 Pups Selected For Brain Weights)...................................................1255 35. Individual Brain Weights Relative To Final Body Weights (F1 - PND 21 Pups Selected For Brain Weights)...................................................1263 36. Individual Macroscopic Findings (F1 - PND 72 Pups Selected For Brain Weights)...................................................1271 37. Individual Final Body And Brain Weights And Brain Measurements (F1 - PND 72 Pups Selected For Brain Weights)...................................................1391 38. Individual Brain Weights Relative To Final Body Weights (F1 - PND 72 Pups Selected For Brain Weights)...................................................1399 Individual Data - Thyroid Function Assessment 39. Individual TSH Values (F0 Dams - Gestation Day 20)..........................................1407 40. Individual TSH Values (F1 Fetuses - Gestation Day 20).......................................1411 41. Individual TSH Values (F0 Dams - Lactation Day 4)............................................1415 42. Individual TSH Values (F1 Pups - PND 4) ............................................................1419 43. Individual TSH Values (F0 Dams - Lactation Day 21)..........................................1423 44. Individual TSH Values (F1 Pups - PND 21) ..........................................................1427 Volume 5 45. Individual Microscopic Findings (F1 Fetuses - Gestation Day 20) .......................1437 46. Individual Microscopic Findings (F1 Pups - PND 4).............................................1517 47. Individual Microscopic Findings (F1 Pups - PND 21)...........................................1597 48. Individual Thyroid Morphometry (F1 Pups - PND 4)...................................................................................................1677 WIL-180017 -19- 3M Corporation MTDID 208 06-128 Volume 5 (continued) Page 49. Individual Thyroid Morphometry (F1 Pups - PND 21).................................................................................................1715 50. Individual Ki-67 Cell Counts (F1) ..........................................................................................................................1755 51. Study Personnel ......................................................................................................1757 52. Study Protocol And Amendments..........................................................................1759 53. Certificate Of Analysis (Sponsor-Provided Data) .................................................1800 54. Analyses Of Dosing Formulations And Toxicokinetics Report (3M Corporation)....................................................................................................1804 55. Animal Room Environmental Conditions .............................................................1817 56. Individual Toxicokinetic Animal Data...................................................................1826 1. Individual Clinical Observations [Positive Findings Only] (Daily Examinations).........................................................................................1827 2. Individual Clinical Observations (1 Hour Post-Dosing).........................................................................................1833 3. Individual Body Weights During Gestation [G]...............................................1834 4. Individual Body Weight Changes During Gestation [G]..................................1838 5. Individual Food Consumption During Gestation [G/Animal/Day]..................1842 6. Individual Food Consumption During Gestation [G/Kg/Day] .........................1846 7. Individual Pregnancy Status..............................................................................1850 Volume 6 57. Pathology Report (WIL Research Laboratories, LLC)..........................................1855 58. rtPCR Results .........................................................................................................1877 59. Clinical Pathology Methods, Procedures And References ....................................1889 WIL-180017 -20- 3M Corporation MTDID 208 06-128 Volume 6 (continued) Page 60. Statistical Analysis Report (BioSTAT Consultants, Inc.)......................................1891 61. WIL Reproductive Historical Control Data Version 2.4 [Crl:CD(SD) Rats] .......1930 62. Developmental Neurotoxicity Method Development Studies (WIL Research Laboratories, LLC) .......................................................................1939 63. WIL FOB Historical Control Data Version 1.0 [Crl:CD(SD) Rats] .....................2089 64. WIL Motor Activity Historical Control Data Version 2.1 [Crl:CD(SD) Rats].....2107 65. WIL Startle Response Historical Control Data Version 2.1 [Crl:CD(SD) Rats]..................................................................................................2128 66. WIL Biel Maze Historical Control Data Version 1.2 [Crl:CD(SD) Rats].............2141 WIL-180017 -21- 3M Corporation MTDID 208 06-128 1 Summary 1.1 Objective The objective of this study was to determine the potential of the test article, MTDID 208, to induce functional and morphological insult to the nervous system, which may arise in the offspring from exposure of the mother during pregnancy and lactation. Additional objectives of this study were to determine the effects of maternal exposure to the test article on maternal and neonatal thyroid status and to establish toxicokinetic data for different compartments in the dam and offspring. 1.2 Study Design Three groups of bred female Crl:CD(SD) rats were administered MTDID 208 [potassium perfluorooctanesulfonate (PFOS)] in the vehicle, 0.5% Tween 20, daily by oral gavage from gestation day 0 through lactation day 20, inclusively (main study phase; 25 females per group) or gestation day 0 through gestation day 19, inclusively (toxicokinetic phase, 10 females per group). The dosage levels were 0.1, 0.3 and 1.0 mg/kg/day administered at a dosage volume of 5 mL/kg. For comparative purposes, concurrent control groups of 25 rats for the main study phase and 10 rats for the toxicokinetic phase received the vehicle (0.5% Tween 20) on a comparable regimen. All females in both phases were observed twice daily for appearance and behavior. Clinical observations, body weights and food consumption were recorded at appropriate intervals. On gestation day 20, all females in the toxicokinetic phase were euthanized and a laparohysterectomy was performed to determine the pregnancy status of each female. All F0 females in the main study phase were allowed to deliver and rear their offspring to lactation day 21 and were then necropsied. The offspring were potentially exposed to the test article in utero WIL-180017 -22- 3M Corporation MTDID 208 06-128 (placental transfer) and through nursing during lactation. All F1 pups were observed daily for moribundity and mortality; all remarkable clinical observations were recorded. Individual pup body weights were recorded on postnatal day (PND) 1, 4, 7, 11, 14, 17 and 21, and at weekly intervals thereafter. On PND 4, litters were standardized to 8 pups per litter, with equal sex distribution when possible. Following culling of the main study phase, a subset (Subset A) of 1 pup/sex/litter (until N=20 pups/sex/group) was assigned to functional observational battery (FOB; on PND 4, 11, 21, 35, 45 and 60), acoustic startle response (PND 20 and 60), locomotor activity (PND 13, 17, 21 and 61) and learning and memory (PND 22). From this subset, 15 pups/sex/group were randomly selected for brain weight and potential neuropathological evaluations on PND 72. The remaining 5 pups/sex/group were euthanized on PND 72 and necropsied; blood and liver samples were collected for analyses as described below. In addition, indicators of physical development (balanopreputial separation and vaginal patency) were evaluated for all F1 selected animals assigned to Subset A. A second subset (Subset B) of 1 pup/sex/group (until N=15 pups/sex/group) was selected for brain weight and potential neuropathological evaluations on PND 21. All F1 animals not selected for behavioral evaluations or thyroid function assessment were euthanized and necropsied on PND 21. For analysis of maternal and neonatal thyroid status and to establish toxicokinetic data for different compartments in the dam and offspring, blood, thyroid, liver and/or brain samples were collected from the dams, fetuses and neonates as follows. WIL-180017 -23- 3M Corporation MTDID 208 06-128 TT 1. Maternal Tissue Collection Day of No. of Phase collection dams Blood Tissues Analysis TK GD 20 Thyroid, 10 Yes a Brain, MTDID 208 serum levels, rtPCR, TSH MS LD 4 MS LD 21 Liver 10 Yes b NA MTDID 208 serum levels, TSH 10 Yes a Thyroid MTDID 208 serum levels, TSH TK = Toxicokinetic Phase; MS = Main Study; GD = Gestation Day; LD = Lactation Day; NA = Not Applicable a = Collected by decapitation b = Collected from the retro-orbital sinus TT 2. Offspring Tissue Collection Day of Phase collection Offspring Blood Tissues Analysis TK GD 20 Fetusesb Thyroid, MTDID 208 serum levels, a Brain, rtPCR, TSH, Yes Liver thyroid cell proliferation assay (1 fetus/sex/litter) MS PND 4 10 Culled litters/groupb Thyroid, MTDID 208 serum levels, Yesa Brain, rtPCR, TSH, thyroid Liver morphometry (1 pup/sex/litter) Thyroid, MTDID 208 serum levels, MS PND 21 1 pup/sex/litterb Yesa Brain, rtPCR, TSH, MSc PND 72 5/sex/group Liver thyroid morphometry Yesa Liver MTDID 208 serum levels, rtPCR TK = Toxicokinetic Phase; MS = Main Study; GD = Gestation Day; PND = Postnatal Day a = Collected by decapitation; pooled by litter for gestation day 20 fetuses and PND 4 pups b = From the same 10 litters/group whose dams were selected for blood sample collection c = Not selected for brain weights All blood samples were collected between 0859 and 1205 hours. Following blood collection, thyroids, brains and livers were collected, weighed (pooled by litter, without regard for sex, on gestation day 20 and PND 4) and/or retained. The thyroids of the WIL-180017 -24- 3M Corporation MTDID 208 06-128 gestation day 20 toxicokinetic phase fetuses (1 fetus/sex/litter) from 10 randomly selected litters/group were microscopically examined and used for a thyroid cell proliferation assay. The thyroids of the main study phase PND 4 pups (10 randomly selected litters/group) and 21 pups (1 pup/sex/litter) were microscopically examined and evaluated using a simple morphometric analysis. The thyroids of all dams and the remaining fetuses/neonates were retained but not examined. Blood, liver and/or brain samples collected on gestation day 20 (toxicokinetic phase), postnatal/lactation day 4, postnatal/lactation day 21 and from the postnatal day 72 pups not selected for brain weights (main study phase) were analyzed for MTDID 208 concentrations in serum and/or for rtPCR. Serum samples collected on gestation day 20, postnatal/lactation day 4 and postnatal/lactation day 21 were also analyzed for TSH levels. 1.3 Results F0 maternal survival, mean length of gestation, the process of parturition, the number of former implantation sites and unaccounted-for sites, viable litter size and pup sex ratio following oral administration of MTDID 208 at dosage levels of 0.1, 0.3 and 1.0 mg/kg/day, were unaffected by test article administration. No MTDID 208-related clinical or internal findings were observed for the F0 females at any dosage level. Mean TSH values in the MTDID 208-treated females were similar to the control group value. Slightly lower mean body weight gains and food consumption were noted in the 1.0 mg/kg/day group during gestation days 0-3, 3-6, 6-9, 9-12 and/or 12-15. Additionally, a slightly lower mean body weight gain and reduced food consumption were noted in the 1.0 mg/kg/day group F0 females during lactation days 1-4. Mean body weights in the 1.0 mg/kg/day group F0 females were generally 3.8% to 5.7% lower than the control group values during lactation days 4 through 21. Postnatal survival, body weights, body weight gains, functional observational battery parameters, startle responsiveness, swimming ability, learning and memory and mean age WIL-180017 -25- 3M Corporation MTDID 208 06-128 and weight at attainment of balanopreputial separation and vaginal patency in the F1 males and females during the pre- and/or post-weaning periods were unaffected by F0 maternal test article administration. In addition, there were no test article-related clinical or internal findings or changes in brain weight, length or width in F1 males or females. Total and ambulatory motor activity counts in the 1.0 mg/kg/day group F1 males were increased compared to the concurrent control group on PND 17. A majority of the males in the 1.0 mg/kg/day group did not habituate to the test environment on PND 17 (an age when rats should begin to show habituation), while all control group males showed some indication of habituation. There were no other test article-related effects on motor activity in either sex at any dosage level on PND 13, 17, 21 or 61. For the F1 fetuses and pups, there were no test article-related alterations in TSH values or any histologic alterations in the thyroid. Mean thyroid follicular epithelial cell height in male pups from the 1.0 mg/kg/day group was higher than the concurrent control group on PND 21; this difference was suspected to be a spurious observation that was related to an extraordinarily low value in the concurrent control group compared to the other groups in this study. A higher mean number of Ki-67-positive proliferative cells in thyroid glands of female fetuses from the 1.0 mg/kg/day group was observed compared to the control group values on gestation day 20; the level of variability observed in this assay and the limited number of samples hindered an interpretation of the toxicologic significance of the observation. Therefore, the assays performed in this study revealed no unequivocal evidence of a test article-related effect on structure or function of the thyroid gland. Test article concentrations in the serum and/or liver of F0 dams and F1 fetuses and pups in the 0.1, 0.3 and 1.0 mg/kg/day groups were in approximately linear proportion to dosage level on each evaluation day (gestation day 20, lactation day/PND 4, lactation day/PND 21 and/or PND 72). For F0 dams, test article concentrations in the serum were WIL-180017 -26- 3M Corporation MTDID 208 06-128 generally higher at all dosage levels during lactation than on gestation day 20, while serum concentrations for F1 fetuses/pups were generally higher at all maternal dosage levels on gestation day 20 than during the pre-weaning period. Test article concentrations in the liver of the F1 fetuses/pups were generally higher at all maternal dosage levels during the pre-weaning period than on gestation day 20 and PND 72. Additionally, test article concentrations in the liver of F0 dams and/or F1 pups in all test article-treated groups were higher than concentrations in the serum on gestation day 20 (dams only) and PND 4, 21 and 72 (pups only), and the gestation day 20 concentrations in the liver of the fetuses from these groups were lower than the serum concentrations. The lowest test article concentrations in both the serum and liver of the F1 generation occurred on PND 72, and the only sex-specific differences were noted for serum concentrations on PND 72, with females having higher values. When F0 dams were compared to F1 fetuses and pups, serum concentrations for dams in all test article-treated groups were lower than the fetal concentrations on gestation day 20 and were higher than pup concentrations on lactation days/PND 4 and 21. In addition, liver concentrations for dams in all test article-treated groups were markedly higher than those for fetuses on gestation day 20. Differences in transcript levels between the control and 1.0 mg/kg/day groups were limited to higher mean Cyp2b2 levels for dams on gestation day 20 and male pups on PND 21, higher mean AcylCoA and Cyp4a1 levels for male pups on PND 21 and a lower Cyp7a1 level for male pups on PND 21. These differences were statistically significant. 1.4 Conclusions Based on the slightly lower maternal body weight gains and food consumption following oral administration of MTDID 208 at a dosage level of 1.0 mg/kg/day to Crl:CD(SD) rats from gestation day 0 through lactation day 20, the no-observed-adverse-effect-level (NOAEL) for maternal toxicity was considered to be 0.3 mg/kg/day. There was no WIL-180017 -27- 3M Corporation MTDID 208 06-128 unequivocal evidence of a test article-related effect on maternal thyroid status or effects on postnatal growth, survival or neonatal thyroid status. The NOAEL for F1 developmental neurotoxicity was considered to be 0.3 mg/kg/day based on increased motor activity and a failure to habituate to the test environment noted in the 1.0 mg/kg/day group F1 males on PND 17. 2 Introduction 2.1 General Study Information This report presents the data from "An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats". Due to software spacing constraints, the study title is presented as "Oral Dev. Neuro/Thyroid Function Study of MTDID 208 in Rats" on the report tables. For clarification of the terminology used to differentiate the generations in the report text, the offspring of the F0 generation were defined as the F1 litters; pups from the F1 litters were selected to constitute the F1 generation. The following computer protocols were used for data collection during the study: WIL-180017 -28- 3M Corporation MTDID 208 06-128 Computer Protocol Type of Data Collected WIL 180017 ...................................................F0 maternal and F1 litter data (including F0 maternal TSH data) WIL 180017J .................................................F1 post-weaning body weight, clinical observation, developmental landmark and necropsy data (for animals not selected for brain weights on PND 72) WIL 180017S.................................................F1 Subset A FOB (open field observations), locomotor activity, startle response and learning and memory data WIL 180017H ................................................F1 FOB data (handling observations) WIL 180017E.................................................F1 Subset B PND 21 necropsy and brain weight/measurement data WIL 180017K ................................................F1 Subset A PND 72 necropsy and brain weight/measurement data WIL 180017T.................................................Toxicokinetic phase maternal clinical observations, body weight, food consumption, pregnancy status and gestation day 20 TSH data WIL 180017C ................................................Toxicokinetic phase gestation day 20 fetal TSH data WIL 180017U ................................................F1 PND 4 TSH data WIL 180017W ...............................................F1 gestation day 20 fetal thyroid cell proliferation assay WIL 180017V ................................................F1 PND 21 TSH and thyroid morphometry data WIL 180017N ................................................F1 PND 4 thyroid morphometry data WIL-180017 -29- 3M Corporation MTDID 208 06-128 2.2 Key Study Dates Date(s) Event(s) 18 April 2006 .................................................Experimental starting date (animal receipt) 2 May 2006 ....................................................Experimental start date (initiation of F0 test article administration) 2 May 2006 - 18 June 2006...........................F0 dose administration period 22 - 25 May 2006 ..........................................Gestation day 20 euthanasia (toxicokinetic phase) 13-19 June 2006.............................................F0 lactation day 21 necropsies and F1 PND 21 necropsies 27 May 2006 - 2 June 2006...........................F1 PND 4 necropsies 27 May 2006 - 28 July 2006..........................F1 developmental indices and behavioral testing 3 - 8 August 2006 ..........................................F1 PND 72 necropsies 21 December 2007 .........................................Experimental termination/ completion date (last dosing formulation analysis) WIL-180017 -30- 3M Corporation 3 Study Design Serum and liver samples of dams and pups analyzed for MTDID 208 Remaining serum samples of dams and pups analyzed for TSH levels Thyroids of 1 pup/sex/litter/group microscopically examined and evaluated using morphometric analysis Main study phase 25 mated females (WIL-180017) per group (1-4) dosed from gestation day 0 through lactation day 20 F0 clinical observations, body weights and food consumption recorded at appropriate intervals F0 females allowed to deliver Necropsies performed on females that failed to deliver F1 pups observed daily; detailed physical examinations and body weights recorded at appropriate intervals F1 pups potentially exposed to the test article in utero and via nursing Blood collected from 10 F0 females/group on lactation day 4; the culled pups of the litters of these same females were euthanized on PND 4 for collection of blood (pooled by litter), thyroid, brain and liver samples MTDID 208 06-128 Toxicokinetic phase 10 mated females (WIL-180017T) per group (1-4) dosed from gestation day 0 through gestation day 19 Maternal clinical observations, body weights and food consumption recorded at appropriate intervals Females euthanized on gestation day 20; blood (pooled by litter), thyroid, liver and brain samples collected from dams and their fetuses Serum and liver samples of dams and fetuses analyzed for MTDID 208 and rtPCR performed on liver samples from control and high dosage groups Remaining serum samples of dams and fetuses were analyzed for TSH levels Thyroids of 1 fetus/litter/group microscopically examined and used for a thyroid cell proliferation assay; dam thyroids WIL-180017 -31- 3M Corporation MTDID 208 06-128 Study Design (continued) F0 females and pups (not selected for behavioral or possible neuropathology evaluations) necropsied on lactation day/PND 21; thyroid, liver and/or brain samples collected from 10 randomly selected dams and from 1 pup/sex/litter of these same dams 20 pups/sex/group selected for post-weaning developmental landmarks and neurobehavioral evaluations; 15 pups/sex/group selected for possible neuropathological evaluation Serum and liver samples of dams and pups analyzed for MTDID 208 and rtPCR performed on liver samples from male pups in the control and high dosage groups Remaining serum samples of dams and pups were analyzed for TSH levels Thyroids of pups microscopically examined including morphometric evaluation; dam thyroids retained Subset A 20 pups/sex/group selected for FOB evaluations on PND 4, 11, 21, 35, 45 and 60; startle response evaluations on PND 20 and 60; motor activity evaluations on PND 13, 17, 21 and 61; learning and memory evaluation on PND 22 Subset B 15 pups/sex/group selected for in situ perfusion; brain weights, brain measurements and possible neuropathological evaluations on PND 21 15 pups/sex/group selected for in situ perfusion; brain weights, brain measurements and possible neuropathological evaluations on PND 72 5 pup/sex/group selected for necropsy on PND 72; collection of blood and liver samples Serum and liver samples analyzed for MTDID 208 WIL-180017 -32- 3M Corporation 4 Experimental Procedures - Materials And Methods MTDID 208 06-128 4.1 Test Article And Vehicle 4.1.1 Test Article Identification The test article, MTDID 208 (potassium perfluoroalkyl sulfonate), was received from 3M Corporation, St. Paul, Minnesota, on 19 April 2006, as follows: TT 3. Test Article Characterization Identification Quantity Received MTDID 208 2 vialsa Potassium perfluoroalkyl Total gross weight: sulfonate (PFOS) 74.3 g Lot no. 217 Exp. date: 31 Aug 2006 [WIL log no. 6912A] a = Vial no. 1 was used in this study. Physical Description Off-White Powder A Certificate of Analysis for the test article was provided by the sponsor and is presented in Appendix 53. The purity of the test article was 86.9%. The test article was stored at room temperature, and was considered stable under this condition. A reserve sample of the test article (approximately 0.1 g) was collected from vial no. 1 on 25 April 2006, and stored in the Archives of WIL Research Laboratories, LLC. WIL-180017 -33- 3M Corporation MTDID 208 06-128 4.1.2 Vehicle Identification The vehicle used in preparation of the test article formulations and for administration to the control group was 0.5% Tween20, prepared using the following components. Tween 20, SigmaUltra (lot no. 014K0104, exp. date: 1 Feb 2008, received from Sigma Aldrich Inc., St. Louis, Missouri) Deionized water (prepared on site) 4.1.3 Preparation The vehicle, 0.5% Tween 20 in deionized water, was prepared in accordance with WIL Research Laboratories, LLC Standard Operating Procedure No. T2-037 (as revised) by adding an appropriate volume of deionized water to a calibrated storage container. The appropriate amount of Tween 20 was weighed into a tared, labeled storage container. While stirring the deionized water, the Tween 20 was slowly transferred into the calibrated storage container. The mixture was then stirred until uniform. The vehicle was then brought to the appropriate volume prior to use. An appropriate amount of the vehicle was dispensed into a labeled storage container. The vehicle control article was stirred continuously throughout use using a magnetic stirrer. Aliquots of the vehicle were prepared for daily dispensation and stored refrigerated. The vehicle was stirred continuously throughout dose administration. Dosing formulations were prepared at the test article concentrations indicated in the following table: WIL-180017 -34- 3M Corporation MTDID 208 06-128 TT 4. Test Article Dosage Levels and Concentration Group Number Test Articlea Dosage Level (mg/kg/day) 2 MTDID 208 0.1 3 MTDID 208 0.3 4 MTDID 208 1.0 a = The formulations were not adjusted for purity. Test Article Concentration (mg/mL) 0.02 0.06 0.2 The appropriate amount of the test article for each formulation was weighed into a plastic weighing vessel. Approximately 70% of the total volume of vehicle was added to a plastic container and the test article was quantitatively transferred to this container. The formulations were mixed until uniform using a magnetic stirrer. Vehicle was added to each container to bring the formulations to the calibration mark and mixed again until uniform. The formulations were sonicated for approximately 5 minutes at approximately 50oC and were periodically inverted/shaken to ensure uniform sonication. The pH values of the first formulations (prepared prior to the initiation of dose administration) were 7.23, 7.35, 6.85 and 6.82 for the 0, 0.02, 0.06 and 0.2 mg/mL dosing formulations, respectively. The test article formulations were prepared approximately weekly as single formulations for each dosage level, divided into aliquots (in plastic storage containers) for daily dispensation and stored under refrigerated conditions for no longer than 8 days. Each daily aliquot was sonicated for approximately 5 minutes at approximately 50oC prior to dose administration. The test article formulations were stirred continuously throughout the preparation, sampling and dose administration procedures. The test article formulations were visually inspected by the deputy director on 25 April 2006, and were found to be visibly homogeneous and acceptable for dose administration. WIL-180017 -35- 3M Corporation MTDID 208 06-128 4.1.4 Sampling And Analysis Prior to the initiation of dose administration, samples (10 mL each) were collected for homogeneity determination on 25 April 2006 from the middle stratum of the vehicle formulation and the top, middle and bottom strata of the 0.02, 0.06 and 0.2 mg/mL dosing formulations. In addition, samples (10 mL each) were collected for resuspension homogeneity and stability determinations on 3 May 2006 from the top and bottom strata of these same dosing formulations following an 8-day refrigerated storage period (after remixing for a minimum of 15 minutes using a magnetic stirrer). Samples (10 mL each) were collected for concentration analysis from the middle stratum of each dosing formulation (including the control group). All samples were placed in plastic storage containers and frozen at approximately -20oC. The samples were shipped to the sponsor (frozen samples on dry ice). Analyses of the test article formulations were conducted by the sponsor using a high performance liquid chromatography/mass spectrometry method. Details about the methodology and results of these analyses are presented in Appendix 54, and the results are summarized in Section 6.1. 4.2 Test System Sexually mature, virgin female Crl:CD(SD) rats from Charles River Laboratories, Inc., Raleigh, North Carolina, were used as the test system on this study. The animal model selected, the Crl:CD(SD) rat, is recognized as appropriate for developmental neurotoxicity studies and has been proven to be susceptible to the effects of developmental neurotoxicants. WIL Research Laboratories, LLC has reproductive and neurotoxicity historical control data for the Crl:CD(SD) rat. WIL-180017 -36- 3M Corporation MTDID 208 06-128 4.3 Organization Of Test Groups, Dosage Levels And Treatment Regimen The test and vehicle control article formulations were administered orally by gavage, via an appropriately sized flexible, Teflon shafted, stainless steel ball-tipped dosing cannula (Natume, Japan). Doses were given once daily from gestation day 0 to lactation day 20 for the main study phase and from gestation day 0 to gestation day 19 for the toxicokinetic satellite phase. A dosage volume of 5 mL/kg was used. Individual dosages were based on the most recently recorded body weights to provide the correct mg/kg/day dose. All animals were dosed at approximately the same time each day. The F0 maternal animals were assigned to study groups as follows: TT 5. Group Assignments - Main Study Phase (WIL-180017) Group Number Test Articlea Dosage Level (mg/kg/day) 1 Vehicle 0 2 MTDID 208 0.1 3 MTDID 208 0.3 4 MTDID 208 1.0 a = The formulations were not adjusted for purity. Dosage Volume (mL/kg) 5 5 5 5 Number of Females 25 25 25 25 TT 6. Group Assignments - Toxicokinetic Phase (WIL-180017T) Group Number Test Articlea Dosage Level (mg/kg/day) 1 Vehicle 0 2 MTDID 208 0.1 3 MTDID 208 0.3 4 MTDID 208 1.0 a = The formulations were not adjusted for purity. Dosage Volume (mL/kg) 5 5 5 5 Number of Females 10 10 10 10 Dosage levels were selected based on results of previous studies in rats. One study assessed neonatal viability through lactation day 5 following oral (gavage) administration WIL-180017 -37- 3M Corporation MTDID 208 06-128 of PFOS to maternal animals 6 weeks prior to mating and through gestation and/or lactation day 4 at dosage levels of 0.4, 0.8, 1.0, 1.2, 1.6 and 2.0 mg/kg/day [1]. In that study, mean maternal body weights were statistically significantly reduced in the 1.6 and 2.0 mg/kg/day groups during gestation [1]. In addition, mean maternal body weight gain during lactation days 1-5 was statistically significantly lower than the control group at 0.8 mg/kg/day and higher [1]. Mean pup weights at birth and on PND 5 were statistically significantly lower than the control group values in all PFOS-treated groups [1]. Furthermore, pup survival from birth to PND 5 was statistically significantly lower in the 1.6 and 2.0 mg/kg/day groups [1]. These results are consistent with the results of a two-generation reproductive toxicity study of PFOS at dosage levels of 0.1, 0.4, 1.6 and 3.2 mg/kg/day [2]. In the two-generation study, F1 pup weights and survival were statistically significantly lower than the control group at dosage levels of 1.6 and 3.2 mg/kg/day, resulting in termination of both of these groups [2]. In addition, statistically significant, lower F2 pup weights were noted in the 0.4 mg/kg/day group on PND 7 and 14 [2]. A third study was performed in which PFOS was administered to rats from gestation day 2-21 at dosage levels of 1, 2, 3, 5 and 10 mg/kg/day [3]. In that study, postnatal survival and pup weights were statistically significantly lower in the 2, 3 and 5 mg/kg/day groups [3]. Because greater than 95% of the pups in the 10 mg/kg/day group did not survive the first day of postnatal life, offspring weights were not evaluated in the 10 mg/kg/day group [3]. In that study, no statistically significant effects were observed on pup weight or survival in the 1 mg/kg/day group [3]. Based on the results of these 3 previous studies, dosage levels of 0.1, 0.3, and 1 mg/kg/day were selected for the present study. The F1 animals were not directly exposed to the test article at any time during the study; the offspring of the F0 parental generation were potentially exposed to the test article in utero and via the milk during the lactation period. Due to the presence of fish meal in WIL-180017 -38- 3M Corporation MTDID 208 06-128 PMI 5002 diet, it is likely that perfluorooctane sulfonate is present at low levels and as a result the F1 animals and possibly control F0 animals could have been exposed to a minor extent through the feed. The selected route of administration for this study was oral (gavage) because this is a possible route of exposure for humans. The number of animals selected for this study was the minimum required to meet U.S. EPA guideline 870.6300 recommendations. 4.4 F0 Maternal Generation 4.4.1 Animal Receipt And Acclimation One hundred seventy six sexually mature female Crl:CD(SD) rats were received from Charles River Laboratories, Inc., Raleigh, North Carolina on 18 April 2006. The animals were 70 days old upon receipt. Each animal was examined by a qualified technician on the day of receipt and weighed the following day. Each rat was uniquely identified by a Monel metal eartag displaying the animal number and housed for a minimum of 14 days for acclimation purposes. During the acclimation period, the rats were observed twice daily for changes in general appearance and behavior. Body weights were recorded prior to the initiation of mating. 4.4.2 Animal Housing Upon arrival and until pairing, all animals were individually housed in clean, stainless steel wire-mesh cages suspended above cage-board. The cage-board was changed at least 3 times per week. The animals were paired for mating in the home cage of the resident male. Following positive evidence of mating, all F0 females were individually housed in plastic maternity cages with nesting material, ground corncob bedding (Bed O'Cobs; WIL-180017 -39- 3M Corporation MTDID 208 06-128 The Andersons, Cob Products Division, Maumee, Ohio). The nesting material is periodically analyzed by the manufacturer for contaminants. No contaminants were present in the bedding at concentrations sufficient to interfere with the outcome of the study. The results of these analyses are maintained at WIL Research Laboratories, LLC. The main study phase and toxicokinetic phase females were housed in the plastic maternity cages through lactation day 21 and gestation day 20, respectively. Following weaning on PND 21, F1 animals in the main study phase were housed by litter in plastic maternity cages with nesting material until PND 27. On PND 28, surviving offspring were housed individually in suspended wire-mesh cages until euthanasia. Females that did not deliver were necropsied on post-mating day 25. The cages were subjected to routine cleaning at a frequency consistent with maintaining good animal health. Animals were housed in accordance with the Guide for the Care and Use of Laboratory Animals [4]. The animal facilities at WIL Research Laboratories, LLC are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International). 4.4.3 Diet, Drinking Water And Maintenance The basal diet used in this study, PMI Nutrition International, LLC, Certified Rodent LabDiet 5002, is a certified feed with appropriate analyses performed by the manufacturer and provided to WIL Research Laboratories, LLC. Feed lots used during the study are documented in the study records. Food jars were equipped with retainers to minimize spillage and were changed and sanitized once per week. Municipal water supplying the facility is sampled for contaminants according to standard operating procedures. The results of the diet and water analyses are maintained at WIL Research Laboratories, LLC. No contaminants were present in animal feed or water at concentrations sufficient to interfere with the objectives of this study. Reverse osmosis-purified (on-site) drinking water, delivered by an automatic watering system, WIL-180017 -40- 3M Corporation MTDID 208 06-128 and the basal diet were provided ad libitum throughout the acclimation period and during the study. 4.4.4 Environmental Conditions All rats were housed throughout the acclimation period and during the study in an environmentally controlled room. The room temperature and humidity controls were set to maintain daily averages of 71oF 5oF (22oC 3oC) and 50% 20% relative humidity. Room temperature and relative humidity were controlled and monitored using the Metasys DDC Electronic Environmental control system. These data were recorded approximately hourly and are summarized in Appendix 55. Actual mean daily temperature ranged from 70.3oF to 70.8oF (21.3oC to 21.6oC) and mean daily relative humidity ranged from 39.8% to 56.4% during the study. Light timers were calibrated to provide a 12-hour light (0600 hours to 1800 hours)/12-hour dark photoperiod. Air handling units were set to provide a minimum of 10 room air changes per hour, 100% fresh air. 4.4.5 Assignment Of Animals To Treatment Groups And Breeding Procedures At the conclusion of the acclimation period, all available females were weighed and examined in detail for physical abnormalities. At the discretion of the study director, each animal judged to be in good health and meeting acceptable body weight (minimum of 220 g) requirements at the time of cohabitation were placed in a suspended wire-mesh cage with a resident male from the same strain and source for mating. Resident males were untreated, sexually mature rats utilized exclusively for mating. These rats were maintained under similar laboratory conditions as the females. A breeding record containing the male and female identification numbers and the date of cohabitation was WIL-180017 -41- 3M Corporation MTDID 208 06-128 prepared. The selected females were approximately 12 weeks old when paired for mating. Positive evidence of mating was confirmed by the presence of a vaginal copulatory plug or the presence of sperm in a vaginal lavage. Each mating pair was examined daily. The day on which evidence of mating was identified was termed gestation day 0, and the animals were separated. The experimental design for the main study phase (WIL-180017) consisted of 3 test article-treated groups and 1 control group, composed of 25 rats each. The experimental design for the toxicokinetic phase (WIL-180017T) consisted of 3 test article-treated groups and 1 control group, composed of 10 rats each. The bred females were assigned to groups using a WIL Toxicology Data Management System (WTDMSTM) computer program which randomized the animals based on stratification of the gestation day 0 body weights in a block design. Body weights for main study phase animals ranged from 236 g to 292 g on gestation day 0. Body weights for toxicokinetic phase animals ranged from 232 g to 289 g on gestation day 0. 5 Parameters Evaluated 5.1 F0 Observations 5.1.1 Clinical Observations And Survival All rats were observed twice daily, once in the morning and once in the afternoon, for moribundity and mortality. Individual clinical observations were recorded daily (prior to test article administration during the treatment period) for each F0 female from gestation day 0 until necropsy. Animals assigned to the main study phase were also observed daily WIL-180017 -42- 3M Corporation MTDID 208 06-128 for signs of toxicity approximately 1 hour following dose administration throughout the treatment period. All significant clinical findings were recorded. Individual clinical observations from the toxicokinetic phase females are presented in Appendix 56. Main study phase females expected to deliver were also observed twice daily during the period of expected parturition and at parturition for dystocia (prolonged labor, delayed labor or other difficulties). 5.1.2 Body Weights Individual maternal body weights were measured on gestation days 0, 3, 6, 9, 12, 15, 18 and 20 for both main study and toxicokinetic phase animals. Individual maternal body weights were measured on lactation days 1, 4, 7, 10, 14, 17 and 21 for main study phase animals. Group mean body weights were calculated for each of these days. Group mean body weight changes were calculated for each corresponding interval of gestation and lactation, and also for gestation days 0-20 and for lactation days 1-21. Individual body weights for the toxicokinetic phase females are presented in Appendix 56. 5.1.3 Food Consumption Individual maternal food consumption was recorded for main study and toxicokinetic phase animals on gestation days 0, 3, 6, 9, 12, 15, 18 and 20. Individual maternal food consumption was also recorded on lactation days 1, 4, 7, 10, 14, 17 and 21 for main study phase animals. Food intake was reported as g/animal/day and g/kg/day for the corresponding body weight change intervals. Individual food consumption data for the toxicokinetic phase animals are presented in Appendix 56. When food consumption could not be determined for an animal during a given interval (due to a weighing error, food spillage, obvious erroneous value, etc.), group mean values were calculated for that interval using the available data. The time periods when food WIL-180017 -43- 3M Corporation MTDID 208 06-128 consumption values were unavailable for a given animal were designated as "NA" (Not Applicable) on the individual report tables. 5.1.4 Parturition All females assigned to the main study were allowed to deliver naturally. During the period of expected parturition, the females were observed twice daily for initiation and completion of parturition and for signs of dystocia. Beginning on the day parturition was initiated (PND 0), pups were sexed and examined for gross malformations, and the numbers of stillbirths and live pups were recorded. Individual gestation length was calculated using the date delivery started. 5.1.5 Macroscopic Examinations All toxicokinetic phase females and their litters on gestation day 20 and 10 randomly selected main study phase F0 females on lactation day 21 were euthanized by decapitation between 0859 and 1153 hours; blood and tissue samples were collected and evaluated as described in Section 5.3. The remaining main study phase females with viable offspring on lactation day 21 and those females that failed to deliver by post-mating day 25 were euthanized by carbon dioxide inhalation. All main study phase females were subjected to a gross examination; the thoracic, abdominal and pelvic cavities were opened and the contents examined. The numbers of implantation sites were recorded for females that delivered, and a pregnancy status was determined for each female that failed to deliver. The toxicokinetic phase females did not receive a gross examination, but were examined for pregnancy status. In addition, the thyroids of the gestation day 20 dams and fetuses and the 10 randomly selected F0 females that were decapitated were preserved in 10% neutral-buffered formalin. The thyroids of 1 fetus/sex/litter from the control and high-dose groups were examined microscopically as described in Section 5.2.10.2 and WIL-180017 -44- 3M Corporation MTDID 208 06-128 used for a thyroid cell proliferation assay as described in Section 5.2.10.3; the remaining fetal thyroids and all maternal thyroids were retained for possible future histopathological assessment. Maternal tissues were preserved in 10% neutral-buffered formalin for possible future histopathologic examination only as deemed necessary by the gross findings. The carcass of each female was then discarded. Uteri with no macroscopic evidence of implantation were opened and subsequently placed in a 10% ammonium sulfide solution for detection of early implantation loss [5]. 5.2 F1 Litter Parameters 5.2.1 Litter Viability And Deaths Each litter was examined daily for survival, and all deaths were recorded. All pups were individually identified by application of tattoo markings on the digits following completion of parturition. A daily record of litter size was maintained. Intact offspring dying from PND 0 to 4 were necropsied using a fresh dissection technique [6]. The stomachs were examined for the presence of milk on PND 0 and 1. A detailed gross necropsy was performed on any pup dying after PND 4; tissues were saved for possible histopathological examination only as deemed necessary by the gross findings. The carcass of each pup was then discarded. 5.2.2 Litter Reduction To reduce variability among the litters, 8 pups/litter, 4 pups/sex when possible, were randomly selected on PND 4. Culled pups from 10 randomly selected litters/group whose dams were selected for blood collection as described in Section 5.3.1.2 were WIL-180017 -45- 3M Corporation MTDID 208 06-128 euthanized on PND 4 between 0904 and 1103 hours by decapitation. Blood and tissue samples were collected for evaluation as described in Section 5.3.1.2, and the thyroids were collected and preserved in 10% neutral-buffered formalin. The thyroid of 1 pup/sex/litter from the control and high-dose groups were examined microscopically as described in Section 5.2.10.2 and Section 5.2.10.3; the remaining neonatal thyroids in each litter were retained for possible future histopathological assessment. Culled pups not selected for blood sample collection were euthanized on PND 4 by intraperitoneal injection of sodium pentobarbital. The carcasses of all culled pups were discarded without examination. 5.2.3 Clinical Observations Litters were examined daily for survival and any adverse changes in appearance or behavior. Each pup received a detailed physical examination on PND 1, 4, 7, 11, 14, 17 and 21 and at weekly intervals thereafter until necropsy on PND 72. Any abnormalities in nursing behavior were recorded. 5.2.4 Body Weights Pups were individually weighed on PND 1, 4, 7, 11, 14, 17, 21 and at weekly intervals thereafter until necropsy (PND 72) and whenever they were removed from their cages for behavioral testing. Mean pup weights are presented by sex for each litter and by group with the following exceptions. Offspring weights that were recorded when the animals were removed from their cages for behavioral testing are maintained in the study records and are not presented in this report. In addition, when body weights could not be determined for an animal during a given interval (due to unscheduled death), group mean values were calculated for that interval using the available data. The time periods when a WIL-180017 -46- 3M Corporation MTDID 208 06-128 given animal was not weighed were designated as "NA" (Not Applicable) on the individual report table. 5.2.5 Sex Determination All pups were sexed on PND 0, 4, 11 and 21. 5.2.6 Calculation Of Litter Parameters Litter parameters were defined as follows: Mean Live Litter Size = Total no. of viable pups PND 0 No. of litters with viable pups PND 0 Postnatal Survival Between Birth and PND 0 or PND 4 = (% Per Litter) (Viable pups per litter on PND 0 or PND 4/No. of pups born per litter) No. of litters/group Postnatal Survival for All Other Intervals (% Per Litter) = (Viable pups per litter at end of interval N/Viable pups per litter at start of interval N) No. of litters/group Where N = PND 0-1, 1-4 (Pre-Selection), 4 (Post-Selection)-7, 7-14, 14-21 or 4 (Post-Selection)-21 x 100 x 100 5.2.7 Weaning And Selection Each dam and litter assigned to the main study remained together until weaning on lactation day 21. Following culling, a subset of 20 pups/sex/group (Subset A) was assigned to functional observational battery (PND 4, 11, 21, 35, 45 and 60), acoustic startle response (PND 20 and 60), locomotor activity (PND 13, 17, 21 and 61) and learning and memory (PND 22). From this subset, 15 animals/sex/group were selected WIL-180017 -47- 3M Corporation MTDID 208 06-128 for brain weight evaluations on PND 72. A second subset of 15 pups/sex/group (Subset B) was selected for brain weight evaluations on PND 21. Indicators of physical development (balanopreputial separation and vaginal patency) were evaluated for all F1 selected animals. The following table summarizes the allocation of offspring for behavioral tests and brain weights. TT 7. Allocation Of Pups For Behavioral Tests And Brain Weights No. Selected Age Evaluation 15/sex/group (B) PND 21 Brain weights 20/sex/group (A)* PND 4, 11, 21 35, 45 and 60 FOB 20/sex/group (A)* PND 20 and 60 Auditory startle 20/sex/group (A)* PND 13, 17, 21 and 61 Locomotor activity 20/sex/group (A)* PND 22 Learning and memory 15/sex/group (A)** PND 72 Brain weights * The same pup subset was used for FOB, auditory startle, locomotor activity and learning and memory evaluation. ** Animals assigned to brain weight assessment on PND 72 were randomly selected from animals previously allocated to FOB, locomotor activity, auditory startle and learning and memory evaluation. All F1 animals not selected for behavioral evaluations or thyroid function assessment were euthanized and necropsied on PND 21. The remaining 5 animals/sex/group of Subset A were necropsied on PND 72; blood and tissue samples were collected for evaluations as described in Section 5.3.1.4. Selected pups retained the dam number and tattoo mark (e.g., 99999-01). Each selected pup was uniquely identified by a metal eartag displaying the identification number following weaning. WIL-180017 -48- 3M Corporation MTDID 208 06-128 5.2.8 Developmental Landmarks, Sensory Function And Neurobehavioral Testing The various investigations described herein were used to assess the maturation and behavioral development of the selected F1 pups. These procedures were concluded when the oldest pups were 66 days of age. 5.2.8.1 Balanopreputial Separation - Subset A Each male pup was observed for balanopreputial separation beginning on PND 35 [7]. The day on which balanopreputial separation was first observed was recorded for each pup. Examination of the pups continued daily until balanopreputial separation was present. Individual body weights were recorded on the day of attainment of this landmark. 5.2.8.2 Vaginal Patency - Subset A Each female pup was observed for vaginal perforation beginning on PND 25 [8]. The day on which the vaginal lumen was first observed to open was recorded for each pup. Examination of the females was continued daily until vaginal patency was present. Individual body weights were recorded on the day of attainment of this landmark. 5.2.8.3 Functional Observational Battery (FOB) - Subset A F1 animals (20 pups/sex/group) were assigned to FOB testing on PND 4, 11, 21, 35, 45 and 60. The same animals were observed at each interval. The FOB utilized at WIL Research Laboratories, LLC is based on previously developed protocols [9, 10, 11, 12, 13, 14]. Testing was performed by the same technicians, when possible, who did not know the animal's group assignment. WIL-180017 -49- 3M Corporation MTDID 208 06-128 F1 animals were observed for the following as described below: Ease of removal from cage Lacrimation/chromodacryorrhea Piloerectiona,b Palpebral closurea,b Red/crusty deposits Eye prominencea,b Mobilitya Convulsions/tremors Groominga,b Bizarre/stereotypic behavior Pupillary responsea,b Forelimb/hindlimb gripstrengtha,b Gaita Ease of handling animal in hand Salivation Fur appearancea,b Respiratory rate/character Mucous membranes/skin color Eye colora,b Muscle tone Hindlimb extensiona,b Arousal Urination/defecation Backinga Tail pinch responsea,b Air righting reflexa,b a = Parameters were not assessed in PND 4 rat pups due to the stage of development. b = Parameters were not assessed in PND 11 rat pups due to the stage of development. 5.2.8.4 Acoustic Startle Response - Subset A An acoustic startle response test was performed on 20 rats/sex/group (1 rat/sex/litter from 20 litters/group) on PND 20 and 60 using the SR-Lab Startle Response System (San Diego Instruments, San Diego, California). The same animals were tested at each interval. Each isolation chamber was composed of a wood core covered with a laboratory-grade plastic laminate and measured 15 x 16 x 23 inches. Each cabinet was equipped with an internal light, a fan, 2 viewing lenses and a white-noise generation system. The animal was placed in a cylindrical enclosure of appropriate size, which was then placed into the isolation cabinet. Each enclosure was equipped with a motion sensor. Acoustic startle response testing was performed in a room equipped with a white-noise generation system set to operate at 7010 decibels (db). Each test session consisted of a 5-minute acclimation period with a 655-db broadband background white noise. The WIL-180017 -50- 3M Corporation MTDID 208 06-128 startle stimulus for each trial was a 1155-db mixed-frequency noise burst stimulus, approximately 20 milliseconds in duration. Responses were recorded during the first 100-milliseconds following the onset of the startle stimulus for each trial. Each test session consisted of 50 trials, with an 8-second intertrial interval. Startle response data were analyzed in 5 blocks of 10 trials each. Startle response measurements obtained were maximum response amplitude (VMAX), average response amplitude (VAVE) and latency to VMAX (TMAX). 5.2.8.5 Locomotor Activity - Subset A Locomotor activity was assessed for 20 rats/sex/group (1 rat/sex/litter from 20 litters/group) on PND 13, 17, 21 and 61. The same animals were tested at each interval. Locomotor activity was measured automatically using the SDI Photobeam Activity System (San Diego Instruments, San Diego, California). This personal computer-controlled system utilizes a series of infrared photobeams surrounding an amber, plastic rectangular cage to quantify an animal's locomotor activity. Four-sided black plastic enclosures were used to surround the amber plastic boxes and decrease the potential for distraction from extraneous environmental stimuli or activity by technicians or adjacent animals. The black enclosures rested on top of the photobeam frame and did not interfere with the path of the beams. Each animal was tested separately. Data were collected in 5-minute epochs (print intervals), and the test session duration was 60 minutes. Data for ambulatory and total locomotor activity were tabulated. Total locomotor activity was defined as a combination of fine locomotor skills (i.e., grooming; interruption of a single photobeam) and ambulatory locomotor activity (e.g., interruption of 2 or more consecutive photobeams). WIL-180017 -51- 3M Corporation MTDID 208 06-128 5.2.8.6 Biel Maze Swimming Trials - Subset A Beginning on PND 22, swimming ability and learning and memory were assessed for 20 rats/sex/group (1 rat/sex/litter from 20 litters/group) using a water-filled 8-unit T-maze [15]. Animals were placed in the maze and were required to traverse the maze and escape by locating a submerged platform. For the learning and memory phases, the time required to traverse the maze and the numbers of errors for all trials were recorded. An error was defined as any instance when an animal deviated from the correct channel with all 4 feet. Each testing interval consisted of 3 phases that were conducted over 7 consecutive days. Phase 1 was an evaluation of swimming ability and motivation to escape from the maze, and was performed on day 1 of the Biel maze procedure. For this evaluation, animals were placed in a straight channel opposite the submerged escape platform, and the time required for each animal to climb up on the escape platform was recorded. Once the animal reached the platform, it was immediately placed at the starting position for another trial for a total of 4 consecutive trials. Phase 2 of the Biel maze procedure evaluated sequential learning. This evaluation was conducted on days 2-6 of the Biel maze procedure. Animals were allowed 2 trials per day for 2 days to solve the maze in path A. Animals were then allowed 2 trials per day for 3 consecutive days to solve the maze in path B (reverse of path A). For each trial, animals were allowed 3 minutes to solve the maze. If an animal did not escape the maze within the allotted 3 minutes, the animal was placed on the escape platform for approximately 20 seconds, then removed from the maze. The minimum intertrial interval was 1 hour. Phase 3 of the Biel maze procedure probed the animal for its memory to solve the maze when challenged in path A. This evaluation was conducted on day 7 of the Biel maze procedure. Each animal was allowed 2 trials to solve the maze in path A. WIL-180017 -52- 3M Corporation MTDID 208 06-128 Biel maze data were evaluated as the mean time to escape over all trials for each of the 3 phases (i.e., swimming ability and motivation, sequential learning and memory) of the Biel maze procedure. Also, the numbers of errors committed were evaluated for phases 2 and 3. 5.2.9 Macroscopic Examinations 5.2.9.1 Offspring Not Selected For Behavioral Evaluations Or Brain Weight Measurements On PND 21, all F1 animals not selected for neurobehavioral evaluations, thyroid function assessments or brain weight measurements were euthanized by carbon dioxide inhalation and subjected to gross examinations. The necropsy included examination of the external surface, all orifices and the cranial, thoracic, abdominal and pelvic cavities, including viscera/contents. Tissues were retained in 10% neutral-buffered formalin only as deemed necessary by the gross findings. Also on PND 21, 1 pup/sex/litter from the same 10 litters/group whose dams were selected for blood sample collection and that were not assigned to neurobehavioral or brain weight measurements were decapitated between 0900 and 1104 hours. Blood and tissue samples were collected for evaluation as described in Section 5.3.1.3, and the thyroids were collected and preserved in 10% neutral-buffered formalin. The thyroids of each pup from the control and high-dose groups were examined microscopically as described in Section 5.2.10.2 and Section 5.2.10.3. WIL-180017 -53- 3M Corporation MTDID 208 06-128 5.2.9.2 Offspring Euthanized At Study Termination (Not Selected For Brain Weight Measurements) Offspring (5 pups/sex/group) scheduled for euthanasia on PND 72 but not allocated for brain weight measurements were euthanized between 0859 and 1043 hours by decapitation; blood and tissue samples were collected for evaluations as described in Section 5.3.1.4. Animals were subjected to a gross examination. The necropsy included examination of the external surface, all orifices and the cranial, thoracic, abdominal and pelvic cavities, including viscera/contents. Organ and tissue samples were preserved in 10% neutral-buffered formalin as deemed necessary by the gross findings. The carcass of each animal was then discarded. 5.2.9.3 Offspring Selected For Brain Weight Measurements Subsets A and B On PND 21, 1 male and 1 female pup from each litter (Subset B; 15 rats/sex/group), were macroscopically examined for neuropathology. The animals were anesthetized by intraperitoneal injection of sodium pentobarbital and perfused in situ with fixative (4% paraformaldehyde/1.4% glutaraldehyde) as described in WIL SOP T3-034, as revised. At the termination of the study (PND 72), 15 rats/sex/group (Subset A) were randomly selected from those pups dedicated to behavioral evaluation (FOB, locomotor activity, acoustic startle and learning and memory tests). The animals were anesthetized by intraperitoneal injection of sodium pentobarbital and perfused in situ with fixative (4% paraformaldehyde/1.4% glutaraldehyde). The whole brains were removed (including olfactory bulbs), weighed and the size (length and width) was recorded. Any abnormal coloration or lesions of the external brain and spinal cord were recorded. On PND 21, brains from all perfused animals were retained for possible future microscopic examination. At study termination (PND 72), the central WIL-180017 -54- 3M Corporation MTDID 208 06-128 and peripheral nervous system tissues from all perfused animals were dissected and preserved for possible future microscopic examination. 5.2.10 Microscopic Examinations 5.2.10.1 Neuropathology The pups selected for macroscopic evaluation on PND 21 and 72 were prepared for possible future microscopic neuropathologic examination. The brains were prepared by embedding in paraffin to prevent artifactual changes in brain morphology due to storage in 10% neutral-buffered formalin. 5.2.10.2 Thyroid Evaluations Thyroids from 1 fetus/sex/litter from each toxicokinetic phase female euthanized on gestation day 20 and 1 pup/sex/litter from 10 randomly selected litters/group euthanized on PND 4 and 21 were processed, embedded in paraffin and retained; however, only the control and high-dose groups were evaluated. The thyroids were prepared for qualitative and semiquantitative histopathological examination by sectioning and staining with hematoxylin and eosin. The histopathologic examination for the pups euthanized on PND 4 and 21 included a simple morphometric analysis as described in Section 3.18 of Appendix 57 (Pathology Report). Microscopic evaluations of the thyroids were conducted by George A. Parker, DVM, PhD, DACVP, DABT, Director, Pathology. The pathology report is presented in Appendix 57. WIL-180017 -55- 3M Corporation MTDID 208 06-128 5.2.10.3 Thyroid Cell Proliferation Assay Thyroids from 1 fetus/sex/litter from 10 randomly selected litters/group on gestation day 20 were prepared and processed for a thyroid cell proliferation assay performed using Ki67 immunohistochemical staining; however, only the control and high-dose groups were evaluated. 5.3 Toxicokinetic Analysis And Thyroid Function Assessment 5.3.1 Sample Collection 5.3.1.1 Gestation Day 20 (Toxicokinetic Phase) On gestation day 20, blood samples (at least 2 mL) were collected from toxicokinetic phase maternal females and viable fetuses between 0859 and 1205 hours via decapitation into tubes without anticoagulant; fetal blood samples were pooled by litter. Following blood collection, livers and brains from each dam and viable fetus were collected and weighed (pooled by litter for the fetus). A small sample of the maternal brain and liver and a single fetal liver and brain were placed in RNAlater, refrigerated for approximately 24 hours and stored frozen until shipped to the sponsor for rtPCR. The remaining brain and liver samples were snap-frozen in liquid nitrogen and stored frozen at approximately -70C until shipped to the sponsor for toxicokinetic analysis. Liver samples from dams and fetuses in the control and high dosage groups were used for rtPCR, while liver samples from the low and mid dosage groups and brain samples were retained by the sponsor for possible future analysis. WIL-180017 -56- 3M Corporation MTDID 208 06-128 5.3.1.2 Lactation Day/PND 4 (Main Study Phase) On lactation day 4, blood samples (at least 1 mL) were collected (prior to dose administration) from the retro-orbital sinus of 10 randomly selected F0 females/group assigned to the main study into tubes without anticoagulant; the females were anesthetized by isoflurane inhalation prior to blood collection. Also on PND 4, the culled pups from litters of these same F0 females used for blood collection were euthanized by decapitation and blood was collected (pooled by litter regardless of sex) into tubes without anticoagulant. All maternal and offspring samples were collected between 0904 and 1103 hours. Following blood collection, the livers and brains of the culled offspring were collected and weighed (pooled by litter). A single neonatal liver and brain were placed in RNAlater and refrigerated until shipped to the sponsor for possible future rtPCR. The remaining brain and liver samples were snap-frozen in liquid nitrogen and stored frozen at approximately -70C until shipped to the sponsor for toxicokinetic analysis. 5.3.1.3 PND 21 (Main Study Phase) On lactation day 21, blood samples (at least 2 mL) were collected from 10 randomly selected F0 females/group via decapitation into tubes without anticoagulant. Also on PND 21, 1 pup/sex/litter (not assigned to neurobehavioral or brain weight measurements) from these same F0 females used for blood collection were euthanized by decapitation and blood was collected into tubes without anticoagulant. All maternal and offspring blood samples were collected between 0900 and 1132 hours. Following blood collection, livers and brains of the offspring were collected and weighed. Thereafter, a small sample of the liver and brain were placed in RNAlater and refrigerated until shipped to the sponsor for rtPCR. The remaining brain and liver samples were snap-frozen in liquid nitrogen and stored frozen at approximately -70C until shipped to the sponsor for toxicokinetic analysis. Liver samples from male pups in the control and high dosage WIL-180017 -57- 3M Corporation MTDID 208 06-128 groups were used for rtPCR; all other samples were retained by the sponsor for possible future analysis. 5.3.1.4 PND 72 (Main Study Phase) On PND 72, blood samples (at least 2 mL) were collected from 5 pups/sex/group (not allocated for brain weight measurements) via decapitation into tubes without anticoagulant; blood samples were collected between 0859 and 1043 hours. Following blood collection, the livers from the offspring were collected and weighed. Thereafter, a small sample of the liver was placed in RNAlater and refrigerated until shipped to the sponsor for possible future rtPCR. The remaining liver samples were snap-frozen in liquid nitrogen and stored frozen at approximately -70C until shipped to the sponsor for toxicokinetic analysis. 5.3.2 Sample Processing And Analysis Blood samples collected on gestation day 20, lactation day/PND 4, lactation day/PND 21 and PND 72 were centrifuged in a refrigerated centrifuge (at approximately 4C). Serum samples were harvested, separated into aliquots (1 with 150 L of serum for toxicokinetic analysis and the other with the remaining volume of serum for TSH analysis). All serum, liver and brain samples were stored frozen at approximately -70C. Toxicokinetic analysis and rtPCR were the responsibility of the sponsor or the sponsor's designee; the results of these analyses are presented in Appendix 54 and Appendix 58, respectively. Serum samples collected on gestation day 20, lactation day/PND 4 and lactation day/PND 21 were analyzed for TSH levels. TSH methods, procedures and references are presented in Appendix 59. WIL-180017 -58- 3M Corporation MTDID 208 06-128 5.4 Statistical Methods All statistical tests were performed using appropriate computing devices or programs. Analyses were conducted using two-tailed tests (except as noted otherwise) for minimum significance levels of 1% and 5%, comparing each test article-treated group to the control group by sex. Each mean was presented with the standard deviation (S.D.) and the number of animals (N) used to calculate the mean. In addition, percent difference from control was presented for body weights, TSH parameters and brain weights. Due to the use of significant figures and the different rounding conventions inherent in the types of software used, the means and standard deviations on the summary and individual tables may differ slightly. Data obtained from nongravid animals were excluded from statistical analyses. Where applicable, the litter was used as the experimental unit. Continuous data variables [mean maternal body weights (gestation and lactation), body weight gains and food consumption at each interval], mean gestation lengths, mean numbers of pups born, former implantation sites, unaccounted-for sites, live litter sizes, litter weights, mean day of attainment of balanopreputial separation or vaginal patency, mean body weight on the day of attainment, brain weights and dimensions of F1 pups, hormone data, thyroid morphometry data, thyroid cell proliferation data, ambulatory counts measured in locomotor activity assessment, continuous functional observational battery data, Biel maze straight channel data and average response for acoustic startle testing were subjected to a parametric one-way analysis of variance (ANOVA) [16] to determine intergroup differences. If the ANOVA revealed statistically significant (p<0.05) intergroup variance, Dunnett's test [17] was used to compare the test articletreated groups to the control group. Mean litter proportions (percent per litter) of males at birth and pup viability during the postnatal period were subjected to the Kruskal Wallis [18] nonparametric ANOVA test to determine intergroup differences. If the ANOVA revealed statistically significant (p<0.05) intergroup variance, Dunn's test [19] was used to compare the test article-treated groups to the control group. Functional observational WIL-180017 -59- 3M Corporation MTDID 208 06-128 battery parameters that yielded scalar and descriptive data were analyzed by the Fisher's Exact Test [20]. Total count measurements from the locomotor activity assessment, peak response and latency to peak response measurements from the auditory startle response data, learning and memory analyses and the number of errors committed during the learning and memory evaluations were analyzed by sex by BioSTAT Consultants, Inc., Portage, Michigan, with a repeated measures analysis of variance (RANOVA) [21]. The statistical analysis summary report is presented in Appendix 60. Factors in the model included ANIMAL, treatment group (TRT), TIME (locomotor activity) or TRIAL (auditory startle response and learning and memory), and the interaction term (TRT*TIME or TRT*TRIAL). The SAS procedure PROC MIXED was used for the analysis with the random effect of animal included as the repeated measurement. The covariance structure across time was selected by comparing Akaike's Information Criterion (AIC) for compound symmetry (CS) and/or first-order autoregressive [AR(1)] structures. The locomotor activity and auditory startle response data were analyzed for the entire test session. The learning and memory data were analyzed by phase (learn path A, learn path B and memory). In addition, the time to escape for an animal that did not escape the maze in the allotted time was considered censored and set equal to the maximum allotted time for statistical analysis. The monotonic dose response relationship was evaluated using sequential linear trend tests based on ordinal spacing of dosage levels. The linear dose by time interaction (LinTRT*TIME) or linear dose by trial interaction (LinTRT*TRIAL) was evaluated and, if significant at the 0.05 level, trend tests on treatment means were performed at the 0.05 level for each time interval or trial. If the linear dose by interaction term was not WIL-180017 -60- 3M Corporation MTDID 208 06-128 significant, the trend test was conducted across the pooled trials of the entire session or phase (as appropriate) only. Nonmonotonic dose responses were evaluated whenever no significant linear trends were detected but the TRT and/or the interaction term (TRT*TIME or TRT*TRIAL) was significant at the 0.01 level. Within the framework of the RANOVA, pairwise comparisons were made for each individual test article-treated group with the control group through linear contrasts. If the interaction term was significant, the comparisons were conducted for each time interval or trial. If only the TRT effect was significant, the comparisons were conducted across the pooled intervals of the entire session or phase (as appropriate). These nonmonotonic dose-response comparisons were conducted at the 0.01 significance level. 5.5 Data Retention The sponsor has title to all documentation records, raw data, specimens or other work product generated during the performance of the study. All work product generated by WIL Research Laboratories, LLC, including raw paper data and specimens, are retained in the Archives at WIL Research Laboratories, LLC, as specified in the study protocol. Appropriate supporting documentation for statistical analyses conducted and reported by BioSTAT Consultants, Inc., is maintained in the Archives at WIL Research Laboratories, LLC. Data generated by the sponsor for analyses of dosing formulations, toxicokinetic analysis and rtPCR will be archived by the sponsor or the sponsor's designee. Reserve samples of the test article, pertinent electronic storage media and the original final report are retained in the Archives at WIL Research Laboratories, LLC in compliance with regulatory requirements. WIL-180017 -61- 3M Corporation 6 Results MTDID 208 06-128 6.1 Analytical Chemistry The Analytical Chemistry Report is presented in Appendix 54. The analyzed dosing formulations were found to contain the amount of test article prescribed in the protocol (85% to 115% of nominal) and were homogeneous (relative standard deviation of 10%), with the following exception. The 0.02 mg/mL formulation prepared on 8 May 2006 for administration to the 0.1 mg/kg/day group was 119.11% of the nominal concentration. This slightly out-of-specification formulation did not negatively impact the outcome of the study because the no-observed-adverse-effect levels for maternal toxicity and developmental neurotoxicity were based on test article-related effects in the 1.0 mg/kg/day (0.2 mg/mL) group, and the formulations for the next lower dosage level (0.3 mg/kg/day [0.06 mg/mL]), where no test article-related effects were observed, were within specification. In addition, analysis of the resuspension samples demonstrated that after 8 days of refrigerated storage and resuspension the dose formulations were stable (90% of time 0) and were homogenous. 6.2 F0 Maternal Generation 6.2.1 Clinical Observations And Survival Clinical observations are summarized in Table 1, Table 2 and Table 3. Individual animal observations are tabulated in Appendix 1. All F0 maternal animals in the control, 0.1, 0.3 and 1.0 mg/kg/day groups survived to the scheduled necropsy. No test article-related clinical findings were noted at the daily examinations or 1 hour following dose administration. Clinical findings noted in the test article-treated groups, including hair loss on the limbs and around the eye, scabbing on the limbs and red material around the WIL-180017 -62- 3M Corporation MTDID 208 06-128 eye(s) or nose, occurred infrequently, at similar frequencies in the control group and/or in a manner that was not dose-related. 6.2.2 Pregnancy Status Pregnancy status is summarized in Table 1. Historical Control Data are presented in Appendix 61. The pregnancy rates in the control, 0.1, 0.3 and 1.0 mg/kg/day groups were 100.0%, 92.0%, 100.0% and 96.0%, respectively. Zero, 2, 0 and 1 females in the same respective groups were nongravid. 6.2.3 Gestation Period 6.2.3.1 Body Weights Body weight and body weight change data during gestation are summarized in Table 4, Table 5 and Figure 1. Individual animal data during gestation are tabulated in Appendix 2 and Appendix 3. Slightly lower (not statistically significant) mean body weight gains were noted in the 1.0 mg/kg/day group F0 females during gestation days 0-3, 3-6, 6-9, 9 12 and 12-15 compared to the control group values. Mean body weight gains in the 1.0 mg/kg/day group females were generally similar to the control group values for the remainder of gestation. As a result of the slightly lower mean body weight gains during gestation days 0-15, mean body weight gain in the 1.0 mg/kg/day group was lower (not statistically significant) when the entire period of gestation (gestation days 0-20) was evaluated. However, the lower mean body weight gain in the 1.0 mg/kg/day group was not of sufficient magnitude to result in statistically significantly lower mean body weights. WIL-180017 -63- 3M Corporation MTDID 208 06-128 Mean body weights and body weight gains in the 0.1 and 0.3 mg/kg/day groups were unaffected by test article administration during gestation. Differences between the control and 0.1 and 0.3 mg/kg/day groups were slight, not statistically significant and not observed in a dose-related manner. 6.2.3.2 Food Consumption Food consumption data during gestation are summarized in Table 6 and Table 7. Individual animal data during gestation are tabulated in Appendix 4 and Appendix 5. Mean food consumption, evaluated as g/animal/day and g/kg/day, in the 1.0 mg/kg/day group F0 females was slightly, but generally statistically significantly (p<0.01), lower than the control group values during gestation days 6-9 and 9-12. Mean food consumption in these females was similar to that in the control group prior to these intervals and for the remainder of gestation. Primarily as a result of the lower food consumption during gestation days 6-9 and 9-12, mean food consumption in the 1.0 mg/kg/day group was lower (p<0.01; g/animal/day) when the entire period of gestation (gestation days 0-20) was evaluated. Corresponding slight reductions in mean body weight gains were noted in these females (see Section 6.2.3.1). Mean food consumption in the 0.1 and 0.3 mg/kg/day groups was unaffected by test article administration during gestation. A statistically significant (p<0.05) decrease in food consumption was noted in the 0.3 mg/kg/day group during gestation days 6-9. However, this difference was not considered to be test article-related because it was transient and not observed with corresponding effects on mean body weights or body weight gains (see Section 6.2.3.1). Other differences from the control group were slight, not statistically significant and/or not observed in a dose-related manner. WIL-180017 -64- 3M Corporation 6.2.4 Lactation Period MTDID 208 06-128 6.2.4.1 Body Weights Body weight and body weight change data during lactation are summarized in Table 8, Table 9 and Figure 2. Individual animal data during lactation are tabulated in Appendix 6 and Appendix 7. A slightly lower mean body weight gain (not statistically significant) was noted in the 1.0 mg/kg/day group F0 females during lactation days 1-4 compared to the control group. Mean body weight gains in this group were generally similar to the control group values throughout the remainder of lactation. None of the differences in mean body weight gains at 1.0 mg/kg/day were statistically significant from the control group during the lactation period. As a result of lower mean body weight gain during gestation (see Section 6.2.3.1) and lactation days 1-4, mean body weights in this group were 3.8% to 5.7% lower (p<0.05 or p<0.01) than the control group values from lactation day 4 through lactation day 21. Mean body weights and body weight gains in the 0.1 and 0.3 mg/kg/day groups were unaffected by test article administration during lactation. Differences from the control group were slight, not statistically significant and not observed in a dose-related manner. 6.2.4.2 Food Consumption Food consumption data during lactation are summarized in Table 10 and Table 11. Individual animal data during lactation are tabulated in Appendix 8 and Appendix 9. Mean food consumption, evaluated as g/animal/day and g/kg/day, in the 1.0 mg/kg/day group F0 females was slightly lower than the control group values during lactation days 1-4. A corresponding slight reduction in mean body weight gain was noted in these females during lactation days 1-4 (see Section 6.2.4.1). Mean food consumption in the 1.0 mg/kg/day group were similar to the control group values during the remainder of WIL-180017 -65- 3M Corporation MTDID 208 06-128 lactation. None of the differences in food consumption at 1.0 mg/kg/day were statistically significant from the control group during the lactation period. Mean food consumption in the 0.1 and 0.3 mg/kg/day groups was unaffected by test article administration during lactation. Differences from the control group were slight and not statistically significant. 6.2.5 Gestation Length and Parturition Gestation length data are summarized in Table 12. Individual animal data are tabulated in Appendix 10. Historical Control Data are presented in Appendix 61. No test article-related effects were noted on mean gestation lengths or the process of parturition at any dosage level. The mean gestation lengths in the 0.1, 0.3 and 1.0 mg/kg/day groups were 21.7, 21.7 and 21.8 days, respectively, compared to mean gestation lengths of 21.9 days in the concurrent control group and 21.9 days in the WIL historical control data. Differences from the concurrent control group were slight and not statistically significant. No signs of dystocia were noted at any dosage level. 6.2.6 F0 Macroscopic Examinations F0 macroscopic examination data are summarized in Table 13, Table 14 and Table 15. Individual animal data are tabulated in Appendix 11, Appendix 12 and Appendix 13. Historical Control Data are presented in Appendix 61. No test article-related internal findings were observed for females that failed to deliver or for females necropsied on lactation day 21 at any dosage level. Macroscopic findings observed in the test article-treated groups occurred infrequently, at similar frequencies in the control group and/or in a manner that was not dose-related. WIL-180017 -66- 3M Corporation MTDID 208 06-128 At the lactation day 21 necropsy, no test article-related effects were observed on the number of former implantation sites and the number of unaccounted-for sites. The differences between the control and test article-treated groups were slight and not statistically significant. 6.3 F1 Litter Data 6.3.1 PND 0 Litter Data And Postnatal Survival Litter data on PND 0 and postnatal survival data are summarized in Table 16 and Table 17. Individual animal data are tabulated in Appendix 14 and Appendix 15. Historical Control Data are presented in Appendix 61. The mean number of pups born, live litter size, percentage of males per litter at birth and postnatal survival between birth and PND 0 (relative to number born), PND 0-1, 1-4 (pre-selection), 4 (post-selection)-7, 7-14, 14-21, and from birth to PND 4 (pre-selection) and PND 4 (post-selection) to PND 21 were unaffected by F0 maternal administration of the test article at all dosage levels. Differences from the control group were slight, not statistically significant and/or did not occur in a dose-related manner. 6.3.2 General Physical Condition And Mortalities Clinical observations are summarized in Table 18. Individual animal observations are tabulated in Appendix 16. The numbers of F1 pups found dead and/or missing, as well as the general physical condition of all F1 pups in this study, were unaffected by maternal test article administration. Pups that were found dead numbered 10, 5, 15 and 10 in the control, 0.1, 0.3 and 1.0 mg/kg/day groups, respectively. Five, 4, 1 and 5 pups in the same respective groups were missing and presumed to have been cannibalized. Small in size was noted for 1(1), 6(5), 2(2) and 7(3) pups (litters) in the control, 0.1, 0.3 and WIL-180017 -67- 3M Corporation MTDID 208 06-128 1.0 mg/kg/day groups, respectively. However, because there was no corresponding effect on pup body weights (see Section 6.3.3) and the finding was noted in a similar number of litters across all groups and generally in litters with 16 or more pups, the observation of small in size was not considered test article-related at any dosage level. An increased incidence of hair loss (primarily on the limbs) was noted in the 0.3 mg/kg/day group. This finding was not considered to be related to F0 maternal test article administration because it occurred primarily in 1 litter and was not noted at the 1.0 mg/kg/day dosage level. Other findings noted in the test article-treated groups occurred infrequently, at similar frequencies in the control group and/or in a manner that was not dose-related. 6.3.3 Offspring Body Weights - Pre-weaning Body weight and body weight change data during the pre-weaning period are summarized in Table 19, Table 20, Figure 3 and Figure 4. Individual animal data during the pre-weaning period are tabulated in Appendix 17 and Appendix 18. Historical Control Data are presented in Appendix 61. Mean pup body weights and body weight changes in the 0.1, 0.3 and 1.0 mg/kg/day group males and females were unaffected by administration of the test article to the F0 maternal animals. No statistically significant differences from the control group were noted. 6.3.4 Macroscopic Examinations - Pre-weaning 6.3.4.1 Offspring Found Dead Macroscopic examination data for found dead pups are summarized in Table 21. Individual animal data are tabulated in Appendix 19. The numbers of pups (litters) found dead from PND 0 through the selection of the F1 generation numbered 10(7), 5(3), 15(11) and 10(8) in the control, 0.1, 0.3 and 1.0 mg/kg/day groups, respectively. No internal WIL-180017 -68- 3M Corporation MTDID 208 06-128 findings that could be attributed to F0 maternal administration of the test article were noted at the necropsies of pups that were found dead. Aside from the presence or absence of milk in the stomach, internal findings included renal papilla not developed in pup no. 25753-13 in the 0.1 mg/kg/day group and malformations consisting of mandibular micrognathia and situs inversus in pup no. 25658-01 in the 1.0 mg/kg/day group. No other internal findings were noted. 6.3.4.2 Offspring Not Selected For Behavioral Evaluations Or Brain Weight Measurements (PND 21) Macroscopic examination data for pups not selected for behavioral evaluations or brain weight measurements on PND 21 are summarized in Table 22. Individual animal data are tabulated in Appendix 20. At the PND 21 necropsies on F1 animals not selected for behavioral evaluations or brain weights, no internal gross findings were observed in the control, 0.1, 0.3 and 1.0 mg/kg/day groups. 6.4 Developmental Landmarks 6.4.1 Balanopreputial Separation - Subset A Balanopreputial separation data are summarized in Table 23. Individual animal data are tabulated in Appendix 21. Historical Control Data are presented in Appendix 61. Mean ages of attainment of balanopreputial separation and mean body weights at the age of attainment were unaffected by administration of the test article to the F0 maternal animals. The mean ages of attainment of balanopreputial separation were 47.0, 45.8 and 45.8 days in the 0.1, 0.3 and 1.0 mg/kg/day groups, respectively, compared to 46.2 days in the control group. Mean body weights (grams) at the age of attainment were 268.2, 252.6 and 243.5 g in the same respective groups compared to 248.1 g in the control WIL-180017 -69- 3M Corporation MTDID 208 06-128 group. Mean body weight at the age of attainment in the 0.1 mg/kg/day group was statistically significantly increased (p<0.05) compared to the concurrent control group. This increase was not considered to be related to F0 maternal test article administration due to the lack of a dose-response. None of the other differences from the control group were statistically significant. 6.4.2 Vaginal Patency - Subset A Vaginal patency data are summarized in Table 24. Individual animal data are tabulated in Appendix 22. Historical Control Data are presented in Appendix 61. Mean ages of attainment of vaginal patency and mean body weights at the age of attainment were unaffected by administration of the test article to the F0 maternal animals. The mean ages of attainment of vaginal patency were 32.7, 32.0 and 32.3 days in the 0.1, 0.3 and 1.0 mg/kg/day groups, respectively, compared to 31.7 days in the control group. Mean body weights (grams) at the age of attainment were 118.6, 110.6 and 110.4 g in the same respective groups compared to 105.8 g in the control group. Mean body weight at the age of attainment in the 0.1 mg/kg/day group was statistically significantly increased (p<0.01) compared to the concurrent control group. This increase was not considered to be related to F0 maternal test article administration due to the lack of a dose-response. None of the other differences from the control group were statistically significant. 6.5 F1 Generation 6.5.1 Clinical Observations and Survival Clinical observations are summarized in Table 25. Individual animal observations are tabulated in Appendix 23. All F1 males and females in the control, 0.1, 0.3 and 1.0 mg/kg/day groups survived to the scheduled necropsy. No test article-related clinical WIL-180017 -70- 3M Corporation MTDID 208 06-128 findings were noted at the daily examinations. Findings noted in the test article-treated groups, including hair loss and scabbing on various body surfaces, occurred infrequently, at similar frequencies in the control group and/or in a manner that was not dose-related. 6.5.2 Offspring Body Weights - Post-weaning Body weight and body weight change data during the post-weaning period are summarized in Table 26, Table 27, Figure 5 and Figure 6. Individual animal data during the post-weaning period are tabulated in Appendix 24 and Appendix 25. Mean body weights and body weight gains in the F1 males and females were unaffected by administration of the test article to the F0 maternal animals. Differences between the control, 0.1, 0.3 and 1.0 mg/kg/day groups were slight and not statistically significant, with the following exception. A statistically significant (p<0.05) higher mean body weight gain was noted in the 0.1 mg/kg/day group males during PND 56-63 compared to the control group. The increase was transient, not observed in a dose-related manner and therefore, not considered test article-related. 6.5.3 Sensory Function And Behavioral Testing 6.5.3.1 Functional Observational Battery - Subset A Functional observational battery data are summarized in Table 28, Table 29, Figure 7, Figure 8, Figure 9 and Figure 10. Individual animal data are tabulated in Appendix 26 and Appendix 27. The endpoints presented in Table 28 and Appendix 26 include handling observations, while Table 29 and Appendix 27 include open field observations. Positive Control Data are presented in Appendix 62. Historical Control Data are presented in Appendix 63. There were no test article-related findings noted for the F1 males or females during the functional observational battery assessments on PND 4, 11, WIL-180017 -71- 3M Corporation MTDID 208 06-128 21, 35, 45 and 60. A statistically significant (p<0.05) decrease in hindlimb grip strength was noted in the 1.0 mg/kg/day group males (66.7 g) compared to the control group (79.8 g) on PND 21. However, the mean value in the 1.0 mg/kg/day group was similar to the mean value in the WIL historical control data (70 26 g), the magnitude of difference (16%) from the control group was small and there was an absence of effects on forelimb grip strength, hindlimb extensor strength, gait, mobility and muscle tone in either sex at all other ages of testing. Therefore, this decrease in hindlimb grip strength was not attributed to F0 maternal test article administration. Other differences from the control group were slight, not statistically significant and/or not observed in a dose-related manner. 6.5.3.2 Locomotor Activity - Subset A Locomotor activity data are summarized in Table 30, Figure 11, Figure 12, Figure 13, Figure 14, Figure 15, Figure 16, Figure 17, Figure 18, Figure 19, Figure 20, Figure 21, Figure 22, Figure 23, Figure 24, Figure 25, Figure 26, Figure 27, Figure 28, Figure 29, Figure 30, Figure 31, Figure 32, Figure 33 and Figure 34. Individual animal data are tabulated in Appendix 28. The Statistical Analysis Report is presented in Appendix 60. Positive Control Data are presented in Appendix 62. Historical Control Data are presented in Appendix 64. All test article-treated groups displayed the expected developmental activity pattern during the pre-weaning period, that is, an "inverted U-shaped pattern", with low levels of activity on PND 13, highest levels of activity on PND 17, and somewhat lower levels on PND 21. On PND 17, total and ambulatory activity during 3 of the 4 session intervals (16-30 minutes, 31-45 minutes and 46-60 minutes) and during the overall 60-minute test session were increased in the 1.0 mg/kg/day group F1 males compared to the concurrent control group; the increases in total activity were statistically significant (p0.030). In addition, 8 males in the 1.0 mg/kg/day group had higher total activity counts during the WIL-180017 -72- 3M Corporation MTDID 208 06-128 46-60 minutes interval than the 0-15 minutes interval, indicating an absence of habituation to the test environment on PND 17 (an age when animals should begin to show habituation), compared to no males in the concurrent control group. As a result, cumulative total activity in these males was 58.0% higher than the concurrent control group. Because the males in the 1.0 mg/kg/day group failed to habituate, the increased motor activity in these males on PND 17 was considered test article-related. Total and ambulatory activity and habituation to the test environment in the 1.0 mg/kg/day group F1 females were generally similar to the concurrent control group on PND 17. There were no test article-related effects on total and ambulatory activity or on habituation patterns in the 1.0 mg/kg/day group males and females on PND 13, 21 or 61. A statistically significant (p=0.027) increase in total activity was noted in the 1.0 mg/kg/day group females during the overall 60-minute test session on PND 21. Because habituation to the test environment in these females was similar to the concurrent control group on PND 21 and no other differences from the concurrent control group in total and ambulatory activity were noted in these females on PND 13, 17, 21 or 61, the increased motor activity noted in the 1.0 mg/kg/day group females on PND 21 was not considered test article-related. Other differences from the control group were slight or within the WIL historical control data ranges. Total and ambulatory activity during the 4 session intervals and during the overall 60-minute test session were increased in the 0.3 mg/kg/day group F1 males compared to the concurrent control group on PND 17; the increases in total activity during the 16-30 minute session interval and during the overall 60-minute test session were statistically significant (p0.031). However, habituation to the test environment in these males was similar to the concurrent control group on PND 17. In addition, no other differences from the concurrent control group in total and ambulatory activity or on habituation patterns were noted in the F1 males and females in the 0.3 mg/kg/day group on PND 13, 17, 21 or 61. Therefore the increased motor activity noted in the 0.3 mg/kg/day group males on PND 17 was not considered test article-related. WIL-180017 -73- 3M Corporation MTDID 208 06-128 Locomotor activity patterns (total activity as well as ambulatory activity counts) in F1 animals in the 0.1 mg/kg/day group were unaffected by F0 maternal test article administration when evaluated on PND 13, 17, 21 and 61. Patterns of habituation in the 0.1 mg/kg/day groups were similar to those in the concurrent control group when the F1 animals were evaluated at PND 13, 17, 21 and 61. Values obtained from the 4 epochs evaluated (0-15 minutes, 16-30 minutes, 31-45 minutes and 46-60 minutes) and the overall 60-minute test session values were comparable to the concurrent control values and the WIL historical control data, with the following exception. A statistically significant (p<0.05) increase in ambulatory motor activity counts was noted in the 0.1 mg/kg/day group females on PND 13, compared to the concurrent control group. This difference was not considered test article-related because it did not occur in a dose-related manner. 6.5.3.3 Acoustic Startle Response- Subset A Acoustic startle response data are summarized in Table 31, Figure 35, Figure 36, Figure 37, Figure 38, Figure 39, Figure 40, Figure 41 and Figure 42. Individual animal data are tabulated in Appendix 29. The Statistical Analysis Report is presented in Appendix 60. Positive Control Data are presented in Appendix 62. Historical Control Data are presented in Appendix 65. The acoustic startle response habituation paradigm was conducted as a longitudinal assessment with selected F1 animals evaluated on PND 20 and again on PND 60. Administration of 0.1, 0.3 and 1.0 mg/kg/day MTDID 208 to the F0 maternal animals had no effect on auditory startle responsiveness. Mean VMAX for all trials combined in the control group males on PND 60 was at least 26% higher than the values in all MTDID 208 groups. These higher mean control values were attributed to 2 males in this group (nos. 25638-07 and 25645-06) with substantially higher values (659.1 and 778.2 millivolts, respectively) compared to the overall control group mean (173.9 millivolts). Therefore, the lower VMAX values in the 0.1, 0.3 and WIL-180017 -74- 3M Corporation MTDID 208 06-128 1.0 mg/kg/day group males on PND 60 were not attributed to maternal MTDID 208 treatment. No statistically significant differences from the control group were noted when analyzed by a repeated measures analysis. No effects were noted in the pattern of the habituation response over the entire 50-block test session in adult animals. 6.5.3.4 Biel Maze Swimming Trials - Subset A Biel maze swimming trial data are summarized in Table 32, Table 33, Figure 43, Figure 44, Figure 45 and Figure 46. Individual animal data are tabulated in Appendix 30 and Appendix 31. The Statistical Analysis Report is presented in Appendix 60. Positive Control Data are presented in Appendix 62. Historical Control Data are presented in Appendix 66. There were no biologically meaningful trends in swimming ability on day 1 or for the times to criterion (mean time to locate the submerged platform) during the learning and memory trials between the MTDID 208-treated F1 male and female pups and the vehicle-treated F1 male and female pups at PND 22. The mean numbers of errors committed during the various phases of evaluation were similar in all MTDID 208-treated test groups and the control group. 6.5.4 Macroscopic Examinations - Post-weaning (Not Selected For Brain Weight Measurements on PND 72) Macroscopic examination data for F1 animals not selected for brain weights on PND 72 are summarized in Table 34. Individual animal data are tabulated in Appendix 32. At the PND 72 necropsies on F1 animals not selected for brain weights, no internal gross findings related to F0 maternal administration to the test article were observed. Internal findings included dilated renal pelvis (unilateral or bilateral) in 1 female, 1 female and 2 males and 2 males in the control, 0.1 and 1.0 mg/kg/day groups, respectively, clear fluid in the uterus in 1 female in each of the control and 1.0 mg/kg/day groups, opacity of WIL-180017 -75- 3M Corporation MTDID 208 06-128 the eyes in 1 male in the 1.0 mg/kg/day group and dark red areas on the thymus of 1 female in the control group. No other internal findings were noted. 6.6 Animals Selected For Perfusion And Brain Weight Measurements 6.6.1 PND 21 6.6.1.1 Macroscopic Examinations Macroscopic examination data for F1 pups selected for perfusion and brain weight measurements on PND 21 are summarized in Table 35. Individual animal data are tabulated in Appendix 33. The pathology report is presented in Appendix 57. At the necropsies of F1 animals selected for brain weights on PND 21, no gross findings were noted in the brain or spinal cord. 6.6.1.2 Brain Weights/Brain Measurements Brain weight and measurement data for PND 21 pups are summarized in Table 36 and Table 37. Individual animal data are tabulated in Appendix 34 and Appendix 35. The pathology report is presented in Appendix 57. There were no test article-related effects on brain weight, length or width in the F1 animals selected for brain weights on PND 21. Differences from the control group were slight, not statistically significant and/or not observed in a dose-related manner. WIL-180017 -76- 3M Corporation 6.6.2 PND 72 MTDID 208 06-128 6.6.2.1 Macroscopic Examinations Macroscopic examination data for F1 animals selected for perfusion and brain weight measurements on PND 72 are summarized in Table 38. Individual animal data are tabulated in Appendix 36. The pathology report is presented in Appendix 57. At the PND 72 necropsies on F1 animals selected for brain weights, no internal gross findings related to F0 maternal administration of the test article were observed. Internal findings on the brain and spinal cord were limited to a brain cyst in 1 male in the control group. 6.6.2.2 Brain Weights/Brain Measurements Brain weight and measurement data for PND 72 animals are summarized in Table 39 and Table 40. Individual animal data are tabulated in Appendix 37 and Appendix 38. The pathology report is presented in Appendix 57. There were no test article-related effects on brain weight, length or width in the F1 animals selected for brain weights on PND 72. Differences from the control group were slight, not statistically significant and/or not observed in a dose-related manner. 6.7 Thyroid Function Assessment 6.7.1 Thyroid Stimulating Hormone Thyroid stimulating hormone data for F0 maternal animals and F1 fetuses and pups are summarized in Table 41, Table 42, Table 43, Table 44 and Table 45. Individual animal data are tabulated in Appendix 39, Appendix 40, Appendix 41, Appendix 42, Appendix 43 and Appendix 44. The Pathology Report is presented in Appendix 57. WIL-180017 -77- 3M Corporation MTDID 208 06-128 On gestation day 20, TSH values of F0 dams and F1 fetuses (pooled males and females by litter) in the MTDID 208-treated groups at 0.1, 0.3 or 1.0 mg/kg/day were lower than control group values, but the difference did not achieve statistical significance. It was noted that the pattern of TSH values in fetuses paralleled the values in the dams, suggesting maternal influence on the fetal values. Initial evaluation of maternal lactation day 4 TSH concentrations revealed apparent non-dose-related lower TSH concentrations in all MTDID-treated groups relative to the control group. In addition, apparent non-dose-related higher TSH concentrations were observed in the F1 pups (pooled males and females by litter) in all MTDID-treated groups relative to the control group. Due to numerous discrepancies between the serum sample analysis list and the order of the sample tubes in the storage box, for the lactation day 4 and PND 4 samples, all lactation day 4 and PND 4 samples were reanalyzed for TSH concentration approximately 34 weeks following the initial analysis. For the reanalysis, the identity of the sample tubes was verified by a second individual. In addition, because the samples were stored frozen for longer than the previously established 6-month frozen stability, 5 serum samples from control group females on lactation day 21 were reanalyzed to assess stability. Although the mean reanalyzed concentration of the lactation day 21 control group samples was only 61.1% 8.5% of the initial results, the decrease was consistent from sample to sample. Because of the consistency of the decrease of TSH concentration in the reanalyzed lactation day 21 control samples, the reanalyzed concentrations of the lactation day/PND 4 samples (when a second individual verified the identity of the sample tubes) were reported. The reanalyzed F0 dam and F1 pup TSH concentrations in the MTDID 208 groups were similar to the control group, indicating no test article-related effect on lactation day 4 F0 dam and PND 4 F1 pup TSH concentrations. TSH values of F0 dams that received MTDID 208 at 0.1, 0.3 or 1.0 mg/kg/day were equivalent to control group values on lactation day 21. TSH values of F1 male pups in WIL-180017 -78- 3M Corporation MTDID 208 06-128 the MTDID 208-treated groups on PND 21 were slightly higher than control group values, but the higher values did not occur in a dose-related manner and the differences did not achieve statistical significance. TSH values of F1 female pups in the MTDID 208-treated groups on PND 21 were equivalent to control group values. The data suggested no unequivocal test article-related effect on TSH values in F0 dams or F1 pups on lactation day/PND 21. 6.7.2 Thyroid Histopathology Thyroid histopathology data for F1 fetuses and pups are summarized in Table 46, Table 47 and Table 48. Individual animal data are tabulated in Appendix 45, Appendix 46 and Appendix 47. The Pathology Report is presented in Appendix 57. There were no test article-related histologic changes in the routinely stained sections of thyroids from GD 20 fetuses, PND 4 pups or PND 21 pups. All histologic changes in the thyroid glands were considered to be incidental findings or related to some aspect of experimental manipulation other than administration of the test article. There was no test article-related alteration in the incidence, severity or histologic character of those incidental and spontaneous tissue alterations. 6.7.3 Thyroid Morphometry Thyroid morphometry data for F1 fetuses and pups are summarized in Table 49 and Table 50. Individual animal data are tabulated in Appendix 48 and Appendix 49. The Pathology Report is presented in Appendix 57. Mean thyroid follicular epithelial cell height of male pups from the 1.0 mg/kg/day group was significantly (p<0.01, Dunnett's test) higher (11%) than that of the control group on PND 21 but not on PND 4, as summarized in Text Tables 8 and 9. This difference was suspected to be spurious due to the extraordinarily low value in the concurrent control group compared to other groups on PND 21 in this study. Mean thyroid follicular colloid area of male and female pups WIL-180017 -79- 3M Corporation MTDID 208 06-128 from the 1.0 mg/kg/day group was similar to that of control group on PND 4 and 21, as summarized in Text Tables 10 and 11. TT 8. Thyroid Follicular Epithelial Cell Height, PND 4 Males Dosage (mg/kg/day) 0 0.1 0.3 Thyroid a 10 0 0 Mean epithelial cell height b 5.49 - - Standard deviation 0.260 - - a = Number of tissues examined from each group. b = micrometers 1.0 10 5.36 0.431 0 10 5.68 0.360 Females 0.1 0.3 0 0 - - - - 1.0 8 5.84 0.304 TT 9. Thyroid Follicular Epithelial Cell Height, PND 21 Males Dosage (mg/kg/day) 0 0.1 0.3 1.0 Thyroid a 10 0 0 10 Mean epithelial cell height b 5.68 - - 6.29** Standard deviation 0.536 - - 0.324 a = Number of tissues examined from each group. b = micrometers ** = Statistically significant at p<0.01 (Dunnett's test) 0 10 6.28 0.450 Females 0.1 0.3 0 0 - - - - 1.0 10 6.38 0.598 WIL-180017 -80- 3M Corporation MTDID 208 06-128 TT 10. Thyroid Follicular Colloid Area, PND 4 Males Dosage (mg/kg/day) 0 0.1 0.3 Thyroid a 10 0 0 Mean follicle area b 1841 - - Standard deviation 318.1 - - a = Number of tissues examined from each group. b = micrometers 1.0 10 1533 368.7 0 10 2181 442.9 Females 0.1 0.3 0 0 - - - - 1.0 8 1969 555.1 TT 11. Thyroid Follicular Colloid Area, PND 21 Males Dosage (mg/kg/day) 0 0.1 0.3 Thyroid a 10 00 Mean follicle area b 7768 - - Standard deviation 1641.1 - - a = Number of tissues examined from each group. b = micrometers 1.0 10 7267 1117.8 0 10 7220 1288.6 Females 0.1 0.3 0 0 - - - - 1.0 10 7677 1857.8 6.8 Toxicokinetics and rtPCR The Toxicokinetic Report and rtPCR Results are presented in Appendix 54 and Appendix 58, respectively. Test article concentrations in the serum and/or liver of F0 dams and F1 fetuses and pups in the 0.1, 0.3 and 1.0 mg/kg/day groups were in approximately linear proportion to dosage level on each day of evaluation (gestation day 20, lactation day/PND 4, lactation day/PND 21 and/or PND 72). For F0 dams, test article concentrations in the serum were generally higher (1.1- to 1.9-fold) at all dosage levels during lactation than on gestation day 20, with values on lactation day 4 similar to those on lactation day 21. Additionally, concentrations in the liver of F0 dams in all test WIL-180017 -81- 3M Corporation MTDID 208 06-128 article-treated groups were higher (approximately 1.8- to 4.8-fold) than concentrations in the serum on gestation day 20. In contrast, test article concentrations in the serum of F1 fetuses and pups were generally higher (1.4- to 2.6-fold) at all maternal dosage levels on gestation day 20 than during the pre-weaning period, with values on PND 4 slightly higher than those on PND 21. Test article concentrations in the serum of F1 pups in the 0.1, 0.3 and 1.0 mg/kg/day groups were markedly lower (88% to 98%) on PND 72 compared to PND 4 (combined by sex) and 21. When analyzed by sex, concentrations for female pups were higher (3.6- to 4.9-fold) than those for male pups on PND 72 at all maternal dosage levels, while concentrations on PND 21 were similar between male and female pups. Test article concentrations in the liver of F1 fetuses and pups did not show all of the same temporal and sex-specific patterns as serum concentrations. Specifically, test article concentrations in the liver were generally higher (1.6- to 3.5-fold) at all maternal dosage levels during the pre-weaning period than on gestation day 20, with values on PND 4 greater than those on PND 21. Additionally, test article concentrations in the liver of pups in the 0.1, 0.3 and 1.0 mg/kg/day groups on PND 21 and 72 were similar between male and female pups. However, analogous to concentrations in the serum, concentrations in the liver for pups in the same groups were markedly lower (83% to 92%) on PND 72 than on PND 4 (combined by sex) and 21. In general, test article concentrations in the liver of pups from all test article-treated groups were higher than concentrations in the serum, with the exception of those on gestation day 20; the gestation day 20 concentrations in the liver of the fetuses from these groups were similar to (at 0.1 mg/kg/day) or lower than (at 0.3 and 1.0 mg/kg/day) the serum concentrations on this day. When F0 dams were compared to F1 fetuses and pups, serum concentrations for dams in all test article-treated groups were lower than the fetal concentrations on gestation day 20 WIL-180017 -82- 3M Corporation MTDID 208 06-128 and were higher than pup concentrations on lactation days/PND 4 and 21. In addition, liver concentrations for dams in all test article-treated groups were markedly higher than those for fetuses on gestation day 20. Differences in transcript levels in liver tissue from F0 dams on gestation day 20 and F1 male pups on PND 21 were observed when the 1.0 mg/kg/day group was compared to the control group. Mean Cyp2b2 levels for dams and male pups in this group were higher (p<0.05) than the control group values on gestation day 20 and PND 21, respectively. Additionally, on PND 21, mean AcylCoA and Cyp4a1 levels for male pups in the 1.0 mg/kg/day group were higher (p<0.05) than the control group, while the mean Cyp7a1 level was lower (p<0.05) than the control group. There were no other statistically significant differences in transcript levels for dams on gestation day 20 or male pups on PND 21, and no statistically significant differences were observed for fetuses on gestation day 20. The rtPCR results are summarized in Text Table 12. WIL-180017 -83- 3M Corporation MTDID 208 06-128 TT 12. rtPCR Results For F0 Dams And F1 Fetuses On Gestation Day 20 And F1 Male Pups On PND 21 Transcript Group 4 AcylCoA -- PCNA -- Malic Enzyme -- Dio1 -- Por -- ApoA1 -- Cyp1a1 -- Cyp3a1 -- Cyp4a1 -- Cyp7a1 -- Cyp2b2 Ugt1A common -- Ugt1a1 -- Ugt1a6 -- Ugt2b -- Group 4 = 1.0 mg/kg/day Gestation Dam Day 20 Group 4 ---------------- Fetus PND 21 Group 4 Male Pup ------- ----- -- = Not significantly different from the control group at 95% confidence interval. = Significantly higher than the control group at 95% confidence interval. = Significantly lower than the control group at 95% confidence interval. 6.9 Thyroid Cell Proliferation Assay Thyroid cell proliferation assay data for F1 fetuses are summarized in Table 51. Individual animal data are tabulated in Appendix 50. The Pathology Report is presented in Appendix 57. The mean number of Ki-67-positive thyroid follicular epithelial cells in female fetuses from the 1.0 mg/kg/day group was significantly (p<0.05) higher (2.1-fold) than that of the control group on gestation day 20, as summarized in Text Table 13. However, the level of variability observed in this assay and the limited number of samples hindered the interpretation of the toxicologic significance of the observation. WIL-180017 -84- 3M Corporation MTDID 208 06-128 TT 13. Ki-67-Positive Follicular Epithelial Cells in Thyroid Gland, Gestation Day 20 Males Females Dosage (mg/kg/day) 0 0.1 0.3 1.0 0 0.1 0.3 1.0 Thyroid a 6 0 0 6 7 0 0 5 Ki-67-positive cells b 40 - - 32 42 - - 88* Standard deviation 23.9 - - 25.3 35.5 - - 18.6 a = Number of tissues examined from each group. b = Mean number of Ki-67-positive cells in 3 each 400X microscopic fields * = Statistically significant at p<0.05 (Dunnett's test) 7 Discussion The objective of this study was to determine the potential of the test article, MTDID 208, to induce functional and morphological insult to the nervous system which may arise in the offspring from exposure of the mother during pregnancy and lactation. Additional objectives of this study were to determine the effects of maternal exposure to the test article on maternal and neonatal thyroid status and to establish toxicokinetic data for different compartments in the dam and offspring. Oral administration of MTDID 208 at dosage levels of 0.1, 0.3 and 1.0 mg/kg/day to F0 maternal animals resulted in a test article-related effect on motor activity in the 1.0 mg/kg/day group F1 males on PND 17. Total and ambulatory activity counts in these males were increased (generally statistically significant; p0.030) compared to the concurrent control group, and a majority of these males failed to habituate to the test environment on PND 17 (an age when rats should begin to habituate), while all control group males showed some indication of habituation. There were no other test article-related effects on motor activity in either sex at any dosage level on PND 13, 17, 21 or 61. There were no test article-related effects on functional observational battery WIL-180017 -85- 3M Corporation MTDID 208 06-128 parameters, startle responsiveness, swimming ability, learning and memory or the attainment of sexual developmental landmarks (mean age and weight at attainment of balanopreputial separation or vaginal patency) at any dosage level. F0 maternal test article administration did not result in any clinical findings in F1 males or females during the pre- or post-weaning periods and did not affect pre- or post-weaning survival, body weights and body weight gains in the F1 animals. There were no test article-related internal findings or effects on brain weight, length or width at any dosage level. The results of the current study are in contrast to a previous study in which administration of PFOS to dams at dosage levels of 0.4 mg/kg/day or higher from 6 weeks prior to mating through lactation day 4 resulted in decreases in pup body weights and postnatal survival [1]. Oral administration of MTDID 208 at dosage levels of 0.1, 0.3 and 1.0 mg/kg/day to F0 maternal animals did not adversely affect the survival of the F0 maternal animals. No MTDID 208-related clinical or internal findings were observed for the F0 females at any dosage level. The mean length of gestation, the process of parturition, the number of former implantation sites and unaccounted-for sites, viable litter size, and pup sex ratio in MTDID 208-treated rats were comparable to the values in control animals. Mean body weight gains in the 1.0 mg/kg/day group F0 females during gestation were slightly lower (not statistically significant) than the control group values during gestation days 0-15. In addition, a slightly lower (not statistically significant) mean body weight gain was noted in the 1.0 mg/kg/day group F0 females during lactation days 1-4. Corresponding effects on food consumption were noted in the 1.0 mg/kg/day group F0 females during gestation days 6-9 and 9-12 and lactation days 1-4. As a result of the effects on body weight gains and food consumption, mean body weights in the 1.0 mg/kg/day group F0 females were generally 3.8% to 5.7% lower (p<0.05 or p<0.01) than the control group values during lactation days 4 through 21. WIL-180017 -86- 3M Corporation MTDID 208 06-128 This study revealed no evidence of test article-related alterations in TSH values for F0 maternal animals, F1 fetuses and F1 pups or any histologic alterations that were visible in routinely stained sections for F1 fetuses and F1 pups. Morphometric analysis revealed higher mean thyroid follicular epithelial cell height in male pups from the 1.0 mg/kg/day group on PND 21, but this was suspected to be a spurious observation that was related to an extraordinarily low value in the concurrent control group compared to the other groups in this study. The number of Ki-67-positive proliferative cells in thyroid glands of female fetuses from the 1.0 mg/kg/day group was higher than control group values on gestation day 20, but the level of variability observed in this assay and the limited number of samples hindered an interpretation of the toxicologic significance of the observation. Therefore, the assays performed in this study revealed no unequivocal evidence of a test article-related effect on structure or function of the thyroid gland. Test article concentrations in the serum and/or liver of F0 dams and F1 fetuses and pups in the 0.1, 0.3 and 1.0 mg/kg/day groups were in approximately linear proportion to dosage level on each evaluation day (gestation day 20, lactation day/PND 4, lactation day/PND 21 and/or PND 72). For F0 dams, test article concentrations in the serum were generally higher at all dosage levels during lactation than on gestation day 20, while serum concentrations for F1 fetuses/pups were generally higher at all maternal dosage levels on gestation day 20 than during the pre-weaning period. Test article concentrations in the liver of the F1 fetuses/pups were generally higher at all maternal dosage levels during the pre-weaning period than on gestation day 20 and PND 72. Additionally, test article concentrations in the liver of F0 dams and/or F1 pups in all test article-treated groups were higher than concentrations in the serum on gestation day 20 (dams only) and PND 4, 21 and 72 (pups only), and the gestation day 20 concentrations in the liver of the fetuses from these groups were lower than the serum concentrations. The lowest test article concentrations in both the serum and liver of the F1 generation occurred on PND 72, and the only sex-specific differences were noted for serum concentrations on PND 72, with females having higher values. When F0 dams were WIL-180017 -87- 3M Corporation MTDID 208 06-128 compared to F1 fetuses and pups, serum concentrations for dams in all test article-treated groups were lower than the fetal concentrations on gestation day 20 and were higher than pup concentrations on lactation days/PND 4 and 21. In addition, liver concentrations for dams in all test article-treated groups were markedly higher than those for fetuses on gestation day 20. Differences in transcript levels between the control and 1.0 mg/kg/day groups were limited to higher mean Cyp2b2 levels for dams on gestation day 20 and male pups on PND 21, higher mean AcylCoA and Cyp4a1 levels for male pups on PND 21 and a lower Cyp7a1 level for male pups on PND 21. These differences were statistically significant. 8 Conclusions Based on the slightly lower maternal body weight gains and food consumption following oral administration of MTDID 208 at a dosage level of 1.0 mg/kg/day to Crl:CD(SD) rats from gestation day 0 through lactation day 20, the no-observed-adverse-effect-level (NOAEL) for maternal toxicity was considered to be 0.3 mg/kg/day. There was no unequivocal evidence of a test article-related effect on maternal thyroid status or effects on postnatal growth, survival or neonatal thyroid status. The NOAEL for F1 developmental neurotoxicity was considered to be 0.3 mg/kg/day based on increased motor activity and a failure to habituate to the test environment noted in the 1.0 mg/kg/day group F1 males on PND 17. WIL- 180017 -88- 3M Corporation MTDID 208 06-128 9 Key Study Personnel and Report Submission Report Submitted By: Donald G. Stump, PhD, DABT " Associate Director, Developmental and Reproductive Toxicology Study Director Report Prepared By: Senior Study Analyst ILc.c&! Kristin M. Roll, MS Study Analyst Report Reviewed By: Melissa J. Beck, PhD Assistant Director, Neurosciences Ak-- \h D. Nemec, BS, DABT Director, Developmental and Reproductive Toxicology M Date \oT&n. Date WIL- 180017 -89- 3M Corporation MTDID 208 06-128 Key Study Personnel and Report Submission (continued) 1 0 , 3 m (3008 Date -- Evelyn Tankhevski, BS Group Supervisor, Study Analysis and Reports iohkdmY Date WIL-180017 -90- 3M Corporation MTDID 208 06-128 10 Quality Assurance Unit Statement 10.1 Phases Inspected Date(s) of Inspection(s) 08-May-2006, 09-May-2006 Phase Inspected Test Article Preparation/ Administration Date(s) Findings Reported to Study Director 09-May-2006 Date(s) Findings Reported to Management 26-Jun-2006 18-May-2006 22-May-2006 08-Jun-2006 Animal Care & Equipment Blood Collection Functional Observational Battery 18-May-2006 22-May-2006 08-Jun-2006 26-Jun-2006 26-Jun-2006 25-Jul-2006 12-Jun-2006 Embedding of Tissues 12-Jun-2006 25-Jul-2006 13-Jun-2006 Necropsy (Perfusions) 13-Jun-2006 25-Jul-2006 25-Sep-2006 25-Sep-2006 26-Sep-2006 07-Nov-2006 07-Nov-2006, 08-Nov-2006 08-Nov-2006 08-Nov-2006 20-Nov-2006, 21-Nov-2006 21-Nov-2006 21-Nov-2006 Study Records (I-8) Study Records (I-13) Study Records (I-7) Study Records (I-1) Study Records (I-3) Study Records (I-6) Study Records (I-5) Study Records (I-4) Study Records (I-10) Study Records (I-15) 25-Sep-2006 25-Sep-2006 26-Sep-2006 07-Nov-2006 08-Nov-2006 08-Nov-2006 08-Nov-2006 21-Nov-2006 21-Nov-2006 21-Nov-2006 18-Oct-2006 18-Oct-2006 18-Oct-2006 20-Dec-2006 20-Dec-2006 20-Dec-2006 20-Dec-2006 20-Dec-2006 20-Dec-2006 20-Dec-2006 Auditor(s) N. Daniels; K. Dobbs K. Dobbs K. Dobbs A. Kinney; A. Deppe K. Dobbs; T. DeVan Booth K. Mentzer; J. Murawski J. Murawski J. Murawski J. Murawski J .Murawski J. Murawski J. Murawski J. Murawski J. Murawski J. Murawski J. Murawski WIL-180017 -91- 3M Corporation MTDID 208 06-128 Date(s) of Inspection(s) 27-Nov-2006 28-Nov-2006 29-Nov-2006 01-Dec-2006, 04-Dec-2006 04-Dec-2006 04-Dec-2006 06-Dec-2006 07-Dec-2006 07-Dec-2006 11-Dec-2006, 12-Dec-2006, 13-Dec-2006, 14-Dec-2006, 15-Dec-2006, 18-Dec-2006, 22-Dec-2006, 08-Jan-2007, 09-Jan-2007, 10-Jan-2007, 11-Jan-2007, 15-Jan-2007, 16-Jan-2007, 17-Jan-2007, 18-Jan-2007, 19-Jan-2007, 22-Jan-2007 21-Apr-2007 21-Apr-2007 21-Apr-2007 22-Apr-2007, 23-Apr-2007 23-Apr-2007 25-Apr-2007 Phase Inspected Study Records (I-2, I-9 and I-14) Study Records (I-11) Study Records (Rx-1) Study Records (N-1) Study Records (N-2) Study Records (N-3) Study Records (C-1) Study Records (C-2) Study Records (I-12) Date(s) Findings Reported to Study Director Date(s) Findings Reported to Management 27-Nov-2006 28-Nov-2006 29-Nov-2006 04-Dec-2006 04-Dec-2006 04-Dec-2006 06-Dec-2006 07-Dec-2006 07-Dec-2006 20-Dec-2006 20-Dec-2006 20-Dec-2006 30-Jan-2007 30-Jan-2007 30-Jan-2007 30-Jan-2007 30-Jan-2007 30-Jan-2007 Draft Report (excluding Pathology Report Appendix) Study Records (H-1) Study Records (H-2) Study Records (H-3) Study Records (P-1) Study Records (C-2 Supplemental, Additional TSH Data Collection) Draft Report (Pathology Appendix) 22-Jan-2007 21-Apr-2007 21-Apr-2007 21-Apr-2007 23-Apr-2007 23-Apr-2007 25-Apr-2007 27-Feb-2007 24-May-2007 24-May-2007 24-May-2007 24-May-2007 24-May-2007 24-May-2007 Auditor(s) J. Murawski J. Murawski J. Murawski J. Murawski J. Murawski J. Murawski J. Murawski J. Murawski J. Murawski J. Murawski J.Murawski J.Murawski J.Murawski J.Murawski J.Murawski J.Murawski This study was inspected in accordance with the U.S. EPA Good Laboratory Practice (GLP) Standards (40 CFR 792), the standard operating procedures of WIL Research WIL-180017 -92- 3M Corporation MTDID 208 06-128 Laboratories, LLC and the sponsor's protocol and protocol amendments with the following exceptions. The data located in Appendix 53 (Certificate of Analysis) were the responsibility of Centre Analytical Laboratories, Inc. The data found in Appendix 54 (Analyses of Dosing Formulations And Toxicokinetics Report) and Appendix 58 (rtPCR Results) were the responsibility of the sponsor or the sponsor's designee and were conducted under non-GLP conditions. Quality Assurance findings, derived from the inspections during the conduct of the study and from the inspections of the raw data and draft report, are documented and have been reported to the study director. A status report is submitted to management monthly. This report accurately reflects the data generated during the study. The methods and procedures used in the study were those specified in the protocol, its amendments and the standard operating procedures of WIL Research Laboratories, LLC. The raw data, the retention sample and the final report will be stored in the Archives at WIL Research Laboratories, LLC or another location specified by the sponsor. WIL-180017 -93- 3M Corporation MTDID 208 06- 128 10.2 Approval This study was inspected according to the criteria discussed in Section 10.1. Report Audited BY: -3%4 Jessidh D. Murawski, BS, RQAP-GLP Senior Compliance Specialist RepohReleased By: ,," , 1 Manager, Qdlity Assurance WIL-180017 -94- 3M Corporation MTDID 208 06-128 11 References 1. Luebker, D.J.; York, R.G.; Hansen, K.J.; Moore, J.A.; Butenhoff, J.L. Neonatal mortality from in utero exposure to perfluorooctanesulfonate (PFOS) in Sprague-Dawley rats: Dose-response, and biochemical and pharmacokinetic parameters. Toxicology 2005, 215, 149-169. 2. Luebker, D.J.; Case, M.T.; York, R.G.; Moore, J.A.; Hansen, K.J.; Butenhoff, J.L. Two-generation reproduction and cross-foster studies of perfluorooctanesulfonate (PFOS) in rats. Toxicology 2005, 215, 126-148. 3. Lau, C.; Thibodeaux, J.R.; Hanson, R.G.; Rogers, J.M.; Grey, B.E.; Stanton, M.E.; Butenhoff, J.L.; Stevenson, L.A. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II: Postnatal Evaluation. Toxicological Sciences 2003, 74, 382-392. 4. National Research Council. Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, Commission on Life Sciences; National Academy Press: Washington, DC, 1996. 5. Salewski, E. Frbemethode zum makroskopischen Nachweis von Implantationsstellen am Uterus der Ratte. [Staining method for a macroscopic test for implantation sites in the uterus of the rat]. Naunyn - Schmiedebergs Archiv fr Experimentelle Pathologie und Pharmakologie 1964, 247, 367. 6. Stuckhardt, J.L.; Poppe, S.M. Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. Teratogenesis, Carcinogenesis and Mutagenesis 1984, 4, 181-188. 7. Korenbrot, C.C.; Huhtaniemi, I.T.; Weiner, R.I. Preputial separation as an external sign of pubertal development in the male rat. Biology of Reproduction 1977, 17, 298-303. 8. Adams, J.; Buelke-Sam, J.; Kimmel, C.A.; Nelson, C.J.; Reiter, L.W.; Sobotka, T.J.; Tilson, H.A.; Nelson, B.K. Collaborative behavioral teratology study: protocol design and testing procedure. Neurobehavioral Toxicology and Teratology 1985, 7, 579-586. WIL-180017 -95- 3M Corporation MTDID 208 06-128 9. Moser, V.C.; McDaniel, K.L.; Phillips, P.M. Rat strain and stock comparisons using a functional observational battery: baseline values and effects of amitraz. Toxicology and Applied Pharmacology 1991, 108(2), 267-283. 10. Irwin, S. Comprehensive observational assessment: Ia. a systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia 1968, 13, 222-257. 11. Gad, S.C. A neuromuscular screen for use in industrial toxicology. Journal of Toxicology and Environmental Health 1982, 9(5-6), 691-704. 12. Moser, V.C.; McCormick, J.P.; Creason, J.P.; MacPhail, R.C. Comparison of chlordimeform and carbaryl using a functional observational battery. Fundamental and Applied Toxicology 1988, 11(2), 189-206. 13. Haggerty, G.C. Development of tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies. Journal of the American College of Toxicology 1989, 8(1), 53-69. 14. O'Donoghue, J.L. Screening for neurotoxicity using a neurologically based examination and neuropathology. Journal of the American College of Toxicology 1989, 8(1), 97-115. 15. Biel, W.C. Early age differences in maze performance in the albino rat. Journal of Genetic Psychology 1940, 56, 439-453. 16. Snedecor, G.W.; Cochran, W.G. One Way Classifications; Analysis of Variance. In Statistical Methods, 7th ed.; The Iowa State University Press: Ames, IA, 1980; pp 215-237. 17. Dunnett, C.W. New tables for multiple comparisons with a control. Biometrics 1964, 20, 482-491. 18. Kruskal, W.H.; Wallis, W.A. Use of ranks in one-criterion variance analysis. Journal of the American Statistical Association 1952, 47, 583-621. 19. Dunn, O.J. Multiple comparisons using rank sums. Technometrics 1964, 6(3), 241-252. 20. Steel, R.G.D.; Torrie, J.H. Principles and Procedures of Statistics, A Biometrical Approach, 2nd ed.; McGraw-Hill Book Company: New York, NY, 1980; pp 504-506. WIL-180017 -96- 3M Corporation MTDID 208 06-128 21. SAS Proprietary Software, Version 8.2, SAS Institute, Inc.: Cary, NC, 1999-2001. 12 Deviations From The Protocol This study was conducted in accordance with the protocol and protocol amendments, except for the following. Protocol Section 7.7.1 states that only rats assigned to the main study phase would be observed 1 hour following dosing and the observations would be recorded. On 6 May 2006 and 7 May 2006, 1 hour post-dosing observations were conducted for all groups in the toxicokinetic phase. Protocol Section 7.8.2 states that F1 animals would be observed at weekly intervals following PND 21. Male no. 25619-04 in the 1.0 mg/kg/day group was observed twice during the week following weaning (on PND 22 and 28). Protocol Section 7.8.4.4 states that for learning and memory tests, the minimum intertrial interval will be 1 hour. The time the animal was placed in the maze was not recorded for control group female no. 25681-10 for trial 12 on 22 June 2006 and for 0.1 mg/kg/day male no. 25753-06 for trial 10 on 22 June 2006. Therefore, it cannot be determined if the animals rested for 1 hour prior to being tested for the next trial. In addition, the time male no. 25676-02 in the 1.0 mg/kg/day group was placed in the maze for trial 8 on 20 June 2006 was not recorded. Therefore, it cannot be determined if the animal rested for 1 hour between trials 7 and 8. Protocol Section 7.8.4.4 states that for learning and memory tests, the time to escape the maze would be recorded. On 20 June 2006 and 22 June 2006, the time to escape the maze was not recorded for male no. 25762-01 (Day 3, Trial 4, Path A) and female no. 25639-04 (Day 7, Trial 12, Path A) in the 1.0 mg/kg/day group. WIL-180017 -97- 3M Corporation MTDID 208 06-128 Protocol Section 7.8.4.4 states that for learning and memory tests, the number of errors would be recorded. The total number of errors was not recorded for female no. 25623-15 in the 0.3 mg/kg/day group for trial 6. Protocol Sections 8.1, 8.2, 8.3, 9.1.1, 9.1.2, 9.1.3 and 9.4.4 state that euthanasia and blood collection for toxicokinetic and/or TSH analyses would be between 0900 and 1100 hours (prior to dose administration, where applicable) for F0 maternal animals on gestation day 20, lactation day 4 and lactation day 21 and for F1 fetuses/pups on gestation day 20 and PND 4, 21 and 72. Euthanasia and blood collection were outside this range as indicated in the following table. Number of Animals or Time of Euthanasia/ Test Period Generation Litters/Group Group Blood Collection (hours) gestation day 20 F0 1 0 mg/kg/day 0859 gestation day 20 F0 1 0.1 mg/kg/day 0859 gestation day 20 F0 3 0.3 mg/kg/day 1106 to 1153 gestation day 20 F0 4 1.0 mg/kg/day 1115 to 1148 gestation day 20 F1 2a 0.1 mg/kg/day 1052 to 1121b gestation day 20 F1 3a 0.3 mg/kg/day 1059 to 1205 b gestation day 20 F1 5a 1.0 mg/kg/day 1049 to 1154 b postnatal day 4 F1 1a 0.3 mg/kg/day 1056 to 1103 b lactation day 21 F0 10 0.1 mg/kg/day 1101 to 1116 lactation day 21 F0 10 0.3 mg/kg/day 1107 to 1125 lactation day 21 F0 10 1.0 mg/kg/day 1117 to 1132 postnatal day 72 F1 1 0 mg/kg/day 0859 a = Number of litters. b = Because blood samples were pooled by litter, regardless of sex, for gestation day 20 fetuses and postnatal day 4 pups, euthanasia/blood collection was considered outside the protocol-specified range for a litter if blood from any fetus/pup in that litter was collected after 1100 hours. WIL-180017 -98- 3M Corporation MTDID 208 06-128 Protocol Sections 9.1.2 and 9.6 state that the thyroids of 1 pup/sex/litter from the control and high-dose groups would be examined microscopically. The thyroid sample representing the PND 4 female for the litter from dam no. 25673 was not sufficient for microscopic examination, therefore there could be no female PND 4 pup thyroid microscopic examination data for dam no. 25673. The United States Environmental Protection Agency Good Laboratory Practice Standards (40 CFR Part 792), 18 September 1989 states that test facilities should have standard operating procedures (SOP) available for collection of specimens. There was no SOP in effect for the procedures used to collect blood via decapitation from gestation day 20 fetuses and PND 4 and 21 pups. These deviations did not negatively impact the quality or integrity of the data nor the outcome of the study. WIL-180017 -99- 3M Corporation MTDID 208 06-128 FIGURES 1 - 46 PROJECT NO.: WIL-180017 SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 450 FIGURE 1 (F0 FEMALES) SUMMARY OF BODY WEIGHTS DURING GESTATION [G] 400 350 MEAN BODY WEIGHT [G] (SE) 300 250 -100- 200 150 100 50 0 0 3 6 9 12 15 18 20 GESTATION DAY 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017 SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 450 FIGURE 2 (F0 FEMALES) SUMMARY OF BODY WEIGHTS DURING LACTATION [G] 400 MEAN BODY WEIGHT [G] (SE) 350 ** * * * ** 300 * 250 -101- 200 150 100 50 0 1 4 7 10 14 17 21 LACTATION DAY 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY * = Significantly different from the control group at 0.05 using Dunnett's test ** = Significantly different from the control group at 0.01 using Dunnett's test PROJECT NO.: WIL-180017 SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 60 FIGURE 3 (F1 MALES - PND 1-21) SUMMARY OF OFFSPRING WEIGHTS [G] 50 MEAN BODY WEIGHT [G] (SE) 40 -102- 30 20 10 0 1 4 7 11 14 17 21 POSTNATAL DAY 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017 SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 60 FIGURE 4 (F1 FEMALES - PND 1-21) SUMMARY OF OFFSPRING WEIGHTS [G] 50 MEAN BODY WEIGHT [G] (SE) 40 -103- 30 20 10 0 1 4 7 11 14 17 21 POSTNATAL DAY 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017J SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 FIGURE 5 (F1 MALES - PND 28-72) SUMMARY OF BODY WEIGHTS [G] MEAN BODY WEIGHT [G] (SE) -104- 500 450 400 350 300 250 200 150 100 50 0 28 35 42 49 56 63 70 72 POSTNATAL DAY 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017J SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 FIGURE 6 (F1 FEMALES - PND 28-72) SUMMARY OF BODY WEIGHTS [G] 500 450 400 MEAN BODY WEIGHT [G] (SE) 350 300 -105- 250 200 150 100 50 0 28 35 42 49 56 63 70 72 POSTNATAL DAY 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 800 FIGURE 7 (F1 MALES) SUMMARY OF MEAN FORELIMB GRIP STRENGTH [G] 700 MEAN FORELIMB GRIP STRENGTH [G] (SE) 600 500 -106- 400 300 200 100 0 POSTNATAL DAY 21 POSTNATAL DAY 35 POSTNATAL DAY 45 POSTNATAL DAY 60 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 600 FIGURE 8 (F1 MALES) SUMMARY OF MEAN HINDLIMB GRIP STRENGTH [G] 500 MEAN HINDLIMB GRIP STRENGTH [G] (SE) 400 -107- 300 200 100 * 0 POSTNATAL DAY 21 POSTNATAL DAY 35 POSTNATAL DAY 45 POSTNATAL DAY 60 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY * = Significantly different from the control group at 0.05 using Dunnett's test PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 800 FIGURE 9 (F1 FEMALES) SUMMARY OF MEAN FORELIMB GRIP STRENGTH [G] 700 MEAN FORELIMB GRIP STRENGTH [G] (SE) 600 500 -108- 400 300 200 100 0 POSTNATAL DAY 21 POSTNATAL DAY 35 POSTNATAL DAY 45 POSTNATAL DAY 60 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 FIGURE 10 (F1 FEMALES) SUMMARY OF MEAN HINDLIMB GRIP STRENGTH [G] 500 450 MEAN HINDLIMB GRIP STRENGTH [G] (SE) 400 350 300 -109- 250 200 150 100 50 0 POSTNATAL DAY 21 POSTNATAL DAY 35 POSTNATAL DAY 45 POSTNATAL DAY 60 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO: 06-128 2500 FIGURE 11 (F1 MALES - PND 13, 17 AND 21) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS BY SESSION MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 2000 1500 -110- 1000 500 0 POSTNATAL DAY 13 POSTNATAL DAY 17 POSTNATAL DAY 21 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 800 FIGURE 12 (F1 MALES - PND 13, 17 AND 21) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS BY SESSION 700 MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 600 500 -111- 400 300 200 100 0 POSTNATAL DAY 13 POSTNATAL DAY 17 POSTNATAL DAY 21 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 3000 FIGURE 13 (F1 MALES - PND 61) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS BY SESSION 2500 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 2000 -112- 1500 1000 500 0 POSTNATAL DAY 61 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 1200 1000 800 600 400 200 0 FIGURE 14 (F1 MALES - PND 61) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS BY SESSION POSTNATAL DAY 61 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY -113- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 250 FIGURE 15 (F1 MALES - PND 13) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 200 150 -114- 100 50 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 70 FIGURE 16 (F1 MALES - PND 13) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 60 50 40 30 20 10 0 0-15 16-30 TIME (MINUTES) 31-45 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -115- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 900 FIGURE 17 (F1 MALES - PND 17) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS 800 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 700 600 500 400 * * * 300 200 100 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY * = Significantly different from the control group at 0.031 * 46-60 -116- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 350 FIGURE 18 (F1 MALES - PND 17) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 300 250 200 150 100 50 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -117- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 700 FIGURE 19 (F1 MALES - PND 21) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS 600 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 500 400 300 200 100 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -118- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 250 FIGURE 20 (F1 MALES - PND 21) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 200 150 -119- 100 50 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 1600 FIGURE 21 (F1 MALES - PND 61) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS 1400 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 1200 1000 800 600 400 200 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -120- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 600 FIGURE 22 (F1 MALES - PND 61) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 500 400 -121- 300 200 100 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 FIGURE 23 (F1 FEMALES - PND 13, 17 AND 21) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS BY SESSION 2000 1800 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 1600 1400 1200 -122- 1000 800 600 400 200 0 POSTNATAL DAY 13 POSTNATAL DAY 17 POSTNATAL DAY 21 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 700 FIGURE 24 (F1 FEMALES - PND 13, 17 AND 21) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS BY SESSION MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 600 500 -123- 400 * 300 200 100 0 POSTNATAL DAY 13 POSTNATAL DAY 17 POSTNATAL DAY 21 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY * = Significantly different from the control group at 0.05 using Dunnett's test PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 3000 FIGURE 25 (F1 FEMALES - PND 61) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS BY SESSION 2500 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 2000 -124- 1500 1000 500 0 POSTNATAL DAY 61 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 1200 1000 800 600 400 200 0 FIGURE 26 (F1 FEMALES - PND 61) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS BY SESSION POSTNATAL DAY 61 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY -125- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 300 FIGURE 27 (F1 FEMALES - PND 13) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 250 200 -126- 150 100 50 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 120 FIGURE 28 (F1 FEMALES - PND 13) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 100 80 60 40 20 0 0-15 16-30 TIME (MINUTES) 31-45 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -127- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 700 FIGURE 29 (F1 FEMALES - PND 17) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS 600 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 500 400 300 200 100 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -128- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 300 FIGURE 30 (F1 FEMALES - PND 17) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 250 200 150 100 50 0 0-15 16-30 TIME (MINUTES) 31-45 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -129- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 700 FIGURE 31 (F1 FEMALES - PND 21) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS 600 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 500 400 300 200 100 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -130- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 250 FIGURE 32 (F1 FEMALES - PND 21) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 200 150 -131- 100 50 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 1400 FIGURE 33 (F1 FEMALES - PND 61) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS 1200 MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) 1000 800 600 400 200 0 0-15 16-30 TIME (MINUTES) 31-45 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 -132- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 600 FIGURE 34 (F1 FEMALES - PND 61) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) 500 400 -133- 300 200 100 0 0-15 0 MG/KG/DAY 16-30 TIME (MINUTES) 31-45 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY 46-60 PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 250 FIGURE 35 (F1 MALES - PND 20) SUMMARY OF STARTLE RESPONSE DATA [Vmax] 200 Vmax [MILLIVOLTS] (SE) 150 -134- 100 50 0 1-10 11-20 0 MG/KG/DAY 21-30 TRIALS 0.1 MG/KG/DAY 0.3 MG/KG/DAY 31-40 1.0 MG/KG/DAY 41-50 PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 35 FIGURE 36 (F1 MALES - PND 20) SUMMARY OF STARTLE RESPONSE DATA [Tmax] 30 Tmax [MILLISECONDS] (SE) 25 20 15 10 5 0 1-10 11-20 0 MG/KG/DAY 21-30 TRIALS 0.1 MG/KG/DAY 0.3 MG/KG/DAY 31-40 1.0 MG/KG/DAY 41-50 -135- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 250 FIGURE 37 (F1 FEMALES - PND 20) SUMMARY OF STARTLE RESPONSE DATA [Vmax] 200 Vmax [MILLIVOLTS] (SE) 150 -136- 100 50 0 1-10 11-20 0 MG/KG/DAY 21-30 TRIALS 0.1 MG/KG/DAY 0.3 MG/KG/DAY 31-40 1.0 MG/KG/DAY 41-50 PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 30 FIGURE 38 (F1 FEMALES - PND 20) SUMMARY OF STARTLE RESPONSE DATA [Tmax] 25 Tmax [MILLISECONDS] (SE) 20 15 10 5 0 1-10 11-20 0 MG/KG/DAY 21-30 TRIALS 0.1 MG/KG/DAY 0.3 MG/KG/DAY 31-40 1.0 MG/KG/DAY 41-50 -137- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 350 FIGURE 39 (F1 MALES - PND 60) SUMMARY OF STARTLE RESPONSE DATA [Vmax] 300 250 Vmax [MILLIVOLTS] (SE) 200 150 100 50 0 1-10 11-20 0 MG/KG/DAY 21-30 TRIALS 0.1 MG/KG/DAY 0.3 MG/KG/DAY 31-40 1.0 MG/KG/DAY 41-50 -138- Tmax [MILLISECONDS] (SE) PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 45 40 35 30 25 20 15 10 5 0 1-10 11-20 0 MG/KG/DAY FIGURE 40 (F1 MALES - PND 60) SUMMARY OF STARTLE RESPONSE DATA [Tmax] 21-30 TRIALS 0.1 MG/KG/DAY 0.3 MG/KG/DAY 31-40 1.0 MG/KG/DAY 41-50 -139- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 140 FIGURE 41 (F1 FEMALES - PND 60) SUMMARY OF STARLE RESPONSE DATA [Vmax] 120 100 Vmax [MILLIVOLTS] (SE) 80 60 40 20 0 1-10 11-20 0 MG/KG/DAY 21-30 TRIALS 0.1 MG/KG/DAY 0.3 MG/KG/DAY 31-40 1.0 MG/KG/DAY 41-50 -140- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 45 FIGURE 42 (F1 FEMALES - PND 60) SUMMARY OF STARTLE RESPONSE DATA [Tmax] 40 35 Tmax [MILLISECONDS] (SE) 30 25 20 15 10 5 0 1-10 11-20 0 MG/KG/DAY 21-30 TRIALS 0.1 MG/KG/DAY 0.3 MG/KG/DAY 31-40 1.0 MG/KG/DAY 41-50 -141- PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 180 FIGURE 43 (F1 MALES - TIME TO ESCAPE - PND 22) SUMMARY OF BIEL MAZE DATA 160 140 MEAN TIME [SECONDS] (SE) 120 100 -142- 80 60 40 20 0 SWIM 1 2 3 4 5 6 7 8 9 10 TRIAL 11 12 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 40 FIGURE 44 (F1 MALES - MEAN NO. OF ERRORS - PND 22) SUMMARY OF BIEL MAZE DATA 35 30 MEAN NO. OF ERRORS (SE) 25 -143- 20 15 10 5 0 1 2 3 4 5 6 7 8 9 10 TRIAL 11 12 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 180 FIGURE 45 (F1 FEMALES - TIME TO ESCAPE - PND 22) SUMMARY OF BIEL MAZE DATA 160 140 MEAN TIME [SECONDS] (SE) 120 100 -144- 80 60 40 20 0 SWIM 1 2 3 4 5 6 7 8 9 10 TRIAL 11 12 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128 40 FIGURE 46 (F1 FEMALES - MEAN NO. OF ERRORS - PND 22) SUMMARY OF BIEL MAZE DATA 35 30 MEAN NO. OF ERRORS (SE) 25 -145- 20 15 10 5 0 1 2 3 4 5 6 7 8 9 10 TRIAL 11 12 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY WIL-180017 3M Corporation -146- MTDID 208 06-128 TABLES 1 - 51 TABLE 1 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MATERNAL SURVIVAL AND PREGNANCY STATUS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DOSE GROUP : 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NO. % NO. % NO. % NO. % FEMALES ON STUDY 25 25 25 25 FEMALES THAT DIED 0 0 0 0 FEMALES THAT WERE EUTH. IN EXTREMIS 0 0 0 0 FEMALES SCHEDULED NONGRAVID GRAVID NO. THAT NO. WITH NO. WITH TO DELIVER FAILED TO DELIVER TOTAL LITTER LOSS VIABLE PUPS 25 0 0.0 25 100.0 0 0.0 0 0.0 25 100.0 25 2 8.0 23 92.0 0 0.0 0 0.0 23 100.0 25 0 0.0 25 100.0 0 0.0 0 0.0 25 100.0 25 1 4.0 24 96.0 0 0.0 0 0.0 24 100.0 TOTAL FEMALES GRAVID 25 100.0 23 92.0 25 100.0 24 96.0 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY MANUALv1.0 10/11/2006 R:10/11/2006 -147- TABLE 2 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.:06-128 ----- F E M A L E ----- ----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 05-02-06 TO 06-19-06 GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 773/22 846/23 885/24 899/25 DISPOSITION -SCHEDULED EUTHANASIA; POST-MATING DAY 25 -SCHEDULED EUTHANASIA; LACTATION DAY 21 0/ 0 25/25 2/ 2 23/23 0/ 0 25/25 1/ 1 24/24 -148- BODY/INTEGUMENT -HAIR LOSS RIGHT FORELIMB 258/ 9 147/ 7 138/ 6 164/ 6 -HAIR LOSS LEFT FORELIMB 258/ 8 146/ 8 113/ 7 148/ 7 -HARD IMMOVABLE MASS LEFT LATERAL NECK 9/ 1 0/ 0 0/ 0 0/ 0 12MM X 13MM X 11MM -HAIR LOSS DORSAL HEAD 7/ 1 0/ 0 0/ 0 0/ 0 -SCABBING DORSAL HEAD 2/ 1 0/ 0 0/ 0 0/ 0 -DRIED RED MATERIAL VENTRAL ABDOMINAL 0/ 0 0/ 0 0/ 0 1/ 1 AREA -HAIR LOSS VENTRAL NECK 34/ 1 0/ 0 0/ 0 0/ 0 -HAIR LOSS LEFT LATERAL NECK 10/ 1 0/ 0 0/ 0 0/ 0 -SCABBING LEFT LATERAL NECK 8/ 1 0/ 0 0/ 0 0/ 0 -SCABBING LEFT FORELIMB 13/ 2 11/ 2 2/ 2 2/ 1 -SCABBING RIGHT FORELIMB 9/ 3 6/ 2 0/ 0 2/ 1 -HARD IMMOVABLE MASS LEFT LATERAL NECK 2/ 1 0/ 0 0/ 0 0/ 0 5MM X 10MM X 10MM ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY TABLE 2 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.:06-128 ----- F E M A L E ----- ----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 05-02-06 TO 06-19-06 GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- BODY/INTEGUMENT -HAIR LOSS RIGHT HINDLIMB -HAIR LOSS LEFT HINDLIMB -SCABBING LEFT HINDLIMB -HAIR LOSS VENTRAL ABDOMINAL AREA -HAIR LOSS VENTRAL THORACIC AREA -HAIR LOSS FACIAL AREA -HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA 20MM X 12MM X 15MM -SOFT MOVABLE MASS VENTRAL THORACIC 17MM X 15MM X 15MM -SCABBING VENTRAL ABDOMINAL AREA -SCABBING FACIAL AREA -HAIR LOSS UROGENITAL AREA AREA 17/ 1 17/ 1 3/ 1 14/ 1 9/ 1 0/ 0 5/ 1 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 1/ 1 9/ 1 0/ 0 0/ 0 0/ 0 0/ 0 2/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 11/ 1 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 2/ 1 0/ 0 1/ 1 0/ 0 4/ 1 0/ 0 -149- EYES/EARS/NOSE -DRIED RED MATERIAL AROUND NOSE 38/12 32/ 8 22/10 22/ 9 -DRIED RED MATERIAL AROUND LEFT EYE 0/ 0 4/ 1 1/ 1 0/ 0 -DRIED RED MATERIAL AROUND RIGHT EYE 0/ 0 0/ 0 16/ 3 1/ 1 -OPACITY RIGHT EYE 0/ 0 0/ 0 37/ 3 0/ 0 -EXOPHTHALMUS RIGHT EYE 0/ 0 0/ 0 11/ 2 0/ 0 -HAIR LOSS AROUND LEFT EYE 0/ 0 1/ 1 0/ 0 0/ 0 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY TABLE 2 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.:06-128 ----- F E M A L E ----- ----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 05-02-06 TO 06-19-06 GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- EYES/EARS/NOSE -HAIR LOSS AROUND RIGHT EYE -HAIR LOSS AROUND NOSE -SCABBING AROUND NOSE -WET RED MATERIAL AROUND NOSE 0/ 0 10/ 1 0/ 0 0/ 0 0/ 0 10/ 1 2/ 1 1/ 1 33/ 3 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 ORAL/DENTAL -WET YELLOW MATERIAL AROUND MOUTH 0/ 0 0/ 0 1/ 1 0/ 0 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PCSUv4.07 10/09/2006 -150- TABLE 3 (F0 - 1 HOUR POST-DOSING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.:06-128 ----- F E M A L E ----- ----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 05-02-06 TO 06-18-06 GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CLINICAL OBSERVATIONS 1 HOUR POST-DOSING ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PCSUv4.07 10/05/2006 R:10/09/2006 -151- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 4 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BODY WEIGHTS DURING GESTATION [G] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 0 MEAN 266. 268. 267. 266. % DIFFERENCE 0.8 0.4 0.0 S.D. 12.8 12.1 12.4 12.6 N 25 23 25 24 DAY 3 MEAN % DIFFERENCE S.D. N 284. 13.5 25 281. -1.1 14.3 23 282. -0.7 12.3 25 280. -1.4 12.4 24 DAY 6 MEAN % DIFFERENCE S.D. N 297. 14.8 25 294. -1.0 15.3 23 294. -1.0 12.1 25 291. -2.0 12.6 24 -152- DAY 9 MEAN % DIFFERENCE S.D. N 310. 16.5 25 308. -0.6 16.1 23 306. -1.3 13.3 25 300. -3.2 13.3 24 DAY 12 MEAN % DIFFERENCE S.D. N 329. 17.6 25 326. -0.9 17.7 23 325. -1.2 14.7 25 317. -3.6 15.3 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 4 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BODY WEIGHTS DURING GESTATION [G] PAGE 2 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 15 MEAN 349. 347. 344. 336. % DIFFERENCE -0.6 -1.4 -3.7 S.D. 20.0 21.5 17.5 16.8 N 25 23 25 24 DAY 18 MEAN % DIFFERENCE S.D. N 388. 21.0 25 388. 0.0 23.7 23 384. -1.0 21.2 25 374. -3.6 21.0 24 DAY 20 MEAN % DIFFERENCE S.D. N 421. 24.5 25 421. 0.0 28.7 23 417. -1.0 25.0 25 407. -3.3 22.8 24 -153- ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGBWSUv5.08 01/23/2007 PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 5 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 0- 3 MEAN 18. 14. 14. 14. S.D. 6.9 6.2 5.8 5.5 N 25 23 25 24 DAY 3- 6 MEAN S.D. N 14. 12. 12. 11. 4.5 6.8 3.7 4.2 25 23 25 24 DAY 6- 9 MEAN S.D. N 12. 14. 12. 9. 6.8 4.4 4.8 5.1 25 23 25 24 DAY 9- 12 MEAN S.D. N 19. 18. 19. 17. 6.4 5.6 5.1 4.3 25 23 25 24 -154- DAY 12- 15 MEAN S.D. N 21. 22. 19. 19. 10.0 6.4 6.3 5.4 25 23 25 24 DAY 15- 18 MEAN S.D. N 38. 41. 40. 38. 10.9 5.6 7.1 7.7 25 23 25 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 5 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G] PAGE 2 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 18- 20 MEAN 33. 33. 33. 33. S.D. 8.0 8.4 6.7 9.8 N 25 23 25 24 DAY 0- 20 MEAN S.D. N 155. 19.3 25 153. 21.7 23 150. 20.3 25 141. 17.3 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGBWSUv5.08 01/23/2007 -155- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 6 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 0- 3 MEAN 21. 20. 20. 20. S.D. 2.1 2.4 1.4 1.6 N 25 23 24 24 DAY 3- 6 MEAN S.D. N 23. 22. 22. 22. 2.5 2.1 2.1 1.5 25 22 24 23 DAY 6- 9 MEAN S.D. N 24. 23. 23.* 22.** 2.0 2.2 2.1 1.4 25 23 24 24 DAY 9- 12 MEAN S.D. N 25. 24. 24. 23.** 2.4 2.5 2.2 2.4 23 20 19 21 -156- DAY 12- 15 MEAN S.D. N 25. 26. 25. 24. 2.0 2.4 2.3 2.6 22 23 23 22 DAY 15- 18 MEAN S.D. N 28. 28. 28. 26. 2.8 2.8 3.1 2.5 21 21 22 20 ----------------------------------------------------------------------------------------------------------------------------------* = Significantly different from the control group at 0.05 using Dunnett's test ** = Significantly different from the control group at 0.01 using Dunnett's test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 6 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] PAGE 2 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 18- 20 MEAN 28. 28. 28. 27. S.D. 2.4 3.6 3.9 2.9 N 23 23 25 24 DAY 0- 20 MEAN S.D. N 25. 24. 24. 23.** 1.5 1.9 1.8 1.4 23 23 24 24 ----------------------------------------------------------------------------------------------------------------------------------** = Significantly different from the control group at 0.01 using Dunnett's test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGFWSUv5.12 10/26/2006 -157- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 7 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 0- 3 MEAN 75. 72. 73. 72. S.D. 7.0 7.3 4.2 5.8 N 25 23 24 24 DAY 3- 6 MEAN S.D. N 79. 77. 78. 77. 7.3 5.8 5.9 4.9 25 22 24 23 DAY 6- 9 MEAN S.D. N 79. 77. 76.* 74.** 4.9 4.3 5.8 3.2 25 23 24 24 DAY 9- 12 MEAN S.D. N 78. 75. 76. 74. 6.8 6.9 4.8 6.9 23 20 19 21 -158- DAY 12- 15 MEAN S.D. N 74. 77. 74. 73. 4.9 4.9 4.3 7.1 22 23 23 22 DAY 15- 18 MEAN S.D. N 76. 77. 77. 74. 6.4 6.4 6.2 5.6 21 21 22 20 ----------------------------------------------------------------------------------------------------------------------------------* = Significantly different from the control group at 0.05 using Dunnett's test ** = Significantly different from the control group at 0.01 using Dunnett's test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 7 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] PAGE 2 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 18- 20 MEAN 70. 69. 69. 69. S.D. 7.0 6.9 8.4 6.6 N 23 23 25 24 DAY 0- 20 MEAN S.D. N 74. 74. 73. 72. 3.4 3.4 3.5 3.0 23 23 24 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGFWSUv5.12 01/23/2007 -159- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 8 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BODY WEIGHTS DURING LACTATION [G] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 1 MEAN 317. 318. 316. 306. % DIFFERENCE 0.3 -0.3 -3.5 S.D. 18.6 20.2 16.5 19.0 N 25 23 25 24 DAY 4 MEAN % DIFFERENCE S.D. N 339. 17.1 25 339. 0.0 23.6 23 336. -0.9 16.3 25 324.* -4.4 20.4 24 DAY 7 MEAN % DIFFERENCE S.D. N 347. 17.0 25 346. -0.3 20.9 23 340. -2.0 13.4 25 331.** -4.6 18.5 24 -160- DAY 10 MEAN % DIFFERENCE S.D. N 359. 17.6 25 360. 0.3 22.3 23 355. -1.1 16.1 25 344.* -4.2 19.4 24 DAY 14 MEAN % DIFFERENCE S.D. N 370. 20.5 25 368. -0.5 20.3 23 362. -2.2 17.6 25 349.** -5.7 20.5 24 DAY 17 MEAN % DIFFERENCE S.D. N 370. 19.8 25 374. 1.1 23.2 23 369. -0.3 20.3 25 354.* -4.3 20.0 24 ----------------------------------------------------------------------------------------------------------------------------------* = Significantly different from the control group at 0.05 using Dunnett's test ** = Significantly different from the control group at 0.01 using Dunnett's test PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 8 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BODY WEIGHTS DURING LACTATION [G] PAGE 2 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 21 MEAN 365. 365. 363. 351.* % DIFFERENCE 0.0 -0.5 -3.8 S.D. 22.5 20.5 17.6 17.1 N 25 23 25 24 ----------------------------------------------------------------------------------------------------------------------------------* = Significantly different from the control group at 0.05 using Dunnett's test PLBWSUv5.05 10/05/2006 -161- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 9 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BODY WEIGHT CHANGES DURING LACTATION [G] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 MEAN 22. 21. 19. 18. S.D. 11.6 8.4 11.3 11.4 N 25 23 25 24 DAY 4- 7 MEAN S.D. N 8. 7. 4. 8. 8.8 9.6 8.2 10.3 25 23 25 24 DAY 7- 10 MEAN S.D. N 12. 14. 14. 12. 6.6 7.5 6.6 9.9 25 23 25 24 DAY 10- 14 MEAN S.D. N 11. 8. 7. 5. 10.6 8.4 9.5 7.2 25 23 25 24 -162- DAY 14- 17 MEAN S.D. N 1. 6. 7. 5. 8.0 10.4 10.8 11.6 25 23 25 24 DAY 17- 21 MEAN S.D. N -6. -9. -6. -4. 12.3 14.3 11.8 9.2 25 23 25 24 DAY 1- 21 MEAN S.D. N 48. 15.8 25 47. 17.9 23 47. 12.8 25 45. 14.8 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES PLBWSUv5.05 10/05/2006 PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 10 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 MEAN 40. 40. 38. 36. S.D. 7.9 6.3 5.3 5.7 N 20 21 20 20 DAY 4- 7 MEAN S.D. N 43. 44. 42. 41. 3.9 4.8 3.4 4.5 22 18 20 20 DAY 7- 10 MEAN S.D. N 54. 56. 53. 51. 5.0 5.4 4.4 4.9 23 20 23 23 DAY 10- 14 MEAN S.D. N 62. 64. 61. 60. 6.8 5.5 5.8 5.5 24 23 25 24 -163- DAY 14- 17 MEAN S.D. N 67. 70. 68. 65. 8.3 6.1 5.8 6.4 25 23 25 24 DAY 17- 21 MEAN S.D. N 72. 76. 73. 72. 7.9 6.3 6.5 6.6 22 22 23 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 10 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY] PAGE 2 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 21 MEAN 57. 60. 58. 55. S.D. 5.9 4.5 4.2 4.9 N 19 21 20 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PLFWSUv5.07 10/05/2006 -164- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 11 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING LACTATION [G/KG/DAY] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 MEAN 122. 121. 116. 113. S.D. 25.1 17.9 14.7 16.0 N 20 21 20 20 DAY 4- 7 MEAN S.D. N 125. 11.8 22 130. 14.8 18 122. 10.6 20 127. 12.1 20 DAY 7- 10 MEAN S.D. N 153. 13.9 23 159. 14.5 20 151. 10.8 23 152. 10.3 23 DAY 10- 14 MEAN S.D. N 170. 18.3 24 177. 14.3 23 171. 14.3 25 174. 10.7 24 -165- DAY 14- 17 MEAN S.D. N 180. 20.4 25 190. 15.8 23 185. 13.2 25 185. 12.4 24 DAY 17- 21 MEAN S.D. N 195. 20.2 22 207. 16.2 22 201. 17.7 23 205. 16.2 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 11 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING LACTATION [G/KG/DAY] PAGE 2 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 21 MEAN 161. 170. 165. 165. S.D. 17.5 11.9 12.3 10.3 N 19 21 20 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PLFWSUv5.07 10/05/2006 -166- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 12 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF GESTATION LENGTHS [DAYS] PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- GESTATION LENGTH (DAYS) MEAN 21.9 21.7 21.7 21.8 S.D. 0.53 0.47 0.48 0.44 N 25 23 25 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PGLv5.06 10/05/2006 -167- TABLE 13 (F0 - FAILED TO DELIVER) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MACROSCOPIC FINDINGS SPONSOR NO.:06-128 SCHEDULED NECROPSY ----------------------------------------------------------------------------------------------------------------------------------- ----- F E M A L E ----- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS IN DOSE GROUP 25 25 25 25 NUMBER OF ANIMALS EXAMINED 0 2 0 1 CERVIX -ENLARGED 0 1 0 0 UTERUS -CONTENTS, THICK YELLOW 0 1 0 0 -CONTENTS, CLEAR FLUID 0 1 0 1 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PGRSI2v4.07 10/05/2006 -168- TABLE 14 (F0 - LACTATION DAY 21) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MACROSCOPIC FINDINGS SPONSOR NO.:06-128 SCHEDULED NECROPSY ----------------------------------------------------------------------------------------------------------------------------------- ----- F E M A L E ----- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS IN DOSE GROUP 25 25 25 25 NUMBER OF ANIMALS EXAMINED 25 23 25 24 KIDNEYS -ENLARGED -CYST(S) 1 0 0 0 1 0 0 0 LIVER -SWOLLEN 1 0 0 0 LUNGS -AREA(S), DARK RED 0 1 0 0 THYMUS -AREA(S), DARK RED 1 1 1 3 THYROID GLANDS -DISCOLORATION, DARK RED 0 0 2 1 UTERUS -CYST(S) 0 0 0 1 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 23 21 23 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PGRSI2v4.07 10/05/2006 -169- TABLE 15 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF IMPLANTATION SITES SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- IMPLANTATION SITES MEAN 16.6 16.1 15.9 16.0 S.D. 3.04 2.52 2.20 1.30 N 25 23 25 24 NUMBER BORN MEAN S.D. N 15.8 3.03 25 15.2 2.24 23 15.1 2.20 25 15.4 1.38 24 UNACCOUNTED SITES MEAN S.D. N 0.8 0.76 25 0.9 0.87 23 0.8 0.83 25 0.6 0.71 24 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group NOTE: ONLY DAMS THAT HAVE DELIVERED ONE OR MORE PUPS ARE INCLUDED IN CALCULATION OF MEAN. PISSUv5.07 10/05/2006 -170- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 16 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF PND 0 LITTER DATA PAGE 1 GROUP : 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER BORN MEAN S.D. N 15.8 3.03 25 15.2 2.24 23 15.1 2.20 25 15.4 1.38 24 SEX AT BIRTH (% MALES PER LITTER) MEAN 48.7 S.D. 9.92 N 25 49.6 12.40 23 49.1 11.78 25 48.9 10.44 24 LIVE LITTER SIZE (PND 0) MEAN 15.6 15.2 15.0 15.1 S.D. 3.01 2.24 2.21 1.65 N 25 23 25 24 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY SEX COMPARED USING DUNN'S, NUMBER BORN, AND LIVE LITTER SIZE COMPARED USING DUNNETT'S ----------------------------------------------------------------------------------------------------------------------------------- MODIFIED STATISTICS USED. * INDICATES PARAMETRIC ANALYSIS AND + INDICATES NON-PARAMETRIC ANALYSIS. None significantly different from control group PPVIASv5.07 10/05/2006 R:10/23/2006 -171- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 17 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF POSTNATAL SURVIVAL [% PER LITTER] PAGE 1 GROUP : 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- PND 0 (RELATIVE TO NUMBER BORN) MEAN 99.0 S.D. 2.78 N 25 100.0 0.00 23 99.0 3.07 25 98.0 4.62 24 PND 0 TO PND 1 MEAN S.D. N 98.9 2.83 25 98.4 3.41 23 99.7 1.67 25 98.7 3.20 24 PND 1 TO PND MEAN S.D. N 4 (PRE-SELECTION) 99.5 1.68 25 99.2 2.12 23 98.1 3.91 25 99.2 3.06 24 PND 4 (POST-SELECTION) TO PND 7 MEAN 98.5 S.D. 5.50 N 25 100.0 0.00 23 98.0 5.91 25 100.0 0.00 24 -172- PND 7 TO PND 14 MEAN 99.5 100.0 100.0 100.0 S.D. 2.50 0.00 0.00 0.00 N 25 23 25 24 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- MODIFIED STATISTICS USED. None significantly different from control group PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 17 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF POSTNATAL SURVIVAL [% PER LITTER] PAGE 2 GROUP : 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- PND 14 TO PND 21 MEAN S.D. N 100.0 0.00 25 100.0 0.00 23 100.0 0.00 25 100.0 0.00 24 BIRTH TO PND 4 (PRE-SELECTION) MEAN 97.5 S.D. 4.90 N 25 97.6 4.01 23 96.7 4.62 25 95.9 6.11 24 PND 4 (POST-SELECTION) TO PND 21 MEAN 98.0 100.0 98.0 100.0 S.D. 5.91 0.00 5.91 0.00 N 25 23 25 24 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY STATISTICS PERFORMED USING DUNN'S ----------------------------------------------------------------------------------------------------------------------------------- MODIFIED STATISTICS USED. None significantly different from control group PPVIASv5.07 10/05/2006 R:10/23/2006 -173- TABLE 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING TOTAL NUMBER OF FINDINGS/NUMBER OF PUPS WITH FINDING ----------------------------------------------------------------------------------------------------------------------------------- FINDING GROUP : 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NORMAL NO REMARKABLE OBSERVATIONS 1732/385 1588/344 1685/372 1646/356 DISPOSITION FOUND DEAD SCHEDULED EUTHANASIA (PND 21) CULLED ON SCHEDULED DAY (PND 4) MISSING 10/ 10 153/153 187/187 5/ 5 5/ 5 144/144 157/157 4/ 4 15/ 15 156/156 166/166 1/ 1 10/ 10 152/152 163/163 5/ 5 BODY/INTEGUMENT LACERATION SMALL IN SIZE SUBCUTANEOUS HEMORRHAGE(S) DISTAL PORTION OF TAIL MISSING SCABBING DRIED RED MATERIAL PALE IN COLOR HAIR LOSS 1/ 1 1/ 1 1/ 1 0/ 0 1/ 1 1/ 1 1/ 1 0/ 0 0/ 0 16/ 6 1/ 1 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 12/ 2 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 48/ 9 2/ 2 20/ 7 0/ 0 3/ 1 5/ 1 0/ 0 0/ 0 0/ 0 -174- CARDIO-PULMONARY LABORED RESPIRATION 0/ 0 1/ 1 0/ 0 0/ 0 ORAL/DENTAL WET RED MATERIAL 1/ 1 0/ 0 0/ 0 0/ 0 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PPOBSIv4.06 10/19/2006 TABLE 19 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 (LITTER AS EXPERIMENTAL UNIT) GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 1 MALES MEAN 7.1 7.2 7.0 6.9 % DIFFERENCE 1.4 -1.4 -2.8 S.D. 0.59 0.74 0.60 0.67 N 25 23 25 24 FEMALES MEAN % DIFFERENCE S.D. N 6.7 0.56 25 6.7 0.0 0.67 23 6.7 0.0 0.55 25 6.6 -1.5 0.58 24 PND 4 (BEFORE SELECTION) MALES MEAN % DIFFERENCE S.D. N 9.6 1.22 25 10.2 6.3 1.19 23 9.9 3.1 0.97 25 9.5 -1.0 1.02 24 -175- FEMALES MEAN % DIFFERENCE S.D. N 9.1 1.17 25 9.6 5.5 1.17 23 9.3 2.2 0.91 25 9.1 0.0 0.87 24 PND 7 MALES MEAN % DIFFERENCE S.D. N 15.3 2.02 25 16.3 6.5 1.88 23 15.7 2.6 1.66 25 15.1 -1.3 1.97 24 ----------------------------------------------------------------------------------------------------------------------------------PND = POSTNATAL DAY None significantly different from control group TABLE 19 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 (LITTER AS EXPERIMENTAL UNIT) GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 7 FEMALES MEAN 14.6 15.3 14.9 14.9 % DIFFERENCE 4.8 2.1 2.1 S.D. 2.07 1.97 1.55 1.77 N 25 23 25 24 PND 11 MALES MEAN % DIFFERENCE S.D. N 25.3 2.97 25 26.0 2.8 2.78 23 25.5 0.8 2.40 25 24.2 -4.3 2.65 24 FEMALES MEAN % DIFFERENCE S.D. N 24.2 3.23 25 24.8 2.5 2.82 23 24.3 0.4 2.15 25 24.0 -0.8 2.36 24 -176- PND 14 MALES MEAN % DIFFERENCE S.D. N 32.9 3.47 25 33.6 2.1 3.11 23 33.2 0.9 2.89 25 31.6 -4.0 3.26 24 FEMALES MEAN % DIFFERENCE S.D. N 31.6 3.83 25 32.1 1.6 3.14 23 31.5 -0.3 2.83 25 31.3 -0.9 3.00 24 ----------------------------------------------------------------------------------------------------------------------------------PND = POSTNATAL DAY None significantly different from control group TABLE 19 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION SUMMARY OF OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 (LITTER AS EXPERIMENTAL UNIT) GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 17 MALES MEAN 40.1 41.3 40.9 38.5 % DIFFERENCE 3.0 2.0 -4.0 S.D. 4.39 3.72 3.73 4.14 N 25 23 25 24 FEMALES MEAN % DIFFERENCE S.D. N 38.5 4.63 25 39.6 2.9 3.66 23 39.0 1.3 3.22 25 38.0 -1.3 3.62 24 PND 21 MALES MEAN % DIFFERENCE S.D. N 52.7 6.48 25 54.7 3.8 5.56 23 54.0 2.5 5.40 25 50.7 -3.8 5.85 24 -177- FEMALES MEAN % DIFFERENCE S.D. N 50.2 6.56 25 51.7 3.0 5.31 23 51.8 3.2 6.18 25 50.1 -0.2 4.75 24 ----------------------------------------------------------------------------------------------------------------------------------PND = POSTNATAL DAY None significantly different from control group PPWSUSNv5.11 10/23/2006 R:10/23/2006 TABLE 20 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 (LITTER AS EXPERIMENTAL UNIT) GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 1 TO 4 (BEFORE SELECTION) MALES MEAN 2.6 3.0 2.8 2.6 S.D. 0.75 0.54 0.52 0.57 N 25 23 25 24 FEMALES MEAN S.D. N 2.4 0.72 25 2.8 0.55 23 2.6 0.49 25 2.5 0.52 24 PND 4 TO 7 MALES MEAN S.D. N 5.7 0.99 25 6.1 0.97 23 5.9 0.90 25 5.7 1.06 24 -178- FEMALES MEAN S.D. N 5.4 1.05 25 5.7 1.00 23 5.5 0.78 25 5.7 0.99 24 PND 7 TO 11 MALES MEAN S.D. N 10.0 1.39 25 9.7 1.18 23 9.8 1.19 25 9.1 1.16 24 FEMALES MEAN S.D. N 9.7 1.51 25 9.5 1.13 23 9.4 1.15 25 9.1 1.10 24 ----------------------------------------------------------------------------------------------------------------------------------PND = POSTNATAL DAY None significantly different from control group TABLE 20 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 (LITTER AS EXPERIMENTAL UNIT) GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 11 TO 14 MALES MEAN 7.6 7.7 7.8 7.4 S.D. 0.91 0.71 1.00 0.96 N 25 23 25 24 FEMALES MEAN S.D. N 7.4 0.91 25 7.3 0.75 23 7.3 1.16 25 7.3 0.94 24 PND 14 TO 17 MALES MEAN S.D. N 7.2 1.42 25 7.7 1.19 23 7.6 1.18 25 6.9 1.47 24 -179- FEMALES MEAN S.D. N 7.0 1.21 25 7.5 1.09 23 7.5 0.98 25 6.7 1.08 24 PND 17 TO 21 MALES MEAN S.D. N 12.6 2.38 25 13.5 2.48 23 13.1 2.36 25 12.3 2.43 24 FEMALES MEAN S.D. N 11.7 2.31 25 12.2 2.19 23 12.8 4.21 25 12.1 1.94 24 ----------------------------------------------------------------------------------------------------------------------------------PND = POSTNATAL DAY None significantly different from control group PPWSUSNv5.11 10/23/2006 PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 21 (F1 - FOUND DEAD PUPS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF PUP NECROPSY FINDINGS PAGE 1 ----------------------------------------------------------------------------------------------------------------------------------- P U P S L I T T E R S DOSE GROUP: 1 2 3 4 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER EXAMINED VISCERALLY 10 5 15 10 7 3 11 8 STOMACH MILK NOT PRESENT MILK PRESENT 3 1 0 6 0 0 3 2 3 1 0 4 0 0 2 2 MALFORMATION MANDIBULAR MICROGNATHIA SITUS INVERSUS 0 0 0 1 0 0 0 1 0 0 0 1 0 0 0 1 VARIATION RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S) 0 1 0 0 0 1 0 0 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PPNSIv4.03 01/23/2007 R:01/23/2007 -180- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 22 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF PUP NECROPSY FINDINGS PAGE 1 ----------------------------------------------------------------------------------------------------------------------------------- P U P S L I T T E R S DOSE GROUP: 1 2 3 4 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER EXAMINED VISCERALLY 103 94 106 102 25 23 25 24 NUMBER WITH FINDINGS 0 0 0 0 0 0 0 0 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PPNSIv4.03 10/05/2006 R:10/10/2006 -181- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF ANIMAL DEVELOPMENTAL PARAMETERS - BALANOPREPUTIAL SEPARATION PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- BALANOPREPUTIAL SEPARATION (PND) MEAN 46.2 47.0 45.8 45.8 S.D. 2.09 3.56 2.63 1.77 N 20 20 20 20 BODY WEIGHT (GRAMS) MEAN % DIFFERENCE S.D. N 248.1 18.08 20 268.2* 8.1 38.92 20 252.6 1.8 20.81 20 243.5 -1.9 21.43 20 ----------------------------------------------------------------------------------------------------------------------------------PND= POSTNATAL DAY * = Significantly different from the control group at 0.05 using Dunnett's test PJTBBv1.16 10/05/2006 R:10/12/2006 -182- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 24 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF ANIMAL DEVELOPMENTAL PARAMETERS - VAGINAL PATENCY PAGE 1 GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- VAGINAL PATENCY (PND) MEAN 31.7 32.7 32.0 32.3 S.D. 1.04 1.45 1.61 0.72 N 20 20 20 20 BODY WEIGHT (GRAMS) MEAN % DIFFERENCE S.D. N 105.8 11.23 20 118.6** 12.1 11.97 20 110.6 4.5 8.86 20 110.4 4.3 9.74 20 ----------------------------------------------------------------------------------------------------------------------------------PND= POSTNATAL DAY ** = Significantly different from the control group at 0.01 using Dunnett's test PJTBBv1.16 10/05/2006 R:10/12/2006 -183- TABLE 25 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.:06-128 ----- M A L E ----- ----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 06-17-06 TO 08-08-06 GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 149/20 159/20 150/20 148/19 DISPOSITION -SCHEDULED EUTHANASIA 20/20 20/20 20/20 20/20 BODY/INTEGUMENT -HAIR LOSS RIGHT FORELIMB -HAIR LOSS LEFT FORELIMB -HAIR LOSS DORSAL NECK -SCABBING DORSAL NECK -HAIR LOSS VENTRAL NECK -SCABBING VENTRAL NECK -SCABBING RIGHT LATERAL THORACIC AREA -SCABBING DORSAL THORACIC AREA -HAIR LOSS DORSAL THORACIC AREA -MOIST ALOPECIA DORSAL NECK -MOIST ALOPECIA LEFT DORSAL HEAD -MOIST ALOPECIA RIGHT DORSAL HEAD 6/ 1 6/ 1 1/ 1 0/ 0 4/ 1 3/ 1 1/ 1 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 5/ 2 3/ 2 1/ 1 1/ 1 0/ 0 0/ 0 0/ 0 2/ 1 1/ 1 0/ 0 0/ 0 0/ 0 2/ 1 3/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 1/ 1 -184- EYES/EARS/NOSE -OPACITY RIGHT EYE 0/ 0 0/ 0 0/ 0 9/ 1 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY TABLE 25 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.:06-128 ----- M A L E ----- ----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 06-17-06 TO 08-08-06 GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- EYES/EARS/NOSE -OPACITY LEFT EYE 0/ 0 0/ 0 0/ 0 9/ 1 -DRIED RED MATERIAL AROUND NOSE 0/ 0 0/ 0 2/ 2 0/ 0 -EXOPHTHALMUS RIGHT EYE 0/ 0 0/ 0 0/ 0 7/ 1 -DRIED RED MATERIAL AROUND LEFT EYE 0/ 0 0/ 0 0/ 0 1/ 1 -DRIED RED MATERIAL AROUND RIGHT EYE 0/ 0 0/ 0 0/ 0 4/ 2 -APPARENT MECHANICAL INJURY RIGHT EYE 0/ 0 0/ 0 0/ 0 1/ 1 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY -185- TABLE 25 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS SPONSOR NO.:06-128 ----- F E M A L E ----- ----------------------------------------------------------------------------------------------------------------------------------- TABLE RANGE: 06-17-06 TO 08-08-06 GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS 155/20 160/20 154/20 160/20 DISPOSITION -SCHEDULED EUTHANASIA 20/20 20/20 20/20 20/20 BODY/INTEGUMENT -HAIR LOSS RIGHT FORELIMB 3/ 2 0/ 0 6/ 2 0/ 0 -HAIR LOSS LEFT FORELIMB 3/ 2 0/ 0 6/ 2 0/ 0 -HAIR LOSS LEFT LATERAL THORACIC AREA 2/ 1 0/ 0 0/ 0 0/ 0 -SCABBING LEFT LATERAL THORACIC AREA 2/ 1 0/ 0 0/ 0 0/ 0 -HAIR LOSS RIGHT HINDLIMB 0/ 0 0/ 0 1/ 1 0/ 0 -HAIR LOSS LEFT HINDLIMB 0/ 0 0/ 0 1/ 1 0/ 0 -HAIR LOSS RIGHT LATERAL THORACIC AREA 1/ 1 0/ 0 0/ 0 0/ 0 -SCABBING RIGHT LATERAL THORACIC AREA 1/ 1 0/ 0 0/ 0 0/ 0 -SCABBING LEFT FORELIMB 1/ 1 0/ 0 0/ 0 0/ 0 -SCABBING RIGHT FORELIMB 1/ 1 0/ 0 0/ 0 0/ 0 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PCSUv4.07 01/23/2007 -186- TABLE 26 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 28 MEAN 88. 92. 90. 85. % DIFFERENCE 4.5 2.3 -3.4 S.D. 10.5 8.9 8.1 10.2 N 20 20 20 20 PND 35 MEAN % DIFFERENCE S.D. N 151. 17.9 20 160. 6.0 15.6 20 156. 3.3 12.1 20 147. -2.6 15.1 20 PND 42 MEAN % DIFFERENCE S.D. N 215. 20.5 20 227. 5.6 21.6 20 222. 3.3 13.6 20 214. -0.5 20.0 20 -187- PND 49 MEAN % DIFFERENCE S.D. N 272. 24.6 20 287. 5.5 27.4 20 280. 2.9 16.7 20 271. -0.4 25.7 20 PND 56 MEAN % DIFFERENCE S.D. N 325. 29.1 20 342. 5.2 30.8 20 335. 3.1 19.0 20 326. 0.3 26.0 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 26 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 63 MEAN 364. 388. 376. 365. % DIFFERENCE 6.6 3.3 0.3 S.D. 32.3 38.5 21.8 31.3 N 20 20 20 20 PND 70 MEAN % DIFFERENCE S.D. N 402. 36.1 20 428. 6.5 44.7 20 416. 3.5 24.3 20 408. 1.5 34.6 20 PND 72 MEAN % DIFFERENCE S.D. N 413. 39.2 20 440. 6.5 46.9 20 428. 3.6 25.1 20 420. 1.7 34.6 20 -188- ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 26 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION SUMMARY OF BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 28 MEAN 80. 84. 82. 80. % DIFFERENCE 5.0 2.5 0.0 S.D. 9.6 9.0 7.4 8.0 N 20 20 20 20 PND 35 MEAN % DIFFERENCE S.D. N 129. 14.4 20 135. 4.7 10.6 20 132. 2.3 10.1 20 130. 0.8 11.0 20 PND 42 MEAN % DIFFERENCE S.D. N 164. 15.4 20 173. 5.5 11.1 20 168. 2.4 14.1 20 164. 0.0 12.5 20 -189- PND 49 MEAN % DIFFERENCE S.D. N 188. 19.0 20 195. 3.7 16.0 20 191. 1.6 17.0 20 188. 0.0 15.9 20 PND 56 MEAN % DIFFERENCE S.D. N 212. 24.2 20 218. 2.8 18.5 20 212. 0.0 20.3 20 210. -0.9 18.8 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 26 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION SUMMARY OF BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 63 MEAN 228. 237. 231. 229. % DIFFERENCE 3.9 1.3 0.4 S.D. 23.5 17.8 22.8 20.9 N 20 20 20 20 PND 70 MEAN % DIFFERENCE S.D. N 243. 28.3 20 254. 4.5 21.1 20 244. 0.4 18.5 20 241. -0.8 23.6 20 PND 72 MEAN % DIFFERENCE S.D. N 245. 25.7 20 255. 4.1 21.7 20 251. 2.4 21.6 20 246. 0.4 23.9 20 -190- ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PJTBWSUv5.14 10/10/2006 TABLE 27 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 28- 35 MEAN 63. 68. 66. 62. S.D. 8.1 7.8 5.4 5.9 N 20 20 20 20 PND 35- 42 MEAN S.D. N 64. 67. 66. 67. 4.8 6.8 4.7 7.7 20 20 20 20 PND 42- 49 MEAN S.D. N 57. 60. 58. 57. 7.0 7.8 5.1 9.1 20 20 20 20 PND 49- 56 MEAN S.D. N 52. 56. 55. 55. 6.5 7.2 7.3 7.0 20 20 20 20 -191- PND 56- 63 MEAN S.D. N 39. 45.* 41. 39. 6.8 9.5 5.5 6.6 20 20 20 20 PND 63- 70 MEAN S.D. N 38. 40. 40. 43. 7.8 8.8 5.8 6.7 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------* = Significantly different from the control group at 0.05 using Dunnett's test MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES TABLE 27 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 70- 72 MEAN 11. 13. 12. 12. S.D. 5.3 4.3 4.2 4.0 N 20 20 20 20 PND 28- 72 MEAN S.D. N 325. 31.7 20 348. 39.7 20 338. 23.0 20 335. 29.2 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES -192- TABLE 27 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION SUMMARY OF BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 28- 35 MEAN 48. 51. 50. 50. S.D. 6.1 3.8 4.2 4.6 N 20 20 20 20 PND 35- 42 MEAN S.D. N 35. 38. 36. 34. 6.5 3.2 8.7 5.5 20 20 20 20 PND 42- 49 MEAN S.D. N 24. 22. 23. 24. 7.2 8.1 5.8 7.9 20 20 20 20 PND 49- 56 MEAN S.D. N 24. 23. 21. 22. 7.7 7.7 8.8 6.3 20 20 20 20 -193- PND 56- 63 MEAN S.D. N 16. 19. 20. 18. 7.9 7.3 6.6 4.0 20 20 20 20 PND 63- 70 MEAN S.D. N 15. 17. 13. 13. 6.6 8.2 9.4 7.2 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES TABLE 27 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION SUMMARY OF BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 70- 72 MEAN 1. 1. 6. 5. S.D. 7.1 6.8 8.7 8.9 N 20 20 20 20 PND 28- 72 MEAN S.D. N 164. 20.5 20 171. 17.6 20 169. 19.5 20 166. 23.2 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES PJTBWSUv5.14 10/10/2006 -194- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 4 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -195- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 4 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 RED DEPOSITS - NOSE ABSENT 20 20 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE PRESENT ABSENT 2 - 1 - 18 20 19 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 SKIN COLOR PINK 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -196- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 4 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -197- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 4 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 RED DEPOSITS - NOSE PRESENT ABSENT - 1 - - 20 19 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE PRESENT ABSENT - - 1 - 20 20 19 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 SKIN COLOR PINK 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -198- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 11 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -199- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 11 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 RED DEPOSITS - NOSE ABSENT 20 20 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 SKIN COLOR PINK 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -200- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 11 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -201- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 11 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 RED DEPOSITS - NOSE ABSENT 20 20 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 SKIN COLOR PINK 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -202- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 PILOERECTION NONE 20 20 20 20 FUR APPEARANCE NORMAL: CLEAN AND GROOMED 20 20 20 20 PALPEBRAL CLOSURE WIDE OPEN 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -203- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 RED DEPOSITS - NOSE ABSENT 20 20 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -204- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 PINK 20 20 20 20 EYE COLOR PINK 20 20 20 20 PUPILLARY RESPONSE PRESENT 20 20 20 20 SKIN COLOR PINK 20 20 20 20 EYE PROMINENCE NORMAL 20 20 20 20 -205- MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 PILOERECTION NONE 20 20 20 20 FUR APPEARANCE NORMAL: CLEAN AND GROOMED 20 20 20 20 PALPEBRAL CLOSURE WIDE OPEN 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -206- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 RED DEPOSITS - NOSE ABSENT 20 20 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -207- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 PINK 20 20 20 20 EYE COLOR PINK 20 20 20 20 PUPILLARY RESPONSE PRESENT 20 20 20 20 SKIN COLOR PINK 20 20 20 20 EYE PROMINENCE NORMAL 20 20 20 20 -208- MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY EASY 20 20 19 19 - - 1 1 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 PILOERECTION NONE 20 20 20 20 FUR APPEARANCE NORMAL: CLEAN AND GROOMED 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -209- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 PALPEBRAL CLOSURE WIDE OPEN 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 RED DEPOSITS - NOSE PRESENT ABSENT 1 1 1 2 19 19 19 18 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -210- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 17 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 EYE COLOR PINK 20 20 20 20 PUPILLARY RESPONSE ABSENT PRESENT - - - 1 20 20 20 19 SKIN COLOR PINK 20 20 20 20 EYE PROMINENCE NORMAL 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -211- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 18 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 PILOERECTION NONE 20 20 20 20 FUR APPEARANCE NORMAL: CLEAN AND GROOMED 20 20 20 20 PALPEBRAL CLOSURE WIDE OPEN 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -212- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 19 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 RED DEPOSITS - NOSE PRESENT ABSENT - - - 1 20 20 20 19 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -213- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 20 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 EYE COLOR PINK 20 20 20 20 PUPILLARY RESPONSE ABSENT PRESENT - 1 - - 20 19 20 20 SKIN COLOR PINK 20 20 20 20 EYE PROMINENCE NORMAL 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -214- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 21 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT PRESENT 20 20 20 19 - - - 1 SALIVATION NONE 20 20 20 20 PILOERECTION NONE 20 20 20 20 FUR APPEARANCE NORMAL: CLEAN AND GROOMED 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -215- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 22 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 PALPEBRAL CLOSURE WIDE OPEN 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 RED DEPOSITS - NOSE PRESENT ABSENT 1 - - - 19 20 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -216- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 23 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 EYE COLOR PINK 20 20 20 20 PUPILLARY RESPONSE ABSENT PRESENT - - - 1 20 20 20 19 SKIN COLOR PINK 20 20 20 20 EYE PROMINENCE NORMAL 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -217- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 24 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY 20 20 20 20 EASE OF HANDLING ANIMAL IN HAND LOW 20 20 20 20 LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 PILOERECTION NONE 20 20 20 20 FUR APPEARANCE NORMAL: CLEAN AND GROOMED 20 20 20 20 PALPEBRAL CLOSURE WIDE OPEN 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -218- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 25 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 RED DEPOSITS - NOSE PRESENT ABSENT - - - 1 20 20 20 19 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 CRUSTY DEPOSITS - MOUTH ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -219- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 26 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 EYE COLOR PINK 20 20 20 20 PUPILLARY RESPONSE PRESENT 20 20 20 20 SKIN COLOR PINK 20 20 20 20 EYE PROMINENCE NORMAL 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -220- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 27 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY EASY 20 18 20 20 - 2 - - EASE OF HANDLING ANIMAL IN HAND LOW 20 18 20 20 MODERATELY LOW - 2 - - LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 PILOERECTION NONE 20 20 20 20 FUR APPEARANCE NORMAL: CLEAN AND GROOMED 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -221- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 28 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 PALPEBRAL CLOSURE WIDE OPEN 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 RED DEPOSITS - NOSE ABSENT 20 20 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 CRUSTY DEPOSITS - MOUTH ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -222- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 29 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 ABSENT 20 20 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 EYE COLOR PINK 20 20 20 20 PUPILLARY RESPONSE PRESENT 20 20 20 20 SKIN COLOR PINK 20 20 20 20 EYE PROMINENCE NORMAL 20 20 20 20 -223- MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 30 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 EASE OF REMOVAL FROM CAGE VERY EASY EASY 20 19 19 20 - 1 1 - EASE OF HANDLING ANIMAL IN HAND LOW 20 19 19 20 MODERATELY LOW - 1 1 - LACRIMATION NONE 20 20 20 20 CHROMODACRYORRHEA ABSENT 20 20 20 20 SALIVATION NONE 20 20 20 20 PILOERECTION NONE 20 20 20 20 FUR APPEARANCE NORMAL: CLEAN AND GROOMED 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -224- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 31 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 PALPEBRAL CLOSURE WIDE OPEN 20 20 20 20 RESPIRATORY RATE NORMAL (80-110) 20 20 20 20 RESPIRATORY CHARACTER NORMAL 20 20 20 20 RED DEPOSITS - EYES ABSENT 20 20 20 20 RED DEPOSITS - NOSE ABSENT 20 20 20 20 RED DEPOSITS - MOUTH ABSENT 20 20 20 20 CRUSTY DEPOSITS - EYES ABSENT 20 20 20 20 CRUSTY DEPOSITS - NOSE ABSENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -225- TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) PROJECT NO.:WIL-180017H ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 32 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 CRUSTY DEPOSITS - MOUTH PRESENT ABSENT - 1 - - 20 19 20 20 MUCOUS MEMBRANES - COLOR PINK 20 20 20 20 EYE COLOR PINK 20 20 20 20 PUPILLARY RESPONSE PRESENT 20 20 20 20 SKIN COLOR PINK 20 20 20 20 EYE PROMINENCE NORMAL 20 20 20 20 MUSCLE TONE FIRM BUT NOT HARD 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED NONE SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP PFOBGv1.52 10/10/2006 R:01/26/2007 -226- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 4 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 19 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL 20 20 20 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 URINATION COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 DEFECATION COUNTS MEAN 0.0 0.0 0.0 0.0 S.D. 0.00 0.00 0.00 0.00 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -227- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 4 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL 20 20 20 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 URINATION COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 DEFECATION COUNTS MEAN 0.0 0.0 0.0 0.0 S.D. 0.00 0.00 0.00 0.00 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -228- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 11 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL 20 20 20 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -229- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 11 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 URINATION COUNTS MEAN S.D. N 0.4 0.60 20 0.5 0.83 20 0.2 0.41 20 0.8 1.11 20 DEFECATION COUNTS MEAN 0.0 0.0 0.0 0.0 S.D. 0.00 0.00 0.00 0.00 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -230- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 11 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL 20 20 20 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -231- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 11 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 URINATION COUNTS MEAN S.D. N 0.4 0.68 20 0.5 0.76 20 0.8 0.79 20 0.5 0.76 20 DEFECATION COUNTS MEAN 0.0 0.0 0.0 0.0 S.D. 0.00 0.00 0.00 0.00 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -232- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL 20 20 20 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -233- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 -234- BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 GROOMING COUNTS MEAN S.D. N 0.7 2.30 20 0.5 1.79 20 0.3 1.13 20 0.0 0.00 20 URINATION COUNTS MEAN S.D. N 0.1 0.22 20 0.1 0.22 20 0.1 0.31 20 0.1 0.22 20 DEFECATION COUNTS MEAN S.D. N 0.3 0.91 20 0.2 0.49 20 0.4 0.99 20 0.2 0.52 20 TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY 20 20 20 20 AIR RIGHTING REFLEX NORMAL 20 20 20 20 HINDLIMB EXTENSOR STRENGTH HINDLIMB RESISTANCE PRESENT 20 20 20 20 FORELIMB GRIPSTRENGTH (AVG) MEAN 138.4 137.4 132.3 119.7 S.D. 34.61 24.09 26.98 24.47 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 HINDLIMB GRIPSTRENGTH (AVG) MEAN 79.8 82.8 84.8 66.7* S.D. 17.51 12.23 16.30 17.09 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED * = Significantly different from the control group at 0.05 using Dunnett's test -235- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL 20 20 20 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -236- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 -237- BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 GROOMING COUNTS MEAN S.D. N 0.3 0.91 20 0.3 1.34 20 0.2 0.49 20 0.0 0.00 20 URINATION COUNTS MEAN S.D. N 0.1 0.22 20 0.2 0.52 20 0.1 0.31 20 0.0 0.00 20 DEFECATION COUNTS MEAN S.D. N 0.1 0.45 20 0.5 0.94 20 0.2 0.52 20 0.0 0.00 20 TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY 20 20 20 20 AIR RIGHTING REFLEX NORMAL 20 20 20 20 HINDLIMB EXTENSOR STRENGTH HINDLIMB RESISTANCE PRESENT 20 20 20 20 FORELIMB GRIPSTRENGTH (AVG) MEAN 142.8 140.5 132.5 129.3 S.D. 32.41 31.10 28.06 26.98 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 21 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 HINDLIMB GRIPSTRENGTH (AVG) MEAN 73.8 79.2 77.5 73.6 S.D. 16.04 12.49 17.72 12.13 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -238- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL SOMEWHAT HIGH 20 19 20 20 - 1 - - BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -239- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 -240- BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 GROOMING COUNTS MEAN S.D. N 0.0 0.00 20 0.1 0.22 20 0.0 0.00 20 0.2 0.67 20 URINATION COUNTS MEAN S.D. N 0.3 0.44 20 0.5 0.69 20 0.7 0.86 20 0.3 0.44 20 DEFECATION COUNTS MEAN S.D. N 0.3 0.80 20 0.1 0.45 20 0.4 1.14 20 0.5 0.89 20 TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY ENERGETIC RESPONSE 18 18 18 19 2 2 2 1 AIR RIGHTING REFLEX NORMAL 20 20 20 20 HINDLIMB EXTENSOR STRENGTH HINDLIMB RESISTANCE PRESENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 FORELIMB GRIPSTRENGTH (AVG) MEAN S.D. N 444.3 109.89 20 449.2 73.47 20 459.8 65.33 20 405.6 76.88 20 HINDLIMB GRIPSTRENGTH (AVG) MEAN 316.8 354.7 358.7 337.0 S.D. 71.99 100.95 77.92 87.04 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -241- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL SOMEWHAT HIGH 19 20 18 19 1 - 2 1 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -242- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 17 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 -243- BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 GROOMING COUNTS MEAN S.D. N 0.1 0.31 20 0.0 0.00 20 0.0 0.00 20 0.1 0.45 20 URINATION COUNTS MEAN S.D. N 0.2 0.52 20 0.6 0.60 20 0.4 0.50 20 0.2 0.52 20 DEFECATION COUNTS MEAN S.D. N 0.3 0.80 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY ENERGETIC RESPONSE 20 19 18 19 - 1 2 1 AIR RIGHTING REFLEX NORMAL 20 20 20 20 HINDLIMB EXTENSOR STRENGTH HINDLIMB RESISTANCE PRESENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 18 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 35 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 FORELIMB GRIPSTRENGTH (AVG) MEAN S.D. N 434.0 77.32 20 430.8 75.65 20 424.7 70.17 20 400.6 59.28 20 HINDLIMB GRIPSTRENGTH (AVG) MEAN 308.0 350.9 323.4 338.9 S.D. 84.52 98.19 75.49 77.20 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -244- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 19 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL LOW NORMAL - - 2 - 20 20 18 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -245- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 20 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 -246- BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 GROOMING COUNTS MEAN S.D. N 0.1 0.45 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 URINATION COUNTS MEAN S.D. N 0.2 0.70 20 0.0 0.00 20 0.2 0.37 20 0.6 0.94 20 DEFECATION COUNTS MEAN S.D. N 0.5 1.00 20 0.0 0.00 20 0.1 0.22 20 0.4 1.79 20 TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY ENERGETIC RESPONSE 19 20 20 20 1 - - - AIR RIGHTING REFLEX NORMAL 20 20 20 20 HINDLIMB EXTENSOR STRENGTH HINDLIMB RESISTANCE PRESENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 21 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 FORELIMB GRIPSTRENGTH (AVG) MEAN S.D. N 626.4 190.23 20 654.4 197.79 20 617.8 159.91 20 679.3 184.36 20 HINDLIMB GRIPSTRENGTH (AVG) MEAN 434.2 441.8 425.3 443.4 S.D. 162.30 165.65 159.93 127.66 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -247- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 22 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL SOMEWHAT HIGH 19 20 18 20 1 - 2 - BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -248- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 23 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 -249- BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 GROOMING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 URINATION COUNTS MEAN S.D. N 0.1 0.22 20 0.1 0.31 20 0.1 0.31 20 0.1 0.31 20 DEFECATION COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY JUMPS OR BITES 20 20 19 20 - - 1 - AIR RIGHTING REFLEX NORMAL 20 20 20 20 HINDLIMB EXTENSOR STRENGTH HINDLIMB RESISTANCE PRESENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 24 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 45 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 FORELIMB GRIPSTRENGTH (AVG) MEAN S.D. N 603.3 186.52 20 597.3 176.64 20 663.1 151.84 20 579.6 149.02 20 HINDLIMB GRIPSTRENGTH (AVG) MEAN 416.6 427.0 429.1 427.2 S.D. 154.75 144.35 126.17 140.45 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -250- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 25 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL 20 20 20 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -251- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 26 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 -252- BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 GROOMING COUNTS MEAN S.D. N 0.0 0.00 20 0.1 0.22 20 0.1 0.31 20 0.0 0.00 20 URINATION COUNTS MEAN S.D. N 0.5 0.51 20 0.6 0.50 20 0.9 0.55 20 0.6 0.50 20 DEFECATION COUNTS MEAN S.D. N 0.3 0.92 20 0.2 0.37 20 0.4 0.93 20 0.2 0.37 20 TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY 20 20 20 20 AIR RIGHTING REFLEX NORMAL 20 20 20 20 HINDLIMB EXTENSOR STRENGTH HINDLIMB RESISTANCE PRESENT 20 20 20 20 FORELIMB GRIPSTRENGTH (AVG) MEAN 472.5 484.5 457.0 448.7 S.D. 134.22 82.19 118.75 123.87 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 27 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 MALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 HINDLIMB GRIPSTRENGTH (AVG) MEAN 336.0 310.3 320.8 315.3 S.D. 102.60 68.03 76.45 81.63 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -253- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 28 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 MOBILITY NORMAL 20 20 20 20 GAIT NORMAL 20 20 20 20 CONVULSIONS-CLONIC ABSENT 20 20 20 20 CONVULSIONS-TONIC ABSENT 20 20 20 20 TREMORS ABSENT 20 20 20 20 AROUSAL NORMAL 20 20 20 20 BIZARRE/STEREOTYPIC BEHAVIOR NONE 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group -254- TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 29 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 -255- BACKING COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 GROOMING COUNTS MEAN S.D. N 0.1 0.22 20 0.0 0.00 20 0.0 0.00 20 0.1 0.22 20 URINATION COUNTS MEAN S.D. N 0.0 0.00 20 0.1 0.22 20 0.0 0.00 20 0.1 0.22 20 DEFECATION COUNTS MEAN S.D. N 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 0.0 0.00 20 TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY ENERGETIC RESPONSE 19 20 20 20 1 - - - AIR RIGHTING REFLEX NORMAL 20 20 20 20 HINDLIMB EXTENSOR STRENGTH HINDLIMB RESISTANCE PRESENT 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group TABLE 29 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 30 SPONSOR:3M CORPORATION SUMMARY OF DETAILED CLINICAL OBSERVATIONS PND 60 SPONSOR NO.:06-128 FEMALES GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS TESTED 20 20 20 20 FORELIMB GRIPSTRENGTH (AVG) MEAN S.D. N 408.9 78.80 20 410.2 74.18 20 441.6 133.21 20 399.1 69.26 20 HINDLIMB GRIPSTRENGTH (AVG) MEAN 295.9 297.3 303.6 286.8 S.D. 72.64 93.51 88.82 63.40 N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DATA PRESENTED ARE NUMBER OF ANIMALS EXHIBITING RESPONSE, UNLESS OTHERWISE NOTED None significantly different from the control group PFOBGv1.52 10/10/2006 R:01/26/2007 -256- PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period PND013 Sex Variable M TOTAL Minutes 0-15 16-30 31-45 46-60 Overall Cumulative TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF MOTOR ACTIVITY COUNTS Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference Control S.D. Linear Trend p-value# 110 NA 60.6 170 54.5 172.2 NT 128 16.4 190.0 NT 130 18.2 155.8 NT Mean % Difference Control S.D. Linear Trend p-value# 67 NA 75.0 139 107.5 117.8 NT 111 65.7 250.6 NT 95 41.8 113.1 NT Mean S.D. Linear Trend p-value# 89 160.0 60 90.3 NT 62 103.8 NT 39 58.4 NT Mean S.D. Linear Trend p-value# 67 107.9 124 213.7 NT 97 192.7 NT 89 153.5 NT Mean S.D. Linear Trend p-value# 83 123 NA NA NT 99 88 NA NA NT 0.938 Mean % Difference Control S.D. N 333 NA 336.3 20 493 48.0 351.8 20 398 19.5 522.2 20 353 6.0 377.0 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.663 0.571 0.420 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -257- PAGE 1 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period PND013 Sex Variable F TOTAL Minutes 0-15 16-30 31-45 46-60 Overall Cumulative TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF MOTOR ACTIVITY COUNTS Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference Control S.D. Linear Trend p-value# 115 NA 107.9 225 95.7 244.9 NT 129 12.2 180.2 NT 102 -11.3 73.1 NT Mean % Difference Control S.D. Linear Trend p-value# 92 NA 94.3 206 123.9 284.3 NT 108 17.4 139.1 NT 81 -12.0 129.7 NT Mean S.D. Linear Trend p-value# 59 100.6 190 258.1 NT 126 145.7 NT 96 168.2 NT Mean S.D. Linear Trend p-value# 78 140.3 174 271.4 NT 74 98.5 NT 113 216.4 NT Mean S.D. Linear Trend p-value# 86 199 109 98 NA NA NA NA NT NT 0.702 Mean % Difference Control S.D. N 343 NA 263.0 20 795 131.8 904.3 20 437 27.4 430.9 20 392 14.3 391.7 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.047 0.913 0.730 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -258- PAGE 2 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period PND017 Sex Variable M TOTAL Minutes 0-15 16-30 31-45 46-60 Overall Cumulative TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF MOTOR ACTIVITY COUNTS Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference Control S.D. Linear Trend p-value# 471 NA 317.8 605 28.5 326.4 NT 732 55.4 387.9 NT 383 -18.7 315.0 0.643 Mean % Difference Control S.D. Linear Trend p-value# 208 NA 199.2 225 8.2 215.3 0.858 410 97.1 262.2 0.031* 370 77.9 333.9 0.023* Mean S.D. Linear Trend p-value# 184 208.8 222 256.4 NT 352 265.9 0.071 427 393.8 0.004* Mean S.D. Linear Trend p-value# 108 203.9 240 251.1 NT 273 246.4 0.076 354 326.4 0.009* Mean S.D. Linear Trend p-value# 243 323 442 383 NA NA NA NA 0.299 0.012* 0.030* Mean % Difference Control S.D. N 971 NA 772.8 20 1293 33.2 832.6 20 1766 81.9 932.3 20 1534 58.0 1200.5 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.071 <0.001* 0.002* AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -259- PAGE 3 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period PND017 Sex Variable F TOTAL Minutes 0-15 16-30 31-45 46-60 Overall Cumulative TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF MOTOR ACTIVITY COUNTS Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference Control S.D. Linear Trend p-value# 544 NA 351.6 607 11.6 208.9 NT 580 6.6 306.9 NT 559 2.8 376.0 NT Mean % Difference Control S.D. Linear Trend p-value# 271 NA 224.2 247 -8.9 241.7 NT 345 27.3 273.4 NT 371 36.9 271.8 NT Mean S.D. Linear Trend p-value# 147 183.4 254 312.4 NT 316 248.5 NT 353 273.2 NT Mean S.D. Linear Trend p-value# 124 185.2 236 304.9 NT 291 248.7 NT 303 330.2 NT Mean 271 336 383 397 S.D. NA NA NA NA Linear Trend p-value# NT NT 0.074 Mean % Difference Control S.D. N 1085 NA 668.1 20 1344 23.9 914.4 20 1532 41.2 924.5 20 1587 46.3 1109.6 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.324 0.295 0.147 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -260- PAGE 4 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period PND021 Sex Variable M TOTAL Minutes 0-15 16-30 31-45 46-60 Overall Cumulative TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF MOTOR ACTIVITY COUNTS Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference Control S.D. Linear Trend p-value# 455 NA 144.9 547 20.2 158.2 NT 513 12.7 136.5 NT 574 26.2 195.1 NT Mean % Difference Control S.D. Linear Trend p-value# 93 NA 115.3 157 68.8 181.0 NT 129 38.7 126.6 NT 128 37.6 207.5 NT Mean S.D. Linear Trend p-value# 63 63.0 106 154.0 NT 49 86.4 NT 100 192.6 NT Mean S.D. Linear Trend p-value# 35 74.1 72 108.1 NT 58 109.1 NT 122 239.7 NT Mean 162 221 187 231 S.D. NA NA NA NA Linear Trend p-value# NT NT 0.162 Mean % Difference Control S.D. N 646 NA 263.0 20 882 36.5 483.6 20 748 15.8 328.7 20 924 43.0 763.6 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.275 0.365 0.112 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -261- PAGE 5 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period PND021 Sex Variable F TOTAL Minutes 0-15 16-30 31-45 46-60 Overall Cumulative TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF MOTOR ACTIVITY COUNTS Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference Control S.D. Linear Trend p-value# 505 NA 128.5 479 -5.1 119.5 NT 563 11.5 169.5 NT 566 12.1 170.8 NT Mean % Difference Control S.D. Linear Trend p-value# 136 NA 184.1 143 5.1 128.3 NT 104 -23.5 111.1 NT 228 67.6 164.7 NT Mean S.D. Linear Trend p-value# 29 49.7 63 76.7 NT 105 130.3 NT 91 154.0 NT Mean S.D. Linear Trend p-value# 71 111.9 35 69.2 NT 64 106.0 NT 93 163.3 NT Mean 185 180 209 245 S.D. NA NA NA NA Linear Trend p-value# NT 0.413 0.027* Mean % Difference Control S.D. N 740 NA 367.2 20 720 -2.7 250.9 20 836 13.0 345.2 20 979 32.3 512.3 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.114 0.020 0.735 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -262- PAGE 6 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period PND061 Sex Variable M TOTAL Minutes 0-15 16-30 31-45 46-60 Overall Cumulative TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF MOTOR ACTIVITY COUNTS Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference Control S.D. Linear Trend p-value# 1296 NA 243.7 1375 6.1 217.9 NT 1397 7.8 295.7 NT 1306 0.8 186.8 NT Mean % Difference Control S.D. Linear Trend p-value# 626 NA 261.6 572 -8.6 172.4 NT 582 -7.0 277.8 NT 591 -5.6 291.0 NT Mean S.D. Linear Trend p-value# 325 248.5 402 220.9 NT 373 249.8 NT 349 253.4 NT Mean S.D. Linear Trend p-value# 235 278.3 303 208.0 NT 276 250.7 NT 284 175.0 NT Mean 621 663 657 632 S.D. NA NA NA NA Linear Trend p-value# NT NT 0.872 Mean % Difference Control S.D. N 2483 NA 818.4 20 2652 6.8 624.4 20 2628 5.8 884.5 20 2529 1.9 567.1 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.856 0.555 0.857 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -263- PAGE 7 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period PND061 Sex Variable F TOTAL Minutes 0-15 16-30 31-45 46-60 Overall Cumulative TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF MOTOR ACTIVITY COUNTS Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference Control S.D. Linear Trend p-value# 1198 NA 211.4 1161 -3.1 211.0 NT 1163 -2.9 246.4 NT 1217 1.6 198.3 NT Mean % Difference Control S.D. Linear Trend p-value# 535 NA 198.9 533 -0.4 197.4 NT 458 -14.4 199.0 NT 585 9.3 156.0 NT Mean S.D. Linear Trend p-value# 329 209.9 407 223.1 NT 318 246.7 NT 361 207.6 NT Mean S.D. Linear Trend p-value# 255 230.8 262 186.3 NT 186 169.5 NT 248 183.3 NT Mean 579 591 531 603 S.D. NA NA NA NA Linear Trend p-value# NT NT 0.937 Mean % Difference Control S.D. N 2316 NA 612.5 20 2364 2.1 587.9 20 2124 -8.3 653.7 20 2412 4.1 592.1 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.472 0.777 0.869 CS --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -264- PAGE 8 TABLE 30 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION SUMMARY OF MOTOR ACTIVITY COUNTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 13 0 TO 15 MINS AMBULATORY MEAN 21. 50. 37. 40. S.D. 20.9 74.4 81.3 70.0 16 TO 30 MINS AMBULATORY MEAN S.D. 11. 23.2 36. 44.8 32. 101.1 22. 47.2 31 TO 45 MINS AMBULATORY MEAN S.D. 26. 68.2 14. 33.7 17. 48.9 6. 19.7 46 TO 60 MINS AMBULATORY MEAN S.D. 17. 45.3 36. 80.5 27. 80.3 28. 61.6 -265- AMBULATORY MEAN S.D. N 75. 135.7 20 136. 121.6 20 113. 218.5 20 96. 160.8 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 30 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION SUMMARY OF MOTOR ACTIVITY COUNTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 17 0 TO 15 MINS AMBULATORY MEAN 163. 224. 278. 131. S.D. 135.8 160.3 187.5 134.6 16 TO 30 MINS AMBULATORY MEAN S.D. 59. 71.4 73. 86.2 144. 115.5 125. 141.5 31 TO 45 MINS AMBULATORY MEAN S.D. 52. 77.7 73. 92.8 121. 108.1 163. 158.8 46 TO 60 MINS AMBULATORY MEAN S.D. 31. 74.6 79. 88.7 93. 104.1 133. 133.1 -266- AMBULATORY MEAN S.D. N 305. 302.8 20 449. 345.2 20 635. 413.2 20 551. 488.1 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 30 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION SUMMARY OF MOTOR ACTIVITY COUNTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 21 0 TO 15 MINS AMBULATORY MEAN 167. 200. 184. 201. S.D. 60.8 61.9 63.2 83.6 16 TO 30 MINS AMBULATORY MEAN S.D. 21. 34.4 37. 47.6 30. 39.2 36. 78.8 31 TO 45 MINS AMBULATORY MEAN S.D. 11. 19.2 24. 43.1 10. 23.4 25. 67.0 46 TO 60 MINS AMBULATORY MEAN S.D. 5. 16.7 13. 28.9 13. 32.3 32. 79.7 -267- AMBULATORY MEAN S.D. N 204. 94.8 20 274. 142.2 20 237. 111.9 20 294. 288.3 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 30 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION SUMMARY OF MOTOR ACTIVITY COUNTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 61 0 TO 15 MINS AMBULATORY MEAN 465. 540. 518. 482. S.D. 112.3 115.5 98.8 104.5 16 TO 30 MINS AMBULATORY MEAN S.D. 205. 97.3 193. 67.0 201. 118.9 207. 120.9 31 TO 45 MINS AMBULATORY MEAN S.D. 95. 80.4 140. 89.1 121. 84.0 106. 91.0 46 TO 60 MINS AMBULATORY MEAN S.D. 76. 111.5 101. 76.1 89. 86.8 90. 60.6 -268- AMBULATORY MEAN S.D. N 840. 304.1 20 974. 271.6 20 929. 312.9 20 886. 235.9 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 30 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION SUMMARY OF MOTOR ACTIVITY COUNTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 13 0 TO 15 MINS AMBULATORY MEAN 31. 75. 34. 21. S.D. 47.3 117.5 62.3 22.1 16 TO 30 MINS AMBULATORY MEAN S.D. 17. 33.7 71. 129.8 28. 48.7 22. 55.7 31 TO 45 MINS AMBULATORY MEAN S.D. 11. 35.5 71. 118.1 30. 49.8 30. 61.8 46 TO 60 MINS AMBULATORY MEAN S.D. 21. 53.8 65. 120.9 18. 37.4 47. 104.2 -269- AMBULATORY MEAN S.D. N 80. 104.6 20 283.* 409.2 20 109. 150.2 20 120. 154.4 20 ----------------------------------------------------------------------------------------------------------------------------------* = Significantly different from the control group at 0.05 using Dunnett's test TABLE 30 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION SUMMARY OF MOTOR ACTIVITY COUNTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 17 0 TO 15 MINS AMBULATORY MEAN 201. 225. 212. 213. S.D. 164.5 102.4 138.8 171.0 16 TO 30 MINS AMBULATORY MEAN S.D. 87. 79.9 76. 86.3 117. 128.8 126. 99.4 31 TO 45 MINS AMBULATORY MEAN S.D. 48. 67.3 82. 120.8 108. 90.8 118. 104.1 46 TO 60 MINS AMBULATORY MEAN S.D. 38. 62.4 78. 116.8 98. 94.1 107. 124.0 -270- AMBULATORY MEAN S.D. N 374. 268.2 20 461. 350.7 20 535. 370.3 20 564. 432.4 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 30 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION SUMMARY OF MOTOR ACTIVITY COUNTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 21 0 TO 15 MINS AMBULATORY MEAN 177. 168. 199. 199. S.D. 52.6 47.5 72.8 68.4 16 TO 30 MINS AMBULATORY MEAN S.D. 37. 59.3 40. 40.8 25. 31.6 62. 60.7 31 TO 45 MINS AMBULATORY MEAN S.D. 4. 12.5 12. 18.4 23. 35.6 18. 42.2 46 TO 60 MINS AMBULATORY MEAN S.D. 15. 27.9 6. 19.1 13. 30.4 19. 45.9 -271- AMBULATORY MEAN S.D. N 234. 117.1 20 227. 78.6 20 259. 115.8 20 298. 164.7 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group TABLE 30 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION SUMMARY OF MOTOR ACTIVITY COUNTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 61 0 TO 15 MINS AMBULATORY MEAN 519. 515. 505. 540. S.D. 105.1 104.3 127.0 108.0 16 TO 30 MINS AMBULATORY MEAN S.D. 209. 91.8 203. 98.0 166. 92.2 234. 74.4 31 TO 45 MINS AMBULATORY MEAN S.D. 121. 87.8 161. 99.8 113. 98.1 137. 88.3 46 TO 60 MINS AMBULATORY MEAN S.D. 91. 100.7 91. 72.3 66. 70.9 92. 78.1 -272- AMBULATORY MEAN S.D. N 940. 283.0 20 971. 273.0 20 850. 297.9 20 1003. 275.9 20 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PMASUMv5.15 10/23/2006 R:10/23/2006 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Variable Sex Blocks TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF STARTLE RESPONSE DATA Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND020 VMAX M 1-10 Mean % Difference Control S.D. Linear Trend p-value# 188.3 NA 69.33 165.5 -12.1 59.04 NT 161.3 -14.3 55.70 NT 162.7 -13.6 68.57 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 164.0 NA 71.58 141.3 -13.8 48.86 NT 142.8 -12.9 55.56 NT 134.2 -18.2 70.14 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 148.4 NA 55.98 130.2 -12.3 56.55 NT 140.6 -5.3 63.72 NT 116.8 -21.3 68.73 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 123.1 NA 49.89 139.6 13.4 47.81 NT 143.1 16.2 59.29 NT 115.6 -6.1 62.87 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 133.3 NA 61.01 129.5 -2.9 49.37 NT 137.4 3.1 47.86 NT 121.0 -9.2 63.22 NT Overall Mean S.D. N Linear Trend p-value# 151.4 NA 20 141.2 NA 20 NT 145.0 NA 20 NT 130.1 NA 20 0.226 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.578 0.374 0.627 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -273- PAGE 1 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Variable Sex Blocks TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF STARTLE RESPONSE DATA Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND020 VMAX F 1-10 Mean % Difference Control S.D. Linear Trend p-value# 200.8 NA 77.89 185.8 -7.5 58.51 NT 169.5 -15.6 75.43 NT 173.6 -13.5 72.22 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 178.3 NA 72.32 163.1 -8.5 67.72 NT 159.8 -10.4 66.95 NT 140.8 -21.0 67.49 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 163.3 NA 74.00 145.2 -11.1 70.10 NT 163.3 0.0 71.98 NT 128.0 -21.6 62.63 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 168.5 NA 68.86 142.7 -15.3 59.87 NT 152.5 -9.5 73.89 NT 120.6 -28.4 63.85 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 147.4 NA 52.11 140.4 -4.7 70.27 NT 126.8 -14.0 67.83 NT 134.1 -9.0 67.19 NT Overall Mean S.D. N Linear Trend p-value# 171.7 NA 20 155.4 NA 20 NT 154.4 NA 20 NT 139.4 NA 20 0.073 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.314 0.511 0.530 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -274- PAGE 2 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Variable Sex Blocks TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF STARTLE RESPONSE DATA Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND020 TMAX M 1-10 Mean % Difference Control S.D. Linear Trend p-value# 26.3 NA 3.77 27.7 5.3 4.96 NT 26.2 -0.4 3.90 NT 26.5 0.8 5.21 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 24.3 NA 4.01 23.9 -1.6 4.13 NT 23.7 -2.5 3.84 NT 25.1 3.3 4.24 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 24.5 NA 4.06 25.1 2.4 5.68 NT 23.7 -3.3 4.29 NT 26.4 7.8 5.03 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 24.3 NA 3.64 24.0 -1.2 4.04 NT 23.0 -5.3 2.86 NT 22.9 -5.8 3.18 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 25.5 NA 5.82 24.0 -5.9 3.96 NT 25.0 -2.0 4.93 NT 24.2 -5.1 4.24 NT Overall Mean S.D. N Linear Trend p-value# 25.0 NA 20 24.9 NA 20 NT 24.3 NA 20 NT 25.0 NA 20 0.856 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.852 0.430 0.299 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -275- PAGE 3 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Variable Sex Blocks TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF STARTLE RESPONSE DATA Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND020 TMAX F 1-10 Mean % Difference Control S.D. Linear Trend p-value# 26.5 NA 6.62 26.1 -1.5 3.95 NT 24.9 -6.0 4.78 NT 26.5 0.0 4.71 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 22.7 NA 2.61 23.8 4.8 2.87 NT 22.3 -1.8 2.65 NT 24.5 7.9 4.96 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 22.6 NA 2.69 23.6 4.4 3.99 NT 22.8 0.9 5.00 NT 23.6 4.4 5.02 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 22.0 NA 2.00 24.2 10.0 3.71 NT 22.3 1.4 2.83 NT 24.3 10.5 4.85 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 23.7 NA 5.11 23.7 0.0 3.45 NT 24.4 3.0 4.67 NT 24.1 1.7 4.53 NT Overall Mean S.D. N Linear Trend p-value# 23.5 NA 20 24.3 NA 20 NT 23.3 NA 20 NT 24.6 NA 20 0.391 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.392 0.741 0.776 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -276- PAGE 4 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Variable Sex Blocks TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF STARTLE RESPONSE DATA Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND060 VMAX M 1-10 Mean % Difference Control S.D. Linear Trend p-value# 246.3 NA 294.08 136.9 -44.4 129.08 NT 162.6 -34.0 113.35 NT 149.6 -39.3 93.03 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 194.7 NA 215.91 112.3 -42.3 91.82 NT 151.7 -22.1 117.82 NT 108.5 -44.3 95.35 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 177.5 NA 236.83 97.6 -45.0 80.75 NT 123.2 -30.6 90.15 NT 79.7 -55.1 66.70 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 142.7 NA 157.72 96.0 -32.7 92.18 NT 95.4 -33.1 67.05 NT 86.0 -39.7 82.05 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 108.2 NA 112.74 101.1 -6.6 110.10 NT 113.1 4.5 90.60 NT 70.8 -34.6 69.90 NT Overall Mean S.D. N Linear Trend p-value# 173.9 NA 20 108.8 NA 20 NT 129.2 NA 20 NT 98.9 NA 20 0.096 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.221 0.349 0.528 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -277- PAGE 5 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Variable Sex Blocks TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF STARTLE RESPONSE DATA Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND060 VMAX F 1-10 Mean % Difference Control S.D. Linear Trend p-value# 117.0 NA 62.93 83.7 -28.5 29.45 NT 92.9 -20.6 52.65 NT 75.5 -35.5 61.68 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 73.1 NA 54.88 60.6 -17.1 28.02 NT 69.7 -4.7 36.89 NT 53.1 -27.4 52.79 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 59.5 NA 30.86 56.3 -5.4 41.41 NT 56.1 -5.7 32.53 NT 46.7 -21.5 33.15 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 51.2 NA 28.27 46.9 -8.4 33.49 NT 58.1 13.5 33.32 NT 52.2 2.0 43.54 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 52.5 NA 28.25 54.0 2.9 35.21 NT 65.0 23.8 49.19 NT 56.2 7.0 56.70 NT Overall Mean S.D. N Linear Trend p-value# 70.6 NA 20 60.3 NA 20 NT 68.4 NA 20 NT 56.8 NA 20 0.323 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.524 0.509 0.116 AR1 --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -278- PAGE 6 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Variable Sex Blocks TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF STARTLE RESPONSE DATA Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND060 TMAX M 1-10 Mean % Difference Control S.D. Linear Trend p-value# 32.0 NA 6.30 34.2 6.9 8.36 NT 32.9 2.8 7.78 NT 32.0 0.0 6.22 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 32.7 NA 9.10 35.4 8.3 8.68 NT 33.1 1.2 7.70 NT 34.0 4.0 10.57 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 31.5 NA 6.08 35.3 12.1 8.58 NT 32.6 3.5 8.15 NT 36.9 17.1 9.84 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 33.9 NA 7.68 36.6 8.0 9.41 NT 31.1 -8.3 8.04 NT 36.4 7.4 9.54 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 35.9 NA 10.06 35.4 -1.4 7.88 NT 35.4 -1.4 9.12 NT 34.2 -4.7 9.37 NT Overall Mean S.D. N Linear Trend p-value# 33.2 NA 20 35.4 NA 20 NT 33.0 NA 20 NT 34.7 NA 20 0.743 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.566 0.364 0.318 CS --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -279- PAGE 7 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Variable Sex Blocks TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF STARTLE RESPONSE DATA Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND060 TMAX F 1-10 Mean % Difference Control S.D. Linear Trend p-value# 31.6 NA 5.06 34.2 8.2 7.60 NT 34.9 10.4 7.72 NT 36.1 14.2 6.67 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 34.8 NA 6.70 35.8 2.9 5.83 NT 36.3 4.3 7.28 NT 34.4 -1.1 8.47 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 37.1 NA 5.04 33.2 -10.5 6.54 NT 34.5 -7.0 6.82 NT 35.8 -3.5 8.21 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 35.6 NA 7.86 37.3 4.8 7.62 NT 36.1 1.4 8.41 NT 35.7 0.3 10.35 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 36.0 NA 6.27 36.9 2.5 7.52 NT 37.4 3.9 10.22 NT 35.9 -0.3 9.60 NT Overall Mean S.D. N Linear Trend p-value# 35.0 NA 20 35.5 NA 20 NT 35.8 NA 20 NT 35.6 NA 20 0.702 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.968 0.460 0.314 CS --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. -280- PAGE 8 TABLE 31 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION SUMMARY OF STARTLE RESPONSE DATA SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 20 Vave (Millivolts) ALL TRIALS MEAN 33.0 30.8 31.1 28.7 S.D. 10.69 10.01 11.05 12.94 NUMBER OF ANIMALS TESTED N 20 20 20 20 PND 60 Vave (Millivolts) ALL TRIALS MEAN S.D. 36.7 38.06 23.6 17.45 26.8 17.42 20.2 13.02 NUMBER OF ANIMALS TESTED N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group -281- TABLE 31 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION SUMMARY OF STARTLE RESPONSE DATA SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- PND 20 Vave (Millivolts) ALL TRIALS MEAN 37.8 34.1 33.7 30.0 S.D. 13.32 12.88 12.94 12.33 NUMBER OF ANIMALS TESTED N 20 20 20 20 PND 60 Vave (Millivolts) ALL TRIALS MEAN S.D. 14.2 6.44 11.7 5.19 13.9 6.57 11.3 8.43 -282- NUMBER OF ANIMALS TESTED N 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group PSRSUMv5.12 10/12/2006 R:10/12/2006 TABLE 32 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF BIEL MAZE DATA SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1 SWIMMING ABILITY MEAN TIME (SECONDS) 8.62 9.10 8.58 11.54 S.D. 2.453 2.901 2.027 6.400 N 20 20 20 20 --------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DAY 1 SWIMMING ABILITY FOR TREATED GROUPS NOT SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP -283- TABLE 32 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF BIEL MAZE DATA SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1 SWIMMING ABILITY MEAN TIME (SECONDS) 8.54 9.59 9.59 8.72 S.D. 2.683 1.946 4.467 1.962 N 20 20 20 20 --------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY DAY 1 SWIMMING ABILITY FOR TREATED GROUPS NOT SIGNIFICANTLY DIFFERENT FROM THE CONTROL GROUP USING DUNNETT'S TEST MANUALv1.0 10/05/2006 R:10/23/2006 -284- PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 1 Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M A LEARNING ESCTIME 1 Mean % Difference S.D. N Linear Trend Control p-value# 78.73 NA 56.080 20 79.27 0.7 58.459 20 NT 71.50 -9.2 53.639 20 NT 79.80 1.4 61.173 20 NT 2 Mean 58.52 66.73 66.14 69.35 % Difference Control NA 14.0 13.0 18.5 S.D. 40.115 44.377 41.239 49.673 N 20 20 20 20 Linear Trend p-value# NT NT NT -285- 3 Mean 54.05 54.33 34.71 43.96 % Difference Control NA 0.5 -35.8 -18.7 S.D. 48.823 47.220 21.907 43.665 N 20 20 20 20 Linear Trend p-value# NT NT NT 4 Mean 52.80 38.34 37.71 40.11 % Difference Control NA -27.4 -28.6 -24.0 S.D. 45.443 38.436 28.372 42.615 N 20 20 20 19 Linear Trend p-value# NT NT NT Overall Mean S.D. N Linear Trend p-value# 61.03 NA 20 59.67 NA 20 NT 52.51 NA 20 NT 58.23 NA 20 0.556 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.748 0.924 0.557 AR1 ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 2 Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M A LEARNING ERRORS 1 Mean % Difference S.D. N Linear Trend Control p-value# 15 NA 10.8 20 14 -6.7 10.2 20 NT 13 -13.3 11.2 20 NT 16 6.7 13.2 20 NT 2 Mean 13 15 14 15 % Difference Control NA 15.4 7.7 15.4 S.D. 10.5 11.7 10.5 13.4 N 20 20 20 20 Linear Trend p-value# NT NT NT -286- 3 Mean 14 12 8 10 % Difference Control NA -14.3 -42.9 -28.6 S.D. 15.1 12.2 6.9 12.7 N 20 20 20 20 Linear Trend p-value# NT NT NT 4 Mean 12 7 9 8 % Difference Control NA -41.7 -25.0 -33.3 S.D. 11.6 9.5 8.7 10.1 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean 13 12 11 12 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.513 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.740 0.829 0.513 AR1 ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Sex Path Type TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 3 Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M B LEARNING ESCTIME 5 Mean % Difference S.D. N Linear Trend Control p-value# 137.70 NA 52.358 20 148.40 7.8 45.579 20 NT 145.03 5.3 53.498 20 NT 153.62 11.6 55.325 20 NT 6 Mean 136.05 140.71 120.70 114.06 % Difference Control NA 3.4 -11.3 -16.2 S.D. 58.799 53.137 66.215 57.104 N 20 20 20 20 Linear Trend p-value# NT NT NT -287- 7 Mean 144.25 129.48 132.08 125.58 % Difference Control NA -10.2 -8.4 -12.9 S.D. 51.920 57.075 56.344 61.184 N 20 20 20 20 Linear Trend p-value# NT NT NT 8 Mean 108.69 109.13 71.50 83.68 % Difference Control NA 0.4 -34.2 -23.0 S.D. 67.266 67.274 55.902 60.728 N 20 20 20 20 Linear Trend p-value# NT NT NT 9 Mean 83.67 102.52 66.82 87.01 % Difference Control NA 22.5 -20.1 4.0 S.D. 60.977 68.748 61.737 67.916 N 20 20 20 20 Linear Trend p-value# NT NT NT 10 Mean 63.49 70.42 72.30 63.87 % Difference Control NA 10.9 13.9 0.6 S.D. 58.001 56.758 67.910 51.948 N 20 20 20 20 Linear Trend p-value# NT NT NT ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 4 Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M B LEARNING ESCTIME Overall Mean S.D. N Linear Trend p-value# 112.31 NA 20 116.77 NA 20 NT 101.40 NA 20 NT 104.64 NA 20 0.299 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.535 0.610 0.267 CS -288- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Sex Path Type TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 5 Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M B LEARNING ERRORS 5 Mean % Difference S.D. N Linear Trend Control p-value# 31 NA 12.6 20 31 32 34 0.0 3.2 9.7 9.2 12.6 14.9 20 20 20 NT NT NT 6 Mean 29 29 25 25 % Difference Control NA 0.0 -13.8 -13.8 S.D. 13.9 13.0 14.7 13.7 N 20 20 20 20 Linear Trend p-value# NT NT NT -289- 7 Mean 32 28 31 28 % Difference Control NA -12.5 -3.1 -12.5 S.D. 12.1 13.8 13.8 14.0 N 20 20 20 20 Linear Trend p-value# NT NT NT 8 Mean 23 23 17 19 % Difference Control NA 0.0 -26.1 -17.4 S.D. 13.6 14.0 14.7 15.1 N 20 20 20 20 Linear Trend p-value# NT NT NT 9 Mean 19 23 15 19 % Difference Control NA 21.1 -21.1 0.0 S.D. 15.7 17.4 16.3 16.1 N 20 20 20 20 Linear Trend p-value# NT NT NT 10 Mean 14 15 17 14 % Difference Control NA 7.1 21.4 0.0 S.D. 13.0 14.7 18.5 14.6 N 20 20 20 20 Linear Trend p-value# NT NT NT ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 6 Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M B LEARNING ERRORS Overall Mean 25 25 23 23 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.384 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.802 0.868 0.641 CS -290- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Sex Path Type PND22 M A MEMORY TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 7 Variable Trial ESCTIME 11 12 Overall Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference S.D. N Linear Trend Control p-value# 74.70 NA 48.210 20 74.98 0.4 49.299 20 NT 83.29 11.5 44.296 20 NT 85.93 15.0 52.157 20 NT Mean % Difference S.D. N Linear Trend Control p-value# 44.38 NA 43.708 20 69.61 56.8 51.904 20 NT 51.43 15.9 34.062 20 NT 63.17 42.3 50.376 20 NT Mean S.D. N Linear Trend p-value# 59.54 NA 20 72.29 NA 20 NT 67.36 NA 20 NT 74.55 NA 20 0.307 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.629 0.372 0.943 CS -291- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Sex Path Type PND22 M A MEMORY TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 8 Variable Trial ERRORS 11 12 Overall Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference S.D. N Linear Trend Control p-value# 21 NA 16.9 20 21 0.0 15.9 20 NT 24 14.3 13.1 20 NT 25 19.0 16.7 20 NT Mean % Difference S.D. N Linear Trend Control p-value# 11 NA 14.4 20 17 54.5 13.5 20 NT 14 27.3 13.3 20 NT 16 45.5 16.2 20 NT Mean 16 19 19 21 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.231 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.650 0.684 0.962 CS -292- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 9 Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F A LEARNING ESCTIME 1 Mean % Difference S.D. N Linear Trend Control p-value# 63.95 NA 45.821 20 81.98 28.2 65.243 20 NT 50.31 -21.3 31.568 20 NT 74.55 16.6 56.967 20 NT 2 Mean 71.55 86.16 56.21 80.65 % Difference Control NA 20.4 -21.4 12.7 S.D. 55.083 57.290 42.679 46.187 N 20 20 20 20 Linear Trend p-value# NT NT NT -293- 3 Mean 61.46 56.72 41.02 67.92 % Difference Control NA -7.7 -33.3 10.5 S.D. 42.016 42.111 31.033 59.104 N 20 20 20 20 Linear Trend p-value# NT NT NT 4 Mean 39.80 43.15 31.69 47.24 % Difference Control NA 8.4 -20.4 18.7 S.D. 39.740 41.878 22.442 45.762 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean S.D. N Linear Trend p-value# 59.19 NA 20 67.00 NA 20 NT 44.81 NA 20 NT 67.59 NA 20 0.912 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.033 0.983 0.997 AR1 ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 10 Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F A LEARNING ERRORS 1 Mean % Difference S.D. N Linear Trend Control p-value# 13 NA 10.7 20 14 7.7 12.9 20 NT 10 -23.1 7.7 20 NT 15 15.4 11.5 20 NT 2 Mean 16 18 12 17 % Difference Control NA 12.5 -25.0 6.3 S.D. 14.2 12.3 9.8 11.4 N 20 20 20 20 Linear Trend p-value# NT NT NT -294- 3 Mean 14 12 9 16 % Difference Control NA -14.3 -35.7 14.3 S.D. 11.7 10.0 8.5 16.0 N 20 20 20 20 Linear Trend p-value# NT NT NT 4 Mean 8 9 6 10 % Difference Control NA 12.5 -25.0 25.0 S.D. 12.7 11.2 7.0 9.6 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean 13 13 9 14 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.967 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.065 0.990 0.992 AR1 ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Sex Path Type TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 11 Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F B LEARNING ESCTIME 5 Mean % Difference S.D. N Linear Trend Control p-value# 154.84 NA 47.173 20 156.05 0.8 43.725 20 NT 157.72 1.9 46.628 20 NT 145.74 -5.9 51.625 20 NT 6 Mean 150.22 123.50 139.91 149.06 % Difference Control NA -17.8 -6.9 -0.8 S.D. 41.379 65.560 61.655 56.800 N 20 20 20 20 Linear Trend p-value# NT NT NT -295- 7 Mean 134.72 119.20 117.25 116.94 % Difference Control NA -11.5 -13.0 -13.2 S.D. 57.907 68.931 67.598 67.633 N 20 20 20 20 Linear Trend p-value# NT NT NT 8 Mean 114.50 97.79 97.85 95.40 % Difference Control NA -14.6 -14.5 -16.7 S.D. 62.597 64.979 71.613 64.422 N 20 20 20 20 Linear Trend p-value# NT NT NT 9 Mean 113.10 80.64 75.29 90.47 % Difference Control NA -28.7 -33.4 -20.0 S.D. 67.774 62.479 64.213 65.982 N 20 20 20 20 Linear Trend p-value# NT NT NT 10 Mean 91.00 72.21 64.07 63.60 % Difference Control NA -20.6 -29.6 -30.1 S.D. 65.705 61.696 52.824 60.844 N 20 20 20 20 Linear Trend p-value# NT NT NT ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 12 Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F B LEARNING ESCTIME Overall Mean S.D. N Linear Trend p-value# 126.40 NA 20 108.23 NA 20 NT 108.68 NA 20 NT 110.20 NA 20 0.171 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.296 0.945 0.866 AR1 -296- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Sex Path Type TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 13 Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F B LEARNING ERRORS 5 Mean % Difference S.D. N Linear Trend Control p-value# 33 NA 11.5 20 32 -3.0 9.3 20 NT 33 0.0 10.3 20 NT 32 -3.0 14.0 20 NT 6 Mean 30 24 29 33 % Difference Control NA -20.0 -3.3 10.0 S.D. 9.3 13.9 15.6 13.4 N 20 20 19 20 Linear Trend p-value# NT NT NT -297- 7 Mean 28 24 27 26 % Difference Control NA -14.3 -3.6 -7.1 S.D. 12.2 14.5 15.3 14.8 N 20 20 20 20 Linear Trend p-value# NT NT NT 8 Mean 22 19 21 21 % Difference Control NA -13.6 -4.5 -4.5 S.D. 12.7 14.7 16.7 15.4 N 20 20 20 20 Linear Trend p-value# NT NT NT 9 Mean 26 18 15 20 % Difference Control NA -30.8 -42.3 -23.1 S.D. 16.2 15.6 12.9 16.7 N 20 20 20 20 Linear Trend p-value# NT NT NT 10 Mean 19 14 14 14 % Difference Control NA -26.3 -26.3 -26.3 S.D. 15.4 14.1 12.5 15.7 N 20 20 20 20 Linear Trend p-value# NT NT NT ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 14 Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F B LEARNING ERRORS Overall Mean 27 22 23 24 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.442 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.217 0.850 0.589 AR1 -298- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Sex Path Type PND22 F A MEMORY TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 15 Variable Trial ESCTIME 11 12 Overall Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference S.D. N Linear Trend Control p-value# 84.58 NA 43.854 20 79.11 -6.5 46.200 20 NT 66.04 -21.9 44.900 20 NT 78.70 -7.0 42.154 20 NT Mean % Difference S.D. N Linear Trend Control p-value# 55.31 NA 44.536 20 52.74 -4.6 43.343 20 NT 69.19 25.1 49.461 20 NT 56.67 2.5 38.853 19 NT Mean S.D. N Linear Trend p-value# 69.94 NA 20 65.92 NA 20 NT 67.61 NA 20 NT 67.12 NA 20 0.865 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.988 0.198 0.358 AR1 -299- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 Period Sex Path Type PND22 F A MEMORY TABLE 33 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF BIEL MAZE SWIM TRIALS PAGE 16 Variable Trial ERRORS 11 12 Overall Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ Mean % Difference S.D. N Linear Trend Control p-value# 22 NA 11.8 20 21 -4.5 15.5 20 NT 19 -13.6 16.9 20 NT 24 9.1 16.2 20 NT Mean % Difference S.D. N Linear Trend Control p-value# 14 NA 13.7 20 13 -7.1 14.1 20 NT 19 35.7 18.0 20 NT 15 7.1 11.4 20 NT Mean 18 17 19 19 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.622 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.918 0.246 0.601 AR1 -300- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. TABLE 34 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MACROSCOPIC FINDINGS SPONSOR NO.:06-128 SCHEDULED NECROPSY ----------------------------------------------------------------------------------------------------------------------------------- ----- M A L E ----- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 5 5 5 5 EYES -EYE(S)- OPACITY 0 0 0 1 KIDNEYS -DILATED PELVIS 0 2 0 2 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 5 3 5 2 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY -301- TABLE 34 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF MACROSCOPIC FINDINGS SPONSOR NO.:06-128 SCHEDULED NECROPSY ----------------------------------------------------------------------------------------------------------------------------------- ----- F E M A L E ----- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 5 5 5 5 KIDNEYS -DILATED PELVIS 1 1 0 0 THYMUS -AREA(S), DARK RED 1 0 0 0 UTERUS -CONTENTS, CLEAR FLUID 1 0 0 1 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 3 4 5 4 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PGRSI2v4.07 10/05/2006 R:01/24/2007 -302- TABLE 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MACROSCOPIC FINDINGS SPONSOR NO.:06-128 SCHEDULED NECROPSY ----------------------------------------------------------------------------------------------------------------------------------- ----- M A L E ----- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 15 15 15 15 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 15 15 15 15 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY -303- TABLE 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF MACROSCOPIC FINDINGS SPONSOR NO.:06-128 SCHEDULED NECROPSY ----------------------------------------------------------------------------------------------------------------------------------- ----- F E M A L E ----- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 15 15 15 15 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 15 15 15 15 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PGRSI2v4.07 10/05/2006 R:01/26/2007 -304- TABLE 36 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- BRAIN (G) MEAN 1.6084 1.6004 1.5806 1.6204 % DIFFERENCE -0.5 -1.7 0.7 S.D. 0.09172 0.07144 0.07315 0.09937 N 15 15 15 15 BRAIN LENGTH(MM) MEAN S.D. N 22.3 0.50 15 22.4 0.29 15 22.2 0.31 15 22.3 0.34 15 BRAIN WIDTH(MM) MEAN S.D. N 15.1 0.34 15 14.9 0.27 15 14.9 0.21 15 15.0 0.22 15 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group -305- TABLE 36 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- BRAIN (G) MEAN 1.5992 1.5702 1.5556 1.5502 % DIFFERENCE -1.8 -2.7 -3.1 S.D. 0.09741 0.06985 0.06085 0.08778 N 15 15 15 15 BRAIN LENGTH(MM) MEAN S.D. N 22.0 0.57 15 21.9 0.39 15 22.2 0.37 15 21.9 0.41 15 BRAIN WIDTH(MM) MEAN S.D. N 14.9 0.40 15 14.7 0.22 15 14.9 0.29 15 14.8 0.31 15 -306- ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group POFBSTv5.10 10/05/2006 R:01/26/2007 TABLE 37 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHT SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- FINAL BODY WT (G) MEAN 54. 53. 53. 53. S.D. 7.9 6.8 5.7 5.3 N 15 15 15 15 BRAIN (G/100 G FINAL BODY WEIGHT) MEAN 3.044 3.055 3.022 3.066 S.D. 0.4336 0.3547 0.3150 0.2147 N 15 15 15 15 ----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group -307- TABLE 37 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHT SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- FINAL BODY WT (G) MEAN 50. 50. 51. 52. S.D. 7.9 6.5 4.9 4.6 N 15 15 15 15 BRAIN (G/100 G FINAL BODY WEIGHT) MEAN 3.264 3.206 3.059 3.023 S.D. 0.4411 0.4200 0.2557 0.2245 N 15 15 15 15 ----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group POFBSTv5.10 10/05/2006 R:01/26/2007 -308- TABLE 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MACROSCOPIC FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ----- M A L E ----- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 15 15 15 15 BRAIN -CYST(S) 1 0 0 0 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 14 15 15 15 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY -309- TABLE 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF MACROSCOPIC FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ----- F E M A L E ----- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 15 15 15 15 NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES 15 15 15 15 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PGRSI2v4.07 10/05/2006 R:01/24/2007 -310- TABLE 39 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- BRAIN (G) MEAN 2.18 2.25 2.16 2.20 % DIFFERENCE 3.2 -0.9 0.9 S.D. 0.088 0.097 0.080 0.105 N 15 15 15 15 BRAIN LENGTH(MM) MEAN S.D. N 20.8 0.36 15 20.8 0.49 15 20.6 0.41 15 20.5 0.44 15 BRAIN WIDTH(MM) MEAN S.D. N 15.5 0.25 15 15.6 0.18 15 15.4 0.27 15 15.5 0.25 15 ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group -311- TABLE 39 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- BRAIN (G) MEAN 1.99 2.02 2.01 2.00 % DIFFERENCE 1.5 1.0 0.5 S.D. 0.104 0.074 0.049 0.070 N 15 15 15 15 BRAIN LENGTH(MM) MEAN S.D. N 19.8 0.46 15 20.0 0.37 15 19.8 0.36 15 19.8 0.43 15 BRAIN WIDTH(MM) MEAN S.D. N 14.9 0.31 15 15.0 0.27 15 15.0 0.18 15 14.9 0.25 15 -312- ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group POFBSTv5.10 10/05/2006 R:01/24/2007 TABLE 40 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHT SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- FINAL BODY WT (G) MEAN 419. 445. 422. 416. S.D. 43.4 42.1 24.5 32.7 N 15 15 15 15 BRAIN (G/100 G FINAL BODY WEIGHT) MEAN 0.526 0.508 0.514 0.531 S.D. 0.0506 0.0367 0.0358 0.0387 N 15 15 15 15 ----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group -313- TABLE 40 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHT SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- FINAL BODY WT (G) MEAN 248. 258. 249. 243. S.D. 27.5 22.8 18.4 23.1 N 15 15 15 15 BRAIN (G/100 G FINAL BODY WEIGHT) MEAN 0.808 0.790 0.813 0.828 S.D. 0.0770 0.0694 0.0646 0.0857 N 15 15 15 15 ----------------------------------------------------------------------------------------------------------------------------------- None significantly different from control group POFBSTv5.10 10/05/2006 R:01/24/2007 -314- TABLE 41 (F0 DAMS - GESTATION DAY 20) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF TSH VALUES SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES ANALYSIS GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TSH (ng/ml) DAY 20 MEAN 12.99 11.96 10.52 10.93 % DIFFERENCE -7.9 -19.0 -15.9 S.D. 3.292 3.048 1.903 2.538 N 10 10 10 10 ----------------------------------------------------------------------------------------------------------------------------------ng/ml = NANOGRAMS/MILLILITER ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PCPSv5.23 10/05/2006 R:10/10/2006 -315- TABLE 42 (F1 FETUSES - GESTATION DAY 20) PROJECT NO.:WIL-180017C ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF TSH VALUES SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- BY LITTER ANALYSIS GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TSH (ng/ml) DAY 20 MEAN 12.08 10.52 9.35 9.70 % DIFFERENCE -12.9 -22.6 -19.7 S.D. 4.389 2.667 2.175 2.125 N 10 10 8 8 ----------------------------------------------------------------------------------------------------------------------------------ng/ml = NANOGRAMS/MILLILITER ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PCPSv5.23 10/05/2006 R:01/23/2007 -316- TABLE 43 (F0 DAMS - LACTATION DAYS 4 AND 21) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF TSH VALUES SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES ANALYSIS GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TSH (ng/mL) DAY 4 MEAN 10.21 11.07 8.53 10.16 % DIFFERENCE 8.4 -16.5 -0.5 S.D. 3.908 4.009 1.073 2.681 N 10 10 10 10 DAY 21 MEAN % DIFFERENCE S.D. N 17.04 6.708 10 17.52 2.8 5.426 10 14.76 -13.4 4.086 10 19.48 14.3 6.270 10 ----------------------------------------------------------------------------------------------------------------------------------ng/mL = NANOGRAMS/MILLILITER ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PCPSv5.24 04/10/2007 R:04/10/2007 -317- TABLE 44 (F1 PUPS - PND 4) PROJECT NO.:WIL-180017U ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF TSH VALUES SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- BY LITTER ANALYSIS GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TSH (ng/mL) DAY 4 MEAN 5.58 5.50 4.79 5.43 % DIFFERENCE -1.4 -14.2 -2.7 S.D. 2.001 0.738 2.203 1.973 N 10 10 10 10 ----------------------------------------------------------------------------------------------------------------------------------ng/mL = NANOGRAMS/MILLILITER ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PCPSv5.24 04/10/2007 R:04/10/2007 -318- TABLE 45 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF TSH VALUES SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES ANALYSIS GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TSH (ng/ml) DAY 21 MEAN 7.63 9.94 9.47 8.79 % DIFFERENCE 30.3 24.1 15.2 S.D. 1.963 2.886 2.565 1.380 N 10 10 10 10 ----------------------------------------------------------------------------------------------------------------------------------ng/ml = NANOGRAMS/MILLILITER ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group -319- TABLE 45 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF TSH VALUES SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES ANALYSIS GROUP: 0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TSH (ng/ml) DAY 21 MEAN 8.80 8.87 8.67 8.41 % DIFFERENCE 0.8 -1.5 -4.4 S.D. 1.863 2.462 2.173 2.072 N 10 9 10 10 ----------------------------------------------------------------------------------------------------------------------------------ng/ml = NANOGRAMS/MILLILITER ----------------------------------------------------------------------------------------------------------------------------------None significantly different from control group PCPSv5.23 10/05/2006 R:10/10/2006 -320- TABLE 46 (F1 FETUSES - GESTATION DAY 20) PROJECT NO.:WIL-180017W ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MICROSCOPIC FINDINGS SPONSOR NO.:06-128 ----- MALE ----- ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 10 0 0 8 THYROID GLANDS TOTAL NUMBER EXAMINED 10 0 0 6 EXAMINED, UNREMARKABLE 0 0 0 0 NOT EXAMINED 0 0 0 2 -DECREASED COLLOID 10 0 0 6 MODERATE 5 NONE NONE 4 SEVERE 5 NONE NONE 2 -LUMINAL DEBRIS, CELLULAR 1 0 0 0 MINIMAL 1 NONE NONE NONE -MITOTIC FIGURES 9 0 0 6 MINIMAL 6 NONE NONE 6 MILD 3 NONE NONE NONE ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY -321- TABLE 46 (F1 FETUSES - GESTATION DAY 20) PROJECT NO.:WIL-180017W ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF MICROSCOPIC FINDINGS SPONSOR NO.:06-128 ----- FEMALE ----- ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 10 0 0 8 THYROID GLANDS TOTAL NUMBER EXAMINED 9 0 0 6 EXAMINED, UNREMARKABLE 0 0 0 0 NOT EXAMINED 1 0 0 2 -DECREASED COLLOID 9 0 0 6 MODERATE 2 NONE NONE 3 SEVERE 7 NONE NONE 3 -MITOTIC FIGURES 9 0 0 6 MINIMAL 4 NONE NONE 1 MILD 5 NONE NONE 5 -CONGESTION 1 0 0 0 MODERATE 1 NONE NONE NONE ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PHSI2v4.24 04/27/2007 R:04/27/2007 -322- TABLE 47 (F1 PUPS - PND 4) PROJECT NO.:WIL-180017N ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MICROSCOPIC FINDINGS SPONSOR NO.:06-128 ----- MALE ----- ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 10 0 0 10 THYROID GLANDS TOTAL NUMBER EXAMINED 10 0 0 10 EXAMINED, UNREMARKABLE 2 0 0 5 -DECREASED COLLOID 4 0 0 3 MINIMAL 4 NONE NONE 3 -LUMINAL DEBRIS, CELLULAR 3 0 0 0 MINIMAL 3 NONE NONE NONE -MITOTIC FIGURES 5 0 0 4 MINIMAL 5 NONE NONE 4 -ONE EXAMINED 0 0 0 1 PRESENT NONE NONE NONE 1 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY -323- TABLE 47 (F1 PUPS - PND 4) PROJECT NO.:WIL-180017N ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF MICROSCOPIC FINDINGS SPONSOR NO.:06-128 ----- FEMALE ----- ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 10 0 0 10 THYROID GLANDS TOTAL NUMBER EXAMINED 10 0 0 8 EXAMINED, UNREMARKABLE 2 0 0 2 NOT EXAMINED 0 0 0 2 -DECREASED COLLOID 2 0 0 2 MINIMAL 2 NONE NONE 2 -MITOTIC FIGURES 8 0 0 3 MINIMAL 7 NONE NONE 3 MILD 1 NONE NONE NONE -ONE EXAMINED 0 0 0 2 PRESENT NONE NONE NONE 2 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PHSI2v4.24 04/27/2007 R:04/27/2007 -324- TABLE 48 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION SUMMARY OF MICROSCOPIC FINDINGS SPONSOR NO.:06-128 ----- MALE ----- ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 10 0 0 10 THYROID GLANDS TOTAL NUMBER EXAMINED 10 0 0 10 EXAMINED, UNREMARKABLE 3 0 0 7 -MITOTIC FIGURES 5 0 0 3 MINIMAL 5 NONE NONE 3 -CYST, ULTIMOBRANCHIAL 4 0 0 0 PRESENT 4 NONE NONE NONE -ECTOPIC THYMUS 1 0 0 0 PRESENT 1 NONE NONE NONE -LUMINAL DEBRIS, CELLULAR 0 0 0 1 MINIMAL NONE NONE NONE 1 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY -325- TABLE 48 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION SUMMARY OF MICROSCOPIC FINDINGS SPONSOR NO.:06-128 ----- FEMALE ----- ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS EXAMINED 10 0 0 10 THYROID GLANDS TOTAL NUMBER EXAMINED 10 0 0 10 EXAMINED, UNREMARKABLE 5 0 0 2 -MITOTIC FIGURES 5 0 0 5 MINIMAL 5 NONE NONE 5 -LUMINAL DEBRIS, CELLULAR 1 0 0 4 MINIMAL 1 NONE NONE 4 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PHSI2v4.24 04/27/2007 R:04/27/2007 -326- WIL-180017N MALES GROUP: TABLE 49 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF THYROID MORPHOMETRY THYROID COLLOID AREAS 1 4 Follicle area (square pixels) Mean 17695 SD 3056.5 N 10 14731 3543.6 10 Follicle area (um 2) Mean SD N 1841 318.1 10 1533 368.7 10 FEMALES GROUP: 1 Follicle area (square pixels) Mean 20961 SD 4256.6 N 10 Follicle area (um 2) Mean SD N 2181 442.9 10 4 18925 5334.4 8 1969 555.1 8 PAGE 1 -327- WIL-180017N MALES GROUP: TABLE 49 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF THYROID MORPHOMETRY THYROID EPITHELIAL MEASUREMENTS 1 4 CELL HEIGHT (PIXELS) Mean SD N 17.02 0.805 10 16.60 1.336 10 CELL HEIGHT (um) Mean SD N 5.49 0.260 10 5.36 0.431 10 FEMALES GROUP: CELL HEIGHT (PIXELS) Mean SD N CELL HEIGHT (um) Mean SD N 1 17.61 1.114 10 5.68 0.360 10 4 18.11 0.942 8 5.84 0.304 8 PAGE 2 -328- WIL-180017V MALES GROUP: TABLE 50 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF THYROID MORPHOMETRY THYROID COLLOID AREAS 1 4 Follicle area (square pixels) Mean 74652 SD 15771.4 N 10 69838 10741.9 10 Follicle area (um 2) Mean SD N 7768 1641.1 10 7267 1117.8 10 FEMALES GROUP: 1 Follicle area (square pixels) Mean 69382 SD 12383.1 N 10 Follicle area (um 2) Mean SD N 7220 1288.6 10 4 73774 17853.8 10 7677 1857.8 10 PAGE 1 -329- WIL-180017V MALES GROUP: TABLE 50 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF THYROID MORPHOMETRY THYROID EPITHELIAL MEASUREMENTS 1 4 CELL HEIGHT (PIXELS) Mean SD N 17.62 1.662 10 19.49 ** 1.004 10 CELL HEIGHT (um) Mean SD N 5.68 0.536 10 6.29 ** 0.324 10 FEMALES GROUP: CELL HEIGHT (PIXELS) Mean SD N CELL HEIGHT (um) Mean SD N 1 19.48 1.395 10 6.28 0.450 10 4 19.77 1.853 10 6.38 0.598 10 ** = Significantly different from the control group at 0.01 using Dunnett's test PAGE 2 -330- WIL-180017W TABLE 51 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF Ki-67 CELL COUNTS MALES GROUP: GESTATION DAY 20 FETUSES 1 4 Ki-67 CELL COUNT Mean SD N 40 23.9 6 32 25.3 6 FEMALES GROUP: Ki-67 CELL COUNT Mean SD N 1 42 35.5 7 4 88 * 18.6 5 PAGE 1 -331- * = Significantly different from the control group at 0.05 using Dunnett's test -332- Final Report Volume 2 of 6 (Appendices 1-17) Study Title An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats Study Number WIL-180017 Data Requirement EPA OPPTS Guideline 870.6300; OECD Draft Guideline 426 Study Director Donald G. Stump, PhD, DABT Study Initiation Date 21 April 2006 Study Completion Date 10 January 2008 Performing Laboratory WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-9281 Sponsor Study Number 06-128 Sponsor 3M Corporation 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 WIL-180017 3M Corporation -333- MTDID 208 06-128 APPENDICES 1-17 APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597 F 0 MG/KG/DAY DISPOSITION 06-13-06 6:53 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25597 F 0 MG/KG/DAY BODY/INTEGUMENT 05-03-06 6:58 1 HAIR LOSS RIGHT FORELIMB 05-03-06 6:58 1 HAIR LOSS LEFT FORELIMB 05-04-06 7:27 1 HAIR LOSS RIGHT FORELIMB 05-04-06 7:27 1 HAIR LOSS LEFT FORELIMB 05-05-06 7:38 1 HAIR LOSS RIGHT FORELIMB 05-05-06 7:38 1 HAIR LOSS LEFT FORELIMB 05-05-06 7:42 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM 05-06-06 7:56 1 HAIR LOSS RIGHT FORELIMB 05-06-06 7:56 1 HAIR LOSS LEFT FORELIMB 05-06-06 7:57 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM 05-07-06 7:57 2 HAIR LOSS RIGHT FORELIMB 05-07-06 7:57 1 HAIR LOSS LEFT FORELIMB 05-07-06 7:57 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM -334- 05-08-06 6:35 2 HAIR LOSS RIGHT FORELIMB 05-08-06 6:35 2 HAIR LOSS LEFT FORELIMB 05-08-06 6:36 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM 05-04-06 8:08 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM 05-02-06 8:26 1 HAIR LOSS RIGHT FORELIMB 05-09-06 7:55 1 HAIR LOSS RIGHT FORELIMB 05-09-06 7:55 1 HAIR LOSS LEFT FORELIMB 05-09-06 7:56 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM 05-10-06 6:27 2 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597 F 0 MG/KG/DAY BODY/INTEGUMENT 05-10-06 6:27 2 HAIR LOSS RIGHT FORELIMB 05-10-06 6:27 1 HAIR LOSS VENTRAL NECK 05-10-06 6:28 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM 05-11-06 6:33 2 HAIR LOSS RIGHT FORELIMB 05-11-06 6:33 2 HAIR LOSS LEFT FORELIMB 05-11-06 6:33 1 HAIR LOSS VENTRAL NECK 05-11-06 6:34 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM 05-12-06 6:31 2 HAIR LOSS LEFT FORELIMB 05-12-06 6:31 2 HAIR LOSS RIGHT FORELIMB 05-12-06 6:31 1 HAIR LOSS VENTRAL NECK 05-12-06 6:32 P HARD IMMOVABLE MASS LEFT LATERAL NECK 12MM X 13MM X 11MM 05-12-06 6:32 1 HAIR LOSS LEFT LATERAL NECK 05-12-06 6:33 P SCABBING LEFT LATERAL NECK 05-13-06 9:07 2 HAIR LOSS RIGHT FORELIMB -335- 05-13-06 9:07 2 HAIR LOSS LEFT FORELIMB 05-13-06 9:08 P SCABBING LEFT LATERAL NECK 05-13-06 9:09 2 HAIR LOSS VENTRAL NECK 05-13-06 9:13 P HARD IMMOVABLE MASS LEFT LATERAL NECK 5MM X 10MM X 10MM 05-14-06 9:03 2 HAIR LOSS RIGHT FORELIMB 05-14-06 9:03 2 HAIR LOSS LEFT FORELIMB 05-14-06 9:03 P HARD IMMOVABLE MASS LEFT LATERAL NECK 5MM X 10MM X 10MM 05-14-06 9:03 P SCABBING LEFT LATERAL NECK 05-15-06 6:38 2 HAIR LOSS LEFT FORELIMB 05-15-06 6:38 2 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597 F 0 MG/KG/DAY BODY/INTEGUMENT 05-15-06 6:38 1 HAIR LOSS VENTRAL NECK 05-15-06 6:38 1 HAIR LOSS LEFT LATERAL NECK 05-15-06 6:38 P SCABBING LEFT LATERAL NECK 05-16-06 8:17 2 HAIR LOSS LEFT FORELIMB 05-16-06 8:17 2 HAIR LOSS RIGHT FORELIMB 05-16-06 8:17 1 HAIR LOSS VENTRAL NECK 05-16-06 8:18 1 HAIR LOSS LEFT LATERAL NECK 05-16-06 8:18 P SCABBING LEFT LATERAL NECK 05-17-06 6:54 2 HAIR LOSS LEFT FORELIMB 05-17-06 6:54 2 HAIR LOSS RIGHT FORELIMB 05-17-06 6:54 1 HAIR LOSS VENTRAL NECK 05-17-06 6:54 1 HAIR LOSS LEFT LATERAL NECK 05-17-06 6:54 P SCABBING LEFT LATERAL NECK 05-18-06 6:35 2 HAIR LOSS LEFT FORELIMB 05-18-06 6:35 2 HAIR LOSS RIGHT FORELIMB 05-18-06 6:35 1 HAIR LOSS VENTRAL NECK 05-18-06 6:35 1 HAIR LOSS LEFT LATERAL NECK -336- 05-18-06 6:35 P SCABBING LEFT LATERAL NECK 05-19-06 6:32 2 HAIR LOSS LEFT FORELIMB 05-19-06 6:32 2 HAIR LOSS RIGHT FORELIMB 05-19-06 6:32 1 HAIR LOSS VENTRAL NECK 05-19-06 6:33 1 HAIR LOSS LEFT LATERAL NECK 05-19-06 6:33 P SCABBING LEFT LATERAL NECK 05-19-06 6:33 P SCABBING RIGHT FORELIMB 05-20-06 6:47 2 HAIR LOSS LEFT FORELIMB 05-20-06 6:47 2 HAIR LOSS RIGHT FORELIMB 05-20-06 6:47 1 HAIR LOSS VENTRAL NECK 05-20-06 6:47 1 HAIR LOSS LEFT LATERAL NECK 05-21-06 6:50 2 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597 F 0 MG/KG/DAY BODY/INTEGUMENT 05-21-06 6:50 2 HAIR LOSS RIGHT FORELIMB 05-21-06 6:50 1 HAIR LOSS VENTRAL NECK 05-21-06 6:50 1 HAIR LOSS LEFT LATERAL NECK 05-22-06 7:05 2 HAIR LOSS LEFT FORELIMB 05-22-06 7:05 2 HAIR LOSS RIGHT FORELIMB 05-22-06 7:05 2 HAIR LOSS VENTRAL NECK 05-22-06 7:05 1 HAIR LOSS LEFT LATERAL NECK 05-23-06 7:47 2 HAIR LOSS LEFT FORELIMB 05-23-06 7:47 2 HAIR LOSS RIGHT FORELIMB 05-23-06 7:47 2 HAIR LOSS VENTRAL NECK 05-23-06 7:47 1 HAIR LOSS LEFT LATERAL NECK 05-24-06 7:07 2 HAIR LOSS LEFT FORELIMB 05-24-06 7:07 2 HAIR LOSS RIGHT FORELIMB 05-24-06 7:07 2 HAIR LOSS VENTRAL NECK 05-25-06 7:04 2 HAIR LOSS RIGHT FORELIMB 05-25-06 7:05 2 HAIR LOSS LEFT FORELIMB 05-25-06 7:05 2 HAIR LOSS VENTRAL NECK -337- 05-26-06 8:22 2 HAIR LOSS RIGHT FORELIMB 05-26-06 8:22 2 HAIR LOSS LEFT FORELIMB 05-26-06 8:23 2 HAIR LOSS VENTRAL NECK 05-27-06 8:40 2 HAIR LOSS RIGHT FORELIMB 05-27-06 8:40 2 HAIR LOSS LEFT FORELIMB 05-27-06 8:40 2 HAIR LOSS VENTRAL NECK 05-28-06 7:17 2 HAIR LOSS RIGHT FORELIMB 05-28-06 7:17 2 HAIR LOSS LEFT FORELIMB 05-28-06 7:17 2 HAIR LOSS VENTRAL NECK 05-28-06 7:18 1 HAIR LOSS RIGHT HINDLIMB 05-28-06 7:18 1 HAIR LOSS LEFT HINDLIMB 05-29-06 6:45 2 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597 F 0 MG/KG/DAY BODY/INTEGUMENT 05-29-06 6:45 2 HAIR LOSS LEFT FORELIMB 05-29-06 6:46 2 HAIR LOSS VENTRAL NECK 05-29-06 6:46 1 HAIR LOSS RIGHT HINDLIMB 05-29-06 6:46 1 HAIR LOSS LEFT HINDLIMB 05-30-06 6:12 3 HAIR LOSS RIGHT FORELIMB 05-30-06 6:12 3 HAIR LOSS LEFT FORELIMB 05-30-06 6:12 2 HAIR LOSS VENTRAL NECK 05-30-06 6:13 1 HAIR LOSS RIGHT HINDLIMB 05-30-06 6:13 1 HAIR LOSS LEFT HINDLIMB 05-30-06 6:14 P SCABBING LEFT HINDLIMB 05-31-06 6:16 3 HAIR LOSS LEFT FORELIMB 05-31-06 6:16 3 HAIR LOSS RIGHT FORELIMB 05-31-06 6:16 2 HAIR LOSS VENTRAL NECK 05-31-06 6:16 1 HAIR LOSS LEFT HINDLIMB 05-31-06 6:16 1 HAIR LOSS RIGHT HINDLIMB 05-31-06 6:17 P SCABBING LEFT HINDLIMB 05-31-06 6:17 1 HAIR LOSS VENTRAL ABDOMINAL AREA -338- 06-01-06 6:13 3 HAIR LOSS LEFT FORELIMB 06-01-06 6:13 3 HAIR LOSS RIGHT FORELIMB 06-01-06 6:13 2 HAIR LOSS VENTRAL NECK 06-01-06 6:13 1 HAIR LOSS LEFT HINDLIMB 06-01-06 6:13 1 HAIR LOSS RIGHT HINDLIMB 06-01-06 6:13 P SCABBING LEFT HINDLIMB 06-01-06 6:14 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-02-06 6:19 3 HAIR LOSS LEFT FORELIMB 06-02-06 6:19 3 HAIR LOSS RIGHT FORELIMB 06-02-06 6:20 2 HAIR LOSS VENTRAL NECK 06-02-06 6:20 1 HAIR LOSS LEFT HINDLIMB 06-02-06 6:20 1 HAIR LOSS RIGHT HINDLIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597 F 0 MG/KG/DAY BODY/INTEGUMENT 06-02-06 6:20 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-03-06 6:11 3 HAIR LOSS LEFT FORELIMB 06-03-06 6:11 3 HAIR LOSS RIGHT FORELIMB 06-03-06 6:11 2 HAIR LOSS VENTRAL NECK 06-03-06 6:11 1 HAIR LOSS LEFT HINDLIMB 06-03-06 6:12 1 HAIR LOSS RIGHT HINDLIMB 06-03-06 6:12 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-04-06 6:11 3 HAIR LOSS LEFT FORELIMB 06-04-06 6:11 3 HAIR LOSS RIGHT FORELIMB 06-04-06 6:11 2 HAIR LOSS VENTRAL NECK 06-04-06 6:11 1 HAIR LOSS LEFT HINDLIMB 06-04-06 6:11 1 HAIR LOSS RIGHT HINDLIMB 06-04-06 6:11 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-05-06 6:49 3 HAIR LOSS RIGHT FORELIMB 06-05-06 6:49 3 HAIR LOSS LEFT FORELIMB 06-05-06 6:49 2 HAIR LOSS VENTRAL NECK 06-05-06 6:50 1 HAIR LOSS VENTRAL ABDOMINAL AREA -339- 06-05-06 6:50 1 HAIR LOSS VENTRAL THORACIC AREA 06-05-06 6:50 1 HAIR LOSS RIGHT HINDLIMB 06-05-06 6:50 1 HAIR LOSS LEFT HINDLIMB 06-06-06 6:42 3 HAIR LOSS RIGHT FORELIMB 06-06-06 6:42 3 HAIR LOSS LEFT FORELIMB 06-06-06 6:42 2 HAIR LOSS VENTRAL NECK 06-06-06 6:42 1 HAIR LOSS RIGHT HINDLIMB 06-06-06 6:42 1 HAIR LOSS LEFT HINDLIMB 06-06-06 6:43 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-06-06 6:43 1 HAIR LOSS VENTRAL THORACIC AREA 06-07-06 6:43 3 HAIR LOSS RIGHT FORELIMB 06-07-06 6:43 3 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597 F 0 MG/KG/DAY BODY/INTEGUMENT 06-07-06 6:43 2 HAIR LOSS VENTRAL NECK 06-07-06 6:43 1 HAIR LOSS RIGHT HINDLIMB 06-07-06 6:43 1 HAIR LOSS LEFT HINDLIMB 06-07-06 6:44 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-07-06 6:44 1 HAIR LOSS VENTRAL THORACIC AREA 06-08-06 6:40 3 HAIR LOSS RIGHT FORELIMB 06-08-06 6:40 3 HAIR LOSS LEFT FORELIMB 06-08-06 6:41 2 HAIR LOSS VENTRAL NECK 06-08-06 6:42 1 HAIR LOSS RIGHT HINDLIMB 06-08-06 6:42 1 HAIR LOSS LEFT HINDLIMB 06-08-06 6:42 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-08-06 6:42 1 HAIR LOSS VENTRAL THORACIC AREA 06-08-06 6:45 P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA 20MM X 12MM X 15MM 06-09-06 6:49 3 HAIR LOSS RIGHT FORELIMB 06-09-06 6:49 3 HAIR LOSS LEFT FORELIMB 06-09-06 6:49 2 HAIR LOSS VENTRAL NECK -340- 06-09-06 6:49 1 HAIR LOSS RIGHT HINDLIMB 06-09-06 6:49 1 HAIR LOSS LEFT HINDLIMB 06-09-06 6:49 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-09-06 6:49 1 HAIR LOSS VENTRAL THORACIC AREA 06-09-06 6:50 P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA 20MM X 12MM X 15MM 06-10-06 7:33 3 HAIR LOSS RIGHT FORELIMB 06-10-06 7:33 3 HAIR LOSS LEFT FORELIMB 06-10-06 7:33 2 HAIR LOSS VENTRAL NECK 06-10-06 7:34 1 HAIR LOSS VENTRAL THORACIC AREA 06-10-06 7:34 2 HAIR LOSS VENTRAL ABDOMINAL AREA 06-10-06 7:34 1 HAIR LOSS RIGHT HINDLIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597 F 0 MG/KG/DAY BODY/INTEGUMENT 06-10-06 7:34 1 HAIR LOSS LEFT HINDLIMB 06-10-06 7:35 P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA 20MM X 12MM X 15MM 06-11-06 7:35 3 HAIR LOSS RIGHT FORELIMB 06-11-06 7:35 3 HAIR LOSS LEFT FORELIMB 06-11-06 7:35 2 HAIR LOSS VENTRAL NECK 06-11-06 7:36 2 HAIR LOSS VENTRAL ABDOMINAL AREA 06-11-06 7:36 1 HAIR LOSS VENTRAL THORACIC AREA 06-11-06 7:36 1 HAIR LOSS RIGHT HINDLIMB 06-11-06 7:36 1 HAIR LOSS LEFT HINDLIMB 06-11-06 7:37 P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA 20MM X 12MM X 15MM 06-12-06 6:55 3 HAIR LOSS RIGHT FORELIMB 06-12-06 6:55 3 HAIR LOSS LEFT FORELIMB 06-12-06 6:55 2 HAIR LOSS VENTRAL NECK 06-12-06 6:56 1 HAIR LOSS RIGHT HINDLIMB 06-12-06 6:56 1 HAIR LOSS LEFT HINDLIMB -341- 06-12-06 6:56 2 HAIR LOSS VENTRAL ABDOMINAL AREA 06-12-06 6:56 1 HAIR LOSS VENTRAL THORACIC AREA 06-12-06 6:57 P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA 20MM X 12MM X 15MM 06-13-06 6:05 3 HAIR LOSS RIGHT FORELIMB 06-13-06 6:05 3 HAIR LOSS LEFT FORELIMB 06-13-06 6:05 2 HAIR LOSS VENTRAL NECK 06-13-06 6:05 1 HAIR LOSS RIGHT HINDLIMB 06-13-06 6:05 1 HAIR LOSS LEFT HINDLIMB 06-13-06 6:06 2 HAIR LOSS VENTRAL ABDOMINAL AREA 06-13-06 6:06 1 HAIR LOSS VENTRAL THORACIC AREA 06-13-06 6:06 1 HAIR LOSS UROGENITAL AREA ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25654 F 0 MG/KG/DAY DISPOSITION 06-13-06 6:53 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25654 F 0 MG/KG/DAY EYES/EARS/NOSE 05-06-06 7:57 1 DRIED RED MATERIAL AROUND NOSE 06-13-06 6:08 1 DRIED RED MATERIAL AROUND NOSE 25632 F 0 MG/KG/DAY DISPOSITION 06-14-06 6:53 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25610 F 0 MG/KG/DAY DISPOSITION 06-15-06 6:57 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25610 F 0 MG/KG/DAY EYES/EARS/NOSE 06-06-06 6:45 1 DRIED RED MATERIAL AROUND NOSE 06-13-06 6:09 1 DRIED RED MATERIAL AROUND NOSE 25618 F 0 MG/KG/DAY DISPOSITION 06-15-06 6:57 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25621 F 0 MG/KG/DAY DISPOSITION 06-15-06 6:57 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25621 F 0 MG/KG/DAY BODY/INTEGUMENT 05-04-06 7:29 1 HAIR LOSS LEFT FORELIMB 05-05-06 7:46 1 HAIR LOSS LEFT FORELIMB 05-06-06 7:58 1 HAIR LOSS LEFT FORELIMB 05-07-06 7:58 1 HAIR LOSS LEFT FORELIMB 05-08-06 6:39 1 HAIR LOSS LEFT FORELIMB 05-03-06 9:27 1 HAIR LOSS LEFT FORELIMB 05-09-06 7:58 1 HAIR LOSS RIGHT FORELIMB 05-09-06 7:58 1 HAIR LOSS LEFT FORELIMB -342- 05-10-06 6:30 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:30 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:37 1 HAIR LOSS LEFT FORELIMB 05-12-06 6:35 1 HAIR LOSS LEFT FORELIMB 05-13-06 9:15 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:06 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:06 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:41 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:41 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:21 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:21 1 HAIR LOSS RIGHT FORELIMB 05-17-06 6:59 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25621 F 0 MG/KG/DAY BODY/INTEGUMENT 05-17-06 6:59 1 HAIR LOSS RIGHT FORELIMB 05-18-06 6:38 1 HAIR LOSS LEFT FORELIMB 05-18-06 6:38 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:35 1 HAIR LOSS LEFT FORELIMB 05-19-06 6:35 1 HAIR LOSS RIGHT FORELIMB 05-20-06 6:51 1 HAIR LOSS LEFT FORELIMB 05-20-06 6:51 1 HAIR LOSS RIGHT FORELIMB 05-21-06 6:52 1 HAIR LOSS LEFT FORELIMB 05-21-06 6:52 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:08 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:08 1 HAIR LOSS RIGHT FORELIMB 05-23-06 7:49 1 HAIR LOSS LEFT FORELIMB 05-23-06 7:49 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:11 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:11 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:35 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:35 1 HAIR LOSS LEFT FORELIMB -343- 05-26-06 8:29 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:29 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:43 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:43 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:20 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:20 1 HAIR LOSS LEFT FORELIMB 05-29-06 6:48 1 HAIR LOSS RIGHT FORELIMB 05-29-06 6:48 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:17 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:17 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:19 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:19 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25621 F 0 MG/KG/DAY BODY/INTEGUMENT 06-01-06 6:16 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:16 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:23 1 HAIR LOSS LEFT FORELIMB 06-02-06 6:23 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:13 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:13 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:14 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:14 1 HAIR LOSS RIGHT FORELIMB 06-05-06 6:51 1 HAIR LOSS RIGHT FORELIMB 06-05-06 6:51 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:45 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:45 1 HAIR LOSS LEFT FORELIMB 06-07-06 6:46 1 HAIR LOSS RIGHT FORELIMB 06-07-06 6:46 1 HAIR LOSS LEFT FORELIMB 06-08-06 6:47 1 HAIR LOSS RIGHT FORELIMB 06-08-06 6:47 1 HAIR LOSS LEFT FORELIMB 06-09-06 6:53 1 HAIR LOSS RIGHT FORELIMB -344- 06-09-06 6:53 1 HAIR LOSS LEFT FORELIMB 06-10-06 7:42 1 HAIR LOSS RIGHT FORELIMB 06-10-06 7:42 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:41 1 HAIR LOSS RIGHT FORELIMB 06-11-06 7:41 1 HAIR LOSS LEFT FORELIMB 06-12-06 6:58 1 HAIR LOSS RIGHT FORELIMB 06-12-06 6:58 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:10 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:10 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:07 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:07 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:06 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25621 F 0 MG/KG/DAY BODY/INTEGUMENT 06-15-06 6:06 1 HAIR LOSS LEFT FORELIMB 25687 F 0 MG/KG/DAY DISPOSITION 06-15-06 6:57 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25633 F 0 MG/KG/DAY DISPOSITION 06-14-06 6:53 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25633 F 0 MG/KG/DAY BODY/INTEGUMENT 05-04-06 7:30 1 HAIR LOSS RIGHT FORELIMB 05-05-06 7:46 1 HAIR LOSS RIGHT FORELIMB 05-05-06 7:46 1 HAIR LOSS LEFT FORELIMB 05-06-06 7:59 1 HAIR LOSS RIGHT FORELIMB 05-07-06 7:58 1 HAIR LOSS RIGHT FORELIMB 05-08-06 6:40 1 HAIR LOSS RIGHT FORELIMB 05-03-06 9:30 1 HAIR LOSS LEFT FORELIMB 05-03-06 9:30 1 HAIR LOSS RIGHT FORELIMB 05-09-06 7:59 1 HAIR LOSS RIGHT FORELIMB 05-09-06 7:59 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:30 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:30 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:38 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:36 1 HAIR LOSS RIGHT FORELIMB -345- 05-13-06 9:16 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:16 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:07 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:07 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:44 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:44 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:21 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:21 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:00 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:00 1 HAIR LOSS RIGHT FORELIMB 05-18-06 6:40 1 HAIR LOSS LEFT FORELIMB 05-18-06 6:40 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25633 F 0 MG/KG/DAY BODY/INTEGUMENT 05-19-06 6:36 1 HAIR LOSS RIGHT FORELIMB 05-20-06 6:52 1 HAIR LOSS RIGHT FORELIMB 05-21-06 6:53 1 HAIR LOSS LEFT FORELIMB 05-21-06 6:53 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:09 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:09 1 HAIR LOSS RIGHT FORELIMB 05-23-06 7:49 1 HAIR LOSS LEFT FORELIMB 05-23-06 7:49 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:12 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:12 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:30 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:30 1 HAIR LOSS LEFT FORELIMB 05-26-06 8:31 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:31 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:43 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:43 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:20 1 HAIR LOSS RIGHT FORELIMB -346- 05-28-06 7:20 1 HAIR LOSS LEFT FORELIMB 05-29-06 6:50 1 HAIR LOSS RIGHT FORELIMB 05-29-06 6:50 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:17 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:17 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:21 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:21 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:17 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:17 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:24 1 HAIR LOSS LEFT FORELIMB 06-02-06 6:24 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:14 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25633 F 0 MG/KG/DAY BODY/INTEGUMENT 06-03-06 6:14 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:16 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:16 1 HAIR LOSS RIGHT FORELIMB 06-05-06 6:52 1 HAIR LOSS RIGHT FORELIMB 06-05-06 6:52 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:46 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:46 1 HAIR LOSS LEFT FORELIMB 06-07-06 6:46 1 HAIR LOSS RIGHT FORELIMB 06-07-06 6:46 1 HAIR LOSS LEFT FORELIMB 06-08-06 6:49 1 HAIR LOSS RIGHT FORELIMB 06-08-06 6:49 1 HAIR LOSS LEFT FORELIMB 06-09-06 6:53 1 HAIR LOSS RIGHT FORELIMB 06-09-06 6:53 1 HAIR LOSS LEFT FORELIMB 06-10-06 7:43 1 HAIR LOSS RIGHT FORELIMB 06-10-06 7:43 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:43 1 HAIR LOSS RIGHT FORELIMB 06-11-06 7:43 1 HAIR LOSS LEFT FORELIMB -347- 06-11-06 7:43 P SCABBING RIGHT FORELIMB 06-12-06 6:58 1 HAIR LOSS RIGHT FORELIMB 06-12-06 6:58 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:10 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:10 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:08 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:08 1 HAIR LOSS LEFT FORELIMB 25681 F 0 MG/KG/DAY DISPOSITION 06-15-06 6:57 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25681 F 0 MG/KG/DAY EYES/EARS/NOSE 06-05-06 6:53 1 DRIED RED MATERIAL AROUND NOSE 06-06-06 6:46 1 DRIED RED MATERIAL AROUND NOSE 06-14-06 6:08 1 DRIED RED MATERIAL AROUND NOSE 25615 F 0 MG/KG/DAY DISPOSITION 06-15-06 6:57 P SCHEDULED EUTHANASIA; LACTATION DAY 21 ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25637 F 0 MG/KG/DAY DISPOSITION 06-16-06 6:43 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25637 F 0 MG/KG/DAY EYES/EARS/NOSE 06-09-06 6:54 1 DRIED RED MATERIAL AROUND NOSE 25638 F 0 MG/KG/DAY DISPOSITION 06-16-06 6:43 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25638 F 0 MG/KG/DAY EYES/EARS/NOSE 06-06-06 6:47 1 DRIED RED MATERIAL AROUND NOSE 25713 F 0 MG/KG/DAY DISPOSITION 06-16-06 6:43 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25713 F 0 MG/KG/DAY EYES/EARS/NOSE 06-05-06 6:56 1 DRIED RED MATERIAL AROUND NOSE 06-06-06 6:47 1 DRIED RED MATERIAL AROUND NOSE 06-07-06 6:49 1 DRIED RED MATERIAL AROUND NOSE 06-07-06 6:49 1 HAIR LOSS AROUND NOSE 06-08-06 6:53 1 DRIED RED MATERIAL AROUND NOSE 06-08-06 6:53 1 HAIR LOSS AROUND NOSE 06-09-06 6:55 1 HAIR LOSS AROUND NOSE 06-10-06 7:45 1 HAIR LOSS AROUND NOSE 06-11-06 7:46 1 HAIR LOSS AROUND NOSE 06-12-06 7:02 1 HAIR LOSS AROUND NOSE 06-13-06 6:12 1 HAIR LOSS AROUND NOSE 06-14-06 6:09 1 HAIR LOSS AROUND NOSE -348- 06-15-06 6:11 1 HAIR LOSS AROUND NOSE 06-16-06 6:08 1 HAIR LOSS AROUND NOSE 25670 F 0 MG/KG/DAY DISPOSITION 06-16-06 6:43 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25657 F 0 MG/KG/DAY DISPOSITION 06-16-06 6:43 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25663 F 0 MG/KG/DAY DISPOSITION 06-16-06 6:43 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25690 F 0 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25690 F 0 MG/KG/DAY EYES/EARS/NOSE 06-12-06 7:05 1 DRIED RED MATERIAL AROUND NOSE 06-13-06 6:12 1 DRIED RED MATERIAL AROUND NOSE 06-14-06 6:10 1 DRIED RED MATERIAL AROUND NOSE 25666 F 0 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25666 F 0 MG/KG/DAY BODY/INTEGUMENT 05-18-06 7:07 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:40 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25666 F 0 MG/KG/DAY BODY/INTEGUMENT 05-19-06 6:40 1 HAIR LOSS RIGHT FORELIMB 05-20-06 6:54 1 HAIR LOSS LEFT FORELIMB 05-20-06 6:54 1 HAIR LOSS RIGHT FORELIMB 05-21-06 6:57 1 HAIR LOSS LEFT FORELIMB 05-21-06 6:57 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:13 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:13 1 HAIR LOSS RIGHT FORELIMB 05-23-06 7:53 1 HAIR LOSS LEFT FORELIMB 05-23-06 7:53 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:17 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:17 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:38 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:38 1 HAIR LOSS LEFT FORELIMB 05-26-06 9:04 1 HAIR LOSS RIGHT FORELIMB 05-26-06 9:04 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:47 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:48 1 HAIR LOSS LEFT FORELIMB -349- 05-28-06 7:22 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:22 1 HAIR LOSS LEFT FORELIMB 05-29-06 6:52 1 HAIR LOSS RIGHT FORELIMB 05-29-06 6:52 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:24 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:24 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:25 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:25 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:20 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:20 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:35 1 HAIR LOSS LEFT FORELIMB 06-02-06 6:35 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 17 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25666 F 0 MG/KG/DAY BODY/INTEGUMENT 06-02-06 6:35 P SCABBING RIGHT FORELIMB 06-03-06 6:17 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:17 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:17 P SCABBING LEFT FORELIMB 06-03-06 6:17 P SCABBING RIGHT FORELIMB 06-04-06 6:21 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:21 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:21 P SCABBING LEFT FORELIMB 06-04-06 6:21 P SCABBING RIGHT FORELIMB 06-05-06 7:00 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:00 1 HAIR LOSS LEFT FORELIMB 06-05-06 7:00 P SCABBING LEFT FORELIMB 06-06-06 6:49 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:49 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:49 P SCABBING LEFT FORELIMB 06-07-06 6:51 2 HAIR LOSS RIGHT FORELIMB 06-07-06 6:51 1 HAIR LOSS LEFT FORELIMB -350- 06-07-06 6:51 P SCABBING LEFT FORELIMB 06-08-06 6:56 2 HAIR LOSS RIGHT FORELIMB 06-08-06 6:56 1 HAIR LOSS LEFT FORELIMB 06-08-06 6:56 P SCABBING LEFT FORELIMB 06-09-06 7:00 2 HAIR LOSS RIGHT FORELIMB 06-09-06 7:00 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:00 P SCABBING LEFT FORELIMB 06-10-06 7:47 2 HAIR LOSS RIGHT FORELIMB 06-10-06 7:47 1 HAIR LOSS LEFT FORELIMB 06-10-06 7:47 P SCABBING LEFT FORELIMB 06-10-06 7:47 P SCABBING RIGHT FORELIMB 06-11-06 7:48 2 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 18 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25666 F 0 MG/KG/DAY BODY/INTEGUMENT 06-11-06 7:48 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:48 P SCABBING RIGHT FORELIMB 06-11-06 7:48 P SCABBING LEFT FORELIMB 06-12-06 7:07 2 HAIR LOSS RIGHT FORELIMB 06-12-06 7:07 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:07 P SCABBING RIGHT FORELIMB 06-13-06 6:13 2 HAIR LOSS RIGHT FORELIMB 06-13-06 6:13 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:13 P SCABBING RIGHT FORELIMB 06-14-06 6:11 2 HAIR LOSS RIGHT FORELIMB 06-14-06 6:11 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:14 2 HAIR LOSS RIGHT FORELIMB 06-15-06 6:14 1 HAIR LOSS LEFT FORELIMB 06-16-06 6:12 2 HAIR LOSS RIGHT FORELIMB 06-16-06 6:12 1 HAIR LOSS LEFT FORELIMB 25692 F 0 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25692 F 0 MG/KG/DAY BODY/INTEGUMENT 05-14-06 9:10 1 HAIR LOSS LEFT FORELIMB -351- 05-15-06 6:48 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:26 P SCABBING LEFT FORELIMB 05-17-06 7:05 P SCABBING LEFT FORELIMB 05-18-06 7:08 P SCABBING LEFT FORELIMB 05-19-06 6:41 1 HAIR LOSS LEFT FORELIMB 05-20-06 6:54 1 HAIR LOSS LEFT FORELIMB 05-21-06 6:58 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:14 1 HAIR LOSS LEFT FORELIMB 05-23-06 7:53 1 HAIR LOSS LEFT FORELIMB 05-25-06 7:39 1 HAIR LOSS LEFT FORELIMB 05-26-06 9:05 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:18 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 19 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25692 F 0 MG/KG/DAY BODY/INTEGUMENT 05-28-06 7:23 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:23 1 HAIR LOSS LEFT FORELIMB 05-29-06 6:53 1 HAIR LOSS RIGHT FORELIMB 05-29-06 6:53 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:25 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:25 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:25 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:25 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:20 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:20 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:35 1 HAIR LOSS LEFT FORELIMB 06-02-06 6:35 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:17 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:21 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:21 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:22 P SCABBING LEFT FORELIMB 06-05-06 7:00 1 HAIR LOSS RIGHT FORELIMB -352- 06-05-06 7:00 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:49 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:49 1 HAIR LOSS LEFT FORELIMB 06-07-06 6:51 1 HAIR LOSS RIGHT FORELIMB 06-07-06 6:51 1 HAIR LOSS LEFT FORELIMB 06-08-06 6:56 1 HAIR LOSS RIGHT FORELIMB 06-08-06 6:56 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:01 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:01 1 HAIR LOSS LEFT FORELIMB 06-10-06 7:48 1 HAIR LOSS RIGHT FORELIMB 06-10-06 7:48 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:49 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 20 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25692 F 0 MG/KG/DAY BODY/INTEGUMENT 06-11-06 7:49 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:09 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:09 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:13 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:13 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:11 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:11 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:14 1 HAIR LOSS RIGHT FORELIMB 06-15-06 6:14 1 HAIR LOSS LEFT FORELIMB 06-16-06 6:12 1 HAIR LOSS RIGHT FORELIMB 06-16-06 6:12 1 HAIR LOSS LEFT FORELIMB 06-17-06 6:12 1 HAIR LOSS RIGHT FORELIMB 06-17-06 6:12 1 HAIR LOSS LEFT FORELIMB 25692 F 0 MG/KG/DAY EYES/EARS/NOSE 06-15-06 6:14 1 DRIED RED MATERIAL AROUND NOSE 06-16-06 6:12 1 DRIED RED MATERIAL AROUND NOSE 06-17-06 6:12 1 DRIED RED MATERIAL AROUND NOSE 25701 F 0 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 -353- 25701 F 0 MG/KG/DAY EYES/EARS/NOSE 06-14-06 6:11 1 DRIED RED MATERIAL AROUND NOSE 06-15-06 6:15 1 DRIED RED MATERIAL AROUND NOSE 25645 F 0 MG/KG/DAY DISPOSITION 06-18-06 6:15 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25645 F 0 MG/KG/DAY BODY/INTEGUMENT 06-03-06 6:19 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:22 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:01 1 HAIR LOSS RIGHT FORELIMB 25661 F 0 MG/KG/DAY DISPOSITION 06-19-06 7:03 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25661 F 0 MG/KG/DAY BODY/INTEGUMENT 05-07-06 8:03 1 HAIR LOSS DORSAL HEAD 05-07-06 8:03 P SCABBING DORSAL HEAD 05-08-06 6:44 1 HAIR LOSS DORSAL HEAD 05-08-06 6:44 P SCABBING DORSAL HEAD 05-09-06 8:04 1 HAIR LOSS DORSAL HEAD ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 21 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25661 F 0 MG/KG/DAY BODY/INTEGUMENT 05-10-06 6:36 1 HAIR LOSS DORSAL HEAD 05-11-06 6:43 1 HAIR LOSS DORSAL HEAD 05-13-06 9:22 1 HAIR LOSS DORSAL HEAD 05-14-06 9:12 1 HAIR LOSS DORSAL HEAD 05-29-06 6:38 1 HAIR LOSS RIGHT FORELIMB 25661 F 0 MG/KG/DAY EYES/EARS/NOSE 06-17-06 6:14 1 DRIED RED MATERIAL AROUND NOSE 25767 F 0 MG/KG/DAY DISPOSITION 06-18-06 6:15 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25767 F 0 MG/KG/DAY BODY/INTEGUMENT 05-07-06 8:03 1 HAIR LOSS RIGHT FORELIMB 05-08-06 6:45 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:04 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:04 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:36 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:36 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:44 1 HAIR LOSS LEFT FORELIMB 05-11-06 6:44 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:42 1 HAIR LOSS LEFT FORELIMB 05-12-06 6:42 1 HAIR LOSS RIGHT FORELIMB -354- 05-13-06 9:23 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:14 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:14 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:50 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:50 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:27 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:27 1 HAIR LOSS RIGHT FORELIMB 05-17-06 7:07 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:07 1 HAIR LOSS RIGHT FORELIMB 05-18-06 7:09 1 HAIR LOSS LEFT FORELIMB 05-18-06 7:09 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:42 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 22 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25767 F 0 MG/KG/DAY BODY/INTEGUMENT 05-19-06 6:42 1 HAIR LOSS RIGHT FORELIMB 05-20-06 6:56 1 HAIR LOSS LEFT FORELIMB 05-20-06 6:56 1 HAIR LOSS RIGHT FORELIMB 05-21-06 6:59 1 HAIR LOSS LEFT FORELIMB 05-21-06 6:59 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:15 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:15 1 HAIR LOSS RIGHT FORELIMB 05-23-06 7:56 1 HAIR LOSS LEFT FORELIMB 05-23-06 7:56 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:19 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:19 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:41 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:41 1 HAIR LOSS LEFT FORELIMB 05-26-06 9:07 1 HAIR LOSS RIGHT FORELIMB 05-26-06 9:07 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:19 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:19 1 HAIR LOSS LEFT FORELIMB -355- 05-28-06 7:12 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:12 1 HAIR LOSS LEFT FORELIMB 05-29-06 6:54 1 HAIR LOSS RIGHT FORELIMB 05-29-06 6:54 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:27 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:27 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:29 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:29 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:22 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:22 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:38 1 HAIR LOSS LEFT FORELIMB 06-02-06 6:38 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 23 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25767 F 0 MG/KG/DAY BODY/INTEGUMENT 06-03-06 6:19 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:19 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:24 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:24 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:03 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:03 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:51 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:51 1 HAIR LOSS LEFT FORELIMB 06-07-06 6:54 1 HAIR LOSS RIGHT FORELIMB 06-07-06 6:54 1 HAIR LOSS LEFT FORELIMB 06-08-06 6:59 1 HAIR LOSS RIGHT FORELIMB 06-08-06 6:59 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:02 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:02 1 HAIR LOSS LEFT FORELIMB 06-10-06 7:55 1 HAIR LOSS RIGHT FORELIMB 06-10-06 7:55 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:50 1 HAIR LOSS RIGHT FORELIMB -356- 06-11-06 7:50 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:11 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:11 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:16 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:16 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:15 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:15 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:16 1 HAIR LOSS RIGHT FORELIMB 06-15-06 6:16 1 HAIR LOSS LEFT FORELIMB 06-16-06 6:14 1 HAIR LOSS RIGHT FORELIMB 06-16-06 6:14 1 HAIR LOSS LEFT FORELIMB 06-17-06 6:14 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 24 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25767 F 0 MG/KG/DAY BODY/INTEGUMENT 06-17-06 6:14 1 HAIR LOSS LEFT FORELIMB 06-18-06 6:06 1 HAIR LOSS RIGHT FORELIMB 06-18-06 6:06 1 HAIR LOSS LEFT FORELIMB 25767 F 0 MG/KG/DAY EYES/EARS/NOSE 06-07-06 6:54 1 DRIED RED MATERIAL AROUND NOSE 06-08-06 6:59 1 DRIED RED MATERIAL AROUND NOSE 06-09-06 7:02 1 DRIED RED MATERIAL AROUND NOSE 06-12-06 7:11 1 DRIED RED MATERIAL AROUND NOSE 06-13-06 6:16 1 DRIED RED MATERIAL AROUND NOSE 06-14-06 6:15 1 DRIED RED MATERIAL AROUND NOSE 06-15-06 6:16 1 DRIED RED MATERIAL AROUND NOSE 06-16-06 6:14 1 DRIED RED MATERIAL AROUND NOSE 06-17-06 6:14 1 DRIED RED MATERIAL AROUND NOSE 06-18-06 6:06 1 DRIED RED MATERIAL AROUND NOSE 25770 F 0 MG/KG/DAY DISPOSITION 06-19-06 7:03 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25770 F 0 MG/KG/DAY BODY/INTEGUMENT 05-07-06 7:53 1 HAIR LOSS LEFT FORELIMB 05-09-06 8:05 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:05 1 HAIR LOSS LEFT FORELIMB -357- 05-10-06 6:37 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:37 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:44 1 HAIR LOSS LEFT FORELIMB 05-11-06 6:44 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:42 1 HAIR LOSS LEFT FORELIMB 05-12-06 6:42 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:23 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:23 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:14 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:14 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:50 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:27 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 25 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25770 F 0 MG/KG/DAY BODY/INTEGUMENT 05-17-06 7:07 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:07 1 HAIR LOSS RIGHT FORELIMB 05-18-06 7:39 1 HAIR LOSS LEFT FORELIMB 05-18-06 7:39 1 HAIR LOSS RIGHT FORELIMB 05-20-06 6:56 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:00 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:00 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:15 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:15 1 HAIR LOSS RIGHT FORELIMB 05-23-06 7:56 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:21 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:46 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:46 1 HAIR LOSS LEFT FORELIMB 05-26-06 9:08 1 HAIR LOSS RIGHT FORELIMB 05-26-06 9:08 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:20 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:12 1 HAIR LOSS RIGHT FORELIMB -358- 05-29-06 6:39 1 HAIR LOSS RIGHT FORELIMB 05-29-06 6:39 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:27 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:27 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:29 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:29 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:23 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:23 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:38 1 HAIR LOSS LEFT FORELIMB 06-02-06 6:38 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:20 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:20 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 26 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25770 F 0 MG/KG/DAY BODY/INTEGUMENT 06-04-06 6:25 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:25 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:03 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:03 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:51 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:51 1 HAIR LOSS LEFT FORELIMB 06-07-06 6:54 1 HAIR LOSS RIGHT FORELIMB 06-07-06 6:54 1 HAIR LOSS LEFT FORELIMB 06-08-06 6:59 1 HAIR LOSS RIGHT FORELIMB 06-08-06 6:59 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:02 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:02 1 HAIR LOSS LEFT FORELIMB 06-10-06 7:55 1 HAIR LOSS RIGHT FORELIMB 06-10-06 7:55 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:51 1 HAIR LOSS RIGHT FORELIMB 06-11-06 7:51 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:12 1 HAIR LOSS RIGHT FORELIMB -359- 06-12-06 7:12 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:16 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:16 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:16 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:16 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:17 1 HAIR LOSS RIGHT FORELIMB 06-15-06 6:17 1 HAIR LOSS LEFT FORELIMB 06-16-06 6:14 1 HAIR LOSS RIGHT FORELIMB 06-16-06 6:14 1 HAIR LOSS LEFT FORELIMB 06-17-06 6:14 1 HAIR LOSS RIGHT FORELIMB 06-17-06 6:14 1 HAIR LOSS LEFT FORELIMB 06-18-06 6:06 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 27 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25770 F 0 MG/KG/DAY BODY/INTEGUMENT 06-18-06 6:07 1 HAIR LOSS LEFT FORELIMB 06-19-06 6:18 1 HAIR LOSS LEFT FORELIMB 06-19-06 6:18 1 HAIR LOSS RIGHT FORELIMB 25702 F 0 MG/KG/DAY DISPOSITION 06-19-06 7:03 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25702 F 0 MG/KG/DAY BODY/INTEGUMENT 05-10-06 6:37 1 HAIR LOSS LEFT FORELIMB 25702 F 0 MG/KG/DAY EYES/EARS/NOSE 05-07-06 7:38 1 DRIED RED MATERIAL AROUND NOSE 06-08-06 7:00 1 DRIED RED MATERIAL AROUND NOSE 06-09-06 7:02 1 DRIED RED MATERIAL AROUND NOSE 06-16-06 6:15 1 DRIED RED MATERIAL AROUND NOSE 06-17-06 6:15 1 DRIED RED MATERIAL AROUND NOSE 06-18-06 6:07 1 DRIED RED MATERIAL AROUND NOSE 25664 F 0.1 MG/KG/DAY DISPOSITION 05-27-06 8:33 P SCHEDULED EUTHANASIA; POST-MATING DAY 25 25648 F 0.1 MG/KG/DAY DISPOSITION 06-13-06 6:53 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25694 F 0.1 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25694 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-07-06 6:56 1 HAIR LOSS LEFT FORELIMB 25694 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-05-06 7:05 1 DRIED RED MATERIAL AROUND NOSE 25668 F 0.1 MG/KG/DAY DISPOSITION 06-14-06 6:53 P SCHEDULED EUTHANASIA; LACTATION DAY 21 -360- 25631 F 0.1 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25631 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-12-06 7:14 1 DRIED RED MATERIAL AROUND NOSE 25660 F 0.1 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25704 F 0.1 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25695 F 0.1 MG/KG/DAY DISPOSITION 05-28-06 7:56 P SCHEDULED EUTHANASIA; POST-MATING DAY 25 25695 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-23-06 8:01 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:49 1 HAIR LOSS RIGHT FORELIMB 25665 F 0.1 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25665 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-27-06 8:50 1 HAIR LOSS RIGHT FORELIMB 05-30-06 6:31 P SCABBING RIGHT FORELIMB 05-31-06 6:34 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:34 P SCABBING RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 28 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25665 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-01-06 6:27 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:45 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:23 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:29 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:29 P SCABBING RIGHT FORELIMB 06-05-06 7:07 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:54 1 HAIR LOSS RIGHT FORELIMB 06-07-06 6:58 1 HAIR LOSS RIGHT FORELIMB 06-07-06 6:58 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:05 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:05 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:06 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:06 1 HAIR LOSS LEFT FORELIMB 25674 F 0.1 MG/KG/DAY DISPOSITION 06-14-06 6:53 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25674 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-11-06 6:48 1 HAIR LOSS LEFT FORELIMB 05-11-06 6:48 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:49 P SCABBING LEFT FORELIMB -361- 05-13-06 9:31 P SCABBING LEFT FORELIMB 05-14-06 9:18 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:57 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:57 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:31 1 HAIR LOSS RIGHT FORELIMB 05-17-06 7:12 1 HAIR LOSS LEFT FORELIMB 05-18-06 7:46 1 HAIR LOSS LEFT FORELIMB 05-19-06 6:49 1 HAIR LOSS LEFT FORELIMB 05-19-06 6:49 1 HAIR LOSS RIGHT FORELIMB 05-20-06 6:59 1 HAIR LOSS LEFT FORELIMB 05-20-06 6:59 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:07 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 29 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25674 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-21-06 7:07 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:20 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:20 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:02 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:02 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:25 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:25 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:11 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:11 1 HAIR LOSS LEFT FORELIMB 05-26-06 8:40 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:50 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:50 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:31 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:31 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:34 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:34 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:28 1 HAIR LOSS LEFT FORELIMB -362- 06-01-06 6:28 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:45 1 HAIR LOSS LEFT FORELIMB 06-02-06 6:45 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:23 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:23 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:31 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:31 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:08 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:08 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:55 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:55 1 HAIR LOSS LEFT FORELIMB 06-07-06 6:58 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 30 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25674 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-07-06 6:58 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:05 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:05 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:06 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:06 1 HAIR LOSS LEFT FORELIMB 06-10-06 8:04 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:04 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:57 1 HAIR LOSS RIGHT FORELIMB 06-11-06 7:57 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:15 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:15 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:19 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:19 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:19 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:19 1 HAIR LOSS LEFT FORELIMB 25652 F 0.1 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25733 F 0.1 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 -363- 25733 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-05-06 7:52 1 HAIR LOSS RIGHT FORELIMB 05-05-06 7:52 1 HAIR LOSS LEFT FORELIMB 05-06-06 8:07 1 HAIR LOSS RIGHT FORELIMB 05-06-06 8:07 1 HAIR LOSS LEFT FORELIMB 05-07-06 8:06 1 HAIR LOSS RIGHT FORELIMB 05-07-06 8:06 1 HAIR LOSS LEFT FORELIMB 05-08-06 6:51 1 HAIR LOSS RIGHT FORELIMB 05-08-06 6:51 1 HAIR LOSS LEFT FORELIMB 05-04-06 9:15 1 HAIR LOSS LEFT FORELIMB 05-04-06 9:15 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:13 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:13 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 31 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25733 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-10-06 6:43 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:43 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:48 1 HAIR LOSS LEFT FORELIMB 05-11-06 6:48 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:50 1 HAIR LOSS LEFT FORELIMB 05-12-06 6:50 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:31 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:31 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:18 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:18 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:59 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:59 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:31 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:31 1 HAIR LOSS RIGHT FORELIMB 05-17-06 7:13 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:13 1 HAIR LOSS RIGHT FORELIMB 05-18-06 7:47 1 HAIR LOSS LEFT FORELIMB -364- 05-18-06 7:47 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:49 1 HAIR LOSS LEFT FORELIMB 05-19-06 6:49 1 HAIR LOSS RIGHT FORELIMB 05-20-06 7:00 1 HAIR LOSS LEFT FORELIMB 05-20-06 7:00 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:08 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:08 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:21 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:21 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:04 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:04 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:25 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 32 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25733 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-25-06 7:50 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:50 1 HAIR LOSS LEFT FORELIMB 05-26-06 8:41 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:41 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:51 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:51 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:28 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:28 1 HAIR LOSS LEFT FORELIMB 05-29-06 6:59 1 HAIR LOSS RIGHT FORELIMB 05-29-06 6:59 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:32 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:32 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:36 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:36 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:29 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:29 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:47 1 HAIR LOSS LEFT FORELIMB -365- 06-02-06 6:47 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:24 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:24 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:32 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:32 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:08 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:08 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:55 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:55 1 HAIR LOSS LEFT FORELIMB 06-07-06 6:59 1 HAIR LOSS RIGHT FORELIMB 06-07-06 6:59 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:06 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 33 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25733 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-08-06 7:06 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:07 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:07 1 HAIR LOSS LEFT FORELIMB 06-10-06 8:05 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:05 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:58 1 HAIR LOSS RIGHT FORELIMB 06-11-06 7:58 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:16 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:16 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:20 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:20 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:20 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:20 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:24 1 HAIR LOSS RIGHT FORELIMB 06-15-06 6:24 1 HAIR LOSS LEFT FORELIMB 25733 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-06-06 6:55 1 DRIED RED MATERIAL AROUND NOSE 06-07-06 6:59 1 DRIED RED MATERIAL AROUND NOSE -366- 25748 F 0.1 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25748 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-05-06 7:53 1 HAIR LOSS RIGHT FORELIMB 05-05-06 7:53 1 HAIR LOSS LEFT FORELIMB 05-06-06 8:07 1 HAIR LOSS RIGHT FORELIMB 05-06-06 8:07 1 HAIR LOSS LEFT FORELIMB 05-07-06 8:06 1 HAIR LOSS RIGHT FORELIMB 05-07-06 8:06 1 HAIR LOSS LEFT FORELIMB 05-08-06 6:52 1 HAIR LOSS RIGHT FORELIMB 05-08-06 6:52 1 HAIR LOSS LEFT FORELIMB 05-04-06 9:16 1 HAIR LOSS LEFT FORELIMB 05-04-06 9:16 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:13 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 34 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25748 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-09-06 8:13 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:43 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:43 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:49 1 HAIR LOSS LEFT FORELIMB 05-11-06 6:49 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:50 1 HAIR LOSS LEFT FORELIMB 05-12-06 6:50 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:32 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:32 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:19 2 HAIR LOSS RIGHT FORELIMB 05-14-06 9:19 2 HAIR LOSS LEFT FORELIMB 05-15-06 7:00 1 HAIR LOSS LEFT FORELIMB 05-15-06 7:00 2 HAIR LOSS RIGHT FORELIMB 05-16-06 8:32 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:32 1 HAIR LOSS RIGHT FORELIMB 05-17-06 7:13 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:13 1 HAIR LOSS RIGHT FORELIMB -367- 05-18-06 7:48 1 HAIR LOSS LEFT FORELIMB 05-18-06 7:48 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:50 1 HAIR LOSS LEFT FORELIMB 05-19-06 6:50 1 HAIR LOSS RIGHT FORELIMB 05-20-06 7:00 1 HAIR LOSS LEFT FORELIMB 05-20-06 7:00 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:08 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:08 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:22 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:22 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:04 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:04 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 35 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25748 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-24-06 7:26 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:26 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:50 1 HAIR LOSS RIGHT FORELIMB 05-26-06 9:11 1 HAIR LOSS RIGHT FORELIMB 05-26-06 9:11 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:51 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:51 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:28 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:28 1 HAIR LOSS LEFT FORELIMB 05-29-06 7:00 1 HAIR LOSS RIGHT FORELIMB 05-30-06 6:32 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:32 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:36 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:36 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:30 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:30 1 HAIR LOSS RIGHT FORELIMB 06-02-06 6:48 1 HAIR LOSS LEFT FORELIMB -368- 06-02-06 6:48 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:24 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:24 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:33 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:33 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:09 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:09 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:56 1 HAIR LOSS RIGHT FORELIMB 06-06-06 6:56 1 HAIR LOSS LEFT FORELIMB 06-07-06 7:01 1 HAIR LOSS RIGHT FORELIMB 06-07-06 7:01 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:07 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 36 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25748 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-08-06 7:07 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:07 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:05 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:05 1 HAIR LOSS LEFT FORELIMB 06-11-06 7:59 1 HAIR LOSS RIGHT FORELIMB 06-11-06 7:59 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:16 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:21 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:21 1 HAIR LOSS RIGHT FORELIMB 06-15-06 6:26 1 HAIR LOSS RIGHT FORELIMB 06-16-06 6:16 1 HAIR LOSS RIGHT FORELIMB 25753 F 0.1 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25753 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-03-06 6:25 1 DRIED RED MATERIAL AROUND NOSE 06-03-06 6:25 1 DRIED RED MATERIAL AROUND LEFT EYE 06-04-06 6:34 1 DRIED RED MATERIAL AROUND NOSE 06-04-06 6:34 1 DRIED RED MATERIAL AROUND LEFT EYE 06-05-06 7:10 2 DRIED RED MATERIAL AROUND NOSE -369- 06-05-06 7:10 1 DRIED RED MATERIAL AROUND LEFT EYE 06-06-06 6:57 2 DRIED RED MATERIAL AROUND NOSE 06-06-06 6:57 1 DRIED RED MATERIAL AROUND LEFT EYE 06-07-06 7:02 2 DRIED RED MATERIAL AROUND NOSE 06-07-06 7:02 1 HAIR LOSS AROUND LEFT EYE 06-07-06 7:03 1 HAIR LOSS AROUND NOSE 06-07-06 7:03 P SCABBING AROUND NOSE 06-08-06 7:08 1 DRIED RED MATERIAL AROUND NOSE 06-08-06 7:08 1 HAIR LOSS AROUND NOSE 06-08-06 7:08 P SCABBING AROUND NOSE 06-09-06 7:09 1 HAIR LOSS AROUND NOSE 06-10-06 8:06 1 HAIR LOSS AROUND NOSE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 37 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25753 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-11-06 7:59 1 HAIR LOSS AROUND NOSE 06-12-06 7:17 1 HAIR LOSS AROUND NOSE 06-13-06 6:21 1 HAIR LOSS AROUND NOSE 06-14-06 6:21 1 DRIED RED MATERIAL AROUND NOSE 06-14-06 6:21 1 HAIR LOSS AROUND NOSE 06-15-06 6:26 1 DRIED RED MATERIAL AROUND NOSE 06-15-06 6:26 1 HAIR LOSS AROUND NOSE 06-16-06 6:17 1 DRIED RED MATERIAL AROUND NOSE 06-16-06 6:17 1 HAIR LOSS AROUND NOSE 25672 F 0.1 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25672 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-07-06 7:03 1 DRIED RED MATERIAL AROUND NOSE 06-08-06 7:09 1 DRIED RED MATERIAL AROUND NOSE 06-09-06 7:10 1 DRIED RED MATERIAL AROUND NOSE 06-12-06 7:18 1 DRIED RED MATERIAL AROUND NOSE 06-13-06 6:21 1 DRIED RED MATERIAL AROUND NOSE 06-14-06 6:22 1 DRIED RED MATERIAL AROUND NOSE 06-15-06 6:27 1 DRIED RED MATERIAL AROUND NOSE -370- 06-16-06 6:18 1 DRIED RED MATERIAL AROUND NOSE 25655 F 0.1 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25655 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-03-06 6:25 1 HAIR LOSS LEFT FORELIMB 06-06-06 6:57 1 HAIR LOSS LEFT FORELIMB 06-07-06 7:04 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:09 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:11 1 HAIR LOSS LEFT FORELIMB 06-10-06 8:06 1 HAIR LOSS LEFT FORELIMB 06-11-06 8:00 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:19 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:22 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:22 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 38 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25727 F 0.1 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25626 F 0.1 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25626 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-01-06 6:31 1 HAIR LOSS LEFT FORELIMB 06-11-06 8:00 1 HAIR LOSS LEFT FORELIMB 25739 F 0.1 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25739 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-08-06 7:10 1 WET RED MATERIAL AROUND NOSE 25749 F 0.1 MG/KG/DAY DISPOSITION 06-16-06 6:44 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25749 F 0.1 MG/KG/DAY EYES/EARS/NOSE 05-06-06 8:08 1 DRIED RED MATERIAL AROUND NOSE 06-12-06 7:22 1 DRIED RED MATERIAL AROUND NOSE 06-13-06 6:23 1 DRIED RED MATERIAL AROUND NOSE 25756 F 0.1 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25741 F 0.1 MG/KG/DAY DISPOSITION 06-18-06 6:15 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25741 F 0.1 MG/KG/DAY EYES/EARS/NOSE 05-06-06 7:38 1 DRIED RED MATERIAL AROUND NOSE 06-14-06 6:24 1 DRIED RED MATERIAL AROUND NOSE 06-15-06 6:29 1 DRIED RED MATERIAL AROUND NOSE 25752 F 0.1 MG/KG/DAY DISPOSITION 06-18-06 6:16 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25752 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-10-06 8:13 1 HAIR LOSS VENTRAL ABDOMINAL AREA -371- 06-10-06 8:13 P SCABBING LEFT HINDLIMB 06-11-06 8:03 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-12-06 7:24 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-12-06 7:25 P SCABBING VENTRAL ABDOMINAL AREA 06-13-06 6:25 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-13-06 6:25 P SCABBING VENTRAL ABDOMINAL AREA 06-14-06 6:25 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-15-06 6:30 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-16-06 6:24 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-17-06 6:17 1 HAIR LOSS VENTRAL ABDOMINAL AREA 06-18-06 6:08 1 HAIR LOSS VENTRAL ABDOMINAL AREA 25758 F 0.1 MG/KG/DAY DISPOSITION 06-19-06 7:03 P SCHEDULED EUTHANASIA; LACTATION DAY 21 ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 39 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25758 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-19-06 6:22 1 HAIR LOSS RIGHT FORELIMB 25719 F 0.1 MG/KG/DAY DISPOSITION 06-19-06 7:03 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25719 F 0.1 MG/KG/DAY BODY/INTEGUMENT 05-27-06 8:23 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:14 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:14 1 HAIR LOSS LEFT FORELIMB 05-29-06 6:39 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:39 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:39 P SCABBING LEFT FORELIMB 05-31-06 6:42 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:42 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:42 P SCABBING LEFT FORELIMB 06-01-06 6:34 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:34 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:34 P SCABBING LEFT FORELIMB 06-02-06 6:59 1 HAIR LOSS LEFT FORELIMB 06-02-06 6:59 P SCABBING LEFT FORELIMB 06-03-06 6:29 1 HAIR LOSS LEFT FORELIMB -372- 06-03-06 6:29 P SCABBING LEFT FORELIMB 06-04-06 6:38 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:38 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:38 P SCABBING LEFT FORELIMB 06-04-06 6:38 P SCABBING RIGHT FORELIMB 06-05-06 7:16 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:16 1 HAIR LOSS LEFT FORELIMB 06-05-06 7:17 P SCABBING LEFT FORELIMB 06-05-06 7:17 P SCABBING RIGHT FORELIMB 06-06-06 7:03 1 HAIR LOSS RIGHT FORELIMB 06-06-06 7:03 1 HAIR LOSS LEFT FORELIMB 06-06-06 7:03 P SCABBING LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 40 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25719 F 0.1 MG/KG/DAY BODY/INTEGUMENT 06-06-06 7:03 P SCABBING RIGHT FORELIMB 06-07-06 7:07 1 HAIR LOSS RIGHT FORELIMB 06-07-06 7:07 1 HAIR LOSS LEFT FORELIMB 06-07-06 7:07 P SCABBING LEFT FORELIMB 06-08-06 7:14 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:14 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:15 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:15 1 HAIR LOSS LEFT FORELIMB 06-10-06 8:14 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:14 1 HAIR LOSS LEFT FORELIMB 06-11-06 8:05 1 HAIR LOSS RIGHT FORELIMB 06-11-06 8:05 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:27 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:27 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:26 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:26 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:26 1 HAIR LOSS RIGHT FORELIMB -373- 06-14-06 6:26 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:33 1 HAIR LOSS RIGHT FORELIMB 06-15-06 6:33 1 HAIR LOSS LEFT FORELIMB 06-16-06 6:24 1 HAIR LOSS RIGHT FORELIMB 06-16-06 6:24 1 HAIR LOSS LEFT FORELIMB 06-17-06 6:18 1 HAIR LOSS RIGHT FORELIMB 06-17-06 6:18 1 HAIR LOSS LEFT FORELIMB 06-18-06 6:09 1 HAIR LOSS RIGHT FORELIMB 06-18-06 6:09 1 HAIR LOSS LEFT FORELIMB 25719 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-14-06 6:27 1 DRIED RED MATERIAL AROUND NOSE 06-15-06 6:33 1 DRIED RED MATERIAL AROUND NOSE 06-16-06 6:24 1 DRIED RED MATERIAL AROUND NOSE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 41 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25719 F 0.1 MG/KG/DAY EYES/EARS/NOSE 06-17-06 6:18 1 DRIED RED MATERIAL AROUND NOSE 06-18-06 6:09 1 DRIED RED MATERIAL AROUND NOSE 25606 F 0.3 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25606 F 0.3 MG/KG/DAY EYES/EARS/NOSE 05-13-06 9:39 1 DRIED RED MATERIAL AROUND NOSE 06-06-06 7:04 1 DRIED RED MATERIAL AROUND NOSE 06-06-06 7:04 1 DRIED RED MATERIAL AROUND LEFT EYE 06-13-06 6:27 1 DRIED RED MATERIAL AROUND NOSE 25614 F 0.3 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25671 F 0.3 MG/KG/DAY DISPOSITION 06-13-06 6:53 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25671 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-16-06 8:39 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:44 1 HAIR LOSS LEFT FORELIMB 25671 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-09-06 7:16 1 DRIED RED MATERIAL AROUND NOSE 06-13-06 6:27 1 DRIED RED MATERIAL AROUND NOSE 25698 F 0.3 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25698 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-04-06 7:35 1 HAIR LOSS RIGHT FORELIMB 05-05-06 7:56 1 HAIR LOSS RIGHT FORELIMB 05-06-06 8:10 1 HAIR LOSS RIGHT FORELIMB -374- 05-07-06 8:11 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:18 1 HAIR LOSS RIGHT FORELIMB 05-10-06 6:51 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:58 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:57 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:40 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:26 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:26 1 HAIR LOSS LEFT FORELIMB 05-15-06 7:05 1 HAIR LOSS LEFT FORELIMB 05-15-06 7:05 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:39 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:39 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 42 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25698 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-17-06 7:21 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:21 1 HAIR LOSS RIGHT FORELIMB 05-18-06 7:53 1 HAIR LOSS LEFT FORELIMB 05-18-06 7:53 1 HAIR LOSS RIGHT FORELIMB 05-20-06 7:07 1 HAIR LOSS LEFT FORELIMB 05-20-06 7:07 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:12 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:12 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:31 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:32 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:10 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:10 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:33 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:33 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:14 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:14 1 HAIR LOSS LEFT FORELIMB 05-26-06 8:44 1 HAIR LOSS RIGHT FORELIMB -375- 05-26-06 8:44 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:58 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:58 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:32 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:32 1 HAIR LOSS LEFT FORELIMB 05-29-06 7:04 1 HAIR LOSS RIGHT FORELIMB 05-29-06 7:04 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:42 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:42 1 HAIR LOSS RIGHT FORELIMB 05-31-06 6:45 1 HAIR LOSS LEFT FORELIMB 05-31-06 6:45 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:36 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 43 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25698 F 0.3 MG/KG/DAY BODY/INTEGUMENT 06-01-06 6:36 1 HAIR LOSS RIGHT FORELIMB 06-02-06 7:02 1 HAIR LOSS LEFT FORELIMB 06-02-06 7:02 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:32 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:32 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:39 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:39 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:18 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:18 1 HAIR LOSS LEFT FORELIMB 06-06-06 7:05 1 HAIR LOSS RIGHT FORELIMB 06-06-06 7:05 1 HAIR LOSS LEFT FORELIMB 06-07-06 7:12 1 HAIR LOSS RIGHT FORELIMB 06-07-06 7:12 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:16 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:16 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:18 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:18 1 HAIR LOSS LEFT FORELIMB -376- 06-10-06 8:19 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:19 1 HAIR LOSS LEFT FORELIMB 06-11-06 8:12 1 HAIR LOSS RIGHT FORELIMB 06-11-06 8:12 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:29 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:29 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:28 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:28 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:29 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:29 1 HAIR LOSS LEFT FORELIMB 25609 F 0.3 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25677 F 0.3 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 44 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25677 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-08-06 7:17 1 DRIED RED MATERIAL AROUND NOSE 25623 F 0.3 MG/KG/DAY DISPOSITION 06-15-06 6:58 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25623 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-14-06 6:31 1 DRIED RED MATERIAL AROUND NOSE 25653 F 0.3 MG/KG/DAY DISPOSITION 06-15-06 6:59 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25653 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-16-06 8:40 1 HAIR LOSS RIGHT FORELIMB 05-17-06 7:22 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:58 1 HAIR LOSS RIGHT FORELIMB 05-20-06 7:07 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:15 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:33 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:12 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:34 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:56 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:46 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:46 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:58 1 HAIR LOSS RIGHT FORELIMB 05-29-06 7:08 1 HAIR LOSS RIGHT FORELIMB -377- 05-30-06 6:43 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:42 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:19 1 HAIR LOSS RIGHT FORELIMB 06-06-06 7:06 1 HAIR LOSS RIGHT FORELIMB 06-07-06 7:15 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:19 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:19 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:21 1 HAIR LOSS RIGHT FORELIMB 06-11-06 8:15 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:30 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:30 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:31 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 45 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25653 F 0.3 MG/KG/DAY BODY/INTEGUMENT 06-15-06 6:36 1 HAIR LOSS RIGHT FORELIMB 25604 F 0.3 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25604 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-20-06 7:08 1 HAIR LOSS LEFT FORELIMB 05-20-06 7:08 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:16 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:33 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:33 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:13 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:34 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:34 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:15 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:47 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:43 1 HAIR LOSS LEFT FORELIMB 06-02-06 7:05 1 HAIR LOSS LEFT FORELIMB 06-02-06 7:05 P SCABBING LEFT FORELIMB 06-04-06 6:42 1 HAIR LOSS LEFT FORELIMB 06-05-06 7:20 1 HAIR LOSS LEFT FORELIMB -378- 06-06-06 7:06 1 HAIR LOSS LEFT FORELIMB 06-07-06 7:15 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:19 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:20 1 HAIR LOSS LEFT FORELIMB 06-10-06 8:21 1 HAIR LOSS LEFT FORELIMB 06-11-06 8:16 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:30 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:30 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:32 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:32 1 HAIR LOSS LEFT FORELIMB 25604 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-12-06 7:30 1 DRIED RED MATERIAL AROUND NOSE 06-14-06 6:32 1 DRIED RED MATERIAL AROUND NOSE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 46 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25678 F 0.3 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25684 F 0.3 MG/KG/DAY DISPOSITION 06-15-06 6:59 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25684 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-04-06 7:37 1 HAIR LOSS RIGHT FORELIMB 05-04-06 7:37 1 HAIR LOSS LEFT FORELIMB 05-05-06 7:57 1 HAIR LOSS RIGHT FORELIMB 05-05-06 7:57 1 HAIR LOSS LEFT FORELIMB 05-06-06 8:12 1 HAIR LOSS RIGHT FORELIMB 05-06-06 8:12 1 HAIR LOSS LEFT FORELIMB 05-07-06 8:12 1 HAIR LOSS RIGHT FORELIMB 05-07-06 8:12 1 HAIR LOSS LEFT FORELIMB 05-08-06 7:01 2 HAIR LOSS RIGHT FORELIMB 05-08-06 7:01 2 HAIR LOSS LEFT FORELIMB 05-03-06 9:38 1 HAIR LOSS LEFT FORELIMB 05-03-06 9:38 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:22 2 HAIR LOSS RIGHT FORELIMB 05-09-06 8:22 2 HAIR LOSS LEFT FORELIMB 05-10-06 6:53 2 HAIR LOSS LEFT FORELIMB -379- 05-10-06 6:53 2 HAIR LOSS RIGHT FORELIMB 05-11-06 7:01 2 HAIR LOSS LEFT FORELIMB 05-11-06 7:01 2 HAIR LOSS RIGHT FORELIMB 05-12-06 7:01 2 HAIR LOSS LEFT FORELIMB 05-12-06 7:01 2 HAIR LOSS RIGHT FORELIMB 05-13-06 9:42 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:42 2 HAIR LOSS LEFT FORELIMB 05-14-06 9:27 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:27 2 HAIR LOSS LEFT FORELIMB 05-15-06 7:09 2 HAIR LOSS LEFT FORELIMB 05-15-06 7:09 2 HAIR LOSS RIGHT FORELIMB 05-16-06 8:41 2 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 47 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25684 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-16-06 8:41 2 HAIR LOSS RIGHT FORELIMB 05-17-06 7:24 2 HAIR LOSS LEFT FORELIMB 05-17-06 7:24 2 HAIR LOSS RIGHT FORELIMB 05-18-06 7:59 2 HAIR LOSS LEFT FORELIMB 05-18-06 7:59 2 HAIR LOSS RIGHT FORELIMB 05-19-06 6:59 2 HAIR LOSS LEFT FORELIMB 05-19-06 6:59 2 HAIR LOSS RIGHT FORELIMB 05-20-06 7:08 1 HAIR LOSS LEFT FORELIMB 05-20-06 7:08 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:17 2 HAIR LOSS LEFT FORELIMB 05-21-06 7:17 2 HAIR LOSS RIGHT FORELIMB 05-21-06 7:17 P SCABBING LEFT FORELIMB 05-22-06 7:34 2 HAIR LOSS LEFT FORELIMB 05-22-06 7:34 2 HAIR LOSS RIGHT FORELIMB 05-23-06 8:14 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:14 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:35 1 HAIR LOSS LEFT FORELIMB -380- 05-24-06 7:35 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:56 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:56 1 HAIR LOSS LEFT FORELIMB 05-26-06 8:48 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:48 1 HAIR LOSS LEFT FORELIMB 05-27-06 9:00 1 HAIR LOSS RIGHT FORELIMB 05-27-06 9:00 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:36 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:36 1 HAIR LOSS LEFT FORELIMB 05-29-06 7:10 1 HAIR LOSS RIGHT FORELIMB 05-29-06 7:10 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:43 2 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 48 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25684 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-30-06 6:43 2 HAIR LOSS RIGHT FORELIMB 05-31-06 6:52 2 HAIR LOSS LEFT FORELIMB 05-31-06 6:52 2 HAIR LOSS RIGHT FORELIMB 06-01-06 6:43 2 HAIR LOSS LEFT FORELIMB 06-01-06 6:43 2 HAIR LOSS RIGHT FORELIMB 06-02-06 7:06 2 HAIR LOSS LEFT FORELIMB 06-02-06 7:06 2 HAIR LOSS RIGHT FORELIMB 06-03-06 6:37 2 HAIR LOSS LEFT FORELIMB 06-03-06 6:37 2 HAIR LOSS RIGHT FORELIMB 06-04-06 6:43 2 HAIR LOSS LEFT FORELIMB 06-04-06 6:43 2 HAIR LOSS RIGHT FORELIMB 06-05-06 7:20 2 HAIR LOSS RIGHT FORELIMB 06-05-06 7:20 2 HAIR LOSS LEFT FORELIMB 06-06-06 7:07 2 HAIR LOSS RIGHT FORELIMB 06-06-06 7:07 2 HAIR LOSS LEFT FORELIMB 06-07-06 7:17 2 HAIR LOSS RIGHT FORELIMB 06-07-06 7:17 2 HAIR LOSS LEFT FORELIMB -381- 06-08-06 7:20 2 HAIR LOSS RIGHT FORELIMB 06-08-06 7:20 2 HAIR LOSS LEFT FORELIMB 06-09-06 7:20 2 HAIR LOSS RIGHT FORELIMB 06-09-06 7:20 2 HAIR LOSS LEFT FORELIMB 06-10-06 8:23 2 HAIR LOSS RIGHT FORELIMB 06-10-06 8:23 2 HAIR LOSS LEFT FORELIMB 06-11-06 8:16 2 HAIR LOSS RIGHT FORELIMB 06-11-06 8:17 2 HAIR LOSS LEFT FORELIMB 06-12-06 7:31 2 HAIR LOSS RIGHT FORELIMB 06-12-06 7:31 2 HAIR LOSS LEFT FORELIMB 06-13-06 6:31 2 HAIR LOSS RIGHT FORELIMB 06-13-06 6:31 2 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 49 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25684 F 0.3 MG/KG/DAY BODY/INTEGUMENT 06-14-06 6:33 2 HAIR LOSS RIGHT FORELIMB 06-14-06 6:33 2 HAIR LOSS LEFT FORELIMB 06-15-06 6:37 2 HAIR LOSS RIGHT FORELIMB 06-15-06 6:37 2 HAIR LOSS LEFT FORELIMB 25684 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-06-06 7:07 1 DRIED RED MATERIAL AROUND NOSE 06-07-06 7:17 1 DRIED RED MATERIAL AROUND NOSE 06-08-06 7:20 1 DRIED RED MATERIAL AROUND NOSE 06-09-06 7:20 1 DRIED RED MATERIAL AROUND NOSE 06-10-06 8:23 1 DRIED RED MATERIAL AROUND NOSE 06-12-06 7:31 2 DRIED RED MATERIAL AROUND NOSE 06-13-06 6:31 2 DRIED RED MATERIAL AROUND NOSE 06-14-06 6:33 2 DRIED RED MATERIAL AROUND NOSE 06-15-06 6:37 2 DRIED RED MATERIAL AROUND NOSE 25684 F 0.3 MG/KG/DAY ORAL/DENTAL 06-14-06 6:34 1 WET YELLOW MATERIAL AROUND MOUTH 25714 F 0.3 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25650 F 0.3 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25650 F 0.3 MG/KG/DAY EYES/EARS/NOSE 05-31-06 6:54 2 DRIED RED MATERIAL AROUND RIGHT EYE -382- 06-02-06 7:08 P OPACITY RIGHT EYE 06-03-06 6:38 P OPACITY RIGHT EYE 06-04-06 6:44 P OPACITY RIGHT EYE 06-05-06 7:22 P OPACITY RIGHT EYE 06-06-06 7:08 P OPACITY RIGHT EYE 06-07-06 7:18 P OPACITY RIGHT EYE 06-08-06 7:21 P OPACITY RIGHT EYE 06-09-06 7:21 P OPACITY RIGHT EYE 06-09-06 7:21 1 HAIR LOSS AROUND RIGHT EYE 06-10-06 8:24 P OPACITY RIGHT EYE 06-10-06 8:24 1 HAIR LOSS AROUND RIGHT EYE 06-11-06 8:18 P OPACITY RIGHT EYE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 50 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25650 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-11-06 8:18 1 HAIR LOSS AROUND RIGHT EYE 06-12-06 7:33 P OPACITY RIGHT EYE 06-12-06 7:33 1 HAIR LOSS AROUND RIGHT EYE 06-13-06 6:31 P OPACITY RIGHT EYE 06-13-06 6:32 1 HAIR LOSS AROUND RIGHT EYE 06-14-06 6:35 P OPACITY RIGHT EYE 06-14-06 6:35 1 HAIR LOSS AROUND RIGHT EYE 06-15-06 6:38 P OPACITY RIGHT EYE 06-15-06 6:38 1 HAIR LOSS AROUND RIGHT EYE 06-16-06 6:26 P OPACITY RIGHT EYE 06-16-06 6:26 1 HAIR LOSS AROUND RIGHT EYE 25735 F 0.3 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25735 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-17-06 7:25 1 HAIR LOSS LEFT FORELIMB 05-18-06 8:01 1 HAIR LOSS LEFT FORELIMB 25722 F 0.3 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25642 F 0.3 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25642 F 0.3 MG/KG/DAY BODY/INTEGUMENT 06-06-06 7:10 1 HAIR LOSS FACIAL AREA -383- 06-07-06 7:19 2 HAIR LOSS FACIAL AREA 06-08-06 7:24 2 HAIR LOSS FACIAL AREA 06-09-06 7:26 2 HAIR LOSS FACIAL AREA 06-10-06 8:26 2 HAIR LOSS FACIAL AREA 06-11-06 8:21 2 HAIR LOSS FACIAL AREA 06-12-06 7:37 2 HAIR LOSS FACIAL AREA 06-13-06 6:34 2 HAIR LOSS FACIAL AREA 06-14-06 6:36 2 HAIR LOSS FACIAL AREA 06-14-06 6:36 P SCABBING FACIAL AREA 06-15-06 6:40 2 HAIR LOSS FACIAL AREA 06-16-06 6:29 2 HAIR LOSS FACIAL AREA 25642 F 0.3 MG/KG/DAY EYES/EARS/NOSE 05-31-06 6:55 3 DRIED RED MATERIAL AROUND RIGHT EYE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 51 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25642 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-01-06 6:45 3 DRIED RED MATERIAL AROUND RIGHT EYE 06-02-06 7:11 2 DRIED RED MATERIAL AROUND RIGHT EYE 06-02-06 7:12 P EXOPHTHALMUS RIGHT EYE 06-03-06 6:39 3 DRIED RED MATERIAL AROUND RIGHT EYE 06-03-06 6:39 P EXOPHTHALMUS RIGHT EYE 06-04-06 6:45 2 DRIED RED MATERIAL AROUND RIGHT EYE 06-04-06 6:45 P EXOPHTHALMUS RIGHT EYE 06-04-06 6:46 2 HAIR LOSS AROUND RIGHT EYE 06-05-06 7:24 3 DRIED RED MATERIAL AROUND RIGHT EYE 06-05-06 7:24 P EXOPHTHALMUS RIGHT EYE 06-05-06 7:24 2 HAIR LOSS AROUND RIGHT EYE 06-05-06 7:24 P OPACITY RIGHT EYE 06-06-06 7:09 3 DRIED RED MATERIAL AROUND RIGHT EYE 06-06-06 7:09 P EXOPHTHALMUS RIGHT EYE 06-06-06 7:09 2 HAIR LOSS AROUND RIGHT EYE 06-06-06 7:09 P OPACITY RIGHT EYE 06-07-06 7:19 3 DRIED RED MATERIAL AROUND RIGHT EYE -384- 06-07-06 7:19 P OPACITY RIGHT EYE 06-07-06 7:19 P EXOPHTHALMUS RIGHT EYE 06-07-06 7:19 2 HAIR LOSS AROUND RIGHT EYE 06-08-06 7:23 3 DRIED RED MATERIAL AROUND RIGHT EYE 06-08-06 7:23 P OPACITY RIGHT EYE 06-08-06 7:23 P EXOPHTHALMUS RIGHT EYE 06-08-06 7:23 2 HAIR LOSS AROUND RIGHT EYE 06-09-06 7:24 3 DRIED RED MATERIAL AROUND RIGHT EYE 06-09-06 7:24 P OPACITY RIGHT EYE 06-09-06 7:24 P EXOPHTHALMUS RIGHT EYE 06-09-06 7:24 3 HAIR LOSS AROUND RIGHT EYE 06-10-06 8:25 1 DRIED RED MATERIAL AROUND RIGHT EYE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 52 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25642 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-10-06 8:25 P OPACITY RIGHT EYE 06-10-06 8:25 P EXOPHTHALMUS RIGHT EYE 06-10-06 8:26 3 HAIR LOSS AROUND RIGHT EYE 06-11-06 8:20 1 DRIED RED MATERIAL AROUND RIGHT EYE 06-11-06 8:20 P EXOPHTHALMUS RIGHT EYE 06-11-06 8:20 P OPACITY RIGHT EYE 06-11-06 8:20 3 HAIR LOSS AROUND RIGHT EYE 06-12-06 7:36 1 DRIED RED MATERIAL AROUND RIGHT EYE 06-12-06 7:36 P OPACITY RIGHT EYE 06-12-06 7:36 3 HAIR LOSS AROUND RIGHT EYE 06-13-06 6:33 P OPACITY RIGHT EYE 06-13-06 6:34 3 HAIR LOSS AROUND RIGHT EYE 06-14-06 6:35 P OPACITY RIGHT EYE 06-14-06 6:36 3 HAIR LOSS AROUND RIGHT EYE 06-15-06 6:39 P OPACITY RIGHT EYE 06-15-06 6:39 3 HAIR LOSS AROUND RIGHT EYE 06-16-06 6:28 P OPACITY RIGHT EYE -385- 06-16-06 6:29 3 HAIR LOSS AROUND RIGHT EYE 25628 F 0.3 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25628 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-14-06 9:29 1 HAIR LOSS RIGHT FORELIMB 05-17-06 7:26 1 HAIR LOSS RIGHT FORELIMB 05-18-06 8:02 1 HAIR LOSS LEFT FORELIMB 05-18-06 8:02 1 HAIR LOSS RIGHT FORELIMB 05-19-06 7:04 1 HAIR LOSS LEFT FORELIMB 05-19-06 7:04 1 HAIR LOSS RIGHT FORELIMB 05-20-06 7:09 1 HAIR LOSS LEFT FORELIMB 05-20-06 7:09 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:19 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:19 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 53 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25628 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-22-06 7:38 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:38 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:15 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:15 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:57 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:57 1 HAIR LOSS LEFT FORELIMB 05-26-06 9:21 1 HAIR LOSS RIGHT FORELIMB 05-26-06 9:21 1 HAIR LOSS LEFT FORELIMB 05-27-06 9:04 1 HAIR LOSS RIGHT FORELIMB 05-27-06 9:04 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:38 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:38 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:48 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:48 1 HAIR LOSS RIGHT FORELIMB 06-06-06 7:11 1 HAIR LOSS RIGHT FORELIMB 06-07-06 7:20 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:25 1 HAIR LOSS RIGHT FORELIMB -386- 06-11-06 8:21 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:40 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:40 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:34 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:34 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:37 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:37 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:40 1 HAIR LOSS RIGHT FORELIMB 06-15-06 6:40 1 HAIR LOSS LEFT FORELIMB 06-16-06 6:30 1 HAIR LOSS RIGHT FORELIMB 06-16-06 6:30 1 HAIR LOSS LEFT FORELIMB 25628 F 0.3 MG/KG/DAY EYES/EARS/NOSE 05-31-06 6:56 2 DRIED RED MATERIAL AROUND RIGHT EYE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 54 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25628 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-01-06 6:48 2 DRIED RED MATERIAL AROUND RIGHT EYE 06-02-06 7:14 P OPACITY RIGHT EYE 06-03-06 6:39 P OPACITY RIGHT EYE 06-04-06 6:47 P OPACITY RIGHT EYE 06-05-06 7:26 1 HAIR LOSS AROUND RIGHT EYE 06-06-06 7:11 1 HAIR LOSS AROUND RIGHT EYE 06-07-06 7:20 1 HAIR LOSS AROUND RIGHT EYE 06-08-06 7:24 1 HAIR LOSS AROUND RIGHT EYE 06-09-06 7:28 1 HAIR LOSS AROUND RIGHT EYE 06-10-06 8:27 P OPACITY RIGHT EYE 06-10-06 8:27 1 HAIR LOSS AROUND RIGHT EYE 06-11-06 8:21 P OPACITY RIGHT EYE 06-11-06 8:21 1 HAIR LOSS AROUND RIGHT EYE 06-12-06 7:41 P OPACITY RIGHT EYE 06-12-06 7:41 1 HAIR LOSS AROUND RIGHT EYE 06-13-06 6:35 P OPACITY RIGHT EYE 06-13-06 6:35 1 HAIR LOSS AROUND RIGHT EYE -387- 06-14-06 6:36 P OPACITY RIGHT EYE 06-14-06 6:36 1 HAIR LOSS AROUND RIGHT EYE 06-15-06 6:40 P OPACITY RIGHT EYE 06-15-06 6:40 1 HAIR LOSS AROUND RIGHT EYE 06-16-06 6:30 P OPACITY RIGHT EYE 06-16-06 6:30 1 HAIR LOSS AROUND RIGHT EYE 05-30-06 10:37 P EXOPHTHALMUS RIGHT EYE 25763 F 0.3 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25766 F 0.3 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25766 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-12-06 7:42 1 DRIED RED MATERIAL AROUND NOSE 25689 F 0.3 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25708 F 0.3 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 55 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25743 F 0.3 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25743 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-15-06 6:42 1 DRIED RED MATERIAL AROUND NOSE 25761 F 0.3 MG/KG/DAY DISPOSITION 06-18-06 6:16 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25761 F 0.3 MG/KG/DAY EYES/EARS/NOSE 05-06-06 7:45 1 DRIED RED MATERIAL AROUND NOSE 25712 F 0.3 MG/KG/DAY DISPOSITION 06-19-06 7:04 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25746 F 0.3 MG/KG/DAY DISPOSITION 06-19-06 7:04 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25746 F 0.3 MG/KG/DAY EYES/EARS/NOSE 06-16-06 6:34 1 DRIED RED MATERIAL AROUND NOSE 25696 F 1.0 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25686 F 1.0 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25686 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-08-06 7:29 1 WET RED MATERIAL AROUND NOSE 25639 F 1.0 MG/KG/DAY DISPOSITION 06-15-06 6:59 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25639 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-21-06 7:22 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:22 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:42 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:42 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:20 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:20 1 HAIR LOSS RIGHT FORELIMB -388- 05-24-06 7:42 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:42 1 HAIR LOSS RIGHT FORELIMB 05-25-06 8:03 1 HAIR LOSS RIGHT FORELIMB 05-25-06 8:03 1 HAIR LOSS LEFT FORELIMB 05-26-06 8:50 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:50 1 HAIR LOSS LEFT FORELIMB 05-27-06 9:06 1 HAIR LOSS RIGHT FORELIMB 05-27-06 9:06 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:43 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:43 1 HAIR LOSS LEFT FORELIMB 05-29-06 7:17 1 HAIR LOSS RIGHT FORELIMB 05-29-06 7:17 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 56 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25639 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-30-06 6:53 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:53 1 HAIR LOSS RIGHT FORELIMB 05-31-06 7:05 1 HAIR LOSS LEFT FORELIMB 05-31-06 7:05 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:55 1 HAIR LOSS LEFT FORELIMB 06-01-06 6:55 1 HAIR LOSS RIGHT FORELIMB 06-02-06 7:24 1 HAIR LOSS LEFT FORELIMB 06-02-06 7:24 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:45 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:45 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:50 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:50 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:32 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:32 1 HAIR LOSS LEFT FORELIMB 06-06-06 7:16 1 HAIR LOSS RIGHT FORELIMB 06-06-06 7:17 1 HAIR LOSS LEFT FORELIMB 06-07-06 7:25 1 HAIR LOSS RIGHT FORELIMB -389- 06-07-06 7:25 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:30 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:30 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:32 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:32 1 HAIR LOSS LEFT FORELIMB 06-10-06 8:33 2 HAIR LOSS RIGHT FORELIMB 06-10-06 8:33 2 HAIR LOSS LEFT FORELIMB 06-10-06 8:33 P SCABBING RIGHT FORELIMB 06-11-06 8:25 2 HAIR LOSS RIGHT FORELIMB 06-11-06 8:25 2 HAIR LOSS LEFT FORELIMB 06-11-06 8:25 P SCABBING RIGHT FORELIMB 06-12-06 7:46 2 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 57 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25639 F 1.0 MG/KG/DAY BODY/INTEGUMENT 06-12-06 7:46 2 HAIR LOSS LEFT FORELIMB 06-13-06 6:42 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:42 2 HAIR LOSS LEFT FORELIMB 06-14-06 6:42 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:42 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:44 1 HAIR LOSS RIGHT FORELIMB 06-15-06 6:44 1 HAIR LOSS LEFT FORELIMB 25658 F 1.0 MG/KG/DAY DISPOSITION 06-15-06 6:59 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25676 F 1.0 MG/KG/DAY DISPOSITION 06-15-06 6:59 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25600 F 1.0 MG/KG/DAY DISPOSITION 06-15-06 6:59 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25600 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-21-06 7:24 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:22 1 HAIR LOSS RIGHT FORELIMB 05-25-06 8:04 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:52 1 HAIR LOSS RIGHT FORELIMB 05-27-06 9:07 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:43 1 HAIR LOSS RIGHT FORELIMB 05-29-06 7:19 1 HAIR LOSS RIGHT FORELIMB -390- 05-30-06 6:54 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:54 1 HAIR LOSS RIGHT FORELIMB 06-01-06 6:58 1 HAIR LOSS RIGHT FORELIMB 06-02-06 7:25 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:46 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:53 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:33 2 HAIR LOSS RIGHT FORELIMB 06-06-06 7:17 2 HAIR LOSS RIGHT FORELIMB 06-07-06 7:26 2 HAIR LOSS RIGHT FORELIMB 06-08-06 7:32 2 HAIR LOSS RIGHT FORELIMB 06-09-06 7:33 2 HAIR LOSS RIGHT FORELIMB 06-10-06 8:34 2 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 58 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25600 F 1.0 MG/KG/DAY BODY/INTEGUMENT 06-10-06 8:34 1 HAIR LOSS LEFT FORELIMB 06-11-06 8:28 2 HAIR LOSS RIGHT FORELIMB 06-11-06 8:28 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:47 2 HAIR LOSS RIGHT FORELIMB 06-12-06 7:47 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:44 2 HAIR LOSS RIGHT FORELIMB 06-13-06 6:44 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:42 2 HAIR LOSS RIGHT FORELIMB 06-14-06 6:42 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:47 2 HAIR LOSS RIGHT FORELIMB 06-15-06 6:47 1 HAIR LOSS LEFT FORELIMB 25600 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-05-06 7:33 1 DRIED RED MATERIAL AROUND NOSE 06-07-06 7:26 1 DRIED RED MATERIAL AROUND NOSE 06-08-06 7:32 1 DRIED RED MATERIAL AROUND NOSE 25603 F 1.0 MG/KG/DAY DISPOSITION 06-15-06 6:59 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25630 F 1.0 MG/KG/DAY DISPOSITION 06-14-06 6:54 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25630 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-06-06 8:17 1 HAIR LOSS RIGHT FORELIMB -391- 05-06-06 8:17 1 HAIR LOSS LEFT FORELIMB 05-07-06 8:18 1 HAIR LOSS RIGHT FORELIMB 05-07-06 8:18 1 HAIR LOSS LEFT FORELIMB 05-08-06 7:10 1 HAIR LOSS RIGHT FORELIMB 05-08-06 7:10 1 HAIR LOSS LEFT FORELIMB 05-03-06 9:29 1 HAIR LOSS LEFT FORELIMB 05-03-06 9:29 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:31 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:31 1 HAIR LOSS LEFT FORELIMB 05-10-06 7:04 1 HAIR LOSS LEFT FORELIMB 05-10-06 7:04 1 HAIR LOSS RIGHT FORELIMB 05-11-06 7:08 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 59 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25630 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-11-06 7:08 1 HAIR LOSS RIGHT FORELIMB 05-12-06 7:11 1 HAIR LOSS LEFT FORELIMB 05-12-06 7:11 2 HAIR LOSS RIGHT FORELIMB 05-13-06 9:52 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:52 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:35 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:35 1 HAIR LOSS LEFT FORELIMB 05-15-06 7:25 1 HAIR LOSS LEFT FORELIMB 05-15-06 7:25 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:51 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:51 1 HAIR LOSS RIGHT FORELIMB 05-17-06 7:35 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:35 1 HAIR LOSS RIGHT FORELIMB 05-18-06 8:11 2 HAIR LOSS LEFT FORELIMB 05-18-06 8:11 2 HAIR LOSS RIGHT FORELIMB 05-19-06 7:10 1 HAIR LOSS LEFT FORELIMB 05-19-06 7:10 1 HAIR LOSS RIGHT FORELIMB -392- 05-20-06 7:14 2 HAIR LOSS LEFT FORELIMB 05-20-06 7:14 2 HAIR LOSS RIGHT FORELIMB 05-21-06 7:26 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:26 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:43 2 HAIR LOSS LEFT FORELIMB 05-22-06 7:43 2 HAIR LOSS RIGHT FORELIMB 05-23-06 8:23 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:23 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:43 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:43 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:18 1 HAIR LOSS RIGHT FORELIMB 05-25-06 7:18 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 60 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25630 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-26-06 8:54 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:54 1 HAIR LOSS LEFT FORELIMB 05-27-06 9:08 1 HAIR LOSS RIGHT FORELIMB 05-27-06 9:08 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:44 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:44 1 HAIR LOSS LEFT FORELIMB 05-29-06 7:20 1 HAIR LOSS RIGHT FORELIMB 05-29-06 7:20 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:54 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:54 1 HAIR LOSS RIGHT FORELIMB 05-31-06 7:07 1 HAIR LOSS LEFT FORELIMB 05-31-06 7:07 1 HAIR LOSS RIGHT FORELIMB 06-01-06 7:00 1 HAIR LOSS LEFT FORELIMB 06-01-06 7:00 1 HAIR LOSS RIGHT FORELIMB 06-02-06 7:26 1 HAIR LOSS LEFT FORELIMB 06-02-06 7:26 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:47 1 HAIR LOSS LEFT FORELIMB -393- 06-03-06 6:47 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:55 2 HAIR LOSS LEFT FORELIMB 06-04-06 6:55 2 HAIR LOSS RIGHT FORELIMB 06-05-06 7:33 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:33 1 HAIR LOSS LEFT FORELIMB 06-06-06 7:18 1 HAIR LOSS RIGHT FORELIMB 06-06-06 7:18 1 HAIR LOSS LEFT FORELIMB 06-07-06 7:26 1 HAIR LOSS RIGHT FORELIMB 06-07-06 7:26 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:34 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:34 1 HAIR LOSS LEFT FORELIMB 06-09-06 7:34 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 61 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25630 F 1.0 MG/KG/DAY BODY/INTEGUMENT 06-09-06 7:34 1 HAIR LOSS LEFT FORELIMB 06-10-06 8:35 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:35 1 HAIR LOSS LEFT FORELIMB 06-11-06 8:29 1 HAIR LOSS RIGHT FORELIMB 06-11-06 8:29 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:48 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:48 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:44 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:44 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:43 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:43 1 HAIR LOSS LEFT FORELIMB 25703 F 1.0 MG/KG/DAY DISPOSITION 06-15-06 6:59 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25673 F 1.0 MG/KG/DAY DISPOSITION 06-14-06 6:55 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25611 F 1.0 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25619 F 1.0 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25705 F 1.0 MG/KG/DAY DISPOSITION 06-15-06 7:00 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25705 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-18-06 8:13 1 HAIR LOSS RIGHT FORELIMB -394- 05-19-06 7:13 1 HAIR LOSS RIGHT FORELIMB 05-20-06 7:15 1 HAIR LOSS LEFT FORELIMB 05-20-06 7:15 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:28 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:28 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:46 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:46 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:25 1 HAIR LOSS LEFT FORELIMB 05-23-06 8:25 1 HAIR LOSS RIGHT FORELIMB 05-24-06 7:45 1 HAIR LOSS LEFT FORELIMB 05-24-06 7:45 1 HAIR LOSS RIGHT FORELIMB 05-25-06 8:05 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 62 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25705 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-25-06 8:05 1 HAIR LOSS LEFT FORELIMB 05-26-06 8:56 1 HAIR LOSS RIGHT FORELIMB 05-26-06 8:56 1 HAIR LOSS LEFT FORELIMB 05-27-06 9:10 1 HAIR LOSS RIGHT FORELIMB 05-27-06 9:10 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:46 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:46 1 HAIR LOSS LEFT FORELIMB 05-29-06 7:22 1 HAIR LOSS RIGHT FORELIMB 05-29-06 7:22 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:56 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:57 1 HAIR LOSS RIGHT FORELIMB 05-31-06 7:09 1 HAIR LOSS LEFT FORELIMB 05-31-06 7:09 1 HAIR LOSS RIGHT FORELIMB 06-01-06 7:01 1 HAIR LOSS LEFT FORELIMB 06-01-06 7:01 1 HAIR LOSS RIGHT FORELIMB 06-02-06 7:29 1 HAIR LOSS LEFT FORELIMB 06-02-06 7:29 1 HAIR LOSS RIGHT FORELIMB -395- 06-03-06 6:51 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:51 1 HAIR LOSS RIGHT FORELIMB 06-04-06 6:57 1 HAIR LOSS LEFT FORELIMB 06-04-06 6:57 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:35 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:35 1 HAIR LOSS LEFT FORELIMB 06-06-06 7:19 1 HAIR LOSS RIGHT FORELIMB 06-06-06 7:19 1 HAIR LOSS LEFT FORELIMB 06-07-06 7:31 1 HAIR LOSS RIGHT FORELIMB 06-07-06 7:31 1 HAIR LOSS LEFT FORELIMB 06-08-06 7:36 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:36 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 63 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25705 F 1.0 MG/KG/DAY BODY/INTEGUMENT 06-09-06 7:36 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:36 1 HAIR LOSS LEFT FORELIMB 06-10-06 8:38 1 HAIR LOSS RIGHT FORELIMB 06-10-06 8:38 1 HAIR LOSS LEFT FORELIMB 06-11-06 8:32 1 HAIR LOSS RIGHT FORELIMB 06-11-06 8:32 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:52 1 HAIR LOSS RIGHT FORELIMB 06-12-06 7:52 1 HAIR LOSS LEFT FORELIMB 06-12-06 7:53 P SCABBING FACIAL AREA 06-13-06 6:45 1 HAIR LOSS RIGHT FORELIMB 06-13-06 6:46 1 HAIR LOSS LEFT FORELIMB 06-13-06 6:46 P SCABBING FACIAL AREA 06-14-06 6:46 1 HAIR LOSS RIGHT FORELIMB 06-14-06 6:46 1 HAIR LOSS LEFT FORELIMB 06-14-06 6:46 1 HAIR LOSS FACIAL AREA 06-14-06 6:46 P SCABBING FACIAL AREA 06-15-06 6:50 1 HAIR LOSS RIGHT FORELIMB -396- 06-15-06 6:50 1 HAIR LOSS LEFT FORELIMB 06-15-06 6:50 1 HAIR LOSS FACIAL AREA 06-15-06 6:50 P SCABBING FACIAL AREA 25705 F 1.0 MG/KG/DAY EYES/EARS/NOSE 05-30-06 6:57 1 DRIED RED MATERIAL AROUND NOSE 05-31-06 7:09 2 DRIED RED MATERIAL AROUND NOSE 05-31-06 7:09 1 DRIED RED MATERIAL AROUND RIGHT EYE 06-02-06 7:29 1 DRIED RED MATERIAL AROUND NOSE 06-03-06 6:51 1 DRIED RED MATERIAL AROUND NOSE 06-05-06 7:35 1 DRIED RED MATERIAL AROUND NOSE 06-06-06 7:19 1 DRIED RED MATERIAL AROUND NOSE 06-07-06 7:31 1 DRIED RED MATERIAL AROUND NOSE 06-08-06 7:36 1 DRIED RED MATERIAL AROUND NOSE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 64 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25705 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-09-06 7:37 1 DRIED RED MATERIAL AROUND NOSE 06-10-06 8:38 1 DRIED RED MATERIAL AROUND NOSE 25691 F 1.0 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25691 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-06-06 7:20 1 DRIED RED MATERIAL AROUND NOSE 25717 F 1.0 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25717 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-07-06 7:32 1 DRIED RED MATERIAL AROUND NOSE 25616 F 1.0 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25616 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-16-06 8:55 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:38 1 HAIR LOSS LEFT FORELIMB 25715 F 1.0 MG/KG/DAY DISPOSITION 06-16-06 6:45 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25757 F 1.0 MG/KG/DAY DISPOSITION 05-30-06 6:11 P SCHEDULED EUTHANASIA; POST-MATING DAY 25 25757 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-08-06 7:13 1 HAIR LOSS RIGHT FORELIMB 05-08-06 7:13 1 HAIR LOSS LEFT FORELIMB 05-05-06 8:34 1 HAIR LOSS LEFT FORELIMB 05-05-06 8:34 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:35 1 HAIR LOSS RIGHT FORELIMB 05-09-06 8:35 1 HAIR LOSS LEFT FORELIMB -397- 05-10-06 7:09 1 HAIR LOSS LEFT FORELIMB 05-10-06 7:09 1 HAIR LOSS RIGHT FORELIMB 05-11-06 7:11 1 HAIR LOSS LEFT FORELIMB 05-11-06 7:11 1 HAIR LOSS RIGHT FORELIMB 05-12-06 7:15 1 HAIR LOSS LEFT FORELIMB 05-12-06 7:15 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:59 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:59 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:38 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:38 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:55 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:55 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 65 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25757 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-17-06 7:39 1 HAIR LOSS LEFT FORELIMB 05-17-06 7:39 1 HAIR LOSS RIGHT FORELIMB 05-18-06 8:15 1 HAIR LOSS LEFT FORELIMB 05-18-06 8:15 1 HAIR LOSS RIGHT FORELIMB 05-19-06 7:16 1 HAIR LOSS LEFT FORELIMB 05-19-06 7:16 1 HAIR LOSS RIGHT FORELIMB 05-20-06 7:17 1 HAIR LOSS LEFT FORELIMB 05-20-06 7:17 1 HAIR LOSS RIGHT FORELIMB 05-21-06 7:29 1 HAIR LOSS LEFT FORELIMB 05-21-06 7:29 1 HAIR LOSS RIGHT FORELIMB 05-22-06 7:50 1 HAIR LOSS LEFT FORELIMB 05-22-06 7:50 1 HAIR LOSS RIGHT FORELIMB 05-23-06 8:27 2 HAIR LOSS LEFT FORELIMB 05-23-06 8:27 2 HAIR LOSS RIGHT FORELIMB 05-23-06 8:27 P SCABBING LEFT FORELIMB 05-24-06 7:47 2 HAIR LOSS LEFT FORELIMB 05-24-06 7:47 2 HAIR LOSS RIGHT FORELIMB -398- 05-24-06 7:47 P SCABBING LEFT FORELIMB 05-25-06 8:07 1 HAIR LOSS RIGHT FORELIMB 05-25-06 8:07 1 HAIR LOSS LEFT FORELIMB 05-26-06 9:26 1 HAIR LOSS RIGHT FORELIMB 05-26-06 9:26 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:26 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:26 1 HAIR LOSS LEFT FORELIMB 05-28-06 7:15 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:15 1 HAIR LOSS LEFT FORELIMB 05-29-06 6:40 1 HAIR LOSS RIGHT FORELIMB 05-29-06 6:40 1 HAIR LOSS LEFT FORELIMB 05-30-06 6:10 2 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 66 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25757 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-30-06 6:10 2 HAIR LOSS LEFT FORELIMB 25762 F 1.0 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25762 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-13-06 6:47 1 DRIED RED MATERIAL AROUND NOSE 25599 F 1.0 MG/KG/DAY DISPOSITION 06-16-06 6:46 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25599 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-08-06 7:38 1 DRIED RED MATERIAL AROUND NOSE 25647 F 1.0 MG/KG/DAY DISPOSITION 06-17-06 6:31 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25647 F 1.0 MG/KG/DAY EYES/EARS/NOSE 05-07-06 8:21 1 DRIED RED MATERIAL AROUND NOSE 25747 F 1.0 MG/KG/DAY DISPOSITION 06-18-06 6:16 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25747 F 1.0 MG/KG/DAY BODY/INTEGUMENT 06-09-06 7:44 P SOFT MOVABLE MASS VENTRAL THORACIC AREA 17MM X 15MM X 15MM 25744 F 1.0 MG/KG/DAY DISPOSITION 06-18-06 6:16 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25707 F 1.0 MG/KG/DAY DISPOSITION 06-17-06 6:32 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25707 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-06-06 7:36 1 DRIED RED MATERIAL VENTRAL ABDOMINAL AREA 05-26-06 9:28 1 HAIR LOSS RIGHT FORELIMB 05-26-06 9:28 1 HAIR LOSS LEFT FORELIMB 05-27-06 8:28 1 HAIR LOSS RIGHT FORELIMB 05-27-06 8:28 1 HAIR LOSS LEFT FORELIMB -399- 05-28-06 7:49 1 HAIR LOSS RIGHT FORELIMB 05-28-06 7:49 1 HAIR LOSS LEFT FORELIMB 05-29-06 7:26 1 HAIR LOSS RIGHT FORELIMB 05-29-06 7:26 1 HAIR LOSS LEFT FORELIMB 05-30-06 7:02 1 HAIR LOSS LEFT FORELIMB 05-30-06 7:02 1 HAIR LOSS RIGHT FORELIMB 05-31-06 7:14 1 HAIR LOSS LEFT FORELIMB 05-31-06 7:14 1 HAIR LOSS RIGHT FORELIMB 06-02-06 7:39 1 HAIR LOSS LEFT FORELIMB 06-02-06 7:39 1 HAIR LOSS RIGHT FORELIMB 06-03-06 6:55 1 HAIR LOSS LEFT FORELIMB 06-03-06 6:55 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 67 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25707 F 1.0 MG/KG/DAY BODY/INTEGUMENT 06-04-06 7:01 1 HAIR LOSS LEFT FORELIMB 06-04-06 7:01 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:41 1 HAIR LOSS RIGHT FORELIMB 06-05-06 7:41 2 HAIR LOSS LEFT FORELIMB 06-06-06 7:23 1 HAIR LOSS RIGHT FORELIMB 06-06-06 7:23 2 HAIR LOSS LEFT FORELIMB 06-07-06 7:35 1 HAIR LOSS RIGHT FORELIMB 06-07-06 7:35 2 HAIR LOSS LEFT FORELIMB 06-08-06 7:39 1 HAIR LOSS RIGHT FORELIMB 06-08-06 7:39 2 HAIR LOSS LEFT FORELIMB 06-09-06 7:44 1 HAIR LOSS RIGHT FORELIMB 06-09-06 7:44 2 HAIR LOSS LEFT FORELIMB 06-10-06 8:45 2 HAIR LOSS RIGHT FORELIMB 06-10-06 8:45 2 HAIR LOSS LEFT FORELIMB 06-11-06 8:36 2 HAIR LOSS RIGHT FORELIMB 06-11-06 8:36 2 HAIR LOSS LEFT FORELIMB 06-12-06 8:02 2 HAIR LOSS RIGHT FORELIMB -400- 06-12-06 8:02 2 HAIR LOSS LEFT FORELIMB 06-13-06 6:49 2 HAIR LOSS RIGHT FORELIMB 06-13-06 6:49 2 HAIR LOSS LEFT FORELIMB 06-14-06 6:50 2 HAIR LOSS RIGHT FORELIMB 06-14-06 6:50 2 HAIR LOSS LEFT FORELIMB 06-15-06 6:53 2 HAIR LOSS RIGHT FORELIMB 06-15-06 6:53 2 HAIR LOSS LEFT FORELIMB 06-16-06 6:40 2 HAIR LOSS RIGHT FORELIMB 06-16-06 6:40 2 HAIR LOSS LEFT FORELIMB 06-17-06 6:24 2 HAIR LOSS RIGHT FORELIMB 06-17-06 6:24 2 HAIR LOSS LEFT FORELIMB 25707 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-16-06 6:40 1 DRIED RED MATERIAL AROUND NOSE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 1 (F0 - DAILY EXAMINATIONS) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 68 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 06-19-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25723 F 1.0 MG/KG/DAY DISPOSITION 06-19-06 7:04 P SCHEDULED EUTHANASIA; LACTATION DAY 21 25723 F 1.0 MG/KG/DAY EYES/EARS/NOSE 06-08-06 7:39 1 DRIED RED MATERIAL AROUND NOSE 06-09-06 7:45 1 DRIED RED MATERIAL AROUND NOSE 06-12-06 8:02 1 DRIED RED MATERIAL AROUND NOSE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT PCRDv4.11 10/05/2006 -401- APPENDIX 2 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 3 6 9 12 15 18 20 25 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597 G 243. 254. 271. 280. 295. 316. 361. 398. NA 25654 G 266. 276. 291. 304. 317. 347. 381. 410. NA 25632 G 275. 300. 324. 341. 354. 375. 412. 450. NA 25610 G 274. 282. 297. 314. 336. 346. 372. 392. NA 25618 G 273. 287. 301. 318. 337. 360. 397. 450. NA 25621 G 269. 295. 311. 327. 344. 365. 402. 435. NA 25687 G 267. 278. 284. 303. 319. 342. 382. 406. NA 25633 G 263. 286. 299. 317. 341. 365. 389. 415. NA 25681 G 262. 283. 298. 314. 327. 350. 388. 421. NA 25615 G 249. 273. 281. 295. 312. 326. 357. 388. NA 25637 G 238. 259. 270. 283. 300. 326. 372. 411. NA 25638 G 257. 276. 285. 300. 311. 337. 378. 410. NA 25713 G 262. 279. 293. 298. 312. 338. 373. 413. NA 25670 G 264. 294. 307. 319. 345. 369. 398. 447. NA 25657 G 280. 287. 310. 323. 349. 372. 414. 445. NA 25663 G 281. 297. 314. 324. 342. 362. 399. 424. NA 25690 G 287. 310. 322. 334. 356. 385. 432. 474. NA 25666 G 279. 298. 312. 318. 334. 357. 399. 423. NA 25692 G 263. 282. 293. 299. 326. 348. 378. 412. NA 25701 G 257. 284. 303. 323. 342. 365. 411. 451. NA 25645 G 246. 263. 274. 277. 296. 309. 333. 362. NA 25661 G 259. 270. 284. 296. 314. 337. 375. 399. NA 25767 G 277. 297. 308. 296. 338. 316. 396. 434. NA 25770 G 280. 283. 300. 319. 334. 358. 391. 425. NA 25702 G 277. 298. 303. 317. 335. 364. 405. 433. NA -402- MEAN S.D. N 266. 284. 297. 310. 329. 349. 388. 421. NA 12.8 13.5 14.8 16.5 17.6 20.0 21.0 24.5 25 25 25 25 25 25 25 25 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 2 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 3 6 9 12 15 18 20 25 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25664 NG 236. 253. 274. 278. 278. 287. 290. 295. 291. 25648 G 255. 252. 283. 300. 322. 346. 391. 436. NA 25694 G 279. 299. 308. 329. 348. 378. 422. 449. NA 25668 G 277. 295. 308. 323. 349. 373. 415. 454. NA 25631 G 273. 286. 295. 315. 330. 349. 391. 420. NA 25660 G 268. 284. 293. 312. 332. 349. 395. 426. NA 25704 G 268. 274. 277. 296. 306. 331. 372. 413. NA 25695 NG 266. 268. 265. 271. 278. 283. 282. 283. 286. 25665 G 258. 265. 274. 287. 304. 320. 356. 379. NA 25674 G 257. 263. 270. 279. 296. 305. 351. 371. NA 25652 G 244. 262. 268. 287. 303. 322. 364. 389. NA 25733 G 257. 275. 287. 300. 316. 340. 383. 415. NA 25748 G 259. 271. 284. 298. 304. 324. 356. 377. NA 25753 G 272. 289. 306. 320. 328. 365. 407. 439. NA 25672 G 275. 290. 312. 317. 344. 360. 407. 431. NA 25655 G 281. 303. 320. 337. 354. 388. 427. 459. NA 25727 G 290. 301. 309. 323. 346. 363. 410. 457. NA 25626 G 282. 295. 305. 317. 332. 355. 392. 434. NA 25739 G 266. 288. 302. 312. 326. 353. 394. 425. NA 25749 G 257. 278. 281. 286. 302. 319. 342. 360. NA 25756 G 244. 257. 271. 282. 307. 321. 365. 403. NA 25741 G 266. 282. 301. 319. 342. 364. 410. 449. NA 25752 G 279. 286. 308. 323. 337. 363. 401. 444. NA 25758 G 278. 287. 300. 311. 331. 351. 385. 424. NA 25719 G 271. 289. 293. 305. 330. 348. 391. 425. NA -403- MEAN S.D. N 268. 281. 294. 308. 326. 347. 388. 421. NA 12.1 14.3 15.3 16.1 17.7 21.5 23.7 28.7 23 23 23 23 23 23 23 23 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 2 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 3 6 9 12 15 18 20 25 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606 G 246. 263. 274. 281. 290. 310. 350. 379. NA 25614 G 265. 280. 296. 305. 330. 354. 405. 441. NA 25671 G 292. 308. 319. 335. 352. 372. 412. 454. NA 25698 G 277. 283. 295. 311. 339. 365. 405. 435. NA 25609 G 271. 291. 305. 320. 334. 353. 398. 423. NA 25677 G 269. 273. 288. 304. 319. 331. 370. 399. NA 25623 G 267. 277. 287. 283. 295. 308. 343. 373. NA 25653 G 265. 277. 286. 301. 320. 332. 365. 396. NA 25604 G 262. 274. 286. 297. 317. 334. 366. 391. NA 25678 G 252. 269. 279. 293. 309. 328. 372. 399. NA 25684 G 248. 263. 274. 290. 312. 316. 354. 376. NA 25714 G 259. 283. 291. 305. 327. 336. 374. 416. NA 25650 G 261. 276. 287. 298. 318. 343. 394. 432. NA 25735 G 271. 285. 296. 306. 324. 347. 376. 407. NA 25722 G 273. 281. 296. 302. 323. 342. 380. 415. NA 25642 G 290. 305. 319. 329. 345. 363. 412. 446. NA 25628 G 284. 298. 303. 310. 331. 352. 383. 420. NA 25763 G 274. 292. 301. 313. 340. 360. 402. 447. NA 25766 G 263. 287. 297. 308. 329. 343. 380. 400. NA 25689 G 262. 281. 292. 302. 327. 345. 384. 412. NA 25708 G 242. 259. 278. 295. 324. 344. 383. 418. NA 25743 G 267. 275. 293. 308. 325. 356. 402. 431. NA 25761 G 276. 281. 300. 311. 322. 352. 380. 423. NA 25712 G 277. 285. 291. 305. 322. 347. 389. 425. NA 25746 G 273. 298. 313. 332. 352. 376. 433. 473. NA -404- MEAN S.D. N 267. 282. 294. 306. 325. 344. 384. 417. NA 12.4 12.3 12.1 13.3 14.7 17.5 21.2 25.0 25 25 25 25 25 25 25 25 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 2 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 3 6 9 12 15 18 20 25 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696 G 237. 259. 273. 283. 297. 316. 362. 395. NA 25686 G 254. 273. 284. 292. 300. 322. 358. 368. NA 25639 G 286. 297. 307. 325. 343. 351. 396. 428. NA 25658 G 274. 292. 298. 312. 335. 354. 387. 405. NA 25676 G 273. 285. 300. 313. 329. 345. 389. 423. NA 25600 G 268. 276. 292. 305. 323. 346. 389. 430. NA 25603 G 267. 275. 284. 291. 303. 315. 351. 373. NA 25630 G 263. 278. 287. 298. 312. 329. 369. 404. NA 25703 G 257. 268. 276. 297. 310. 329. 377. 414. NA 25673 G 250. 263. 271. 286. 302. 315. 355. 386. NA 25611 G 250. 264. 271. 273. 286. 306. 343. 374. NA 25619 G 256. 266. 276. 279. 288. 302. 311. 369. NA 25705 G 261. 278. 294. 301. 318. 337. 369. 399. NA 25691 G 267. 288. 302. 309. 325. 350. 386. 421. NA 25717 G 277. 291. 295. 302. 321. 347. 379. 413. NA 25616 G 282. 304. 313. 316. 335. 359. 397. 431. NA 25715 G 287. 304. 313. 321. 342. 367. 414. 459. NA 25757 NG 273. 280. 283. 286. 300. 302. 298. 304. 315. 25762 G 269. 289. 297. 308. 323. 335. 374. 415. NA 25599 G 259. 277. 289. 296. 315. 337. 373. 416. NA 25647 G 255. 269. 282. 286. 308. 326. 364. 388. NA 25747 G 267. 282. 304. 312. 326. 344. 383. 417. NA 25744 G 272. 279. 297. 302. 317. 336. 379. 401. NA 25707 G 285. 288. 299. 299. 322. 335. 375. 405. NA 25723 G 272. 275. 283. 292. 317. 349. 391. 433. NA -405- MEAN S.D. N 266. 280. 291. 300. 317. 336. 374. 407. NA 12.6 12.4 12.6 13.3 15.3 16.8 21.0 22.8 24 24 24 24 24 24 24 24 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGBWv4.05 01/23/2007 APPENDIX 3 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 20-25 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597 G 11. 17. 9. 15. 21. 45. 37. NA 155. 25654 G 10. 15. 13. 13. 30. 34. 29. NA 144. 25632 G 25. 24. 17. 13. 21. 37. 38. NA 175. 25610 G 8. 15. 17. 22. 10. 26. 20. NA 118. 25618 G 14. 14. 17. 19. 23. 37. 53. NA 177. 25621 G 26. 16. 16. 17. 21. 37. 33. NA 166. 25687 G 11. 6. 19. 16. 23. 40. 24. NA 139. 25633 G 23. 13. 18. 24. 24. 24. 26. NA 152. 25681 G 21. 15. 16. 13. 23. 38. 33. NA 159. 25615 G 24. 8. 14. 17. 14. 31. 31. NA 139. 25637 G 21. 11. 13. 17. 26. 46. 39. NA 173. 25638 G 19. 9. 15. 11. 26. 41. 32. NA 153. 25713 G 17. 14. 5. 14. 26. 35. 40. NA 151. 25670 G 30. 13. 12. 26. 24. 29. 49. NA 183. 25657 G 7. 23. 13. 26. 23. 42. 31. NA 165. 25663 G 16. 17. 10. 18. 20. 37. 25. NA 143. 25690 G 23. 12. 12. 22. 29. 47. 42. NA 187. 25666 G 19. 14. 6. 16. 23. 42. 24. NA 144. 25692 G 19. 11. 6. 27. 22. 30. 34. NA 149. 25701 G 27. 19. 20. 19. 23. 46. 40. NA 194. 25645 G 17. 11. 3. 19. 13. 24. 29. NA 116. 25661 G 11. 14. 12. 18. 23. 38. 24. NA 140. 25767 G 20. 11. -12. 42. -22. 80. 38. NA 157. 25770 G 3. 17. 19. 15. 24. 33. 34. NA 145. 25702 G 21. 5. 14. 18. 29. 41. 28. NA 156. -406- MEAN S.D. N 18. 14. 12. 19. 21. 38. 33. NA 155. 6.9 4.5 6.8 6.4 10.0 10.9 8.0 19.3 25 25 25 25 25 25 25 25 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 3 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 20-25 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25664 NG 17. 21. 4. 0. 9. 3. 5. -4. 59. 25648 G -3. 31. 17. 22. 24. 45. 45. NA 181. 25694 G 20. 9. 21. 19. 30. 44. 27. NA 170. 25668 G 18. 13. 15. 26. 24. 42. 39. NA 177. 25631 G 13. 9. 20. 15. 19. 42. 29. NA 147. 25660 G 16. 9. 19. 20. 17. 46. 31. NA 158. 25704 G 6. 3. 19. 10. 25. 41. 41. NA 145. 25695 NG 2. -3. 6. 7. 5. -1. 1. 3. 17. 25665 G 7. 9. 13. 17. 16. 36. 23. NA 121. 25674 G 6. 7. 9. 17. 9. 46. 20. NA 114. 25652 G 18. 6. 19. 16. 19. 42. 25. NA 145. 25733 G 18. 12. 13. 16. 24. 43. 32. NA 158. 25748 G 12. 13. 14. 6. 20. 32. 21. NA 118. 25753 G 17. 17. 14. 8. 37. 42. 32. NA 167. 25672 G 15. 22. 5. 27. 16. 47. 24. NA 156. 25655 G 22. 17. 17. 17. 34. 39. 32. NA 178. 25727 G 11. 8. 14. 23. 17. 47. 47. NA 167. 25626 G 13. 10. 12. 15. 23. 37. 42. NA 152. 25739 G 22. 14. 10. 14. 27. 41. 31. NA 159. 25749 G 21. 3. 5. 16. 17. 23. 18. NA 103. 25756 G 13. 14. 11. 25. 14. 44. 38. NA 159. 25741 G 16. 19. 18. 23. 22. 46. 39. NA 183. 25752 G 7. 22. 15. 14. 26. 38. 43. NA 165. 25758 G 9. 13. 11. 20. 20. 34. 39. NA 146. 25719 G 18. 4. 12. 25. 18. 43. 34. NA 154. -407- MEAN S.D. N 14. 12. 14. 18. 22. 41. 33. NA 153. 6.2 6.8 4.4 5.6 6.4 5.6 8.4 21.7 23 23 23 23 23 23 23 23 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 3 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 20-25 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606 G 17. 11. 7. 9. 20. 40. 29. NA 133. 25614 G 15. 16. 9. 25. 24. 51. 36. NA 176. 25671 G 16. 11. 16. 17. 20. 40. 42. NA 162. 25698 G 6. 12. 16. 28. 26. 40. 30. NA 158. 25609 G 20. 14. 15. 14. 19. 45. 25. NA 152. 25677 G 4. 15. 16. 15. 12. 39. 29. NA 130. 25623 G 10. 10. -4. 12. 13. 35. 30. NA 106. 25653 G 12. 9. 15. 19. 12. 33. 31. NA 131. 25604 G 12. 12. 11. 20. 17. 32. 25. NA 129. 25678 G 17. 10. 14. 16. 19. 44. 27. NA 147. 25684 G 15. 11. 16. 22. 4. 38. 22. NA 128. 25714 G 24. 8. 14. 22. 9. 38. 42. NA 157. 25650 G 15. 11. 11. 20. 25. 51. 38. NA 171. 25735 G 14. 11. 10. 18. 23. 29. 31. NA 136. 25722 G 8. 15. 6. 21. 19. 38. 35. NA 142. 25642 G 15. 14. 10. 16. 18. 49. 34. NA 156. 25628 G 14. 5. 7. 21. 21. 31. 37. NA 136. 25763 G 18. 9. 12. 27. 20. 42. 45. NA 173. 25766 G 24. 10. 11. 21. 14. 37. 20. NA 137. 25689 G 19. 11. 10. 25. 18. 39. 28. NA 150. 25708 G 17. 19. 17. 29. 20. 39. 35. NA 176. 25743 G 8. 18. 15. 17. 31. 46. 29. NA 164. 25761 G 5. 19. 11. 11. 30. 28. 43. NA 147. 25712 G 8. 6. 14. 17. 25. 42. 36. NA 148. 25746 G 25. 15. 19. 20. 24. 57. 40. NA 200. -408- MEAN S.D. N 14. 12. 12. 19. 19. 40. 33. NA 150. 5.8 3.7 4.8 5.1 6.3 7.1 6.7 20.3 25 25 25 25 25 25 25 25 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 3 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 20-25 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696 G 22. 14. 10. 14. 19. 46. 33. NA 158. 25686 G 19. 11. 8. 8. 22. 36. 10. NA 114. 25639 G 11. 10. 18. 18. 8. 45. 32. NA 142. 25658 G 18. 6. 14. 23. 19. 33. 18. NA 131. 25676 G 12. 15. 13. 16. 16. 44. 34. NA 150. 25600 G 8. 16. 13. 18. 23. 43. 41. NA 162. 25603 G 8. 9. 7. 12. 12. 36. 22. NA 106. 25630 G 15. 9. 11. 14. 17. 40. 35. NA 141. 25703 G 11. 8. 21. 13. 19. 48. 37. NA 157. 25673 G 13. 8. 15. 16. 13. 40. 31. NA 136. 25611 G 14. 7. 2. 13. 20. 37. 31. NA 124. 25619 G 10. 10. 3. 9. 14. 9. 58. NA 113. 25705 G 17. 16. 7. 17. 19. 32. 30. NA 138. 25691 G 21. 14. 7. 16. 25. 36. 35. NA 154. 25717 G 14. 4. 7. 19. 26. 32. 34. NA 136. 25616 G 22. 9. 3. 19. 24. 38. 34. NA 149. 25715 G 17. 9. 8. 21. 25. 47. 45. NA 172. 25757 NG 7. 3. 3. 14. 2. -4. 6. 11. 31. 25762 G 20. 8. 11. 15. 12. 39. 41. NA 146. 25599 G 18. 12. 7. 19. 22. 36. 43. NA 157. 25647 G 14. 13. 4. 22. 18. 38. 24. NA 133. 25747 G 15. 22. 8. 14. 18. 39. 34. NA 150. 25744 G 7. 18. 5. 15. 19. 43. 22. NA 129. 25707 G 3. 11. 0. 23. 13. 40. 30. NA 120. 25723 G 3. 8. 9. 25. 32. 42. 42. NA 161. -409- MEAN S.D. N 14. 11. 9. 17. 19. 38. 33. NA 141. 5.5 4.2 5.1 4.3 5.4 7.7 9.8 17.3 24 24 24 24 24 24 24 24 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGBWv4.05 01/23/2007 APPENDIX 4 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597 G 19. 22. 22. 26. NA NA 29. 23. 25654 G 22. 23. 25. 26. NA NA NA NA 25632 G 26. 31. 28. 31. 26. 26. 30. 28. 25610 G 20. 26. 27. 29. 27. 31. 34. 27. 25618 G 23. 24. 24. 26. 26. 29. 33. 26. 25621 G 21. 23. 23. 23. 24. 29. 29. 24. 25687 G 21. 21. 23. NA 22. 26. 26. 23. 25633 G 23. 25. 24. 25. 26. 25. 27. 25. 25681 G 21. 23. 25. 23. 25. 28. 28. 24. 25615 G 20. 24. 24. 24. 23. NA 29. 24. 25637 G 17. 19. 21. 22. 23. 28. 28. 22. 25638 G 19. 22. 25. 22. 27. 29. 27. 24. 25713 G 21. 22. 23. 21. 22. 27. 26. 23. 25670 G 20. 23. 25. 25. 27. 25. 31. 25. 25657 G 18. 20. 23. 23. 25. 28. 29. 24. 25663 G 18. 21. 25. 24. 28. 31. 29. 25. 25690 G 21. 23. 24. 27. 28. 33. 25. 26. 25666 G 23. 25. 25. 25. 26. 33. 30. 26. 25692 G 22. 22. 23. 24. 25. 28. 27. 24. 25701 G 22. 24. 28. 26. 26. 31. 28. 26. 25645 G 19. 20. 20. NA NA 21. NA NA 25661 G 19. 21. 22. 24. 26. 27. 27. 24. 25767 G 21. 22. 22. 26. 22. NA 28. 23. 25770 G 17. 27. 26. 29. 29. 28. 28. 26. 25702 G 21. 24. 23. 23. 26. 28. 23. 24. -410- MEAN S.D. N 21. 23. 24. 25. 25. 28. 28. 25. 2.1 2.5 2.0 2.4 2.0 2.8 2.4 1.5 25 25 25 23 22 21 23 23 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 4 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25664 NG 17. 22. 18. 22. 20. 21. 21. 20. 25648 G 13. 23. 22. 26. 28. NA 35. 24. 25694 G 23. 25. 27. 27. 30. 32. 32. 28. 25668 G 21. 24. 25. 20. 28. NA 32. 25. 25631 G 20. 23. 23. 24. 26. 30. 27. 25. 25660 G 20. 24. 24. 25. 24. 29. 30. 25. 25704 G 21. 20. 22. 23. 25. 28. 32. 24. 25695 NG 16. 17. 18. 17. 18. 21. 18. 18. 25665 G 18. 20. 20. 21. 23. 25. 24. 22. 25674 G 18. 19. 19. 21. 21. 28. 25. 21. 25652 G 19. NA 22. NA 24. 27. 27. 23. 25733 G 22. 24. 24. NA 26. 30. 25. 25. 25748 G 18. 19. 21. 22. 25. 27. 23. 22. 25753 G 20. 22. 25. 22. 27. 27. 27. 24. 25672 G 20. 23. 24. 25. 26. 32. 27. 25. 25655 G 22. 25. 28. 29. 31. 34. 28. 28. 25727 G 21. 23. 24. NA 25. 28. 33. 25. 25626 G 22. 23. 25. 24. 28. 28. 29. 25. 25739 G 21. 22. 24. 21. 27. 30. 27. 25. 25749 G 19. 18. 20. 24. 22. 27. 23. 22. 25756 G 17. 21. 21. 22. 25. 25. 26. 22. 25741 G 21. 22. 24. 24. 26. 29. 31. 25. 25752 G 19. 24. 25. 24. 25. 27. 30. 25. 25758 G 18. 21. 22. 25. 25. 21. 21. 22. 25719 G 25. 25. 23. 29. 29. 30. 30. 27. -411- MEAN S.D. N 20. 22. 23. 24. 26. 28. 28. 24. 2.4 2.1 2.2 2.5 2.4 2.8 3.6 1.9 23 22 23 20 23 21 23 23 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 4 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606 G 19. 20. 19. 21. 21. 24. 24. 21. 25614 G 19. 22. 21. 26. 26. 31. 31. 25. 25671 G 23. 24. 25. 29. 26. 30. 34. 27. 25698 G 20. 22. 23. 24. 28. 30. 31. 25. 25609 G 23. 25. 24. 25. 26. 31. 29. 26. 25677 G 18. 21. 23. 23. 24. 27. 26. 23. 25623 G 19. 21. 17. 19. 22. NA 25. 20. 25653 G 19. 21. 22. 23. 24. 26. 27. 23. 25604 G 19. 20. 20. 23. 23. 25. 23. 22. 25678 G 20. 21. 21. 21. 23. 28. 26. 23. 25684 G 19. 23. 23. NA 20. NA 29. 22. 25714 G 20. 22. 24. 26. 24. 28. 31. 25. 25650 G 20. 22. 22. NA NA 29. 29. 24. 25735 G 19. 20. 22. 23. 24. 24. 28. 23. 25722 G 21. 22. 23. 24. 25. 26. 30. 24. 25642 G 22. 24. 26. NA 29. 35. 32. 28. 25628 G 20. 21. 22. 24. 24. 24. 16. 22. 25763 G 22. NA 24. NA 25. NA 29. 25. 25766 G 19. 22. 24. 26. 25. 30. 21. 24. 25689 G 21. 25. 25. NA NA 29. 28. 25. 25708 G 19. 21. 24. 25. 26. 28. 29. 24. 25743 G 18. 21. 21. 22. 27. 26. 25. 23. 25761 G 19. 24. 23. 24. 27. 27. 30. 25. 25712 G 21. 24. 25. 24. 26. 27. 26. 25. 25746 G NA 29. NA NA 29. 35. 32. NA -412- MEAN S.D. N 20. 22. 23. 24. 25. 28. 28. 24. 1.4 2.1 2.1 2.2 2.3 3.1 3.9 1.8 24 24 24 19 23 22 25 24 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 4 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696 G 22. 23. 22. 24. NA 27. 26. 24. 25686 G 21. 22. 22. 23. 23. 23. 20. 22. 25639 G 19. 21. 23. 22. 21. 28. 28. 23. 25658 G 21. 24. 23. 26. 27. 27. 21. 24. 25676 G 21. 23. 23. 24. 24. 26. 30. 24. 25600 G 19. 22. 21. 23. 25. 28. 29. 24. 25603 G 17. 22. 21. 19. 25. 26. 25. 22. 25630 G 21. 22. 21. NA 24. 28. 32. 24. 25703 G 19. 21. 22. 23. 24. 29. 29. 24. 25673 G 19. 21. 21. 20. 21. 22. 26. 21. 25611 G 18. 19. 19. 19. 20. 22. 24. 20. 25619 G 18. 21. 20. 19. 19. 22. 26. 20. 25705 G 20. 22. 22. 21. 26. 25. 27. 23. 25691 G 18. 21. 21. 22. 26. 26. 31. 23. 25717 G 21. 20. 23. 23. 26. 30. 29. 25. 25616 G 23. 23. 24. 23. 23. 27. 26. 24. 25715 G 22. 24. 26. 25. NA NA 30. 25. 25757 NG 19. 20. 21. 22. 20. 20. 21. 20. 25762 G 20. 21. 21. 21. 20. 22. 30. 22. 25599 G 20. 25. 22. NA 23. NA 25. 23. 25647 G 18. 20. 21. 22. 26. 27. 24. 23. 25747 G 21. 24. 22. NA 22. NA 27. 23. 25744 G 19. NA 22. 24. 23. 28. 27. 24. 25707 G 21. 23. 21. 27. 27. NA 28. 24. 25723 G 17. 21. 21. 27. 29. 28. 27. 24. -413- MEAN S.D. N 20. 22. 22. 23. 24. 26. 27. 23. 1.6 1.5 1.4 2.4 2.6 2.5 2.9 1.4 24 23 24 21 22 20 24 24 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGFWv4.08 10/26/2006 APPENDIX 5 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597 G 76. 84. 80. 90. NA NA 76. 76. 25654 G 81. 81. 84. 84. NA NA NA NA 25632 G 90. 99. 84. 89. 71. 66. 70. 79. 25610 G 72. 90. 88. 89. 79. 86. 89. 83. 25618 G 82. 82. 77. 79. 74. 77. 78. 76. 25621 G 74. 76. 72. 68. 68. 76. 69. 70. 25687 G 77. 75. 78. NA 66. 72. 66. 71. 25633 G 84. 85. 78. 76. 74. 66. 67. 75. 25681 G 77. 79. 82. 72. 74. 76. 69. 73. 25615 G 77. 87. 83. 79. 72. NA 78. 77. 25637 G 68. 72. 76. 75. 73. 80. 71. 72. 25638 G 71. 78. 85. 72. 83. 81. 69. 75. 25713 G 77. 77. 78. 69. 68. 76. 66. 72. 25670 G 72. 76. 80. 75. 76. 65. 73. 73. 25657 G 63. 67. 73. 68. 69. 71. 67. 69. 25663 G 62. 69. 78. 72. 80. 81. 70. 73. 25690 G 70. 73. 73. 78. 75. 81. 55. 72. 25666 G 80. 82. 79. 77. 75. 87. 73. 76. 25692 G 81. 76. 78. 77. 74. 77. 68. 74. 25701 G 81. 82. 89. 78. 73. 80. 65. 76. 25645 G 75. 74. 72. NA NA 65. NA NA 25661 G 72. 76. 76. 79. 80. 76. 70. 76. 25767 G 73. 73. 73. 82. 67. NA 67. 69. 25770 G 60. 92. 84. 89. 84. 75. 69. 77. 25702 G 73. 80. 74. 71. 74. 73. 55. 70. -414- MEAN S.D. N 75. 79. 79. 78. 74. 76. 70. 74. 7.0 7.3 4.9 6.8 4.9 6.4 7.0 3.4 25 25 25 23 22 21 23 23 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 5 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25664 NG 69. 83. 65. 79. 71. 73. 72. 73. 25648 G 51. 86. 75. 84. 84. NA 85. 74. 25694 G 80. 82. 85. 80. 83. 80. 73. 80. 25668 G 73. 79. 79. 60. 78. NA 74. 72. 25631 G 71. 79. 75. 74. 76. 81. 67. 75. 25660 G 72. 83. 79. 78. 70. 78. 73. 75. 25704 G 77. 72. 77. 76. 78. 80. 81. 76. 25695 NG 60. 64. 67. 62. 64. 74. 64. 65. 25665 G 69. 74. 71. 71. 74. 74. 65. 72. 25674 G 69. 71. 69. 73. 70. 85. 69. 70. 25652 G 75. NA 79. NA 77. 79. 72. 75. 25733 G 83. 85. 82. NA 79. 83. 63. 78. 25748 G 68. 68. 72. 73. 80. 79. 63. 71. 25753 G 71. 74. 80. 68. 78. 70. 64. 70. 25672 G 71. 76. 76. 76. 74. 83. 64. 73. 25655 G 75. 80. 85. 84. 84. 83. 63. 78. 25727 G 71. 75. 76. NA 70. 72. 76. 71. 25626 G 76. 77. 80. 74. 81. 75. 70. 74. 25739 G 76. 75. 78. 66. 79. 80. 66. 75. 25749 G 71. 64. 70. 82. 71. 82. 66. 73. 25756 G 68. 80. 76. 75. 80. 73. 68. 72. 25741 G 77. 75. 77. 73. 74. 75. 72. 73. 25752 G 67. 81. 79. 73. 71. 71. 71. 73. 25758 G 64. 71. 72. 78. 73. 57. 52. 66. 25719 G 89. 86. 77. 91. 86. 81. 74. 81. -415- MEAN S.D. N 72. 77. 77. 75. 77. 77. 69. 74. 7.3 5.8 4.3 6.9 4.9 6.4 6.9 3.4 23 22 23 20 23 21 23 23 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 5 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606 G 75. 74. 68. 73. 70. 73. 66. 70. 25614 G 70. 76. 70. 82. 76. 82. 73. 75. 25671 G 77. 76. 76. 84. 72. 77. 79. 76. 25698 G 71. 76. 76. 74. 80. 78. 74. 74. 25609 G 82. 84. 77. 76. 76. 82. 71. 77. 25677 G 66. 75. 78. 74. 74. 77. 68. 72. 25623 G 70. 74. 60. 66. 73. NA 70. 66. 25653 G 70. 74. 75. 74. 74. 74. 71. 72. 25604 G 71. 71. 68. 75. 71. 71. 61. 70. 25678 G 77. 77. 73. 70. 72. 80. 67. 73. 25684 G 74. 86. 82. NA 64. NA 79. 72. 25714 G 74. 77. 81. 82. 72. 79. 78. 77. 25650 G 74. 78. 75. NA NA 79. 70. 74. 25735 G 68. 69. 73. 73. 71. 66. 71. 70. 25722 G 76. 76. 77. 77. 75. 72. 75. 73. 25642 G 74. 77. 80. NA 82. 90. 75. 80. 25628 G 69. 70. 72. 75. 70. 65. 40. 66. 25763 G 78. NA 78. NA 71. NA 68. 73. 25766 G 69. 75. 79. 82. 74. 83. 54. 74. 25689 G 77. 87. 84. NA NA 79. 70. 77. 25708 G 76. 78. 84. 81. 78. 77. 72. 75. 25743 G 66. 74. 70. 69. 79. 69. 60. 69. 25761 G 68. 82. 75. 76. 80. 74. 75. 76. 25712 G 75. 83. 84. 76. 78. 73. 64. 76. 25746 G NA 95. NA NA 80. 86. 71. NA -416- MEAN S.D. N 73. 78. 76. 76. 74. 77. 69. 73. 4.2 5.9 5.8 4.8 4.3 6.2 8.4 3.5 24 24 24 19 23 22 25 24 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE APPENDIX 5 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696 G 89. 86. 79. 83. NA 80. 69. 79. 25686 G 80. 79. 76. 78. 74. 68. 55. 72. 25639 G 65. 70. 73. 66. 61. 75. 68. 67. 25658 G 74. 81. 75. 80. 78. 73. 53. 72. 25676 G 75. 78. 75. 75. 71. 71. 74. 72. 25600 G 70. 77. 70. 73. 75. 76. 71. 73. 25603 G 63. 79. 73. 64. 81. 78. 69. 72. 25630 G 77. 78. 72. NA 75. 80. 83. 75. 25703 G 72. 77. 77. 76. 75. 82. 73. 76. 25673 G 74. 79. 75. 68. 68. 66. 70. 69. 25611 G 70. 71. 70. 68. 68. 68. 67. 68. 25619 G 69. 77. 72. 67. 64. 72. 76. 68. 25705 G 74. 77. 74. 68. 79. 71. 70. 72. 25691 G 65. 71. 69. 69. 77. 71. 77. 69. 25717 G 74. 68. 77. 74. 78. 83. 73. 76. 25616 G 78. 74. 76. 71. 66. 71. 63. 70. 25715 G 74. 78. 82. 75. NA NA 69. 71. 25757 NG 69. 71. 74. 75. 66. 67. 70. 69. 25762 G 72. 72. 69. 66. 61. 62. 76. 67. 25599 G 75. 88. 75. NA 71. NA 63. 72. 25647 G 69. 72. 74. 74. 82. 78. 64. 74. 25747 G 76. 82. 71. NA 66. NA 68. 70. 25744 G 69. NA 73. 77. 70. 78. 69. 74. 25707 G 73. 78. 70. 87. 82. NA 72. 74. 25723 G 62. 75. 73. 89. 87. 76. 66. 73. -417- MEAN S.D. N 72. 77. 74. 74. 73. 74. 69. 72. 5.8 4.9 3.2 6.9 7.1 5.6 6.6 3.0 24 23 24 21 22 20 24 24 G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGFWv4.08 01/23/2007 APPENDIX 6 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING LACTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1 4 7 10 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597 272. 308. 318. 328. 350. 347. 350. 25654 313. 325. 349. 347. 349. 350. 341. 25632 342. 353. 353. 362. 368. 361. 358. 25610 332. 348. 350. 359. 367. 350. 374. 25618 323. 348. 350. 370. 377. 383. 379. 25621 318. 364. 366. 385. 404. 397. 389. 25687 319. 345. 336. 350. 357. 360. 352. 25633 315. 341. 351. 366. 364. 357. 384. 25681 316. 336. 346. 360. 378. 370. 360. 25615 308. 337. 325. 349. 345. 353. 334. 25637 301. 324. 328. 336. 358. 369. 340. 25638 290. 305. 311. 331. 340. 333. 332. 25713 303. 323. 341. 354. 349. 365. 358. 25670 304. 354. 357. 365. 389. 394. 381. 25657 341. 354. 355. 358. 397. 396. 397. 25663 356. 359. 379. 398. 411. 403. 411. 25690 342. 357. 365. 381. 387. 396. 394. 25666 314. 351. 351. 369. 382. 377. 362. 25692 315. 332. 345. 348. 366. 376. 361. 25701 318. 345. 356. 367. 377. 371. 364. 25645 288. 301. 315. 327. 329. 337. 318. 25661 314. 327. 343. 353. 360. 361. 348. 25767 328. 343. 358. 379. 373. 381. 377. 25770 331. 338. 356. 362. 369. 373. 370. 25702 324. 353. 369. 373. 395. 398. 382. -418- MEAN S.D. N 317. 18.6 25 339. 17.1 25 347. 17.0 25 359. 17.6 25 370. 20.5 25 370. 19.8 25 365. 22.5 25 APPENDIX 6 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING LACTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1 4 7 10 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25648 316. 328. 331. 352. 372. 357. 391. 25694 335. 361. 370. 378. 388. 389. 374. 25668 315. 351. 375. 383. 389. 394. 389. 25631 327. 354. 351. 368. 370. 374. 374. 25660 323. 347. 355. 377. 377. 374. 371. 25704 304. 309. 332. 346. 346. 360. 350. 25665 290. 316. 321. 330. 329. 334. 343. 25674 275. 291. 306. 316. 325. 317. 320. 25652 307. 326. 329. 339. 344. 361. 333. 25733 312. 326. 340. 346. 364. 363. 345. 25748 316. 341. 338. 344. 349. 355. 332. 25753 324. 336. 346. 366. 375. 379. 370. 25672 329. 354. 344. 383. 379. 392. 377. 25655 369. 391. 388. 410. 407. 402. 381. 25727 345. 369. 374. 380. 384. 393. 375. 25626 325. 350. 344. 357. 378. 398. 375. 25739 319. 346. 344. 359. 378. 379. 359. 25749 285. 311. 324. 334. 353. 361. 371. 25756 300. 314. 321. 337. 359. 349. 346. 25741 331. 363. 376. 383. 382. 406. 391. 25752 335. 351. 363. 379. 389. 409. 392. 25758 326. 348. 348. 364. 364. 381. 361. 25719 308. 308. 333. 347. 354. 369. 374. -419- MEAN S.D. N 318. 20.2 23 339. 23.6 23 346. 20.9 23 360. 22.3 23 368. 20.3 23 374. 23.2 23 365. 20.5 23 APPENDIX 6 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING LACTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1 4 7 10 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606 285. 306. 314. 309. 329. 317. 317. 25614 320. 327. 342. 360. 369. 369. 354. 25671 345. 352. 353. 369. 390. 405. 400. 25698 335. 339. 354. 375. 388. 391. 383. 25609 325. 339. 344. 352. 370. 375. 350. 25677 309. 321. 328. 339. 341. 347. 364. 25623 293. 304. 312. 331. 329. 335. 338. 25653 303. 338. 335. 347. 370. 370. 350. 25604 305. 326. 335. 348. 354. 361. 363. 25678 314. 335. 334. 345. 356. 352. 362. 25684 294. 324. 341. 356. 356. 351. 373. 25714 319. 348. 352. 362. 378. 374. 361. 25650 313. 332. 339. 352. 360. 369. 367. 25735 322. 354. 348. 366. 366. 374. 377. 25722 314. 348. 339. 362. 370. 375. 361. 25642 336. 365. 347. 355. 357. 376. 363. 25628 291. 315. 319. 339. 338. 364. 347. 25763 319. 313. 322. 344. 350. 358. 362. 25766 310. 340. 344. 369. 365. 390. 370. 25689 316. 352. 352. 369. 359. 381. 380. 25708 334. 355. 360. 377. 386. 385. 367. 25743 323. 331. 351. 359. 348. 377. 372. 25761 321. 334. 339. 351. 360. 356. 346. 25712 311. 338. 340. 346. 368. 368. 358. 25746 353. 359. 363. 384. 395. 410. 397. -420- MEAN S.D. N 316. 16.5 25 336. 16.3 25 340. 13.4 25 355. 16.1 25 362. 17.6 25 369. 20.3 25 363. 17.6 25 APPENDIX 6 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING LACTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1 4 7 10 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696 281. 293. 292. 302. 305. 319. 316. 25686 292. 304. 313. 329. 329. 330. 334. 25639 325. 347. 361. 362. 377. 365. 349. 25658 308. 332. 336. 366. 366. 377. 387. 25676 335. 339. 333. 344. 348. 354. 345. 25600 314. 330. 360. 359. 369. 368. 360. 25603 288. 314. 324. 331. 340. 332. 342. 25630 299. 320. 324. 348. 356. 370. 355. 25703 312. 319. 338. 358. 348. 349. 353. 25673 275. 300. 317. 323. 329. 325. 332. 25611 266. 286. 302. 312. 317. 318. 314. 25619 281. 296. 302. 310. 320. 322. 329. 25705 313. 328. 328. 356. 358. 349. 361. 25691 317. 351. 356. 362. 364. 355. 350. 25717 310. 311. 330. 348. 353. 377. 358. 25616 328. 354. 345. 360. 364. 368. 371. 25715 341. 366. 351. 376. 386. 378. 370. 25762 319. 324. 338. 350. 358. 368. 357. 25599 292. 330. 329. 349. 343. 361. 352. 25647 308. 320. 321. 331. 326. 340. 338. 25747 307. 350. 357. 359. 378. 373. 359. 25744 294. 317. 331. 349. 345. 371. 366. 25707 316. 316. 322. 336. 349. 359. 360. 25723 315. 321. 339. 326. 342. 369. 354. -421- MEAN S.D. N 306. 19.0 24 324. 20.4 24 331. 18.5 24 344. 19.4 24 349. 20.5 24 354. 20.0 24 351. 17.1 24 PLBWv4.04 10/05/2006 APPENDIX 7 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING LACTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597 36. 10. 10. 22. -3. 3. 78. 25654 12. 24. -2. 2. 1. -9. 28. 25632 11. 0. 9. 6. -7. -3. 16. 25610 16. 2. 9. 8. -17. 24. 42. 25618 25. 2. 20. 7. 6. -4. 56. 25621 46. 2. 19. 19. -7. -8. 71. 25687 26. -9. 14. 7. 3. -8. 33. 25633 26. 10. 15. -2. -7. 27. 69. 25681 20. 10. 14. 18. -8. -10. 44. 25615 29. -12. 24. -4. 8. -19. 26. 25637 23. 4. 8. 22. 11. -29. 39. 25638 15. 6. 20. 9. -7. -1. 42. 25713 20. 18. 13. -5. 16. -7. 55. 25670 50. 3. 8. 24. 5. -13. 77. 25657 13. 1. 3. 39. -1. 1. 56. 25663 3. 20. 19. 13. -8. 8. 55. 25690 15. 8. 16. 6. 9. -2. 52. 25666 37. 0. 18. 13. -5. -15. 48. 25692 17. 13. 3. 18. 10. -15. 46. 25701 27. 11. 11. 10. -6. -7. 46. 25645 13. 14. 12. 2. 8. -19. 30. 25661 13. 16. 10. 7. 1. -13. 34. 25767 15. 15. 21. -6. 8. -4. 49. 25770 7. 18. 6. 7. 4. -3. 39. 25702 29. 16. 4. 22. 3. -16. 58. -422- MEAN S.D. N 22. 8. 12. 11. 1. -6. 48. 11.6 8.8 6.6 10.6 8.0 12.3 15.8 25 25 25 25 25 25 25 APPENDIX 7 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING LACTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25648 12. 3. 21. 20. -15. 34. 75. 25694 26. 9. 8. 10. 1. -15. 39. 25668 36. 24. 8. 6. 5. -5. 74. 25631 27. -3. 17. 2. 4. 0. 47. 25660 24. 8. 22. 0. -3. -3. 48. 25704 5. 23. 14. 0. 14. -10. 46. 25665 26. 5. 9. -1. 5. 9. 53. 25674 16. 15. 10. 9. -8. 3. 45. 25652 19. 3. 10. 5. 17. -28. 26. 25733 14. 14. 6. 18. -1. -18. 33. 25748 25. -3. 6. 5. 6. -23. 16. 25753 12. 10. 20. 9. 4. -9. 46. 25672 25. -10. 39. -4. 13. -15. 48. 25655 22. -3. 22. -3. -5. -21. 12. 25727 24. 5. 6. 4. 9. -18. 30. 25626 25. -6. 13. 21. 20. -23. 50. 25739 27. -2. 15. 19. 1. -20. 40. 25749 26. 13. 10. 19. 8. 10. 86. 25756 14. 7. 16. 22. -10. -3. 46. 25741 32. 13. 7. -1. 24. -15. 60. 25752 16. 12. 16. 10. 20. -17. 57. 25758 22. 0. 16. 0. 17. -20. 35. 25719 0. 25. 14. 7. 15. 5. 66. -423- MEAN S.D. N 21. 7. 14. 8. 6. -9. 47. 8.4 9.6 7.5 8.4 10.4 14.3 17.9 23 23 23 23 23 23 23 APPENDIX 7 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING LACTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606 21. 8. -5. 20. -12. 0. 32. 25614 7. 15. 18. 9. 0. -15. 34. 25671 7. 1. 16. 21. 15. -5. 55. 25698 4. 15. 21. 13. 3. -8. 48. 25609 14. 5. 8. 18. 5. -25. 25. 25677 12. 7. 11. 2. 6. 17. 55. 25623 11. 8. 19. -2. 6. 3. 45. 25653 35. -3. 12. 23. 0. -20. 47. 25604 21. 9. 13. 6. 7. 2. 58. 25678 21. -1. 11. 11. -4. 10. 48. 25684 30. 17. 15. 0. -5. 22. 79. 25714 29. 4. 10. 16. -4. -13. 42. 25650 19. 7. 13. 8. 9. -2. 54. 25735 32. -6. 18. 0. 8. 3. 55. 25722 34. -9. 23. 8. 5. -14. 47. 25642 29. -18. 8. 2. 19. -13. 27. 25628 24. 4. 20. -1. 26. -17. 56. 25763 -6. 9. 22. 6. 8. 4. 43. 25766 30. 4. 25. -4. 25. -20. 60. 25689 36. 0. 17. -10. 22. -1. 64. 25708 21. 5. 17. 9. -1. -18. 33. 25743 8. 20. 8. -11. 29. -5. 49. 25761 13. 5. 12. 9. -4. -10. 25. 25712 27. 2. 6. 22. 0. -10. 47. 25746 6. 4. 21. 11. 15. -13. 44. -424- MEAN S.D. N 19. 4. 14. 7. 7. -6. 47. 11.3 8.2 6.6 9.5 10.8 11.8 12.8 25 25 25 25 25 25 25 APPENDIX 7 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING LACTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696 12. -1. 10. 3. 14. -3. 35. 25686 12. 9. 16. 0. 1. 4. 42. 25639 22. 14. 1. 15. -12. -16. 24. 25658 24. 4. 30. 0. 11. 10. 79. 25676 4. -6. 11. 4. 6. -9. 10. 25600 16. 30. -1. 10. -1. -8. 46. 25603 26. 10. 7. 9. -8. 10. 54. 25630 21. 4. 24. 8. 14. -15. 56. 25703 7. 19. 20. -10. 1. 4. 41. 25673 25. 17. 6. 6. -4. 7. 57. 25611 20. 16. 10. 5. 1. -4. 48. 25619 15. 6. 8. 10. 2. 7. 48. 25705 15. 0. 28. 2. -9. 12. 48. 25691 34. 5. 6. 2. -9. -5. 33. 25717 1. 19. 18. 5. 24. -19. 48. 25616 26. -9. 15. 4. 4. 3. 43. 25715 25. -15. 25. 10. -8. -8. 29. 25762 5. 14. 12. 8. 10. -11. 38. 25599 38. -1. 20. -6. 18. -9. 60. 25647 12. 1. 10. -5. 14. -2. 30. 25747 43. 7. 2. 19. -5. -14. 52. 25744 23. 14. 18. -4. 26. -5. 72. 25707 0. 6. 14. 13. 10. 1. 44. 25723 6. 18. -13. 16. 27. -15. 39. -425- MEAN S.D. N 18. 8. 12. 5. 5. -4. 45. 11.4 10.3 9.9 7.2 11.6 9.2 14.8 24 24 24 24 24 24 24 PLBWv4.04 10/05/2006 APPENDIX 8 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597 39. 40. 49. 59. 58. 64. 52. 25654 53. NA NA 52. 56. 56. 54. 25632 34. 40. 52. 59. 66. 70. 55. 25610 26. 35. 43. 49. 48. 59. 44. 25618 43. 44. 57. 63. 70. 78. 60. 25621 40. 45. 57. 63. 72. 77. 60. 25687 62. NA NA 59. 65. 73. 65. 25633 30. 34. 42. 44. 46. 52. 42. 25681 41. 41. 58. 65. 69. 71. 58. 25615 43. 42. 56. 64. 69. 73. 59. 25637 40. 46. 58. 69. 79. 81. 64. 25638 33. 41. 54. 65. 74. 75. 58. 25713 NA NA 57. 61. 71. 74. NA 25670 43. 44. 55. 66. 75. 77. 61. 25657 41. 43. 54. 68. 72. 78. 61. 25663 34. 47. 62. 64. 73. 84. 62. 25690 36. 43. 51. 60. 74. 75. 58. 25666 38. 40. 57. 66. 70. 68. 58. 25692 NA 45. 55. 68. 71. 77. NA 25701 45. 43. 52. NA 61. 73. 56. 25645 NA 44. 50. 56. 58. 68. NA 25661 NA 45. 52. 59. 64. NA NA 25767 40. 44. 58. 63. 65. 71. 58. 25770 NA 46. 57. 68. 67. NA NA 25702 46. 52. 62. 75. 74. NA NA -426- MEAN 40. 43. 54. 62. 67. 72. 57. S.D. 7.9 3.9 5.0 6.8 8.3 7.9 5.9 N 20 22 23 24 25 22 19 NA = NOT APPLICABLE APPENDIX 8 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25648 35. 36. NA 62. 71. 78. 58. 25694 43. 45. 59. 72. 70. 79. 63. 25668 35. 43. 49. 59. 68. 68. 54. 25631 44. 45. 58. 67. 73. 80. 62. 25660 46. 41. 59. 69. 70. 77. 61. 25704 33. 45. 57. 63. 75. 76. 59. 25665 34. NA 46. 56. 59. 67. 53. 25674 33. 38. 46. 52. 57. 63. 49. 25652 58. NA NA 65. 74. 73. 67. 25733 34. 43. NA 63. 71. 66. 56. 25748 38. 42. 54. 58. 66. 79. 58. 25753 NA NA 55. 61. 60. 84. NA 25672 39. 40. 57. 64. 70. 77. 59. 25655 43. 47. 62. 64. 65. 77. 61. 25727 40. NA 55. 63. 74. 72. 61. 25626 36. NA 55. 63. 73. 75. 61. 25739 43. 44. 58. 67. 75. 78. 62. 25749 33. 42. 51. 59. 64. 79. 56. 25756 41. 46. 61. 73. 73. 87. 65. 25741 49. 51. 59. 69. 75. 80. 65. 25752 37. 51. 63. 72. 77. 88. 66. 25758 42. 43. 55. 66. 74. 76. 60. 25719 NA 56. 67. 73. 82. NA NA -427- MEAN 40. 44. 56. 64. 70. 76. 60. S.D. 6.3 4.8 5.4 5.5 6.1 6.3 4.5 N 21 18 20 23 23 22 21 NA = NOT APPLICABLE APPENDIX 8 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606 35. 42. 47. 59. 60. 67. 53. 25614 35. 42. 52. 55. 61. 67. 53. 25671 41. 36. NA 69. 72. 75. 60. 25698 27. 36. 54. 59. 63. 69. 52. 25609 39. 41. 48. 59. 64. 66. 54. 25677 31. NA 48. 61. 63. 69. 56. 25623 NA NA 53. 53. 58. 64. NA 25653 42. NA 53. 68. 75. 81. 65. 25604 31. 40. 48. 58. 64. 79. 55. 25678 35. 37. 49. 59. 69. 73. 55. 25684 38. 45. NA 61. 65. 83. 60. 25714 42. 47. 51. 60. 66. 77. 58. 25650 41. 44. 54. 67. 74. 76. 61. 25735 44. 43. 56. 64. 69. 78. 60. 25722 43. NA 54. 62. 65. 75. 61. 25642 44. 39. 50. 57. 69. 77. 57. 25628 NA NA 57. 58. 72. 72. NA 25763 NA 37. 47. 58. 64. 64. NA 25766 32. 39. 51. 50. 61. 62. 50. 25689 46. 44. 60. 68. 73. 84. 64. 25708 43. 44. 57. 67. 70. 80. 61. 25743 34. 42. 47. 56. 66. 70. 54. 25761 38. 47. 57. 69. 72. 80. 62. 25712 NA 45. 53. 66. 69. NA NA 25746 NA 43. 63. 74. 84. NA NA -428- MEAN 38. 42. 53. 61. 68. 73. 58. S.D. 5.3 3.4 4.4 5.8 5.8 6.5 4.2 N 20 20 23 25 25 23 20 NA = NOT APPLICABLE APPENDIX 8 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696 38. 37. 47. 55. 60. 72. 53. 25686 35. 41. 48. 56. 56. 72. 52. 25639 44. 51. 56. 69. 68. 66. 60. 25658 42. 42. 59. 64. 72. 72. 59. 25676 37. 41. 48. 58. 61. 75. 54. 25600 48. 52. 56. 70. 77. 77. 64. 25603 39. 40. 52. 55. 59. 75. 54. 25630 35. 43. NA 67. 76. 81. 62. 25703 36. 44. 58. 61. 68. 72. 57. 25673 30. 36. 44. 51. 57. 60. 47. 25611 28. 43. 48. 55. 60. 68. 51. 25619 30. 37. 46. 56. 58. 66. 50. 25705 34. 37. 53. 59. 58. 73. 54. 25691 37. 44. 58. 65. 68. 73. 59. 25717 28. 42. 51. 58. 69. 73. 55. 25616 40. 42. 55. 67. 71. 87. 62. 25715 36. 39. 54. 64. 69. 75. 57. 25762 NA NA 52. 63. 64. 69. NA 25599 36. 35. 47. 52. 64. 66. 51. 25647 33. 37. 43. 52. 55. 59. 47. 25747 NA NA 53. 63. 66. 79. NA 25744 NA NA 57. 63. 73. 84. NA 25707 25. NA 54. 63. 68. 72. 58. 25723 NA 45. 45. 59. 67. 70. NA -429- MEAN 36. 41. 51. 60. 65. 72. 55. S.D. 5.7 4.5 4.9 5.5 6.4 6.6 4.9 N 20 20 23 24 24 24 20 NA = NOT APPLICABLE PLFWv4.06 10/05/2006 APPENDIX 9 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597 134. 128. 152. 174. 166. 183. 160. 25654 166. NA NA 149. 160. 162. 159. 25632 98. 113. 145. 162. 181. 194. 154. 25610 76. 100. 121. 135. 134. 163. 124. 25618 128. 126. 158. 168. 184. 205. 166. 25621 117. 123. 152. 159. 180. 196. 160. 25687 187. NA NA 167. 181. 205. 188. 25633 91. 98. 117. 121. 127. 140. 119. 25681 126. 120. 164. 176. 184. 195. 165. 25615 133. 127. 166. 184. 198. 212. 176. 25637 128. 141. 175. 199. 217. 228. 190. 25638 111. 133. 168. 193. 220. 225. 181. 25713 NA NA 164. 173. 199. 204. NA 25670 131. 124. 152. 175. 191. 198. 168. 25657 118. 121. 151. 180. 181. 196. 164. 25663 95. 127. 159. 158. 179. 206. 160. 25690 103. 119. 137. 156. 189. 190. 155. 25666 114. 114. 158. 176. 184. 184. 162. 25692 NA 133. 159. 190. 191. 209. NA 25701 136. 123. 144. NA 163. 198. 157. 25645 NA 143. 156. 171. 174. 207. NA 25661 NA 134. 149. 165. 177. NA NA 25767 119. 125. 157. 168. 172. 187. 160. 25770 NA 133. 159. 186. 181. NA NA 25702 136. 144. 167. 195. 186. NA NA -430- MEAN S.D. N NA = NOT APPLICABLE 122. 25.1 20 125. 11.8 22 153. 13.9 23 170. 18.3 24 180. 20.4 25 195. 20.2 22 161. 17.5 19 APPENDIX 9 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25648 109. 109. NA 171. 195. 209. 166. 25694 124. 123. 158. 188. 180. 207. 170. 25668 105. 118. 129. 153. 173. 173. 146. 25631 129. 127. 161. 182. 196. 214. 172. 25660 137. 117. 161. 183. 186. 206. 169. 25704 107. 140. 168. 182. 212. 214. 176. 25665 112. NA 141. 170. 178. 198. 164. 25674 117. 127. 148. 162. 178. 197. 160. 25652 183. NA NA 190. 210. 210. 201. 25733 107. 129. NA 177. 195. 186. 164. 25748 116. 124. 158. 167. 188. 230. 171. 25753 NA NA 154. 164. 159. 224. NA 25672 114. 115. 157. 168. 181. 200. 162. 25655 113. 121. 155. 156. 160. 196. 155. 25727 112. NA 146. 165. 190. 188. 163. 25626 107. NA 157. 171. 188. 194. 169. 25739 129. 128. 165. 182. 198. 211. 175. 25749 111. 132. 155. 172. 179. 216. 168. 25756 134. 145. 185. 210. 206. 250. 196. 25741 141. 138. 155. 180. 190. 201. 173. 25752 108. 143. 170. 188. 193. 219. 176. 25758 125. 124. 154. 181. 198. 205. 169. 25719 NA 174. 197. 208. 227. NA NA -431- MEAN S.D. N NA = NOT APPLICABLE 121. 17.9 21 130. 14.8 18 159. 14.5 20 177. 14.3 23 190. 15.8 23 207. 16.2 22 170. 11.9 21 APPENDIX 9 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606 118. 135. 151. 185. 186. 211. 170. 25614 108. 125. 148. 151. 165. 185. 152. 25671 117. 102. NA 182. 181. 186. 161. 25698 80. 104. 148. 154. 162. 178. 142. 25609 117. 120. 138. 163. 172. 182. 154. 25677 98. NA 144. 179. 183. 194. 167. 25623 NA NA 165. 161. 175. 190. NA 25653 131. NA 155. 189. 203. 225. 188. 25604 98. 121. 140. 165. 179. 218. 161. 25678 108. 110. 144. 168. 195. 204. 160. 25684 123. 135. NA 171. 184. 229. 175. 25714 126. 134. 143. 162. 176. 209. 163. 25650 127. 131. 156. 188. 203. 207. 176. 25735 130. 123. 157. 175. 186. 207. 168. 25722 130. NA 154. 169. 174. 204. 173. 25642 125. 110. 142. 160. 188. 208. 160. 25628 NA NA 173. 171. 205. 202. NA 25763 NA 116. 141. 167. 181. 178. NA 25766 98. 114. 143. 136. 161. 163. 141. 25689 138. 125. 166. 187. 197. 220. 179. 25708 125. 123. 154. 175. 181. 213. 167. 25743 104. 123. 132. 158. 182. 187. 153. 25761 116. 139. 165. 194. 201. 228. 180. 25712 NA 133. 155. 185. 188. NA NA 25746 NA 119. 168. 190. 208. NA NA -432- MEAN S.D. N NA = NOT APPLICABLE 116. 14.7 20 122. 10.6 20 151. 10.8 23 171. 14.3 25 185. 13.2 25 201. 17.7 23 165. 12.3 20 APPENDIX 9 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAY 1- 4 4- 7 7-10 10-14 14-17 17-21 1-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696 132. 126. 158. 181. 192. 226. 176. 25686 117. 133. 150. 170. 170. 217. 163. 25639 131. 144. 155. 186. 183. 185. 169. 25658 131. 126. 168. 175. 194. 188. 167. 25676 110. 122. 142. 168. 174. 214. 157. 25600 149. 151. 156. 192. 209. 212. 182. 25603 130. 125. 159. 164. 176. 223. 167. 25630 113. 134. NA 190. 209. 223. 183. 25703 114. 134. 167. 173. 195. 205. 168. 25673 104. 117. 138. 156. 174. 182. 150. 25611 101. 146. 156. 175. 189. 215. 169. 25619 104. 124. 150. 178. 181. 202. 162. 25705 106. 113. 155. 165. 164. 206. 158. 25691 111. 124. 162. 179. 189. 207. 168. 25717 90. 131. 150. 165. 189. 198. 161. 25616 117. 120. 156. 185. 194. 235. 174. 25715 102. 109. 148. 168. 181. 201. 155. 25762 NA NA 151. 178. 176. 190. NA 25599 116. 106. 139. 150. 182. 185. 151. 25647 105. 115. 132. 158. 165. 174. 144. 25747 NA NA 148. 171. 176. 216. NA 25744 NA NA 168. 182. 204. 228. NA 25707 79. NA 164. 184. 192. 200. 172. 25723 NA 136. 135. 177. 188. 193. NA -433- MEAN S.D. N NA = NOT APPLICABLE 113. 16.0 20 127. 12.1 20 152. 10.3 23 174. 10.7 24 185. 12.4 24 205. 16.2 24 165. 10.3 20 PLFWv4.06 10/05/2006 APPENDIX 10 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL GESTATION LENGTHS [DAYS] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1 2 3 4 ----------------------------------------------------------------------------------------------------------------------------------- GESTATION GESTATION GESTATION GESTATION ANIMAL LENGTH ANIMAL LENGTH ANIMAL LENGTH ANIMAL LENGTH ----------------------------------------------------------------------------------------------------------------------------------- 25597 21. 25648 21. 25606 22. 25696 22. 25654 21. 25694 22. 25614 22. 25686 22. 25632 22. 25668 21. 25671 21. 25639 22. 25610 22. 25631 22. 25698 21. 25658 22. 25618 22. 25660 22. 25609 22. 25676 22. 25621 22. 25704 22. 25677 21. 25600 22. 25687 22. 25665 22. 25623 22. 25603 22. 25633 21. 25674 21. 25653 22. 25630 21. 25681 22. 25652 22. 25604 21. 25703 22. 25615 22. 25733 21. 25678 21. 25673 21. 25637 22. 25748 22. 25684 22. 25611 22. 25638 22. 25753 22. 25714 22. 25619 22. 25713 22. 25672 22. 25650 22. 25705 21. 25670 22. 25655 22. 25735 22. 25691 22. 25657 22. 25727 21. 25722 22. 25717 22. -434- 25663 22. 25626 21. 25642 22. 25616 22. 25690 21. 25739 22. 25628 21. 25715 21. 25666 21. 25749 21. 25763 22. 25762 22. 25692 22. 25756 22. 25766 21. 25599 21. 25701 22. 25741 22. 25689 22. 25647 22. 25645 23. 25752 22. 25708 22. 25747 22. 25661 23. 25758 22. 25743 21. 25744 22. 25767 22. 25719 22. 25761 22. 25707 21. 25770 22. 25712 22. 25723 22. 25702 22. 25746 22. ----------------------------------------------------------------------------------------------------------------------------------- MEAN 21.9 21.7 21.7 21.8 S.D. 0.53 0.47 0.48 0.44 N 25 23 25 24 ----------------------------------------------------------------------------------------------------------------------------------- 1- 0 MG/KG/DAY 2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY 4- 1.0 MG/KG/DAY PGLv5.06 10/05/2006 PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 11 (F0 - FAILED TO DELIVER) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 1 ANIMAL NO. 25664 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/27/06 DATE OF DEATH: 05/27/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: NONGRAVID- AMMONIUM SULFIDE NEGATIVE P UTERUS GROSS: CONTENTS, THICK YELLOW P BOTH HORNS CERVIX GROSS: ENLARGED P NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -435- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 11 (F0 - FAILED TO DELIVER) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 2 ANIMAL NO. 25695 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: NONGRAVID- AMMONIUM SULFIDE NEGATIVE P UTERUS GROSS: CONTENTS, CLEAR FLUID P BOTH HORNS NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -436- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 11 (F0 - FAILED TO DELIVER) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 3 ANIMAL NO. 25757 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: NONGRAVID- AMMONIUM SULFIDE NEGATIVE P UTERUS GROSS: CONTENTS, CLEAR FLUID P BOTH HORNS NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PGRHv4.54 10/05/2006 -437- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 1 ANIMAL NO. 25597 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 6,11 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -438- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 2 ANIMAL NO. 25654 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -439- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 3 ANIMAL NO. 25632 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,9 THYMUS GROSS: AREA(S), DARK RED P FEW, PINPOINT NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -440- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 4 ANIMAL NO. 25610 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 4,3 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -441- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 5 ANIMAL NO. 25618 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -442- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 6 ANIMAL NO. 25621 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -443- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 7 ANIMAL NO. 25687 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -444- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 8 ANIMAL NO. 25633 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 6,8 KIDNEYS GROSS: ENLARGED P BILATERAL KIDNEYS GROSS: CYST(S) P MULTIPLE, PINPOINT TO 3 MM IN DIAMETER, IN CORTEX AND MEDULLA, BILATERAL LIVER GROSS: SWOLLEN P ALL LOBES NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA -445- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 9 ANIMAL NO. 25681 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 11,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -446- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 10 ANIMAL NO. 25615 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 11,4 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -447- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 11 ANIMAL NO. 25637 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -448- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 12 ANIMAL NO. 25638 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -449- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 13 ANIMAL NO. 25713 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 6,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -450- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 14 ANIMAL NO. 25670 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 12,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -451- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 15 ANIMAL NO. 25657 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -452- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 16 ANIMAL NO. 25663 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 2,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -453- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 17 ANIMAL NO. 25690 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,12 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -454- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 18 ANIMAL NO. 25666 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,5 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -455- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 19 ANIMAL NO. 25692 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -456- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 20 ANIMAL NO. 25701 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -457- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 21 ANIMAL NO. 25645 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/18/06 DATE OF DEATH: 06/18/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -458- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 22 ANIMAL NO. 25661 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/19/06 DATE OF DEATH: 06/19/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -459- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 23 ANIMAL NO. 25767 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/18/06 DATE OF DEATH: 06/18/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -460- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 24 ANIMAL NO. 25770 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/19/06 DATE OF DEATH: 06/19/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 5,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -461- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 25 ANIMAL NO. 25702 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/19/06 DATE OF DEATH: 06/19/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,11 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -462- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 26 ANIMAL NO. 25648 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -463- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 27 ANIMAL NO. 25694 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -464- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 28 ANIMAL NO. 25668 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -465- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 29 ANIMAL NO. 25631 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 5,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -466- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 30 ANIMAL NO. 25660 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -467- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 31 ANIMAL NO. 25704 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,6 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -468- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 32 ANIMAL NO. 25665 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 6,6 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -469- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 33 ANIMAL NO. 25674 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -470- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 34 ANIMAL NO. 25652 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,5 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -471- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 35 ANIMAL NO. 25733 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,8 THYMUS GROSS: AREA(S), DARK RED P MULTIPLE, PINPOINT NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -472- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 36 ANIMAL NO. 25748 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,3 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -473- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 37 ANIMAL NO. 25753 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,11 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -474- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 38 ANIMAL NO. 25672 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 12,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -475- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 39 ANIMAL NO. 25655 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,9 LUNGS GROSS: AREA(S), DARK RED P MULTIPLE, PINPOINT TO 3 MM IN DIAMETER, ALL LOBES NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -476- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 40 ANIMAL NO. 25727 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 12,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -477- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 41 ANIMAL NO. 25626 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -478- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 42 ANIMAL NO. 25739 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,5 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -479- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 43 ANIMAL NO. 25749 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 5,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -480- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 44 ANIMAL NO. 25756 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -481- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 45 ANIMAL NO. 25741 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/18/06 DATE OF DEATH: 06/18/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,11 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -482- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 46 ANIMAL NO. 25752 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/18/06 DATE OF DEATH: 06/18/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -483- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 47 ANIMAL NO. 25758 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/19/06 DATE OF DEATH: 06/19/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -484- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 48 ANIMAL NO. 25719 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/19/06 DATE OF DEATH: 06/19/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -485- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 49 ANIMAL NO. 25606 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -486- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 50 ANIMAL NO. 25614 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -487- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 51 ANIMAL NO. 25671 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,6 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -488- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 52 ANIMAL NO. 25698 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -489- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 53 ANIMAL NO. 25609 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,6 THYMUS GROSS: AREA(S), DARK RED P MULTIPLE, PINPOINT THYROID GLANDS GROSS: DISCOLORATION, DARK RED P BILATERAL NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -490- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 54 ANIMAL NO. 25677 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,4 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -491- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 55 ANIMAL NO. 25623 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -492- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 56 ANIMAL NO. 25653 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -493- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 57 ANIMAL NO. 25604 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,4 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -494- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 58 ANIMAL NO. 25678 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -495- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 59 ANIMAL NO. 25684 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 6,6 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -496- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 60 ANIMAL NO. 25714 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -497- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 61 ANIMAL NO. 25650 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 11,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -498- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 62 ANIMAL NO. 25735 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 4,11 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -499- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 63 ANIMAL NO. 25722 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -500- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 64 ANIMAL NO. 25642 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -501- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 65 ANIMAL NO. 25628 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,8 THYROID GLANDS GROSS: DISCOLORATION, DARK RED P BILATERAL NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -502- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 66 ANIMAL NO. 25763 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -503- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 67 ANIMAL NO. 25766 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 6,6 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -504- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 68 ANIMAL NO. 25689 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -505- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 69 ANIMAL NO. 25708 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -506- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 70 ANIMAL NO. 25743 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -507- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 71 ANIMAL NO. 25761 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/18/06 DATE OF DEATH: 06/18/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 6,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -508- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 72 ANIMAL NO. 25712 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/19/06 DATE OF DEATH: 06/19/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 5,13 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -509- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 73 ANIMAL NO. 25746 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/19/06 DATE OF DEATH: 06/19/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -510- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 74 ANIMAL NO. 25696 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -511- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 75 ANIMAL NO. 25686 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 5,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -512- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 76 ANIMAL NO. 25639 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -513- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 77 ANIMAL NO. 25658 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -514- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 78 ANIMAL NO. 25676 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,8 THYMUS GROSS: AREA(S), DARK RED P MULTIPLE, PINPOINT NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -515- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 79 ANIMAL NO. 25600 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,8 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -516- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 80 ANIMAL NO. 25603 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,6 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -517- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 81 ANIMAL NO. 25630 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 5,9 THYMUS GROSS: AREA(S), DARK RED P MULTIPLE, PINPOINT THYROID GLANDS GROSS: DISCOLORATION, DARK RED P BILATERAL NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -518- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 82 ANIMAL NO. 25703 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 11,4 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -519- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 83 ANIMAL NO. 25673 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -520- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 84 ANIMAL NO. 25611 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,5 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -521- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 85 ANIMAL NO. 25619 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,5 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -522- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 86 ANIMAL NO. 25705 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,6 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -523- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 87 ANIMAL NO. 25691 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -524- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 88 ANIMAL NO. 25717 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 4,11 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -525- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 89 ANIMAL NO. 25616 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 5,10 THYMUS GROSS: AREA(S), DARK RED P MULTIPLE, PINPOINT NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -526- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 90 ANIMAL NO. 25715 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 9,8 UTERUS GROSS: CYST(S) P TWO, 2 MM IN DIAMETER, ON SEROSAL SURFACE, LEFT HORN NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -527- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 91 ANIMAL NO. 25762 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,7 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -528- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 92 ANIMAL NO. 25599 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,9 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -529- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 93 ANIMAL NO. 25647 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 11,5 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -530- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 94 ANIMAL NO. 25747 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/18/06 DATE OF DEATH: 06/18/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 7,11 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -531- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 95 ANIMAL NO. 25744 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/18/06 DATE OF DEATH: 06/18/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 11,6 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -532- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 96 ANIMAL NO. 25707 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/17/06 DATE OF DEATH: 06/17/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 10,5 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -533- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 97 ANIMAL NO. 25723 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/19/06 DATE OF DEATH: 06/19/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT) P 8,10 NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PGRHv4.54 10/05/2006 -534- APPENDIX 13 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL IMPLANTATION SITES SPONSOR NO.:06-128 0 MG/KG/DAY DAM IMPLANTATION PUPS UNACCOUNTED NO. SITES BORN SITES ----------------------------------------------------------------------------------------------------------------------------------- 25597 17 17 0 25654 15 15 0 25632 16 16 0 25610 7 5 2 25618 19 18 1 25621 18 16 2 25687 18 17 1 25633 14 14 0 25681 18 17 1 25615 15 14 1 25637 18 17 1 25638 18 18 0 25713 16 16 0 25670 20 19 1 25657 20 19 1 25663 11 11 0 25690 20 19 1 -535- 25666 14 14 0 25692 16 14 2 25701 19 19 0 25645 15 15 0 25661 17 16 1 25767 19 17 2 25770 15 14 1 25702 20 18 2 ----------------------------------------------------------------------------------------------------------------------------------- MEAN 16.6 15.8 0.8 S.D. 3.04 3.03 0.76 N 25 25 25 NOTE: ONLY DAMS THAT HAVE DELIVERED ONE OR MORE PUPS ARE INCLUDED IN CALCULATION OF MEAN. APPENDIX 13 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL IMPLANTATION SITES SPONSOR NO.:06-128 0.1 MG/KG/DAY DAM IMPLANTATION PUPS UNACCOUNTED NO. SITES BORN SITES ----------------------------------------------------------------------------------------------------------------------------------- 25648 18 17 1 25694 18 18 0 25668 17 17 0 25631 15 15 0 25660 16 15 1 25704 13 13 0 25665 12 12 0 25674 16 16 0 25652 13 13 0 25733 16 15 1 25748 10 10 0 25753 19 18 1 25672 19 18 1 25655 17 16 1 25727 19 17 2 25626 18 16 2 25739 15 14 1 -536- 25749 13 11 2 25756 16 16 0 25741 18 17 1 25752 18 15 3 25758 15 14 1 25719 19 17 2 ----------------------------------------------------------------------------------------------------------------------------------- MEAN 16.1 15.2 0.9 S.D. 2.52 2.24 0.87 N 23 23 23 NOTE: ONLY DAMS THAT HAVE DELIVERED ONE OR MORE PUPS ARE INCLUDED IN CALCULATION OF MEAN. APPENDIX 13 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL IMPLANTATION SITES SPONSOR NO.:06-128 0.3 MG/KG/DAY DAM IMPLANTATION PUPS UNACCOUNTED NO. SITES BORN SITES ----------------------------------------------------------------------------------------------------------------------------------- 25606 14 14 0 25614 19 18 1 25671 16 13 3 25698 16 15 1 25609 15 15 0 25677 14 13 1 25623 17 15 2 25653 14 14 0 25604 13 12 1 25678 15 15 0 25684 12 12 0 25714 15 13 2 25650 19 19 0 25735 15 14 1 25722 16 16 0 25642 15 15 0 25628 18 17 1 -537- 25763 20 19 1 25766 12 11 1 25689 15 15 0 25708 17 15 2 25743 18 18 0 25761 15 15 0 25712 18 17 1 25746 19 18 1 ----------------------------------------------------------------------------------------------------------------------------------- MEAN 15.9 15.1 0.8 S.D. 2.20 2.20 0.83 N 25 25 25 NOTE: ONLY DAMS THAT HAVE DELIVERED ONE OR MORE PUPS ARE INCLUDED IN CALCULATION OF MEAN. APPENDIX 13 (F0) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL IMPLANTATION SITES SPONSOR NO.:06-128 1.0 MG/KG/DAY DAM IMPLANTATION PUPS UNACCOUNTED NO. SITES BORN SITES ----------------------------------------------------------------------------------------------------------------------------------- 25696 17 16 1 25686 15 15 0 25639 16 16 0 25658 16 15 1 25676 17 15 2 25600 17 17 0 25603 16 15 1 25630 14 14 0 25703 15 15 0 25673 16 15 1 25611 15 15 0 25619 15 14 1 25705 14 13 1 25691 17 16 1 25717 15 15 0 25616 15 15 0 25715 17 17 0 -538- 25762 15 15 0 25599 19 19 0 25647 16 14 2 25747 18 17 1 25744 17 15 2 25707 15 14 1 25723 18 18 0 ----------------------------------------------------------------------------------------------------------------------------------- MEAN 16.0 15.4 0.6 S.D. 1.30 1.38 0.71 N 24 24 24 NOTE: ONLY DAMS THAT HAVE DELIVERED ONE OR MORE PUPS ARE INCLUDED IN CALCULATION OF MEAN. PIISv4.09 10/05/2006 APPENDIX 14 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL LITTER VIABILITY SPONSOR NO.:06-128 -------------------------------------------- LITTERS FROM GROUP 1: 0 MG/KG/DAY -------------------------------------------- NUMBER OF VIABLE PUPS --------------------------------------------------------------------- BEFORE AFTER NO. DEAD NO. VIABLE SELECTION SELECTION DAY 0 DAY 0 DAY 1 DAY 4 DAY 4 DAY 7 DAY 14 DAY 21 --------------------------------------- ---------------------------------------------------------------------- DAM # M F U M % F % TOTAL M F M F M F M F M F M F -------- -------- ---------------------------- -------- -------- -------- -------- -------- -------- 25597 0 0 0 7/ 7 100 10/10 100 17 7 10 7 10 4 4 4 4 4 4 4 4 25654 0 0 0 9/ 9 100 6/ 6 100 15 9 6 9 6 4 4 4 3 4 3 4 3 25632 0 0 0 8/ 8 100 8/ 8 100 16 8 8 8 8 4 4 4 4 4 4 4 4 25610 0 0 0 2/ 2 100 3/ 3 100 5 2 3 2 3 2 3 2 3 2 3 2 3 25618 0 0 0 10/10 100 8/ 8 100 18 10 8 10 8 4 4 4 4 4 4 4 4 25621 0 0 0 8/ 8 100 8/ 8 100 16 8 8 8 8 4 4 4 4 4 4 4 4 25687 0 0 0 8/ 8 100 9/ 9 100 17 8 9 8 8 4 4 4 4 4 4 4 4 25633 0 0 0 9/ 9 100 5/ 5 100 14 9 5 9 5 4 4 4 4 3 4 3 4 25681 0 0 0 7/ 7 100 10/10 100 17 7 9 7 9 4 4 4 4 4 4 4 4 25615 0 0 0 6/ 6 100 8/ 8 100 14 6 8 6 8 4 4 4 4 4 4 4 4 25637 1 0 0 8/ 9 89 8/ 8 100 16 8 8 8 8 4 4 4 4 4 4 4 4 25638 0 0 0 8/ 8 100 10/10 100 18 8 8 7 8 4 4 4 4 4 4 4 4 25713 0 0 0 11/11 100 5/ 5 100 16 11 5 11 5 4 4 4 4 4 4 4 4 25670 0 0 0 11/11 100 8/ 8 100 19 11 8 11 8 4 4 4 4 4 4 4 4 25657 0 0 0 8/ 8 100 11/11 100 19 8 10 8 10 4 4 4 4 4 4 4 4 25663 0 0 0 6/ 6 100 5/ 5 100 11 6 5 6 5 4 4 4 4 4 4 4 4 25690 0 0 0 7/ 7 100 12/12 100 19 7 12 7 12 4 4 4 4 4 4 4 4 25666 0 0 0 7/ 7 100 7/ 7 100 14 7 7 7 7 4 4 4 4 4 4 4 4 25692 1 0 0 4/ 5 80 9/ 9 100 13 4 9 4 9 4 4 4 4 4 4 4 4 25701 0 0 0 9/ 9 100 10/10 100 19 9 10 9 10 4 4 4 4 4 4 4 4 25645 0 0 0 6/ 6 100 9/ 9 100 15 6 9 6 9 4 4 4 4 4 4 4 4 25661 0 0 0 9/ 9 100 7/ 7 100 16 9 7 9 7 4 4 2 4 2 4 2 4 25767 0 0 0 6/ 6 100 11/11 100 17 6 11 6 11 4 4 4 4 4 4 4 4 25770 0 0 0 5/ 5 100 9/ 9 100 14 5 9 5 9 4 4 4 4 4 4 4 4 25702 2 0 0 10/12 83 6/ 6 100 16 9 6 9 6 4 4 4 4 4 4 4 4 -539- TOTAL 4 0 0 189/193 202/202 391 188 198 187 197 98 99 96 98 95 98 95 98 ----------------------------------------------------------------------------------------------------------------------------------- M = MALE, F = FEMALE, U = UNDETERMINED APPENDIX 14 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL LITTER VIABILITY SPONSOR NO.:06-128 -------------------------------------------- LITTERS FROM GROUP 2: 0.1 MG/KG/DAY -------------------------------------------- NUMBER OF VIABLE PUPS --------------------------------------------------------------------- BEFORE AFTER NO. DEAD NO. VIABLE SELECTION SELECTION DAY 0 DAY 0 DAY 1 DAY 4 DAY 4 DAY 7 DAY 14 DAY 21 --------------------------------------- ---------------------------------------------------------------------- DAM # M F U M % F % TOTAL M F M F M F M F M F M F -------- -------- ---------------------------- -------- -------- -------- -------- -------- -------- 25648 0 0 0 10/10 100 7/ 7 100 17 10 7 10 7 4 4 4 4 4 4 4 4 25694 0 0 0 8/ 8 100 10/10 100 18 8 10 8 10 4 4 4 4 4 4 4 4 25668 0 0 0 4/ 4 100 13/13 100 17 3 12 3 12 3 5 3 5 3 5 3 5 25631 0 0 0 5/ 5 100 10/10 100 15 5 10 5 10 4 4 4 4 4 4 4 4 25660 0 0 0 8/ 8 100 7/ 7 100 15 8 7 8 7 4 4 4 4 4 4 4 4 25704 0 0 0 7/ 7 100 6/ 6 100 13 7 6 7 6 4 4 4 4 4 4 4 4 25665 0 0 0 4/ 4 100 8/ 8 100 12 4 8 4 8 4 4 4 4 4 4 4 4 25674 0 0 0 9/ 9 100 7/ 7 100 16 9 7 9 7 4 4 4 4 4 4 4 4 25652 0 0 0 6/ 6 100 7/ 7 100 13 6 7 6 7 4 4 4 4 4 4 4 4 25733 0 0 0 7/ 7 100 8/ 8 100 15 7 8 7 8 4 4 4 4 4 4 4 4 25748 0 0 0 7/ 7 100 3/ 3 100 10 7 3 7 3 5 3 5 3 5 3 5 3 25753 0 0 0 7/ 7 100 11/11 100 18 6 11 6 10 4 4 4 4 4 4 4 4 25672 0 0 0 8/ 8 100 10/10 100 18 8 9 8 9 4 4 4 4 4 4 4 4 25655 0 0 0 10/10 100 6/ 6 100 16 10 6 10 6 4 4 4 4 4 4 4 4 25727 0 0 0 8/ 8 100 9/ 9 100 17 7 9 7 9 4 4 4 4 4 4 4 4 25626 0 0 0 7/ 7 100 9/ 9 100 16 7 9 7 9 4 4 4 4 4 4 4 4 25739 0 0 0 10/10 100 4/ 4 100 14 10 4 10 4 4 4 4 4 4 4 4 4 25749 0 0 0 6/ 6 100 5/ 5 100 11 6 4 6 4 4 4 4 4 4 4 4 4 25756 0 0 0 7/ 7 100 9/ 9 100 16 7 9 7 9 4 4 4 4 4 4 4 4 25741 0 0 0 7/ 7 100 10/10 100 17 7 10 7 10 4 4 4 4 4 4 4 4 25752 0 0 0 9/ 9 100 6/ 6 100 15 9 6 8 6 4 4 4 4 4 4 4 4 25758 0 0 0 6/ 6 100 8/ 8 100 14 6 8 6 8 4 4 4 4 4 4 4 4 25719 0 0 0 12/12 100 5/ 5 100 17 12 5 11 5 4 4 4 4 4 4 4 4 -540- TOTAL 0 0 0 172/172 178/178 350 169 175 167 174 92 92 92 92 92 92 92 92 ----------------------------------------------------------------------------------------------------------------------------------- M = MALE, F = FEMALE, U = UNDETERMINED APPENDIX 14 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL LITTER VIABILITY SPONSOR NO.:06-128 -------------------------------------------- LITTERS FROM GROUP 3: 0.3 MG/KG/DAY -------------------------------------------- NUMBER OF VIABLE PUPS --------------------------------------------------------------------- BEFORE AFTER NO. DEAD NO. VIABLE SELECTION SELECTION DAY 0 DAY 0 DAY 1 DAY 4 DAY 4 DAY 7 DAY 14 DAY 21 --------------------------------------- ---------------------------------------------------------------------- DAM # M F U M % F % TOTAL M F M F M F M F M F M F -------- -------- ---------------------------- -------- -------- -------- -------- -------- -------- 25606 0 0 0 3/ 3 100 11/11 100 14 3 11 3 11 3 5 3 5 3 5 3 5 25614 0 0 0 12/12 100 6/ 6 100 18 12 6 12 6 4 4 4 4 4 4 4 4 25671 0 0 0 5/ 5 100 8/ 8 100 13 5 8 5 8 4 4 4 4 4 4 4 4 25698 0 0 0 5/ 5 100 10/10 100 15 5 10 5 9 4 4 4 4 4 4 4 4 25609 0 0 0 6/ 6 100 9/ 9 100 15 6 9 6 9 4 4 4 4 4 4 4 4 25677 0 0 0 7/ 7 100 6/ 6 100 13 7 6 6 5 4 4 4 4 4 4 4 4 25623 2 0 0 7/ 9 78 6/ 6 100 13 7 6 7 6 4 4 4 3 4 3 4 3 25653 0 0 0 7/ 7 100 7/ 7 100 14 7 7 7 7 4 4 4 4 4 4 4 4 25604 0 0 0 7/ 7 100 5/ 5 100 12 7 5 7 5 4 4 4 4 4 4 4 4 25678 0 0 0 7/ 7 100 8/ 8 100 15 7 8 7 8 4 4 4 4 4 4 4 4 25684 0 0 0 5/ 5 100 7/ 7 100 12 4 7 4 7 4 4 4 4 4 4 4 4 25714 0 0 0 6/ 6 100 7/ 7 100 13 6 7 6 7 4 4 4 4 4 4 4 4 25650 0 0 0 12/12 100 7/ 7 100 19 12 7 12 7 4 4 4 4 4 4 4 4 25735 0 0 0 6/ 6 100 8/ 8 100 14 6 8 6 8 4 4 4 4 4 4 4 4 25722 1 0 0 10/11 91 5/ 5 100 15 10 5 10 5 4 4 4 4 4 4 4 4 25642 0 0 0 8/ 8 100 7/ 7 100 15 8 7 8 7 4 4 4 3 4 3 4 3 25628 0 0 0 9/ 9 100 8/ 8 100 17 9 8 8 8 4 4 4 4 4 4 4 4 25763 0 0 0 8/ 8 100 11/11 100 19 8 11 8 11 4 4 3 3 3 3 3 3 25766 0 0 0 6/ 6 100 5/ 5 100 11 6 5 5 5 4 4 4 4 4 4 4 4 25689 0 0 0 6/ 6 100 9/ 9 100 15 6 9 6 9 4 4 4 4 4 4 4 4 25708 0 0 0 9/ 9 100 6/ 6 100 15 9 6 9 6 4 4 4 4 4 4 4 4 25743 0 0 0 10/10 100 8/ 8 100 18 10 8 9 8 4 4 4 4 4 4 4 4 25761 0 0 0 7/ 7 100 8/ 8 100 15 7 8 7 8 4 4 4 4 4 4 4 4 25712 0 1 0 5/ 5 100 11/12 92 16 5 11 5 11 4 4 4 4 4 4 4 4 25746 0 0 0 11/11 100 7/ 7 100 18 11 7 10 7 4 4 4 4 4 4 4 4 -541- TOTAL 3 1 0 184/187 190/191 374 183 190 178 188 99 101 98 98 98 98 98 98 ----------------------------------------------------------------------------------------------------------------------------------- M = MALE, F = FEMALE, U = UNDETERMINED APPENDIX 14 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL LITTER VIABILITY SPONSOR NO.:06-128 -------------------------------------------- LITTERS FROM GROUP 4: 1.0 MG/KG/DAY -------------------------------------------- NUMBER OF VIABLE PUPS --------------------------------------------------------------------- BEFORE AFTER NO. DEAD NO. VIABLE SELECTION SELECTION DAY 0 DAY 0 DAY 1 DAY 4 DAY 4 DAY 7 DAY 14 DAY 21 --------------------------------------- ---------------------------------------------------------------------- DAM # M F U M % F % TOTAL M F M F M F M F M F M F -------- -------- ---------------------------- -------- -------- -------- -------- -------- -------- 25696 0 0 0 10/10 100 6/ 6 100 16 10 6 10 6 4 4 4 4 4 4 4 4 25686 0 0 0 8/ 8 100 7/ 7 100 15 8 7 8 7 4 4 4 4 4 4 4 4 25639 0 0 0 8/ 8 100 8/ 8 100 16 8 8 8 8 4 4 4 4 4 4 4 4 25658 0 1 0 7/ 7 100 7/ 8 88 14 7 6 7 6 4 4 4 4 4 4 4 4 25676 1 0 0 6/ 7 86 8/ 8 100 14 6 8 6 8 4 4 4 4 4 4 4 4 25600 0 0 0 4/ 4 100 13/13 100 17 4 13 4 13 4 4 4 4 4 4 4 4 25603 0 0 0 5/ 5 100 10/10 100 15 5 10 5 10 4 4 4 4 4 4 4 4 25630 0 0 0 7/ 7 100 7/ 7 100 14 7 7 7 7 4 4 4 4 4 4 4 4 25703 0 0 0 5/ 5 100 10/10 100 15 5 10 5 10 4 4 4 4 4 4 4 4 25673 0 0 0 9/ 9 100 6/ 6 100 15 9 6 9 6 4 4 4 4 4 4 4 4 25611 1 2 0 7/ 8 88 5/ 7 71 12 7 5 7 5 4 4 4 4 4 4 4 4 25619 0 0 0 6/ 6 100 8/ 8 100 14 6 8 6 8 4 4 4 4 4 4 4 4 25705 0 0 0 7/ 7 100 6/ 6 100 13 7 6 7 6 4 4 4 4 4 4 4 4 25691 0 0 0 8/ 8 100 8/ 8 100 16 8 7 8 7 4 4 4 4 4 4 4 4 25717 1 0 0 7/ 8 88 7/ 7 100 14 6 7 6 7 4 4 4 4 4 4 4 4 25616 0 0 0 8/ 8 100 7/ 7 100 15 8 7 8 7 4 4 4 4 4 4 4 4 25715 0 0 0 8/ 8 100 9/ 9 100 17 7 8 7 8 4 4 4 4 4 4 4 4 25762 0 0 0 6/ 6 100 9/ 9 100 15 6 9 6 9 4 4 4 4 4 4 4 4 25599 0 0 0 10/10 100 9/ 9 100 19 10 9 9 9 4 4 4 4 4 4 4 4 25647 1 0 0 7/ 8 88 6/ 6 100 13 7 6 7 6 4 4 4 4 4 4 4 4 25747 0 0 0 7/ 7 100 10/10 100 17 7 10 7 10 4 4 4 4 4 4 4 4 25744 0 0 0 6/ 6 100 9/ 9 100 15 6 9 6 9 4 4 4 4 4 4 4 4 25707 0 0 0 8/ 8 100 6/ 6 100 14 8 6 8 4 4 4 4 4 4 4 4 4 25723 0 0 0 13/13 100 5/ 5 100 18 13 5 13 5 4 4 4 4 4 4 4 4 -542- TOTAL 4 3 0 177/181 186/189 363 175 183 174 181 96 96 96 96 96 96 96 96 ----------------------------------------------------------------------------------------------------------------------------------- M = MALE, F = FEMALE, U = UNDETERMINED PPLVv4.02 10/05/2006 APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 1: 0 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25597 23-MAY-06 C a21 C A a21 C a21 a21 C C C a21 C C C a21 A M M M M M M M F F F F F F F F F F 25654 23-MAY-06 C a21 C C a21 C a21 C A A a21 C 5 a21 C M M M M M M M M M F F F F F F 25632 24-MAY-06 C a21 C a21 C a21 A C A a21 C C C C a21 a21 M M M M M M M M F F F F F F F F 25610 25-MAY-06 a21 a21 a21 a21 a21 M M F F F 25618 25-MAY-06 C a21 C C C C a21 A a21 C a21 C C C a21 C A a21 M M M M M M M M M M F F F F F F F F -543- 25621 25-MAY-06 a21 a21 a21 C C C A C a21 A C a21 C C C a21 M M M M M M M M F F F F F F F F 25687 25-MAY-06 C C a21 a21 a21 C A C C a21 C 3 C a21 A a21 C M M M M M M M M F F F F F F F F F 25633 24-MAY-06 11 C C a21 A C C C a21 C a21 a21 A a21 M M M M M M M M M F F F F F 25681 25-MAY-06 A C a21 C a21 a21 a21 C C A a21 C C a21 C C 1 M M M M F M M M F F F F F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 1: 0 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25615 25-MAY-06 a21 C A C a21 a21 C a21 a21 A C C a21 C M M M M M M F F F F F F F F 25637 26-MAY-06 0 C a21 C C A C a21 C a21 a21 C C a21 a21 C A M M M M M M M M F F M F F F F F F 25638 26-MAY-06 a21 4 C a21 a21 C A C C C a21 1 C C a21 a21 1 A M M M M M M M M F F F F F F F F F F 25713 26-MAY-06 C A C a21 a21 C C a21 C C C a21 a21 a21 C A M M M M M M M M M M M F F F F F 25670 26-MAY-06 C C a21 a21 C a21 C C A C C C C C a21 a21 a21 A C M M M M M M M M M M M F F F F F F F F -544- 25657 26-MAY-06 a21 a21 C C C C a21 A C A C a21 a21 C a21 C C 1 C M M M M M M M M F F F F F F F F F F F 25663 26-MAY-06 C a21 a21 A C a21 a21 a21 A a21 C M M M M M M F F F F F 25690 26-MAY-06 A C a21 C a21 C a21 C a21 C C C C C C C a21 a21 A M M M M M M M F F F F F F F F F F F F 25666 26-MAY-06 A a21 C C a21 C a21 a21 A C C C a21 a21 M M M M M M M F F F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 1: 0 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25692 27-MAY-06 0 a21 a21 A a21 a21 A C C C C a21 C a21 M M M M M F F F F F F F F F 25701 27-MAY-06 C a21 a21 C C a21 C C A a21 a21 C C C C a21 C A C M F M M M M M M M M F F F F F F F F F 25645 28-MAY-06 a21 a21 C a21 C A a21 A C C a21 a21 C C C M M M M M M F F F F F F F F F 25661 29-MAY-06 C 7 7 a21 a21 C C C C a21 a21 a21 C a21 C C M M M M M M M M M F F F F F F F 25767 28-MAY-06 a21 C a21 C a21 a21 a21 C a21 C C a21 C C C a21 C M M M M M M F F F F F F F F F F F -545- 25770 29-MAY-06 a21 a21 a21 a21 C C a21 C a21 C a21 C C a21 M M M M M F F F F F F F F F 25702 29-MAY-06 0 0 a21 a21 C C a21 C C 1 C a21 a21 C a21 a21 C a21 M M M M M M M M M M M M F F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 2: 0.1 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25648 23-MAY-06 C C a21 C C C A a21 C a21 a21 A C a21 C a21 C M M M M M M M M M M F F F F F F F 25694 25-MAY-06 C C a21 A a21 C C a21 a21 C a21 C A C a21 C C C M M M M M M F F F F M M F F F F F F 25668 24-MAY-06 1 1 a21 a21 a21 a21 a21 C C a21 C a21 C C C a21 C M F M M M F F F F F F F F F F F F 25631 25-MAY-06 C a21 a21 A A C a21 C C a21 C C a21 C a21 M M M M F F M F F F F F F F F 25660 25-MAY-06 A a21 C A C a21 a21 C C a21 C C a21 a21 C M M M F M M M M M F F F F F F -546- 25704 25-MAY-06 a21 C A a21 C a21 C a21 A C a21 a21 C M M M M M M M F F F F F F 25665 25-MAY-06 A a21 a21 a21 a21 a21 A C C a21 C C M M M M F F F F F F F F 25674 24-MAY-06 C A C a21 a21 C a21 C C C A C a21 a21 C a21 M M M M M M M M M F F F F F F F 25652 25-MAY-06 a21 a21 a21 A C C C a21 C a21 a21 C A M M M M M M F F F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 2: 0.1 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25733 25-MAY-06 a21 C a21 C C a21 A A C C a21 a21 C C a21 M M M M M M M F F F F F F F F 25748 26-MAY-06 A a21 C a21 a21 a21 C A a21 a21 M M M M M M M F F F 25753 26-MAY-06 C a21 a21 a21 C A 1 C a21 C C C 4 C A a21 a21 C M M M M M M M F F F F F F F F F F F 25672 26-MAY-06 1 a21 C C a21 A C C a21 C a21 a21 C C A a21 C C F M M M M M M M M F F F F F F F F F 25655 26-MAY-06 A C a21 C C C a21 C C a21 a21 a21 A C a21 C M M M M M M M M M M F F F F F F -547- 25727 26-MAY-06 1 a21 C C a21 a21 A C a21 a21 C C a21 C C A C M M M M M M M M F F F F F F F F F 25626 26-MAY-06 a21 C C A C a21 a21 a21 a21 C C A C C a21 C M M M M M M M F F F F F F F F F 25739 27-MAY-06 a21 C C C C a21 A C a21 C a21 A a21 a21 M M M M M M M M M M F F F F 25749 26-MAY-06 1 a21 a21 A C C a21 a21 a21 a21 A F M M M M M M F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 2: 0.1 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25756 27-MAY-06 a21 C a21 a21 A C C C C C a21 C A C a21 a21 M M M M M M M F F F F F F F F F 25741 28-MAY-06 a21 a21 a21 C C C A C A C C C C a21 a21 a21 C M M M M M M M F F F F F F F F F F 25752 28-MAY-06 a21 C a21 C a21 2 C C A C a21 C A a21 a21 M M M M M M M M M F F F F F F 25758 29-MAY-06 a21 a21 C C a21 a21 C a21 a21 a21 C a21 C C M M M M M M F F F F F F F F 25719 29-MAY-06 C 4 a21 a21 C C a21 C a21 C C C a21 a21 a21 C a21 M M M M M M M M M M M M F F F F F -548- ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 3: 0.3 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25606 24-MAY-06 a21 a21 a21 a21 a21 C C a21 C C a21 a21 C C M M M F F F F F F F F F F F 25614 24-MAY-06 C C C a21 a21 C a21 C C A C C a21 C a21 C A a21 M M M M M M M M M M M M F F F F F F 25671 23-MAY-06 C a21 a21 A a21 A C a21 a21 C C C a21 M M M M M F F F F F F F F 25698 24-MAY-06 C a21 a21 a21 A a21 C C C a21 C A C a21 3 M M M F M M F F F F F F F F F 25609 25-MAY-06 C a21 a21 A C a21 C C C C A a21 C a21 a21 M M M M M M F F F F F F F F F -549- 25677 24-MAY-06 4 a21 C a21 A C a21 A 4 a21 C a21 a21 M M M M M M M F F F F F F 25623 25-MAY-06 0 0 a21 a21 a21 C C A C C C 7 a21 a21 A M M M M M M M M M F F F F F F 25653 25-MAY-06 C A a21 C a21 a21 a21 C C C a21 a21 A C M M M M F F M F F F M F F M 25604 24-MAY-06 C a21 a21 A C a21 C a21 C a21 a21 A M M M M M M M F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 3: 0.3 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25678 24-MAY-06 C A a21 C C a21 a21 a21 C a21 A C a21 C C M M M M M M M F F F F F F F F 25684 25-MAY-06 1 a21 a21 A a21 A C a21 C C a21 a21 M M M M M F F F F F F F 25714 26-MAY-06 C A a21 C a21 a21 C a21 a21 a21 C C A M M M M M M F F F F F F F 25650 26-MAY-06 a21 a21 C C C C C a21 C C A C a21 a21 C C A C a21 F M M M M M M M M M M M M F F F F F F 25735 26-MAY-06 a21 C C a21 A a21 a21 A C a21 C C C a21 M M M M M M F F F F F F F F -550- 25722 26-MAY-06 A C C a21 a21 C C C C a21 a21 a21 a21 C A 0 M M M M M M M M M M F F F F F M 25642 26-MAY-06 C a21 C a21 A C C a21 C 6 C A a21 C a21 M M M M M M M M F F F F F F F 25628 26-MAY-06 a21 C C C a21 2 A C a21 C C C C a21 a21 a21 A M M M M M M M M M F F F F F F F F 25763 27-MAY-06 C a21 5 a21 C C a21 C a21 a21 C C C C a21 6 C C C M M M M M M M M F F F F F F F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 3: 0.3 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25766 26-MAY-06 A a21 a21 3 C A a21 a21 a21 C a21 M M M M F F F F F M M 25689 27-MAY-06 C A a21 a21 C a21 a21 C C C C a21 a21 A C M M M M M M F F F F F F F F F 25708 27-MAY-06 A C C a21 C C a21 C a21 C a21 a21 C a21 A M M M M M M M M M F F F F F F 25743 27-MAY-06 C a21 C a21 C C 2 A a21 C a21 a21 C C C A C a21 M M M M M M M M M M F F F F F F F F 25761 28-MAY-06 C C C a21 a21 a21 a21 a21 a21 C C C a21 C a21 M M M M M M M F F F F F F F F -551- 25712 29-MAY-06 0 a21 a21 C a21 a21 a21 a21 C C C C C C C a21 a21 F M M M M M F F F F F F F F F F F 25746 29-MAY-06 C 2 a21 C C a21 a21 C C C a21 a21 C a21 a21 C a21 C M M M M M M M M M M M F F F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 4: 1.0 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25696 24-MAY-06 C C C A C a21 a21 C a21 C A C a21 a21 C a21 M M M M M M M M M M F F F F F F 25686 24-MAY-06 a21 a21 a21 A C C C C a21 A a21 C C C a21 M M M M M M M M F F F F F F F 25639 25-MAY-06 C C a21 A a21 A C C a21 C a21 a21 C a21 C C M M M F M M M M M F F F F F F F 25658 25-MAY-06 0 1 a21 a21 a21 C C A C a21 C C a21 A a21 F F M M M M M M M F F F F F F 25676 25-MAY-06 0 A a21 a21 C a21 C a21 a21 C C a21 C C A M M M M M M M F F F F F F F F -552- 25600 25-MAY-06 a21 A a21 a21 a21 C C C C C a21 a21 C C A C C M M M M F F F F F F F F F F F F F 25603 25-MAY-06 a21 a21 C A a21 a21 a21 C C A C a21 C C C M M M M M F F F F F F F F F F 25630 24-MAY-06 a21 C C A a21 a21 C C A a21 a21 C a21 C M M M M M M M F F F F F F F 25703 25-MAY-06 C a21 A a21 a21 C C a21 a21 A C C C a21 C M M M M M F F F F F F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 4: 1.0 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25673 24-MAY-06 C C a21 a21 C C C a21 A A a21 a21 C a21 C M M M M M M M M M F F F F F F 25611 26-MAY-06 0 0 0 C a21 C A a21 C a21 A a21 a21 C a21 M F F M M M M M M M F F F F F 25619 26-MAY-06 a21 C a21 A a21 C C a21 C a21 C A C a21 M M M M M M F F F F F F F F 25705 25-MAY-06 a21 C C C a21 a21 A A a21 a21 a21 C C M M M M M M M F F F F F F 25691 26-MAY-06 C a21 C C a21 a21 A C C C A a21 1 a21 a21 C F M M M M M M M M F F F F F F F -553- 25717 26-MAY-06 0 1 a21 A C a21 a21 C C C a21 C a21 a21 A M M M M M M M M F F F F F F F 25616 26-MAY-06 C a21 a21 C A C C C C a21 a21 a21 a21 A C M M M M M M M F F F F M F F F 25715 26-MAY-06 1 1 C a21 C a21 A a21 C A C C a21 C a21 C a21 M F M M M M M M M F F F F F F F F 25762 27-MAY-06 A C a21 C a21 a21 a21 a21 C C A C C a21 C M M M M M M F F F F F F F F F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA APPENDIX 15 (F1) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION INDIVIDUAL PUP VIABILITY SPONSOR NO.:06-128 -------------------------------------------------------- LITTERS FROM GROUP 4: 1.0 MG/KG/DAY -------------------------------------------------------- DAY OF DAM # BIRTH PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 ----------------------------------------------------------------------------------------------------------------------------------- 25599 26-MAY-06 C C a21 C C A C 2 a21 a21 A a21 C C C C a21 C a21 M M M M M M M M M M F F F F F F F F F 25647 27-MAY-06 0 C C a21 C a21 A a21 C C A a21 a21 a21 M M M M M M M F F F F F M F 25747 28-MAY-06 a21 C a21 a21 a21 C C a21 a21 C C C a21 C a21 C C M M M M M M M F F F F F F F F F F 25744 28-MAY-06 a21 C a21 a21 C a21 C a21 C C a21 C a21 a21 C M M M M M M F F F F F F F F F 25707 27-MAY-06 C C a21 C a21 C a21 a21 a21 a21 2 a21 3 a21 M M M M M M M M F F F F F F -554- 25723 29-MAY-06 C C C C a21 a21 C C C C C a21 a21 C a21 a21 a21 a21 M M M M M M M M M M M M F F F F M F ----------------------------------------------------------------------------------------------------------------------------------A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA PLITRv4.02 10/05/2006 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25597 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 -555- 25654 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M LACERATION 1 VENTRAL ABDOMINAL AREA CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25654 13 F FOUND DEAD 5 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 25632 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 -556- 25610 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 F SCHEDULED EUTHANASIA 21 4 F SCHEDULED EUTHANASIA 21 5 F SCHEDULED EUTHANASIA 21 25618 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25618 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 9 M SCHEDULED EUTHANASIA 21 10 M CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 18 F SCHEDULED EUTHANASIA 21 -557- 25621 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25687 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F FOUND DEAD 3 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 17 F CULLED ON SCHEDULED DAY 4 -558- 25633 1 M MISSING 11 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 M SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25681 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 F SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 16 F CULLED ON SCHEDULED DAY 4 17 F MISSING 1 -559- 25615 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25637 1 M FOUND DEAD 0 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 M SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 -560- 25638 1 M SCHEDULED EUTHANASIA 21 2 M FOUND DEAD 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M SCABBING 1 FACIAL AREA DRIED RED MATERIAL 4 FACIAL AREA CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25638 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F MISSING 1 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 17 F MISSING 1 25713 1 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M SCHEDULED EUTHANASIA 21 9 M CULLED ON SCHEDULED DAY 4 10 M CULLED ON SCHEDULED DAY 4 11 M CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 -561- 25670 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25670 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 10 M CULLED ON SCHEDULED DAY 4 11 M CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 17 F SCHEDULED EUTHANASIA 21 19 F CULLED ON SCHEDULED DAY 4 -562- 25657 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25657 17 F CULLED ON SCHEDULED DAY 4 18 F MISSING 1 19 F CULLED ON SCHEDULED DAY 4 25663 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 F SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 -563- 25690 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25690 16 F CULLED ON SCHEDULED DAY 4 17 F SCHEDULED EUTHANASIA 21 18 F SCHEDULED EUTHANASIA 21 25666 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 -564- 25692 1 M FOUND DEAD 0 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 F SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25692 14 F SCHEDULED EUTHANASIA 21 25701 1 M CULLED ON SCHEDULED DAY 4 2 F SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 10 M SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 17 F CULLED ON SCHEDULED DAY 4 19 F CULLED ON SCHEDULED DAY 4 -565- 25645 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 7 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25645 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 25661 1 M CULLED ON SCHEDULED DAY 4 2 M SUBCUTANEOUS HEMORRHAGE(S) 7 VENTRAL ABDOMINAL AREA PALE IN COLOR 7 FOUND DEAD 7 3 M FOUND DEAD 7 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F WET RED MATERIAL 7 AROUND MOUTH SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 16 F CULLED ON SCHEDULED DAY 4 -566- APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25767 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 F SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 17 F SMALL IN SIZE 4 CULLED ON SCHEDULED DAY 4 -567- 25770 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 F CULLED ON SCHEDULED DAY 4 7 F SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25770 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 25702 1 M FOUND DEAD 0 2 M FOUND DEAD 0 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 M FOUND DEAD 1 11 M CULLED ON SCHEDULED DAY 4 12 M SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 17 F CULLED ON SCHEDULED DAY 4 18 F SCHEDULED EUTHANASIA 21 -568- APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25648 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 8 M SCHEDULED EUTHANASIA 21 9 M CULLED ON SCHEDULED DAY 4 10 M SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 17 F CULLED ON SCHEDULED DAY 4 -569- 25694 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 5 M PALE IN COLOR 11 LABORED RESPIRATION 11 SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 M SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25694 12 M CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 17 F CULLED ON SCHEDULED DAY 4 18 F CULLED ON SCHEDULED DAY 4 25668 1 M FOUND DEAD 1 2 F FOUND DEAD 1 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 F SCHEDULED EUTHANASIA 21 7 F SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 17 F CULLED ON SCHEDULED DAY 4 -570- 25631 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 17 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25631 6 F CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 -571- 25660 2 M SCHEDULED EUTHANASIA 21 3 M SMALL IN SIZE 1 CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 25704 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 18 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25704 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 25665 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 F SCHEDULED EUTHANASIA 21 6 F SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 -572- 25674 1 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 19 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25674 9 M CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F SMALL IN SIZE 7 SMALL IN SIZE 11 SMALL IN SIZE 14 SMALL IN SIZE 17 SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 -573- 25652 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 25733 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 20 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25733 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 25748 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 10 F SCHEDULED EUTHANASIA 21 -574- 25753 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 7 M FOUND DEAD 1 8 F CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 21 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25753 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F FOUND DEAD 4 14 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 17 F SCHEDULED EUTHANASIA 21 18 F CULLED ON SCHEDULED DAY 4 -575- 25672 1 F MISSING 1 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 M SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 16 F SMALL IN SIZE 1 SMALL IN SIZE 4 SMALL IN SIZE 7 SMALL IN SIZE 11 SMALL IN SIZE 14 SMALL IN SIZE 17 SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 22 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25672 17 F CULLED ON SCHEDULED DAY 4 18 F CULLED ON SCHEDULED DAY 4 25655 1 M SUBCUTANEOUS HEMORRHAGE(S) 0 AROUND MOUTH 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 M SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 -576- 25727 1 M MISSING 1 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 23 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25727 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 17 F CULLED ON SCHEDULED DAY 4 25626 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 -577- 25739 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 24 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25739 6 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M SCHEDULED EUTHANASIA 21 10 M CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 25749 1 F MISSING 1 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F SCHEDULED EUTHANASIA 21 -578- 25756 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 25 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25756 12 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 25741 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 8 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 17 F CULLED ON SCHEDULED DAY 4 -579- 25752 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M FOUND DEAD 2 PARTIALLY CANNIBALIZED APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 26 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25752 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F SCHEDULED EUTHANASIA 21 25758 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F SMALL IN SIZE 11 SMALL IN SIZE 14 SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 -580- 25719 1 M CULLED ON SCHEDULED DAY 4 2 M MISSING 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 27 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25719 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M SCHEDULED EUTHANASIA 21 10 M CULLED ON SCHEDULED DAY 4 11 M CULLED ON SCHEDULED DAY 4 12 M CULLED ON SCHEDULED DAY 4 13 F SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 14 F SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 17 F SCHEDULED EUTHANASIA 21 -581- APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 28 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25606 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 F SCHEDULED EUTHANASIA 21 5 F SCHEDULED EUTHANASIA 21 6 F CULLED ON SCHEDULED DAY 4 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 -582- 25614 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 11 M CULLED ON SCHEDULED DAY 4 12 M CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 29 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25614 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 18 F SCHEDULED EUTHANASIA 21 25671 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 -583- 25698 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 F SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 F CULLED ON SCHEDULED DAY 4 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 30 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25698 15 F FOUND DEAD 3 25609 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 F CULLED ON SCHEDULED DAY 4 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F SCHEDULED EUTHANASIA 21 -584- 25677 1 M FOUND DEAD 4 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 9 F FOUND DEAD 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 31 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25623 1 M FOUND DEAD 0 2 M FOUND DEAD 0 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F FOUND DEAD 7 13 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 -585- 25653 1 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 F SCHEDULED EUTHANASIA 21 6 F SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 M SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 14 M CULLED ON SCHEDULED DAY 4 25604 1 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 32 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25604 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 25678 1 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 -586- 25684 1 M MISSING 1 2 M SCHEDULED EUTHANASIA 21 HAIR LOSS 21 RIGHT FORELIMB APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 33 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25684 2 M HAIR LOSS 21 LEFT FORELIMB 3 M HAIR LOSS 14 RIGHT FORELIMB HAIR LOSS 14 LEFT FORELIMB HAIR LOSS 17 RIGHT FORELIMB HAIR LOSS 17 RIGHT HINDLIMB HAIR LOSS 17 LEFT FORELIMB HAIR LOSS 17 LEFT HINDLIMB SCHEDULED EUTHANASIA 21 HAIR LOSS 21 RIGHT FORELIMB -587- HAIR LOSS 21 LEFT FORELIMB 4 M HAIR LOSS 14 RIGHT FORELIMB HAIR LOSS 14 LEFT FORELIMB HAIR LOSS 17 RIGHT FORELIMB HAIR LOSS 17 LEFT FORELIMB HAIR LOSS 21 RIGHT FORELIMB APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 34 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25684 4 M HAIR LOSS 21 LEFT FORELIMB 5 M HAIR LOSS 14 RIGHT FORELIMB HAIR LOSS 14 LEFT FORELIMB HAIR LOSS 17 RIGHT FORELIMB HAIR LOSS 17 LEFT FORELIMB SCHEDULED EUTHANASIA 21 HAIR LOSS 21 RIGHT FORELIMB HAIR LOSS 21 LEFT FORELIMB 6 F HAIR LOSS 14 RIGHT FORELIMB -588- HAIR LOSS 14 LEFT FORELIMB HAIR LOSS 17 RIGHT FORELIMB HAIR LOSS 17 RIGHT HINDLIMB HAIR LOSS 17 LEFT FORELIMB HAIR LOSS 21 RIGHT FORELIMB HAIR LOSS 21 LEFT FORELIMB APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 35 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25684 7 F CULLED ON SCHEDULED DAY 4 8 F HAIR LOSS 14 RIGHT FORELIMB HAIR LOSS 14 LEFT FORELIMB HAIR LOSS 17 RIGHT FORELIMB HAIR LOSS 17 LEFT FORELIMB HAIR LOSS 21 RIGHT FORELIMB HAIR LOSS 21 LEFT FORELIMB SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F HAIR LOSS 14 -589- RIGHT FORELIMB HAIR LOSS 14 LEFT FORELIMB HAIR LOSS 17 RIGHT FORELIMB HAIR LOSS 17 LEFT FORELIMB HAIR LOSS 21 RIGHT FORELIMB HAIR LOSS 21 LEFT FORELIMB APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 36 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25684 11 F SCHEDULED EUTHANASIA 21 12 F HAIR LOSS 14 RIGHT FORELIMB HAIR LOSS 14 LEFT FORELIMB HAIR LOSS 17 RIGHT FORELIMB HAIR LOSS 17 LEFT FORELIMB HAIR LOSS 21 RIGHT FORELIMB HAIR LOSS 21 LEFT FORELIMB SCHEDULED EUTHANASIA 21 -590- 25714 1 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 25650 1 F SMALL IN SIZE 0 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 37 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25650 1 F SMALL IN SIZE 1 SMALL IN SIZE 7 SMALL IN SIZE 4 SMALL IN SIZE 11 SMALL IN SIZE 14 SMALL IN SIZE 17 SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M SCHEDULED EUTHANASIA 21 9 M CULLED ON SCHEDULED DAY 4 10 M CULLED ON SCHEDULED DAY 4 12 M CULLED ON SCHEDULED DAY 4 13 M SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 16 F CULLED ON SCHEDULED DAY 4 18 F CULLED ON SCHEDULED DAY 4 19 F SCHEDULED EUTHANASIA 21 -591- 25735 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 38 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25735 4 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 25722 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 M SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 16 M FOUND DEAD 0 -592- 25642 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 39 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25642 4 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F FOUND DEAD 6 11 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 -593- 25628 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M FOUND DEAD 2 8 M CULLED ON SCHEDULED DAY 4 9 M SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 17 F SMALL IN SIZE 7 SMALL IN SIZE 11 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 40 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25628 17 F SMALL IN SIZE 14 SMALL IN SIZE 17 25763 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M FOUND DEAD 5 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F FOUND DEAD 6 17 F CULLED ON SCHEDULED DAY 4 18 F CULLED ON SCHEDULED DAY 4 19 F CULLED ON SCHEDULED DAY 4 -594- 25766 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M FOUND DEAD 3 5 F CULLED ON SCHEDULED DAY 4 7 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 41 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25766 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 M CULLED ON SCHEDULED DAY 4 11 M SCHEDULED EUTHANASIA 21 25689 1 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 F SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 14 F HAIR LOSS 14 DORSAL HEAD 15 F CULLED ON SCHEDULED DAY 4 -595- 25708 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 42 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25708 9 M SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 25743 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M FOUND DEAD 2 9 M SCHEDULED EUTHANASIA 21 10 M CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 17 F CULLED ON SCHEDULED DAY 4 18 F SCHEDULED EUTHANASIA 21 -596- 25761 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 43 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25761 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 -597- 25712 1 F FOUND DEAD 0 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 F SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 44 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25712 17 F SCHEDULED EUTHANASIA 21 25746 1 M CULLED ON SCHEDULED DAY 4 2 M FOUND DEAD 2 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 M CULLED ON SCHEDULED DAY 4 11 M SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 17 F SCHEDULED EUTHANASIA 21 18 F CULLED ON SCHEDULED DAY 4 -598- APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 45 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25696 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M SCHEDULED EUTHANASIA 21 10 M CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 16 F SCHEDULED EUTHANASIA 21 -599- 25686 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 F SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 46 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25639 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 M SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 16 F CULLED ON SCHEDULED DAY 4 -600- 25658 1 F FOUND DEAD 0 2 F SMALL IN SIZE 0 MISSING 1 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 47 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25658 15 F SCHEDULED EUTHANASIA 21 25676 1 M FOUND DEAD 0 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 -601- 25600 1 M SCHEDULED EUTHANASIA 21 3 M SCABBING 4 DORSAL ABDOMINAL AREA SCABBING 7 DORSAL ABDOMINAL AREA SCABBING 11 DORSAL ABDOMINAL AREA SCABBING 17 DORSAL ABDOMINAL AREA SCHEDULED EUTHANASIA 21 SCABBING 14 DORSAL ABDOMINAL AREA APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 48 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25600 4 M SCHEDULED EUTHANASIA 21 5 F SCHEDULED EUTHANASIA 21 6 F CULLED ON SCHEDULED DAY 4 7 F CULLED ON SCHEDULED DAY 4 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 16 F CULLED ON SCHEDULED DAY 4 17 F CULLED ON SCHEDULED DAY 4 -602- 25603 1 M SCHEDULED EUTHANASIA 21 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 F SCHEDULED EUTHANASIA 21 7 F SCHEDULED EUTHANASIA 21 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 49 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25630 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 -603- 25703 1 M CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 F CULLED ON SCHEDULED DAY 4 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 25673 1 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 50 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25673 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M LACERATION 1 DORSAL THORACIC AREA CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 -604- 25611 1 M FOUND DEAD 0 2 F FOUND DEAD 0 3 F FOUND DEAD 0 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 8 M SCHEDULED EUTHANASIA 21 9 M CULLED ON SCHEDULED DAY 4 10 M SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 51 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25619 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 -605- 25705 1 M SMALL IN SIZE 1 SMALL IN SIZE 4 SMALL IN SIZE 7 SMALL IN SIZE 11 SMALL IN SIZE 14 SMALL IN SIZE 17 SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 52 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25705 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 25691 1 F CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 F FOUND DEAD 1 14 F SCHEDULED EUTHANASIA 21 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 -606- 25717 1 M FOUND DEAD 0 2 M MISSING 1 3 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 M SCHEDULED EUTHANASIA 21 8 M CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 53 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25717 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 25616 1 M DISTAL PORTION OF TAIL MISSING 0 DISTAL PORTION OF TAIL MISSING 1 DISTAL PORTION OF TAIL MISSING 4 CULLED ON SCHEDULED DAY 4 2 M SCHEDULED EUTHANASIA 21 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 F CULLED ON SCHEDULED DAY 4 9 F CULLED ON SCHEDULED DAY 4 10 F SCHEDULED EUTHANASIA 21 11 F SCHEDULED EUTHANASIA 21 12 M SCHEDULED EUTHANASIA 21 13 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 -607- 25715 1 M MISSING 1 2 F MISSING 1 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 54 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25715 8 M SCHEDULED EUTHANASIA 21 9 M CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 17 F SCHEDULED EUTHANASIA 21 25762 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M SCHEDULED EUTHANASIA 21 7 F SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F CULLED ON SCHEDULED DAY 4 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 -608- 25599 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 55 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25599 5 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 M FOUND DEAD 2 9 M SCHEDULED EUTHANASIA 21 10 M SCHEDULED EUTHANASIA 21 12 F SCHEDULED EUTHANASIA 21 13 F CULLED ON SCHEDULED DAY 4 14 F CULLED ON SCHEDULED DAY 4 15 F CULLED ON SCHEDULED DAY 4 16 F CULLED ON SCHEDULED DAY 4 17 F SCHEDULED EUTHANASIA 21 18 F CULLED ON SCHEDULED DAY 4 19 F SCHEDULED EUTHANASIA 21 -609- 25647 1 M FOUND DEAD 0 2 M LACERATION 0 TAIL CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 12 F SCHEDULED EUTHANASIA 21 13 M SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 56 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25747 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F CULLED ON SCHEDULED DAY 4 11 F CULLED ON SCHEDULED DAY 4 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F CULLED ON SCHEDULED DAY 4 17 F CULLED ON SCHEDULED DAY 4 -610- 25744 1 M SCHEDULED EUTHANASIA 21 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M SCHEDULED EUTHANASIA 21 5 M CULLED ON SCHEDULED DAY 4 6 M SCHEDULED EUTHANASIA 21 7 F CULLED ON SCHEDULED DAY 4 8 F SCHEDULED EUTHANASIA 21 9 F CULLED ON SCHEDULED DAY 4 10 F CULLED ON SCHEDULED DAY 4 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 57 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25744 11 F SCHEDULED EUTHANASIA 21 12 F CULLED ON SCHEDULED DAY 4 13 F SCHEDULED EUTHANASIA 21 14 F SCHEDULED EUTHANASIA 21 15 F CULLED ON SCHEDULED DAY 4 25707 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M SCHEDULED EUTHANASIA 21 4 M CULLED ON SCHEDULED DAY 4 5 M SCHEDULED EUTHANASIA 21 6 M CULLED ON SCHEDULED DAY 4 7 M SCHEDULED EUTHANASIA 21 8 M SCHEDULED EUTHANASIA 21 9 F SCHEDULED EUTHANASIA 21 10 F SCHEDULED EUTHANASIA 21 11 F MISSING 2 12 F SCHEDULED EUTHANASIA 21 13 F FOUND DEAD 3 14 F SCHEDULED EUTHANASIA 21 -611- 25723 1 M CULLED ON SCHEDULED DAY 4 2 M CULLED ON SCHEDULED DAY 4 3 M CULLED ON SCHEDULED DAY 4 4 M CULLED ON SCHEDULED DAY 4 5 M SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 6 M SMALL IN SIZE 21 APPENDIX 16 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 58 SPONSOR:3M CORPORATION INDIVIDUAL PUP CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PRE-WEANING ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY PUP # SEX PUP GROSS OBSERVATION POSTNATAL DAY ----------------------------------------------------------------------------------------------------------------------------------- 25723 6 M SCHEDULED EUTHANASIA 21 7 M CULLED ON SCHEDULED DAY 4 8 M CULLED ON SCHEDULED DAY 4 9 M CULLED ON SCHEDULED DAY 4 10 M CULLED ON SCHEDULED DAY 4 11 M CULLED ON SCHEDULED DAY 4 12 M SCHEDULED EUTHANASIA 21 13 F SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 14 F CULLED ON SCHEDULED DAY 4 15 F SCHEDULED EUTHANASIA 21 16 F SCHEDULED EUTHANASIA 21 17 M SMALL IN SIZE 7 SMALL IN SIZE 11 SMALL IN SIZE 14 SMALL IN SIZE 17 SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 18 F SMALL IN SIZE 11 SMALL IN SIZE 14 SMALL IN SIZE 17 SMALL IN SIZE 21 SCHEDULED EUTHANASIA 21 -612- PPOBSv4.06 10/19/2006 APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597-01 M 6.5 8.0 NA NA NA NA NA 25597-02 M 6.7 7.9 13.3 21.5 27.6 31.2 40.5 25597-03 M 6.2 7.5 NA NA NA NA NA 25597-04 M 6.4 8.5 14.7 23.6 28.8 31.8 41.2 25597-05 M 5.8 7.5 12.4 20.5 26.8 31.0 39.1 25597-06 M 5.6 7.1 NA NA NA NA NA 25597-07 M 5.8 7.9 12.5 20.6 26.5 32.2 39.2 25597-08 F 6.0 8.0 13.3 20.4 26.3 29.7 40.0 25597-09 F 5.8 7.8 NA NA NA NA NA 25597-10 F 5.8 7.8 NA NA NA NA NA 25597-11 F 6.5 8.5 NA NA NA NA NA 25597-12 F 5.2 6.0 9.7 15.6 21.6 25.0 31.8 25597-13 F 6.4 8.1 NA NA NA NA NA 25597-14 F 5.8 7.6 NA NA NA NA NA 25597-15 F 6.2 8.2 NA NA NA NA NA 25597-16 F 6.0 7.5 11.7 17.8 23.6 27.9 36.6 25597-17 F 6.2 7.6 13.1 20.9 25.3 28.0 35.0 -613- MALES MEAN 6.1 7.8 13.2 21.6 27.4 31.6 40.0 FEMALES MEAN 6.0 7.7 12.0 18.7 24.2 27.7 35.9 25654-01 M 25654-02 M 25654-03 M 25654-04 M 25654-05 M 6.3 7.5 NA NA NA NA NA 6.0 8.1 13.1 21.3 28.2 33.4 43.8 6.3 8.3 NA NA NA NA NA 6.2 8.4 NA NA NA NA NA 6.7 8.9 15.7 23.3 30.6 37.3 47.5 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25654-06 M 6.0 7.0 NA NA NA NA NA 25654-07 M 5.9 8.0 14.8 22.9 30.4 37.1 46.0 25654-08 M 6.1 6.5 NA NA NA NA NA 25654-09 M 6.1 8.0 14.5 23.0 29.5 36.1 44.1 25654-10 F 6.2 7.6 13.3 21.2 27.6 33.8 42.0 25654-11 F 5.9 7.6 12.8 17.9 25.1 31.0 38.7 25654-12 F 6.0 8.5 NA NA NA NA NA 25654-13 F 5.7 7.2 NA NA NA NA NA 25654-14 F 5.9 7.7 12.6 20.2 27.0 33.1 43.5 25654-15 F 6.1 7.5 NA NA NA NA NA MALES MEAN 6.2 7.9 14.5 22.6 29.7 36.0 45.4 FEMALES MEAN 6.0 7.7 12.9 19.8 26.6 32.6 41.4 -614- 25632-01 M 25632-02 M 25632-03 M 25632-04 M 25632-05 M 25632-06 M 25632-07 M 25632-08 M 25632-09 F 25632-10 F 25632-11 F 25632-12 F 8.5 11.8 NA NA NA NA NA 7.4 11.0 16.6 26.6 35.7 41.0 54.2 7.4 10.8 NA NA NA NA NA 7.5 10.9 16.7 25.3 34.0 41.8 56.8 7.5 10.7 NA NA NA NA NA 8.0 11.3 18.0 27.2 34.8 43.2 57.2 7.6 10.9 16.2 24.2 29.7 37.7 47.2 7.8 11.6 NA NA NA NA NA 7.8 11.1 17.7 26.0 32.0 39.6 49.2 8.2 11.4 18.6 28.3 36.5 43.6 57.7 7.5 10.4 NA NA NA NA NA 7.2 10.1 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25632-13 F 7.3 10.6 NA NA NA NA NA 25632-14 F 6.8 10.1 NA NA NA NA NA 25632-15 F 7.3 10.2 15.7 25.3 33.2 39.6 51.0 25632-16 F 7.4 10.6 16.9 25.8 33.3 39.9 52.1 MALES MEAN FEMALES MEAN 7.7 11.1 16.9 25.8 33.6 40.9 53.9 7.4 10.6 17.2 26.4 33.8 40.7 52.5 25610-01 M 25610-02 M 25610-03 F 25610-04 F 25610-05 F 8.4 13.0 20.9 31.4 38.6 45.1 62.1 8.4 12.9 21.0 31.9 39.1 45.4 62.3 8.0 12.5 19.7 29.7 36.0 42.8 55.9 7.4 11.7 18.2 28.9 36.0 42.3 57.2 8.1 12.7 20.5 31.8 39.1 44.7 61.2 -615- MALES MEAN FEMALES MEAN 8.4 13.0 21.0 31.7 38.9 45.3 62.2 7.8 12.3 19.5 30.1 37.0 43.3 58.1 25618-01 M 25618-02 M 25618-03 M 25618-04 M 25618-05 M 25618-06 M 25618-07 M 25618-08 M 25618-09 M 6.5 9.5 NA NA NA NA NA 7.1 10.0 16.0 25.4 30.5 38.5 52.9 7.8 10.4 NA NA NA NA NA 6.7 9.5 NA NA NA NA NA 7.1 10.8 NA NA NA NA NA 7.0 9.1 NA NA NA NA NA 6.8 9.5 15.1 25.4 32.9 40.2 53.8 6.8 9.6 15.1 24.4 31.2 39.2 51.7 7.4 9.5 14.5 24.8 32.4 39.4 55.3 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25618-10 M 7.0 9.9 NA NA NA NA NA 25618-11 F 7.0 10.3 16.0 27.4 34.1 41.8 57.7 25618-12 F 7.1 10.1 NA NA NA NA NA 25618-13 F 6.7 8.6 NA NA NA NA NA 25618-14 F 6.6 9.1 NA NA NA NA NA 25618-15 F 6.0 8.8 13.9 24.0 31.0 37.7 50.1 25618-16 F 6.2 8.1 NA NA NA NA NA 25618-17 F 6.4 8.9 13.8 23.9 29.8 37.7 48.5 25618-18 F 7.2 9.7 15.1 24.7 32.7 39.6 55.0 MALES MEAN 7.0 9.8 15.2 25.0 31.8 39.3 53.4 FEMALES MEAN 6.7 9.2 14.7 25.0 31.9 39.2 52.8 -616- 25621-01 M 25621-02 M 25621-03 M 25621-04 M 25621-05 M 25621-06 M 25621-07 M 25621-08 M 25621-09 F 25621-10 F 25621-11 F 25621-12 F 25621-13 F 7.9 9.8 16.3 25.9 33.5 40.8 56.4 7.5 9.9 16.2 26.3 33.7 41.0 55.2 7.4 9.4 15.5 24.6 33.2 40.5 53.4 7.7 10.6 NA NA NA NA NA 7.7 10.1 NA NA NA NA NA 6.7 9.6 NA NA NA NA NA 7.3 9.8 16.2 26.0 32.3 40.5 51.7 7.1 9.7 NA NA NA NA NA 6.7 9.0 16.3 25.4 33.6 40.9 53.4 7.2 10.1 17.1 26.5 32.7 41.1 52.6 7.0 9.5 NA NA NA NA NA 7.2 9.6 16.0 25.7 32.1 39.3 52.4 7.3 9.8 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25621-14 F 7.0 9.2 NA NA NA NA NA 25621-15 F 7.0 9.4 NA NA NA NA NA 25621-16 F 7.4 9.8 16.8 26.4 33.9 41.6 53.7 MALES MEAN 7.4 9.9 16.1 25.7 33.2 40.7 54.2 FEMALES MEAN 7.1 9.6 16.6 26.0 33.1 40.7 53.0 -617- 25687-01 M 25687-02 M 25687-03 M 25687-04 M 25687-05 M 25687-06 M 25687-07 M 25687-08 M 25687-09 F 25687-10 F 25687-11 F 25687-12 F 25687-13 F 25687-14 F 25687-15 F 25687-16 F 7.3 11.1 NA NA NA NA NA 7.0 10.6 NA NA NA NA NA 6.4 9.5 14.3 22.9 31.6 38.6 50.3 7.5 10.7 15.3 24.8 32.7 39.8 53.4 6.8 10.5 15.6 26.2 34.3 42.1 53.7 7.4 10.0 NA NA NA NA NA 6.9 10.4 15.0 24.6 31.4 39.1 50.2 7.1 10.7 NA NA NA NA NA 7.0 10.2 NA NA NA NA NA 6.6 9.9 14.7 23.4 30.2 37.1 43.9 7.0 10.2 NA NA NA NA NA 6.7 NA NA NA NA NA NA 6.5 10.2 NA NA NA NA NA 6.6 10.0 14.1 23.2 31.1 38.4 48.7 6.9 10.1 14.8 24.4 30.5 37.9 46.8 6.8 10.0 14.8 24.5 32.2 38.3 48.4 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25687-17 F 7.0 10.5 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.1 10.4 15.1 24.6 32.5 39.9 51.9 6.8 10.1 14.6 23.9 31.0 37.9 47.0 25633-01 M 25633-02 M 25633-03 M 25633-04 M 25633-05 M 25633-06 M 25633-07 M 25633-08 M 25633-09 M 25633-10 F 25633-11 F 25633-12 F 25633-13 F 25633-14 F 5.4 7.0 9.3 NA NA NA NA 5.4 6.6 NA NA NA NA NA 5.4 6.9 NA NA NA NA NA 5.3 6.8 9.3 15.2 22.0 27.2 35.3 5.5 7.3 10.2 16.8 22.4 27.5 32.3 6.1 7.8 NA NA NA NA NA 5.6 7.5 NA NA NA NA NA 5.9 7.5 NA NA NA NA NA 6.0 7.8 10.2 17.2 23.0 28.0 35.9 4.2 5.3 NA NA NA NA NA 5.5 7.0 9.7 16.0 22.6 27.9 34.9 5.2 6.1 7.7 12.8 18.3 23.4 29.9 5.0 6.4 8.4 13.9 19.2 25.0 30.3 4.9 6.5 8.6 14.5 20.0 25.2 32.3 -618- MALES MEAN 5.6 7.2 9.8 16.4 22.5 27.6 34.5 FEMALES MEAN 5.0 6.3 8.6 14.3 20.0 25.4 31.9 25681-01 M 25681-02 M 25681-03 M 7.1 10.1 15.2 23.9 34.4 37.9 43.8 7.0 9.6 NA NA NA NA NA 6.1 8.3 12.3 21.2 33.3 36.5 43.3 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25681-04 M 7.5 11.0 NA NA NA NA NA 25681-05 F 6.3 9.1 14.5 23.4 30.6 38.0 46.7 25681-06 M 7.9 11.1 17.1 27.1 34.8 43.0 57.2 25681-07 M 7.4 10.5 17.2 26.9 34.7 43.1 55.3 25681-08 M 7.5 10.5 NA NA NA NA NA 25681-09 F 7.0 10.0 NA NA NA NA NA 25681-10 F 6.6 9.5 15.1 24.5 32.5 37.8 46.1 25681-11 F 6.0 8.7 13.4 22.6 29.7 36.0 45.1 25681-12 F 6.7 9.5 NA NA NA NA NA 25681-13 F 6.4 9.4 NA NA NA NA NA 25681-14 F 6.6 9.4 15.6 24.7 32.3 39.9 48.6 25681-15 F 6.8 8.9 NA NA NA NA NA 25681-16 F 7.0 9.5 NA NA NA NA NA -619- MALES MEAN FEMALES MEAN 7.2 10.2 15.5 24.8 34.3 40.1 49.9 6.6 9.3 14.7 23.8 31.3 37.9 46.6 25615-01 M 25615-02 M 25615-03 M 25615-04 M 25615-05 M 25615-06 M 25615-07 F 25615-08 F 25615-09 F 8.2 11.6 17.5 26.6 34.2 40.3 56.6 7.9 11.0 NA NA NA NA NA 7.2 10.6 16.5 26.3 31.1 38.5 52.7 6.9 10.4 NA NA NA NA NA 7.7 11.3 17.9 27.1 34.8 38.9 52.2 7.5 10.3 16.5 26.1 32.4 40.3 56.7 6.4 8.8 NA NA NA NA NA 7.4 10.5 16.7 26.1 33.1 40.4 56.2 7.2 10.1 15.6 24.1 31.9 38.3 52.2 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25615-10 F 6.7 9.4 14.9 24.2 29.5 35.1 47.0 25615-11 F 7.1 10.2 NA NA NA NA NA 25615-12 F 6.8 9.7 NA NA NA NA NA 25615-13 F 6.8 10.2 15.1 25.0 32.8 38.2 53.4 25615-14 F 6.9 10.1 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.6 10.9 17.1 26.5 33.1 39.5 54.6 6.9 9.9 15.6 24.9 31.8 38.0 52.2 -620- 25637-02 M 25637-03 M 25637-04 M 25637-05 M 25637-06 M 25637-07 M 25637-08 M 25637-09 F 25637-10 F 25637-11 M 25637-12 F 25637-13 F 25637-14 F 25637-15 F 25637-16 F 7.7 10.7 NA NA NA NA NA 7.9 10.9 17.2 28.7 36.2 44.9 60.2 7.5 10.9 NA NA NA NA NA 6.7 9.1 NA NA NA NA NA 7.0 9.7 15.9 27.6 33.8 42.0 57.6 6.9 9.8 NA NA NA NA NA 7.1 9.7 15.6 26.7 34.9 44.0 62.3 7.0 9.5 NA NA NA NA NA 7.3 10.1 16.6 27.9 36.4 46.1 64.2 7.6 10.5 15.8 27.8 36.1 45.9 59.1 7.3 10.3 NA NA NA NA NA 6.9 9.4 NA NA NA NA NA 7.3 10.3 15.9 27.4 35.9 44.9 61.3 7.1 10.0 16.8 29.2 37.8 43.9 61.1 6.8 9.9 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25637-17 F 6.9 9.6 16.1 27.3 33.3 42.3 55.0 MALES MEAN FEMALES MEAN 7.3 10.2 16.1 27.7 35.3 44.2 59.8 7.1 9.9 16.4 28.0 35.9 44.3 60.4 25638-01 M 25638-02 M 25638-03 M 25638-04 M 25638-05 M 25638-06 M 25638-07 M 25638-08 M 25638-09 F 25638-10 F 25638-11 F 25638-13 F 25638-14 F 25638-15 F 25638-16 F 25638-18 F 7.6 11.1 16.1 27.0 34.7 41.6 57.2 8.3 NA NA NA NA NA NA 7.2 10.4 NA NA NA NA NA 7.8 10.5 14.8 24.8 33.0 40.7 53.8 7.6 10.9 16.1 27.3 35.6 41.9 56.3 6.1 8.0 NA NA NA NA NA 7.4 10.5 15.8 25.5 31.3 39.1 48.9 7.1 10.3 NA NA NA NA NA 7.2 10.2 NA NA NA NA NA 7.6 10.0 NA NA NA NA NA 6.8 10.0 15.0 25.4 33.5 40.0 53.7 7.0 10.0 NA NA NA NA NA 7.2 10.2 NA NA NA NA NA 6.8 9.5 14.7 25.4 34.2 43.2 55.0 6.6 9.8 14.6 24.5 32.9 39.7 54.7 6.5 8.6 12.6 20.7 26.5 34.1 41.2 -621- MALES MEAN FEMALES MEAN 7.4 10.2 15.7 26.2 33.7 40.8 54.1 7.0 9.8 14.2 24.0 31.8 39.3 51.2 25713-01 M 7.1 10.0 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25713-02 M 7.1 9.5 15.5 26.4 32.9 40.1 49.8 25713-03 M 7.8 10.3 NA NA NA NA NA 25713-04 M 7.0 9.0 14.2 24.5 30.8 36.4 47.2 25713-05 M 7.5 8.7 14.4 25.6 33.3 41.4 56.2 25713-06 M 7.5 10.0 NA NA NA NA NA 25713-07 M 7.0 9.4 NA NA NA NA NA 25713-08 M 7.1 9.0 14.3 25.0 31.6 39.7 56.5 25713-09 M 7.1 9.0 NA NA NA NA NA 25713-10 M 7.4 9.8 NA NA NA NA NA 25713-11 M 6.8 9.2 NA NA NA NA NA 25713-12 F 7.0 9.8 14.4 25.3 32.5 41.1 54.6 25713-13 F 6.5 9.2 15.2 26.6 33.0 39.2 54.2 25713-14 F 7.1 9.3 15.0 25.0 31.4 39.1 51.3 25713-15 F 6.8 8.5 NA NA NA NA NA 25713-16 F 7.5 9.6 15.3 26.2 31.8 38.7 47.9 -622- MALES MEAN 7.2 9.4 14.6 25.4 32.2 39.4 52.4 FEMALES MEAN 7.0 9.3 15.0 25.8 32.2 39.5 52.0 25670-01 M 25670-02 M 25670-03 M 25670-04 M 25670-05 M 25670-06 M 25670-07 M 7.2 9.2 NA NA NA NA NA 7.6 10.2 NA NA NA NA NA 6.9 9.2 15.3 26.7 37.6 42.6 57.1 6.9 8.3 14.2 25.6 33.7 41.4 54.5 7.3 9.4 NA NA NA NA NA 6.2 7.6 11.5 21.1 28.4 35.4 46.1 7.4 10.1 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25670-08 M 6.6 8.4 NA NA NA NA NA 25670-09 M 7.2 9.2 14.7 26.6 33.9 42.8 53.5 25670-10 M 7.5 9.5 NA NA NA NA NA 25670-11 M 6.9 8.9 NA NA NA NA NA 25670-12 F 6.5 8.7 NA NA NA NA NA 25670-13 F 6.4 7.4 NA NA NA NA NA 25670-14 F 6.7 8.6 NA NA NA NA NA 25670-15 F 7.1 8.5 13.3 24.1 32.3 40.0 50.2 25670-16 F 6.0 7.4 10.7 20.4 29.1 36.5 47.8 25670-17 F 7.0 8.7 13.8 23.9 31.3 38.6 51.2 25670-18 F 6.9 8.8 13.3 24.4 31.3 40.3 52.0 25670-19 F 7.2 9.1 NA NA NA NA NA MALES MEAN 7.1 9.1 13.9 25.0 33.4 40.6 52.8 FEMALES MEAN 6.7 8.4 12.8 23.2 31.0 38.9 50.3 -623- 25657-01 M 25657-02 M 25657-03 M 25657-04 M 25657-05 M 25657-06 M 25657-07 M 25657-08 M 25657-09 F 25657-10 F 7.4 10.2 16.6 28.2 37.9 47.5 63.8 6.9 9.6 16.2 27.0 35.5 45.1 58.1 7.0 9.7 NA NA NA NA NA 6.3 8.6 NA NA NA NA NA 7.1 9.3 NA NA NA NA NA 7.3 10.1 NA NA NA NA NA 7.0 9.5 16.5 27.4 34.9 45.0 57.8 6.2 9.4 15.4 26.3 33.3 44.4 57.9 6.4 8.7 NA NA NA NA NA 6.7 8.8 15.4 25.1 31.7 40.6 53.0 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25657-11 F 7.0 9.9 NA NA NA NA NA 25657-12 F 6.7 9.2 15.5 26.4 34.3 43.5 56.4 25657-13 F 6.7 8.9 15.2 25.5 34.3 42.2 52.8 25657-14 F 7.1 10.0 NA NA NA NA NA 25657-15 F 5.6 8.2 13.7 22.3 30.2 38.3 50.8 25657-16 F 6.7 9.4 NA NA NA NA NA 25657-17 F 7.0 9.7 NA NA NA NA NA 25657-19 F 6.2 9.0 NA NA NA NA NA MALES MEAN 6.9 9.6 16.2 27.2 35.4 45.5 59.4 FEMALES MEAN 6.6 9.2 15.0 24.8 32.6 41.2 53.3 -624- 25663-01 M 25663-02 M 25663-03 M 25663-04 M 25663-05 M 25663-06 M 25663-07 F 25663-08 F 25663-09 F 25663-10 F 7.9 11.1 NA NA NA NA NA 7.8 11.1 17.2 28.6 36.7 45.6 62.8 7.8 11.2 17.5 28.8 36.6 44.5 61.7 8.3 11.7 18.2 28.9 35.1 43.5 55.0 7.0 10.1 NA NA NA NA NA 8.6 12.2 18.4 29.1 37.3 46.1 62.2 7.3 10.1 15.4 26.0 33.4 41.2 56.1 7.7 11.7 18.4 29.6 37.2 45.8 61.6 6.8 9.7 14.6 24.3 30.0 38.5 49.8 7.3 10.5 16.6 26.9 35.3 43.7 59.6 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25663-11 F 7.8 10.9 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.9 11.2 17.8 28.9 36.4 44.9 60.4 7.4 10.6 16.3 26.7 34.0 42.3 56.8 25690-01 M 25690-02 M 25690-03 M 25690-04 M 25690-05 M 25690-06 M 25690-07 M 25690-08 F 25690-09 F 25690-10 F 25690-11 F 25690-12 F 25690-13 F 25690-14 F 25690-15 F 25690-16 F 25690-17 F 25690-18 F 6.7 8.4 12.9 22.8 29.2 38.4 50.6 6.7 8.6 NA NA NA NA NA 7.0 8.8 13.6 23.6 30.9 40.5 55.1 6.7 8.9 NA NA NA NA NA 6.8 9.4 14.2 25.0 32.4 40.8 54.0 7.1 8.9 NA NA NA NA NA 7.0 9.5 15.0 25.0 33.3 41.3 55.7 6.5 8.2 NA NA NA NA NA 6.1 8.1 11.4 20.2 28.2 35.3 47.2 6.5 8.4 NA NA NA NA NA 6.6 8.7 NA NA NA NA NA 6.8 8.9 NA NA NA NA NA 6.1 7.8 NA NA NA NA NA 6.7 8.8 NA NA NA NA NA 6.7 8.2 NA NA NA NA NA 6.9 8.4 NA NA NA NA NA 6.4 8.5 13.2 23.4 30.6 38.8 52.1 6.4 8.2 12.4 22.1 29.4 38.4 51.5 -625- NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25690-19 F 6.4 8.1 12.9 22.5 28.2 37.9 48.4 MALES MEAN 6.9 8.9 13.9 24.1 31.5 40.3 53.9 FEMALES MEAN 6.5 8.4 12.5 22.1 29.1 37.6 49.8 25666-01 M 25666-02 M 25666-03 M 25666-04 M 25666-05 M 25666-06 M 25666-07 M 25666-08 F 25666-09 F 25666-10 F 25666-11 F 25666-12 F 25666-13 F 25666-14 F 7.4 10.1 15.9 26.7 32.4 41.2 51.0 6.7 9.5 13.9 23.7 31.3 39.9 52.5 7.2 10.1 NA NA NA NA NA 6.8 9.1 NA NA NA NA NA 6.9 9.7 14.6 25.2 33.7 41.4 51.3 6.8 9.7 NA NA NA NA NA 6.9 9.7 14.8 24.5 33.0 40.6 51.4 6.5 9.0 14.0 24.2 33.0 39.9 50.2 6.6 9.0 14.1 23.9 30.0 38.6 44.2 6.2 8.8 NA NA NA NA NA 6.6 8.5 NA NA NA NA NA 7.0 10.0 NA NA NA NA NA 6.5 8.5 12.5 23.0 30.6 37.6 47.3 6.5 9.1 14.2 24.5 31.8 39.1 50.3 -626- MALES MEAN 7.0 9.7 14.8 25.0 32.6 40.8 51.6 FEMALES MEAN 6.6 9.0 13.7 23.9 31.4 38.8 48.0 25692-02 M 25692-03 M 25692-04 M 8.0 10.6 17.4 29.1 37.6 47.4 63.5 7.1 10.1 15.7 26.8 33.9 42.6 55.7 7.4 10.3 16.2 28.3 36.8 46.6 60.3 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25692-05 M 7.5 9.7 15.0 26.8 34.4 43.6 57.1 25692-06 F 7.2 10.4 16.3 27.2 35.4 43.7 58.2 25692-07 F 6.8 9.1 15.0 26.0 34.5 41.1 50.0 25692-08 F 6.8 8.9 NA NA NA NA NA 25692-09 F 6.9 9.4 NA NA NA NA NA 25692-10 F 7.3 9.7 NA NA NA NA NA 25692-11 F 7.2 10.2 NA NA NA NA NA 25692-12 F 7.3 10.0 16.0 26.5 33.3 41.3 54.1 25692-13 F 6.7 8.5 NA NA NA NA NA 25692-14 F 6.9 9.3 15.3 26.2 34.4 43.8 57.1 MALES MEAN FEMALES MEAN 7.5 10.2 16.1 27.8 35.7 45.1 59.2 7.0 9.5 15.7 26.5 34.4 42.5 54.9 -627- 25701-01 M 25701-02 F 25701-03 M 25701-04 M 25701-05 M 25701-06 M 25701-07 M 25701-08 M 25701-09 M 25701-10 M 25701-11 F 25701-12 F 6.4 8.6 NA NA NA NA NA 6.4 9.1 14.3 23.1 29.9 36.1 50.8 7.0 9.6 15.4 24.0 31.1 38.0 52.5 6.5 8.9 NA NA NA NA NA 6.7 8.9 NA NA NA NA NA 6.7 9.0 14.0 21.6 28.4 34.5 46.6 6.1 8.1 NA NA NA NA NA 5.9 8.3 NA NA NA NA NA 6.8 9.1 14.2 22.8 29.3 36.0 49.7 6.4 8.8 14.0 22.1 28.7 35.6 45.2 6.5 9.1 14.5 22.5 29.1 34.7 48.5 6.3 8.9 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25701-13 F 6.5 8.3 NA NA NA NA NA 25701-14 F 5.7 7.1 NA NA NA NA NA 25701-15 F 5.7 7.8 NA NA NA NA NA 25701-16 F 6.4 8.3 13.2 21.8 28.8 35.4 49.2 25701-17 F 6.4 8.3 NA NA NA NA NA 25701-18 F 6.2 8.7 13.7 22.4 29.0 36.5 48.4 25701-19 F 6.7 8.5 NA NA NA NA NA MALES MEAN 6.5 8.8 14.4 22.6 29.4 36.0 48.5 FEMALES MEAN 6.3 8.4 13.9 22.5 29.2 35.7 49.2 -628- 25645-01 M 25645-02 M 25645-03 M 25645-04 M 25645-05 M 25645-06 M 25645-07 F 25645-08 F 25645-09 F 25645-10 F 25645-11 F 25645-12 F 25645-13 F 25645-14 F 5.9 6.6 10.1 18.5 26.4 31.9 40.2 7.2 8.4 13.0 22.4 30.6 36.9 49.9 7.3 8.1 NA NA NA NA NA 7.2 8.6 13.8 21.1 28.4 33.8 45.3 8.1 9.7 NA NA NA NA NA 7.4 8.4 13.2 22.6 29.2 34.9 44.6 6.8 8.1 13.0 22.4 29.0 34.6 45.6 7.0 7.8 12.5 21.8 28.1 33.9 44.2 7.0 8.1 NA NA NA NA NA 7.0 7.5 NA NA NA NA NA 6.9 8.2 13.4 22.4 29.8 35.6 48.6 6.6 7.5 12.2 21.1 29.2 35.3 44.6 6.6 7.6 NA NA NA NA NA 7.3 9.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 17 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25645-15 F 6.5 7.6 NA NA NA NA NA MALES MEAN 7.2 8.3 12.5 21.2 28.7 34.4 45.0 FEMALES MEAN 6.9 8.0 12.8 21.9 29.0 34.9 45.8 25661-01 M 25661-02 M 25661-03 M 25661-04 M 25661-05 M 25661-06 M 25661-07 M 25661-08 M 25661-09 M 25661-10 F 25661-11 F 25661-12 F 25661-13 F 25661-14 F 25661-15 F 25661-16 F 7.9 9.9 NA NA NA NA NA 7.3 8.4 13.9 NA NA NA NA 7.6 9.6 NA NA NA NA NA 7.8 9.4 15.7 28.7 37.8 46.1 61.2 7.1 8.9 14.5 26.7 34.7 42.8 57.1 7.9 9.6 NA NA NA NA NA 7.6 9.2 NA NA NA NA NA 6.8 8.2 NA NA NA NA NA 7.5 9.6 NA NA NA NA NA 7.5 9.0 14.5 26.8 36.1 44.2 57.2 7.0 8.5 13.9 26.3 36.0 43.8 56.7 7.1 9.5 15.2 28.6 38.7 47.5 63.2 7.5 9.8 NA NA NA NA NA 7.1 8.7 16.0 28.3 38.2 45.5 58.3 7.5 9.4 NA NA NA NA NA 7.1 8.9 NA NA NA NA NA -629- MALES MEAN 7.5 9.2 14.7 27.7 36.3 44.5 59.2 FEMALES MEAN 7.3 9.1 14.9 27.5 37.3 45.3 58.9 25767-01 M 7.3 9.1 15.1 26.3 34.7 41.2 51.9 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 18 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25767-02 M 7.2 9.4 NA NA NA NA NA 25767-03 M 7.0 9.6 15.1 23.8 32.8 40.4 55.6 25767-04 M 6.6 9.0 NA NA NA NA NA 25767-05 M 7.0 10.1 15.7 27.3 36.5 43.5 52.6 25767-06 M 7.7 10.5 15.6 26.6 34.6 42.0 52.2 25767-07 F 6.8 8.8 14.0 24.5 31.2 38.1 50.2 25767-08 F 7.4 9.8 NA NA NA NA NA 25767-09 F 5.9 7.7 10.6 19.5 27.4 33.8 44.1 25767-10 F 7.1 9.8 NA NA NA NA NA 25767-11 F 6.5 7.9 NA NA NA NA NA 25767-12 F 7.5 9.6 14.7 25.4 34.2 39.3 51.0 25767-13 F 6.9 9.9 NA NA NA NA NA 25767-14 F 5.8 7.8 NA NA NA NA NA 25767-15 F 6.6 9.7 NA NA NA NA NA 25767-16 F 7.7 10.6 16.2 28.0 34.8 41.0 52.3 25767-17 F 4.5 4.8 NA NA NA NA NA -630- MALES MEAN 7.1 9.6 15.4 26.0 34.7 41.8 53.1 FEMALES MEAN 6.6 8.8 13.9 24.4 31.9 38.1 49.4 25770-01 M 25770-02 M 25770-03 M 25770-04 M 25770-05 M 25770-06 F 6.3 8.8 14.7 25.1 32.8 37.5 47.7 6.7 9.5 15.9 28.6 34.9 40.4 51.1 6.7 8.9 16.0 27.3 36.4 41.1 52.0 6.4 8.2 14.1 25.1 32.4 38.0 50.2 7.1 10.0 NA NA NA NA NA 6.6 9.0 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 19 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25770-07 F 6.4 8.2 14.4 24.7 32.0 37.7 49.1 25770-08 F 7.1 9.5 NA NA NA NA NA 25770-09 F 6.5 8.7 15.3 26.2 34.6 40.0 50.1 25770-10 F 6.4 8.0 NA NA NA NA NA 25770-11 F 6.5 8.5 14.6 24.0 32.7 37.8 48.7 25770-12 F 5.8 7.6 NA NA NA NA NA 25770-13 F 6.3 8.7 NA NA NA NA NA 25770-14 F 6.3 8.6 15.2 26.0 34.9 39.9 50.3 MALES MEAN 6.6 9.1 15.2 26.5 34.1 39.3 50.3 FEMALES MEAN 6.4 8.5 14.9 25.2 33.6 38.9 49.6 -631- 25702-03 M 25702-04 M 25702-05 M 25702-06 M 25702-07 M 25702-08 M 25702-09 M 25702-11 M 25702-12 M 25702-13 F 25702-14 F 25702-15 F 25702-16 F 25702-17 F 6.7 9.3 15.9 27.6 38.2 45.5 60.3 7.3 10.0 17.2 28.6 38.3 45.2 60.5 6.6 8.9 NA NA NA NA NA 7.1 10.4 NA NA NA NA NA 7.1 9.5 16.3 26.7 35.8 42.8 53.4 6.6 9.3 NA NA NA NA NA 6.8 9.4 NA NA NA NA NA 6.3 8.3 NA NA NA NA NA 7.2 10.0 17.0 27.6 36.8 44.6 58.3 6.2 8.5 15.1 25.5 34.6 41.3 54.7 6.1 7.4 NA NA NA NA NA 7.0 9.3 15.2 26.6 35.7 43.6 57.3 6.9 9.8 16.5 26.3 35.5 43.2 53.9 6.7 8.9 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 20 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25702-18 F 6.5 8.8 14.6 25.4 34.4 42.0 53.6 MALES MEAN 6.9 9.5 16.6 27.6 37.3 44.5 58.1 FEMALES MEAN 6.6 8.8 15.4 26.0 35.1 42.5 54.9 MALES MEAN S.D. N FEMALES MEAN S.D. N 7.1 0.59 25 6.7 0.56 25 9.6 1.22 25 9.1 1.17 25 15.3 2.02 25 14.6 2.07 25 25.3 2.97 25 24.2 3.23 25 32.9 3.47 25 31.6 3.83 25 40.1 4.39 25 38.5 4.63 25 52.7 6.48 25 50.2 6.56 25 -632- APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 21 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25648-01 M 6.2 8.2 NA NA NA NA NA 25648-02 M 6.6 8.2 NA NA NA NA NA 25648-03 M 6.6 8.6 15.0 23.5 31.1 40.5 51.5 25648-04 M 6.1 8.0 NA NA NA NA NA 25648-05 M 6.1 8.2 NA NA NA NA NA 25648-06 M 6.5 8.1 NA NA NA NA NA 25648-07 M 5.8 7.8 13.5 21.3 27.9 35.9 46.8 25648-08 M 6.5 8.5 14.8 23.1 30.3 39.2 49.6 25648-09 M 6.3 7.7 NA NA NA NA NA 25648-10 M 6.8 8.0 13.8 21.4 28.5 36.1 46.4 25648-11 F 5.9 7.9 12.7 20.4 28.2 36.6 44.8 25648-12 F 6.0 8.1 14.0 22.8 29.8 37.0 46.5 25648-13 F 5.9 7.8 NA NA NA NA NA 25648-14 F 5.6 7.2 12.7 21.1 28.9 37.0 46.0 25648-15 F 6.1 8.0 NA NA NA NA NA 25648-16 F 5.5 7.3 13.3 20.3 27.0 35.1 43.9 25648-17 F 5.8 7.6 NA NA NA NA NA -633- MALES MEAN 6.4 8.1 14.3 22.3 29.5 37.9 48.6 FEMALES MEAN 5.8 7.7 13.2 21.2 28.5 36.4 45.3 25694-01 M 25694-02 M 25694-03 M 25694-04 M 25694-05 M 6.3 9.2 NA NA NA NA NA 6.3 8.6 NA NA NA NA NA 6.1 8.2 13.5 24.3 32.0 41.1 56.5 6.6 9.5 16.1 26.3 34.6 44.0 56.8 6.4 9.5 16.6 27.5 36.0 45.2 60.3 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 22 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25694-06 M 6.9 9.9 NA NA NA NA NA 25694-07 F 6.5 9.6 NA NA NA NA NA 25694-08 F 6.1 9.3 15.1 24.5 32.7 41.5 55.2 25694-09 F 5.9 8.5 13.7 24.3 33.5 41.8 54.6 25694-10 F 5.4 7.9 NA NA NA NA NA 25694-11 M 6.6 9.5 15.7 26.0 35.7 45.7 61.6 25694-12 M 6.4 9.4 NA NA NA NA NA 25694-13 F 5.5 7.7 12.3 21.6 29.2 37.5 48.7 25694-14 F 5.9 8.5 NA NA NA NA NA 25694-15 F 6.2 8.9 15.2 25.6 34.0 42.3 57.9 25694-16 F 5.7 7.8 NA NA NA NA NA 25694-17 F 5.8 8.6 NA NA NA NA NA 25694-18 F 5.4 7.5 NA NA NA NA NA -634- MALES MEAN 6.5 9.2 15.5 26.0 34.6 44.0 58.8 FEMALES MEAN 5.8 8.4 14.1 24.0 32.4 40.8 54.1 25668-03 M 25668-04 M 25668-05 M 25668-06 F 25668-07 F 25668-08 F 25668-09 F 25668-10 F 25668-11 F 6.2 9.2 13.3 21.8 29.9 36.4 48.6 7.1 9.8 14.6 22.3 29.3 37.5 48.7 6.3 9.0 13.3 21.4 29.4 35.1 47.5 6.6 9.3 13.7 21.6 29.5 36.3 45.8 6.1 8.5 12.7 20.8 28.7 35.6 46.3 5.8 8.4 NA NA NA NA NA 6.0 9.3 NA NA NA NA NA 5.5 8.3 12.4 20.0 27.6 33.6 44.2 6.3 9.5 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 23 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25668-12 F 5.6 7.6 10.9 19.0 26.0 33.6 43.4 25668-13 F 5.8 8.9 NA NA NA NA NA 25668-14 F 6.1 9.0 NA NA NA NA NA 25668-15 F 7.1 10.0 NA NA NA NA NA 25668-16 F 5.4 7.5 11.0 19.0 26.9 34.3 44.7 25668-17 F 6.2 9.1 NA NA NA NA NA MALES MEAN 6.5 9.3 13.7 21.8 29.5 36.3 48.3 FEMALES MEAN 6.0 8.8 12.1 20.1 27.7 34.7 44.9 -635- 25631-01 M 25631-02 M 25631-03 M 25631-04 M 25631-05 F 25631-06 F 25631-07 M 25631-08 F 25631-09 F 25631-10 F 25631-11 F 25631-12 F 25631-13 F 25631-14 F 8.0 11.3 NA NA NA NA NA 8.0 12.1 18.4 27.7 37.0 42.9 57.4 7.6 10.6 15.5 25.5 35.3 42.9 55.2 7.7 11.3 17.8 27.2 34.5 42.3 55.2 7.1 10.5 16.5 25.6 33.8 41.0 52.0 7.3 11.3 NA NA NA NA NA 7.6 11.1 17.3 27.7 35.0 44.8 58.1 7.5 10.9 NA NA NA NA NA 6.8 10.2 NA NA NA NA NA 7.0 10.2 15.5 25.6 33.0 42.0 53.9 7.4 11.3 NA NA NA NA NA 7.5 10.5 NA NA NA NA NA 6.8 10.4 16.2 25.6 33.4 41.3 54.4 7.6 11.5 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 24 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25631-15 F 7.2 10.6 16.8 26.0 33.1 40.0 52.6 MALES MEAN FEMALES MEAN 7.8 11.3 17.3 27.0 35.5 43.2 56.5 7.2 10.7 16.3 25.7 33.3 41.1 53.2 25660-01 M 25660-02 M 25660-03 M 25660-04 F 25660-05 M 25660-06 M 25660-07 M 25660-08 M 25660-09 M 25660-10 F 25660-11 F 25660-12 F 25660-13 F 25660-14 F 25660-15 F 7.3 10.2 16.4 25.4 31.6 38.5 52.7 7.8 11.4 18.4 27.9 36.1 42.5 57.8 4.8 7.3 NA NA NA NA NA 7.8 11.4 18.8 28.8 35.1 42.0 57.6 7.8 10.7 NA NA NA NA NA 8.2 11.7 19.1 30.4 38.8 45.9 64.0 7.9 11.5 19.1 29.8 37.9 45.6 63.0 7.6 11.3 NA NA NA NA NA 7.4 10.7 NA NA NA NA NA 7.3 10.8 16.8 26.6 33.9 40.9 53.4 7.4 10.6 NA NA NA NA NA 7.1 10.5 NA NA NA NA NA 7.3 10.4 17.1 26.7 35.0 42.6 57.3 7.7 11.3 17.5 27.9 35.0 41.2 58.5 6.9 10.4 NA NA NA NA NA -636- MALES MEAN FEMALES MEAN 7.4 10.6 18.3 28.4 36.1 43.1 59.4 7.4 10.8 17.6 27.5 34.8 41.7 56.7 25704-01 M 25704-02 M 8.0 11.5 17.8 27.2 34.9 42.9 56.4 7.8 11.1 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 25 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25704-03 M 8.0 11.5 18.2 27.2 32.6 40.7 54.1 25704-04 M 7.9 11.0 17.8 26.7 34.1 41.6 57.2 25704-05 M 8.8 11.8 NA NA NA NA NA 25704-06 M 8.6 12.0 18.7 28.7 35.9 44.8 60.4 25704-07 M 7.6 10.5 NA NA NA NA NA 25704-08 F 7.5 11.0 17.8 26.7 33.6 42.4 54.4 25704-09 F 7.7 11.3 17.8 26.8 32.8 41.2 51.7 25704-10 F 7.5 11.7 NA NA NA NA NA 25704-11 F 7.6 10.8 17.2 26.9 33.9 40.4 53.5 25704-12 F 7.9 10.9 16.5 25.7 31.8 39.3 51.5 25704-13 F 7.6 10.6 NA NA NA NA NA MALES MEAN FEMALES MEAN 8.1 11.3 18.1 27.5 34.4 42.5 57.0 7.6 11.1 17.3 26.5 33.0 40.8 52.8 -637- 25665-01 M 25665-02 M 25665-03 M 25665-04 M 25665-05 F 25665-06 F 25665-07 F 25665-08 F 25665-09 F 25665-10 F 25665-11 F 6.7 10.9 16.1 23.8 29.7 36.0 48.5 6.1 9.4 13.5 20.6 27.6 33.3 44.7 6.9 10.4 15.8 24.4 30.8 36.8 52.5 6.4 9.4 13.3 20.7 26.9 31.7 42.0 6.6 10.0 15.2 24.3 30.5 37.0 51.1 6.7 9.5 14.1 21.4 27.2 32.3 43.8 5.9 8.4 12.8 21.0 26.2 31.9 44.0 6.3 9.0 NA NA NA NA NA 6.8 10.4 NA NA NA NA NA 6.3 9.5 15.0 23.1 32.2 35.1 49.6 5.7 8.4 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 26 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25665-12 F 6.1 9.4 NA NA NA NA NA MALES MEAN FEMALES MEAN 6.5 10.0 14.7 22.4 28.8 34.5 46.9 6.3 9.3 14.3 22.5 29.0 34.1 47.1 25674-01 M 25674-02 M 25674-03 M 25674-04 M 25674-05 M 25674-06 M 25674-07 M 25674-08 M 25674-09 M 25674-10 F 25674-11 F 25674-12 F 25674-13 F 25674-14 F 25674-15 F 25674-16 F 5.8 8.0 NA NA NA NA NA 5.5 7.7 12.6 19.9 25.9 31.7 42.1 5.7 8.1 NA NA NA NA NA 5.9 8.7 14.4 21.7 28.7 35.0 48.4 6.2 7.8 12.1 18.7 25.7 29.4 43.0 5.8 8.7 NA NA NA NA NA 5.9 8.1 13.4 21.3 28.3 34.3 46.6 6.1 8.3 NA NA NA NA NA 6.1 7.9 NA NA NA NA NA 5.9 8.3 NA NA NA NA NA 5.6 8.2 13.6 22.2 27.4 33.9 44.3 5.6 8.3 NA NA NA NA NA 5.8 8.0 13.5 20.9 28.9 34.8 48.5 5.1 6.1 8.8 14.1 20.7 26.4 34.2 6.1 7.9 NA NA NA NA NA 5.8 8.1 13.4 21.4 28.5 35.0 48.3 -638- MALES MEAN 5.9 8.1 13.1 20.4 27.2 32.6 45.0 FEMALES MEAN 5.7 7.8 12.3 19.7 26.4 32.5 43.8 25652-01 M 7.7 12.0 19.2 28.6 38.0 43.7 58.1 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 27 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25652-02 M 7.1 10.6 17.6 25.5 33.6 40.1 51.2 25652-03 M 7.1 11.2 17.7 27.4 35.4 40.5 54.3 25652-04 M 8.2 12.1 19.3 28.5 36.1 42.0 52.1 25652-05 M 7.8 11.1 NA NA NA NA NA 25652-06 M 8.0 11.1 NA NA NA NA NA 25652-07 F 6.9 9.9 NA NA NA NA NA 25652-08 F 7.0 10.4 17.4 26.6 36.1 39.5 51.1 25652-09 F 6.5 9.6 NA NA NA NA NA 25652-10 F 7.3 11.0 17.7 27.1 33.2 40.5 54.0 25652-11 F 7.6 10.6 16.8 25.4 32.2 37.6 48.0 25652-12 F 7.4 11.2 NA NA NA NA NA 25652-13 F 6.4 8.7 14.2 22.5 27.7 35.2 41.6 MALES MEAN FEMALES MEAN 7.7 11.4 18.5 27.5 35.8 41.6 53.9 7.0 10.2 16.5 25.4 32.3 38.2 48.7 -639- 25733-01 M 25733-02 M 25733-03 M 25733-04 M 25733-05 M 25733-06 M 25733-07 M 25733-08 F 25733-09 F 25733-10 F 6.4 9.4 13.6 21.5 28.4 36.5 42.4 6.5 8.5 NA NA NA NA NA 6.6 9.1 13.5 21.5 30.8 36.5 45.3 6.1 7.5 NA NA NA NA NA 6.7 9.4 NA NA NA NA NA 6.9 9.6 13.4 21.5 29.4 37.3 46.5 6.7 9.1 13.7 21.3 26.1 35.6 38.9 6.4 9.4 13.2 22.1 26.4 34.6 41.1 6.9 9.7 NA NA NA NA NA 6.3 8.7 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 28 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25733-11 F 6.5 9.0 13.1 20.4 28.2 35.2 42.4 25733-12 F 6.4 9.1 13.0 21.7 27.8 34.2 42.9 25733-13 F 6.6 8.5 NA NA NA NA NA 25733-14 F 6.5 9.1 NA NA NA NA NA 25733-15 F 6.3 8.0 12.2 20.6 27.4 36.6 45.1 MALES MEAN 6.6 8.9 13.6 21.5 28.7 36.5 43.3 FEMALES MEAN 6.5 8.9 12.9 21.2 27.5 35.2 42.9 25748-01 M 25748-02 M 25748-03 M 25748-04 M 25748-05 M 25748-06 M 25748-07 M 25748-08 F 25748-09 F 25748-10 F 9.0 12.8 18.4 28.4 33.6 41.7 55.9 9.0 13.3 19.0 28.1 35.1 42.0 59.7 8.0 12.1 NA NA NA NA NA 8.3 12.2 18.3 28.5 36.4 43.2 60.5 8.6 12.7 19.1 28.0 37.4 42.9 60.8 8.5 12.8 19.0 28.7 37.1 44.9 62.2 8.9 12.7 NA NA NA NA NA 8.4 12.2 18.2 27.3 32.5 39.7 51.7 8.5 13.0 18.6 28.6 35.8 41.8 58.9 6.7 9.9 14.6 22.8 29.7 36.2 49.7 -640- MALES MEAN FEMALES MEAN 8.6 12.7 18.8 28.3 35.9 42.9 59.8 7.9 11.7 17.1 26.2 32.7 39.2 53.4 25753-01 M 25753-02 M 25753-03 M 7.7 10.0 NA NA NA NA NA 8.3 10.6 17.0 27.1 33.4 40.1 58.6 7.2 9.6 15.5 24.5 31.4 38.3 56.1 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 29 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25753-04 M 7.2 9.6 16.0 26.3 32.6 40.0 55.7 25753-05 M 7.3 9.9 NA NA NA NA NA 25753-06 M 8.3 10.6 16.9 27.6 32.1 39.9 53.3 25753-08 F 7.2 9.9 NA NA NA NA NA 25753-09 F 7.8 10.5 17.0 27.0 34.3 41.1 59.1 25753-10 F 7.9 10.6 NA NA NA NA NA 25753-11 F 6.6 9.6 NA NA NA NA NA 25753-12 F 7.0 10.2 NA NA NA NA NA 25753-13 F 7.4 NA NA NA NA NA NA 25753-14 F 7.3 10.2 NA NA NA NA NA 25753-15 F 7.4 9.4 16.1 25.9 32.5 38.1 49.7 25753-16 F 7.4 10.9 17.4 27.8 35.4 41.5 58.4 25753-17 F 7.6 11.2 18.2 27.7 34.7 42.9 57.0 25753-18 F 6.4 8.3 NA NA NA NA NA -641- MALES MEAN FEMALES MEAN 7.7 10.1 16.4 26.4 32.4 39.6 55.9 7.3 10.1 17.2 27.1 34.2 40.9 56.1 25672-02 M 25672-03 M 25672-04 M 25672-05 M 25672-06 M 25672-07 M 25672-08 M 25672-09 M 7.9 10.6 16.3 26.7 35.1 42.9 58.4 7.5 10.4 NA NA NA NA NA 8.5 11.5 NA NA NA NA NA 7.4 9.8 16.2 26.3 35.0 41.8 52.8 7.2 9.5 15.6 26.2 33.1 41.7 49.2 8.5 11.5 NA NA NA NA NA 8.2 11.7 NA NA NA NA NA 7.5 11.0 16.4 26.8 35.0 43.4 54.2 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 30 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25672-10 F 6.7 8.4 NA NA NA NA NA 25672-11 F 7.7 10.6 17.6 28.3 36.4 44.1 58.6 25672-12 F 6.4 8.7 13.7 23.1 30.7 38.5 49.7 25672-13 F 5.9 8.6 NA NA NA NA NA 25672-14 F 7.2 9.6 NA NA NA NA NA 25672-15 F 7.6 10.3 17.0 27.3 33.2 41.9 51.8 25672-16 F 4.7 5.6 9.0 17.2 24.1 31.2 39.8 25672-17 F 7.2 10.3 NA NA NA NA NA 25672-18 F 7.8 10.4 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.8 10.8 16.1 26.5 34.6 42.5 53.7 6.8 9.2 14.3 24.0 31.1 38.9 50.0 -642- 25655-01 M 25655-02 M 25655-03 M 25655-04 M 25655-05 M 25655-06 M 25655-07 M 25655-08 M 25655-09 M 25655-10 M 25655-11 F 25655-12 F 25655-13 F 6.7 9.0 15.4 23.4 29.2 35.6 44.8 7.3 10.1 NA NA NA NA NA 7.6 10.8 17.6 28.3 34.6 41.7 53.8 7.2 10.5 NA NA NA NA NA 7.1 9.9 NA NA NA NA NA 6.9 9.4 NA NA NA NA NA 6.7 9.5 14.9 24.2 31.9 37.6 50.8 7.4 11.0 NA NA NA NA NA 7.7 11.4 NA NA NA NA NA 7.2 10.5 17.3 29.4 36.6 43.2 58.4 6.8 9.0 15.2 26.6 33.2 41.1 52.4 7.2 10.1 16.2 26.8 34.2 41.5 53.2 6.6 9.3 15.5 26.1 30.8 37.4 47.2 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 31 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25655-14 F 5.7 7.2 NA NA NA NA NA 25655-15 F 7.0 9.8 15.5 27.4 33.3 39.3 51.5 25655-16 F 6.2 8.4 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.2 10.2 16.3 26.3 33.1 39.5 52.0 6.6 9.0 15.6 26.7 32.9 39.8 51.1 -643- 25727-02 M 25727-03 M 25727-04 M 25727-05 M 25727-06 M 25727-07 M 25727-08 M 25727-09 F 25727-10 F 25727-11 F 25727-12 F 25727-13 F 25727-14 F 25727-15 F 25727-16 F 6.4 9.2 13.5 22.1 30.5 38.3 48.5 6.0 7.9 NA NA NA NA NA 6.4 8.7 NA NA NA NA NA 6.5 8.4 12.5 21.0 29.9 39.8 49.2 6.6 8.6 12.7 22.1 29.8 39.1 48.6 6.4 9.1 13.7 23.6 31.1 41.3 49.2 6.7 9.1 NA NA NA NA NA 6.0 7.8 11.9 20.0 27.7 36.5 46.6 6.0 8.1 11.8 21.5 29.0 37.9 47.3 6.0 8.1 NA NA NA NA NA 6.2 7.9 NA NA NA NA NA 6.1 8.7 12.7 22.1 31.3 41.2 51.1 6.5 8.4 NA NA NA NA NA 5.6 7.8 NA NA NA NA NA 5.6 7.8 11.0 18.3 24.3 33.9 38.6 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 32 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25727-17 F 5.6 6.9 NA NA NA NA NA MALES MEAN 6.4 8.7 13.1 22.2 30.3 39.6 48.9 FEMALES MEAN 6.0 7.9 11.9 20.5 28.1 37.4 45.9 25626-01 M 25626-02 M 25626-03 M 25626-04 M 25626-05 M 25626-06 M 25626-07 M 25626-08 F 25626-09 F 25626-10 F 25626-11 F 25626-12 F 25626-13 F 25626-14 F 25626-15 F 25626-16 F 6.0 8.0 14.0 24.6 33.3 41.9 56.8 6.5 9.0 NA NA NA NA NA 6.2 8.6 NA NA NA NA NA 6.1 8.4 14.5 25.8 32.9 42.1 53.0 6.3 8.7 NA NA NA NA NA 5.9 8.2 13.4 23.4 31.3 39.9 51.9 6.6 9.6 16.7 27.8 36.8 46.1 60.7 5.5 7.1 12.7 22.5 30.6 37.8 47.2 5.9 7.7 13.7 24.3 32.3 40.8 49.8 6.0 7.9 NA NA NA NA NA 5.8 7.7 NA NA NA NA NA 5.9 8.1 13.5 24.6 30.7 39.3 50.6 6.3 8.5 NA NA NA NA NA 5.9 8.0 NA NA NA NA NA 5.6 7.9 13.6 24.4 32.7 41.1 52.8 5.3 7.4 NA NA NA NA NA -644- MALES MEAN 6.2 8.6 14.7 25.4 33.6 42.5 55.6 FEMALES MEAN 5.8 7.8 13.4 24.0 31.6 39.8 50.1 25739-01 M 8.1 11.0 17.6 29.3 37.1 47.1 66.0 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 33 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25739-02 M 8.4 11.4 NA NA NA NA NA 25739-03 M 8.5 11.2 NA NA NA NA NA 25739-04 M 8.5 11.0 NA NA NA NA NA 25739-05 M 8.0 10.9 NA NA NA NA NA 25739-06 M 8.5 11.6 19.4 30.6 38.7 48.6 65.0 25739-07 M 8.2 11.7 18.6 30.0 36.5 47.3 59.9 25739-08 M 8.2 11.2 NA NA NA NA NA 25739-09 M 7.9 10.6 17.5 28.7 37.8 46.5 63.2 25739-10 M 8.4 11.2 NA NA NA NA NA 25739-11 F 8.0 10.4 17.6 29.1 38.3 46.9 61.6 25739-12 F 7.2 10.0 16.8 27.8 35.6 47.0 60.9 25739-13 F 7.6 10.4 17.3 28.6 37.8 46.8 60.8 25739-14 F 7.3 10.7 17.7 28.7 37.6 46.6 61.3 -645- MALES MEAN FEMALES MEAN 8.3 11.2 18.3 29.7 37.5 47.4 63.5 7.5 10.4 17.4 28.6 37.3 46.8 61.2 25749-02 M 25749-03 M 25749-04 M 25749-05 M 25749-06 M 25749-07 M 25749-08 F 25749-09 F 25749-10 F 7.4 11.2 16.4 25.5 34.0 39.9 54.3 7.7 11.6 17.7 27.9 36.8 43.3 58.5 7.4 11.0 16.5 26.2 32.9 41.4 51.9 7.4 10.9 NA NA NA NA NA 7.9 11.6 NA NA NA NA NA 7.2 10.3 15.7 25.5 33.2 39.4 52.8 6.9 10.5 16.4 26.0 32.8 39.0 52.0 7.4 10.5 16.2 25.5 33.2 39.7 54.4 7.1 10.7 15.8 25.5 32.9 38.6 52.5 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 34 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25749-11 F 7.2 10.6 16.1 25.0 30.8 37.5 51.0 MALES MEAN FEMALES MEAN 7.5 11.1 16.6 26.3 34.2 41.0 54.4 7.2 10.6 16.1 25.5 32.4 38.7 52.5 25756-01 M 25756-02 M 25756-03 M 25756-04 M 25756-05 M 25756-06 M 25756-07 M 25756-08 F 25756-09 F 25756-10 F 25756-11 F 25756-12 F 25756-13 F 25756-14 F 25756-15 F 25756-16 F 7.2 10.4 16.2 26.4 34.2 41.8 54.5 6.6 6.5 NA NA NA NA NA 7.5 10.2 15.9 26.4 34.0 42.5 61.8 7.2 10.4 15.7 26.3 34.6 42.2 56.2 8.2 11.4 17.9 28.6 36.3 44.0 57.8 7.8 10.8 NA NA NA NA NA 7.0 10.0 NA NA NA NA NA 6.8 10.2 NA NA NA NA NA 7.3 10.7 NA NA NA NA NA 7.7 10.9 NA NA NA NA NA 7.4 10.3 15.4 25.6 34.5 42.3 57.3 6.5 9.3 NA NA NA NA NA 7.0 9.3 15.1 25.2 33.4 41.3 55.5 7.1 10.2 NA NA NA NA NA 7.5 10.8 16.4 26.8 35.1 44.0 58.8 6.8 10.1 15.8 26.4 33.7 41.7 56.9 -646- MALES MEAN FEMALES MEAN 7.4 10.0 16.4 26.9 34.8 42.6 57.6 7.1 10.2 15.7 26.0 34.2 42.3 57.1 25741-01 M 7.7 10.1 17.3 26.5 33.8 41.2 52.7 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 35 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25741-02 M 8.2 11.7 19.7 30.3 38.9 47.4 64.0 25741-03 M 8.0 11.5 19.2 29.5 38.0 45.3 58.8 25741-04 M 7.8 10.9 NA NA NA NA NA 25741-05 M 6.9 9.9 NA NA NA NA NA 25741-06 M 8.2 11.3 NA NA NA NA NA 25741-07 M 8.1 10.3 17.2 28.1 34.7 42.4 56.2 25741-08 F 8.0 11.2 NA NA NA NA NA 25741-09 F 7.8 10.6 18.1 28.6 35.4 42.8 54.6 25741-10 F 6.9 9.5 NA NA NA NA NA 25741-11 F 7.8 11.1 NA NA NA NA NA 25741-12 F 7.2 11.0 NA NA NA NA NA 25741-13 F 6.4 8.8 NA NA NA NA NA 25741-14 F 6.8 9.3 15.7 24.9 33.2 41.4 53.8 25741-15 F 7.7 10.7 18.4 29.2 36.9 45.7 58.5 25741-16 F 7.6 10.5 17.7 28.7 36.1 43.9 56.6 25741-17 F 7.3 9.5 NA NA NA NA NA -647- MALES MEAN FEMALES MEAN 7.8 10.8 18.4 28.6 36.4 44.1 57.9 7.4 10.2 17.5 27.9 35.4 43.5 55.9 25752-01 M 25752-02 M 25752-03 M 25752-04 M 25752-05 M 25752-06 M 7.6 11.2 18.6 30.2 38.1 48.0 64.4 8.1 11.9 NA NA NA NA NA 7.3 10.9 18.0 29.3 38.9 47.6 63.4 8.4 11.8 NA NA NA NA NA 7.4 10.3 16.6 27.1 34.9 43.4 57.8 7.1 NA NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 36 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25752-07 M 7.7 11.4 NA NA NA NA NA 25752-08 M 7.0 10.2 NA NA NA NA NA 25752-09 M 7.6 11.6 19.2 30.6 39.3 48.4 63.3 25752-10 F 7.0 10.5 NA NA NA NA NA 25752-11 F 7.6 10.8 18.4 29.7 39.1 48.5 66.2 25752-12 F 7.5 11.2 NA NA NA NA NA 25752-13 F 7.0 11.2 18.8 31.7 39.6 48.2 61.5 25752-14 F 7.1 10.9 18.5 30.0 39.9 48.5 64.3 25752-15 F 7.2 10.3 17.1 28.2 36.4 45.6 60.3 MALES MEAN FEMALES MEAN 7.6 11.2 18.1 29.3 37.8 46.9 62.2 7.2 10.8 18.2 29.9 38.8 47.7 63.1 -648- 25758-01 M 25758-02 M 25758-03 M 25758-04 M 25758-05 M 25758-06 M 25758-07 F 25758-08 F 25758-09 F 25758-10 F 25758-11 F 25758-12 F 25758-13 F 7.3 10.1 17.1 27.8 35.9 43.7 60.6 6.8 9.9 15.8 26.8 34.8 42.9 57.9 7.3 9.9 NA NA NA NA NA 7.5 10.7 NA NA NA NA NA 8.1 11.4 18.5 29.3 38.3 46.1 62.2 7.4 10.6 16.8 27.7 36.1 44.2 59.7 7.4 10.7 NA NA NA NA NA 7.1 10.0 16.5 28.1 35.8 44.4 59.0 6.6 9.7 16.4 26.9 34.1 41.6 56.6 6.4 9.5 14.4 23.7 31.1 39.4 52.0 7.1 10.9 NA NA NA NA NA 6.2 8.5 12.1 19.3 25.5 31.7 40.2 6.8 9.0 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 37 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25758-14 F 6.8 9.2 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.4 10.4 17.1 27.9 36.3 44.2 60.1 6.8 9.7 14.9 24.5 31.6 39.3 52.0 25719-01 M 25719-02 M 25719-03 M 25719-04 M 25719-05 M 25719-06 M 25719-07 M 25719-08 M 25719-09 M 25719-10 M 25719-11 M 25719-12 M 25719-13 F 25719-14 F 25719-15 F 25719-16 F 6.7 9.7 NA NA NA NA NA 5.5 NA NA NA NA NA NA 6.9 9.7 16.4 27.0 34.3 41.9 55.0 7.1 10.5 17.7 28.5 36.2 42.9 56.6 6.7 9.9 NA NA NA NA NA 7.2 10.3 NA NA NA NA NA 7.6 11.1 19.2 30.2 37.3 44.6 61.5 6.5 9.1 NA NA NA NA NA 6.6 10.1 17.3 28.3 36.6 46.1 62.3 6.6 9.8 NA NA NA NA NA 6.7 9.8 NA NA NA NA NA 6.5 9.6 NA NA NA NA NA 5.8 8.0 14.0 22.9 30.3 38.0 46.9 6.2 8.5 14.5 24.6 31.6 39.2 50.6 6.9 10.2 17.7 28.5 36.5 43.9 58.3 6.2 9.2 NA NA NA NA NA -649- NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 38 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25719-17 F 6.4 9.4 15.7 26.4 33.5 41.3 52.9 MALES MEAN FEMALES MEAN 6.7 10.0 17.7 28.5 36.1 43.9 58.9 6.3 9.1 15.5 25.6 33.0 40.6 52.2 MALES MEAN S.D. N FEMALES MEAN S.D. N 7.2 0.74 23 6.7 0.67 23 10.2 1.19 23 9.6 1.17 23 16.3 1.88 23 15.3 1.97 23 26.0 2.78 23 24.8 2.82 23 33.6 3.11 23 32.1 3.14 23 41.3 3.72 23 39.6 3.66 23 54.7 5.56 23 51.7 5.31 23 -650- APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 39 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606-01 M 7.3 11.1 18.4 26.3 32.2 39.5 51.7 25606-02 M 7.7 10.9 18.8 27.3 33.9 40.9 54.3 25606-03 M 7.2 10.7 18.3 26.9 33.8 40.8 52.9 25606-04 F 7.5 10.7 17.6 25.4 31.8 37.2 50.9 25606-05 F 7.1 10.2 16.7 24.3 30.1 37.3 50.6 25606-06 F 7.2 10.4 NA NA NA NA NA 25606-07 F 7.0 10.3 NA NA NA NA NA 25606-08 F 7.3 11.0 17.8 25.7 31.7 37.0 50.3 25606-09 F 6.7 9.8 NA NA NA NA NA 25606-10 F 6.7 10.0 NA NA NA NA NA 25606-11 F 7.3 10.4 17.4 25.1 30.7 36.7 51.5 25606-12 F 7.4 11.2 18.0 25.3 31.1 36.4 49.4 25606-13 F 7.5 10.8 NA NA NA NA NA 25606-14 F 6.8 9.6 NA NA NA NA NA -651- MALES MEAN FEMALES MEAN 7.4 10.9 18.5 26.8 33.3 40.4 53.0 7.1 10.4 17.5 25.2 31.1 36.9 50.5 25614-01 M 25614-02 M 25614-03 M 25614-04 M 25614-05 M 25614-06 M 25614-07 M 25614-08 M 7.2 9.7 NA NA NA NA NA 6.8 9.3 NA NA NA NA NA 6.6 8.8 NA NA NA NA NA 6.8 8.3 13.7 22.0 29.9 36.7 49.3 6.8 9.8 16.2 24.4 31.6 39.6 55.3 7.0 9.8 NA NA NA NA NA 6.3 8.2 14.0 21.8 29.4 35.0 47.8 6.8 9.5 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 40 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25614-09 M 7.2 9.2 NA NA NA NA NA 25614-10 M 7.1 9.9 16.1 24.5 32.2 38.6 51.7 25614-11 M 7.0 9.1 NA NA NA NA NA 25614-12 M 6.9 8.6 NA NA NA NA NA 25614-13 F 6.2 8.3 13.9 21.4 27.9 34.8 46.9 25614-14 F 6.7 9.0 NA NA NA NA NA 25614-15 F 6.0 7.4 12.2 19.6 26.0 32.1 44.5 25614-16 F 6.7 8.4 NA NA NA NA NA 25614-17 F 5.7 7.2 12.6 20.3 17.2 33.0 42.5 25614-18 F 6.2 7.8 13.4 20.9 27.9 34.3 47.3 MALES MEAN 6.9 9.2 15.0 23.2 30.8 37.5 51.0 FEMALES MEAN 6.3 8.0 13.0 20.6 24.8 33.6 45.3 -652- 25671-01 M 25671-02 M 25671-03 M 25671-04 M 25671-05 M 25671-06 F 25671-07 F 25671-08 F 25671-09 F 25671-10 F 25671-11 F 25671-12 F 6.9 9.5 NA NA NA NA NA 6.4 9.0 15.1 24.8 33.4 42.7 51.7 7.2 9.8 16.2 27.0 36.2 45.8 56.4 6.2 8.7 14.6 24.2 32.9 41.6 49.3 7.0 9.1 14.2 23.8 31.2 39.6 50.4 6.2 8.1 13.9 23.8 31.7 39.9 47.5 6.2 8.8 NA NA NA NA NA 6.4 9.1 15.2 25.1 33.0 41.5 50.8 5.9 8.6 14.2 22.6 29.7 38.0 46.4 6.8 9.4 NA NA NA NA NA 6.4 8.9 NA NA NA NA NA 6.3 8.3 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 41 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25671-13 F 7.0 9.0 13.1 21.7 29.1 37.3 46.1 MALES MEAN 6.7 9.2 15.0 25.0 33.4 42.4 52.0 FEMALES MEAN 6.4 8.8 14.1 23.3 30.9 39.2 47.7 25698-01 M 25698-02 M 25698-03 M 25698-04 F 25698-05 M 25698-06 M 25698-07 F 25698-08 F 25698-09 F 25698-10 F 25698-11 F 25698-12 F 25698-13 F 25698-14 F 25698-15 F 6.5 8.4 NA NA NA NA NA 6.1 7.7 12.4 20.2 28.9 35.3 45.0 6.6 8.2 13.5 20.6 28.8 34.8 45.0 6.3 8.4 13.4 21.5 30.4 36.0 46.4 6.3 8.1 12.7 20.5 28.3 34.3 43.1 6.1 7.2 11.4 17.5 26.2 31.9 41.3 6.1 7.9 NA NA NA NA NA 5.6 6.1 NA NA NA NA NA 5.6 7.4 NA NA NA NA NA 6.0 8.4 13.2 21.8 30.1 36.9 47.2 6.1 8.3 NA NA NA NA NA 6.0 8.2 12.7 20.5 27.8 35.9 42.4 6.1 8.3 NA NA NA NA NA 6.5 8.6 12.7 19.5 27.5 34.0 43.6 5.8 NA NA NA NA NA NA -653- MALES MEAN 6.3 7.9 12.5 19.7 28.1 34.1 43.6 FEMALES MEAN 6.0 8.0 13.0 20.8 29.0 35.7 44.9 25609-01 M 25609-02 M 7.6 11.0 NA NA NA NA NA 7.1 9.4 13.6 20.5 25.9 32.8 42.3 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 42 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25609-03 M 7.4 9.4 14.6 23.6 29.2 37.0 50.8 25609-04 M 7.5 10.6 15.8 24.5 28.8 35.7 47.7 25609-05 M 7.9 10.5 NA NA NA NA NA 25609-06 M 8.6 11.3 16.5 25.8 33.0 40.7 57.0 25609-07 F 7.8 10.8 NA NA NA NA NA 25609-08 F 7.3 10.0 NA NA NA NA NA 25609-09 F 7.7 10.9 NA NA NA NA NA 25609-10 F 7.7 10.8 NA NA NA NA NA 25609-11 F 7.2 10.2 15.9 24.2 28.7 36.1 44.7 25609-12 F 7.9 10.8 17.3 26.6 33.1 40.1 56.5 25609-13 F 7.2 10.5 NA NA NA NA NA 25609-14 F 7.4 10.8 15.4 23.9 30.5 37.3 51.3 25609-15 F 7.7 11.0 17.2 26.5 32.2 39.1 52.1 -654- MALES MEAN FEMALES MEAN 7.7 10.4 15.1 23.6 29.2 36.6 49.5 7.5 10.6 16.5 25.3 31.1 38.2 51.2 25677-01 M 25677-02 M 25677-03 M 25677-04 M 25677-05 M 25677-06 M 25677-07 M 25677-08 F 25677-09 F 7.4 NA NA NA NA NA NA 6.9 10.1 15.6 23.8 33.0 39.7 50.5 6.5 9.9 NA NA NA NA NA 6.6 10.1 15.2 23.6 31.7 40.5 49.0 6.9 10.5 16.4 24.8 32.2 40.4 52.3 6.9 10.2 NA NA NA NA NA 7.2 11.2 16.6 26.3 34.5 42.6 56.8 5.9 9.9 15.4 23.7 31.1 39.5 49.5 6.3 NA NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 43 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25677-10 F 6.3 9.6 14.9 23.6 31.2 38.2 48.9 25677-11 F 6.2 9.1 NA NA NA NA NA 25677-12 F 5.9 8.1 12.8 20.9 29.8 36.7 45.3 25677-13 F 6.8 10.6 16.0 24.4 32.9 39.7 52.0 MALES MEAN FEMALES MEAN 6.9 10.3 16.0 24.6 32.9 40.8 52.2 6.2 9.5 14.8 23.2 31.3 38.5 48.9 -655- 25623-03 M 25623-04 M 25623-05 M 25623-06 M 25623-07 M 25623-08 M 25623-09 M 25623-10 F 25623-11 F 25623-12 F 25623-13 F 25623-14 F 25623-15 F 6.6 9.8 13.4 21.8 29.1 36.0 47.1 6.8 9.9 13.8 23.2 30.3 37.0 49.6 7.3 10.5 14.6 24.8 31.9 39.5 52.2 6.9 10.4 NA NA NA NA NA 6.9 9.7 NA NA NA NA NA 6.9 10.4 14.8 23.3 28.5 36.2 47.8 6.8 9.9 NA NA NA NA NA 6.2 8.9 NA NA NA NA NA 6.6 9.5 NA NA NA NA NA 7.0 7.7 NA NA NA NA NA 6.7 9.8 13.8 23.2 30.2 36.5 50.6 6.6 9.0 12.9 22.2 29.4 36.2 48.8 5.8 8.6 12.1 19.9 25.1 31.6 41.3 MALES MEAN FEMALES MEAN 6.9 10.1 14.2 23.3 30.0 37.2 49.2 6.5 8.9 12.9 21.8 28.2 34.8 46.9 25653-01 M 7.6 10.7 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 44 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25653-02 M 7.6 10.4 16.9 26.9 34.5 42.7 56.0 25653-03 M 7.0 9.6 15.2 25.4 35.0 42.8 58.5 25653-04 M 7.6 10.1 NA NA NA NA NA 25653-05 F 7.7 10.4 15.4 25.3 34.3 42.3 58.6 25653-06 F 7.3 9.9 15.8 25.4 34.2 41.6 55.7 25653-07 M 7.0 9.6 15.7 25.5 33.9 42.9 58.8 25653-08 F 6.1 8.1 NA NA NA NA NA 25653-09 F 7.3 9.9 NA NA NA NA NA 25653-10 F 7.1 8.9 NA NA NA NA NA 25653-11 M 7.6 10.1 15.9 26.2 35.4 44.1 57.9 25653-12 F 7.3 9.5 15.5 25.3 34.7 43.2 55.2 25653-13 F 7.2 9.4 15.0 24.2 30.6 39.0 50.8 25653-14 M 8.3 11.3 NA NA NA NA NA -656- MALES MEAN FEMALES MEAN 7.5 10.3 15.9 26.0 34.7 43.1 57.8 7.1 9.4 15.4 25.1 33.5 41.5 55.1 25604-01 M 25604-02 M 25604-03 M 25604-04 M 25604-05 M 25604-06 M 25604-07 M 25604-08 F 25604-09 F 7.1 11.2 NA NA NA NA NA 6.3 9.1 15.7 24.7 31.5 38.4 50.5 7.3 10.8 18.2 27.6 36.5 43.3 58.9 6.9 11.2 18.1 27.1 35.0 42.7 54.8 6.3 9.5 NA NA NA NA NA 6.7 10.4 17.1 25.5 34.1 40.3 54.7 6.5 10.3 NA NA NA NA NA 6.4 9.9 16.3 24.5 31.7 37.9 51.1 5.7 8.7 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 45 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25604-10 F 6.4 9.8 15.6 24.6 32.5 37.8 48.8 25604-11 F 5.9 9.0 14.8 23.8 31.7 38.6 49.6 25604-12 F 6.4 10.3 17.5 26.2 32.7 40.0 49.4 MALES MEAN FEMALES MEAN 6.7 10.4 17.3 26.2 34.3 41.2 54.7 6.2 9.5 16.1 24.8 32.2 38.6 49.7 25678-01 M 25678-02 M 25678-03 M 25678-04 M 25678-05 M 25678-06 M 25678-07 M 25678-08 F 25678-09 F 25678-10 F 25678-11 F 25678-12 F 25678-13 F 25678-14 F 6.1 8.8 NA NA NA NA NA 5.5 7.9 13.9 23.4 30.6 37.7 49.0 6.2 9.4 17.0 27.1 35.0 42.3 54.5 6.3 9.2 NA NA NA NA NA 6.6 9.0 NA NA NA NA NA 6.3 9.1 15.8 26.8 33.8 41.2 53.9 5.8 8.3 15.1 25.3 32.9 40.2 53.2 6.5 9.5 16.9 26.1 34.0 41.7 56.3 6.2 9.0 NA NA NA NA NA 5.9 8.5 15.3 24.5 33.2 39.9 52.7 6.1 8.6 15.3 24.5 32.0 37.8 48.7 6.2 8.8 NA NA NA NA NA 5.5 7.6 12.9 22.5 29.6 37.0 49.1 6.2 9.2 NA NA NA NA NA -657- NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 46 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25678-15 F 4.6 7.0 NA NA NA NA NA MALES MEAN 6.1 8.8 15.5 25.7 33.1 40.4 52.7 FEMALES MEAN 5.9 8.5 15.1 24.4 32.2 39.1 51.7 25684-02 M 25684-03 M 25684-04 M 25684-05 M 25684-06 F 25684-07 F 25684-08 F 25684-09 F 25684-10 F 25684-11 F 25684-12 F 8.0 11.5 18.6 28.5 36.9 43.3 59.5 7.3 10.6 16.0 25.3 33.5 39.1 54.6 7.3 10.2 15.4 24.2 30.5 37.0 50.1 7.7 10.6 16.4 26.2 35.3 43.3 59.2 7.3 11.0 17.1 25.8 31.8 39.5 55.2 6.8 9.7 NA NA NA NA NA 6.9 9.5 14.1 22.4 30.3 37.6 52.7 6.1 8.9 NA NA NA NA NA 7.1 10.2 NA NA NA NA NA 6.5 9.5 13.9 21.7 29.2 35.8 47.4 7.4 10.4 15.9 24.8 31.8 38.9 53.6 -658- MALES MEAN FEMALES MEAN 7.6 10.7 16.6 26.1 34.1 40.7 55.9 6.9 9.9 15.3 23.7 30.8 38.0 52.2 25714-01 M 25714-02 M 25714-03 M 25714-04 M 25714-05 M 25714-06 M 8.1 11.4 NA NA NA NA NA 7.7 11.0 17.5 28.1 33.3 42.6 55.8 7.7 11.4 17.8 29.2 36.5 44.4 61.8 8.2 11.1 NA NA NA NA NA 7.9 11.4 18.2 27.7 35.3 43.3 57.4 7.8 10.8 17.0 27.1 34.6 42.7 60.1 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 47 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25714-07 F 7.6 10.8 NA NA NA NA NA 25714-08 F 7.5 11.0 17.5 25.6 32.6 38.5 55.6 25714-09 F 7.5 10.6 17.0 26.4 33.6 40.8 56.8 25714-10 F 7.2 10.4 16.5 26.8 33.4 40.5 56.4 25714-11 F 7.6 10.6 NA NA NA NA NA 25714-12 F 7.4 10.4 NA NA NA NA NA 25714-13 F 7.2 10.8 17.2 27.4 33.4 41.4 54.4 MALES MEAN FEMALES MEAN 7.9 11.2 17.6 28.0 34.9 43.3 58.8 7.4 10.7 17.1 26.6 33.3 40.3 55.8 -659- 25650-01 F 25650-02 M 25650-03 M 25650-04 M 25650-05 M 25650-06 M 25650-07 M 25650-08 M 25650-09 M 25650-10 M 25650-11 M 25650-12 M 25650-13 M 25650-14 F 25650-15 F 4.1 5.2 8.4 15.3 21.8 29.4 37.9 7.4 9.7 15.3 25.5 33.3 41.6 57.2 7.3 10.0 NA NA NA NA NA 6.8 9.3 NA NA NA NA NA 6.0 7.2 NA NA NA NA NA 7.1 9.5 NA NA NA NA NA 7.5 9.7 NA NA NA NA NA 6.7 10.4 16.9 28.0 36.4 45.7 58.2 7.1 9.5 NA NA NA NA NA 7.9 10.1 NA NA NA NA NA 6.8 9.3 15.2 25.7 32.2 41.7 54.8 7.7 10.7 NA NA NA NA NA 6.7 9.3 14.2 25.2 32.7 41.9 53.8 7.3 10.4 16.4 26.7 34.3 43.0 58.7 7.1 9.8 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 48 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25650-16 F 7.3 9.6 NA NA NA NA NA 25650-17 F 6.7 9.2 14.7 26.5 33.4 42.4 52.8 25650-18 F 7.0 9.3 NA NA NA NA NA 25650-19 F 6.4 8.6 13.5 23.8 30.9 39.3 51.6 MALES MEAN 7.1 9.6 15.4 26.1 33.7 42.7 56.0 FEMALES MEAN 6.6 8.9 13.3 23.1 30.1 38.5 50.3 -660- 25735-01 M 25735-02 M 25735-03 M 25735-04 M 25735-05 M 25735-06 M 25735-07 F 25735-08 F 25735-09 F 25735-10 F 25735-11 F 25735-12 F 25735-13 F 7.9 11.5 17.0 27.5 37.6 43.5 59.2 7.3 10.4 NA NA NA NA NA 7.6 11.2 NA NA NA NA NA 7.6 11.5 18.0 29.1 39.0 45.8 60.6 7.8 11.4 18.4 29.3 36.6 43.6 55.2 7.9 11.5 18.9 30.4 40.6 48.9 64.6 7.3 11.0 17.2 27.9 37.0 42.8 58.0 6.6 9.9 15.6 26.1 32.4 38.7 47.4 6.9 10.2 NA NA NA NA NA 7.6 11.5 17.9 28.6 38.1 44.9 58.0 7.1 10.6 NA NA NA NA NA 7.2 10.4 NA NA NA NA NA 6.9 10.5 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 49 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25735-14 F 7.0 10.4 16.3 26.8 36.1 43.2 57.9 MALES MEAN FEMALES MEAN 7.7 11.3 18.1 29.1 38.5 45.5 59.9 7.1 10.6 16.8 27.4 35.9 42.4 55.3 25722-01 M 25722-02 M 25722-03 M 25722-04 M 25722-05 M 25722-06 M 25722-07 M 25722-08 M 25722-09 M 25722-10 M 25722-11 F 25722-12 F 25722-13 F 25722-14 F 25722-15 F 6.6 8.1 13.2 22.1 27.9 33.8 44.6 6.3 9.0 NA NA NA NA NA 6.5 9.4 NA NA NA NA NA 6.4 8.1 12.6 20.6 30.0 35.1 47.2 6.3 8.3 13.5 21.8 29.2 34.7 47.6 6.6 8.6 NA NA NA NA NA 6.5 8.8 NA NA NA NA NA 6.7 8.8 NA NA NA NA NA 6.9 9.6 NA NA NA NA NA 6.2 9.2 13.3 22.3 30.6 35.7 47.8 6.8 9.5 14.9 23.5 31.5 37.1 47.8 6.6 9.5 14.8 23.7 31.8 37.5 49.5 6.9 9.6 14.6 23.2 31.5 36.5 52.3 6.5 9.5 NA NA NA NA NA 6.6 8.9 14.1 24.3 29.2 36.3 45.7 -661- MALES MEAN 6.5 8.8 13.2 21.7 29.4 34.8 46.8 FEMALES MEAN 6.7 9.4 14.6 23.7 31.0 36.9 48.8 25642-01 M 25642-02 M 7.8 10.3 NA NA NA NA NA 7.4 10.3 17.3 27.3 36.6 46.7 59.7 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 50 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25642-03 M 7.5 9.8 NA NA NA NA NA 25642-04 M 8.1 11.0 18.4 29.6 37.9 46.3 62.8 25642-05 M 7.8 10.7 16.9 27.8 34.1 42.8 54.6 25642-06 M 8.1 11.2 NA NA NA NA NA 25642-07 M 6.7 8.7 NA NA NA NA NA 25642-08 M 8.7 11.6 18.6 28.9 36.1 43.8 63.1 25642-09 F 6.9 8.9 NA NA NA NA NA 25642-10 F 6.9 9.2 NA NA NA NA NA 25642-11 F 7.4 10.0 NA NA NA NA NA 25642-12 F 7.5 10.2 16.7 27.7 33.3 41.8 52.8 25642-13 F 7.6 10.1 16.4 27.3 33.9 41.4 54.2 25642-14 F 7.7 10.2 NA NA NA NA NA 25642-15 F 7.2 10.5 16.9 27.3 35.4 42.7 56.5 -662- MALES MEAN FEMALES MEAN 7.8 10.5 17.8 28.4 36.2 44.9 60.1 7.3 9.9 16.7 27.4 34.2 42.0 54.5 25628-01 M 25628-02 M 25628-03 M 25628-04 M 25628-05 M 25628-06 M 25628-07 M 25628-08 M 25628-09 M 5.8 8.6 13.6 23.1 30.8 38.6 51.6 6.4 8.8 NA NA NA NA NA 6.5 8.7 NA NA NA NA NA 5.9 8.4 NA NA NA NA NA 6.7 9.3 14.3 24.9 33.5 41.7 54.7 5.5 NA NA NA NA NA NA 5.7 8.2 13.0 23.5 30.3 38.1 49.8 6.0 8.5 NA NA NA NA NA 6.3 8.7 13.8 24.3 32.3 40.1 52.6 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 51 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25628-10 F 5.6 7.6 NA NA NA NA NA 25628-11 F 6.0 8.3 NA NA NA NA NA 25628-12 F 5.6 8.3 NA NA NA NA NA 25628-13 F 5.7 8.5 NA NA NA NA NA 25628-14 F 6.6 8.4 13.8 23.9 33.1 40.4 52.6 25628-15 F 6.4 9.2 14.9 24.2 32.8 42.3 55.4 25628-16 F 5.7 8.1 12.6 22.1 30.7 38.2 50.9 25628-17 F 5.5 6.2 9.4 18.3 24.0 31.7 40.3 MALES MEAN 6.1 8.7 13.7 24.0 31.7 39.6 52.2 FEMALES MEAN 5.9 8.1 12.7 22.1 30.2 38.2 49.8 -663- 25763-01 M 25763-02 M 25763-03 M 25763-04 M 25763-05 M 25763-06 M 25763-07 M 25763-08 M 25763-09 F 25763-10 F 25763-11 F 25763-12 F 25763-13 F 25763-14 F 6.2 7.9 NA NA NA NA NA 6.3 9.0 14.7 26.7 35.1 45.0 52.8 5.9 7.6 NA NA NA NA NA 6.4 8.1 13.5 24.6 33.3 42.1 50.4 6.7 9.3 NA NA NA NA NA 6.8 8.8 NA NA NA NA NA 6.4 8.3 13.0 24.5 33.1 43.3 51.5 6.6 7.7 NA NA NA NA NA 6.5 8.8 14.2 25.8 33.5 42.3 53.1 6.5 8.4 14.0 25.1 33.2 42.3 51.4 5.5 6.9 NA NA NA NA NA 5.7 8.1 NA NA NA NA NA 6.1 7.3 NA NA NA NA NA 5.8 7.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 52 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25763-15 F 6.4 7.8 13.4 25.1 33.5 42.8 54.3 25763-16 F 5.3 7.5 NA NA NA NA NA 25763-17 F 5.8 7.5 NA NA NA NA NA 25763-18 F 6.2 8.2 NA NA NA NA NA 25763-19 F 6.4 7.7 NA NA NA NA NA MALES MEAN 6.4 8.3 13.7 25.3 33.8 43.5 51.6 FEMALES MEAN 6.0 7.8 13.9 25.3 33.4 42.5 52.9 -664- 25766-01 M 25766-02 M 25766-03 M 25766-04 M 25766-05 F 25766-06 F 25766-07 F 25766-08 F 25766-09 F 25766-10 M 25766-11 M 6.9 9.6 13.1 21.7 26.5 32.7 38.9 7.2 10.1 14.7 23.3 29.1 33.6 44.9 7.0 9.3 13.8 22.7 27.7 33.6 44.8 6.8 NA NA NA NA NA NA 7.1 10.0 NA NA NA NA NA 6.3 8.6 12.7 20.6 25.0 30.3 37.2 6.5 9.4 13.6 23.0 28.5 34.7 46.2 6.7 9.3 13.9 22.0 26.7 32.5 43.4 6.4 8.7 12.6 20.1 24.8 30.9 41.4 6.9 9.5 NA NA NA NA NA 6.7 9.8 13.8 21.6 26.4 31.8 42.2 MALES MEAN 6.9 9.7 13.9 22.3 27.4 32.9 42.7 FEMALES MEAN 6.6 9.2 13.2 21.4 26.3 32.1 42.1 25689-01 M 25689-02 M 8.3 11.0 NA NA NA NA NA 7.4 10.6 17.5 28.5 37.0 45.1 62.8 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 53 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25689-03 M 7.9 10.9 17.7 29.8 37.0 44.3 64.0 25689-04 M 7.6 10.3 16.4 27.9 36.3 44.6 63.2 25689-05 M 7.7 10.7 NA NA NA NA NA 25689-06 M 7.6 10.8 16.3 28.4 37.1 45.1 60.6 25689-07 F 7.6 10.0 16.1 27.5 34.8 43.4 58.8 25689-08 F 7.4 9.4 NA NA NA NA NA 25689-09 F 7.4 10.3 NA NA NA NA NA 25689-10 F 7.7 11.6 NA NA NA NA NA 25689-11 F 7.7 10.6 NA NA NA NA NA 25689-12 F 7.2 10.4 16.6 28.3 37.6 45.9 62.5 25689-13 F 7.5 10.4 16.5 26.9 34.9 42.3 59.4 25689-14 F 7.4 9.6 15.4 26.8 34.8 42.8 55.5 25689-15 F 7.0 9.8 NA NA NA NA NA -665- MALES MEAN FEMALES MEAN 7.8 10.7 17.0 28.7 36.9 44.8 62.7 7.4 10.2 16.2 27.4 35.5 43.6 59.1 25708-01 M 25708-02 M 25708-03 M 25708-04 M 25708-05 M 25708-06 M 25708-07 M 25708-08 M 25708-09 M 7.3 10.8 17.7 28.6 36.8 44.5 56.0 7.5 10.6 NA NA NA NA NA 7.6 10.9 NA NA NA NA NA 7.8 11.4 17.6 27.5 35.0 42.4 57.6 7.7 10.3 NA NA NA NA NA 7.1 10.6 NA NA NA NA NA 7.1 10.7 15.4 26.9 35.6 43.7 56.1 7.5 11.1 NA NA NA NA NA 6.8 9.7 15.0 25.2 33.1 41.0 55.5 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 54 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25708-10 F 6.8 8.8 NA NA NA NA NA 25708-11 F 7.0 9.8 14.8 26.3 34.0 41.4 52.2 25708-12 F 5.9 8.1 12.0 21.3 28.0 35.7 46.3 25708-13 F 7.1 9.6 NA NA NA NA NA 25708-14 F 6.7 9.6 14.9 24.4 32.0 40.1 52.9 25708-15 F 6.6 9.1 14.6 25.0 31.1 38.5 49.4 MALES MEAN FEMALES MEAN 7.4 10.7 16.4 27.1 35.1 42.9 56.3 6.7 9.2 14.1 24.3 31.3 38.9 50.2 -666- 25743-01 M 25743-02 M 25743-03 M 25743-04 M 25743-05 M 25743-06 M 25743-07 M 25743-08 M 25743-09 M 25743-10 M 25743-11 F 25743-12 F 25743-13 F 25743-14 F 25743-15 F 25743-16 F 6.1 8.3 NA NA NA NA NA 6.4 9.0 14.8 24.8 33.3 39.3 53.0 6.3 8.7 NA NA NA NA NA 5.3 7.0 11.9 21.5 28.7 34.9 45.8 6.2 8.3 NA NA NA NA NA 5.7 7.5 NA NA NA NA NA 6.1 NA NA NA NA NA NA 5.3 7.4 12.6 21.6 30.3 34.8 45.5 6.4 8.5 15.5 26.3 34.3 41.4 56.3 6.5 8.9 NA NA NA NA NA 5.7 8.0 12.9 21.9 29.5 36.2 47.1 5.1 7.3 11.8 20.2 27.7 34.4 45.2 6.3 9.0 NA NA NA NA NA 5.5 8.2 NA NA NA NA NA 6.0 8.2 NA NA NA NA NA 5.2 7.0 11.8 20.9 27.8 34.6 42.8 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 55 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25743-17 F 5.9 8.1 NA NA NA NA NA 25743-18 F 5.5 7.6 13.2 23.0 28.9 37.3 50.6 MALES MEAN 6.0 8.2 13.7 23.6 31.7 37.6 50.2 FEMALES MEAN 5.7 7.9 12.4 21.5 28.5 35.6 46.4 25761-01 M 25761-02 M 25761-03 M 25761-04 M 25761-05 M 25761-06 M 25761-07 M 25761-08 F 25761-09 F 25761-10 F 25761-11 F 25761-12 F 25761-13 F 25761-14 F 25761-15 F 7.8 10.4 NA NA NA NA NA 7.5 10.7 NA NA NA NA NA 8.5 11.2 NA NA NA NA NA 7.7 10.3 16.7 28.3 36.4 45.1 58.6 7.4 10.2 16.3 28.4 36.6 44.5 57.6 7.6 11.0 17.7 29.1 37.3 46.7 60.1 7.8 11.2 18.2 30.0 39.0 48.9 65.5 7.0 9.6 15.8 27.9 36.6 44.4 59.7 7.3 9.5 15.8 27.8 36.5 46.0 57.6 8.0 11.0 NA NA NA NA NA 7.5 10.5 NA NA NA NA NA 7.1 10.2 NA NA NA NA NA 7.5 10.4 16.2 28.3 36.6 44.7 52.2 7.3 10.1 NA NA NA NA NA 7.1 10.2 16.2 27.3 36.0 44.3 57.4 -667- MALES MEAN FEMALES MEAN 7.8 10.7 17.2 29.0 37.3 46.3 60.5 7.4 10.2 16.0 27.8 36.4 44.9 56.7 25712-02 M 6.2 9.4 15.9 26.0 34.2 43.1 55.2 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 56 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25712-03 M 7.1 9.3 15.4 25.1 32.3 40.9 55.9 25712-04 M 6.8 10.1 NA NA NA NA NA 25712-05 M 7.1 9.7 15.7 25.7 33.5 41.3 56.4 25712-06 M 7.5 10.9 18.4 29.6 37.3 46.8 61.9 25712-07 F 7.2 10.5 16.8 27.2 34.2 42.4 50.8 25712-08 F 6.3 9.2 14.5 22.9 30.7 39.2 51.8 25712-09 F 7.5 10.9 NA NA NA NA NA 25712-10 F 7.0 10.3 NA NA NA NA NA 25712-11 F 7.0 9.3 NA NA NA NA NA 25712-12 F 7.3 9.9 NA NA NA NA NA 25712-13 F 7.8 11.2 NA NA NA NA NA 25712-14 F 6.7 9.6 NA NA NA NA NA 25712-15 F 7.5 9.9 NA NA NA NA NA 25712-16 F 6.9 9.9 16.4 26.6 33.8 42.8 56.8 25712-17 F 7.7 10.2 17.3 26.6 34.3 42.6 56.3 -668- MALES MEAN FEMALES MEAN 6.9 9.9 16.4 26.6 34.3 43.0 57.4 7.2 10.1 16.3 25.8 33.3 41.8 53.9 25746-01 M 25746-02 M 25746-03 M 25746-04 M 25746-05 M 25746-06 M 25746-07 M 7.0 9.8 NA NA NA NA NA 7.3 NA NA NA NA NA NA 7.3 9.3 15.7 26.7 36.1 44.9 64.1 7.0 9.5 NA NA NA NA NA 6.8 9.1 NA NA NA NA NA 7.2 10.0 16.7 26.4 35.1 44.1 61.5 7.3 10.9 17.5 27.7 37.1 45.7 64.2 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 57 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25746-08 M 7.2 9.7 NA NA NA NA NA 25746-09 M 6.9 9.7 NA NA NA NA NA 25746-10 M 7.2 10.5 NA NA NA NA NA 25746-11 M 7.5 10.2 16.6 27.5 36.9 45.8 60.6 25746-12 F 6.5 9.3 15.2 25.2 33.6 41.8 54.7 25746-13 F 6.7 9.3 NA NA NA NA NA 25746-14 F 5.8 8.0 13.5 22.3 31.4 40.8 107.7 25746-15 F 6.4 9.0 15.2 25.3 34.4 42.7 71.7 25746-16 F 6.8 9.4 NA NA NA NA NA 25746-17 F 7.6 10.4 17.0 28.0 37.0 46.2 62.6 25746-18 F 6.5 8.8 NA NA NA NA NA MALES MEAN 7.2 9.9 16.6 27.1 36.3 45.1 62.6 FEMALES MEAN 6.6 9.2 15.2 25.2 34.1 42.9 74.2 -669- MALES MEAN S.D. N 7.0 0.60 25 FEMALES MEAN S.D. N 6.7 0.55 25 NA = NOT APPLICABLE 9.9 0.97 25 9.3 0.91 25 15.7 1.66 25 14.9 1.55 25 25.5 2.40 25 24.3 2.15 25 33.2 2.89 25 31.5 2.83 25 40.9 3.73 25 39.0 3.22 25 54.0 5.40 25 51.8 6.18 25 APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 58 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696-01 M 8.2 11.1 NA NA NA NA NA 25696-02 M 7.1 9.7 NA NA NA NA NA 25696-03 M 7.5 9.8 NA NA NA NA NA 25696-04 M 7.9 11.0 16.7 25.5 31.5 38.3 52.2 25696-05 M 8.2 11.2 NA NA NA NA NA 25696-06 M 7.8 10.0 15.0 21.8 29.2 35.6 48.2 25696-07 M 7.6 10.6 15.5 24.4 31.5 38.1 52.4 25696-08 M 8.0 10.9 NA NA NA NA NA 25696-09 M 7.5 9.9 15.0 22.6 30.2 35.6 49.3 25696-10 M 8.3 10.2 NA NA NA NA NA 25696-11 F 6.9 9.8 16.2 24.4 30.9 37.8 49.5 25696-12 F 7.1 9.0 NA NA NA NA NA 25696-13 F 7.2 10.1 16.6 24.5 31.3 37.8 52.2 25696-14 F 7.5 10.1 15.2 23.1 30.1 36.3 49.4 25696-15 F 7.3 9.9 NA NA NA NA NA 25696-16 F 7.1 9.7 15.6 24.4 32.4 38.9 53.0 -670- MALES MEAN FEMALES MEAN 7.8 10.4 15.6 23.6 30.6 36.9 50.5 7.2 9.8 15.9 24.1 31.2 37.7 51.0 25686-01 M 25686-02 M 25686-03 M 25686-04 M 25686-05 M 25686-06 M 7.0 10.1 16.3 25.6 33.1 38.1 49.8 6.5 8.9 14.8 22.9 29.8 35.6 46.5 6.5 9.3 15.0 24.5 32.1 36.8 50.1 6.6 9.4 15.6 23.6 29.5 34.7 46.6 6.5 8.9 NA NA NA NA NA 6.1 8.3 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 59 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25686-07 M 6.3 8.9 NA NA NA NA NA 25686-08 M 6.3 8.6 NA NA NA NA NA 25686-09 F 6.0 8.7 14.4 22.8 29.9 35.1 47.1 25686-10 F 5.6 7.8 12.7 20.7 27.0 32.1 41.7 25686-11 F 6.6 9.0 15.5 23.9 31.0 36.3 48.1 25686-12 F 6.3 8.4 NA NA NA NA NA 25686-13 F 5.7 8.2 NA NA NA NA NA 25686-14 F 5.8 8.2 NA NA NA NA NA 25686-15 F 6.0 7.9 12.6 20.1 26.5 32.1 43.2 MALES MEAN 6.5 9.1 15.4 24.2 31.1 36.3 48.3 FEMALES MEAN 6.0 8.3 13.8 21.9 28.6 33.9 45.0 -671- 25639-01 M 25639-02 M 25639-03 M 25639-04 F 25639-05 M 25639-06 M 25639-07 M 25639-08 M 25639-09 M 25639-10 F 25639-11 F 25639-12 F 25639-13 F 7.5 10.7 NA NA NA NA NA 7.0 9.5 NA NA NA NA NA 7.4 9.5 16.3 26.0 34.6 42.1 52.8 7.0 10.0 17.6 27.3 35.3 43.0 53.4 7.0 10.6 16.0 24.6 33.4 41.1 51.9 7.6 10.6 17.8 26.6 34.7 41.4 51.1 7.6 11.3 NA NA NA NA NA 7.8 10.6 NA NA NA NA NA 7.1 10.5 18.1 28.1 36.5 43.8 55.9 5.4 7.1 NA NA NA NA NA 7.1 9.4 16.6 24.1 34.4 41.3 53.3 6.5 9.6 15.9 24.8 33.7 40.3 52.5 6.6 8.7 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 60 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25639-14 F 7.3 10.2 16.1 26.0 34.8 40.9 52.3 25639-15 F 5.6 7.3 NA NA NA NA NA 25639-16 F 6.8 9.8 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.4 10.4 17.1 26.3 34.8 42.1 52.9 6.5 9.0 16.6 25.6 34.6 41.4 52.9 25658-03 M 25658-04 M 25658-05 M 25658-06 M 25658-07 M 25658-08 M 25658-09 M 25658-10 F 25658-11 F 25658-12 F 25658-13 F 25658-14 F 25658-15 F 7.6 8.5 13.6 22.0 29.7 38.2 49.1 7.5 8.8 13.1 20.6 28.5 36.2 45.3 7.0 8.5 13.2 21.0 29.3 36.8 47.0 7.6 8.8 NA NA NA NA NA 6.9 8.1 NA NA NA NA NA 7.6 9.6 14.7 23.2 29.8 37.8 46.0 7.0 8.1 NA NA NA NA NA 7.4 8.8 14.6 22.5 30.4 36.7 47.7 7.0 8.8 NA NA NA NA NA 7.6 8.8 NA NA NA NA NA 6.7 8.0 13.0 20.6 28.8 36.5 46.9 7.2 8.3 13.1 21.2 27.8 35.4 42.7 6.7 8.3 12.9 20.4 28.1 36.2 45.7 -672- MALES MEAN 7.3 8.6 13.7 21.7 29.3 37.3 46.9 FEMALES MEAN 7.1 8.5 13.4 21.2 28.8 36.2 45.8 25676-02 M 25676-03 M 8.3 11.4 18.7 26.8 31.8 37.0 53.6 8.6 11.5 19.1 28.1 35.6 42.7 59.9 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 61 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25676-04 M 7.7 10.4 17.9 25.8 32.8 38.1 55.4 25676-05 M 7.5 10.3 NA NA NA NA NA 25676-06 M 8.6 11.5 19.2 27.8 35.7 42.2 58.4 25676-07 M 8.1 10.8 NA NA NA NA NA 25676-08 F 7.7 10.0 17.1 25.9 32.3 38.7 53.9 25676-09 F 8.0 10.8 18.3 26.3 33.3 38.7 54.8 25676-10 F 7.3 9.5 NA NA NA NA NA 25676-11 F 7.7 9.6 NA NA NA NA NA 25676-12 F 8.2 10.8 18.5 27.2 34.8 40.5 54.5 25676-13 F 7.2 9.6 NA NA NA NA NA 25676-14 F 7.8 10.3 NA NA NA NA NA 25676-15 F 8.1 10.5 18.0 25.7 32.5 38.0 51.6 MALES MEAN FEMALES MEAN 8.1 11.0 18.7 27.1 34.0 40.0 56.8 7.8 10.1 18.0 26.3 33.2 39.0 53.7 -673- 25600-01 M 25600-02 M 25600-03 M 25600-04 M 25600-05 F 25600-06 F 25600-07 F 25600-08 F 25600-09 F 25600-10 F 7.2 10.1 17.1 26.6 34.9 43.3 58.9 7.3 11.1 17.6 26.4 35.1 43.5 57.7 7.7 10.6 17.0 26.4 36.0 44.8 59.0 7.2 10.4 16.8 27.2 34.9 43.0 57.3 6.7 9.9 16.2 25.2 33.2 41.6 54.9 6.5 9.6 NA NA NA NA NA 6.9 10.5 NA NA NA NA NA 7.0 10.0 NA NA NA NA NA 6.8 9.4 NA NA NA NA NA 7.2 10.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 62 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25600-11 F 7.2 11.0 18.3 28.8 36.7 44.5 62.1 25600-12 F 6.7 10.4 17.0 27.4 35.3 43.9 58.0 25600-13 F 7.2 10.8 NA NA NA NA NA 25600-14 F 7.1 9.6 NA NA NA NA NA 25600-15 F 7.1 11.0 18.7 28.1 35.9 44.7 58.7 25600-16 F 7.0 9.4 NA NA NA NA NA 25600-17 F 7.0 11.0 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.4 10.6 17.1 26.7 35.2 43.7 58.2 7.0 10.2 17.6 27.4 35.3 43.7 58.4 -674- 25603-01 M 25603-02 M 25603-03 M 25603-04 M 25603-05 M 25603-06 F 25603-07 F 25603-08 F 25603-09 F 25603-10 F 25603-11 F 25603-12 F 25603-13 F 25603-14 F 7.2 10.2 16.1 24.2 31.5 37.8 55.7 6.4 8.1 13.9 21.4 28.2 34.0 49.8 7.0 9.9 NA NA NA NA NA 7.1 10.7 16.7 24.6 30.1 36.6 51.2 6.7 9.3 15.5 24.0 30.9 37.3 55.6 6.6 9.6 15.4 23.4 29.7 35.4 53.6 6.2 9.2 14.7 22.0 28.4 33.5 49.6 6.8 8.6 NA NA NA NA NA 6.2 8.2 NA NA NA NA NA 6.9 10.1 15.7 24.3 29.1 36.3 51.8 6.3 8.2 NA NA NA NA NA 6.8 9.5 15.5 24.7 30.6 36.6 52.8 7.0 10.2 NA NA NA NA NA 6.9 10.1 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 63 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25603-15 F 6.9 10.0 NA NA NA NA NA MALES MEAN 6.9 9.6 15.6 23.6 30.2 36.4 53.1 FEMALES MEAN 6.7 9.4 15.3 23.6 29.5 35.5 52.0 25630-01 M 25630-02 M 25630-03 M 25630-04 M 25630-05 M 25630-06 M 25630-07 M 25630-08 F 25630-09 F 25630-10 F 25630-11 F 25630-12 F 25630-13 F 25630-14 F 6.4 9.4 15.4 24.6 32.6 41.0 53.9 6.4 9.8 NA NA NA NA NA 6.7 9.4 NA NA NA NA NA 6.7 10.4 16.6 25.6 33.2 42.8 54.0 6.3 9.5 15.5 24.1 32.3 41.8 53.8 6.6 9.7 15.9 25.1 33.5 43.7 54.2 6.3 9.8 NA NA NA NA NA 6.3 9.3 NA NA NA NA NA 6.3 9.0 14.6 23.2 31.0 38.6 47.4 6.1 9.0 14.6 22.1 30.9 38.7 50.3 6.2 9.4 15.8 24.9 33.0 41.8 53.7 6.1 8.9 NA NA NA NA NA 5.9 9.0 14.8 23.5 31.9 39.2 50.8 6.9 10.4 NA NA NA NA NA -675- MALES MEAN 6.5 9.7 15.9 24.9 32.9 42.3 54.0 FEMALES MEAN 6.3 9.3 15.0 23.4 31.7 39.6 50.6 25703-01 M 25703-02 M 25703-03 M 7.4 9.7 NA NA NA NA NA 7.5 10.7 18.6 28.7 36.7 44.4 58.3 7.5 10.2 17.6 27.4 34.1 42.0 54.7 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 64 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25703-04 M 7.7 10.7 18.5 29.3 37.3 44.7 61.7 25703-05 M 7.3 9.7 17.2 26.4 34.6 43.6 59.6 25703-06 F 7.6 10.0 NA NA NA NA NA 25703-07 F 6.8 9.0 NA NA NA NA NA 25703-08 F 6.6 8.4 15.5 24.6 31.9 38.7 52.4 25703-09 F 6.7 9.3 16.3 26.0 33.7 40.8 54.4 25703-10 F 6.7 8.9 16.2 25.4 31.6 39.1 50.1 25703-11 F 6.5 8.0 NA NA NA NA NA 25703-12 F 7.5 9.8 NA NA NA NA NA 25703-13 F 7.2 9.5 NA NA NA NA NA 25703-14 F 7.2 10.0 18.1 27.5 35.7 42.3 56.3 25703-15 F 7.1 9.0 NA NA NA NA NA MALES MEAN FEMALES MEAN 7.5 10.2 18.0 28.0 35.7 43.7 58.6 7.0 9.2 16.5 25.9 33.2 40.2 53.3 -676- 25673-01 M 25673-02 M 25673-03 M 25673-04 M 25673-05 M 25673-06 M 25673-07 M 25673-08 M 25673-09 M 25673-10 F 6.5 8.8 NA NA NA NA NA 5.7 8.1 NA NA NA NA NA 6.3 8.3 13.3 19.7 25.7 32.0 41.1 6.3 8.9 13.8 21.6 28.3 34.3 44.4 6.1 7.9 NA NA NA NA NA 6.5 8.4 NA NA NA NA NA 6.8 9.6 NA NA NA NA NA 6.3 8.3 12.9 20.0 25.2 31.2 39.4 6.4 9.1 13.7 21.4 26.4 32.3 39.9 5.7 8.5 13.2 19.6 24.0 29.6 37.7 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 65 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25673-11 F 6.0 8.1 13.2 19.9 26.5 32.6 41.7 25673-12 F 6.2 8.7 13.9 22.1 28.7 34.4 44.6 25673-13 F 6.1 8.6 NA NA NA NA NA 25673-14 F 6.1 8.3 12.7 19.1 25.2 31.0 40.0 25673-15 F 6.0 8.3 NA NA NA NA NA MALES MEAN 6.3 8.6 13.4 20.7 26.4 32.5 41.2 FEMALES MEAN 6.0 8.4 13.3 20.2 26.1 31.9 41.0 -677- 25611-04 M 25611-05 M 25611-06 M 25611-07 M 25611-08 M 25611-09 M 25611-10 M 25611-11 F 25611-12 F 25611-13 F 25611-14 F 25611-15 F 7.8 11.1 NA NA NA NA NA 8.1 11.0 16.3 23.7 31.1 37.9 51.5 8.0 11.0 NA NA NA NA NA 7.7 10.6 16.6 24.6 31.1 38.4 50.4 7.8 10.9 16.5 24.5 33.1 39.9 52.6 7.5 10.7 NA NA NA NA NA 7.3 10.7 16.2 23.8 32.3 38.0 50.5 7.2 10.1 15.5 24.1 29.0 36.4 46.7 7.9 10.7 15.4 23.4 32.3 38.5 49.6 7.7 10.7 16.8 24.2 32.7 38.5 50.5 7.8 10.1 NA NA NA NA NA 8.5 11.4 17.4 25.3 34.1 40.4 53.7 MALES MEAN FEMALES MEAN 7.7 10.9 16.4 24.2 31.9 38.6 51.3 7.8 10.6 16.3 24.3 32.0 38.5 50.1 25619-01 M 6.8 9.5 14.6 22.7 29.7 33.3 45.8 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 66 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25619-02 M 5.8 8.3 NA NA NA NA NA 25619-03 M 7.0 10.0 16.0 24.9 33.2 37.6 49.8 25619-04 M 6.0 8.1 11.9 18.4 24.1 28.4 35.3 25619-05 M 7.0 9.9 15.3 25.4 32.8 37.5 50.8 25619-06 M 6.4 8.8 NA NA NA NA NA 25619-07 F 6.9 9.1 NA NA NA NA NA 25619-08 F 6.7 9.0 14.2 23.7 30.7 36.2 48.4 25619-09 F 6.0 8.2 NA NA NA NA NA 25619-10 F 6.2 8.4 12.7 21.6 27.6 31.6 39.5 25619-11 F 6.2 8.5 NA NA NA NA NA 25619-12 F 6.5 9.1 14.4 23.7 27.7 32.5 40.8 25619-13 F 6.0 8.0 NA NA NA NA NA 25619-14 F 6.0 8.5 13.5 22.2 29.3 34.0 47.5 -678- MALES MEAN 6.5 9.1 14.5 22.9 30.0 34.2 45.4 FEMALES MEAN 6.3 8.6 13.7 22.8 28.8 33.6 44.1 25705-01 M 25705-02 M 25705-03 M 25705-04 M 25705-05 M 25705-06 M 25705-07 M 25705-08 F 25705-09 F 4.3 5.8 9.9 17.0 23.5 26.3 33.2 6.5 10.0 NA NA NA NA NA 7.2 10.5 NA NA NA NA NA 6.6 10.2 NA NA NA NA NA 6.7 10.3 17.2 27.3 36.0 42.1 55.7 6.4 9.6 16.0 24.5 32.3 36.6 49.7 6.5 10.0 16.8 26.3 33.8 41.2 50.5 6.8 11.1 18.1 27.8 34.8 40.7 50.8 6.5 9.9 16.5 25.7 34.7 39.6 52.3 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 67 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25705-10 F 6.4 9.8 17.0 26.3 35.4 41.0 55.4 25705-11 F 6.5 10.0 17.0 26.9 36.3 41.6 55.0 25705-12 F 6.9 10.5 NA NA NA NA NA 25705-13 F 6.6 9.8 NA NA NA NA NA MALES MEAN FEMALES MEAN 6.3 9.5 15.0 23.8 31.4 36.6 47.3 6.6 10.2 17.2 26.7 35.3 40.7 53.4 -679- 25691-01 F 25691-02 M 25691-03 M 25691-04 M 25691-05 M 25691-06 M 25691-07 M 25691-08 M 25691-09 M 25691-10 F 25691-11 F 25691-12 F 25691-14 F 25691-15 F 6.6 8.9 NA NA NA NA NA 6.7 9.0 14.4 25.1 35.5 41.3 56.0 6.1 8.9 NA NA NA NA NA 6.9 9.2 NA NA NA NA NA 7.0 9.8 15.8 26.7 35.4 40.4 51.7 7.1 10.2 16.1 26.8 36.9 44.6 56.4 6.6 9.8 16.7 27.8 37.2 43.1 50.8 7.0 10.4 NA NA NA NA NA 7.1 10.3 NA NA NA NA NA 6.0 8.5 NA NA NA NA NA 7.0 10.1 17.4 29.2 36.0 45.2 53.3 6.7 9.6 15.9 27.8 38.1 45.7 58.0 6.8 9.9 17.4 27.7 37.6 45.0 57.8 7.2 10.3 17.2 28.9 37.4 46.3 61.1 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 68 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25691-16 F 6.1 8.4 NA NA NA NA NA MALES MEAN 6.8 9.7 15.8 26.6 36.3 42.4 53.7 FEMALES MEAN 6.6 9.4 17.0 28.4 37.3 45.6 57.6 25717-03 M 25717-04 M 25717-05 M 25717-06 M 25717-07 M 25717-08 M 25717-09 F 25717-10 F 25717-11 F 25717-12 F 25717-13 F 25717-14 F 25717-15 F 6.2 7.6 12.2 20.8 26.7 34.9 46.4 6.2 7.6 12.0 21.0 26.4 33.9 45.0 5.9 7.6 NA NA NA NA NA 6.7 8.2 13.5 22.8 29.0 35.6 49.5 6.2 8.0 13.1 21.7 27.9 35.8 46.6 5.5 7.0 NA NA NA NA NA 6.5 8.1 NA NA NA NA NA 4.5 5.8 NA NA NA NA NA 5.9 7.2 11.1 19.6 25.6 33.4 44.8 5.5 7.0 NA NA NA NA NA 6.3 8.2 12.2 20.9 26.7 34.7 45.6 6.1 7.2 11.9 20.5 28.1 35.1 46.5 6.4 7.9 12.3 21.0 26.8 33.8 42.3 -680- MALES MEAN 6.1 7.7 12.7 21.6 27.5 35.1 46.9 FEMALES MEAN 5.9 7.3 11.9 20.5 26.8 34.3 44.8 25616-01 M 25616-02 M 25616-03 M 25616-04 M 6.3 9.8 NA NA NA NA NA 6.3 9.8 15.8 26.6 34.8 43.7 56.1 7.2 11.3 18.5 29.8 37.3 45.9 62.9 6.9 10.5 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 69 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25616-05 M 6.9 10.5 16.2 27.4 33.7 43.5 51.6 25616-06 M 7.2 11.1 NA NA NA NA NA 25616-07 M 7.1 11.4 NA NA NA NA NA 25616-08 F 7.2 11.1 NA NA NA NA NA 25616-09 F 6.7 9.8 NA NA NA NA NA 25616-10 F 6.5 9.5 14.9 24.8 33.2 41.5 54.4 25616-11 F 7.0 10.5 16.9 27.7 35.8 45.1 56.4 25616-12 M 7.3 11.0 17.1 28.7 35.7 46.2 61.3 25616-13 F 5.8 8.4 13.1 23.7 31.7 39.7 52.4 25616-14 F 6.2 9.2 14.7 26.0 32.6 42.3 52.4 25616-15 F 6.6 9.7 NA NA NA NA NA MALES MEAN FEMALES MEAN 6.9 10.7 16.9 28.1 35.4 44.8 58.0 6.6 9.7 14.9 25.6 33.3 42.2 53.9 -681- 25715-03 M 25715-04 M 25715-05 M 25715-06 M 25715-07 M 25715-08 M 25715-09 M 25715-10 F 25715-11 F 25715-12 F 25715-13 F 6.0 8.3 NA NA NA NA NA 6.5 9.1 15.9 25.8 34.8 43.2 55.3 6.8 9.8 NA NA NA NA NA 6.5 8.9 15.1 25.4 33.7 41.3 55.4 6.5 9.2 14.6 25.0 32.2 40.0 49.3 7.1 9.2 15.8 25.4 34.1 42.4 57.1 6.6 8.8 NA NA NA NA NA 5.9 8.0 13.7 23.2 29.7 38.0 47.6 6.4 9.2 NA NA NA NA NA 6.2 9.1 NA NA NA NA NA 6.3 9.2 14.9 24.8 33.9 41.9 54.5 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 70 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25715-14 F 6.4 8.7 NA NA NA NA NA 25715-15 F 6.4 9.3 15.4 26.0 34.9 42.5 55.8 25715-16 F 6.6 9.2 NA NA NA NA NA 25715-17 F 6.0 8.3 13.9 24.0 31.8 38.6 50.2 MALES MEAN 6.6 9.0 15.4 25.4 33.7 41.7 54.3 FEMALES MEAN 6.3 8.9 14.5 24.5 32.6 40.3 52.0 -682- 25762-01 M 25762-02 M 25762-03 M 25762-04 M 25762-05 M 25762-06 M 25762-07 F 25762-08 F 25762-09 F 25762-10 F 25762-11 F 25762-12 F 25762-13 F 25762-14 F 6.8 9.1 13.6 23.7 31.5 38.4 48.0 6.5 8.6 NA NA NA NA NA 7.2 10.2 15.5 26.9 35.7 42.7 58.5 6.6 9.0 NA NA NA NA NA 6.6 8.9 13.5 24.9 32.6 39.3 52.2 7.4 10.0 14.5 25.7 33.3 40.6 53.9 5.9 7.7 12.2 22.0 29.9 36.7 48.0 6.8 9.8 14.5 24.5 32.3 38.9 50.9 6.6 9.2 NA NA NA NA NA 6.4 8.3 NA NA NA NA NA 6.5 8.8 13.7 23.0 30.6 36.2 46.9 6.6 8.8 NA NA NA NA NA 6.0 8.1 NA NA NA NA NA 6.7 9.6 14.3 25.3 32.6 39.4 52.9 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 71 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25762-15 F 6.3 9.2 NA NA NA NA NA MALES MEAN 6.9 9.3 14.3 25.3 33.3 40.3 53.2 FEMALES MEAN 6.4 8.8 13.7 23.7 31.4 37.8 49.7 25599-01 M 25599-02 M 25599-03 M 25599-04 M 25599-05 M 25599-06 M 25599-07 M 25599-08 M 25599-09 M 25599-10 M 25599-11 F 25599-12 F 25599-13 F 25599-14 F 25599-15 F 25599-16 F 25599-17 F 25599-18 F 5.5 7.1 NA NA NA NA NA 5.4 7.2 NA NA NA NA NA 5.7 6.7 9.6 17.6 24.6 31.3 40.1 6.2 7.9 NA NA NA NA NA 5.7 7.1 NA NA NA NA NA 5.9 7.7 11.5 20.7 26.9 34.9 44.3 6.2 8.6 NA NA NA NA NA 5.4 NA NA NA NA NA NA 5.4 6.9 10.3 18.7 25.4 33.1 42.1 5.9 8.0 12.3 20.9 28.3 36.2 45.8 6.1 7.8 12.1 20.4 25.8 32.8 41.0 6.1 8.4 12.3 22.3 29.9 37.0 49.2 5.8 7.9 NA NA NA NA NA 5.2 6.3 NA NA NA NA NA 5.1 6.3 NA NA NA NA NA 5.9 7.9 NA NA NA NA NA 5.7 7.6 11.0 20.1 27.1 34.5 43.2 5.5 7.2 NA NA NA NA NA -683- NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 72 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25599-19 F 5.7 7.4 11.2 20.6 29.1 34.5 44.4 MALES MEAN 5.7 7.5 10.9 19.5 26.3 33.9 43.1 FEMALES MEAN 5.7 7.4 11.7 20.9 28.0 34.7 44.5 25647-02 M 25647-03 M 25647-04 M 25647-05 M 25647-06 M 25647-07 M 25647-08 F 25647-09 F 25647-10 F 25647-11 F 25647-12 F 25647-13 M 25647-14 F 6.3 8.6 NA NA NA NA NA 5.5 7.8 NA NA NA NA NA 6.3 8.5 12.2 20.5 27.0 32.2 42.2 6.1 8.8 NA NA NA NA NA 5.2 6.8 9.4 15.7 22.0 25.6 33.1 5.4 6.8 10.0 16.8 23.0 26.4 30.3 5.8 8.0 12.6 20.6 26.9 31.5 42.6 6.6 8.8 NA NA NA NA NA 5.7 7.7 NA NA NA NA NA 7.0 9.7 14.5 23.4 28.3 34.5 44.6 6.8 9.8 14.2 23.3 29.9 34.2 45.8 6.4 9.1 12.8 20.8 27.5 31.8 39.8 6.2 8.9 13.3 21.8 29.1 34.7 44.4 -684- MALES MEAN 5.9 8.1 11.1 18.5 24.9 29.0 36.4 FEMALES MEAN 6.4 8.8 13.7 22.3 28.6 33.7 44.4 25747-01 M 25747-02 M 25747-03 M 25747-04 M 6.5 8.1 13.0 21.4 26.5 33.1 43.6 7.2 9.3 NA NA NA NA NA 7.3 8.9 14.7 24.9 30.9 39.0 53.9 7.8 10.2 16.0 25.7 31.6 40.5 57.1 NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 73 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25747-05 M 7.2 9.3 16.3 26.8 32.9 41.7 55.6 25747-06 M 7.4 9.9 NA NA NA NA NA 25747-07 M 7.7 10.5 NA NA NA NA NA 25747-08 F 7.5 10.0 15.9 26.0 32.0 39.8 56.1 25747-09 F 6.3 8.4 13.8 22.5 28.6 35.2 49.4 25747-10 F 6.5 8.1 NA NA NA NA NA 25747-11 F 6.5 8.6 NA NA NA NA NA 25747-12 F 6.7 8.6 NA NA NA NA NA 25747-13 F 6.8 8.9 15.6 26.7 31.9 39.2 55.0 25747-14 F 6.7 9.0 NA NA NA NA NA 25747-15 F 6.9 9.0 14.8 24.5 30.9 37.2 50.9 25747-16 F 6.7 8.9 NA NA NA NA NA 25747-17 F 6.9 9.5 NA NA NA NA NA -685- MALES MEAN 7.3 9.5 15.0 24.7 30.5 38.6 52.6 FEMALES MEAN 6.8 8.9 15.0 24.9 30.9 37.9 52.9 25744-01 M 25744-02 M 25744-03 M 25744-04 M 25744-05 M 25744-06 M 25744-07 F 25744-08 F 25744-09 F 7.9 11.1 16.7 26.9 35.7 42.8 58.1 7.5 9.7 NA NA NA NA NA 8.6 11.4 18.4 29.0 37.3 45.0 62.9 7.7 11.0 17.0 27.3 34.2 42.0 57.4 8.1 10.5 NA NA NA NA NA 7.9 10.6 16.8 27.7 36.0 44.5 58.8 7.0 9.8 NA NA NA NA NA 7.1 9.2 14.6 25.0 32.0 38.6 53.7 7.2 9.4 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 74 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25744-10 F 7.3 9.4 NA NA NA NA NA 25744-11 F 7.9 11.1 17.6 28.4 36.4 44.1 58.8 25744-12 F 7.4 10.2 NA NA NA NA NA 25744-13 F 7.2 10.5 16.4 26.9 35.1 41.3 55.1 25744-14 F 7.4 10.1 16.1 26.7 35.4 41.9 57.4 25744-15 F 7.7 10.4 NA NA NA NA NA MALES MEAN FEMALES MEAN 8.0 10.7 17.2 27.7 35.8 43.6 59.3 7.4 10.0 16.2 26.8 34.7 41.5 56.3 -686- 25707-01 M 25707-02 M 25707-03 M 25707-04 M 25707-05 M 25707-06 M 25707-07 M 25707-08 M 25707-09 F 25707-10 F 25707-11 F 25707-12 F 25707-13 F 6.6 8.5 NA NA NA NA NA 6.2 7.8 NA NA NA NA NA 5.8 8.1 13.9 23.2 30.7 36.9 46.5 6.5 8.6 NA NA NA NA NA 6.4 8.6 14.0 24.9 32.1 40.5 50.9 6.0 8.5 NA NA NA NA NA 6.1 8.4 14.7 25.0 31.7 39.0 48.4 6.6 8.9 14.5 25.1 32.5 39.5 50.0 6.1 8.6 13.8 23.9 32.2 39.1 50.1 5.5 7.9 12.8 22.9 29.5 37.0 46.9 5.9 NA NA NA NA NA NA 6.3 8.4 14.4 24.4 30.7 37.4 47.8 5.5 NA NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 75 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25707-14 F 6.2 8.5 15.4 25.6 33.2 41.3 49.8 MALES MEAN 6.3 8.4 14.3 24.6 31.8 39.0 49.0 FEMALES MEAN 5.9 8.4 14.1 24.2 31.4 38.7 48.7 25723-01 M 25723-02 M 25723-03 M 25723-04 M 25723-05 M 25723-06 M 25723-07 M 25723-08 M 25723-09 M 25723-10 M 25723-11 M 25723-12 M 25723-13 F 25723-14 F 25723-15 F 25723-16 F 25723-17 M 6.2 8.0 NA NA NA NA NA 6.3 9.3 NA NA NA NA NA 6.2 8.7 NA NA NA NA NA 6.0 7.8 NA NA NA NA NA 6.2 8.6 13.8 21.7 29.2 35.0 48.2 6.1 8.6 12.9 21.1 28.8 33.2 41.6 6.5 9.0 NA NA NA NA NA 6.8 9.9 NA NA NA NA NA 6.9 9.5 NA NA NA NA NA 6.1 7.9 NA NA NA NA NA 6.4 8.8 NA NA NA NA NA 7.2 10.4 17.0 27.2 36.3 41.3 60.1 5.3 7.1 11.2 19.1 26.0 31.8 41.8 6.1 8.5 NA NA NA NA NA 6.4 9.0 15.0 23.2 30.4 37.2 51.3 6.1 8.4 13.8 21.7 30.2 35.9 49.3 5.5 6.4 9.4 14.9 21.6 25.5 35.3 -687- NA = NOT APPLICABLE APPENDIX 17 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 76 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1 4 7 11 14 17 21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25723-18 F 5.5 7.0 10.9 17.3 23.6 28.3 37.9 MALES MEAN 6.3 8.7 13.3 21.2 29.0 33.8 46.3 FEMALES MEAN 5.9 8.0 12.7 20.3 27.6 33.3 45.1 MALES MEAN S.D. N FEMALES MEAN S.D. N 6.9 0.67 24 6.6 0.58 24 9.5 1.02 24 9.1 0.87 24 15.1 1.97 24 14.9 1.77 24 24.2 2.65 24 24.0 2.36 24 31.6 3.26 24 31.3 3.00 24 38.5 4.14 24 38.0 3.62 24 50.7 5.85 24 50.1 4.75 24 PPWTNv4.19 10/23/2006 -688- -689- Final Report Volume 3 of 6 (Appendices 18-31) Study Title An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats Study Number WIL-180017 Data Requirement EPA OPPTS Guideline 870.6300; OECD Draft Guideline 426 Study Director Donald G. Stump, PhD, DABT Study Initiation Date 21 April 2006 Study Completion Date 10 January 2008 Performing Laboratory WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-9281 Sponsor Study Number 06-128 Sponsor 3M Corporation 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 WIL-180017 3M Corporation -690- MTDID 208 06-128 APPENDICES 18-31 APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25597-01 M 1.5 NA NA NA NA NA 25597-02 M 1.2 5.4 8.2 6.1 3.6 9.3 25597-03 M 1.3 NA NA NA NA NA 25597-04 M 2.1 6.2 8.9 5.2 3.0 9.4 25597-05 M 1.7 4.9 8.1 6.3 4.2 8.1 25597-06 M 1.5 NA NA NA NA NA 25597-07 M 2.1 4.6 8.1 5.9 5.7 7.0 25597-08 F 2.0 5.3 7.1 5.9 3.4 10.3 25597-09 F 2.0 NA NA NA NA NA 25597-10 F 2.0 NA NA NA NA NA 25597-11 F 2.0 NA NA NA NA NA 25597-12 F 0.8 3.7 5.9 6.0 3.4 6.8 25597-13 F 1.7 NA NA NA NA NA 25597-14 F 1.8 NA NA NA NA NA 25597-15 F 2.0 NA NA NA NA NA 25597-16 F 1.5 4.2 6.1 5.8 4.3 8.7 25597-17 F 1.4 5.5 7.8 4.4 2.7 7.0 -691- MALES MEAN 1.6 5.3 8.3 5.9 4.1 8.5 FEMALES MEAN 1.7 4.7 6.7 5.5 3.5 8.2 25654-01 M 25654-02 M 25654-03 M 25654-04 M 25654-05 M 1.2 NA NA NA NA NA 2.1 5.0 8.2 6.9 5.2 10.4 2.0 NA NA NA NA NA 2.2 NA NA NA NA NA 2.2 6.8 7.6 7.3 6.7 10.2 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25654-06 M 1.0 NA NA NA NA NA 25654-07 M 2.1 6.8 8.1 7.5 6.7 8.9 25654-08 M 0.4 NA NA NA NA NA 25654-09 M 1.9 6.5 8.5 6.5 6.6 8.0 25654-10 F 1.4 5.7 7.9 6.4 6.2 8.2 25654-11 F 1.7 5.2 5.1 7.2 5.9 7.7 25654-12 F 2.5 NA NA NA NA NA 25654-13 F 1.5 NA NA NA NA NA 25654-14 F 1.8 4.9 7.6 6.8 6.1 10.4 25654-15 F 1.4 NA NA NA NA NA MALES MEAN 1.7 6.3 8.1 7.1 6.3 9.4 FEMALES MEAN 1.7 5.3 6.9 6.8 6.1 8.8 -692- 25632-01 M 25632-02 M 25632-03 M 25632-04 M 25632-05 M 25632-06 M 25632-07 M 25632-08 M 25632-09 F 25632-10 F 25632-11 F 25632-12 F 3.3 NA NA NA NA NA 3.6 5.6 10.0 9.1 5.3 13.2 3.4 NA NA NA NA NA 3.4 5.8 8.6 8.7 7.8 15.0 3.2 NA NA NA NA NA 3.3 6.7 9.2 7.6 8.4 14.0 3.3 5.3 8.0 5.5 8.0 9.5 3.8 NA NA NA NA NA 3.3 6.6 8.3 6.0 7.6 9.6 3.2 7.2 9.7 8.2 7.1 14.1 2.9 NA NA NA NA NA 2.9 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25632-13 F 3.3 NA NA NA NA NA 25632-14 F 3.3 NA NA NA NA NA 25632-15 F 2.9 5.5 9.6 7.9 6.4 11.4 25632-16 F 3.2 6.3 8.9 7.5 6.6 12.2 MALES MEAN 3.4 5.9 9.0 7.7 7.4 12.9 FEMALES MEAN 3.1 6.4 9.1 7.4 6.9 11.8 25610-01 M 25610-02 M 25610-03 F 25610-04 F 25610-05 F 4.6 7.9 10.5 7.2 6.5 17.0 4.5 8.1 10.9 7.2 6.3 16.9 4.5 7.2 10.0 6.3 6.8 13.1 4.3 6.5 10.7 7.1 6.3 14.9 4.6 7.8 11.3 7.3 5.6 16.5 -693- MALES MEAN 4.6 8.0 10.7 7.2 6.4 17.0 FEMALES MEAN 4.5 7.2 10.7 6.9 6.2 14.8 25618-01 M 25618-02 M 25618-03 M 25618-04 M 25618-05 M 25618-06 M 25618-07 M 25618-08 M 25618-09 M 3.0 NA NA NA NA NA 2.9 6.0 9.4 5.1 8.0 14.4 2.6 NA NA NA NA NA 2.8 NA NA NA NA NA 3.7 NA NA NA NA NA 2.1 NA NA NA NA NA 2.7 5.6 10.3 7.5 7.3 13.6 2.8 5.5 9.3 6.8 8.0 12.5 2.1 5.0 10.3 7.6 7.0 15.9 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25618-10 M 2.9 NA NA NA NA NA 25618-11 F 3.3 5.7 11.4 6.7 7.7 15.9 25618-12 F 3.0 NA NA NA NA NA 25618-13 F 1.9 NA NA NA NA NA 25618-14 F 2.5 NA NA NA NA NA 25618-15 F 2.8 5.1 10.1 7.0 6.7 12.4 25618-16 F 1.9 NA NA NA NA NA 25618-17 F 2.5 4.9 10.1 5.9 7.9 10.8 25618-18 F 2.5 5.4 9.6 8.0 6.9 15.4 MALES MEAN 2.8 5.5 9.8 6.8 7.6 14.1 FEMALES MEAN 2.6 5.3 10.3 6.9 7.3 13.6 -694- 25621-01 M 25621-02 M 25621-03 M 25621-04 M 25621-05 M 25621-06 M 25621-07 M 25621-08 M 25621-09 F 25621-10 F 25621-11 F 25621-12 F 25621-13 F 1.9 6.5 9.6 7.6 7.3 15.6 2.4 6.3 10.1 7.4 7.3 14.2 2.0 6.1 9.1 8.6 7.3 12.9 2.9 NA NA NA NA NA 2.4 NA NA NA NA NA 2.9 NA NA NA NA NA 2.5 6.4 9.8 6.3 8.2 11.2 2.6 NA NA NA NA NA 2.3 7.3 9.1 8.2 7.3 12.5 2.9 7.0 9.4 6.2 8.4 11.5 2.5 NA NA NA NA NA 2.4 6.4 9.7 6.4 7.2 13.1 2.5 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25621-14 F 2.2 NA NA NA NA NA 25621-15 F 2.4 NA NA NA NA NA 25621-16 F 2.4 7.0 9.6 7.5 7.7 12.1 MALES MEAN 2.5 6.3 9.7 7.5 7.5 13.5 FEMALES MEAN 2.5 6.9 9.5 7.1 7.7 12.3 -695- 25687-01 M 25687-02 M 25687-03 M 25687-04 M 25687-05 M 25687-06 M 25687-07 M 25687-08 M 25687-09 F 25687-10 F 25687-11 F 25687-13 F 25687-14 F 25687-15 F 25687-16 F 3.8 NA NA NA NA NA 3.6 NA NA NA NA NA 3.1 4.8 8.6 8.7 7.0 11.7 3.2 4.6 9.5 7.9 7.1 13.6 3.7 5.1 10.6 8.1 7.8 11.6 2.6 NA NA NA NA NA 3.5 4.6 9.6 6.8 7.7 11.1 3.6 NA NA NA NA NA 3.2 NA NA NA NA NA 3.3 4.8 8.7 6.8 6.9 6.8 3.2 NA NA NA NA NA 3.7 NA NA NA NA NA 3.4 4.1 9.1 7.9 7.3 10.3 3.2 4.7 9.6 6.1 7.4 8.9 3.2 4.8 9.7 7.7 6.1 10.1 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25687-17 F 3.5 NA NA NA NA NA MALES MEAN 3.4 4.8 9.6 7.9 7.4 12.0 FEMALES MEAN 3.3 4.6 9.3 7.1 6.9 9.0 25633-01 M 25633-02 M 25633-03 M 25633-04 M 25633-05 M 25633-06 M 25633-07 M 25633-08 M 25633-09 M 25633-10 F 25633-11 F 25633-12 F 25633-13 F 25633-14 F 1.6 2.3 NA NA NA NA 1.2 NA NA NA NA NA 1.5 NA NA NA NA NA 1.5 2.5 5.9 6.8 5.2 8.1 1.8 2.9 6.6 5.6 5.1 4.8 1.7 NA NA NA NA NA 1.9 NA NA NA NA NA 1.6 NA NA NA NA NA 1.8 2.4 7.0 5.8 5.0 7.9 1.1 NA NA NA NA NA 1.5 2.7 6.3 6.6 5.3 7.0 0.9 1.6 5.1 5.5 5.1 6.5 1.4 2.0 5.5 5.3 5.8 5.3 1.6 2.1 5.9 5.5 5.2 7.1 -696- MALES MEAN 1.6 2.5 6.5 6.1 5.1 6.9 FEMALES MEAN 1.3 2.1 5.7 5.7 5.4 6.5 25681-01 M 25681-02 M 25681-03 M 3.0 5.1 8.7 10.5 3.5 5.9 2.6 NA NA NA NA NA 2.2 4.0 8.9 12.1 3.2 6.8 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25681-04 M 3.5 NA NA NA NA NA 25681-05 F 2.8 5.4 8.9 7.2 7.4 8.7 25681-06 M 3.2 6.0 10.0 7.7 8.2 14.2 25681-07 M 3.1 6.7 9.7 7.8 8.4 12.2 25681-08 M 3.0 NA NA NA NA NA 25681-09 F 3.0 NA NA NA NA NA 25681-10 F 2.9 5.6 9.4 8.0 5.3 8.3 25681-11 F 2.7 4.7 9.2 7.1 6.3 9.1 25681-12 F 2.8 NA NA NA NA NA 25681-13 F 3.0 NA NA NA NA NA 25681-14 F 2.8 6.2 9.1 7.6 7.6 8.7 25681-15 F 2.1 NA NA NA NA NA 25681-16 F 2.5 NA NA NA NA NA -697- MALES MEAN 2.9 5.5 9.3 9.5 5.8 9.8 FEMALES MEAN 2.7 5.5 9.2 7.5 6.7 8.7 25615-01 M 25615-02 M 25615-03 M 25615-04 M 25615-05 M 25615-06 M 25615-07 F 25615-08 F 25615-09 F 3.4 5.9 9.1 7.6 6.1 16.3 3.1 NA NA NA NA NA 3.4 5.9 9.8 4.8 7.4 14.2 3.5 NA NA NA NA NA 3.6 6.6 9.2 7.7 4.1 13.3 2.8 6.2 9.6 6.3 7.9 16.4 2.4 NA NA NA NA NA 3.1 6.2 9.4 7.0 7.3 15.8 2.9 5.5 8.5 7.8 6.4 13.9 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25615-10 F 2.7 5.5 9.3 5.3 5.6 11.9 25615-11 F 3.1 NA NA NA NA NA 25615-12 F 2.9 NA NA NA NA NA 25615-13 F 3.4 4.9 9.9 7.8 5.4 15.2 25615-14 F 3.2 NA NA NA NA NA MALES MEAN 3.3 6.2 9.4 6.6 6.4 15.1 FEMALES MEAN 3.0 5.5 9.3 7.0 6.2 14.2 -698- 25637-02 M 25637-03 M 25637-04 M 25637-05 M 25637-06 M 25637-07 M 25637-08 M 25637-09 F 25637-10 F 25637-11 M 25637-12 F 25637-13 F 25637-14 F 25637-15 F 25637-16 F 3.0 NA NA NA NA NA 3.0 6.3 11.5 7.5 8.7 15.3 3.4 NA NA NA NA NA 2.4 NA NA NA NA NA 2.7 6.2 11.7 6.2 8.2 15.6 2.9 NA NA NA NA NA 2.6 5.9 11.1 8.2 9.1 18.3 2.5 NA NA NA NA NA 2.8 6.5 11.3 8.5 9.7 18.1 2.9 5.3 12.0 8.3 9.8 13.2 3.0 NA NA NA NA NA 2.5 NA NA NA NA NA 3.0 5.6 11.5 8.5 9.0 16.4 2.9 6.8 12.4 8.6 6.1 17.2 3.1 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25637-17 F 2.7 6.5 11.2 6.0 9.0 12.7 MALES MEAN 2.9 5.9 11.6 7.6 9.0 15.6 FEMALES MEAN 2.8 6.4 11.6 7.9 8.5 16.1 25638-01 M 25638-03 M 25638-04 M 25638-05 M 25638-06 M 25638-07 M 25638-08 M 25638-09 F 25638-10 F 25638-11 F 25638-13 F 25638-14 F 25638-15 F 25638-16 F 25638-18 F 3.5 5.0 10.9 7.7 6.9 15.6 3.2 NA NA NA NA NA 2.7 4.3 10.0 8.2 7.7 13.1 3.3 5.2 11.2 8.3 6.3 14.4 1.9 NA NA NA NA NA 3.1 5.3 9.7 5.8 7.8 9.8 3.2 NA NA NA NA NA 3.0 NA NA NA NA NA 2.4 NA NA NA NA NA 3.2 5.0 10.4 8.1 6.5 13.7 3.0 NA NA NA NA NA 3.0 NA NA NA NA NA 2.7 5.2 10.7 8.8 9.0 11.8 3.2 4.8 9.9 8.4 6.8 15.0 2.1 4.0 8.1 5.8 7.6 7.1 -699- MALES MEAN 3.0 5.0 10.5 7.5 7.2 13.2 FEMALES MEAN 2.8 4.8 9.8 7.8 7.5 11.9 25713-01 M 25713-02 M 2.9 NA NA NA NA NA 2.4 6.0 10.9 6.5 7.2 9.7 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25713-03 M 2.5 NA NA NA NA NA 25713-04 M 2.0 5.2 10.3 6.3 5.6 10.8 25713-05 M 1.2 5.7 11.2 7.7 8.1 14.8 25713-06 M 2.5 NA NA NA NA NA 25713-07 M 2.4 NA NA NA NA NA 25713-08 M 1.9 5.3 10.7 6.6 8.1 16.8 25713-09 M 1.9 NA NA NA NA NA 25713-10 M 2.4 NA NA NA NA NA 25713-11 M 2.4 NA NA NA NA NA 25713-12 F 2.8 4.6 10.9 7.2 8.6 13.5 25713-13 F 2.7 6.0 11.4 6.4 6.2 15.0 25713-14 F 2.2 5.7 10.0 6.4 7.7 12.2 25713-15 F 1.7 NA NA NA NA NA 25713-16 F 2.1 5.7 10.9 5.6 6.9 9.2 -700- MALES MEAN 2.2 5.6 10.8 6.8 7.3 13.0 FEMALES MEAN 2.3 5.5 10.8 6.4 7.4 12.5 25670-01 M 25670-02 M 25670-03 M 25670-04 M 25670-05 M 25670-06 M 25670-07 M 25670-08 M 2.0 NA NA NA NA NA 2.6 NA NA NA NA NA 2.3 6.1 11.4 10.9 5.0 14.5 1.4 5.9 11.4 8.1 7.7 13.1 2.1 NA NA NA NA NA 1.4 3.9 9.6 7.3 7.0 10.7 2.7 NA NA NA NA NA 1.8 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25670-09 M 2.0 5.5 11.9 7.3 8.9 10.7 25670-10 M 2.0 NA NA NA NA NA 25670-11 M 2.0 NA NA NA NA NA 25670-12 F 2.2 NA NA NA NA NA 25670-13 F 1.0 NA NA NA NA NA 25670-14 F 1.9 NA NA NA NA NA 25670-15 F 1.4 4.8 10.8 8.2 7.7 10.2 25670-16 F 1.4 3.3 9.7 8.7 7.4 11.3 25670-17 F 1.7 5.1 10.1 7.4 7.3 12.6 25670-18 F 1.9 4.5 11.1 6.9 9.0 11.7 25670-19 F 1.9 NA NA NA NA NA MALES MEAN 2.0 5.4 11.1 8.4 7.2 12.3 FEMALES MEAN 1.7 4.4 10.4 7.8 7.9 11.5 -701- 25657-01 M 25657-02 M 25657-03 M 25657-04 M 25657-05 M 25657-06 M 25657-07 M 25657-08 M 25657-09 F 25657-10 F 25657-11 F 2.8 6.4 11.6 9.7 9.6 16.3 2.7 6.6 10.8 8.5 9.6 13.0 2.7 NA NA NA NA NA 2.3 NA NA NA NA NA 2.2 NA NA NA NA NA 2.8 NA NA NA NA NA 2.5 7.0 10.9 7.5 10.1 12.8 3.2 6.0 10.9 7.0 11.1 13.5 2.3 NA NA NA NA NA 2.1 6.6 9.7 6.6 8.9 12.4 2.9 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25657-12 F 2.5 6.3 10.9 7.9 9.2 12.9 25657-13 F 2.2 6.3 10.3 8.8 7.9 10.6 25657-14 F 2.9 NA NA NA NA NA 25657-15 F 2.6 5.5 8.6 7.9 8.1 12.5 25657-16 F 2.7 NA NA NA NA NA 25657-17 F 2.7 NA NA NA NA NA 25657-19 F 2.8 NA NA NA NA NA MALES MEAN 2.7 6.5 11.1 8.2 10.1 13.9 FEMALES MEAN 2.6 6.2 9.9 7.8 8.5 12.1 -702- 25663-01 M 25663-02 M 25663-03 M 25663-04 M 25663-05 M 25663-06 M 25663-07 F 25663-08 F 25663-09 F 25663-10 F 3.2 NA NA NA NA NA 3.3 6.1 11.4 8.1 8.9 17.2 3.4 6.3 11.3 7.8 7.9 17.2 3.4 6.5 10.7 6.2 8.4 11.5 3.1 NA NA NA NA NA 3.6 6.2 10.7 8.2 8.8 16.1 2.8 5.3 10.6 7.4 7.8 14.9 4.0 6.7 11.2 7.6 8.6 15.8 2.9 4.9 9.7 5.7 8.5 11.3 3.2 6.1 10.3 8.4 8.4 15.9 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25663-11 F 3.1 NA NA NA NA NA MALES MEAN 3.3 6.3 11.0 7.6 8.5 15.5 FEMALES MEAN 3.2 5.8 10.5 7.3 8.3 14.5 25690-01 M 25690-02 M 25690-03 M 25690-04 M 25690-05 M 25690-06 M 25690-07 M 25690-08 F 25690-09 F 25690-10 F 25690-11 F 25690-12 F 25690-13 F 25690-14 F 25690-15 F 25690-16 F 25690-17 F 25690-18 F 1.7 4.5 9.9 6.4 9.2 12.2 1.9 NA NA NA NA NA 1.8 4.8 10.0 7.3 9.6 14.6 2.2 NA NA NA NA NA 2.6 4.8 10.8 7.4 8.4 13.2 1.8 NA NA NA NA NA 2.5 5.5 10.0 8.3 8.0 14.4 1.7 NA NA NA NA NA 2.0 3.3 8.8 8.0 7.1 11.9 1.9 NA NA NA NA NA 2.1 NA NA NA NA NA 2.1 NA NA NA NA NA 1.7 NA NA NA NA NA 2.1 NA NA NA NA NA 1.5 NA NA NA NA NA 1.5 NA NA NA NA NA 2.1 4.7 10.2 7.2 8.2 13.3 1.8 4.2 9.7 7.3 9.0 13.1 -703- NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25690-19 F 1.7 4.8 9.6 5.7 9.7 10.5 MALES MEAN 2.1 4.9 10.2 7.4 8.8 13.6 FEMALES MEAN 1.9 4.3 9.6 7.1 8.5 12.2 25666-01 M 25666-02 M 25666-03 M 25666-04 M 25666-05 M 25666-06 M 25666-07 M 25666-08 F 25666-09 F 25666-10 F 25666-11 F 25666-12 F 25666-13 F 25666-14 F 2.7 5.8 10.8 5.7 8.8 9.8 2.8 4.4 9.8 7.6 8.6 12.6 2.9 NA NA NA NA NA 2.3 NA NA NA NA NA 2.8 4.9 10.6 8.5 7.7 9.9 2.9 NA NA NA NA NA 2.8 5.1 9.7 8.5 7.6 10.8 2.5 5.0 10.2 8.8 6.9 10.3 2.4 5.1 9.8 6.1 8.6 5.6 2.6 NA NA NA NA NA 1.9 NA NA NA NA NA 3.0 NA NA NA NA NA 2.0 4.0 10.5 7.6 7.0 9.7 2.6 5.1 10.3 7.3 7.3 11.2 -704- MALES MEAN 2.7 5.1 10.2 7.6 8.2 10.8 FEMALES MEAN 2.4 4.8 10.2 7.5 7.5 9.2 25692-02 M 25692-03 M 25692-04 M 2.6 6.8 11.7 8.5 9.8 16.1 3.0 5.6 11.1 7.1 8.7 13.1 2.9 5.9 12.1 8.5 9.8 13.7 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25692-05 M 2.2 5.3 11.8 7.6 9.2 13.5 25692-06 F 3.2 5.9 10.9 8.2 8.3 14.5 25692-07 F 2.3 5.9 11.0 8.5 6.6 8.9 25692-08 F 2.1 NA NA NA NA NA 25692-09 F 2.5 NA NA NA NA NA 25692-10 F 2.4 NA NA NA NA NA 25692-11 F 3.0 NA NA NA NA NA 25692-12 F 2.7 6.0 10.5 6.8 8.0 12.8 25692-13 F 1.8 NA NA NA NA NA 25692-14 F 2.4 6.0 10.9 8.2 9.4 13.3 MALES MEAN 2.7 5.9 11.7 7.9 9.4 14.1 FEMALES MEAN 2.5 6.0 10.8 7.9 8.1 12.4 -705- 25701-01 M 25701-02 F 25701-03 M 25701-04 M 25701-05 M 25701-06 M 25701-07 M 25701-08 M 25701-09 M 25701-10 M 25701-11 F 25701-12 F 2.2 NA NA NA NA NA 2.7 5.2 8.8 6.8 6.2 14.7 2.6 5.8 8.6 7.1 6.9 14.5 2.4 NA NA NA NA NA 2.2 NA NA NA NA NA 2.3 5.0 7.6 6.8 6.1 12.1 2.0 NA NA NA NA NA 2.4 NA NA NA NA NA 2.3 5.1 8.6 6.5 6.7 13.7 2.4 5.2 8.1 6.6 6.9 9.6 2.6 5.4 8.0 6.6 5.6 13.8 2.6 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25701-13 F 1.8 NA NA NA NA NA 25701-14 F 1.4 NA NA NA NA NA 25701-15 F 2.1 NA NA NA NA NA 25701-16 F 1.9 4.9 8.6 7.0 6.6 13.8 25701-17 F 1.9 NA NA NA NA NA 25701-18 F 2.5 5.0 8.7 6.6 7.5 11.9 25701-19 F 1.8 NA NA NA NA NA MALES MEAN 2.3 5.3 8.2 6.8 6.7 12.5 FEMALES MEAN 2.1 5.1 8.5 6.8 6.5 13.6 -706- 25645-01 M 25645-02 M 25645-03 M 25645-04 M 25645-05 M 25645-06 M 25645-07 F 25645-08 F 25645-09 F 25645-10 F 25645-11 F 25645-12 F 25645-13 F 25645-14 F 0.7 3.5 8.4 7.9 5.5 8.3 1.2 4.6 9.4 8.2 6.3 13.0 0.8 NA NA NA NA NA 1.4 5.2 7.3 7.3 5.4 11.5 1.6 NA NA NA NA NA 1.0 4.8 9.4 6.6 5.7 9.7 1.3 4.9 9.4 6.6 5.6 11.0 0.8 4.7 9.3 6.3 5.8 10.3 1.1 NA NA NA NA NA 0.5 NA NA NA NA NA 1.3 5.2 9.0 7.4 5.8 13.0 0.9 4.7 8.9 8.1 6.1 9.3 1.0 NA NA NA NA NA 1.9 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 17 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25645-15 F 1.1 NA NA NA NA NA MALES MEAN 1.1 4.5 8.6 7.5 5.7 10.6 FEMALES MEAN 1.1 4.9 9.2 7.1 5.8 10.9 25661-01 M 25661-02 M 25661-03 M 25661-04 M 25661-05 M 25661-06 M 25661-07 M 25661-08 M 25661-09 M 25661-10 F 25661-11 F 25661-12 F 25661-13 F 25661-14 F 25661-15 F 25661-16 F 2.0 NA NA NA NA NA 1.1 5.5 NA NA NA NA 2.0 NA NA NA NA NA 1.6 6.3 13.0 9.1 8.3 15.1 1.8 5.6 12.2 8.0 8.1 14.3 1.7 NA NA NA NA NA 1.6 NA NA NA NA NA 1.4 NA NA NA NA NA 2.1 NA NA NA NA NA 1.5 5.5 12.3 9.3 8.1 13.0 1.5 5.4 12.4 9.7 7.8 12.9 2.4 5.7 13.4 10.1 8.8 15.7 2.3 NA NA NA NA NA 1.6 7.3 12.3 9.9 7.3 12.8 1.9 NA NA NA NA NA 1.8 NA NA NA NA NA -707- MALES MEAN 1.7 5.8 12.6 8.6 8.2 14.7 FEMALES MEAN 1.9 6.0 12.6 9.8 8.0 13.6 25767-01 M 1.8 6.0 11.2 8.4 6.5 10.7 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 18 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25767-02 M 2.2 NA NA NA NA NA 25767-03 M 2.6 5.5 8.7 9.0 7.6 15.2 25767-04 M 2.4 NA NA NA NA NA 25767-05 M 3.1 5.6 11.6 9.2 7.0 9.1 25767-06 M 2.8 5.1 11.0 8.0 7.4 10.2 25767-07 F 2.0 5.2 10.5 6.7 6.9 12.1 25767-08 F 2.4 NA NA NA NA NA 25767-09 F 1.8 2.9 8.9 7.9 6.4 10.3 25767-10 F 2.7 NA NA NA NA NA 25767-11 F 1.4 NA NA NA NA NA 25767-12 F 2.1 5.1 10.7 8.8 5.1 11.7 25767-13 F 3.0 NA NA NA NA NA 25767-14 F 2.0 NA NA NA NA NA 25767-15 F 3.1 NA NA NA NA NA 25767-16 F 2.9 5.6 11.8 6.8 6.2 11.3 25767-17 F 0.3 NA NA NA NA NA -708- MALES MEAN 2.5 5.6 10.6 8.7 7.1 11.3 FEMALES MEAN 2.2 4.7 10.5 7.6 6.2 11.4 25770-01 M 25770-02 M 25770-03 M 25770-04 M 25770-05 M 25770-06 F 2.5 5.9 10.4 7.7 4.7 10.2 2.8 6.4 12.7 6.3 5.5 10.7 2.2 7.1 11.3 9.1 4.7 10.9 1.8 5.9 11.0 7.3 5.6 12.2 2.9 NA NA NA NA NA 2.4 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 19 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25770-07 F 1.8 6.2 10.3 7.3 5.7 11.4 25770-08 F 2.4 NA NA NA NA NA 25770-09 F 2.2 6.6 10.9 8.4 5.4 10.1 25770-10 F 1.6 NA NA NA NA NA 25770-11 F 2.0 6.1 9.4 8.7 5.1 10.9 25770-12 F 1.8 NA NA NA NA NA 25770-13 F 2.4 NA NA NA NA NA 25770-14 F 2.3 6.6 10.8 8.9 5.0 10.4 MALES MEAN 2.4 6.3 11.4 7.6 5.1 11.0 FEMALES MEAN 2.1 6.4 10.4 8.3 5.3 10.7 -709- 25702-03 M 25702-04 M 25702-05 M 25702-06 M 25702-07 M 25702-08 M 25702-09 M 25702-11 M 25702-12 M 25702-13 F 25702-14 F 25702-15 F 25702-16 F 25702-17 F 2.6 6.6 11.7 10.6 7.3 14.8 2.7 7.2 11.4 9.7 6.9 15.3 2.3 NA NA NA NA NA 3.3 NA NA NA NA NA 2.4 6.8 10.4 9.1 7.0 10.6 2.7 NA NA NA NA NA 2.6 NA NA NA NA NA 2.0 NA NA NA NA NA 2.8 7.0 10.6 9.2 7.8 13.7 2.3 6.6 10.4 9.1 6.7 13.4 1.3 NA NA NA NA NA 2.3 5.9 11.4 9.1 7.9 13.7 2.9 6.7 9.8 9.2 7.7 10.7 2.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 20 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25702-18 F 2.3 5.8 10.8 9.0 7.6 11.6 MALES MEAN 2.6 6.9 11.0 9.7 7.3 13.6 FEMALES MEAN 2.2 6.3 10.6 9.1 7.5 12.4 MALES MEAN S.D. N FEMALES MEAN S.D. N 2.6 0.75 25 2.4 0.72 25 5.7 0.99 25 5.4 1.05 25 10.0 1.39 25 9.7 1.51 25 7.6 0.91 25 7.4 0.91 25 7.2 1.42 25 7.0 1.21 25 12.6 2.38 25 11.7 2.31 25 -710- APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 21 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25648-01 M 2.0 NA NA NA NA NA 25648-02 M 1.6 NA NA NA NA NA 25648-03 M 2.0 6.4 8.5 7.6 9.4 11.0 25648-04 M 1.9 NA NA NA NA NA 25648-05 M 2.1 NA NA NA NA NA 25648-06 M 1.6 NA NA NA NA NA 25648-07 M 2.0 5.7 7.8 6.6 8.0 10.9 25648-08 M 2.0 6.3 8.3 7.2 8.9 10.4 25648-09 M 1.4 NA NA NA NA NA 25648-10 M 1.2 5.8 7.6 7.1 7.6 10.3 25648-11 F 2.0 4.8 7.7 7.8 8.4 8.2 25648-12 F 2.1 5.9 8.8 7.0 7.2 9.5 25648-13 F 1.9 NA NA NA NA NA 25648-14 F 1.6 5.5 8.4 7.8 8.1 9.0 25648-15 F 1.9 NA NA NA NA NA 25648-16 F 1.8 6.0 7.0 6.7 8.1 8.8 25648-17 F 1.8 NA NA NA NA NA -711- MALES MEAN 1.8 6.1 8.1 7.1 8.5 10.7 FEMALES MEAN 1.9 5.6 8.0 7.3 8.0 8.9 25694-01 M 25694-02 M 25694-03 M 25694-04 M 25694-05 M 2.9 NA NA NA NA NA 2.3 NA NA NA NA NA 2.1 5.3 10.8 7.7 9.1 15.4 2.9 6.6 10.2 8.3 9.4 12.8 3.1 7.1 10.9 8.5 9.2 15.1 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 22 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25694-06 M 3.0 NA NA NA NA NA 25694-07 F 3.1 NA NA NA NA NA 25694-08 F 3.2 5.8 9.4 8.2 8.8 13.7 25694-09 F 2.6 5.2 10.6 9.2 8.3 12.8 25694-10 F 2.5 NA NA NA NA NA 25694-11 M 2.9 6.2 10.3 9.7 10.0 15.9 25694-12 M 3.0 NA NA NA NA NA 25694-13 F 2.2 4.6 9.3 7.6 8.3 11.2 25694-14 F 2.6 NA NA NA NA NA 25694-15 F 2.7 6.3 10.4 8.4 8.3 15.6 25694-16 F 2.1 NA NA NA NA NA 25694-17 F 2.8 NA NA NA NA NA 25694-18 F 2.1 NA NA NA NA NA -712- MALES MEAN 2.8 6.3 10.6 8.6 9.4 14.8 FEMALES MEAN 2.6 5.5 9.9 8.4 8.4 13.3 25668-03 M 25668-04 M 25668-05 M 25668-06 F 25668-07 F 25668-08 F 25668-09 F 25668-10 F 25668-11 F 3.0 4.1 8.5 8.1 6.5 12.2 2.7 4.8 7.7 7.0 8.2 11.2 2.7 4.3 8.1 8.0 5.7 12.4 2.7 4.4 7.9 7.9 6.8 9.5 2.4 4.2 8.1 7.9 6.9 10.7 2.6 NA NA NA NA NA 3.3 NA NA NA NA NA 2.8 4.1 7.6 7.6 6.0 10.6 3.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 23 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25668-12 F 2.0 3.3 8.1 7.0 7.6 9.8 25668-13 F 3.1 NA NA NA NA NA 25668-14 F 2.9 NA NA NA NA NA 25668-15 F 2.9 NA NA NA NA NA 25668-16 F 2.1 3.5 8.0 7.9 7.4 10.4 25668-17 F 2.9 NA NA NA NA NA MALES MEAN 2.8 4.4 8.1 7.7 6.8 11.9 FEMALES MEAN 2.7 3.9 7.9 7.7 6.9 10.2 -713- 25631-01 M 25631-02 M 25631-03 M 25631-04 M 25631-05 F 25631-06 F 25631-07 M 25631-08 F 25631-09 F 25631-10 F 25631-11 F 25631-12 F 25631-13 F 25631-14 F 3.3 NA NA NA NA NA 4.1 6.3 9.3 9.3 5.9 14.5 3.0 4.9 10.0 9.8 7.6 12.3 3.6 6.5 9.4 7.3 7.8 12.9 3.4 6.0 9.1 8.2 7.2 11.0 4.0 NA NA NA NA NA 3.5 6.2 10.4 7.3 9.8 13.3 3.4 NA NA NA NA NA 3.4 NA NA NA NA NA 3.2 5.3 10.1 7.4 9.0 11.9 3.9 NA NA NA NA NA 3.0 NA NA NA NA NA 3.6 5.8 9.4 7.8 7.9 13.1 3.9 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 24 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25631-15 F 3.4 6.2 9.2 7.1 6.9 12.6 MALES MEAN 3.5 6.0 9.8 8.4 7.8 13.3 FEMALES MEAN 3.5 5.8 9.5 7.6 7.8 12.2 25660-01 M 25660-02 M 25660-03 M 25660-04 F 25660-05 M 25660-06 M 25660-07 M 25660-08 M 25660-09 M 25660-10 F 25660-11 F 25660-12 F 25660-13 F 25660-14 F 25660-15 F 2.9 6.2 9.0 6.2 6.9 14.2 3.6 7.0 9.5 8.2 6.4 15.3 2.5 NA NA NA NA NA 3.6 7.4 10.0 6.3 6.9 15.6 2.9 NA NA NA NA NA 3.5 7.4 11.3 8.4 7.1 18.1 3.6 7.6 10.7 8.1 7.7 17.4 3.7 NA NA NA NA NA 3.3 NA NA NA NA NA 3.5 6.0 9.8 7.3 7.0 12.5 3.2 NA NA NA NA NA 3.4 NA NA NA NA NA 3.1 6.7 9.6 8.3 7.6 14.7 3.6 6.2 10.4 7.1 6.2 17.3 3.5 NA NA NA NA NA -714- MALES MEAN 3.3 7.1 10.1 7.7 7.0 16.3 FEMALES MEAN 3.4 6.6 10.0 7.3 6.9 15.0 25704-01 M 25704-02 M 3.5 6.3 9.4 7.7 8.0 13.5 3.3 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 25 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25704-03 M 3.5 6.7 9.0 5.4 8.1 13.4 25704-04 M 3.1 6.8 8.9 7.4 7.5 15.6 25704-05 M 3.0 NA NA NA NA NA 25704-06 M 3.4 6.7 10.0 7.2 8.9 15.6 25704-07 M 2.9 NA NA NA NA NA 25704-08 F 3.5 6.8 8.9 6.9 8.8 12.0 25704-09 F 3.6 6.5 9.0 6.0 8.4 10.5 25704-10 F 4.2 NA NA NA NA NA 25704-11 F 3.2 6.4 9.7 7.0 6.5 13.1 25704-12 F 3.0 5.6 9.2 6.1 7.5 12.2 25704-13 F 3.0 NA NA NA NA NA MALES MEAN 3.2 6.6 9.3 6.9 8.1 14.5 FEMALES MEAN 3.4 6.3 9.2 6.5 7.8 12.0 -715- 25665-01 M 25665-02 M 25665-03 M 25665-04 M 25665-05 F 25665-06 F 25665-07 F 25665-08 F 25665-09 F 25665-10 F 25665-11 F 4.2 5.2 7.7 5.9 6.3 12.5 3.3 4.1 7.1 7.0 5.7 11.4 3.5 5.4 8.6 6.4 6.0 15.7 3.0 3.9 7.4 6.2 4.8 10.3 3.4 5.2 9.1 6.2 6.5 14.1 2.8 4.6 7.3 5.8 5.1 11.5 2.5 4.4 8.2 5.2 5.7 12.1 2.7 NA NA NA NA NA 3.6 NA NA NA NA NA 3.2 5.5 8.1 9.1 2.9 14.5 2.7 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 26 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25665-12 F 3.3 NA NA NA NA NA MALES MEAN 3.5 4.7 7.7 6.4 5.7 12.5 FEMALES MEAN 3.0 4.9 8.2 6.6 5.1 13.1 25674-01 M 25674-02 M 25674-03 M 25674-04 M 25674-05 M 25674-06 M 25674-07 M 25674-08 M 25674-09 M 25674-10 F 25674-11 F 25674-12 F 25674-13 F 25674-14 F 25674-15 F 25674-16 F 2.2 NA NA NA NA NA 2.2 4.9 7.3 6.0 5.8 10.4 2.4 NA NA NA NA NA 2.8 5.7 7.3 7.0 6.3 13.4 1.6 4.3 6.6 7.0 3.7 13.6 2.9 NA NA NA NA NA 2.2 5.3 7.9 7.0 6.0 12.3 2.2 NA NA NA NA NA 1.8 NA NA NA NA NA 2.4 NA NA NA NA NA 2.6 5.4 8.6 5.2 6.5 10.4 2.7 NA NA NA NA NA 2.2 5.5 7.4 8.0 5.9 13.7 1.0 2.7 5.3 6.6 5.7 7.8 1.8 NA NA NA NA NA 2.3 5.3 8.0 7.1 6.5 13.3 -716- MALES MEAN 2.3 5.1 7.3 6.8 5.5 12.4 FEMALES MEAN 2.1 4.7 7.3 6.7 6.2 11.3 25652-01 M 4.3 7.2 9.4 9.4 5.7 14.4 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 27 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25652-02 M 3.5 7.0 7.9 8.1 6.5 11.1 25652-03 M 4.1 6.5 9.7 8.0 5.1 13.8 25652-04 M 3.9 7.2 9.2 7.6 5.9 10.1 25652-05 M 3.3 NA NA NA NA NA 25652-06 M 3.1 NA NA NA NA NA 25652-07 F 3.0 NA NA NA NA NA 25652-08 F 3.4 7.0 9.2 9.5 3.4 11.6 25652-09 F 3.1 NA NA NA NA NA 25652-10 F 3.7 6.7 9.4 6.1 7.3 13.5 25652-11 F 3.0 6.2 8.6 6.8 5.4 10.4 25652-12 F 3.8 NA NA NA NA NA 25652-13 F 2.3 5.5 8.3 5.2 7.5 6.4 MALES MEAN 3.7 7.0 9.1 8.3 5.8 12.4 FEMALES MEAN 3.2 6.4 8.9 6.9 5.9 10.5 -717- 25733-01 M 25733-02 M 25733-03 M 25733-04 M 25733-05 M 25733-06 M 25733-07 M 25733-08 F 25733-09 F 25733-10 F 3.0 4.2 7.9 6.9 8.1 5.9 2.0 NA NA NA NA NA 2.5 4.4 8.0 9.3 5.7 8.8 1.4 NA NA NA NA NA 2.7 NA NA NA NA NA 2.7 3.8 8.1 7.9 7.9 9.2 2.4 4.6 7.6 4.8 9.5 3.3 3.0 3.8 8.9 4.3 8.2 6.5 2.8 NA NA NA NA NA 2.4 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 28 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25733-11 F 2.5 4.1 7.3 7.8 7.0 7.2 25733-12 F 2.7 3.9 8.7 6.1 6.4 8.7 25733-13 F 1.9 NA NA NA NA NA 25733-14 F 2.6 NA NA NA NA NA 25733-15 F 1.7 4.2 8.4 6.8 9.2 8.5 MALES MEAN 2.4 4.3 7.9 7.2 7.8 6.8 FEMALES MEAN 2.5 4.0 8.3 6.3 7.7 7.7 25748-01 M 25748-02 M 25748-03 M 25748-04 M 25748-05 M 25748-06 M 25748-07 M 25748-08 F 25748-09 F 25748-10 F 3.8 5.6 10.0 5.2 8.1 14.2 4.3 5.7 9.1 7.0 6.9 17.7 4.1 NA NA NA NA NA 3.9 6.1 10.2 7.9 6.8 17.3 4.1 6.4 8.9 9.4 5.5 17.9 4.3 6.2 9.7 8.4 7.8 17.3 3.8 NA NA NA NA NA 3.8 6.0 9.1 5.2 7.2 12.0 4.5 5.6 10.0 7.2 6.0 17.1 3.2 4.7 8.2 6.9 6.5 13.5 -718- MALES MEAN 4.0 6.0 9.6 7.6 7.0 16.9 FEMALES MEAN 3.8 5.4 9.1 6.4 6.6 14.2 25753-01 M 25753-02 M 25753-03 M 2.3 NA NA NA NA NA 2.3 6.4 10.1 6.3 6.7 18.5 2.4 5.9 9.0 6.9 6.9 17.8 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 29 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25753-04 M 2.4 6.4 10.3 6.3 7.4 15.7 25753-05 M 2.6 NA NA NA NA NA 25753-06 M 2.3 6.3 10.7 4.5 7.8 13.4 25753-08 F 2.7 NA NA NA NA NA 25753-09 F 2.7 6.5 10.0 7.3 6.8 18.0 25753-10 F 2.7 NA NA NA NA NA 25753-11 F 3.0 NA NA NA NA NA 25753-12 F 3.2 NA NA NA NA NA 25753-14 F 2.9 NA NA NA NA NA 25753-15 F 2.0 6.7 9.8 6.6 5.6 11.6 25753-16 F 3.5 6.5 10.4 7.6 6.1 16.9 25753-17 F 3.6 7.0 9.5 7.0 8.2 14.1 25753-18 F 1.9 NA NA NA NA NA -719- MALES MEAN 2.4 6.3 10.0 6.0 7.2 16.4 FEMALES MEAN 2.8 6.7 9.9 7.1 6.7 15.2 25672-02 M 25672-03 M 25672-04 M 25672-05 M 25672-06 M 25672-07 M 25672-08 M 25672-09 M 25672-10 F 2.7 5.7 10.4 8.4 7.8 15.5 2.9 NA NA NA NA NA 3.0 NA NA NA NA NA 2.4 6.4 10.1 8.7 6.8 11.0 2.3 6.1 10.6 6.9 8.6 7.5 3.0 NA NA NA NA NA 3.5 NA NA NA NA NA 3.5 5.4 10.4 8.2 8.4 10.8 1.7 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 30 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25672-11 F 2.9 7.0 10.7 8.1 7.7 14.5 25672-12 F 2.3 5.0 9.4 7.6 7.8 11.2 25672-13 F 2.7 NA NA NA NA NA 25672-14 F 2.4 NA NA NA NA NA 25672-15 F 2.7 6.7 10.3 5.9 8.7 9.9 25672-16 F 0.9 3.4 8.2 6.9 7.1 8.6 25672-17 F 3.1 NA NA NA NA NA 25672-18 F 2.6 NA NA NA NA NA MALES MEAN 2.9 5.9 10.4 8.1 7.9 11.2 FEMALES MEAN 2.4 5.5 9.7 7.1 7.8 11.1 -720- 25655-01 M 25655-02 M 25655-03 M 25655-04 M 25655-05 M 25655-06 M 25655-07 M 25655-08 M 25655-09 M 25655-10 M 25655-11 F 25655-12 F 25655-13 F 25655-14 F 2.3 6.4 8.0 5.8 6.4 9.2 2.8 NA NA NA NA NA 3.2 6.8 10.7 6.3 7.1 12.1 3.3 NA NA NA NA NA 2.8 NA NA NA NA NA 2.5 NA NA NA NA NA 2.8 5.4 9.3 7.7 5.7 13.2 3.6 NA NA NA NA NA 3.7 NA NA NA NA NA 3.3 6.8 12.1 7.2 6.6 15.2 2.2 6.2 11.4 6.6 7.9 11.3 2.9 6.1 10.6 7.4 7.3 11.7 2.7 6.2 10.6 4.7 6.6 9.8 1.5 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 31 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25655-15 F 2.8 5.7 11.9 5.9 6.0 12.2 25655-16 F 2.2 NA NA NA NA NA MALES MEAN 3.0 6.4 10.0 6.8 6.5 12.4 FEMALES MEAN 2.4 6.1 11.1 6.2 7.0 11.3 25727-02 M 25727-03 M 25727-04 M 25727-05 M 25727-06 M 25727-07 M 25727-08 M 25727-09 F 25727-10 F 25727-11 F 25727-12 F 25727-13 F 25727-14 F 25727-15 F 25727-16 F 2.8 4.3 8.6 8.4 7.8 10.2 1.9 NA NA NA NA NA 2.3 NA NA NA NA NA 1.9 4.1 8.5 8.9 9.9 9.4 2.0 4.1 9.4 7.7 9.3 9.5 2.7 4.6 9.9 7.5 10.2 7.9 2.4 NA NA NA NA NA 1.8 4.1 8.1 7.7 8.8 10.1 2.1 3.7 9.7 7.5 8.9 9.4 2.1 NA NA NA NA NA 1.7 NA NA NA NA NA 2.6 4.0 9.4 9.2 9.9 9.9 1.9 NA NA NA NA NA 2.2 NA NA NA NA NA 2.2 3.2 7.3 6.0 9.6 4.7 -721- NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 32 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25727-17 F 1.3 NA NA NA NA NA MALES MEAN 2.3 4.3 9.1 8.1 9.3 9.3 FEMALES MEAN 2.0 3.8 8.6 7.6 9.3 8.5 25626-01 M 25626-02 M 25626-03 M 25626-04 M 25626-05 M 25626-06 M 25626-07 M 25626-08 F 25626-09 F 25626-10 F 25626-11 F 25626-12 F 25626-13 F 25626-14 F 25626-15 F 25626-16 F 2.0 6.0 10.6 8.7 8.6 14.9 2.5 NA NA NA NA NA 2.4 NA NA NA NA NA 2.3 6.1 11.3 7.1 9.2 10.9 2.4 NA NA NA NA NA 2.3 5.2 10.0 7.9 8.6 12.0 3.0 7.1 11.1 9.0 9.3 14.6 1.6 5.6 9.8 8.1 7.2 9.4 1.8 6.0 10.6 8.0 8.5 9.0 1.9 NA NA NA NA NA 1.9 NA NA NA NA NA 2.2 5.4 11.1 6.1 8.6 11.3 2.2 NA NA NA NA NA 2.1 NA NA NA NA NA 2.3 5.7 10.8 8.3 8.4 11.7 2.1 NA NA NA NA NA -722- MALES MEAN 2.4 6.1 10.8 8.2 8.9 13.1 FEMALES MEAN 2.0 5.7 10.6 7.6 8.2 10.4 25739-01 M 2.9 6.6 11.7 7.8 10.0 18.9 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 33 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25739-02 M 3.0 NA NA NA NA NA 25739-03 M 2.7 NA NA NA NA NA 25739-04 M 2.5 NA NA NA NA NA 25739-05 M 2.9 NA NA NA NA NA 25739-06 M 3.1 7.8 11.2 8.1 9.9 16.4 25739-07 M 3.5 6.9 11.4 6.5 10.8 12.6 25739-08 M 3.0 NA NA NA NA NA 25739-09 M 2.7 6.9 11.2 9.1 8.7 16.7 25739-10 M 2.8 NA NA NA NA NA 25739-11 F 2.4 7.2 11.5 9.2 8.6 14.7 25739-12 F 2.8 6.8 11.0 7.8 11.4 13.9 25739-13 F 2.8 6.9 11.3 9.2 9.0 14.0 25739-14 F 3.4 7.0 11.0 8.9 9.0 14.7 -723- MALES MEAN 2.9 7.1 11.4 7.9 9.9 16.2 FEMALES MEAN 2.9 7.0 11.2 8.8 9.5 14.3 25749-02 M 25749-03 M 25749-04 M 25749-05 M 25749-06 M 25749-07 M 25749-08 F 25749-09 F 25749-10 F 3.8 5.2 9.1 8.5 5.9 14.4 3.9 6.1 10.2 8.9 6.5 15.2 3.6 5.5 9.7 6.7 8.5 10.5 3.5 NA NA NA NA NA 3.7 NA NA NA NA NA 3.1 5.4 9.8 7.7 6.2 13.4 3.6 5.9 9.6 6.8 6.2 13.0 3.1 5.7 9.3 7.7 6.5 14.7 3.6 5.1 9.7 7.4 5.7 13.9 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 34 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25749-11 F 3.4 5.5 8.9 5.8 6.7 13.5 MALES MEAN 3.6 5.6 9.7 8.0 6.8 13.4 FEMALES MEAN 3.4 5.6 9.4 6.9 6.3 13.8 25756-01 M 3.2 5.8 10.2 7.8 7.6 12.7 25756-02 M -0.1 NA NA NA NA NA 25756-03 M 2.7 5.7 10.5 7.6 8.5 19.3 25756-04 M 3.2 5.3 10.6 8.3 7.6 14.0 25756-05 M 3.2 6.5 10.7 7.7 7.7 13.8 25756-06 M 3.0 NA NA NA NA NA 25756-07 M 3.0 NA NA NA NA NA 25756-08 F 3.4 NA NA NA NA NA 25756-09 F 3.4 NA NA NA NA NA 25756-10 F 3.2 NA NA NA NA NA 25756-11 F 2.9 5.1 10.2 8.9 7.8 15.0 25756-12 F 2.8 NA NA NA NA NA 25756-13 F 2.3 5.8 10.1 8.2 7.9 14.2 25756-14 F 3.1 NA NA NA NA NA 25756-15 F 3.3 5.6 10.4 8.3 8.9 14.8 25756-16 F 3.3 5.7 10.6 7.3 8.0 15.2 -724- MALES MEAN 2.6 5.8 10.5 7.9 7.9 15.0 FEMALES MEAN 3.1 5.6 10.3 8.2 8.2 14.8 25741-01 M 2.4 7.2 9.2 7.3 7.4 11.5 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 35 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25741-02 M 3.5 8.0 10.6 8.6 8.5 16.6 25741-03 M 3.5 7.7 10.3 8.5 7.3 13.5 25741-04 M 3.1 NA NA NA NA NA 25741-05 M 3.0 NA NA NA NA NA 25741-06 M 3.1 NA NA NA NA NA 25741-07 M 2.2 6.9 10.9 6.6 7.7 13.8 25741-08 F 3.2 NA NA NA NA NA 25741-09 F 2.8 7.5 10.5 6.8 7.4 11.8 25741-10 F 2.6 NA NA NA NA NA 25741-11 F 3.3 NA NA NA NA NA 25741-12 F 3.8 NA NA NA NA NA 25741-13 F 2.4 NA NA NA NA NA 25741-14 F 2.5 6.4 9.2 8.3 8.2 12.4 25741-15 F 3.0 7.7 10.8 7.7 8.8 12.8 25741-16 F 2.9 7.2 11.0 7.4 7.8 12.7 25741-17 F 2.2 NA NA NA NA NA -725- MALES MEAN 3.0 7.5 10.3 7.8 7.7 13.9 FEMALES MEAN 2.9 7.2 10.4 7.6 8.1 12.4 25752-01 M 25752-02 M 25752-03 M 25752-04 M 25752-05 M 25752-07 M 3.6 7.4 11.6 7.9 9.9 16.4 3.8 NA NA NA NA NA 3.6 7.1 11.3 9.6 8.7 15.8 3.4 NA NA NA NA NA 2.9 6.3 10.5 7.8 8.5 14.4 3.7 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 36 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25752-08 M 3.2 NA NA NA NA NA 25752-09 M 4.0 7.6 11.4 8.7 9.1 14.9 25752-10 F 3.5 NA NA NA NA NA 25752-11 F 3.2 7.6 11.3 9.4 9.4 17.7 25752-12 F 3.7 NA NA NA NA NA 25752-13 F 4.2 7.6 12.9 7.9 8.6 13.3 25752-14 F 3.8 7.6 11.5 9.9 8.6 15.8 25752-15 F 3.1 6.8 11.1 8.2 9.2 14.7 MALES MEAN 3.5 7.1 11.2 8.5 9.1 15.4 FEMALES MEAN 3.6 7.4 11.7 8.9 9.0 15.4 -726- 25758-01 M 25758-02 M 25758-03 M 25758-04 M 25758-05 M 25758-06 M 25758-07 F 25758-08 F 25758-09 F 25758-10 F 25758-11 F 25758-12 F 25758-13 F 2.8 7.0 10.7 8.1 7.8 16.9 3.1 5.9 11.0 8.0 8.1 15.0 2.6 NA NA NA NA NA 3.2 NA NA NA NA NA 3.3 7.1 10.8 9.0 7.8 16.1 3.2 6.2 10.9 8.4 8.1 15.5 3.3 NA NA NA NA NA 2.9 6.5 11.6 7.7 8.6 14.6 3.1 6.7 10.5 7.2 7.5 15.0 3.1 4.9 9.3 7.4 8.3 12.6 3.8 NA NA NA NA NA 2.3 3.6 7.2 6.2 6.2 8.5 2.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 37 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25758-14 F 2.4 NA NA NA NA NA MALES MEAN 3.0 6.6 10.9 8.4 8.0 15.9 FEMALES MEAN 2.9 5.4 9.7 7.1 7.7 12.7 25719-01 M 25719-03 M 25719-04 M 25719-05 M 25719-06 M 25719-07 M 25719-08 M 25719-09 M 25719-10 M 25719-11 M 25719-12 M 25719-13 F 25719-14 F 25719-15 F 25719-16 F 25719-17 F 3.0 NA NA NA NA NA 2.8 6.7 10.6 7.3 7.6 13.1 3.4 7.2 10.8 7.7 6.7 13.7 3.2 NA NA NA NA NA 3.1 NA NA NA NA NA 3.5 8.1 11.0 7.1 7.3 16.9 2.6 NA NA NA NA NA 3.5 7.2 11.0 8.3 9.5 16.2 3.2 NA NA NA NA NA 3.1 NA NA NA NA NA 3.1 NA NA NA NA NA 2.2 6.0 8.9 7.4 7.7 8.9 2.3 6.0 10.1 7.0 7.6 11.4 3.3 7.5 10.8 8.0 7.4 14.4 3.0 NA NA NA NA NA 3.0 6.3 10.7 7.1 7.8 11.6 MALES MEAN 3.1 7.3 10.9 7.6 7.8 15.0 FEMALES MEAN 2.8 6.5 10.1 7.4 7.6 11.6 -727- MALES MEAN S.D. N 3.0 0.54 23 FEMALES MEAN S.D. N 2.8 0.55 23 NA = NOT APPLICABLE 6.1 0.97 23 5.7 1.00 23 9.7 1.18 23 9.5 1.13 23 7.7 0.71 23 7.3 0.75 23 7.7 1.19 23 7.5 1.09 23 13.5 2.48 23 12.2 2.19 23 APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 38 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25606-01 M 3.8 7.3 7.9 5.9 7.3 12.2 25606-02 M 3.2 7.9 8.5 6.6 7.0 13.4 25606-03 M 3.5 7.6 8.6 6.9 7.0 12.1 25606-04 F 3.2 6.9 7.8 6.4 5.4 13.7 25606-05 F 3.1 6.5 7.6 5.8 7.2 13.3 25606-06 F 3.2 NA NA NA NA NA 25606-07 F 3.3 NA NA NA NA NA 25606-08 F 3.7 6.8 7.9 6.0 5.3 13.3 25606-09 F 3.1 NA NA NA NA NA 25606-10 F 3.3 NA NA NA NA NA 25606-11 F 3.1 7.0 7.7 5.6 6.0 14.8 25606-12 F 3.8 6.8 7.3 5.8 5.3 13.0 25606-13 F 3.3 NA NA NA NA NA 25606-14 F 2.8 NA NA NA NA NA -728- MALES MEAN 3.5 7.6 8.3 6.5 7.1 12.6 FEMALES MEAN 3.3 6.8 7.7 5.9 5.8 13.6 25614-01 M 25614-02 M 25614-03 M 25614-04 M 25614-05 M 25614-06 M 25614-07 M 25614-08 M 2.5 NA NA NA NA NA 2.5 NA NA NA NA NA 2.2 NA NA NA NA NA 1.5 5.4 8.3 7.9 6.8 12.6 3.0 6.4 8.2 7.2 8.0 15.7 2.8 NA NA NA NA NA 1.9 5.8 7.8 7.6 5.6 12.8 2.7 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 39 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25614-09 M 2.0 NA NA NA NA NA 25614-10 M 2.8 6.2 8.4 7.7 6.4 13.1 25614-11 M 2.1 NA NA NA NA NA 25614-12 M 1.7 NA NA NA NA NA 25614-13 F 2.1 5.6 7.5 6.5 6.9 12.1 25614-14 F 2.3 NA NA NA NA NA 25614-15 F 1.4 4.8 7.4 6.4 6.1 12.4 25614-16 F 1.7 NA NA NA NA NA 25614-17 F 1.5 5.4 7.7 -3.1 15.8 9.5 25614-18 F 1.6 5.6 7.5 7.0 6.4 13.0 MALES MEAN 2.3 6.0 8.2 7.6 6.7 13.6 FEMALES MEAN 1.8 5.4 7.5 4.2 8.8 11.8 -729- 25671-01 M 25671-02 M 25671-03 M 25671-04 M 25671-05 M 25671-06 F 25671-07 F 25671-08 F 25671-09 F 25671-10 F 25671-11 F 25671-12 F 2.6 NA NA NA NA NA 2.6 6.1 9.7 8.6 9.3 9.0 2.6 6.4 10.8 9.2 9.6 10.6 2.5 5.9 9.6 8.7 8.7 7.7 2.1 5.1 9.6 7.4 8.4 10.8 1.9 5.8 9.9 7.9 8.2 7.6 2.6 NA NA NA NA NA 2.7 6.1 9.9 7.9 8.5 9.3 2.7 5.6 8.4 7.1 8.3 8.4 2.6 NA NA NA NA NA 2.5 NA NA NA NA NA 2.0 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 40 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25671-13 F 2.0 4.1 8.6 7.4 8.2 8.8 MALES MEAN 2.5 5.9 9.9 8.5 9.0 9.5 FEMALES MEAN 2.4 5.4 9.2 7.6 8.3 8.5 25698-01 M 25698-02 M 25698-03 M 25698-04 F 25698-05 M 25698-06 M 25698-07 F 25698-08 F 25698-09 F 25698-10 F 25698-11 F 25698-12 F 25698-13 F 25698-14 F 1.9 NA NA NA NA NA 1.6 4.7 7.8 8.7 6.4 9.7 1.6 5.3 7.1 8.2 6.0 10.2 2.1 5.0 8.1 8.9 5.6 10.4 1.8 4.6 7.8 7.8 6.0 8.8 1.1 4.2 6.1 8.7 5.7 9.4 1.8 NA NA NA NA NA 0.5 NA NA NA NA NA 1.8 NA NA NA NA NA 2.4 4.8 8.6 8.3 6.8 10.3 2.2 NA NA NA NA NA 2.2 4.5 7.8 7.3 8.1 6.5 2.2 NA NA NA NA NA 2.1 4.1 6.8 8.0 6.5 9.6 -730- MALES MEAN 1.6 4.7 7.2 8.4 6.0 9.5 FEMALES MEAN 1.9 4.6 7.8 8.1 6.8 9.2 25609-01 M 25609-02 M 25609-03 M 3.4 NA NA NA NA NA 2.3 4.2 6.9 5.4 6.9 9.5 2.0 5.2 9.0 5.6 7.8 13.8 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 41 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25609-04 M 3.1 5.2 8.7 4.3 6.9 12.0 25609-05 M 2.6 NA NA NA NA NA 25609-06 M 2.7 5.2 9.3 7.2 7.7 16.3 25609-07 F 3.0 NA NA NA NA NA 25609-08 F 2.7 NA NA NA NA NA 25609-09 F 3.2 NA NA NA NA NA 25609-10 F 3.1 NA NA NA NA NA 25609-11 F 3.0 5.7 8.3 4.5 7.4 8.6 25609-12 F 2.9 6.5 9.3 6.5 7.0 16.4 25609-13 F 3.3 NA NA NA NA NA 25609-14 F 3.4 4.6 8.5 6.6 6.8 14.0 25609-15 F 3.3 6.2 9.3 5.7 6.9 13.0 MALES MEAN 2.7 5.0 8.5 5.6 7.3 12.9 FEMALES MEAN 3.1 5.8 8.9 5.8 7.0 13.0 -731- 25677-02 M 25677-03 M 25677-04 M 25677-05 M 25677-06 M 25677-07 M 25677-08 F 25677-10 F 25677-11 F 25677-12 F 3.2 5.5 8.2 9.2 6.7 10.8 3.4 NA NA NA NA NA 3.5 5.1 8.4 8.1 8.8 8.5 3.6 5.9 8.4 7.4 8.2 11.9 3.3 NA NA NA NA NA 4.0 5.4 9.7 8.2 8.1 14.2 4.0 5.5 8.3 7.4 8.4 10.0 3.3 5.3 8.7 7.6 7.0 10.7 2.9 NA NA NA NA NA 2.2 4.7 8.1 8.9 6.9 8.6 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 42 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25677-13 F 3.8 5.4 8.4 8.5 6.8 12.3 MALES MEAN 3.5 5.5 8.7 8.2 8.0 11.4 FEMALES MEAN 3.2 5.2 8.4 8.1 7.3 10.4 25623-03 M 25623-04 M 25623-05 M 25623-06 M 25623-07 M 25623-08 M 25623-09 M 25623-10 F 25623-11 F 25623-12 F 25623-13 F 25623-14 F 25623-15 F 3.2 3.6 8.4 7.3 6.9 11.1 3.1 3.9 9.4 7.1 6.7 12.6 3.2 4.1 10.2 7.1 7.6 12.7 3.5 NA NA NA NA NA 2.8 NA NA NA NA NA 3.5 4.4 8.5 5.2 7.7 11.6 3.1 NA NA NA NA NA 2.7 NA NA NA NA NA 2.9 NA NA NA NA NA 0.7 NA NA NA NA NA 3.1 4.0 9.4 7.0 6.3 14.1 2.4 3.9 9.3 7.2 6.8 12.6 2.8 3.5 7.8 5.2 6.5 9.7 -732- MALES MEAN 3.2 4.0 9.1 6.7 7.2 12.0 FEMALES MEAN 2.4 3.8 8.8 6.5 6.5 12.1 25653-01 M 25653-02 M 25653-03 M 25653-04 M 3.1 NA NA NA NA NA 2.8 6.5 10.0 7.6 8.2 13.3 2.6 5.6 10.2 9.6 7.8 15.7 2.5 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 43 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25653-05 F 2.7 5.0 9.9 9.0 8.0 16.3 25653-06 F 2.6 5.9 9.6 8.8 7.4 14.1 25653-07 M 2.6 6.1 9.8 8.4 9.0 15.9 25653-08 F 2.0 NA NA NA NA NA 25653-09 F 2.6 NA NA NA NA NA 25653-10 F 1.8 NA NA NA NA NA 25653-11 M 2.5 5.8 10.3 9.2 8.7 13.8 25653-12 F 2.2 6.0 9.8 9.4 8.5 12.0 25653-13 F 2.2 5.6 9.2 6.4 8.4 11.8 25653-14 M 3.0 NA NA NA NA NA MALES MEAN 2.7 6.0 10.1 8.7 8.4 14.7 FEMALES MEAN 2.3 5.6 9.6 8.4 8.1 13.6 -733- 25604-01 M 25604-02 M 25604-03 M 25604-04 M 25604-05 M 25604-06 M 25604-07 M 25604-08 F 25604-09 F 25604-10 F 25604-11 F 4.1 NA NA NA NA NA 2.8 6.6 9.0 6.8 6.9 12.1 3.5 7.4 9.4 8.9 6.8 15.6 4.3 6.9 9.0 7.9 7.7 12.1 3.2 NA NA NA NA NA 3.7 6.7 8.4 8.6 6.2 14.4 3.8 NA NA NA NA NA 3.5 6.4 8.2 7.2 6.2 13.2 3.0 NA NA NA NA NA 3.4 5.8 9.0 7.9 5.3 11.0 3.1 5.8 9.0 7.9 6.9 11.0 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 44 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25604-12 F 3.9 7.2 8.7 6.5 7.3 9.4 MALES MEAN 3.6 6.9 9.0 8.1 6.9 13.6 FEMALES MEAN 3.4 6.3 8.7 7.4 6.4 11.2 25678-01 M 25678-02 M 25678-03 M 25678-04 M 25678-05 M 25678-06 M 25678-07 M 25678-08 F 25678-09 F 25678-10 F 25678-11 F 25678-12 F 25678-13 F 25678-14 F 25678-15 F 2.7 NA NA NA NA NA 2.4 6.0 9.5 7.2 7.1 11.3 3.2 7.6 10.1 7.9 7.3 12.2 2.9 NA NA NA NA NA 2.4 NA NA NA NA NA 2.8 6.7 11.0 7.0 7.4 12.7 2.5 6.8 10.2 7.6 7.3 13.0 3.0 7.4 9.2 7.9 7.7 14.6 2.8 NA NA NA NA NA 2.6 6.8 9.2 8.7 6.7 12.8 2.5 6.7 9.2 7.5 5.8 10.9 2.6 NA NA NA NA NA 2.1 5.3 9.6 7.1 7.4 12.1 3.0 NA NA NA NA NA 2.4 NA NA NA NA NA -734- MALES MEAN 2.7 6.8 10.2 7.4 7.3 12.3 FEMALES MEAN 2.6 6.6 9.3 7.8 6.9 12.6 25684-02 M 25684-03 M 3.5 7.1 9.9 8.4 6.4 16.2 3.3 5.4 9.3 8.2 5.6 15.5 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 45 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25684-04 M 2.9 5.2 8.8 6.3 6.5 13.1 25684-05 M 2.9 5.8 9.8 9.1 8.0 15.9 25684-06 F 3.7 6.1 8.7 6.0 7.7 15.7 25684-07 F 2.9 NA NA NA NA NA 25684-08 F 2.6 4.6 8.3 7.9 7.3 15.1 25684-09 F 2.8 NA NA NA NA NA 25684-10 F 3.1 NA NA NA NA NA 25684-11 F 3.0 4.4 7.8 7.5 6.6 11.6 25684-12 F 3.0 5.5 8.9 7.0 7.1 14.7 MALES MEAN 3.2 5.9 9.5 8.0 6.6 15.2 FEMALES MEAN 3.0 5.2 8.4 7.1 7.2 14.3 -735- 25714-01 M 25714-02 M 25714-03 M 25714-04 M 25714-05 M 25714-06 M 25714-07 F 25714-08 F 25714-09 F 25714-10 F 25714-11 F 25714-12 F 3.3 NA NA NA NA NA 3.3 6.5 10.6 5.2 9.3 13.2 3.7 6.4 11.4 7.3 7.9 17.4 2.9 NA NA NA NA NA 3.5 6.8 9.5 7.6 8.0 14.1 3.0 6.2 10.1 7.5 8.1 17.4 3.2 NA NA NA NA NA 3.5 6.5 8.1 7.0 5.9 17.1 3.1 6.4 9.4 7.2 7.2 16.0 3.2 6.1 10.3 6.6 7.1 15.9 3.0 NA NA NA NA NA 3.0 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 46 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25714-13 F 3.6 6.4 10.2 6.0 8.0 13.0 MALES MEAN 3.3 6.5 10.4 6.9 8.3 15.5 FEMALES MEAN 3.2 6.4 9.5 6.7 7.1 15.5 25650-01 F 25650-02 M 25650-03 M 25650-04 M 25650-05 M 25650-06 M 25650-07 M 25650-08 M 25650-09 M 25650-10 M 25650-11 M 25650-12 M 25650-13 M 25650-14 F 25650-15 F 25650-16 F 25650-17 F 25650-18 F 1.1 3.2 6.9 6.5 7.6 8.5 2.3 5.6 10.2 7.8 8.3 15.6 2.7 NA NA NA NA NA 2.5 NA NA NA NA NA 1.2 NA NA NA NA NA 2.4 NA NA NA NA NA 2.2 NA NA NA NA NA 3.7 6.5 11.1 8.4 9.3 12.5 2.4 NA NA NA NA NA 2.2 NA NA NA NA NA 2.5 5.9 10.5 6.5 9.5 13.1 3.0 NA NA NA NA NA 2.6 4.9 11.0 7.5 9.2 11.9 3.1 6.0 10.3 7.6 8.7 15.7 2.7 NA NA NA NA NA 2.3 NA NA NA NA NA 2.5 5.5 11.8 6.9 9.0 10.4 2.3 NA NA NA NA NA -736- NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 47 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25650-19 F 2.2 4.9 10.3 7.1 8.4 12.3 MALES MEAN 2.5 5.7 10.7 7.6 9.1 13.3 FEMALES MEAN 2.3 4.9 9.8 7.0 8.4 11.7 25735-01 M 25735-02 M 25735-03 M 25735-04 M 25735-05 M 25735-06 M 25735-07 F 25735-08 F 25735-09 F 25735-10 F 25735-11 F 25735-12 F 25735-13 F 25735-14 F 3.6 5.5 10.5 10.1 5.9 15.7 3.1 NA NA NA NA NA 3.6 NA NA NA NA NA 3.9 6.5 11.1 9.9 6.8 14.8 3.6 7.0 10.9 7.3 7.0 11.6 3.6 7.4 11.5 10.2 8.3 15.7 3.7 6.2 10.7 9.1 5.8 15.2 3.3 5.7 10.5 6.3 6.3 8.7 3.3 NA NA NA NA NA 3.9 6.4 10.7 9.5 6.8 13.1 3.5 NA NA NA NA NA 3.2 NA NA NA NA NA 3.6 NA NA NA NA NA 3.4 5.9 10.5 9.3 7.1 14.7 -737- MALES MEAN 3.6 6.6 11.0 9.4 7.0 14.5 FEMALES MEAN 3.5 6.1 10.6 8.6 6.5 12.9 25722-01 M 25722-02 M 25722-03 M 1.5 5.1 8.9 5.8 5.9 10.8 2.7 NA NA NA NA NA 2.9 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 48 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25722-04 M 1.7 4.5 8.0 9.4 5.1 12.1 25722-05 M 2.0 5.2 8.3 7.4 5.5 12.9 25722-06 M 2.0 NA NA NA NA NA 25722-07 M 2.3 NA NA NA NA NA 25722-08 M 2.1 NA NA NA NA NA 25722-09 M 2.7 NA NA NA NA NA 25722-10 M 3.0 4.1 9.0 8.3 5.1 12.1 25722-11 F 2.7 5.4 8.6 8.0 5.6 10.7 25722-12 F 2.9 5.3 8.9 8.1 5.7 12.0 25722-13 F 2.7 5.0 8.6 8.3 5.0 15.8 25722-14 F 3.0 NA NA NA NA NA 25722-15 F 2.3 5.2 10.2 4.9 7.1 9.4 MALES MEAN 2.3 4.7 8.6 7.7 5.4 12.0 FEMALES MEAN 2.7 5.2 9.1 7.3 5.9 12.0 -738- 25642-01 M 25642-02 M 25642-03 M 25642-04 M 25642-05 M 25642-06 M 25642-07 M 25642-08 M 25642-09 F 25642-10 F 2.5 NA NA NA NA NA 2.9 7.0 10.0 9.3 10.1 13.0 2.3 NA NA NA NA NA 2.9 7.4 11.2 8.3 8.4 16.5 2.9 6.2 10.9 6.3 8.7 11.8 3.1 NA NA NA NA NA 2.0 NA NA NA NA NA 2.9 7.0 10.3 7.2 7.7 19.3 2.0 NA NA NA NA NA 2.3 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 49 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25642-11 F 2.6 NA NA NA NA NA 25642-12 F 2.7 6.5 11.0 5.6 8.5 11.0 25642-13 F 2.5 6.3 10.9 6.6 7.5 12.8 25642-14 F 2.5 NA NA NA NA NA 25642-15 F 3.3 6.4 10.4 8.1 7.3 13.8 MALES MEAN 2.7 6.9 10.6 7.8 8.7 15.2 FEMALES MEAN 2.6 6.4 10.8 6.8 7.8 12.5 -739- 25628-01 M 25628-02 M 25628-03 M 25628-04 M 25628-05 M 25628-07 M 25628-08 M 25628-09 M 25628-10 F 25628-11 F 25628-12 F 25628-13 F 25628-14 F 25628-15 F 25628-16 F 2.8 5.0 9.5 7.7 7.8 13.0 2.4 NA NA NA NA NA 2.2 NA NA NA NA NA 2.5 NA NA NA NA NA 2.6 5.0 10.6 8.6 8.2 13.0 2.5 4.8 10.5 6.8 7.8 11.7 2.5 NA NA NA NA NA 2.4 5.1 10.5 8.0 7.8 12.5 2.0 NA NA NA NA NA 2.3 NA NA NA NA NA 2.7 NA NA NA NA NA 2.8 NA NA NA NA NA 1.8 5.4 10.1 9.2 7.3 12.2 2.8 5.7 9.3 8.6 9.5 13.1 2.4 4.5 9.5 8.6 7.5 12.7 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 50 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25628-17 F 0.7 3.2 8.9 5.7 7.7 8.6 MALES MEAN 2.5 5.0 10.3 7.8 7.9 12.6 FEMALES MEAN 2.2 4.7 9.5 8.0 8.0 11.7 25763-01 M 25763-02 M 25763-03 M 25763-04 M 25763-05 M 25763-06 M 25763-07 M 25763-08 M 25763-09 F 25763-10 F 25763-11 F 25763-12 F 25763-13 F 25763-14 F 25763-15 F 25763-16 F 25763-17 F 25763-18 F 1.7 NA NA NA NA NA 2.7 5.7 12.0 8.4 9.9 7.8 1.7 NA NA NA NA NA 1.7 5.4 11.1 8.7 8.8 8.3 2.6 NA NA NA NA NA 2.0 NA NA NA NA NA 1.9 4.7 11.5 8.6 10.2 8.2 1.1 NA NA NA NA NA 2.3 5.4 11.6 7.7 8.8 10.8 1.9 5.6 11.1 8.1 9.1 9.1 1.4 NA NA NA NA NA 2.4 NA NA NA NA NA 1.2 NA NA NA NA NA 1.4 NA NA NA NA NA 1.4 5.6 11.7 8.4 9.3 11.5 2.2 NA NA NA NA NA 1.7 NA NA NA NA NA 2.0 NA NA NA NA NA -740- NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 51 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25763-19 F 1.3 NA NA NA NA NA MALES MEAN 1.9 5.3 11.5 8.6 9.6 8.1 FEMALES MEAN 1.7 5.5 11.5 8.1 9.1 10.5 25766-01 M 25766-02 M 25766-03 M 25766-05 F 25766-06 F 25766-07 F 25766-08 F 25766-09 F 25766-10 M 25766-11 M 2.7 3.5 8.6 4.8 6.2 6.2 2.9 4.6 8.6 5.8 4.5 11.3 2.3 4.5 8.9 5.0 5.9 11.2 2.9 NA NA NA NA NA 2.3 4.1 7.9 4.4 5.3 6.9 2.9 4.2 9.4 5.5 6.2 11.5 2.6 4.6 8.1 4.7 5.8 10.9 2.3 3.9 7.5 4.7 6.1 10.5 2.6 NA NA NA NA NA 3.1 4.0 7.8 4.8 5.4 10.4 -741- MALES MEAN 2.7 4.2 8.5 5.1 5.5 9.8 FEMALES MEAN 2.6 4.2 8.2 4.8 5.9 10.0 25689-01 M 25689-02 M 25689-03 M 25689-04 M 25689-05 M 25689-06 M 25689-07 F 2.7 NA NA NA NA NA 3.2 6.9 11.0 8.5 8.1 17.7 3.0 6.8 12.1 7.2 7.3 19.7 2.7 6.1 11.5 8.4 8.3 18.6 3.0 NA NA NA NA NA 3.2 5.5 12.1 8.7 8.0 15.5 2.4 6.1 11.4 7.3 8.6 15.4 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 52 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25689-08 F 2.0 NA NA NA NA NA 25689-09 F 2.9 NA NA NA NA NA 25689-10 F 3.9 NA NA NA NA NA 25689-11 F 2.9 NA NA NA NA NA 25689-12 F 3.2 6.2 11.7 9.3 8.3 16.6 25689-13 F 2.9 6.1 10.4 8.0 7.4 17.1 25689-14 F 2.2 5.8 11.4 8.0 8.0 12.7 25689-15 F 2.8 NA NA NA NA NA MALES MEAN 3.0 6.3 11.7 8.2 7.9 17.9 FEMALES MEAN 2.8 6.1 11.2 8.2 8.1 15.5 -742- 25708-01 M 25708-02 M 25708-03 M 25708-04 M 25708-05 M 25708-06 M 25708-07 M 25708-08 M 25708-09 M 25708-10 F 25708-11 F 25708-12 F 25708-13 F 25708-14 F 3.5 6.9 10.9 8.2 7.7 11.5 3.1 NA NA NA NA NA 3.3 NA NA NA NA NA 3.6 6.2 9.9 7.5 7.4 15.2 2.6 NA NA NA NA NA 3.5 NA NA NA NA NA 3.6 4.7 11.5 8.7 8.1 12.4 3.6 NA NA NA NA NA 2.9 5.3 10.2 7.9 7.9 14.5 2.0 NA NA NA NA NA 2.8 5.0 11.5 7.7 7.4 10.8 2.2 3.9 9.3 6.7 7.7 10.6 2.5 NA NA NA NA NA 2.9 5.3 9.5 7.6 8.1 12.8 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 53 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25708-15 F 2.5 5.5 10.4 6.1 7.4 10.9 MALES MEAN 3.3 5.8 10.6 8.1 7.8 13.4 FEMALES MEAN 2.5 4.9 10.2 7.0 7.7 11.3 25743-01 M 25743-02 M 25743-03 M 25743-04 M 25743-05 M 25743-06 M 25743-08 M 25743-09 M 25743-10 M 25743-11 F 25743-12 F 25743-13 F 25743-14 F 25743-15 F 25743-16 F 25743-17 F 2.2 NA NA NA NA NA 2.6 5.8 10.0 8.5 6.0 13.7 2.4 NA NA NA NA NA 1.7 4.9 9.6 7.2 6.2 10.9 2.1 NA NA NA NA NA 1.8 NA NA NA NA NA 2.1 5.2 9.0 8.7 4.5 10.7 2.1 7.0 10.8 8.0 7.1 14.9 2.4 NA NA NA NA NA 2.3 4.9 9.0 7.6 6.7 10.9 2.2 4.5 8.4 7.5 6.7 10.8 2.7 NA NA NA NA NA 2.7 NA NA NA NA NA 2.2 NA NA NA NA NA 1.8 4.8 9.1 6.9 6.8 8.2 2.2 NA NA NA NA NA -743- NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 54 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25743-18 F 2.1 5.6 9.8 5.9 8.4 13.3 MALES MEAN 2.2 5.7 9.9 8.1 6.0 12.6 FEMALES MEAN 2.3 5.0 9.1 7.0 7.2 10.8 25761-01 M 25761-02 M 25761-03 M 25761-04 M 25761-05 M 25761-06 M 25761-07 M 25761-08 F 25761-09 F 25761-10 F 25761-11 F 25761-12 F 25761-13 F 25761-14 F 25761-15 F 2.6 NA NA NA NA NA 3.2 NA NA NA NA NA 2.7 NA NA NA NA NA 2.6 6.4 11.6 8.1 8.7 13.5 2.8 6.1 12.1 8.2 7.9 13.1 3.4 6.7 11.4 8.2 9.4 13.4 3.4 7.0 11.8 9.0 9.9 16.6 2.6 6.2 12.1 8.7 7.8 15.3 2.2 6.3 12.0 8.7 9.5 11.6 3.0 NA NA NA NA NA 3.0 NA NA NA NA NA 3.1 NA NA NA NA NA 2.9 5.8 12.1 8.3 8.1 7.5 2.8 NA NA NA NA NA 3.1 6.0 11.1 8.7 8.3 13.1 -744- MALES MEAN 3.0 6.6 11.7 8.4 9.0 14.2 FEMALES MEAN 2.8 6.1 11.8 8.6 8.4 11.9 25712-02 M 25712-03 M 3.2 6.5 10.1 8.2 8.9 12.1 2.2 6.1 9.7 7.2 8.6 15.0 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 55 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25712-04 M 3.3 NA NA NA NA NA 25712-05 M 2.6 6.0 10.0 7.8 7.8 15.1 25712-06 M 3.4 7.5 11.2 7.7 9.5 15.1 25712-07 F 3.3 6.3 10.4 7.0 8.2 8.4 25712-08 F 2.9 5.3 8.4 7.8 8.5 12.6 25712-09 F 3.4 NA NA NA NA NA 25712-10 F 3.3 NA NA NA NA NA 25712-11 F 2.3 NA NA NA NA NA 25712-12 F 2.6 NA NA NA NA NA 25712-13 F 3.4 NA NA NA NA NA 25712-14 F 2.9 NA NA NA NA NA 25712-15 F 2.4 NA NA NA NA NA 25712-16 F 3.0 6.5 10.2 7.2 9.0 14.0 25712-17 F 2.5 7.1 9.3 7.7 8.3 13.7 -745- MALES MEAN 2.9 6.5 10.3 7.7 8.7 14.3 FEMALES MEAN 2.9 6.3 9.6 7.4 8.5 12.2 25746-01 M 25746-03 M 25746-04 M 25746-05 M 25746-06 M 25746-07 M 25746-08 M 25746-09 M 2.8 NA NA NA NA NA 2.0 6.4 11.0 9.4 8.8 19.2 2.5 NA NA NA NA NA 2.3 NA NA NA NA NA 2.8 6.7 9.7 8.7 9.0 17.4 3.6 6.6 10.2 9.4 8.6 18.5 2.5 NA NA NA NA NA 2.8 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 56 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25746-10 M 3.3 NA NA NA NA NA 25746-11 M 2.7 6.4 10.9 9.4 8.9 14.8 25746-12 F 2.8 5.9 10.0 8.4 8.2 12.9 25746-13 F 2.6 NA NA NA NA NA 25746-14 F 2.2 5.5 8.8 9.1 9.4 66.9 25746-15 F 2.6 6.2 10.1 9.1 8.3 29.0 25746-16 F 2.6 NA NA NA NA NA 25746-17 F 2.8 6.6 11.0 9.0 9.2 16.4 25746-18 F 2.3 NA NA NA NA NA MALES MEAN 2.7 6.5 10.5 9.2 8.8 17.5 FEMALES MEAN 2.6 6.1 10.0 8.9 8.8 31.3 -746- MALES MEAN S.D. N 2.8 0.52 25 FEMALES MEAN S.D. N 2.6 0.49 25 NA = NOT APPLICABLE 5.9 0.90 25 5.5 0.78 25 9.8 1.19 25 9.4 1.15 25 7.8 1.00 25 7.3 1.16 25 7.6 1.18 25 7.5 0.98 25 13.1 2.36 25 12.8 4.21 25 APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 57 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25696-01 M 2.9 NA NA NA NA NA 25696-02 M 2.6 NA NA NA NA NA 25696-03 M 2.3 NA NA NA NA NA 25696-04 M 3.1 5.7 8.8 6.0 6.8 13.9 25696-05 M 3.0 NA NA NA NA NA 25696-06 M 2.2 5.0 6.8 7.4 6.4 12.6 25696-07 M 3.0 4.9 8.9 7.1 6.6 14.3 25696-08 M 2.9 NA NA NA NA NA 25696-09 M 2.4 5.1 7.6 7.6 5.4 13.7 25696-10 M 1.9 NA NA NA NA NA 25696-11 F 2.9 6.4 8.2 6.5 6.9 11.7 25696-12 F 1.9 NA NA NA NA NA 25696-13 F 2.9 6.5 7.9 6.8 6.5 14.4 25696-14 F 2.6 5.1 7.9 7.0 6.2 13.1 25696-15 F 2.6 NA NA NA NA NA 25696-16 F 2.6 5.9 8.8 8.0 6.5 14.1 -747- MALES MEAN 2.6 5.2 8.0 7.0 6.3 13.6 FEMALES MEAN 2.6 6.0 8.2 7.1 6.5 13.3 25686-01 M 25686-02 M 25686-03 M 25686-04 M 25686-05 M 25686-06 M 3.1 6.2 9.3 7.5 5.0 11.7 2.4 5.9 8.1 6.9 5.8 10.9 2.8 5.7 9.5 7.6 4.7 13.3 2.8 6.2 8.0 5.9 5.2 11.9 2.4 NA NA NA NA NA 2.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 58 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25686-07 M 2.6 NA NA NA NA NA 25686-08 M 2.3 NA NA NA NA NA 25686-09 F 2.7 5.7 8.4 7.1 5.2 12.0 25686-10 F 2.2 4.9 8.0 6.3 5.1 9.6 25686-11 F 2.4 6.5 8.4 7.1 5.3 11.8 25686-12 F 2.1 NA NA NA NA NA 25686-13 F 2.5 NA NA NA NA NA 25686-14 F 2.4 NA NA NA NA NA 25686-15 F 1.9 4.7 7.5 6.4 5.6 11.1 MALES MEAN 2.6 6.0 8.7 7.0 5.2 12.0 FEMALES MEAN 2.3 5.5 8.1 6.7 5.3 11.1 -748- 25639-01 M 25639-02 M 25639-03 M 25639-04 F 25639-05 M 25639-06 M 25639-07 M 25639-08 M 25639-09 M 25639-10 F 25639-11 F 25639-12 F 25639-13 F 3.2 NA NA NA NA NA 2.5 NA NA NA NA NA 2.1 6.8 9.7 8.6 7.5 10.7 3.0 7.6 9.7 8.0 7.7 10.4 3.6 5.4 8.6 8.8 7.7 10.8 3.0 7.2 8.8 8.1 6.7 9.7 3.7 NA NA NA NA NA 2.8 NA NA NA NA NA 3.4 7.6 10.0 8.4 7.3 12.1 1.7 NA NA NA NA NA 2.3 7.2 7.5 10.3 6.9 12.0 3.1 6.3 8.9 8.9 6.6 12.2 2.1 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 59 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25639-14 F 2.9 5.9 9.9 8.8 6.1 11.4 25639-15 F 1.7 NA NA NA NA NA 25639-16 F 3.0 NA NA NA NA NA MALES MEAN 3.0 6.8 9.3 8.5 7.3 10.8 FEMALES MEAN 2.5 6.8 9.0 9.0 6.8 11.5 25658-03 M 25658-04 M 25658-05 M 25658-06 M 25658-07 M 25658-08 M 25658-09 M 25658-10 F 25658-11 F 25658-12 F 25658-13 F 25658-14 F 25658-15 F 0.9 5.1 8.4 7.7 8.5 10.9 1.3 4.3 7.5 7.9 7.7 9.1 1.5 4.7 7.8 8.3 7.5 10.2 1.2 NA NA NA NA NA 1.2 NA NA NA NA NA 2.0 5.1 8.5 6.6 8.0 8.2 1.1 NA NA NA NA NA 1.4 5.8 7.9 7.9 6.3 11.0 1.8 NA NA NA NA NA 1.2 NA NA NA NA NA 1.3 5.0 7.6 8.2 7.7 10.4 1.1 4.8 8.1 6.6 7.6 7.3 1.6 4.6 7.5 7.7 8.1 9.5 -749- MALES MEAN 1.3 4.8 8.1 7.6 7.9 9.6 FEMALES MEAN 1.4 5.1 7.8 7.6 7.4 9.6 25676-02 M 25676-03 M 3.1 7.3 8.1 5.0 5.2 16.6 2.9 7.6 9.0 7.5 7.1 17.2 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 60 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25676-04 M 2.7 7.5 7.9 7.0 5.3 17.3 25676-05 M 2.8 NA NA NA NA NA 25676-06 M 2.9 7.7 8.6 7.9 6.5 16.2 25676-07 M 2.7 NA NA NA NA NA 25676-08 F 2.3 7.1 8.8 6.4 6.4 15.2 25676-09 F 2.8 7.5 8.0 7.0 5.4 16.1 25676-10 F 2.2 NA NA NA NA NA 25676-11 F 1.9 NA NA NA NA NA 25676-12 F 2.6 7.7 8.7 7.6 5.7 14.0 25676-13 F 2.4 NA NA NA NA NA 25676-14 F 2.5 NA NA NA NA NA 25676-15 F 2.4 7.5 7.7 6.8 5.5 13.6 MALES MEAN 2.9 7.5 8.4 6.9 6.0 16.8 FEMALES MEAN 2.4 7.5 8.3 7.0 5.8 14.7 -750- 25600-01 M 25600-02 M 25600-03 M 25600-04 M 25600-05 F 25600-06 F 25600-07 F 25600-08 F 25600-09 F 25600-10 F 2.9 7.0 9.5 8.3 8.4 15.6 3.8 6.5 8.8 8.7 8.4 14.2 2.9 6.4 9.4 9.6 8.8 14.2 3.2 6.4 10.4 7.7 8.1 14.3 3.2 6.3 9.0 8.0 8.4 13.3 3.1 NA NA NA NA NA 3.6 NA NA NA NA NA 3.0 NA NA NA NA NA 2.6 NA NA NA NA NA 3.0 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 61 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25600-11 F 3.8 7.3 10.5 7.9 7.8 17.6 25600-12 F 3.7 6.6 10.4 7.9 8.6 14.1 25600-13 F 3.6 NA NA NA NA NA 25600-14 F 2.5 NA NA NA NA NA 25600-15 F 3.9 7.7 9.4 7.8 8.8 14.0 25600-16 F 2.4 NA NA NA NA NA 25600-17 F 4.0 NA NA NA NA NA MALES MEAN 3.2 6.6 9.5 8.6 8.4 14.6 FEMALES MEAN 3.3 7.0 9.8 7.9 8.4 14.8 -751- 25603-01 M 25603-02 M 25603-03 M 25603-04 M 25603-05 M 25603-06 F 25603-07 F 25603-08 F 25603-09 F 25603-10 F 25603-11 F 25603-12 F 25603-13 F 25603-14 F 3.0 5.9 8.1 7.3 6.3 17.9 1.7 5.8 7.5 6.8 5.8 15.8 2.9 NA NA NA NA NA 3.6 6.0 7.9 5.5 6.5 14.6 2.6 6.2 8.5 6.9 6.4 18.3 3.0 5.8 8.0 6.3 5.7 18.2 3.0 5.5 7.3 6.4 5.1 16.1 1.8 NA NA NA NA NA 2.0 NA NA NA NA NA 3.2 5.6 8.6 4.8 7.2 15.5 1.9 NA NA NA NA NA 2.7 6.0 9.2 5.9 6.0 16.2 3.2 NA NA NA NA NA 3.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 62 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25603-15 F 3.1 NA NA NA NA NA MALES MEAN 2.8 6.0 8.0 6.6 6.3 16.7 FEMALES MEAN 2.7 5.7 8.3 5.9 6.0 16.5 25630-01 M 25630-02 M 25630-03 M 25630-04 M 25630-05 M 25630-06 M 25630-07 M 25630-08 F 25630-09 F 25630-10 F 25630-11 F 25630-12 F 25630-13 F 25630-14 F 3.0 6.0 9.2 8.0 8.4 12.9 3.4 NA NA NA NA NA 2.7 NA NA NA NA NA 3.7 6.2 9.0 7.6 9.6 11.2 3.2 6.0 8.6 8.2 9.5 12.0 3.1 6.2 9.2 8.4 10.2 10.5 3.5 NA NA NA NA NA 3.0 NA NA NA NA NA 2.7 5.6 8.6 7.8 7.6 8.8 2.9 5.6 7.5 8.8 7.8 11.6 3.2 6.4 9.1 8.1 8.8 11.9 2.8 NA NA NA NA NA 3.1 5.8 8.7 8.4 7.3 11.6 3.5 NA NA NA NA NA -752- MALES MEAN 3.2 6.1 9.0 8.1 9.4 11.7 FEMALES MEAN 3.0 5.9 8.5 8.3 7.9 11.0 25703-01 M 25703-02 M 25703-03 M 2.3 NA NA NA NA NA 3.2 7.9 10.1 8.0 7.7 13.9 2.7 7.4 9.8 6.7 7.9 12.7 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 63 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25703-04 M 3.0 7.8 10.8 8.0 7.4 17.0 25703-05 M 2.4 7.5 9.2 8.2 9.0 16.0 25703-06 F 2.4 NA NA NA NA NA 25703-07 F 2.2 NA NA NA NA NA 25703-08 F 1.8 7.1 9.1 7.3 6.8 13.7 25703-09 F 2.6 7.0 9.7 7.7 7.1 13.6 25703-10 F 2.2 7.3 9.2 6.2 7.5 11.0 25703-11 F 1.5 NA NA NA NA NA 25703-12 F 2.3 NA NA NA NA NA 25703-13 F 2.3 NA NA NA NA NA 25703-14 F 2.8 8.1 9.4 8.2 6.6 14.0 25703-15 F 1.9 NA NA NA NA NA MALES MEAN 2.7 7.7 10.0 7.7 8.0 14.9 FEMALES MEAN 2.2 7.4 9.4 7.4 7.0 13.1 -753- 25673-01 M 25673-02 M 25673-03 M 25673-04 M 25673-05 M 25673-06 M 25673-07 M 25673-08 M 25673-09 M 25673-10 F 2.3 NA NA NA NA NA 2.4 NA NA NA NA NA 2.0 5.0 6.4 6.0 6.3 9.1 2.6 4.9 7.8 6.7 6.0 10.1 1.8 NA NA NA NA NA 1.9 NA NA NA NA NA 2.8 NA NA NA NA NA 2.0 4.6 7.1 5.2 6.0 8.2 2.7 4.6 7.7 5.0 5.9 7.6 2.8 4.7 6.4 4.4 5.6 8.1 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 64 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25673-11 F 2.1 5.1 6.7 6.6 6.1 9.1 25673-12 F 2.5 5.2 8.2 6.6 5.7 10.2 25673-13 F 2.5 NA NA NA NA NA 25673-14 F 2.2 4.4 6.4 6.1 5.8 9.0 25673-15 F 2.3 NA NA NA NA NA MALES MEAN 2.3 4.8 7.3 5.7 6.1 8.8 FEMALES MEAN 2.4 4.9 6.9 5.9 5.8 9.1 -754- 25611-04 M 25611-05 M 25611-06 M 25611-07 M 25611-08 M 25611-09 M 25611-10 M 25611-11 F 25611-12 F 25611-13 F 25611-14 F 25611-15 F 3.3 NA NA NA NA NA 2.9 5.3 7.4 7.4 6.8 13.6 3.0 NA NA NA NA NA 2.9 6.0 8.0 6.5 7.3 12.0 3.1 5.6 8.0 8.6 6.8 12.7 3.2 NA NA NA NA NA 3.4 5.5 7.6 8.5 5.7 12.5 2.9 5.4 8.6 4.9 7.4 10.3 2.8 4.7 8.0 8.9 6.2 11.1 3.0 6.1 7.4 8.5 5.8 12.0 2.3 NA NA NA NA NA 2.9 6.0 7.9 8.8 6.3 13.3 MALES MEAN 3.1 5.6 7.8 7.8 6.7 12.7 FEMALES MEAN 2.8 5.6 8.0 7.8 6.4 11.7 25619-01 M 2.7 5.1 8.1 7.0 3.6 12.5 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 65 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25619-02 M 2.5 NA NA NA NA NA 25619-03 M 3.0 6.0 8.9 8.3 4.4 12.2 25619-04 M 2.1 3.8 6.5 5.7 4.3 6.9 25619-05 M 2.9 5.4 10.1 7.4 4.7 13.3 25619-06 M 2.4 NA NA NA NA NA 25619-07 F 2.2 NA NA NA NA NA 25619-08 F 2.3 5.2 9.5 7.0 5.5 12.2 25619-09 F 2.2 NA NA NA NA NA 25619-10 F 2.2 4.3 8.9 6.0 4.0 7.9 25619-11 F 2.3 NA NA NA NA NA 25619-12 F 2.6 5.3 9.3 4.0 4.8 8.3 25619-13 F 2.0 NA NA NA NA NA 25619-14 F 2.5 5.0 8.7 7.1 4.7 13.5 -755- MALES MEAN 2.6 5.1 8.4 7.1 4.3 11.2 FEMALES MEAN 2.3 5.0 9.1 6.0 4.8 10.5 25705-01 M 25705-02 M 25705-03 M 25705-04 M 25705-05 M 25705-06 M 25705-07 M 25705-08 F 25705-09 F 1.5 4.1 7.1 6.5 2.8 6.9 3.5 NA NA NA NA NA 3.3 NA NA NA NA NA 3.6 NA NA NA NA NA 3.6 6.9 10.1 8.7 6.1 13.6 3.2 6.4 8.5 7.8 4.3 13.1 3.5 6.8 9.5 7.5 7.4 9.3 4.3 7.0 9.7 7.0 5.9 10.1 3.4 6.6 9.2 9.0 4.9 12.7 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 66 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25705-10 F 3.4 7.2 9.3 9.1 5.6 14.4 25705-11 F 3.5 7.0 9.9 9.4 5.3 13.4 25705-12 F 3.6 NA NA NA NA NA 25705-13 F 3.2 NA NA NA NA NA MALES MEAN 3.2 6.1 8.8 7.6 5.2 10.7 FEMALES MEAN 3.6 7.0 9.5 8.6 5.4 12.7 -756- 25691-01 F 25691-02 M 25691-03 M 25691-04 M 25691-05 M 25691-06 M 25691-07 M 25691-08 M 25691-09 M 25691-10 F 25691-11 F 25691-12 F 25691-14 F 25691-15 F 2.3 NA NA NA NA NA 2.3 5.4 10.7 10.4 5.8 14.7 2.8 NA NA NA NA NA 2.3 NA NA NA NA NA 2.8 6.0 10.9 8.7 5.0 11.3 3.1 5.9 10.7 10.1 7.7 11.8 3.2 6.9 11.1 9.4 5.9 7.7 3.4 NA NA NA NA NA 3.2 NA NA NA NA NA 2.5 NA NA NA NA NA 3.1 7.3 11.8 6.8 9.2 8.1 2.9 6.3 11.9 10.3 7.6 12.3 3.1 7.5 10.3 9.9 7.4 12.8 3.1 6.9 11.7 8.5 8.9 14.8 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 67 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25691-16 F 2.3 NA NA NA NA NA MALES MEAN 2.9 6.1 10.9 9.7 6.1 11.4 FEMALES MEAN 2.8 7.0 11.4 8.9 8.3 12.0 25717-03 M 25717-04 M 25717-05 M 25717-06 M 25717-07 M 25717-08 M 25717-09 F 25717-10 F 25717-11 F 25717-12 F 25717-13 F 25717-14 F 25717-15 F 1.4 4.6 8.6 5.9 8.2 11.5 1.4 4.4 9.0 5.4 7.5 11.1 1.7 NA NA NA NA NA 1.5 5.3 9.3 6.2 6.6 13.9 1.8 5.1 8.6 6.2 7.9 10.8 1.5 NA NA NA NA NA 1.6 NA NA NA NA NA 1.3 NA NA NA NA NA 1.3 3.9 8.5 6.0 7.8 11.4 1.5 NA NA NA NA NA 1.9 4.0 8.7 5.8 8.0 10.9 1.1 4.7 8.6 7.6 7.0 11.4 1.5 4.4 8.7 5.8 7.0 8.5 -757- MALES MEAN 1.6 4.9 8.9 5.9 7.6 11.8 FEMALES MEAN 1.5 4.3 8.6 6.3 7.5 10.6 25616-01 M 25616-02 M 25616-03 M 25616-04 M 3.5 NA NA NA NA NA 3.5 6.0 10.8 8.2 8.9 12.4 4.1 7.2 11.3 7.5 8.6 17.0 3.6 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 68 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25616-05 M 3.6 5.7 11.2 6.3 9.8 8.1 25616-06 M 3.9 NA NA NA NA NA 25616-07 M 4.3 NA NA NA NA NA 25616-08 F 3.9 NA NA NA NA NA 25616-09 F 3.1 NA NA NA NA NA 25616-10 F 3.0 5.4 9.9 8.4 8.3 12.9 25616-11 F 3.5 6.4 10.8 8.1 9.3 11.3 25616-12 M 3.7 6.1 11.6 7.0 10.5 15.1 25616-13 F 2.6 4.7 10.6 8.0 8.0 12.7 25616-14 F 3.0 5.5 11.3 6.6 9.7 10.1 25616-15 F 3.1 NA NA NA NA NA MALES MEAN 3.8 6.3 11.2 7.3 9.5 13.2 FEMALES MEAN 3.2 5.5 10.7 7.8 8.8 11.8 -758- 25715-03 M 25715-04 M 25715-05 M 25715-06 M 25715-07 M 25715-08 M 25715-09 M 25715-10 F 25715-11 F 25715-12 F 25715-13 F 2.3 NA NA NA NA NA 2.6 6.8 9.9 9.0 8.4 12.1 3.0 NA NA NA NA NA 2.4 6.2 10.3 8.3 7.6 14.1 2.7 5.4 10.4 7.2 7.8 9.3 2.1 6.6 9.6 8.7 8.3 14.7 2.2 NA NA NA NA NA 2.1 5.7 9.5 6.5 8.3 9.6 2.8 NA NA NA NA NA 2.9 NA NA NA NA NA 2.9 5.7 9.9 9.1 8.0 12.6 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 69 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25715-14 F 2.3 NA NA NA NA NA 25715-15 F 2.9 6.1 10.6 8.9 7.6 13.3 25715-16 F 2.6 NA NA NA NA NA 25715-17 F 2.3 5.6 10.1 7.8 6.8 11.6 MALES MEAN 2.5 6.3 10.1 8.3 8.0 12.6 FEMALES MEAN 2.6 5.8 10.0 8.1 7.7 11.8 -759- 25762-01 M 25762-02 M 25762-03 M 25762-04 M 25762-05 M 25762-06 M 25762-07 F 25762-08 F 25762-09 F 25762-10 F 25762-11 F 25762-12 F 25762-13 F 25762-14 F 2.3 4.5 10.1 7.8 6.9 9.6 2.1 NA NA NA NA NA 3.0 5.3 11.4 8.8 7.0 15.8 2.4 NA NA NA NA NA 2.3 4.6 11.4 7.7 6.7 12.9 2.6 4.5 11.2 7.6 7.3 13.3 1.8 4.5 9.8 7.9 6.8 11.3 3.0 4.7 10.0 7.8 6.6 12.0 2.6 NA NA NA NA NA 1.9 NA NA NA NA NA 2.3 4.9 9.3 7.6 5.6 10.7 2.2 NA NA NA NA NA 2.1 NA NA NA NA NA 2.9 4.7 11.0 7.3 6.8 13.5 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 70 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25762-15 F 2.9 NA NA NA NA NA MALES MEAN 2.5 4.7 11.0 8.0 7.0 12.9 FEMALES MEAN 2.4 4.7 10.0 7.7 6.5 11.9 25599-01 M 25599-02 M 25599-03 M 25599-04 M 25599-05 M 25599-06 M 25599-07 M 25599-09 M 25599-10 M 25599-11 F 25599-12 F 25599-13 F 25599-14 F 25599-15 F 25599-16 F 25599-17 F 25599-18 F 1.6 NA NA NA NA NA 1.8 NA NA NA NA NA 1.0 2.9 8.0 7.0 6.7 8.8 1.7 NA NA NA NA NA 1.4 NA NA NA NA NA 1.8 3.8 9.2 6.2 8.0 9.4 2.4 NA NA NA NA NA 1.5 3.4 8.4 6.7 7.7 9.0 2.1 4.3 8.6 7.4 7.9 9.6 1.7 4.3 8.3 5.4 7.0 8.2 2.3 3.9 10.0 7.6 7.1 12.2 2.1 NA NA NA NA NA 1.1 NA NA NA NA NA 1.2 NA NA NA NA NA 2.0 NA NA NA NA NA 1.9 3.4 9.1 7.0 7.4 8.7 1.7 NA NA NA NA NA -760- NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 71 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25599-19 F 1.7 3.8 9.4 8.5 5.4 9.9 MALES MEAN 1.7 3.6 8.6 6.8 7.6 9.2 FEMALES MEAN 1.7 3.9 9.2 7.1 6.7 9.8 25647-02 M 25647-03 M 25647-04 M 25647-05 M 25647-06 M 25647-07 M 25647-08 F 25647-09 F 25647-10 F 25647-11 F 25647-12 F 25647-13 M 25647-14 F 2.3 NA NA NA NA NA 2.3 NA NA NA NA NA 2.2 3.7 8.3 6.5 5.2 10.0 2.7 NA NA NA NA NA 1.6 2.6 6.3 6.3 3.6 7.5 1.4 3.2 6.8 6.2 3.4 3.9 2.2 4.6 8.0 6.3 4.6 11.1 2.2 NA NA NA NA NA 2.0 NA NA NA NA NA 2.7 4.8 8.9 4.9 6.2 10.1 3.0 4.4 9.1 6.6 4.3 11.6 2.7 3.7 8.0 6.7 4.3 8.0 2.7 4.4 8.5 7.3 5.6 9.7 -761- MALES MEAN 2.2 3.3 7.4 6.4 4.1 7.4 FEMALES MEAN 2.5 4.6 8.6 6.3 5.2 10.6 25747-01 M 25747-02 M 25747-03 M 25747-04 M 1.6 4.9 8.4 5.1 6.6 10.5 2.1 NA NA NA NA NA 1.6 5.8 10.2 6.0 8.1 14.9 2.4 5.8 9.7 5.9 8.9 16.6 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 72 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25747-05 M 2.1 7.0 10.5 6.1 8.8 13.9 25747-06 M 2.5 NA NA NA NA NA 25747-07 M 2.8 NA NA NA NA NA 25747-08 F 2.5 5.9 10.1 6.0 7.8 16.3 25747-09 F 2.1 5.4 8.7 6.1 6.6 14.2 25747-10 F 1.6 NA NA NA NA NA 25747-11 F 2.1 NA NA NA NA NA 25747-12 F 1.9 NA NA NA NA NA 25747-13 F 2.1 6.7 11.1 5.2 7.3 15.8 25747-14 F 2.3 NA NA NA NA NA 25747-15 F 2.1 5.8 9.7 6.4 6.3 13.7 25747-16 F 2.2 NA NA NA NA NA 25747-17 F 2.6 NA NA NA NA NA -762- MALES MEAN 2.2 5.9 9.7 5.8 8.1 14.0 FEMALES MEAN 2.2 6.0 9.9 5.9 7.0 15.0 25744-01 M 25744-02 M 25744-03 M 25744-04 M 25744-05 M 25744-06 M 25744-07 F 25744-08 F 25744-09 F 3.2 5.6 10.2 8.8 7.1 15.3 2.2 NA NA NA NA NA 2.8 7.0 10.6 8.3 7.7 17.9 3.3 6.0 10.3 6.9 7.8 15.4 2.4 NA NA NA NA NA 2.7 6.2 10.9 8.3 8.5 14.3 2.8 NA NA NA NA NA 2.1 5.4 10.4 7.0 6.6 15.1 2.2 NA NA NA NA NA NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 73 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25744-10 F 2.1 NA NA NA NA NA 25744-11 F 3.2 6.5 10.8 8.0 7.7 14.7 25744-12 F 2.8 NA NA NA NA NA 25744-13 F 3.3 5.9 10.5 8.2 6.2 13.8 25744-14 F 2.7 6.0 10.6 8.7 6.5 15.5 25744-15 F 2.7 NA NA NA NA NA MALES MEAN 2.8 6.2 10.5 8.1 7.8 15.7 FEMALES MEAN 2.7 6.0 10.6 8.0 6.8 14.8 -763- 25707-01 M 25707-02 M 25707-03 M 25707-04 M 25707-05 M 25707-06 M 25707-07 M 25707-08 M 25707-09 F 25707-10 F 25707-12 F 1.9 NA NA NA NA NA 1.6 NA NA NA NA NA 2.3 5.8 9.3 7.5 6.2 9.6 2.1 NA NA NA NA NA 2.2 5.4 10.9 7.2 8.4 10.4 2.5 NA NA NA NA NA 2.3 6.3 10.3 6.7 7.3 9.4 2.3 5.6 10.6 7.4 7.0 10.5 2.5 5.2 10.1 8.3 6.9 11.0 2.4 4.9 10.1 6.6 7.5 9.9 2.1 6.0 10.0 6.3 6.7 10.4 NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 74 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25707-14 F 2.3 6.9 10.2 7.6 8.1 8.5 MALES MEAN 2.2 5.8 10.3 7.2 7.2 10.0 FEMALES MEAN 2.3 5.8 10.1 7.2 7.3 10.0 25723-01 M 25723-02 M 25723-03 M 25723-04 M 25723-05 M 25723-06 M 25723-07 M 25723-08 M 25723-09 M 25723-10 M 25723-11 M 25723-12 M 25723-13 F 25723-14 F 25723-15 F 25723-16 F 25723-17 M 1.8 NA NA NA NA NA 3.0 NA NA NA NA NA 2.5 NA NA NA NA NA 1.8 NA NA NA NA NA 2.4 5.2 7.9 7.5 5.8 13.2 2.5 4.3 8.2 7.7 4.4 8.4 2.5 NA NA NA NA NA 3.1 NA NA NA NA NA 2.6 NA NA NA NA NA 1.8 NA NA NA NA NA 2.4 NA NA NA NA NA 3.2 6.6 10.2 9.1 5.0 18.8 1.8 4.1 7.9 6.9 5.8 10.0 2.4 NA NA NA NA NA 2.6 6.0 8.2 7.2 6.8 14.1 2.3 5.4 7.9 8.5 5.7 13.4 0.9 3.0 5.5 6.7 3.9 9.8 -764- NA = NOT APPLICABLE APPENDIX 18 (F1 - PRE-WEANING) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 75 SPONSOR:3M CORPORATION INDIVIDUAL OFFSPRING WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- POSTNATAL DAY PUP NUMBER SEX 1- 4 4- 7 7-11 11-14 14-17 17-21 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25723-18 F 1.5 3.9 6.4 6.3 4.7 9.6 MALES MEAN 2.3 4.8 8.0 7.8 4.8 12.6 FEMALES MEAN 2.1 4.9 7.6 7.2 5.8 11.8 MALES MEAN S.D. N FEMALES MEAN S.D. N 2.6 0.57 24 2.5 0.52 24 5.7 1.06 24 5.7 0.99 24 9.1 1.16 24 9.1 1.10 24 7.4 0.96 24 7.3 0.94 24 6.9 1.47 24 6.7 1.08 24 12.3 2.43 24 12.1 1.94 24 PPWTNv4.19 10/23/2006 -765- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 19 (F1 - FOUND DEAD PUPS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL PUP NECROPSY FINDINGS PAGE 1 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 1: 0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25654 13 F 5 NO REMARKABLE OBSERVATIONS 25687 12 F 3 NO REMARKABLE OBSERVATIONS 25637 1 M 0 STOMACH MILK NOT PRESENT P 25638 2 M 4 NO REMARKABLE OBSERVATIONS 25692 1 M 0 STOMACH MILK NOT PRESENT P 25661 2 M 7 3 M 7 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25702 1 M 0 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P ABDOMINAL AND URINARY/REPRODUCTIVE 2 M 0 STOMACH MILK NOT PRESENT P 10 M 1 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P ABDOMINAL AND URINARY/REPRODUCTIVE -766- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 19 (F1 - FOUND DEAD PUPS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL PUP NECROPSY FINDINGS PAGE 2 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 2: 0.1 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25668 1 M 1 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P ABDOMINAL AND URINARY/REPRODUCTIVE 2 F 1 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P ABDOMINAL AND URINARY/REPRODUCTIVE 25753 7 M 1 STOMACH MILK NOT PRESENT P 13 F 4 VARIATION RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S) P KIDNEY, LEFT (WOO AND HOAR GRADE 0) 25752 6 M 2 GENERAL COMMENT CANNIBALIZED P GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT -767- PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 19 (F1 - FOUND DEAD PUPS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL PUP NECROPSY FINDINGS PAGE 3 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 3: 0.3 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25698 15 F 3 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P ABDOMINAL AND URINARY/REPRODUCTIVE 25677 1 M 4 9 F 4 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25623 1 M 0 STOMACH MILK PRESENT P 2 M 0 STOMACH MILK PRESENT P 12 F 7 NO REMARKABLE OBSERVATIONS 25722 16 M 0 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P THORACIC, ABDOMINAL AND URINARY/REPRODUCTIVE 25642 10 F 6 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P ABDOMINAL AND URINARY/REPRODUCTIVE 25628 6 M 2 NO REMARKABLE OBSERVATIONS 25763 3 M 5 NO REMARKABLE OBSERVATIONS 16 F 6 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P ABDOMINAL AND URINARY/REPRODUCTIVE 25766 4 M 3 GENERAL COMMENT TOO AUTOLYZED TO EXAMINE P ABDOMINAL AND URINARY/REPRODUCTIVE 25743 7 M 2 NO REMARKABLE OBSERVATIONS 25712 1 F 0 STOMACH MILK PRESENT P 25746 2 M 2 NO REMARKABLE OBSERVATIONS -768- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 19 (F1 - FOUND DEAD PUPS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL PUP NECROPSY FINDINGS PAGE 4 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 4: 1.0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25658 1 F 0 MALFORMATION MANDIBULAR MICROGNATHIA P MALFORMATION SITUS INVERSUS P TRACHEA, ESOPHAGUS, HEART, GREAT AND MAJOR VESSELS, LUNGS, LIVER, STOMACH, PANCREAS, SPLEEN, KIDNEYS, ADRENAL GLANDS AND INTESTINE LATERALLY TRANSPOSED STOMACH MILK NOT PRESENT P 25676 1 M 0 STOMACH MILK NOT PRESENT P 25611 1 M 0 STOMACH MILK NOT PRESENT P 2 F 0 STOMACH MILK NOT PRESENT P 3 F 0 STOMACH MILK NOT PRESENT P 25691 13 F 1 STOMACH MILK PRESENT P 25717 1 M 0 STOMACH MILK NOT PRESENT P 25599 8 M 2 NO REMARKABLE OBSERVATIONS 25647 1 M 0 STOMACH MILK PRESENT P 25707 13 F 3 NO REMARKABLE OBSERVATIONS -769- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT PPNRDv4.13 01/23/2007 R:01/23/2007 APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 1: 0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25597 2 M 21 NO REMARKABLE OBSERVATIONS 5 M 21 NO REMARKABLE OBSERVATIONS 8 F 21 NO REMARKABLE OBSERVATIONS 12 F 21 NO REMARKABLE OBSERVATIONS 25654 2 M 21 7 M 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25632 4 M 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25610 1 M 21 2 M 21 3 F 21 4 F 21 5 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25618 2 M 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25621 2 M 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25687 3 M 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25633 9 M 21 12 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -770- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 1: 0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25681 5 F 21 NO REMARKABLE OBSERVATIONS 7 M 21 NO REMARKABLE OBSERVATIONS 25615 1 M 21 13 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25637 8 M 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25638 4 M 21 15 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25713 4 M 21 5 M 21 13 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -771- 25670 4 M 21 15 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25657 2 M 21 12 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25663 3 M 21 6 M 21 7 F 21 8 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25690 3 M 21 5 M 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 1: 0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25690 (CONTINUED) 7 M 21 NO REMARKABLE OBSERVATIONS 9 F 21 NO REMARKABLE OBSERVATIONS 17 F 21 NO REMARKABLE OBSERVATIONS 18 F 21 NO REMARKABLE OBSERVATIONS 25666 2 M 21 5 M 21 7 M 21 8 F 21 13 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25692 2 M 21 3 M 21 5 M 21 6 F 21 12 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -772- 25701 2 F 21 3 M 21 6 M 21 10 M 21 11 F 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25645 1 M 21 2 M 21 4 M 21 7 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 1: 0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25645 (CONTINUED) 11 F 21 NO REMARKABLE OBSERVATIONS 12 F 21 NO REMARKABLE OBSERVATIONS 25661 4 M 21 5 M 21 10 F 21 11 F 21 12 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25767 1 M 21 3 M 21 5 M 21 6 M 21 7 F 21 9 F 21 12 F 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -773- 25770 1 M 21 2 M 21 3 M 21 4 M 21 7 F 21 9 F 21 11 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25702 3 M 21 4 M 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 1: 0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25702 (CONTINUED) 7 M 21 NO REMARKABLE OBSERVATIONS 12 M 21 NO REMARKABLE OBSERVATIONS 13 F 21 NO REMARKABLE OBSERVATIONS 15 F 21 NO REMARKABLE OBSERVATIONS 16 F 21 NO REMARKABLE OBSERVATIONS 18 F 21 NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT -774- APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 2: 0.1 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25648 3 M 21 NO REMARKABLE OBSERVATIONS 8 M 21 NO REMARKABLE OBSERVATIONS 11 F 21 NO REMARKABLE OBSERVATIONS 16 F 21 NO REMARKABLE OBSERVATIONS 25694 3 M 21 9 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25668 3 M 21 4 M 21 5 M 21 6 F 21 7 F 21 10 F 21 12 F 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25631 2 M 21 3 M 21 10 F 21 13 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25660 7 M 21 10 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25704 1 M 21 6 M 21 8 F 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -775- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 2: 0.1 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25665 3 M 21 NO REMARKABLE OBSERVATIONS 4 M 21 NO REMARKABLE OBSERVATIONS 6 F 21 NO REMARKABLE OBSERVATIONS 10 F 21 NO REMARKABLE OBSERVATIONS 25674 7 M 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25652 2 M 21 10 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25733 3 M 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25748 2 M 21 4 M 21 6 M 21 9 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25753 2 M 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25672 2 M 21 12 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25655 3 M 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25727 2 M 21 13 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -776- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 2: 0.1 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25626 6 M 21 NO REMARKABLE OBSERVATIONS 9 F 21 NO REMARKABLE OBSERVATIONS 25739 1 M 21 6 M 21 9 M 21 11 F 21 13 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25749 2 M 21 3 M 21 7 M 21 8 F 21 9 F 21 10 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25756 1 M 21 3 M 21 4 M 21 11 F 21 15 F 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25741 1 M 21 2 M 21 3 M 21 14 F 21 15 F 21 16 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -777- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 2: 0.1 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25752 1 M 21 NO REMARKABLE OBSERVATIONS 3 M 21 NO REMARKABLE OBSERVATIONS 5 M 21 NO REMARKABLE OBSERVATIONS 11 F 21 NO REMARKABLE OBSERVATIONS 14 F 21 NO REMARKABLE OBSERVATIONS 15 F 21 NO REMARKABLE OBSERVATIONS 25758 1 M 21 2 M 21 5 M 21 6 M 21 8 F 21 9 F 21 10 F 21 12 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25719 3 M 21 4 M 21 7 M 21 9 M 21 13 F 21 14 F 21 15 F 21 17 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -778- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 3: 0.3 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25606 1 M 21 NO REMARKABLE OBSERVATIONS 2 M 21 NO REMARKABLE OBSERVATIONS 3 M 21 NO REMARKABLE OBSERVATIONS 4 F 21 NO REMARKABLE OBSERVATIONS 5 F 21 NO REMARKABLE OBSERVATIONS 8 F 21 NO REMARKABLE OBSERVATIONS 11 F 21 NO REMARKABLE OBSERVATIONS 12 F 21 NO REMARKABLE OBSERVATIONS 25614 7 M 21 13 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25671 2 M 21 5 M 21 8 F 21 13 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25698 6 M 21 10 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25609 2 M 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25677 2 M 21 7 M 21 10 F 21 12 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25623 5 M 21 NO REMARKABLE OBSERVATIONS -779- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 3: 0.3 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25653 6 F 21 NO REMARKABLE OBSERVATIONS 7 M 21 NO REMARKABLE OBSERVATIONS 11 M 21 NO REMARKABLE OBSERVATIONS 12 F 21 NO REMARKABLE OBSERVATIONS 25604 2 M 21 3 M 21 8 F 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25678 6 M 21 8 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25684 2 M 21 3 M 21 8 F 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25714 3 M 21 5 M 21 9 F 21 10 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25650 8 M 21 13 M 21 14 F 21 19 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25735 1 M 21 7 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -780- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 3: 0.3 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25722 4 M 21 NO REMARKABLE OBSERVATIONS 13 F 21 NO REMARKABLE OBSERVATIONS 25642 2 M 21 8 M 21 13 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25628 5 M 21 15 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25763 2 M 21 4 M 21 7 M 21 9 F 21 10 F 21 15 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -781- 25766 2 M 21 3 M 21 7 F 21 9 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25689 3 M 21 4 M 21 6 M 21 7 F 21 12 F 21 13 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25708 4 M 21 NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 3: 0.3 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25708 (CONTINUED) 7 M 21 NO REMARKABLE OBSERVATIONS 9 M 21 NO REMARKABLE OBSERVATIONS 11 F 21 NO REMARKABLE OBSERVATIONS 12 F 21 NO REMARKABLE OBSERVATIONS 14 F 21 NO REMARKABLE OBSERVATIONS 25743 2 M 21 4 M 21 9 M 21 11 F 21 12 F 21 18 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25761 4 M 21 5 M 21 6 M 21 7 M 21 8 F 21 9 F 21 13 F 21 15 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25712 2 M 21 3 M 21 5 M 21 6 M 21 7 F 21 8 F 21 16 F 21 17 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -782- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 3: 0.3 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25746 3 M 21 NO REMARKABLE OBSERVATIONS 6 M 21 NO REMARKABLE OBSERVATIONS 7 M 21 NO REMARKABLE OBSERVATIONS 11 M 21 NO REMARKABLE OBSERVATIONS 12 F 21 NO REMARKABLE OBSERVATIONS 14 F 21 NO REMARKABLE OBSERVATIONS 15 F 21 NO REMARKABLE OBSERVATIONS 17 F 21 NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT -783- APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 4: 1.0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25696 9 M 21 NO REMARKABLE OBSERVATIONS 13 F 21 NO REMARKABLE OBSERVATIONS 25686 3 M 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25639 5 M 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25658 3 M 21 15 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25676 6 M 21 9 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25600 1 M 21 3 M 21 5 F 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -784- 25603 1 M 21 2 M 21 6 F 21 12 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25630 5 M 21 10 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25703 2 M 21 5 M 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 4: 1.0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25703 (CONTINUED) 9 F 21 NO REMARKABLE OBSERVATIONS 14 F 21 NO REMARKABLE OBSERVATIONS 25673 3 M 21 12 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25611 5 M 21 10 M 21 12 F 21 13 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25619 1 M 21 8 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25705 1 M 21 9 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -785- 25691 2 M 21 5 M 21 12 F 21 15 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25717 6 M 21 7 M 21 11 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25616 3 M 21 10 F 21 11 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 17 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 4: 1.0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25616 (CONTINUED) 12 M 21 NO REMARKABLE OBSERVATIONS 25715 4 M 21 6 M 21 8 M 21 13 F 21 15 F 21 17 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25762 3 M 21 5 M 21 6 M 21 7 F 21 8 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25599 3 M 21 9 M 21 10 M 21 12 F 21 17 F 21 19 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25647 4 M 21 6 M 21 8 F 21 12 F 21 13 M 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -786- GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 18 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 4: 1.0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25747 1 M 21 NO REMARKABLE OBSERVATIONS 3 M 21 NO REMARKABLE OBSERVATIONS 4 M 21 NO REMARKABLE OBSERVATIONS 5 M 21 NO REMARKABLE OBSERVATIONS 8 F 21 NO REMARKABLE OBSERVATIONS 9 F 21 NO REMARKABLE OBSERVATIONS 13 F 21 NO REMARKABLE OBSERVATIONS 15 F 21 NO REMARKABLE OBSERVATIONS 25744 1 M 21 3 M 21 4 M 21 6 M 21 8 F 21 11 F 21 13 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS -787- 25707 3 M 21 5 M 21 7 M 21 8 M 21 9 F 21 10 F 21 12 F 21 14 F 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS 25723 5 M 21 6 M 21 12 M 21 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 19 SPONSOR:3M CORPORATION INDIVIDUAL PUP NECROPSY FINDINGS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PUP LACT GROUP 4: 1.0 MG/KG/DAY NO. SEX DAY TISSUE FINDING GRADE ----------------------------------------------------------------------------------------------------------------------------------- 25723 (CONTINUED) 13 F 21 NO REMARKABLE OBSERVATIONS 15 F 21 NO REMARKABLE OBSERVATIONS 16 F 21 NO REMARKABLE OBSERVATIONS 17 M 21 NO REMARKABLE OBSERVATIONS 18 F 21 NO REMARKABLE OBSERVATIONS GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT PPNRDv4.13 10/05/2006 R:10/10/2006 -788- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 21 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL ANIMAL DEVELOPMENTAL PARAMETERS - BALANOPREPUTIAL SEPARATION PAGE 1 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- DAY OF WEIGHT PND===> ANIMAL RESPONSE GRAMS 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 47 222.4 N N N N N Y 25654-09 48 250.9 N N N N N N Y 25632-07 46 230.6 N N N N Y 25633-05 48 222.2 N N N N N N Y 25618-08 47 252.4 N N N N N Y 25621-07 43 243.2 N Y 25687-07 47 261.9 N N N N N Y 25681-01 47 246.1 N N N N N Y 25615-03 47 260.5 N N N N N Y 25637-06 42 238.4 Y 25638-07 44 225.1 N N Y 25713-02 49 272.9 N N N N N N N Y 25670-09 44 240.9 N N Y 25657-08 45 267.2 N N N Y 25663-04 45 261.6 N N N Y 25690-01 48 261.3 N N N N N N Y 25666-01 45 265.4 N N N Y 25692-04 49 281.0 N N N N N N N Y 25701-09 44 234.3 N N Y 25645-06 49 223.8 N N N N N N N Y -789- MEAN 46.2 248.1 S.D. 2.09 18.08 N 20 20 ----------------------------------------------------------------------------------------------------------------------------------- N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 21 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL ANIMAL DEVELOPMENTAL PARAMETERS - BALANOPREPUTIAL SEPARATION PAGE 2 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- DAY OF WEIGHT PND===> ANIMAL RESPONSE GRAMS 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 46 246.6 N N N N Y 25674-02 50 246.2 N N N N N N N N Y 25694-04 56 377.6 N N N N N N N N N N N N N N Y 25631-04 45 279.0 N N N Y 25660-01 45 242.2 N N N Y 25704-03 45 238.0 N N N Y 25665-01 49 256.5 N N N N N N N Y 25652-04 45 273.6 N N N Y 25733-07 48 237.2 N N N N N N Y 25748-01 45 275.2 N N N Y 25753-06 42 245.4 Y 25672-06 46 239.2 N N N N Y 25655-01 48 245.8 N N N N N N Y 25727-07 46 246.7 N N N N Y 25626-04 44 245.4 N N Y 25749-04 45 259.2 N N N Y 25739-07 49 292.3 N N N N N N N Y 25756-05 47 306.7 N N N N N Y 25741-07 55 356.7 N N N N N N N N N N N N N Y 25752-09 43 255.4 N Y -790- MEAN 47.0 268.2 S.D. 3.56 38.92 N 20 20 ----------------------------------------------------------------------------------------------------------------------------------- N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 21 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL ANIMAL DEVELOPMENTAL PARAMETERS - BALANOPREPUTIAL SEPARATION PAGE 3 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- DAY OF WEIGHT PND===> ANIMAL RESPONSE GRAMS 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 47 258.5 N N N N N Y 25614-10 44 253.7 N N Y 25698-05 46 232.4 N N N N Y 25677-05 44 246.5 N N Y 25604-04 44 256.4 N N Y 25678-02 48 272.1 N N N N N N Y 25609-04 54 317.6 N N N N N N N N N N N N Y 25623-08 45 256.0 N N N Y 25653-02 46 242.5 N N N N Y 25684-04 43 241.0 N Y 25714-02 42 231.2 Y 25650-11 46 253.9 N N N N Y 25735-05 45 260.3 N N N Y 25722-01 46 254.8 N N N N Y 25642-05 47 279.3 N N N N N Y 25628-07 45 218.1 N N N Y 25766-01 49 245.5 N N N N N N N Y 25689-02 44 250.1 N N Y 25708-01 43 233.0 N Y 25743-08 47 248.8 N N N N N Y -791- MEAN 45.8 252.6 S.D. 2.63 20.81 N 20 20 ----------------------------------------------------------------------------------------------------------------------------------- N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 21 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL ANIMAL DEVELOPMENTAL PARAMETERS - BALANOPREPUTIAL SEPARATION PAGE 4 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- DAY OF WEIGHT PND===> ANIMAL RESPONSE GRAMS 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 48 265.5 N N N N N N Y 25686-04 45 253.2 N N N Y 25630-04 45 244.8 N N N Y 25673-09 49 235.5 N N N N N N N Y 25639-06 45 266.7 N N N Y 25658-08 46 266.3 N N N N Y 25676-02 42 229.5 Y 25600-02 48 273.4 N N N N N N Y 25603-04 45 249.1 N N N Y 25703-03 46 249.0 N N N N Y 25705-07 43 238.7 N Y 25611-07 46 228.9 N N N N Y 25619-04 46 187.4 N N N N Y 25691-07 45 238.2 N N N Y 25717-04 48 279.1 N N N N N N Y 25616-05 44 251.3 N N Y 25715-07 45 238.0 N N N Y 25599-06 46 226.7 N N N N Y 25762-01 45 232.5 N N N Y 25647-07 48 217.1 N N N N N N Y -792- MEAN 45.8 243.5 S.D. 1.77 21.43 N 20 20 ----------------------------------------------------------------------------------------------------------------------------------- N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY PJTBBv1.16 10/05/2006 R:10/10/2006 PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 22 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL ANIMAL DEVELOPMENTAL PARAMETERS - VAGINAL PATENCY PAGE 1 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- DAY OF WEIGHT PND===> ANIMAL RESPONSE GRAMS 28 29 30 31 32 33 34 35 36 ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 33 92.9 N N N N N Y 25654-10 33 97.2 N N N N N Y 25632-09 30 96.2 N N Y 25633-13 32 79.0 N N N N Y 25618-17 32 112.1 N N N N Y 25621-10 31 113.6 N N N Y 25687-15 32 109.8 N N N N Y 25681-10 32 106.6 N N N N Y 25615-10 31 104.8 N N N Y 25637-17 31 114.0 N N N Y 25638-18 33 96.2 N N N N N Y 25713-16 32 107.3 N N N N Y 25670-18 33 129.0 N N N N N Y 25657-10 29 103.9 N Y 25663-09 31 105.1 N N N Y 25690-19 32 118.2 N N N N Y 25666-09 32 111.1 N N N N Y 25692-07 32 117.7 N N N N Y 25701-18 31 109.0 N N N Y 25645-08 31 92.0 N N N Y -793- MEAN 31.7 105.8 S.D. 1.04 11.23 N 20 20 ----------------------------------------------------------------------------------------------------------------------------------- N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 22 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL ANIMAL DEVELOPMENTAL PARAMETERS - VAGINAL PATENCY PAGE 2 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- DAY OF WEIGHT PND===> ANIMAL RESPONSE GRAMS 28 29 30 31 32 33 34 35 36 ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 31 106.9 N N N Y 25674-11 33 110.2 N N N N N Y 25694-13 32 112.3 N N N N Y 25631-05 33 126.0 N N N N N Y 25660-04 36 155.1 N N N N N N N N Y 25704-09 33 129.0 N N N N N Y 25665-07 32 104.3 N N N N Y 25652-13 32 105.6 N N N N Y 25733-08 35 120.2 N N N N N N N Y 25748-08 33 119.1 N N N N N Y 25753-15 31 109.5 N N N Y 25672-15 34 124.4 N N N N N N Y 25655-13 33 113.7 N N N N N Y 25727-16 34 107.4 N N N N N N Y 25626-12 34 128.1 N N N N N N Y 25749-11 31 109.1 N N N Y 25739-12 30 117.0 N N Y 25756-13 33 119.4 N N N N N Y 25741-09 32 126.7 N N N N Y 25752-13 32 128.1 N N N N Y -794- MEAN 32.7 118.6 S.D. 1.45 11.97 N 20 20 ----------------------------------------------------------------------------------------------------------------------------------- N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 22 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL ANIMAL DEVELOPMENTAL PARAMETERS - VAGINAL PATENCY PAGE 3 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- DAY OF WEIGHT PND===> ANIMAL RESPONSE GRAMS 28 29 30 31 32 33 34 35 36 ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 35 122.3 N N N N N N N Y 25614-17 31 99.9 N N N Y 25698-12 32 100.8 N N N N Y 25677-08 30 107.2 N N Y 25604-12 33 117.8 N N N N N Y 25678-11 34 124.9 N N N N N N Y 25609-11 33 117.3 N N N N N Y 25623-15 32 111.0 N N N N Y 25653-13 33 121.2 N N N N N Y 25684-06 32 115.4 N N N N Y 25714-13 28 94.2 Y 25650-17 31 114.6 N N N Y 25735-08 30 101.2 N N Y 25722-15 32 105.8 N N N N Y 25628-17 32 94.7 N N N N Y 25766-06 34 115.1 N N N N N N Y 25689-14 31 115.5 N N N Y 25708-15 32 111.3 N N N N Y 25743-16 33 110.0 N N N N N Y 25642-12 31 111.9 N N N Y -795- MEAN 32.0 110.6 S.D. 1.61 8.86 N 20 20 ----------------------------------------------------------------------------------------------------------------------------------- N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 22 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL ANIMAL DEVELOPMENTAL PARAMETERS - VAGINAL PATENCY PAGE 4 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- DAY OF WEIGHT PND===> ANIMAL RESPONSE GRAMS 28 29 30 31 32 33 34 35 36 ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 32 113.8 N N N N Y 25686-10 33 107.2 N N N N N Y 25630-09 34 121.9 N N N N N N Y 25673-10 34 98.3 N N N N N N Y 25639-04 32 120.2 N N N N Y 25658-14 32 102.6 N N N N Y 25676-15 32 117.0 N N N N Y 25600-15 32 126.6 N N N N Y 25603-10 32 115.7 N N N N Y 25703-10 32 109.4 N N N N Y 25705-08 32 123.7 N N N N Y 25611-11 32 106.6 N N N N Y 25619-12 32 99.9 N N N N Y 25691-11 33 121.4 N N N N N Y 25717-15 32 102.8 N N N N Y 25616-14 32 119.3 N N N N Y 25715-10 32 103.7 N N N N Y 25599-11 32 96.8 N N N N Y 25762-11 31 96.4 N N N Y 25647-11 32 105.5 N N N N Y -796- MEAN 32.3 110.4 S.D. 0.72 9.74 N 20 20 ----------------------------------------------------------------------------------------------------------------------------------- N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY PJTBBv1.16 10/05/2006 R:10/10/2006 APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 M 0 MG/KG/DAY DISPOSITION 08-03-06 6:55 P SCHEDULED EUTHANASIA 25654-09 M 0 MG/KG/DAY DISPOSITION 08-03-06 6:56 P SCHEDULED EUTHANASIA 25632-07 M 0 MG/KG/DAY DISPOSITION 08-04-06 7:06 P SCHEDULED EUTHANASIA 25633-05 M 0 MG/KG/DAY DISPOSITION 08-04-06 7:07 P SCHEDULED EUTHANASIA 25618-08 M 0 MG/KG/DAY DISPOSITION 08-05-06 7:14 P SCHEDULED EUTHANASIA 25621-07 M 0 MG/KG/DAY DISPOSITION 08-05-06 7:10 P SCHEDULED EUTHANASIA 25687-07 M 0 MG/KG/DAY DISPOSITION 08-05-06 7:10 P SCHEDULED EUTHANASIA 25681-01 M 0 MG/KG/DAY DISPOSITION 08-05-06 7:14 P SCHEDULED EUTHANASIA 25615-03 M 0 MG/KG/DAY DISPOSITION 08-05-06 7:10 P SCHEDULED EUTHANASIA 25637-06 M 0 MG/KG/DAY DISPOSITION 08-06-06 7:45 P SCHEDULED EUTHANASIA 25638-07 M 0 MG/KG/DAY DISPOSITION 08-06-06 7:45 P SCHEDULED EUTHANASIA 25713-02 M 0 MG/KG/DAY DISPOSITION 08-06-06 7:50 P SCHEDULED EUTHANASIA 25713-02 M 0 MG/KG/DAY BODY/INTEGUMENT 07-14-06 7:45 1 HAIR LOSS DORSAL NECK 07-21-06 8:41 1 HAIR LOSS VENTRAL NECK 07-28-06 10:11 1 HAIR LOSS VENTRAL NECK 07-28-06 10:12 P SCABBING VENTRAL NECK 08-04-06 6:32 P SCABBING VENTRAL NECK -797- 08-04-06 6:32 1 HAIR LOSS VENTRAL NECK 08-04-06 6:32 P SCABBING RIGHT LATERAL THORACIC AREA 08-06-06 7:07 P SCABBING VENTRAL NECK 08-06-06 7:07 1 HAIR LOSS VENTRAL NECK 07-14-06 10:17 P MOIST ALOPECIA DORSAL NECK 25670-09 M 0 MG/KG/DAY DISPOSITION 08-06-06 7:45 P SCHEDULED EUTHANASIA 25657-08 M 0 MG/KG/DAY DISPOSITION 08-06-06 7:45 P SCHEDULED EUTHANASIA 25663-04 M 0 MG/KG/DAY DISPOSITION 08-06-06 7:45 P SCHEDULED EUTHANASIA 25690-01 M 0 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA 25666-01 M 0 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA 25692-04 M 0 MG/KG/DAY DISPOSITION 08-07-06 7:22 P SCHEDULED EUTHANASIA 25692-04 M 0 MG/KG/DAY BODY/INTEGUMENT 07-08-06 6:40 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25692-04 M 0 MG/KG/DAY BODY/INTEGUMENT 07-08-06 6:40 1 HAIR LOSS LEFT FORELIMB 07-15-06 6:13 1 HAIR LOSS LEFT FORELIMB 07-15-06 6:13 1 HAIR LOSS RIGHT FORELIMB 07-22-06 8:44 1 HAIR LOSS RIGHT FORELIMB 07-22-06 8:44 1 HAIR LOSS LEFT FORELIMB 07-29-06 6:16 2 HAIR LOSS RIGHT FORELIMB 07-29-06 6:16 2 HAIR LOSS LEFT FORELIMB 08-05-06 6:36 1 HAIR LOSS LEFT FORELIMB 08-05-06 6:36 1 HAIR LOSS RIGHT FORELIMB 08-07-06 7:08 1 HAIR LOSS RIGHT FORELIMB 08-07-06 7:08 1 HAIR LOSS LEFT FORELIMB 25701-09 M 0 MG/KG/DAY DISPOSITION 08-07-06 7:22 P SCHEDULED EUTHANASIA 25645-06 M 0 MG/KG/DAY DISPOSITION 08-08-06 7:17 P SCHEDULED EUTHANASIA 25648-07 M 0.1 MG/KG/DAY DISPOSITION 08-03-06 6:57 P SCHEDULED EUTHANASIA 25674-02 M 0.1 MG/KG/DAY DISPOSITION 08-04-06 7:06 P SCHEDULED EUTHANASIA 25694-04 M 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:10 P SCHEDULED EUTHANASIA 25631-04 M 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:15 P SCHEDULED EUTHANASIA -798- 25660-01 M 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:10 P SCHEDULED EUTHANASIA 25704-03 M 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:10 P SCHEDULED EUTHANASIA 25665-01 M 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:10 P SCHEDULED EUTHANASIA 25652-04 M 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25652-04 M 0.1 MG/KG/DAY BODY/INTEGUMENT 07-06-06 7:04 1 HAIR LOSS DORSAL NECK 07-06-06 7:04 P SCABBING DORSAL NECK 25733-07 M 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:15 P SCHEDULED EUTHANASIA 25748-01 M 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA 25753-06 M 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA 25672-06 M 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA 25655-01 M 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA 25727-07 M 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25626-04 M 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA 25749-04 M 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:46 P SCHEDULED EUTHANASIA 25739-07 M 0.1 MG/KG/DAY DISPOSITION 08-07-06 7:23 P SCHEDULED EUTHANASIA 25756-05 M 0.1 MG/KG/DAY DISPOSITION 08-07-06 7:23 P SCHEDULED EUTHANASIA 25741-07 M 0.1 MG/KG/DAY DISPOSITION 08-08-06 7:17 P SCHEDULED EUTHANASIA 25752-09 M 0.1 MG/KG/DAY DISPOSITION 08-08-06 7:17 P SCHEDULED EUTHANASIA 25671-04 M 0.3 MG/KG/DAY DISPOSITION 08-03-06 6:55 P SCHEDULED EUTHANASIA 25614-10 M 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:06 P SCHEDULED EUTHANASIA 25698-05 M 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:08 P SCHEDULED EUTHANASIA 25677-05 M 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:08 P SCHEDULED EUTHANASIA 25604-04 M 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:06 P SCHEDULED EUTHANASIA 25678-02 M 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:08 P SCHEDULED EUTHANASIA 25678-02 M 0.3 MG/KG/DAY EYES/EARS/NOSE 06-28-06 7:04 1 DRIED RED MATERIAL AROUND NOSE 25609-04 M 0.3 MG/KG/DAY DISPOSITION 08-05-06 7:15 P SCHEDULED EUTHANASIA 25623-08 M 0.3 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25653-02 M 0.3 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25653-02 M 0.3 MG/KG/DAY EYES/EARS/NOSE 06-22-06 6:35 1 DRIED RED MATERIAL AROUND NOSE -799- 25684-04 M 0.3 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25684-04 M 0.3 MG/KG/DAY BODY/INTEGUMENT 06-22-06 6:36 1 HAIR LOSS RIGHT FORELIMB 06-22-06 6:36 1 HAIR LOSS LEFT FORELIMB 06-29-06 6:33 1 HAIR LOSS LEFT FORELIMB 06-29-06 6:33 1 HAIR LOSS RIGHT FORELIMB 25714-02 M 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25650-11 M 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:51 P SCHEDULED EUTHANASIA 25735-05 M 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25722-01 M 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25642-05 M 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25628-07 M 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25766-01 M 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25689-02 M 0.3 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA 25708-01 M 0.3 MG/KG/DAY DISPOSITION 08-07-06 7:23 P SCHEDULED EUTHANASIA 25708-01 M 0.3 MG/KG/DAY BODY/INTEGUMENT 08-05-06 6:42 P SCABBING DORSAL THORACIC AREA 08-05-06 6:42 1 HAIR LOSS DORSAL THORACIC AREA 08-07-06 7:12 P SCABBING DORSAL NECK 08-07-06 7:12 1 HAIR LOSS DORSAL NECK 07-29-06 6:19 P SCABBING DORSAL THORACIC AREA 25743-08 M 0.3 MG/KG/DAY DISPOSITION 08-07-06 7:23 P SCHEDULED EUTHANASIA 25743-08 M 0.3 MG/KG/DAY BODY/INTEGUMENT 07-29-06 6:21 1 HAIR LOSS RIGHT FORELIMB 08-05-06 6:43 1 HAIR LOSS LEFT FORELIMB 08-05-06 6:43 1 HAIR LOSS RIGHT FORELIMB 08-07-06 7:13 1 HAIR LOSS RIGHT FORELIMB 25696-04 M 1.0 MG/KG/DAY DISPOSITION 08-04-06 7:08 P SCHEDULED EUTHANASIA 25686-04 M 1.0 MG/KG/DAY DISPOSITION 08-04-06 7:08 P SCHEDULED EUTHANASIA 25630-04 M 1.0 MG/KG/DAY DISPOSITION 08-04-06 7:08 P SCHEDULED EUTHANASIA 25673-09 M 1.0 MG/KG/DAY DISPOSITION 08-04-06 7:09 P SCHEDULED EUTHANASIA 25639-06 M 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:16 P SCHEDULED EUTHANASIA -800- 25658-08 M 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25676-02 M 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25600-02 M 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25603-04 M 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25603-04 M 1.0 MG/KG/DAY BODY/INTEGUMENT 07-20-06 9:39 1 HAIR LOSS LEFT FORELIMB 07-27-06 7:50 1 HAIR LOSS RIGHT FORELIMB 07-27-06 7:50 1 HAIR LOSS LEFT FORELIMB 08-05-06 6:44 1 HAIR LOSS LEFT FORELIMB 08-05-06 6:44 1 HAIR LOSS RIGHT FORELIMB 25703-03 M 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25705-07 M 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:16 P SCHEDULED EUTHANASIA 25611-07 M 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25619-04 M 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:51 P SCHEDULED EUTHANASIA 25619-04 M 1.0 MG/KG/DAY EYES/EARS/NOSE 06-17-06 11:31 P OPACITY RIGHT EYE 06-17-06 11:31 P OPACITY LEFT EYE 06-23-06 6:54 P OPACITY RIGHT EYE 06-23-06 6:54 P OPACITY LEFT EYE 06-30-06 6:22 P OPACITY LEFT EYE 06-30-06 6:22 P OPACITY RIGHT EYE 06-30-06 6:24 P EXOPHTHALMUS RIGHT EYE 06-30-06 6:24 1 DRIED RED MATERIAL AROUND RIGHT EYE 07-07-06 6:49 P OPACITY LEFT EYE 07-07-06 6:49 P OPACITY RIGHT EYE 07-07-06 6:50 P EXOPHTHALMUS RIGHT EYE 07-07-06 6:50 1 DRIED RED MATERIAL AROUND RIGHT EYE 07-14-06 7:52 P OPACITY RIGHT EYE 07-14-06 7:53 P OPACITY LEFT EYE 07-14-06 7:53 P EXOPHTHALMUS RIGHT EYE 07-21-06 8:50 P OPACITY RIGHT EYE -801- 07-21-06 8:50 P OPACITY LEFT EYE 07-21-06 8:51 P EXOPHTHALMUS RIGHT EYE 07-21-06 8:51 1 DRIED RED MATERIAL AROUND RIGHT EYE 07-28-06 10:22 P OPACITY RIGHT EYE 07-28-06 10:22 P OPACITY LEFT EYE 07-28-06 10:22 P EXOPHTHALMUS RIGHT EYE 08-04-06 6:46 P OPACITY RIGHT EYE 08-04-06 6:46 P OPACITY LEFT EYE 08-04-06 6:47 P EXOPHTHALMUS RIGHT EYE 08-06-06 7:13 P OPACITY LEFT EYE 08-06-06 7:13 P OPACITY RIGHT EYE 08-06-06 7:13 P EXOPHTHALMUS RIGHT EYE ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25619-04 M 1.0 MG/KG/DAY EYES/EARS/NOSE 06-29-06 7:16 P APPARENT MECHANICAL INJURY RIGHT EYE 25691-07 M 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:51 P SCHEDULED EUTHANASIA 25717-04 M 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:52 P SCHEDULED EUTHANASIA 25616-05 M 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25715-07 M 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25599-06 M 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25599-06 M 1.0 MG/KG/DAY EYES/EARS/NOSE 07-14-06 7:55 1 DRIED RED MATERIAL AROUND LEFT EYE 07-14-06 7:55 1 DRIED RED MATERIAL AROUND RIGHT EYE 25762-01 M 1.0 MG/KG/DAY DISPOSITION 08-07-06 7:23 P SCHEDULED EUTHANASIA 25647-07 M 1.0 MG/KG/DAY DISPOSITION 08-07-06 7:23 P SCHEDULED EUTHANASIA 25647-07 M 1.0 MG/KG/DAY BODY/INTEGUMENT 07-27-06 9:42 P MOIST ALOPECIA LEFT DORSAL HEAD 07-27-06 9:42 P MOIST ALOPECIA RIGHT DORSAL HEAD 25597-17 F 0 MG/KG/DAY DISPOSITION 08-03-06 6:55 P SCHEDULED EUTHANASIA 25597-17 F 0 MG/KG/DAY BODY/INTEGUMENT 08-01-06 7:18 1 HAIR LOSS RIGHT FORELIMB 08-01-06 7:18 1 HAIR LOSS LEFT FORELIMB 08-03-06 6:36 1 HAIR LOSS RIGHT FORELIMB 08-03-06 6:36 1 HAIR LOSS LEFT FORELIMB -802- 08-03-06 6:37 P SCABBING LEFT FORELIMB 08-03-06 6:38 P SCABBING RIGHT FORELIMB 25654-10 F 0 MG/KG/DAY DISPOSITION 08-03-06 6:56 P SCHEDULED EUTHANASIA 25632-09 F 0 MG/KG/DAY DISPOSITION 08-04-06 7:09 P SCHEDULED EUTHANASIA 25633-13 F 0 MG/KG/DAY DISPOSITION 08-04-06 7:09 P SCHEDULED EUTHANASIA 25618-17 F 0 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25621-10 F 0 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25687-15 F 0 MG/KG/DAY DISPOSITION 08-05-06 7:16 P SCHEDULED EUTHANASIA 25681-10 F 0 MG/KG/DAY DISPOSITION 08-05-06 7:17 P SCHEDULED EUTHANASIA 25615-10 F 0 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25637-17 F 0 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA 25638-18 F 0 MG/KG/DAY DISPOSITION 08-06-06 7:47 P SCHEDULED EUTHANASIA ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25713-16 F 0 MG/KG/DAY DISPOSITION 08-06-06 7:52 P SCHEDULED EUTHANASIA 25670-18 F 0 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25670-18 F 0 MG/KG/DAY BODY/INTEGUMENT 07-21-06 8:57 1 HAIR LOSS LEFT LATERAL THORACIC AREA 07-21-06 8:57 P SCABBING LEFT LATERAL THORACIC AREA 07-28-06 10:26 1 HAIR LOSS LEFT LATERAL THORACIC AREA 07-28-06 10:26 P SCABBING LEFT LATERAL THORACIC AREA 07-28-06 10:26 1 HAIR LOSS RIGHT LATERAL THORACIC AREA 07-28-06 10:27 P SCABBING RIGHT LATERAL THORACIC AREA 25657-10 F 0 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25663-09 F 0 MG/KG/DAY DISPOSITION 08-06-06 7:52 P SCHEDULED EUTHANASIA 25690-19 F 0 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25666-09 F 0 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25692-07 F 0 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA 25692-07 F 0 MG/KG/DAY BODY/INTEGUMENT 08-07-06 7:15 1 HAIR LOSS RIGHT FORELIMB 08-07-06 7:15 1 HAIR LOSS LEFT FORELIMB 25701-18 F 0 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA 25645-08 F 0 MG/KG/DAY DISPOSITION 08-08-06 7:17 P SCHEDULED EUTHANASIA -803- 25648-12 F 0.1 MG/KG/DAY DISPOSITION 08-03-06 6:57 P SCHEDULED EUTHANASIA 25674-11 F 0.1 MG/KG/DAY DISPOSITION 08-04-06 7:07 P SCHEDULED EUTHANASIA 25694-13 F 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25631-05 F 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:11 P SCHEDULED EUTHANASIA 25660-04 F 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:17 P SCHEDULED EUTHANASIA 25704-09 F 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25665-07 F 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25652-13 F 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25733-08 F 0.1 MG/KG/DAY DISPOSITION 08-05-06 7:18 P SCHEDULED EUTHANASIA 25748-08 F 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25753-15 F 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25672-15 F 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25655-13 F 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25727-16 F 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:53 P SCHEDULED EUTHANASIA 25626-12 F 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25749-11 F 0.1 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25739-12 F 0.1 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA 25756-13 F 0.1 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA 25741-09 F 0.1 MG/KG/DAY DISPOSITION 08-08-06 7:18 P SCHEDULED EUTHANASIA 25752-13 F 0.1 MG/KG/DAY DISPOSITION 08-08-06 7:18 P SCHEDULED EUTHANASIA 25671-06 F 0.3 MG/KG/DAY DISPOSITION 08-03-06 6:56 P SCHEDULED EUTHANASIA 25614-17 F 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:07 P SCHEDULED EUTHANASIA 25698-12 F 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:09 P SCHEDULED EUTHANASIA 25677-08 F 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:07 P SCHEDULED EUTHANASIA 25604-12 F 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:10 P SCHEDULED EUTHANASIA 25678-11 F 0.3 MG/KG/DAY DISPOSITION 08-04-06 7:10 P SCHEDULED EUTHANASIA 25609-11 F 0.3 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25623-15 F 0.3 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25653-13 F 0.3 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA -804- 25684-06 F 0.3 MG/KG/DAY DISPOSITION 08-05-06 7:18 P SCHEDULED EUTHANASIA 25684-06 F 0.3 MG/KG/DAY BODY/INTEGUMENT 06-22-06 6:37 1 HAIR LOSS RIGHT FORELIMB 06-22-06 6:37 1 HAIR LOSS LEFT FORELIMB 06-29-06 6:40 1 HAIR LOSS LEFT FORELIMB 06-29-06 6:40 1 HAIR LOSS RIGHT FORELIMB 25714-13 F 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:48 P SCHEDULED EUTHANASIA 25650-17 F 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25735-08 F 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:53 P SCHEDULED EUTHANASIA 25722-15 F 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25722-15 F 0.3 MG/KG/DAY BODY/INTEGUMENT 07-14-06 8:01 1 HAIR LOSS RIGHT FORELIMB 07-14-06 8:01 1 HAIR LOSS LEFT FORELIMB 07-21-06 9:01 1 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25722-15 F 0.3 MG/KG/DAY BODY/INTEGUMENT 07-21-06 9:02 1 HAIR LOSS LEFT FORELIMB 07-21-06 9:02 1 HAIR LOSS RIGHT HINDLIMB 07-21-06 9:02 1 HAIR LOSS LEFT HINDLIMB 08-04-06 6:58 1 HAIR LOSS RIGHT FORELIMB 08-04-06 6:58 1 HAIR LOSS LEFT FORELIMB 08-06-06 7:21 1 HAIR LOSS LEFT FORELIMB 08-06-06 7:21 1 HAIR LOSS RIGHT FORELIMB 25628-17 F 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25766-06 F 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25689-14 F 0.3 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA 25708-15 F 0.3 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA 25743-16 F 0.3 MG/KG/DAY DISPOSITION 08-07-06 7:25 P SCHEDULED EUTHANASIA 25642-12 F 0.3 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25696-11 F 1.0 MG/KG/DAY DISPOSITION 08-04-06 7:10 P SCHEDULED EUTHANASIA 25686-10 F 1.0 MG/KG/DAY DISPOSITION 08-04-06 7:07 P SCHEDULED EUTHANASIA 25630-09 F 1.0 MG/KG/DAY DISPOSITION 08-04-06 7:10 P SCHEDULED EUTHANASIA 25673-10 F 1.0 MG/KG/DAY DISPOSITION 08-04-06 7:11 P SCHEDULED EUTHANASIA -805- 25639-04 F 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:18 P SCHEDULED EUTHANASIA 25658-14 F 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:19 P SCHEDULED EUTHANASIA 25676-15 F 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25600-15 F 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25603-10 F 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:19 P SCHEDULED EUTHANASIA 25703-10 F 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25705-08 F 1.0 MG/KG/DAY DISPOSITION 08-05-06 7:12 P SCHEDULED EUTHANASIA 25611-11 F 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25619-12 F 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25691-11 F 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25717-15 F 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25616-14 F 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT APPENDIX 23 (F1) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 06-17-06 TO 08-08-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25715-10 F 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:49 P SCHEDULED EUTHANASIA 25599-11 F 1.0 MG/KG/DAY DISPOSITION 08-06-06 7:53 P SCHEDULED EUTHANASIA 25762-11 F 1.0 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA 25647-11 F 1.0 MG/KG/DAY DISPOSITION 08-07-06 7:24 P SCHEDULED EUTHANASIA ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT PCRDv4.11 01/23/2007 -806- APPENDIX 24 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES PND 28 35 42 49 56 63 70 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 1: 0 MG/KG/DAY ------------------------------------------- 25597-04 75. 127. 188. 234. 274. 307. 334. 339. 25654-09 77. 135. 205. 257. 310. 347. 386. 386. 25632-07 79. 137. 197. 250. 299. 334. 372. 383. 25633-05 61. 108. 172. 231. 291. 325. 373. 383. 25618-08 87. 149. 212. 267. 319. 364. 393. 404. 25621-07 98. 167. 236. 288. 337. 374. 404. 413. 25687-07 94. 160. 226. 276. 324. 364. 403. 407. 25681-01 82. 145. 208. 261. 309. 346. 389. 401. 25615-03 90. 155. 220. 283. 338. 373. 404. 414. 25637-06 97. 174. 239. 307. 369. 419. 455. 477. 25638-07 86. 145. 207. 263. 312. 346. 386. 404. 25713-02 88. 154. 218. 274. 323. 350. 382. 392. 25670-09 96. 168. 223. 296. 353. 403. 441. 462. 25657-08 99. 177. 246. 313. 381. 419. 468. 484. 25663-04 101. 167. 233. 293. 348. 393. 439. 453. 25690-01 87. 151. 214. 270. 324. 351. 392. 405. 25666-01 97. 165. 239. 298. 357. 399. 454. 465. 25692-04 100. 163. 231. 280. 329. 376. 413. 423. 25701-09 88. 153. 215. 278. 327. 374. 408. 415. 25645-06 75. 123. 175. 224. 268. 311. 338. 346. -807- MEAN S.D. N 88. 10.5 20 151. 17.9 20 215. 20.5 20 272. 24.6 20 325. 29.1 20 364. 32.3 20 402. 36.1 20 413. 39.2 20 APPENDIX 24 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES PND 28 35 42 49 56 63 70 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 2: 0.1 MG/KG/DAY ------------------------------------------- 25648-07 87. 148. 216. 271. 322. 356. 399. 407. 25674-02 76. 132. 191. 234. 286. 318. 351. 362. 25694-04 103. 172. 242. 314. 377. 430. 473. 487. 25631-04 101. 181. 255. 326. 389. 447. 500. 514. 25660-01 90. 151. 215. 278. 324. 374. 409. 421. 25704-03 91. 151. 213. 268. 321. 357. 401. 409. 25665-01 84. 147. 208. 255. 307. 343. 370. 388. 25652-04 96. 174. 248. 315. 385. 444. 503. 520. 25733-07 74. 138. 199. 247. 298. 337. 375. 383. 25748-01 99. 174. 250. 313. 363. 412. 450. 467. 25753-06 100. 179. 247. 314. 366. 403. 434. 448. 25672-06 89. 153. 207. 265. 317. 358. 380. 396. 25655-01 82. 138. 192. 258. 309. 348. 380. 384. 25727-07 86. 151. 215. 277. 339. 393. 437. 453. 25626-04 96. 164. 229. 284. 341. 386. 428. 434. 25749-04 91. 164. 233. 289. 350. 388. 428. 435. 25739-07 101. 164. 234. 292. 362. 405. 449. 462. 25756-05 103. 180. 260. 329. 384. 449. 499. 516. 25741-07 100. 175. 243. 298. 358. 412. 447. 465. 25752-09 102. 175. 245. 308. 352. 402. 440. 455. -808- MEAN S.D. N 92. 160. 227. 287. 342. 388. 428. 440. 8.9 15.6 21.6 27.4 30.8 38.5 44.7 46.9 20 20 20 20 20 20 20 20 APPENDIX 24 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES PND 28 35 42 49 56 63 70 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 3: 0.3 MG/KG/DAY ------------------------------------------- 25671-04 83. 146. 219. 280. 348. 390. 432. 456. 25614-10 96. 168. 236. 297. 364. 404. 446. 460. 25698-05 79. 135. 199. 255. 317. 366. 409. 419. 25677-05 91. 160. 225. 281. 337. 373. 403. 415. 25604-04 95. 168. 241. 304. 364. 410. 464. 474. 25678-02 87. 152. 219. 278. 342. 388. 425. 442. 25609-04 92. 156. 226. 284. 330. 376. 413. 431. 25623-08 88. 159. 231. 292. 354. 396. 445. 454. 25653-02 93. 156. 217. 267. 323. 356. 398. 411. 25684-04 91. 164. 231. 295. 342. 382. 417. 426. 25714-02 100. 168. 230. 279. 332. 366. 412. 419. 25650-11 95. 163. 228. 289. 340. 381. 415. 430. 25735-05 97. 165. 232. 297. 352. 398. 435. 448. 25722-01 84. 154. 218. 280. 333. 376. 422. 430. 25642-05 99. 169. 237. 295. 346. 385. 425. 433. 25628-07 82. 137. 195. 249. 295. 334. 370. 385. 25766-01 74. 136. 195. 246. 294. 320. 357. 366. 25689-02 105. 170. 228. 295. 342. 388. 421. 433. 25708-01 95. 162. 226. 279. 323. 365. 401. 407. 25743-08 79. 136. 206. 264. 324. 371. 413. 426. -809- MEAN S.D. N 90. 156. 222. 280. 335. 376. 416. 428. 8.1 12.1 13.6 16.7 19.0 21.8 24.3 25.1 20 20 20 20 20 20 20 20 APPENDIX 24 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES PND 28 35 42 49 56 63 70 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 4: 1.0 MG/KG/DAY ------------------------------------------- 25696-04 91. 157. 225. 277. 331. 366. 413. 434. 25686-04 86. 153. 225. 287. 344. 379. 422. 433. 25630-04 98. 156. 225. 275. 338. 382. 422. 434. 25673-09 72. 124. 185. 238. 296. 327. 362. 377. 25639-06 93. 161. 236. 301. 353. 402. 442. 455. 25658-08 86. 150. 227. 294. 350. 392. 448. 459. 25676-02 93. 162. 229. 279. 328. 363. 407. 417. 25600-02 97. 165. 226. 287. 341. 379. 408. 418. 25603-04 91. 158. 225. 281. 324. 368. 409. 420. 25703-03 91. 149. 217. 273. 322. 353. 394. 403. 25705-07 88. 155. 232. 301. 357. 408. 456. 463. 25611-07 86. 150. 204. 245. 283. 310. 351. 358. 25619-04 70. 125. 172. 221. 279. 308. 348. 360. 25691-07 85. 150. 212. 275. 333. 375. 421. 425. 25717-04 86. 148. 223. 292. 348. 387. 431. 449. 25616-05 92. 157. 231. 305. 359. 404. 462. 475. 25715-07 80. 144. 211. 272. 331. 374. 425. 433. 25599-06 78. 133. 198. 238. 307. 346. 387. 399. 25762-01 83. 144. 207. 261. 326. 366. 404. 419. 25647-07 56. 104. 165. 223. 272. 305. 346. 361. -810- MEAN S.D. N 85. 10.2 20 147. 15.1 20 214. 20.0 20 271. 25.7 20 326. 26.0 20 365. 31.3 20 408. 34.6 20 420. 34.6 20 APPENDIX 24 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES PND 28 35 42 49 56 63 70 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 1: 0 MG/KG/DAY ------------------------------------------- 25597-17 65. 106. 137. 158. 173. 195. 202. 209. 25654-10 71. 113. 157. 176. 195. 216. 223. 227. 25632-09 83. 128. 164. 187. 209. 226. 246. 246. 25633-13 56. 99. 144. 174. 198. 223. 230. 243. 25618-17 81. 132. 181. 202. 222. 240. 262. 256. 25621-10 92. 153. 180. 215. 265. 267. 285. 283. 25687-15 81. 126. 159. 179. 202. 215. 229. 237. 25681-10 80. 121. 150. 169. 190. 193. 207. 208. 25615-10 82. 135. 171. 203. 237. 243. 266. 270. 25637-17 92. 146. 186. 214. 237. 267. 288. 277. 25638-18 69. 111. 143. 169. 187. 202. 218. 215. 25713-16 81. 125. 159. 183. 202. 224. 234. 228. 25670-18 88. 148. 178. 217. 243. 260. 279. 269. 25657-10 92. 140. 171. 184. 209. 233. 261. 273. 25663-09 87. 131. 170. 189. 212. 238. 255. 245. 25690-19 86. 141. 181. 217. 238. 258. 276. 281. 25666-09 81. 133. 166. 189. 207. 220. 232. 236. 25692-07 86. 135. 176. 197. 225. 229. 245. 248. 25701-18 86. 139. 174. 191. 216. 232. 244. 245. 25645-08 72. 115. 137. 154. 170. 187. 187. 197. -811- MEAN S.D. N 80. 129. 164. 188. 212. 228. 243. 245. 9.6 14.4 15.4 19.0 24.2 23.5 28.3 25.7 20 20 20 20 20 20 20 20 APPENDIX 24 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES PND 28 35 42 49 56 63 70 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 2: 0.1 MG/KG/DAY ------------------------------------------- 25648-12 86. 137. 175. 184. 190. 232. 249. 251. 25674-11 76. 126. 163. 183. 212. 232. 245. 246. 25694-13 82. 131. 173. 191. 216. 232. 250. 239. 25631-05 84. 140. 174. 200. 225. 244. 257. 267. 25660-04 96. 152. 189. 206. 226. 254. 271. 260. 25704-09 90. 138. 179. 203. 236. 247. 254. 269. 25665-07 75. 124. 162. 176. 191. 210. 220. 223. 25652-13 73. 125. 164. 182. 213. 235. 252. 250. 25733-08 72. 120. 152. 164. 187. 194. 211. 218. 25748-08 84. 133. 169. 193. 215. 227. 249. 244. 25753-15 84. 138. 170. 188. 217. 241. 245. 255. 25672-15 78. 132. 175. 191. 200. 225. 237. 236. 25655-13 78. 131. 175. 199. 227. 245. 270. 272. 25727-16 68. 116. 157. 183. 214. 230. 260. 263. 25626-12 84. 134. 173. 203. 228. 244. 260. 267. 25749-11 85. 136. 175. 206. 236. 252. 266. 258. 25739-12 99. 146. 188. 218. 241. 251. 283. 287. 25756-13 86. 130. 166. 185. 196. 213. 227. 221. 25741-09 94. 154. 193. 208. 238. 260. 269. 273. 25752-13 101. 153. 192. 236. 253. 268. 303. 303. -812- MEAN S.D. N 84. 135. 173. 195. 218. 237. 254. 255. 9.0 10.6 11.1 16.0 18.5 17.8 21.1 21.7 20 20 20 20 20 20 20 20 APPENDIX 24 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES PND 28 35 42 49 56 63 70 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 3: 0.3 MG/KG/DAY ------------------------------------------- 25671-06 77. 120. 165. 187. 207. 228. 240. 250. 25614-17 78. 128. 167. 193. 208. 229. 242. 246. 25698-12 73. 123. 157. 175. 206. 217. 234. 237. 25677-08 91. 148. 189. 210. 231. 251. 256. 272. 25604-12 82. 132. 168. 190. 219. 231. 240. 252. 25678-11 82. 131. 172. 196. 219. 231. 248. 253. 25609-11 78. 126. 163. 189. 204. 230. 251. 244. 25623-15 78. 135. 170. 178. 219. 240. 258. 253. 25653-13 85. 132. 155. 170. 193. 208. 217. 228. 25684-06 86. 136. 177. 206. 212. 236. 252. 249. 25714-13 94. 147. 179. 207. 222. 245. 252. 261. 25650-17 93. 141. 193. 220. 246. 284. 264. 279. 25735-08 85. 136. 182. 212. 245. 262. 274. 297. 25722-15 78. 120. 163. 187. 201. 227. 237. 252. 25628-17 71. 115. 149. 181. 204. 221. 246. 260. 25766-06 70. 119. 156. 170. 181. 197. 216. 223. 25689-14 94. 147. 177. 198. 211. 239. 252. 240. 25708-15 84. 135. 154. 175. 189. 203. 222. 220. 25743-16 73. 121. 139. 157. 171. 190. 209. 211. 25642-12 86. 142. 186. 213. 244. 259. 277. 285. -813- MEAN S.D. N 82. 132. 168. 191. 212. 231. 244. 251. 7.4 10.1 14.1 17.0 20.3 22.8 18.5 21.6 20 20 20 20 20 20 20 20 APPENDIX 24 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES PND 28 35 42 49 56 63 70 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 4: 1.0 MG/KG/DAY ------------------------------------------- 25696-11 84. 137. 174. 191. 221. 236. 246. 246. 25686-10 72. 125. 156. 173. 203. 223. 236. 236. 25630-09 80. 124. 160. 179. 189. 208. 220. 220. 25673-10 63. 105. 142. 161. 184. 198. 214. 219. 25639-04 92. 143. 182. 219. 245. 266. 293. 296. 25658-14 75. 125. 165. 192. 215. 237. 254. 268. 25676-15 88. 139. 173. 193. 215. 230. 239. 240. 25600-15 95. 148. 173. 186. 200. 220. 241. 239. 25603-10 86. 132. 162. 181. 201. 213. 230. 229. 25703-10 83. 131. 169. 189. 205. 229. 249. 241. 25705-08 90. 147. 184. 205. 231. 251. 268. 260. 25611-11 78. 125. 157. 172. 188. 205. 216. 219. 25619-12 72. 124. 160. 203. 232. 256. 273. 278. 25691-11 86. 137. 179. 206. 222. 241. 257. 272. 25717-15 73. 124. 153. 186. 218. 232. 241. 261. 25616-14 85. 145. 183. 215. 239. 262. 270. 268. 25715-10 78. 128. 152. 179. 199. 217. 208. 231. 25599-11 73. 117. 151. 177. 199. 221. 231. 246. 25762-11 78. 124. 147. 163. 178. 188. 201. 198. 25647-11 76. 125. 165. 196. 223. 239. 245. 260. -814- MEAN S.D. N 80. 130. 164. 188. 210. 229. 241. 246. 8.0 11.0 12.5 15.9 18.8 20.9 23.6 23.9 20 20 20 20 20 20 20 20 PJTBWv4.22 10/10/2006 APPENDIX 25 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES PND 28- 35 35- 42 42- 49 49- 56 56- 63 63- 70 70- 72 28- 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 1: 0 MG/KG/DAY ------------------------------------------- 25597-04 52. 60. 47. 40. 33. 26. 5. 264. 25654-09 59. 69. 53. 53. 36. 39. 0. 309. 25632-07 58. 60. 53. 49. 35. 38. 11. 304. 25633-05 48. 64. 59. 60. 34. 48. 10. 322. 25618-08 61. 63. 55. 51. 46. 28. 11. 316. 25621-07 69. 69. 53. 48. 37. 30. 9. 315. 25687-07 66. 66. 51. 48. 40. 39. 4. 313. 25681-01 63. 63. 53. 48. 37. 43. 13. 319. 25615-03 65. 66. 63. 55. 35. 32. 10. 324. 25637-06 77. 65. 68. 63. 49. 37. 22. 380. 25638-07 59. 62. 56. 48. 34. 40. 18. 318. 25713-02 66. 64. 56. 49. 27. 32. 10. 304. 25670-09 72. 55. 74. 57. 50. 38. 21. 366. 25657-08 77. 69. 67. 68. 39. 49. 16. 385. 25663-04 66. 66. 60. 55. 45. 47. 14. 352. 25690-01 64. 63. 57. 54. 27. 41. 12. 318. 25666-01 68. 74. 60. 58. 42. 55. 11. 367. 25692-04 63. 67. 50. 49. 47. 38. 9. 323. 25701-09 65. 62. 63. 50. 46. 34. 7. 327. 25645-06 47. 53. 48. 45. 43. 27. 8. 271. -815- MEAN S.D. N 63. 64. 57. 52. 39. 38. 11. 325. 8.1 4.8 7.0 6.5 6.8 7.8 5.3 31.7 20 20 20 20 20 20 20 20 APPENDIX 25 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES PND 28- 35 35- 42 42- 49 49- 56 56- 63 63- 70 70- 72 28- 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 2: 0.1 MG/KG/DAY ------------------------------------------- 25648-07 60. 68. 55. 51. 34. 43. 8. 320. 25674-02 56. 59. 43. 52. 32. 33. 11. 286. 25694-04 69. 70. 72. 63. 53. 43. 14. 384. 25631-04 80. 75. 71. 63. 58. 53. 14. 413. 25660-01 60. 64. 63. 46. 51. 35. 11. 330. 25704-03 61. 62. 55. 53. 36. 44. 8. 319. 25665-01 63. 60. 48. 52. 36. 28. 17. 304. 25652-04 78. 74. 66. 71. 58. 60. 16. 424. 25733-07 64. 61. 49. 51. 39. 38. 8. 309. 25748-01 75. 76. 64. 50. 49. 38. 17. 368. 25753-06 79. 68. 67. 52. 38. 31. 14. 349. 25672-06 64. 55. 58. 52. 41. 22. 16. 307. 25655-01 56. 54. 65. 52. 38. 32. 5. 302. 25727-07 65. 64. 62. 62. 54. 45. 15. 367. 25626-04 68. 65. 55. 58. 44. 42. 7. 339. 25749-04 72. 70. 56. 61. 37. 41. 6. 344. 25739-07 64. 69. 59. 70. 44. 44. 13. 362. 25756-05 78. 80. 68. 56. 65. 50. 18. 414. 25741-07 75. 67. 55. 60. 54. 35. 18. 365. 25752-09 73. 69. 63. 45. 49. 38. 15. 353. -816- MEAN S.D. N 68. 67. 60. 56. 45. 40. 13. 348. 7.8 6.8 7.8 7.2 9.5 8.8 4.3 39.7 20 20 20 20 20 20 20 20 APPENDIX 25 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES PND 28- 35 35- 42 42- 49 49- 56 56- 63 63- 70 70- 72 28- 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 3: 0.3 MG/KG/DAY ------------------------------------------- 25671-04 64. 73. 61. 68. 42. 43. 24. 373. 25614-10 72. 68. 61. 67. 40. 42. 14. 364. 25698-05 57. 64. 56. 62. 48. 43. 11. 341. 25677-05 69. 65. 56. 55. 36. 31. 11. 324. 25604-04 73. 73. 63. 61. 45. 54. 10. 379. 25678-02 65. 67. 59. 64. 46. 38. 17. 355. 25609-04 64. 69. 58. 46. 47. 37. 18. 339. 25623-08 71. 72. 61. 62. 42. 49. 8. 366. 25653-02 63. 61. 50. 56. 33. 42. 12. 318. 25684-04 73. 67. 64. 47. 40. 34. 10. 335. 25714-02 69. 62. 49. 52. 35. 45. 8. 320. 25650-11 68. 65. 61. 51. 41. 34. 15. 335. 25735-05 68. 67. 66. 55. 46. 37. 13. 351. 25722-01 70. 65. 62. 52. 43. 46. 9. 347. 25642-05 70. 68. 58. 51. 39. 40. 8. 334. 25628-07 55. 58. 54. 47. 39. 36. 16. 303. 25766-01 62. 59. 51. 49. 26. 37. 9. 292. 25689-02 65. 58. 67. 48. 46. 33. 12. 328. 25708-01 67. 64. 54. 44. 42. 36. 6. 312. 25743-08 56. 70. 58. 60. 47. 42. 13. 347. -817- MEAN S.D. N 66. 66. 58. 55. 41. 40. 12. 338. 5.4 4.7 5.1 7.3 5.5 5.8 4.2 23.0 20 20 20 20 20 20 20 20 APPENDIX 25 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- MALES PND 28- 35 35- 42 42- 49 49- 56 56- 63 63- 70 70- 72 28- 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 4: 1.0 MG/KG/DAY ------------------------------------------- 25696-04 66. 68. 52. 54. 35. 46. 21. 343. 25686-04 68. 72. 62. 57. 35. 42. 12. 348. 25630-04 57. 70. 50. 63. 44. 41. 12. 335. 25673-09 53. 61. 53. 58. 31. 36. 15. 306. 25639-06 67. 76. 64. 52. 49. 40. 14. 362. 25658-08 64. 77. 67. 56. 41. 57. 11. 373. 25676-02 70. 67. 50. 49. 36. 44. 10. 325. 25600-02 68. 61. 60. 54. 38. 29. 10. 321. 25603-04 67. 67. 57. 42. 44. 41. 11. 329. 25703-03 58. 68. 56. 50. 31. 41. 9. 312. 25705-07 67. 77. 70. 55. 52. 48. 7. 375. 25611-07 64. 54. 41. 39. 27. 41. 7. 272. 25619-04 56. 47. 48. 58. 29. 40. 12. 290. 25691-07 65. 62. 62. 59. 42. 46. 4. 340. 25717-04 63. 75. 68. 57. 38. 44. 19. 364. 25616-05 65. 74. 74. 54. 45. 58. 13. 383. 25715-07 64. 67. 61. 59. 43. 51. 9. 353. 25599-06 54. 66. 40. 68. 39. 41. 12. 321. 25762-01 61. 63. 54. 65. 40. 38. 15. 335. 25647-07 48. 61. 57. 50. 33. 41. 15. 305. -818- MEAN S.D. N 62. 67. 57. 55. 39. 43. 12. 335. 5.9 7.7 9.1 7.0 6.6 6.7 4.0 29.2 20 20 20 20 20 20 20 20 APPENDIX 25 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES PND 28- 35 35- 42 42- 49 49- 56 56- 63 63- 70 70- 72 28- 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 1: 0 MG/KG/DAY ------------------------------------------- 25597-17 41. 31. 21. 15. 22. 7. 7. 144. 25654-10 42. 44. 19. 20. 21. 6. 4. 156. 25632-09 46. 35. 23. 22. 17. 20. 0. 163. 25633-13 43. 44. 31. 24. 25. 7. 13. 187. 25618-17 51. 49. 22. 20. 18. 22. -5. 176. 25621-10 61. 27. 35. 50. 1. 18. -2. 191. 25687-15 46. 32. 21. 23. 14. 14. 8. 157. 25681-10 41. 29. 19. 21. 3. 14. 1. 129. 25615-10 53. 36. 32. 34. 6. 23. 4. 189. 25637-17 54. 40. 28. 23. 30. 21. -10. 186. 25638-18 42. 32. 27. 17. 16. 16. -3. 146. 25713-16 45. 34. 24. 19. 22. 10. -5. 148. 25670-18 60. 30. 39. 26. 17. 20. -10. 182. 25657-10 47. 31. 13. 26. 24. 27. 13. 181. 25663-09 44. 39. 19. 23. 26. 17. -10. 157. 25690-19 55. 40. 36. 21. 20. 18. 6. 196. 25666-09 52. 33. 23. 18. 13. 12. 4. 154. 25692-07 49. 41. 21. 28. 3. 16. 3. 162. 25701-18 54. 35. 17. 25. 17. 12. 0. 159. 25645-08 44. 22. 17. 16. 17. 0. 10. 126. -819- MEAN S.D. N 48. 35. 24. 24. 16. 15. 1. 164. 6.1 6.5 7.2 7.7 7.9 6.6 7.1 20.5 20 20 20 20 20 20 20 20 APPENDIX 25 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES PND 28- 35 35- 42 42- 49 49- 56 56- 63 63- 70 70- 72 28- 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 2: 0.1 MG/KG/DAY ------------------------------------------- 25648-12 51. 39. 8. 7. 41. 17. 2. 165. 25674-11 50. 38. 20. 28. 20. 13. 2. 171. 25694-13 49. 42. 18. 25. 16. 18. -12. 157. 25631-05 56. 35. 26. 25. 19. 13. 10. 183. 25660-04 56. 37. 18. 20. 27. 17. -11. 164. 25704-09 48. 40. 24. 33. 12. 7. 15. 178. 25665-07 49. 38. 14. 16. 19. 9. 3. 148. 25652-13 53. 39. 18. 31. 22. 18. -2. 178. 25733-08 48. 32. 12. 22. 8. 17. 7. 146. 25748-08 49. 36. 24. 22. 12. 22. -5. 160. 25753-15 54. 32. 18. 30. 24. 4. 9. 170. 25672-15 55. 43. 16. 9. 25. 13. -1. 159. 25655-13 53. 44. 24. 28. 19. 25. 2. 194. 25727-16 47. 42. 26. 31. 16. 30. 3. 195. 25626-12 50. 39. 30. 26. 15. 17. 7. 184. 25749-11 51. 39. 30. 30. 17. 13. -8. 173. 25739-12 47. 42. 31. 23. 10. 32. 4. 188. 25756-13 44. 36. 19. 11. 18. 14. -6. 136. 25741-09 60. 39. 15. 31. 22. 9. 4. 179. 25752-13 53. 39. 44. 17. 15. 35. 1. 203. -820- MEAN S.D. N 51. 38. 22. 23. 19. 17. 1. 171. 3.8 3.2 8.1 7.7 7.3 8.2 6.8 17.6 20 20 20 20 20 20 20 20 APPENDIX 25 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES PND 28- 35 35- 42 42- 49 49- 56 56- 63 63- 70 70- 72 28- 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 3: 0.3 MG/KG/DAY ------------------------------------------- 25671-06 43. 46. 21. 21. 21. 12. 10. 172. 25614-17 51. 38. 26. 15. 21. 13. 4. 168. 25698-12 49. 34. 19. 31. 12. 17. 3. 164. 25677-08 57. 41. 21. 21. 21. 5. 16. 181. 25604-12 50. 37. 22. 29. 12. 9. 12. 170. 25678-11 50. 41. 23. 24. 12. 18. 5. 171. 25609-11 48. 37. 26. 15. 26. 21. -7. 166. 25623-15 57. 36. 8. 40. 21. 18. -5. 175. 25653-13 47. 23. 15. 23. 14. 10. 11. 143. 25684-06 50. 41. 29. 7. 23. 16. -3. 163. 25714-13 53. 32. 29. 15. 23. 7. 9. 167. 25650-17 48. 52. 27. 27. 38. -20. 14. 186. 25735-08 51. 46. 29. 34. 17. 12. 23. 212. 25722-15 42. 43. 24. 14. 27. 9. 15. 173. 25628-17 44. 34. 32. 23. 17. 26. 14. 189. 25766-06 49. 37. 15. 10. 16. 19. 7. 153. 25689-14 53. 31. 21. 13. 28. 13. -12. 146. 25708-15 51. 20. 21. 14. 15. 18. -2. 136. 25743-16 48. 19. 18. 14. 19. 19. 3. 138. 25642-12 57. 44. 26. 32. 15. 18. 8. 200. -821- MEAN S.D. N 50. 36. 23. 21. 20. 13. 6. 169. 4.2 8.7 5.8 8.8 6.6 9.4 8.7 19.5 20 20 20 20 20 20 20 20 APPENDIX 25 (F1 - POST-WEANING) PROJECT NO.:WIL-180017J ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- FEMALES PND 28- 35 35- 42 42- 49 49- 56 56- 63 63- 70 70- 72 28- 72 ----------------------------------------------------------------------------------------------------------------------------------- ANIMALS FROM GROUP 4: 1.0 MG/KG/DAY ------------------------------------------- 25696-11 53. 37. 17. 30. 16. 10. 0. 163. 25686-10 53. 31. 18. 29. 20. 13. 1. 165. 25630-09 44. 36. 19. 10. 19. 12. 0. 140. 25673-10 42. 38. 18. 23. 14. 16. 5. 156. 25639-04 51. 39. 36. 27. 21. 27. 3. 204. 25658-14 50. 39. 27. 24. 21. 18. 14. 193. 25676-15 51. 34. 20. 21. 15. 9. 1. 151. 25600-15 53. 25. 13. 14. 21. 20. -1. 144. 25603-10 46. 30. 19. 20. 13. 17. -1. 143. 25703-10 48. 38. 20. 16. 24. 20. -7. 159. 25705-08 58. 37. 21. 27. 20. 17. -8. 170. 25611-11 46. 33. 14. 16. 17. 11. 3. 141. 25619-12 51. 37. 42. 29. 24. 17. 5. 206. 25691-11 51. 42. 28. 16. 19. 16. 15. 187. 25717-15 51. 29. 33. 32. 14. 9. 20. 188. 25616-14 61. 38. 32. 23. 23. 8. -2. 184. 25715-10 50. 24. 27. 20. 18. -9. 23. 154. 25599-11 44. 34. 27. 21. 23. 10. 15. 173. 25762-11 46. 23. 17. 15. 10. 13. -3. 121. 25647-11 49. 40. 30. 28. 15. 6. 15. 184. -822- MEAN S.D. N 50. 34. 24. 22. 18. 13. 5. 166. 4.6 5.5 7.9 6.3 4.0 7.2 8.9 23.2 20 20 20 20 20 20 20 20 PJTBWv4.22 10/10/2006 PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 1 PND 4 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 1 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -823- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 2 PND 4 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 1 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -824- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 3 PND 4 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -825- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 4 PND 4 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -826- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 5 PND 4 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -827- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 6 PND 4 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 1 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -828- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 7 PND 4 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -829- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 8 PND 4 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -830- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 9 PND 4 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -831- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 10 PND 4 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -832- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 11 PND 4 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 1 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -833- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 12 PND 4 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -834- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 13 PND 4 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -835- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 14 PND 4 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-13 25650-17 25735-08 25722-15 25642-10 25628-17 25766-06 25689-14 25708-15 25743-16 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 1 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -836- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 15 PND 4 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -837- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 16 PND 4 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -838- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 17 PND 11 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -839- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 18 PND 11 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -840- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 19 PND 11 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -841- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 20 PND 11 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -842- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 21 PND 11 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -843- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 22 PND 11 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -844- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 23 PND 11 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -845- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 24 PND 11 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -846- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 25 PND 11 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -847- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 26 PND 11 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -848- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 27 PND 11 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -849- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 28 PND 11 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -850- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 29 PND 11 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -851- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 30 PND 11 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -852- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 31 PND 11 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -853- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 32 PND 11 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : _ _ _ _ _ _ _ _ _ _ FUR APPEARANCE : _ _ _ _ _ _ _ _ _ _ PALPEBRAL CLOSURE : _ _ _ _ _ _ _ _ _ _ RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : _ _ _ _ _ _ _ _ _ _ PUPILLARY RESPONSE : _ _ _ _ _ _ _ _ _ _ SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : _ _ _ _ _ _ _ _ _ _ MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -854- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 33 PND 21 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -855- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 34 PND 21 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -856- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 35 PND 21 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -857- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 36 PND 21 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -858- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 37 PND 21 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -859- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 38 PND 21 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -860- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 39 PND 21 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -861- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 40 PND 21 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -862- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 41 PND 21 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -863- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 42 PND 21 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -864- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 43 PND 21 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -865- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 44 PND 21 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -866- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 45 PND 21 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -867- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 46 PND 21 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -868- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 47 PND 21 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -869- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 48 PND 21 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -870- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 49 PND 35 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -871- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 50 PND 35 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 1 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -872- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 51 PND 35 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -873- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 52 PND 35 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 1 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -874- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 53 PND 35 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 1 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -875- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 54 PND 35 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 2 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -876- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 55 PND 35 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 1 2 1 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -877- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 56 PND 35 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 2 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 1 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -878- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 57 PND 35 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -879- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 58 PND 35 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -880- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 59 PND 35 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 1 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -881- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 60 PND 35 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -882- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 61 PND 35 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -883- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 62 PND 35 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -884- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 63 PND 35 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -885- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 64 PND 35 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 1 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -886- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 65 PND 45 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 1 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -887- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 66 PND 45 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -888- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 67 PND 45 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -889- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 68 PND 45 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -890- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 69 PND 45 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -891- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 70 PND 45 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -892- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 71 PND 45 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -893- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 72 PND 45 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 2 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 1 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -894- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 73 PND 45 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -895- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 74 PND 45 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -896- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 75 PND 45 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -897- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 76 PND 45 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -898- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 77 PND 45 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -899- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 78 PND 45 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -900- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 79 PND 45 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 1 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -901- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 80 PND 45 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -902- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 81 PND 60 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -903- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 82 PND 60 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -904- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 83 PND 60 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 2 1 1 2 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 2 1 1 2 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -905- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 84 PND 60 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -906- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 85 PND 60 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -907- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 86 PND 60 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -908- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 87 PND 60 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -909- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 88 PND 60 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -910- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 89 PND 60 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -911- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 90 PND 60 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -912- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 91 PND 60 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 2 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 2 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 1 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -913- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 92 PND 60 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -914- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 93 PND 60 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -915- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 94 PND 60 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 2 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 2 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -916- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 95 PND 60 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -917- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 96 PND 60 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1 1 1 1 1 1 1 1 1 1 EASE OF HANDLING ANIMAL IN HAND: 1 1 1 1 1 1 1 1 1 1 LACRIMATION : 1 1 1 1 1 1 1 1 1 1 CHROMODACRYORRHEA : 1 1 1 1 1 1 1 1 1 1 SALIVATION : 1 1 1 1 1 1 1 1 1 1 PILOERECTION : 1 1 1 1 1 1 1 1 1 1 FUR APPEARANCE : 1 1 1 1 1 1 1 1 1 1 PALPEBRAL CLOSURE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY RATE : 1 1 1 1 1 1 1 1 1 1 RESPIRATORY CHARACTER : 1 1 1 1 1 1 1 1 1 1 RED DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 RED DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - EYES : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - NOSE : 2 2 2 2 2 2 2 2 2 2 CRUSTY DEPOSITS - MOUTH : 2 2 2 2 2 2 2 2 2 2 MUCOUS MEMBRANES - COLOR : 1 1 1 1 1 1 1 1 1 1 EYE COLOR : 1 1 1 1 1 1 1 1 1 1 PUPILLARY RESPONSE : 2 2 2 2 2 2 2 2 2 2 SKIN COLOR : 1 1 1 1 1 1 1 1 1 1 EYE PROMINENCE : 1 1 1 1 1 1 1 1 1 1 MUSCLE TONE : 1 1 1 1 1 1 1 1 1 1 ----------------------------------------------------------------------------------------------------------------------------------- -W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION -918- PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 97 PARAMETER SCORING CRITERIA ----------------------------------------------------------------------------------------------------------------------------------- EASE OF REMOVAL FROM CAGE : 1-VERY EASY 2-EASY 3-MODERATELY DIFFICULT 4-FREEZES 5-DIFFICULT 6-VERY DIFFICULT EASE OF HANDLING ANIMAL IN HAND: 1-LOW 2-MODERATELY LOW 3-MODERATELY HIGH 4-HIGH LACRIMATION : 1-NONE 2-SLIGHT 3-SEVERE CHROMODACRYORRHEA : 1-ABSENT 2-PRESENT SALIVATION : 1-NONE 2-SLIGHT 3-SEVERE PILOERECTION : 1-NONE 2-SLIGHT 3-SEVERE FUR APPEARANCE : 1-NORMAL: CLEAN AND GROOMED 2-SLIGHTLY SOILED 3-VERY SOILED, CRUSTY PALPEBRAL CLOSURE : 1-WIDE OPEN 4-COMPLETELY SHUT 2-SLIGHTLY DROOPING 3-DROOPING (HALF-CLOSED) -919- RESPIRATORY RATE : 1-NORMAL (80-110) 2-DECREASED (<80) 3-INCREASED (>110) RESPIRATORY CHARACTER : 1-NORMAL 2-RALES 3-RETCHING 4-DYSPNEIC 5-GASPING PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 98 PARAMETER SCORING CRITERIA ----------------------------------------------------------------------------------------------------------------------------------- RED DEPOSITS - EYES : 1-PRESENT 2-ABSENT RED DEPOSITS - NOSE : 1-PRESENT 2-ABSENT RED DEPOSITS - MOUTH : 1-PRESENT 2-ABSENT CRUSTY DEPOSITS - EYES : 1-PRESENT 2-ABSENT CRUSTY DEPOSITS - NOSE : 1-PRESENT 2-ABSENT CRUSTY DEPOSITS - MOUTH : 1-PRESENT 2-ABSENT MUCOUS MEMBRANES - COLOR : 1-PINK 4-DARKENED, BROWN 2-PALE 5-BRIGHT, DEEP RED FLUSH 3-DARKENED EYE COLOR : 1-PINK 4-DARKENED, BROWN 2-PALE 5-BRIGHT, DEEP RED FLUSH 3-DARKENED -920- PUPILLARY RESPONSE : 1-ABSENT 2-PRESENT SKIN COLOR : 1-PINK 4-DARKENED, BROWN 2-PALE 5-BRIGHT, DEEP RED FLUSH 3-DARKENED PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS PAGE 99 PARAMETER SCORING CRITERIA ----------------------------------------------------------------------------------------------------------------------------------- EYE PROMINENCE : 1-NORMAL 2-EXOPHTHALMUS 3-ENOPHTHALMUS MUSCLE TONE : 1-FIRM BUT NOT HARD 2-SOFT AND FLABBY 3-TENSE AND HARD PFOBGv1.52 10/10/2006 R:01/26/2007 -921- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 1 PND 4 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -922- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 2 PND 4 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -923- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 3 PND 4 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 _ CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -924- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 4 PND 4 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -925- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 5 PND 4 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -926- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 6 PND 4 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -927- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 7 PND 4 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -928- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 8 PND 4 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -929- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 9 PND 4 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -930- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 10 PND 4 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -931- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 11 PND 4 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -932- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 12 PND 4 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -933- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 13 PND 4 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -934- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 14 PND 4 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-17 25735-08 25722-15 25642-10 25628-17 25766-06 25689-14 25708-15 25743-16 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -935- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 15 PND 4 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -936- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 16 PND 4 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : _ _ _ _ _ _ _ _ _ GAIT : _ _ _ _ _ _ _ _ _ CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : _ _ _ _ _ _ _ _ _ GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -937- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 17 PND 11 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 2 0 0 0 0 1 0 0 1 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -938- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 18 PND 11 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 1 1 1 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -939- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 19 PND 11 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 0 1 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -940- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 20 PND 11 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 1 1 3 2 1 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -941- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 21 PND 11 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 0 0 0 0 0 0 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -942- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 22 PND 11 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 1 0 1 0 0 0 0 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -943- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 23 PND 11 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 2 3 1 0 0 0 1 0 0 0 2 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -944- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 24 PND 11 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 3 2 2 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -945- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 25 PND 11 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 2 0 0 0 0 1 2 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -946- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 26 PND 11 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 0 0 1 0 0 1 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -947- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 27 PND 11 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 0 1 0 0 0 1 0 1 0 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -948- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 28 PND 11 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 1 0 1 0 0 3 0 1 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -949- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 29 PND 11 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 1 2 2 1 0 0 0 2 1 0 1 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -950- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 30 PND 11 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 1 0 2 0 1 0 0 0 1 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -951- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 31 PND 11 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ _ _ URINATION : 3 0 0 0 1 0 1 0 0 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -952- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 32 PND 11 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : _ _ _ _ _ _ _ _ _ URINATION : 0 1 1 0 0 0 0 0 1 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : _ _ _ _ _ _ _ _ _ AIR RIGHTING REFLEX : _ _ _ _ _ _ _ _ _ HINDLIMB EXTENSOR STRENGTH : _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 1: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 2: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH TRIAL 3: _ _ _ _ _ _ _ _ _ FORELIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ HINDLIMB GRIPSTRENGTH (AVG) : _ _ _ _ _ _ _ _ _ ----------------------------------------------------------------------------------------------------------------------------------- -953- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 33 PND 21 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 3 10 0 1 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 120. 125. 115. 95. 150. 55. 145. 125. 225. 140. 155. HINDLIMB GRIPSTRENGTH TRIAL 1: 100. 75. 50. 55. 60. 50. 55. 75. 125. 65. 80. FORELIMB GRIPSTRENGTH TRIAL 2: 90. 85. 120. 95. 105. 95. 100. 120. 180. 190. 160. HINDLIMB GRIPSTRENGTH TRIAL 2: 45. 90. 75. 45. 80. 80. 90. 70. 85. 80. 60. FORELIMB GRIPSTRENGTH TRIAL 3: 120. 105. 135. 55. 125. 120. 120. 115. 180. 120. 95. HINDLIMB GRIPSTRENGTH TRIAL 3: 65. 75. 45. 55. 80. 75. 80. 80. 60. 85. 60. FORELIMB GRIPSTRENGTH (AVG) : 110.0 105.0 123.3 81.7 126.7 90.0 121.7 120.0 195.0 150.0 136.7 HINDLIMB GRIPSTRENGTH (AVG) : 70.0 80.0 56.7 51.7 73.3 68.3 75.0 75.0 90.0 76.7 66.7 ----------------------------------------------------------------------------------------------------------------------------------- -954- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 34 PND 21 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 1 0 DEFECATION : 1 0 0 0 0 0 0 4 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 120. 230. 220. 155. 160. 135. 180. 185. 150. HINDLIMB GRIPSTRENGTH TRIAL 1: 90. 170. 85. 80. 100. 85. 70. 90. 110. FORELIMB GRIPSTRENGTH TRIAL 2: 150. 200. 85. 110. 115. 110. 175. 80. 140. HINDLIMB GRIPSTRENGTH TRIAL 2: 60. 135. 75. 95. 90. 90. 105. 85. 65. FORELIMB GRIPSTRENGTH TRIAL 3: 80. 220. 195. 150. 185. 115. 210. 200. 170. HINDLIMB GRIPSTRENGTH TRIAL 3: 40. 95. 85. 65. 105. 75. 80. 100. 110. FORELIMB GRIPSTRENGTH (AVG) : 116.7 216.7 166.7 138.3 153.3 120.0 188.3 155.0 153.3 HINDLIMB GRIPSTRENGTH (AVG) : 63.3 133.3 81.7 80.0 98.3 83.3 85.0 91.7 95.0 ----------------------------------------------------------------------------------------------------------------------------------- -955- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 35 PND 21 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 8 0 0 0 0 0 0 0 0 1 0 URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 2 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 155. 105. 135. 85. 100. 120. 130. 135. 115. 95. 145. HINDLIMB GRIPSTRENGTH TRIAL 1: 50. 65. 75. 100. 80. 95. 60. 90. 50. 100. 65. FORELIMB GRIPSTRENGTH TRIAL 2: 125. 100. 155. 145. 155. 175. 145. 150. 140. 100. 160. HINDLIMB GRIPSTRENGTH TRIAL 2: 95. 45. 75. 65. 95. 90. 65. 95. 105. 70. 90. FORELIMB GRIPSTRENGTH TRIAL 3: 80. 65. 150. 175. 210. 160. 140. 125. 120. 200. 140. HINDLIMB GRIPSTRENGTH TRIAL 3: 75. 90. 105. 75. 115. 85. 85. 100. 60. 120. 75. FORELIMB GRIPSTRENGTH (AVG) : 120.0 90.0 146.7 135.0 155.0 151.7 138.3 136.7 125.0 131.7 148.3 HINDLIMB GRIPSTRENGTH (AVG) : 73.3 66.7 85.0 80.0 96.7 90.0 70.0 95.0 71.7 96.7 76.7 ----------------------------------------------------------------------------------------------------------------------------------- -956- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 36 PND 21 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 1 URINATION : 0 0 0 0 1 0 0 0 0 DEFECATION : 0 0 1 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 140. 135. 90. 120. 160. 215. 160. 140. 215. HINDLIMB GRIPSTRENGTH TRIAL 1: 80. 65. 115. 55. 75. 115. 90. 70. 150. FORELIMB GRIPSTRENGTH TRIAL 2: 105. 115. 55. 155. 115. 120. 145. 220. 160. HINDLIMB GRIPSTRENGTH TRIAL 2: 75. 75. 65. 85. 85. 65. 100. 115. 90. FORELIMB GRIPSTRENGTH TRIAL 3: 75. 170. 90. 175. 165. 135. 155. 180. 100. HINDLIMB GRIPSTRENGTH TRIAL 3: 45. 45. 75. 105. 65. 95. 90. 95. 75. FORELIMB GRIPSTRENGTH (AVG) : 106.7 140.0 78.3 150.0 146.7 156.7 153.3 180.0 158.3 HINDLIMB GRIPSTRENGTH (AVG) : 66.7 61.7 85.0 81.7 75.0 91.7 93.3 93.3 105.0 ----------------------------------------------------------------------------------------------------------------------------------- -957- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 37 PND 21 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 5 0 0 0 0 0 0 0 0 0 0 URINATION : 1 0 0 0 0 0 0 0 1 0 0 DEFECATION : 0 0 0 0 0 0 2 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 180. 140. 100. 75. 170. 115. 105. 245. 120. 145. 110. HINDLIMB GRIPSTRENGTH TRIAL 1: 65. 85. 45. 45. 115. 95. 100. 155. 70. 95. 75. FORELIMB GRIPSTRENGTH TRIAL 2: 140. 185. 85. 75. 165. 100. 75. 120. 75. 125. 135. HINDLIMB GRIPSTRENGTH TRIAL 2: 65. 110. 75. 75. 110. 80. 45. 110. 75. 40. 145. FORELIMB GRIPSTRENGTH TRIAL 3: 85. 140. 90. 120. 130. 120. 120. 190. 125. 115. 150. HINDLIMB GRIPSTRENGTH TRIAL 3: 65. 95. 65. 75. 85. 70. 60. 105. 120. 100. 115. FORELIMB GRIPSTRENGTH (AVG) : 135.0 155.0 91.7 90.0 155.0 111.7 100.0 185.0 106.7 128.3 131.7 HINDLIMB GRIPSTRENGTH (AVG) : 65.0 96.7 61.7 65.0 103.3 81.7 68.3 123.3 88.3 78.3 111.7 ----------------------------------------------------------------------------------------------------------------------------------- -958- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 38 PND 21 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 1 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 4 0 1 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 210. 145. 125. 170. 165. 160. 110. 140. 120. HINDLIMB GRIPSTRENGTH TRIAL 1: 105. 90. 85. 70. 55. 75. 70. 110. 90. FORELIMB GRIPSTRENGTH TRIAL 2: 100. 165. 190. 170. 145. 85. 70. 120. 105. HINDLIMB GRIPSTRENGTH TRIAL 2: 80. 105. 85. 75. 70. 65. 85. 105. 70. FORELIMB GRIPSTRENGTH TRIAL 3: 170. 100. 190. 170. 115. 150. 165. 90. 120. HINDLIMB GRIPSTRENGTH TRIAL 3: 80. 80. 100. 70. 100. 75. 110. 75. 80. FORELIMB GRIPSTRENGTH (AVG) : 160.0 136.7 168.3 170.0 141.7 131.7 115.0 116.7 115.0 HINDLIMB GRIPSTRENGTH (AVG) : 88.3 91.7 90.0 71.7 75.0 71.7 88.3 96.7 80.0 ----------------------------------------------------------------------------------------------------------------------------------- -959- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 39 PND 21 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 1 0 0 0 0 DEFECATION : 0 0 0 0 1 0 1 0 0 2 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 170. 165. 130. 75. 90. 135. 110. 115. 75. 130. 120. HINDLIMB GRIPSTRENGTH TRIAL 1: 95. 75. 60. 30. 80. 55. 50. 50. 80. 120. 50. FORELIMB GRIPSTRENGTH TRIAL 2: 120. 105. 120. 150. 135. 155. 120. 80. 170. 200. 170. HINDLIMB GRIPSTRENGTH TRIAL 2: 70. 50. 75. 40. 105. 65. 65. 45. 140. 110. 75. FORELIMB GRIPSTRENGTH TRIAL 3: 100. 130. 220. 170. 175. 85. 160. 120. 125. 120. 115. HINDLIMB GRIPSTRENGTH TRIAL 3: 50. 45. 70. 40. 90. 80. 55. 50. 65. 80. 70. FORELIMB GRIPSTRENGTH (AVG) : 130.0 133.3 156.7 131.7 133.3 125.0 130.0 105.0 123.3 150.0 135.0 HINDLIMB GRIPSTRENGTH (AVG) : 71.7 56.7 68.3 36.7 91.7 66.7 56.7 48.3 95.0 103.3 65.0 ----------------------------------------------------------------------------------------------------------------------------------- -960- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 40 PND 21 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 115. 65. 90. 120. 135. 85. 65. 180. 45. HINDLIMB GRIPSTRENGTH TRIAL 1: 80. 75. 75. 70. 65. 45. 55. 75. 50. FORELIMB GRIPSTRENGTH TRIAL 2: 180. 75. 105. 120. 105. 95. 80. 100. 65. HINDLIMB GRIPSTRENGTH TRIAL 2: 90. 30. 65. 65. 75. 45. 40. 85. 40. FORELIMB GRIPSTRENGTH TRIAL 3: 120. 100. 190. 90. 115. 135. 95. 90. 60. HINDLIMB GRIPSTRENGTH TRIAL 3: 80. 65. 70. 60. 55. 80. 70. 75. 40. FORELIMB GRIPSTRENGTH (AVG) : 138.3 80.0 128.3 110.0 118.3 105.0 80.0 123.3 56.7 HINDLIMB GRIPSTRENGTH (AVG) : 83.3 56.7 70.0 65.0 65.0 56.7 55.0 78.3 43.3 ----------------------------------------------------------------------------------------------------------------------------------- -961- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 41 PND 21 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 4 0 0 0 0 0 0 0 0 0 1 URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 100. 190. 130. 130. 160. 205. 165. 80. 120. 85. 145. HINDLIMB GRIPSTRENGTH TRIAL 1: 55. 95. 85. 45. 80. 155. 70. 50. 65. 80. 40. FORELIMB GRIPSTRENGTH TRIAL 2: 110. 145. 145. 75. 155. 120. 125. 175. 190. 85. 150. HINDLIMB GRIPSTRENGTH TRIAL 2: 80. 80. 65. 45. 60. 75. 65. 70. 85. 65. 55. FORELIMB GRIPSTRENGTH TRIAL 3: 110. 160. 125. 140. 220. 230. 85. 150. 180. 115. 170. HINDLIMB GRIPSTRENGTH TRIAL 3: 45. 60. 40. 50. 90. 125. 60. 75. 80. 85. 60. FORELIMB GRIPSTRENGTH (AVG) : 106.7 165.0 133.3 115.0 178.3 185.0 125.0 135.0 163.3 95.0 155.0 HINDLIMB GRIPSTRENGTH (AVG) : 60.0 78.3 63.3 46.7 76.7 118.3 65.0 65.0 76.7 76.7 51.7 ----------------------------------------------------------------------------------------------------------------------------------- -962- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 42 PND 21 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 1 0 DEFECATION : 0 0 0 0 0 0 0 2 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 210. 195. 130. 85. 195. 50. 120. 170. 145. HINDLIMB GRIPSTRENGTH TRIAL 1: 95. 70. 70. 65. 95. 45. 80. 65. 85. FORELIMB GRIPSTRENGTH TRIAL 2: 155. 200. 105. 135. 205. 60. 120. 170. 165. HINDLIMB GRIPSTRENGTH TRIAL 2: 75. 75. 50. 95. 75. 70. 85. 55. 75. FORELIMB GRIPSTRENGTH TRIAL 3: 195. 140. 120. 140. 120. 120. 120. 170. 155. HINDLIMB GRIPSTRENGTH TRIAL 3: 115. 95. 95. 75. 100. 55. 75. 80. 75. FORELIMB GRIPSTRENGTH (AVG) : 186.7 178.3 118.3 120.0 173.3 76.7 120.0 170.0 155.0 HINDLIMB GRIPSTRENGTH (AVG) : 95.0 80.0 71.7 78.3 90.0 56.7 80.0 66.7 78.3 ----------------------------------------------------------------------------------------------------------------------------------- -963- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 43 PND 21 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 6 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 3 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 75. 120. 190. 170. 120. 165. 115. 70. 135. 140. 185. HINDLIMB GRIPSTRENGTH TRIAL 1: 100. 75. 75. 75. 75. 60. 125. 45. 50. 120. 75. FORELIMB GRIPSTRENGTH TRIAL 2: 120. 105. 200. 165. 125. 170. 95. 140. 115. 220. 75. HINDLIMB GRIPSTRENGTH TRIAL 2: 65. 70. 80. 50. 105. 80. 75. 50. 55. 80. 85. FORELIMB GRIPSTRENGTH TRIAL 3: 125. 125. 150. 120. 170. 130. 120. 75. 125. 130. 145. HINDLIMB GRIPSTRENGTH TRIAL 3: 70. 70. 70. 75. 85. 105. 75. 60. 70. 65. 75. FORELIMB GRIPSTRENGTH (AVG) : 106.7 116.7 180.0 151.7 138.3 155.0 110.0 95.0 125.0 163.3 135.0 HINDLIMB GRIPSTRENGTH (AVG) : 78.3 71.7 75.0 66.7 88.3 81.7 91.7 51.7 58.3 88.3 78.3 ----------------------------------------------------------------------------------------------------------------------------------- -964- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 44 PND 21 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 1 0 0 0 2 1 0 0 0 DEFECATION : 0 0 0 1 1 1 3 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 145. 125. 95. 185. 110. 145. 120. 180. 240. HINDLIMB GRIPSTRENGTH TRIAL 1: 90. 110. 70. 80. 65. 120. 60. 70. 80. FORELIMB GRIPSTRENGTH TRIAL 2: 170. 165. 55. 110. 145. 135. 175. 115. 220. HINDLIMB GRIPSTRENGTH TRIAL 2: 60. 65. 45. 70. 80. 120. 75. 65. 95. FORELIMB GRIPSTRENGTH TRIAL 3: 155. 130. 100. 165. 130. 170. 190. 120. 205. HINDLIMB GRIPSTRENGTH TRIAL 3: 85. 75. 105. 90. 90. 90. 135. 85. 85. FORELIMB GRIPSTRENGTH (AVG) : 156.7 140.0 83.3 153.3 128.3 150.0 161.7 138.3 221.7 HINDLIMB GRIPSTRENGTH (AVG) : 78.3 83.3 73.3 80.0 78.3 110.0 90.0 73.3 86.7 ----------------------------------------------------------------------------------------------------------------------------------- -965- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 45 PND 21 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 2 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 1 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 145. 80. 60. 60. 115. 160. 170. 100. 230. 200. 90. HINDLIMB GRIPSTRENGTH TRIAL 1: 120. 80. 55. 85. 70. 85. 80. 55. 80. 155. 60. FORELIMB GRIPSTRENGTH TRIAL 2: 170. 110. 110. 210. 110. 80. 140. 100. 105. 145. 125. HINDLIMB GRIPSTRENGTH TRIAL 2: 55. 70. 55. 115. 90. 60. 60. 75. 95. 110. 45. FORELIMB GRIPSTRENGTH TRIAL 3: 170. 90. 170. 95. 115. 170. 160. 130. 130. 220. 70. HINDLIMB GRIPSTRENGTH TRIAL 3: 75. 60. 60. 40. 55. 75. 60. 65. 60. 125. 75. FORELIMB GRIPSTRENGTH (AVG) : 161.7 93.3 113.3 121.7 113.3 136.7 156.7 110.0 155.0 188.3 95.0 HINDLIMB GRIPSTRENGTH (AVG) : 83.3 70.0 56.7 80.0 71.7 73.3 66.7 65.0 78.3 130.0 60.0 ----------------------------------------------------------------------------------------------------------------------------------- -966- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 46 PND 21 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 1 0 0 URINATION : 1 0 0 0 0 0 0 0 0 DEFECATION : 1 0 0 0 0 0 0 0 2 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 140. 130. 150. 100. 60. 145. 175. 85. 155. HINDLIMB GRIPSTRENGTH TRIAL 1: 95. 80. 95. 60. 30. 120. 65. 70. 50. FORELIMB GRIPSTRENGTH TRIAL 2: 90. 215. 75. 120. 105. 160. 165. 175. 130. HINDLIMB GRIPSTRENGTH TRIAL 2: 90. 85. 80. 75. 95. 95. 80. 75. 65. FORELIMB GRIPSTRENGTH TRIAL 3: 130. 180. 120. 75. 145. 105. 140. 175. 170. HINDLIMB GRIPSTRENGTH TRIAL 3: 110. 90. 95. 45. 50. 95. 80. 70. 105. FORELIMB GRIPSTRENGTH (AVG) : 120.0 175.0 115.0 98.3 103.3 136.7 160.0 145.0 151.7 HINDLIMB GRIPSTRENGTH (AVG) : 98.3 85.0 90.0 60.0 58.3 103.3 75.0 71.7 73.3 ----------------------------------------------------------------------------------------------------------------------------------- -967- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 47 PND 21 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 130. 130. 80. 75. 150. 150. 120. 120. 155. 120. 75. HINDLIMB GRIPSTRENGTH TRIAL 1: 50. 95. 65. 30. 75. 100. 75. 60. 55. 75. 105. FORELIMB GRIPSTRENGTH TRIAL 2: 165. 160. 165. 120. 215. 140. 90. 170. 100. 125. 85. HINDLIMB GRIPSTRENGTH TRIAL 2: 75. 75. 65. 75. 105. 60. 55. 75. 120. 55. 70. FORELIMB GRIPSTRENGTH TRIAL 3: 60. 110. 80. 125. 135. 120. 120. 125. 170. 135. 170. HINDLIMB GRIPSTRENGTH TRIAL 3: 65. 90. 100. 45. 105. 70. 70. 80. 95. 80. 50. FORELIMB GRIPSTRENGTH (AVG) : 118.3 133.3 108.3 106.7 166.7 136.7 110.0 138.3 141.7 126.7 110.0 HINDLIMB GRIPSTRENGTH (AVG) : 63.3 86.7 76.7 50.0 95.0 76.7 66.7 71.7 90.0 70.0 75.0 ----------------------------------------------------------------------------------------------------------------------------------- -968- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 48 PND 21 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 205. 50. 160. 120. 135. 135. 75. 170. 55. HINDLIMB GRIPSTRENGTH TRIAL 1: 75. 75. 85. 60. 65. 80. 75. 75. 40. FORELIMB GRIPSTRENGTH TRIAL 2: 190. 100. 100. 125. 155. 155. 100. 145. 150. HINDLIMB GRIPSTRENGTH TRIAL 2: 100. 80. 75. 80. 65. 75. 45. 75. 95. FORELIMB GRIPSTRENGTH TRIAL 3: 170. 100. 205. 145. 170. 110. 115. 160. 65. HINDLIMB GRIPSTRENGTH TRIAL 3: 75. 45. 95. 65. 60. 75. 55. 120. 40. FORELIMB GRIPSTRENGTH (AVG) : 188.3 83.3 155.0 130.0 153.3 133.3 96.7 158.3 90.0 HINDLIMB GRIPSTRENGTH (AVG) : 83.3 66.7 85.0 68.3 63.3 76.7 58.3 90.0 58.3 ----------------------------------------------------------------------------------------------------------------------------------- -969- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 49 PND 35 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 1 1 0 0 0 0 0 0 0 DEFECATION : 0 0 1 3 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 3 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 220. 435. 435. 295. 295. 355. 605. 420. 430. 380. 500. HINDLIMB GRIPSTRENGTH TRIAL 1: 305. 315. 410. 265. 245. 420. 390. 440. 365. 365. 225. FORELIMB GRIPSTRENGTH TRIAL 2: 310. 450. 240. 365. 435. 340. 590. 435. 520. 370. 385. HINDLIMB GRIPSTRENGTH TRIAL 2: 205. 215. 295. 265. 480. 230. 325. 235. 265. 245. 240. FORELIMB GRIPSTRENGTH TRIAL 3: 425. 365. 215. 295. 380. 500. 455. 520. 525. 510. 575. HINDLIMB GRIPSTRENGTH TRIAL 3: 255. 395. 380. 260. 325. 265. 305. 255. 345. 380. 245. FORELIMB GRIPSTRENGTH (AVG) : 318.3 416.7 296.7 318.3 370.0 398.3 550.0 458.3 491.7 420.0 486.7 HINDLIMB GRIPSTRENGTH (AVG) : 255.0 308.3 361.7 263.3 350.0 305.0 340.0 310.0 325.0 330.0 236.7 ----------------------------------------------------------------------------------------------------------------------------------- -970- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 50 PND 35 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 1 1 1 0 0 0 DEFECATION : 0 0 0 0 0 2 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 3 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 455. 495. 535. 650. 510. 385. 570. 190. 270. HINDLIMB GRIPSTRENGTH TRIAL 1: 340. 480. 570. 315. 270. 395. 220. 190. 140. FORELIMB GRIPSTRENGTH TRIAL 2: 455. 565. 545. 775. 665. 560. 500. 365. 410. HINDLIMB GRIPSTRENGTH TRIAL 2: 340. 310. 565. 480. 430. 355. 225. 175. 235. FORELIMB GRIPSTRENGTH TRIAL 3: 320. 535. 460. 795. 485. 585. 270. 250. 480. HINDLIMB GRIPSTRENGTH TRIAL 3: 440. 475. 310. 300. 280. 325. 185. 245. 255. FORELIMB GRIPSTRENGTH (AVG) : 410.0 531.7 513.3 740.0 553.3 510.0 446.7 268.3 386.7 HINDLIMB GRIPSTRENGTH (AVG) : 373.3 421.7 481.7 365.0 326.7 358.3 210.0 203.3 210.0 ----------------------------------------------------------------------------------------------------------------------------------- -971- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 51 PND 35 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 4 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 1 0 1 2 1 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 3 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 290. 355. 425. 480. 355. 500. 450. 395. 505. 445. 350. HINDLIMB GRIPSTRENGTH TRIAL 1: 455. 475. 210. 280. 250. 240. 280. 310. 245. 450. 465. FORELIMB GRIPSTRENGTH TRIAL 2: 320. 440. 400. 480. 445. 330. 520. 365. 370. 340. 500. HINDLIMB GRIPSTRENGTH TRIAL 2: 410. 495. 470. 290. 525. 200. 315. 615. 315. 545. 330. FORELIMB GRIPSTRENGTH TRIAL 3: 475. 325. 595. 495. 380. 335. 475. 430. 325. 500. 600. HINDLIMB GRIPSTRENGTH TRIAL 3: 305. 350. 300. 510. 400. 270. 465. 305. 410. 575. 295. FORELIMB GRIPSTRENGTH (AVG) : 361.7 373.3 473.3 485.0 393.3 388.3 481.7 396.7 400.0 428.3 483.3 HINDLIMB GRIPSTRENGTH (AVG) : 390.0 440.0 326.7 360.0 391.7 236.7 353.3 410.0 323.3 523.3 363.3 ----------------------------------------------------------------------------------------------------------------------------------- -972- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 52 PND 35 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 1 URINATION : 0 1 1 2 1 0 0 0 0 DEFECATION : 0 0 2 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 3 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 355. 650. 285. 440. 555. 610. 445. 610. 560. HINDLIMB GRIPSTRENGTH TRIAL 1: 525. 455. 195. 515. 620. 300. 305. 250. 185. FORELIMB GRIPSTRENGTH TRIAL 2: 465. 460. 280. 395. 590. 585. 375. 560. 535. HINDLIMB GRIPSTRENGTH TRIAL 2: 430. 600. 170. 345. 505. 180. 205. 365. 270. FORELIMB GRIPSTRENGTH TRIAL 3: 465. 360. 380. 435. 575. 530. 435. 510. 510. HINDLIMB GRIPSTRENGTH TRIAL 3: 320. 270. 270. 335. 545. 225. 220. 210. 110. FORELIMB GRIPSTRENGTH (AVG) : 428.3 490.0 315.0 423.3 573.3 575.0 418.3 560.0 535.0 HINDLIMB GRIPSTRENGTH (AVG) : 425.0 441.7 211.7 398.3 556.7 235.0 243.3 275.0 188.3 ----------------------------------------------------------------------------------------------------------------------------------- -973- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 53 PND 35 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 3 1 0 0 0 1 1 0 2 0 0 DEFECATION : 0 0 0 0 0 1 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 3 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 305. 425. 480. 400. 490. 335. 310. 310. 405. 380. 495. HINDLIMB GRIPSTRENGTH TRIAL 1: 410. 345. 460. 255. 395. 450. 205. 250. 370. 135. 300. FORELIMB GRIPSTRENGTH TRIAL 2: 395. 460. 330. 470. 390. 440. 420. 510. 455. 405. 430. HINDLIMB GRIPSTRENGTH TRIAL 2: 280. 520. 515. 500. 475. 330. 360. 550. 235. 220. 330. FORELIMB GRIPSTRENGTH TRIAL 3: 410. 555. 290. 540. 450. 410. 405. 405. 550. 400. 470. HINDLIMB GRIPSTRENGTH TRIAL 3: 350. 590. 435. 320. 350. 425. 520. 365. 410. 350. 460. FORELIMB GRIPSTRENGTH (AVG) : 370.0 480.0 366.7 470.0 443.3 395.0 378.3 408.3 470.0 395.0 465.0 HINDLIMB GRIPSTRENGTH (AVG) : 346.7 485.0 470.0 358.3 406.7 401.7 361.7 388.3 338.3 235.0 363.3 ----------------------------------------------------------------------------------------------------------------------------------- -974- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 54 PND 35 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 1 0 1 2 0 1 1 0 0 DEFECATION : 0 0 0 5 0 0 1 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 3 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 650. 495. 540. 605. 415. 390. 520. 485. 510. HINDLIMB GRIPSTRENGTH TRIAL 1: 250. 380. 455. 375. 355. 215. 230. 330. 155. FORELIMB GRIPSTRENGTH TRIAL 2: 560. 615. 615. 520. 440. 325. 575. 490. 410. HINDLIMB GRIPSTRENGTH TRIAL 2: 320. 475. 530. 390. 300. 330. 255. 285. 220. FORELIMB GRIPSTRENGTH TRIAL 3: 500. 515. 470. 595. 525. 495. 430. 530. 445. HINDLIMB GRIPSTRENGTH TRIAL 3: 385. 455. 350. 330. 600. 335. 215. 305. 230. FORELIMB GRIPSTRENGTH (AVG) : 570.0 541.7 541.7 573.3 460.0 403.3 508.3 501.7 455.0 HINDLIMB GRIPSTRENGTH (AVG) : 318.3 436.7 445.0 365.0 418.3 293.3 233.3 306.7 201.7 ----------------------------------------------------------------------------------------------------------------------------------- -975- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 55 PND 35 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 3 0 0 0 0 0 0 0 URINATION : 0 1 0 1 0 0 1 0 0 0 0 DEFECATION : 0 0 0 0 1 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 3 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 565. 410. 455. 265. 495. 405. 505. 605. 285. 575. 325. HINDLIMB GRIPSTRENGTH TRIAL 1: 270. 270. 380. 270. 545. 365. 360. 335. 300. 330. 190. FORELIMB GRIPSTRENGTH TRIAL 2: 395. 285. 325. 495. 375. 435. 505. 555. 545. 410. 370. HINDLIMB GRIPSTRENGTH TRIAL 2: 325. 370. 420. 325. 345. 475. 410. 550. 420. 555. 210. FORELIMB GRIPSTRENGTH TRIAL 3: 355. 490. 435. 350. 465. 405. 385. 515. 505. 305. 410. HINDLIMB GRIPSTRENGTH TRIAL 3: 400. 690. 370. 415. 385. 300. 390. 285. 480. 335. 270. FORELIMB GRIPSTRENGTH (AVG) : 438.3 395.0 405.0 370.0 445.0 415.0 465.0 558.3 445.0 430.0 368.3 HINDLIMB GRIPSTRENGTH (AVG) : 331.7 443.3 390.0 336.7 425.0 380.0 386.7 390.0 400.0 406.7 223.3 ----------------------------------------------------------------------------------------------------------------------------------- -976- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 56 PND 35 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 1 0 0 0 0 1 0 0 DEFECATION : 0 3 2 0 0 0 1 2 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 500. 390. 260. 275. 330. 310. 335. 560. 280. HINDLIMB GRIPSTRENGTH TRIAL 1: 340. 345. 260. 245. 575. 245. 305. 190. 165. FORELIMB GRIPSTRENGTH TRIAL 2: 550. 460. 235. 485. 495. 360. 320. 525. 325. HINDLIMB GRIPSTRENGTH TRIAL 2: 385. 385. 255. 255. 280. 215. 210. 235. 180. FORELIMB GRIPSTRENGTH TRIAL 3: 495. 290. 375. 355. 300. 320. 265. 520. 215. HINDLIMB GRIPSTRENGTH TRIAL 3: 365. 470. 280. 315. 515. 270. 260. 245. 90. FORELIMB GRIPSTRENGTH (AVG) : 515.0 380.0 290.0 371.7 375.0 330.0 306.7 535.0 273.3 HINDLIMB GRIPSTRENGTH (AVG) : 363.3 400.0 265.0 271.7 456.7 243.3 258.3 223.3 145.0 ----------------------------------------------------------------------------------------------------------------------------------- -977- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 57 PND 35 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 1 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 1 0 0 2 0 0 0 0 DEFECATION : 0 0 0 2 0 0 1 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 430. 375. 425. 265. 385. 475. 515. 505. 555. 355. 340. HINDLIMB GRIPSTRENGTH TRIAL 1: 280. 240. 460. 360. 525. 305. 250. 450. 555. 190. 180. FORELIMB GRIPSTRENGTH TRIAL 2: 475. 380. 245. 275. 555. 475. 500. 355. 535. 405. 385. HINDLIMB GRIPSTRENGTH TRIAL 2: 275. 265. 390. 265. 375. 520. 450. 150. 280. 200. 295. FORELIMB GRIPSTRENGTH TRIAL 3: 500. 360. 355. 295. 450. 600. 320. 465. 525. 400. 435. HINDLIMB GRIPSTRENGTH TRIAL 3: 305. 335. 460. 295. 245. 375. 235. 370. 295. 230. 255. FORELIMB GRIPSTRENGTH (AVG) : 468.3 371.7 341.7 278.3 463.3 516.7 445.0 441.7 538.3 386.7 386.7 HINDLIMB GRIPSTRENGTH (AVG) : 286.7 280.0 436.7 306.7 381.7 400.0 311.7 323.3 376.7 206.7 243.3 ----------------------------------------------------------------------------------------------------------------------------------- -978- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 58 PND 35 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 4 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 1 0 0 URINATION : 0 0 0 0 0 1 0 0 0 DEFECATION : 0 0 0 0 0 0 0 3 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 455. 395. 405. 290. 455. 385. 535. 465. 345. HINDLIMB GRIPSTRENGTH TRIAL 1: 265. 275. 485. 255. 380. 505. 270. 165. 65. FORELIMB GRIPSTRENGTH TRIAL 2: 505. 585. 445. 440. 510. 595. 485. 380. 255. HINDLIMB GRIPSTRENGTH TRIAL 2: 385. 265. 380. 330. 305. 360. 300. 110. 125. FORELIMB GRIPSTRENGTH TRIAL 3: 525. 500. 420. 405. 615. 595. 485. 370. 280. HINDLIMB GRIPSTRENGTH TRIAL 3: 420. 275. 300. 330. 335. 335. 285. 185. 130. FORELIMB GRIPSTRENGTH (AVG) : 495.0 493.3 423.3 378.3 526.7 525.0 501.7 405.0 293.3 HINDLIMB GRIPSTRENGTH (AVG) : 356.7 271.7 388.3 305.0 340.0 400.0 285.0 153.3 106.7 ----------------------------------------------------------------------------------------------------------------------------------- -979- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 59 PND 35 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 1 0 1 0 0 1 0 1 1 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 3 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 415. 385. 420. 405. 460. 550. 430. 250. 460. 370. 510. HINDLIMB GRIPSTRENGTH TRIAL 1: 245. 500. 370. 355. 245. 365. 300. 285. 420. 560. 375. FORELIMB GRIPSTRENGTH TRIAL 2: 355. 260. 485. 460. 360. 405. 575. 335. 565. 430. 480. HINDLIMB GRIPSTRENGTH TRIAL 2: 260. 340. 375. 425. 260. 345. 210. 230. 255. 410. 485. FORELIMB GRIPSTRENGTH TRIAL 3: 270. 425. 355. 455. 340. 320. 360. 250. 440. 435. 445. HINDLIMB GRIPSTRENGTH TRIAL 3: 215. 470. 425. 365. 520. 440. 465. 285. 245. 410. 555. FORELIMB GRIPSTRENGTH (AVG) : 346.7 356.7 420.0 440.0 386.7 425.0 455.0 278.3 488.3 411.7 478.3 HINDLIMB GRIPSTRENGTH (AVG) : 240.0 436.7 390.0 381.7 341.7 383.3 325.0 266.7 306.7 460.0 471.7 ----------------------------------------------------------------------------------------------------------------------------------- -980- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 60 PND 35 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 1 0 1 1 0 0 0 2 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 590. 580. 270. 490. 480. 540. 460. 500. 510. HINDLIMB GRIPSTRENGTH TRIAL 1: 455. 405. 200. 365. 285. 305. 175. 260. 255. FORELIMB GRIPSTRENGTH TRIAL 2: 555. 600. 280. 490. 520. 510. 315. 525. 550. HINDLIMB GRIPSTRENGTH TRIAL 2: 385. 675. 435. 370. 450. 195. 215. 315. 230. FORELIMB GRIPSTRENGTH TRIAL 3: 480. 550. 355. 455. 565. 215. 385. 275. 345. HINDLIMB GRIPSTRENGTH TRIAL 3: 600. 525. 235. 510. 420. 110. 200. 220. 250. FORELIMB GRIPSTRENGTH (AVG) : 541.7 576.7 301.7 478.3 521.7 421.7 386.7 433.3 468.3 HINDLIMB GRIPSTRENGTH (AVG) : 480.0 535.0 290.0 415.0 385.0 203.3 196.7 265.0 245.0 ----------------------------------------------------------------------------------------------------------------------------------- -981- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 61 PND 35 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 4 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 1 1 0 0 1 0 0 0 0 0 1 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 3 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 335. 465. 365. 550. 355. 460. 445. 460. 450. 490. 420. HINDLIMB GRIPSTRENGTH TRIAL 1: 195. 290. 265. 380. 230. 330. 300. 330. 350. 275. 535. FORELIMB GRIPSTRENGTH TRIAL 2: 405. 390. 440. 565. 500. 340. 445. 400. 410. 465. 485. HINDLIMB GRIPSTRENGTH TRIAL 2: 370. 435. 540. 310. 245. 300. 300. 245. 360. 490. 400. FORELIMB GRIPSTRENGTH TRIAL 3: 355. 295. 425. 570. 355. 360. 430. 425. 500. 485. 455. HINDLIMB GRIPSTRENGTH TRIAL 3: 300. 235. 275. 340. 245. 215. 270. 285. 420. 320. 475. FORELIMB GRIPSTRENGTH (AVG) : 365.0 383.3 410.0 561.7 403.3 386.7 440.0 428.3 453.3 480.0 453.3 HINDLIMB GRIPSTRENGTH (AVG) : 288.3 320.0 360.0 343.3 240.0 281.7 290.0 286.7 376.7 361.7 470.0 ----------------------------------------------------------------------------------------------------------------------------------- -982- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 62 PND 35 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 4 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 1 1 0 0 1 0 0 0 1 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 3 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 500. 355. 295. 390. 505. 545. 445. 450. 405. HINDLIMB GRIPSTRENGTH TRIAL 1: 675. 350. 235. 380. 315. 225. 270. 205. 315. FORELIMB GRIPSTRENGTH TRIAL 2: 405. 450. 305. 360. 540. 205. 535. 480. 260. HINDLIMB GRIPSTRENGTH TRIAL 2: 480. 340. 265. 220. 405. 120. 270. 350. 365. FORELIMB GRIPSTRENGTH TRIAL 3: 515. 380. 205. 410. 570. 425. 515. 460. 275. HINDLIMB GRIPSTRENGTH TRIAL 3: 245. 310. 165. 515. 400. 220. 185. 240. 485. FORELIMB GRIPSTRENGTH (AVG) : 473.3 395.0 268.3 386.7 538.3 391.7 498.3 463.3 313.3 HINDLIMB GRIPSTRENGTH (AVG) : 466.7 333.3 221.7 371.7 373.3 188.3 241.7 265.0 388.3 ----------------------------------------------------------------------------------------------------------------------------------- -983- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 63 PND 35 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 1 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 3 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 495. 425. 425. 375. 220. 485. 220. 425. 500. 465. 335. HINDLIMB GRIPSTRENGTH TRIAL 1: 265. 350. 210. 230. 280. 395. 485. 250. 360. 405. 560. FORELIMB GRIPSTRENGTH TRIAL 2: 295. 410. 325. 265. 430. 400. 210. 460. 350. 575. 415. HINDLIMB GRIPSTRENGTH TRIAL 2: 330. 260. 290. 450. 360. 350. 215. 245. 370. 400. 325. FORELIMB GRIPSTRENGTH TRIAL 3: 290. 295. 405. 390. 365. 475. 380. 445. 545. 430. 465. HINDLIMB GRIPSTRENGTH TRIAL 3: 510. 540. 500. 325. 375. 520. 265. 265. 290. 300. 330. FORELIMB GRIPSTRENGTH (AVG) : 360.0 376.7 385.0 343.3 338.3 453.3 270.0 443.3 465.0 490.0 405.0 HINDLIMB GRIPSTRENGTH (AVG) : 368.3 383.3 333.3 335.0 338.3 421.7 321.7 253.3 340.0 368.3 405.0 ----------------------------------------------------------------------------------------------------------------------------------- -984- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 64 PND 35 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 4 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 2 URINATION : 0 1 2 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 355. 520. 480. 485. 380. 320. 500. 540. 265. HINDLIMB GRIPSTRENGTH TRIAL 1: 220. 215. 370. 215. 245. 245. 275. 165. 165. FORELIMB GRIPSTRENGTH TRIAL 2: 485. 455. 435. 290. 450. 310. 440. 295. 460. HINDLIMB GRIPSTRENGTH TRIAL 2: 550. 410. 595. 220. 570. 325. 455. 255. 215. FORELIMB GRIPSTRENGTH TRIAL 3: 455. 445. 455. 325. 360. 275. 425. 370. 470. HINDLIMB GRIPSTRENGTH TRIAL 3: 360. 505. 485. 200. 440. 440. 245. 195. 150. FORELIMB GRIPSTRENGTH (AVG) : 431.7 473.3 456.7 366.7 396.7 301.7 455.0 401.7 398.3 HINDLIMB GRIPSTRENGTH (AVG) : 376.7 376.7 483.3 211.7 418.3 336.7 325.0 205.0 176.7 ----------------------------------------------------------------------------------------------------------------------------------- -985- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 65 PND 45 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 2 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 1 0 0 3 0 0 0 0 DEFECATION : 0 0 0 3 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 3 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 680. 655. 610. 560. 825. 820. 965. 895. 915. 255. 695. HINDLIMB GRIPSTRENGTH TRIAL 1: 285. 245. 525. 710. 450. 890. 640. 420. 810. 440. 170. FORELIMB GRIPSTRENGTH TRIAL 2: 390. 590. 640. 715. 895. 1015. 725. 860. 885. 250. 630. HINDLIMB GRIPSTRENGTH TRIAL 2: 270. 370. 405. 385. 575. 690. 620. 495. 560. 230. 360. FORELIMB GRIPSTRENGTH TRIAL 3: 535. 585. 560. 770. 790. 890. 875. 620. 720. 515. 435. HINDLIMB GRIPSTRENGTH TRIAL 3: 270. 355. 475. 530. 575. 805. 515. 625. 695. 305. 440. FORELIMB GRIPSTRENGTH (AVG) : 535.0 610.0 603.3 681.7 836.7 908.3 855.0 791.7 840.0 340.0 586.7 HINDLIMB GRIPSTRENGTH (AVG) : 275.0 323.3 468.3 541.7 533.3 795.0 591.7 513.3 688.3 325.0 323.3 ----------------------------------------------------------------------------------------------------------------------------------- -986- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 66 PND 45 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 2 0 0 0 1 3 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 530. 495. 770. 435. 665. 865. 395. 410. 560. HINDLIMB GRIPSTRENGTH TRIAL 1: 335. 585. 245. 355. 620. 365. 280. 315. 200. FORELIMB GRIPSTRENGTH TRIAL 2: 245. 930. 755. 785. 870. 520. 275. 245. 255. HINDLIMB GRIPSTRENGTH TRIAL 2: 455. 665. 395. 390. 460. 270. 255. 260. 140. FORELIMB GRIPSTRENGTH TRIAL 3: 285. 900. 480. 630. 680. 790. 405. 375. 270. HINDLIMB GRIPSTRENGTH TRIAL 3: 280. 735. 270. 370. 425. 305. 330. 355. 255. FORELIMB GRIPSTRENGTH (AVG) : 353.3 775.0 668.3 616.7 738.3 725.0 358.3 343.3 361.7 HINDLIMB GRIPSTRENGTH (AVG) : 356.7 661.7 303.3 371.7 501.7 313.3 288.3 310.0 198.3 ----------------------------------------------------------------------------------------------------------------------------------- -987- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 67 PND 45 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 735. 845. 980. 1040. 905. 845. 820. 790. 870. 505. 870. HINDLIMB GRIPSTRENGTH TRIAL 1: 230. 645. 630. 510. 580. 700. 490. 655. 710. 300. 685. FORELIMB GRIPSTRENGTH TRIAL 2: 560. 600. 660. 1085. 695. 1000. 760. 935. 700. 415. 780. HINDLIMB GRIPSTRENGTH TRIAL 2: 250. 510. 705. 425. 620. 680. 735. 510. 465. 325. 575. FORELIMB GRIPSTRENGTH TRIAL 3: 625. 520. 725. 1150. 565. 820. 740. 830. 880. 605. 875. HINDLIMB GRIPSTRENGTH TRIAL 3: 305. 505. 645. 645. 605. 560. 690. 610. 670. 305. 800. FORELIMB GRIPSTRENGTH (AVG) : 640.0 655.0 788.3 1091.7 721.7 888.3 773.3 851.7 816.7 508.3 841.7 HINDLIMB GRIPSTRENGTH (AVG) : 261.7 553.3 660.0 526.7 601.7 646.7 638.3 591.7 615.0 310.0 686.7 ----------------------------------------------------------------------------------------------------------------------------------- -988- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 68 PND 45 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 770. 740. 520. 1025. 470. 525. 395. 395. 525. HINDLIMB GRIPSTRENGTH TRIAL 1: 510. 445. 335. 370. 365. 250. 250. 195. 260. FORELIMB GRIPSTRENGTH TRIAL 2: 440. 510. 465. 415. 270. 360. 220. 500. 335. HINDLIMB GRIPSTRENGTH TRIAL 2: 310. 160. 380. 410. 345. 270. 270. 300. 235. FORELIMB GRIPSTRENGTH TRIAL 3: 495. 565. 510. 855. 495. 440. 460. 320. 515. HINDLIMB GRIPSTRENGTH TRIAL 3: 390. 230. 265. 220. 255. 235. 310. 355. 315. FORELIMB GRIPSTRENGTH (AVG) : 568.3 605.0 498.3 765.0 411.7 441.7 358.3 405.0 458.3 HINDLIMB GRIPSTRENGTH (AVG) : 403.3 278.3 326.7 333.3 321.7 251.7 276.7 283.3 270.0 ----------------------------------------------------------------------------------------------------------------------------------- -989- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 69 PND 45 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 2 3 3 2 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 1 0 1 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 545. 850. 690. 790. 780. 780. 595. 895. 875. 840. 530. HINDLIMB GRIPSTRENGTH TRIAL 1: 350. 605. 420. 500. 465. 560. 700. 560. 545. 655. 245. FORELIMB GRIPSTRENGTH TRIAL 2: 620. 885. 705. 735. 775. 860. 595. 495. 895. 610. 390. HINDLIMB GRIPSTRENGTH TRIAL 2: 235. 505. 385. 650. 400. 595. 850. 635. 660. 615. 390. FORELIMB GRIPSTRENGTH TRIAL 3: 705. 695. 520. 655. 810. 805. 510. 805. 805. 775. 735. HINDLIMB GRIPSTRENGTH TRIAL 3: 435. 585. 320. 400. 470. 660. 590. 700. 700. 615. 195. FORELIMB GRIPSTRENGTH (AVG) : 623.3 810.0 638.3 726.7 788.3 815.0 566.7 731.7 858.3 741.7 551.7 HINDLIMB GRIPSTRENGTH (AVG) : 340.0 565.0 375.0 516.7 445.0 605.0 713.3 631.7 635.0 628.3 276.7 ----------------------------------------------------------------------------------------------------------------------------------- -990- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 70 PND 45 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 1 0 0 DEFECATION : 0 0 0 1 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 665. 805. 505. 720. 535. 610. 355. 300. 555. HINDLIMB GRIPSTRENGTH TRIAL 1: 390. 285. 400. 465. 330. 305. 140. 270. 345. FORELIMB GRIPSTRENGTH TRIAL 2: 705. 740. 315. 880. 285. 560. 365. 315. 445. HINDLIMB GRIPSTRENGTH TRIAL 2: 275. 320. 140. 600. 465. 305. 290. 225. 265. FORELIMB GRIPSTRENGTH TRIAL 3: 490. 355. 415. 480. 705. 455. 315. 230. 410. HINDLIMB GRIPSTRENGTH TRIAL 3: 355. 235. 345. 440. 255. 210. 165. 225. 275. FORELIMB GRIPSTRENGTH (AVG) : 620.0 633.3 411.7 693.3 508.3 541.7 345.0 281.7 470.0 HINDLIMB GRIPSTRENGTH (AVG) : 340.0 280.0 295.0 501.7 350.0 273.3 198.3 240.0 295.0 ----------------------------------------------------------------------------------------------------------------------------------- -991- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 71 PND 45 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 2 3 0 1 0 1 2 2 0 0 0 DEFECATION : 0 8 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 875. 710. 880. 795. 780. 745. 875. 845. 815. 680. 945. HINDLIMB GRIPSTRENGTH TRIAL 1: 465. 380. 640. 365. 455. 670. 475. 445. 550. 635. 410. FORELIMB GRIPSTRENGTH TRIAL 2: 740. 635. 925. 540. 930. 840. 660. 895. 1030. 845. 790. HINDLIMB GRIPSTRENGTH TRIAL 2: 500. 520. 675. 550. 515. 510. 495. 635. 520. 485. 765. FORELIMB GRIPSTRENGTH TRIAL 3: 890. 605. 975. 595. 910. 775. 815. 930. 870. 855. 730. HINDLIMB GRIPSTRENGTH TRIAL 3: 410. 630. 645. 575. 480. 510. 500. 810. 610. 620. 490. FORELIMB GRIPSTRENGTH (AVG) : 835.0 650.0 926.7 643.3 873.3 786.7 783.3 890.0 905.0 793.3 821.7 HINDLIMB GRIPSTRENGTH (AVG) : 458.3 510.0 653.3 496.7 483.3 563.3 490.0 630.0 560.0 580.0 555.0 ----------------------------------------------------------------------------------------------------------------------------------- -992- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 72 PND 45 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 1 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 665. 650. 675. 415. 800. 460. 810. 395. 295. HINDLIMB GRIPSTRENGTH TRIAL 1: 300. 435. 490. 345. 355. 355. 270. 190. 210. FORELIMB GRIPSTRENGTH TRIAL 2: 595. 320. 610. 575. 750. 605. 415. 300. 290. HINDLIMB GRIPSTRENGTH TRIAL 2: 250. 250. 365. 385. 500. 350. 295. 170. 265. FORELIMB GRIPSTRENGTH TRIAL 3: 635. 605. 305. 525. 575. 485. 630. 380. 265. HINDLIMB GRIPSTRENGTH TRIAL 3: 415. 320. 315. 260. 165. 490. 315. 335. 270. FORELIMB GRIPSTRENGTH (AVG) : 631.7 525.0 530.0 505.0 708.3 516.7 618.3 358.3 283.3 HINDLIMB GRIPSTRENGTH (AVG) : 321.7 335.0 390.0 330.0 340.0 398.3 293.3 231.7 248.3 ----------------------------------------------------------------------------------------------------------------------------------- -993- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 73 PND 45 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 1 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 480. 695. 555. 725. 765. 700. 670. 775. 775. 745. 750. HINDLIMB GRIPSTRENGTH TRIAL 1: 145. 285. 680. 540. 550. 560. 600. 420. 485. 255. 210. FORELIMB GRIPSTRENGTH TRIAL 2: 400. 685. 485. 645. 930. 545. 800. 625. 750. 400. 495. HINDLIMB GRIPSTRENGTH TRIAL 2: 295. 525. 510. 440. 645. 585. 645. 835. 695. 180. 230. FORELIMB GRIPSTRENGTH TRIAL 3: 475. 530. 495. 705. 880. 680. 905. 900. 770. 790. 645. HINDLIMB GRIPSTRENGTH TRIAL 3: 220. 205. 660. 510. 580. 555. 620. 445. 635. 315. 220. FORELIMB GRIPSTRENGTH (AVG) : 451.7 636.7 511.7 691.7 858.3 641.7 791.7 766.7 765.0 645.0 630.0 HINDLIMB GRIPSTRENGTH (AVG) : 220.0 338.3 616.7 496.7 591.7 566.7 621.7 566.7 605.0 250.0 220.0 ----------------------------------------------------------------------------------------------------------------------------------- -994- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 74 PND 45 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 4 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 385. 810. 825. 950. 675. 650. 400. 320. 385. HINDLIMB GRIPSTRENGTH TRIAL 1: 155. 310. 430. 750. 570. 705. 315. 340. 290. FORELIMB GRIPSTRENGTH TRIAL 2: 535. 680. 610. 840. 500. 405. 195. 205. 245. HINDLIMB GRIPSTRENGTH TRIAL 2: 470. 280. 535. 125. 620. 390. 220. 125. 240. FORELIMB GRIPSTRENGTH TRIAL 3: 330. 795. 605. 735. 885. 250. 215. 320. 275. HINDLIMB GRIPSTRENGTH TRIAL 3: 215. 340. 480. 415. 430. 315. 225. 215. 210. FORELIMB GRIPSTRENGTH (AVG) : 416.7 761.7 680.0 841.7 686.7 435.0 270.0 281.7 301.7 HINDLIMB GRIPSTRENGTH (AVG) : 280.0 310.0 481.7 430.0 540.0 470.0 253.3 226.7 246.7 ----------------------------------------------------------------------------------------------------------------------------------- -995- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 75 PND 45 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 1 0 0 1 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 660. 645. 750. 825. 765. 885. 775. 910. 665. 840. 650. HINDLIMB GRIPSTRENGTH TRIAL 1: 165. 525. 645. 690. 605. 675. 500. 605. 415. 300. 330. FORELIMB GRIPSTRENGTH TRIAL 2: 420. 635. 805. 860. 700. 745. 670. 825. 810. 705. 660. HINDLIMB GRIPSTRENGTH TRIAL 2: 190. 620. 390. 705. 650. 315. 505. 665. 750. 425. 415. FORELIMB GRIPSTRENGTH TRIAL 3: 580. 535. 770. 750. 785. 470. 540. 785. 720. 670. 650. HINDLIMB GRIPSTRENGTH TRIAL 3: 270. 530. 385. 610. 630. 500. 490. 610. 640. 500. 365. FORELIMB GRIPSTRENGTH (AVG) : 553.3 605.0 775.0 811.7 750.0 700.0 661.7 840.0 731.7 738.3 653.3 HINDLIMB GRIPSTRENGTH (AVG) : 208.3 558.3 473.3 668.3 628.3 496.7 498.3 626.7 601.7 408.3 370.0 ----------------------------------------------------------------------------------------------------------------------------------- -996- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 76 PND 45 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 915. 410. 585. 345. 810. 295. 365. 395. 475. HINDLIMB GRIPSTRENGTH TRIAL 1: 500. 365. 300. 420. 445. 140. 270. 355. 230. FORELIMB GRIPSTRENGTH TRIAL 2: 790. 540. 465. 210. 585. 420. 250. 260. 500. HINDLIMB GRIPSTRENGTH TRIAL 2: 390. 430. 345. 155. 465. 220. 265. 270. 205. FORELIMB GRIPSTRENGTH TRIAL 3: 675. 335. 515. 510. 410. 215. 350. 380. 375. HINDLIMB GRIPSTRENGTH TRIAL 3: 530. 270. 370. 320. 490. 240. 305. 405. 305. FORELIMB GRIPSTRENGTH (AVG) : 793.3 428.3 521.7 355.0 601.7 310.0 321.7 345.0 450.0 HINDLIMB GRIPSTRENGTH (AVG) : 473.3 355.0 338.3 298.3 466.7 200.0 280.0 343.3 246.7 ----------------------------------------------------------------------------------------------------------------------------------- -997- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 77 PND 45 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 4 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 1 1 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 570. 550. 855. 880. 830. 525. 610. 765. 870. 740. 660. HINDLIMB GRIPSTRENGTH TRIAL 1: 400. 395. 550. 690. 420. 510. 585. 390. 690. 505. 480. FORELIMB GRIPSTRENGTH TRIAL 2: 645. 455. 815. 770. 575. 680. 690. 720. 945. 860. 490. HINDLIMB GRIPSTRENGTH TRIAL 2: 330. 465. 580. 580. 455. 360. 665. 520. 470. 555. 365. FORELIMB GRIPSTRENGTH TRIAL 3: 535. 815. 825. 990. 780. 520. 615. 795. 845. 780. 740. HINDLIMB GRIPSTRENGTH TRIAL 3: 365. 520. 685. 650. 525. 490. 505. 635. 545. 670. 410. FORELIMB GRIPSTRENGTH (AVG) : 583.3 606.7 831.7 880.0 728.3 575.0 638.3 760.0 886.7 793.3 630.0 HINDLIMB GRIPSTRENGTH (AVG) : 365.0 460.0 605.0 640.0 466.7 453.3 585.0 515.0 568.3 576.7 418.3 ----------------------------------------------------------------------------------------------------------------------------------- -998- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 78 PND 45 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 4 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 5 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 655. 805. 640. 780. 820. 320. 350. 370. 695. HINDLIMB GRIPSTRENGTH TRIAL 1: 345. 520. 310. 305. 425. 235. 275. 165. 350. FORELIMB GRIPSTRENGTH TRIAL 2: 465. 670. 670. 740. 885. 490. 405. 370. 705. HINDLIMB GRIPSTRENGTH TRIAL 2: 340. 460. 355. 270. 505. 250. 220. 295. 330. FORELIMB GRIPSTRENGTH TRIAL 3: 530. 610. 415. 705. 880. 495. 490. 395. 690. HINDLIMB GRIPSTRENGTH TRIAL 3: 255. 295. 385. 465. 430. 195. 240. 275. 290. FORELIMB GRIPSTRENGTH (AVG) : 550.0 695.0 575.0 741.7 861.7 435.0 415.0 378.3 696.7 HINDLIMB GRIPSTRENGTH (AVG) : 313.3 425.0 350.0 346.7 453.3 226.7 245.0 245.0 323.3 ----------------------------------------------------------------------------------------------------------------------------------- -999- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 79 PND 45 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 1 0 0 1 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 645. 710. 435. 555. 675. 760. 460. 680. 700. 910. 575. HINDLIMB GRIPSTRENGTH TRIAL 1: 620. 380. 540. 380. 690. 515. 470. 485. 520. 575. 460. FORELIMB GRIPSTRENGTH TRIAL 2: 730. 685. 805. 630. 645. 655. 645. 755. 960. 550. 845. HINDLIMB GRIPSTRENGTH TRIAL 2: 560. 620. 525. 365. 580. 590. 580. 415. 430. 670. 500. FORELIMB GRIPSTRENGTH TRIAL 3: 685. 800. 765. 505. 825. 655. 560. 525. 735. 725. 725. HINDLIMB GRIPSTRENGTH TRIAL 3: 490. 465. 520. 525. 580. 565. 560. 610. 515. 585. 640. FORELIMB GRIPSTRENGTH (AVG) : 686.7 731.7 668.3 563.3 715.0 690.0 555.0 653.3 798.3 728.3 715.0 HINDLIMB GRIPSTRENGTH (AVG) : 556.7 488.3 528.3 423.3 616.7 556.7 536.7 503.3 488.3 610.0 533.3 ----------------------------------------------------------------------------------------------------------------------------------- -1000- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 80 PND 45 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 280. 415. 280. 345. 465. 380. 805. 395. 385. HINDLIMB GRIPSTRENGTH TRIAL 1: 585. 265. 430. 245. 450. 250. 285. 270. 200. FORELIMB GRIPSTRENGTH TRIAL 2: 460. 460. 465. 305. 505. 645. 745. 380. 170. HINDLIMB GRIPSTRENGTH TRIAL 2: 360. 165. 320. 225. 365. 220. 515. 150. 115. FORELIMB GRIPSTRENGTH TRIAL 3: 675. 415. 560. 530. 475. 460. 615. 315. 330. HINDLIMB GRIPSTRENGTH TRIAL 3: 435. 405. 385. 285. 310. 325. 275. 105. 165. FORELIMB GRIPSTRENGTH (AVG) : 471.7 430.0 435.0 393.3 481.7 495.0 721.7 363.3 295.0 HINDLIMB GRIPSTRENGTH (AVG) : 460.0 278.3 378.3 251.7 375.0 265.0 358.3 175.0 160.0 ----------------------------------------------------------------------------------------------------------------------------------- -1001- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 81 PND 60 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 1 0 0 0 0 1 1 0 1 0 1 DEFECATION : 0 0 0 3 0 0 3 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 455. 660. 230. 660. 825. 365. 575. 550. 425. 330. 520. HINDLIMB GRIPSTRENGTH TRIAL 1: 455. 680. 235. 430. 370. 205. 305. 365. 160. 270. 270. FORELIMB GRIPSTRENGTH TRIAL 2: 415. 1060. 290. 590. 670. 305. 560. 455. 630. 550. 270. HINDLIMB GRIPSTRENGTH TRIAL 2: 460. 640. 320. 360. 500. 220. 550. 395. 220. 385. 155. FORELIMB GRIPSTRENGTH TRIAL 3: 590. 1015. 495. 495. 445. 355. 325. 625. 670. 300. 565. HINDLIMB GRIPSTRENGTH TRIAL 3: 515. 445. 240. 445. 485. 420. 265. 440. 210. 195. 365. FORELIMB GRIPSTRENGTH (AVG) : 486.7 911.7 338.3 581.7 646.7 341.7 486.7 543.3 575.0 393.3 451.7 HINDLIMB GRIPSTRENGTH (AVG) : 476.7 588.3 265.0 411.7 451.7 281.7 373.3 400.0 196.7 283.3 263.3 ----------------------------------------------------------------------------------------------------------------------------------- -1002- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 82 PND 60 GROUP: 0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 1 0 0 0 1 1 1 1 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 465. 545. 435. 355. 480. 430. 490. 235. 335. HINDLIMB GRIPSTRENGTH TRIAL 1: 240. 555. 245. 325. 185. 365. 280. 295. 260. FORELIMB GRIPSTRENGTH TRIAL 2: 250. 560. 300. 550. 350. 420. 360. 545. 370. HINDLIMB GRIPSTRENGTH TRIAL 2: 190. 415. 200. 215. 545. 270. 365. 270. 305. FORELIMB GRIPSTRENGTH TRIAL 3: 405. 205. 475. 255. 570. 375. 580. 410. 330. HINDLIMB GRIPSTRENGTH TRIAL 3: 175. 220. 325. 305. 610. 355. 240. 205. 225. FORELIMB GRIPSTRENGTH (AVG) : 373.3 436.7 403.3 386.7 466.7 408.3 476.7 396.7 345.0 HINDLIMB GRIPSTRENGTH (AVG) : 201.7 396.7 256.7 281.7 446.7 330.0 295.0 256.7 263.3 ----------------------------------------------------------------------------------------------------------------------------------- -1003- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 83 PND 60 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 1 1 0 1 1 0 0 1 1 0 1 DEFECATION : 1 0 0 0 0 0 0 0 1 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 705. 495. 515. 410. 440. 510. 610. 415. 565. 490. 995. HINDLIMB GRIPSTRENGTH TRIAL 1: 705. 220. 330. 400. 390. 415. 215. 275. 225. 335. 475. FORELIMB GRIPSTRENGTH TRIAL 2: 575. 355. 360. 520. 335. 425. 530. 595. 325. 570. 370. HINDLIMB GRIPSTRENGTH TRIAL 2: 565. 275. 410. 240. 240. 270. 200. 295. 335. 265. 315. FORELIMB GRIPSTRENGTH TRIAL 3: 780. 560. 665. 400. 395. 625. 585. 355. 505. 405. 475. HINDLIMB GRIPSTRENGTH TRIAL 3: 290. 230. 495. 205. 295. 320. 430. 290. 300. 250. 325. FORELIMB GRIPSTRENGTH (AVG) : 686.7 470.0 513.3 443.3 390.0 520.0 575.0 455.0 465.0 488.3 613.3 HINDLIMB GRIPSTRENGTH (AVG) : 520.0 241.7 411.7 281.7 308.3 335.0 281.7 286.7 286.7 283.3 371.7 ----------------------------------------------------------------------------------------------------------------------------------- -1004- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 84 PND 60 GROUP: 0.1 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 1 0 0 0 0 0 0 0 0 URINATION : 1 1 0 0 1 1 0 1 0 DEFECATION : 0 0 0 0 0 1 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 440. 560. 380. 490. 610. 385. 560. 470. 510. HINDLIMB GRIPSTRENGTH TRIAL 1: 200. 200. 195. 235. 370. 255. 265. 365. 275. FORELIMB GRIPSTRENGTH TRIAL 2: 285. 455. 630. 455. 515. 575. 250. 275. 435. HINDLIMB GRIPSTRENGTH TRIAL 2: 270. 335. 390. 160. 280. 505. 390. 220. 270. FORELIMB GRIPSTRENGTH TRIAL 3: 470. 340. 390. 415. 650. 430. 595. 230. 410. HINDLIMB GRIPSTRENGTH TRIAL 3: 230. 245. 280. 270. 410. 260. 330. 255. 330. FORELIMB GRIPSTRENGTH (AVG) : 398.3 451.7 466.7 453.3 591.7 463.3 468.3 325.0 451.7 HINDLIMB GRIPSTRENGTH (AVG) : 233.3 260.0 288.3 221.7 353.3 340.0 328.3 280.0 291.7 ----------------------------------------------------------------------------------------------------------------------------------- -1005- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 85 PND 60 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 1 0 0 1 0 0 URINATION : 2 1 1 1 1 1 0 1 1 0 1 DEFECATION : 0 0 0 0 0 1 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 810. 500. 525. 560. 540. 335. 610. 375. 530. 625. 610. HINDLIMB GRIPSTRENGTH TRIAL 1: 510. 325. 180. 325. 580. 445. 355. 330. 435. 425. 200. FORELIMB GRIPSTRENGTH TRIAL 2: 1040. 505. 525. 305. 540. 355. 445. 630. 460. 510. 510. HINDLIMB GRIPSTRENGTH TRIAL 2: 560. 250. 400. 220. 445. 350. 465. 495. 340. 320. 170. FORELIMB GRIPSTRENGTH TRIAL 3: 905. 435. 315. 470. 315. 470. 220. 545. 505. 230. 280. HINDLIMB GRIPSTRENGTH TRIAL 3: 430. 280. 255. 230. 345. 400. 225. 215. 365. 335. 240. FORELIMB GRIPSTRENGTH (AVG) : 918.3 480.0 455.0 445.0 465.0 386.7 425.0 516.7 498.3 455.0 466.7 HINDLIMB GRIPSTRENGTH (AVG) : 500.0 285.0 278.3 258.3 456.7 398.3 348.3 346.7 380.0 360.0 203.3 ----------------------------------------------------------------------------------------------------------------------------------- -1006- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 86 PND 60 GROUP: 0.3 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 1 1 2 1 1 0 1 0 1 DEFECATION : 0 0 3 3 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 230. 395. 250. 440. 325. 430. 475. 405. 530. HINDLIMB GRIPSTRENGTH TRIAL 1: 225. 220. 175. 460. 205. 295. 290. 315. 300. FORELIMB GRIPSTRENGTH TRIAL 2: 455. 400. 635. 375. 475. 400. 265. 325. 510. HINDLIMB GRIPSTRENGTH TRIAL 2: 520. 170. 425. 290. 270. 295. 160. 390. 260. FORELIMB GRIPSTRENGTH TRIAL 3: 400. 415. 270. 330. 295. 405. 465. 475. 510. HINDLIMB GRIPSTRENGTH TRIAL 3: 280. 330. 250. 225. 230. 365. 290. 370. 200. FORELIMB GRIPSTRENGTH (AVG) : 361.7 403.3 385.0 381.7 365.0 411.7 401.7 401.7 516.7 HINDLIMB GRIPSTRENGTH (AVG) : 341.7 240.0 283.3 325.0 235.0 318.3 246.7 358.3 253.3 ----------------------------------------------------------------------------------------------------------------------------------- -1007- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 87 PND 60 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 1 0 1 1 0 1 1 0 1 0 DEFECATION : 0 1 0 0 1 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 430. 495. 505. 310. 340. 705. 545. 290. 755. 385. 275. HINDLIMB GRIPSTRENGTH TRIAL 1: 270. 320. 390. 260. 250. 400. 440. 330. 450. 395. 160. FORELIMB GRIPSTRENGTH TRIAL 2: 480. 305. 320. 285. 330. 420. 725. 385. 690. 375. 620. HINDLIMB GRIPSTRENGTH TRIAL 2: 540. 340. 300. 205. 365. 420. 240. 265. 525. 270. 250. FORELIMB GRIPSTRENGTH TRIAL 3: 510. 395. 660. 315. 245. 565. 640. 325. 765. 330. 260. HINDLIMB GRIPSTRENGTH TRIAL 3: 315. 365. 555. 250. 260. 410. 390. 365. 420. 395. 200. FORELIMB GRIPSTRENGTH (AVG) : 473.3 398.3 495.0 303.3 305.0 563.3 636.7 333.3 736.7 363.3 385.0 HINDLIMB GRIPSTRENGTH (AVG) : 375.0 341.7 415.0 238.3 291.7 410.0 356.7 320.0 465.0 353.3 203.3 ----------------------------------------------------------------------------------------------------------------------------------- -1008- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 88 PND 60 GROUP: 1.0 MG/KG/DAY SEX: MALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 1 0 1 1 0 1 1 0 1 DEFECATION : 0 0 0 0 0 0 1 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 315. 375. 655. 660. 285. 335. 590. 595. 415. HINDLIMB GRIPSTRENGTH TRIAL 1: 280. 250. 325. 270. 230. 220. 315. 315. 175. FORELIMB GRIPSTRENGTH TRIAL 2: 420. 320. 445. 295. 360. 355. 525. 245. 285. HINDLIMB GRIPSTRENGTH TRIAL 2: 365. 240. 315. 200. 210. 260. 265. 330. 165. FORELIMB GRIPSTRENGTH TRIAL 3: 620. 565. 535. 560. 235. 330. 510. 855. 255. HINDLIMB GRIPSTRENGTH TRIAL 3: 460. 225. 365. 305. 190. 230. 340. 585. 180. FORELIMB GRIPSTRENGTH (AVG) : 451.7 420.0 545.0 505.0 293.3 340.0 541.7 565.0 318.3 HINDLIMB GRIPSTRENGTH (AVG) : 368.3 238.3 335.0 258.3 210.0 236.7 306.7 410.0 173.3 ----------------------------------------------------------------------------------------------------------------------------------- -1009- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 89 PND 60 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 1 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 3 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 660. 390. 325. 315. 335. 590. 365. 390. 510. 390. 205. HINDLIMB GRIPSTRENGTH TRIAL 1: 270. 350. 325. 395. 435. 305. 445. 160. 315. 350. 255. FORELIMB GRIPSTRENGTH TRIAL 2: 575. 515. 500. 345. 765. 590. 285. 460. 370. 370. 510. HINDLIMB GRIPSTRENGTH TRIAL 2: 355. 450. 445. 405. 415. 315. 165. 290. 225. 245. 200. FORELIMB GRIPSTRENGTH TRIAL 3: 540. 420. 600. 445. 370. 275. 580. 240. 560. 270. 415. HINDLIMB GRIPSTRENGTH TRIAL 3: 515. 515. 250. 245. 390. 245. 470. 230. 310. 180. 230. FORELIMB GRIPSTRENGTH (AVG) : 591.7 441.7 475.0 368.3 490.0 485.0 410.0 363.3 480.0 343.3 376.7 HINDLIMB GRIPSTRENGTH (AVG) : 380.0 438.3 340.0 348.3 413.3 288.3 360.0 226.7 283.3 258.3 228.3 ----------------------------------------------------------------------------------------------------------------------------------- -1010- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 90 PND 60 GROUP: 0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 355. 510. 285. 445. 315. 435. 365. 505. 275. HINDLIMB GRIPSTRENGTH TRIAL 1: 155. 280. 255. 270. 345. 235. 355. 340. 230. FORELIMB GRIPSTRENGTH TRIAL 2: 420. 470. 365. 505. 625. 380. 375. 205. 210. HINDLIMB GRIPSTRENGTH TRIAL 2: 190. 380. 235. 205. 335. 295. 205. 240. 120. FORELIMB GRIPSTRENGTH TRIAL 3: 335. 285. 720. 295. 215. 185. 390. 455. 135. HINDLIMB GRIPSTRENGTH TRIAL 3: 220. 225. 515. 170. 295. 175. 300. 320. 170. FORELIMB GRIPSTRENGTH (AVG) : 370.0 421.7 456.7 415.0 385.0 333.3 376.7 388.3 206.7 HINDLIMB GRIPSTRENGTH (AVG) : 188.3 295.0 335.0 215.0 325.0 235.0 286.7 300.0 173.3 ----------------------------------------------------------------------------------------------------------------------------------- -1011- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 91 PND 60 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 1 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 335. 270. 345. 405. 380. 455. 290. 390. 285. 590. 170. HINDLIMB GRIPSTRENGTH TRIAL 1: 490. 255. 285. 350. 280. 205. 390. 195. 160. 410. 170. FORELIMB GRIPSTRENGTH TRIAL 2: 680. 535. 315. 430. 210. 395. 490. 510. 430. 365. 450. HINDLIMB GRIPSTRENGTH TRIAL 2: 570. 235. 320. 395. 200. 350. 400. 355. 290. 300. 200. FORELIMB GRIPSTRENGTH TRIAL 3: 575. 305. 610. 405. 285. 560. 365. 375. 510. 470. 550. HINDLIMB GRIPSTRENGTH TRIAL 3: 575. 305. 340. 365. 160. 225. 370. 355. 255. 415. 185. FORELIMB GRIPSTRENGTH (AVG) : 530.0 370.0 423.3 413.3 291.7 470.0 381.7 425.0 408.3 475.0 390.0 HINDLIMB GRIPSTRENGTH (AVG) : 545.0 265.0 315.0 370.0 213.3 260.0 386.7 301.7 235.0 375.0 185.0 ----------------------------------------------------------------------------------------------------------------------------------- -1012- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 92 PND 60 GROUP: 0.1 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 400. 405. 475. 515. 390. 505. 255. 455. 245. HINDLIMB GRIPSTRENGTH TRIAL 1: 190. 235. 220. 205. 315. 250. 225. 445. 170. FORELIMB GRIPSTRENGTH TRIAL 2: 600. 395. 425. 430. 455. 465. 260. 380. 220. HINDLIMB GRIPSTRENGTH TRIAL 2: 390. 240. 230. 175. 300. 205. 225. 465. 160. FORELIMB GRIPSTRENGTH TRIAL 3: 365. 300. 415. 370. 735. 410. 360. 395. 250. HINDLIMB GRIPSTRENGTH TRIAL 3: 225. 315. 240. 365. 675. 340. 240. 275. 165. FORELIMB GRIPSTRENGTH (AVG) : 455.0 366.7 438.3 438.3 526.7 460.0 291.7 410.0 238.3 HINDLIMB GRIPSTRENGTH (AVG) : 268.3 263.3 230.0 248.3 430.0 265.0 230.0 395.0 165.0 ----------------------------------------------------------------------------------------------------------------------------------- -1013- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 93 PND 60 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 1060. 370. 540. 640. 490. 320. 415. 505. 565. 570. 255. HINDLIMB GRIPSTRENGTH TRIAL 1: 680. 410. 275. 325. 335. 385. 280. 435. 375. 425. 170. FORELIMB GRIPSTRENGTH TRIAL 2: 920. 400. 450. 250. 285. 630. 260. 480. 365. 305. 455. HINDLIMB GRIPSTRENGTH TRIAL 2: 650. 290. 310. 390. 255. 385. 230. 175. 355. 400. 220. FORELIMB GRIPSTRENGTH TRIAL 3: 840. 345. 205. 560. 660. 490. 505. 645. 405. 465. 470. HINDLIMB GRIPSTRENGTH TRIAL 3: 495. 165. 230. 465. 315. 340. 275. 220. 265. 270. 340. FORELIMB GRIPSTRENGTH (AVG) : 940.0 371.7 398.3 483.3 478.3 480.0 393.3 543.3 445.0 446.7 393.3 HINDLIMB GRIPSTRENGTH (AVG) : 608.3 288.3 271.7 393.3 301.7 370.0 261.7 276.7 331.7 365.0 243.3 ----------------------------------------------------------------------------------------------------------------------------------- -1014- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 94 PND 60 GROUP: 0.3 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 445. 230. 405. 225. 470. 590. 510. 410. 210. HINDLIMB GRIPSTRENGTH TRIAL 1: 330. 170. 165. 305. 280. 275. 240. 220. 240. FORELIMB GRIPSTRENGTH TRIAL 2: 465. 490. 330. 405. 535. 450. 310. 305. 315. HINDLIMB GRIPSTRENGTH TRIAL 2: 375. 290. 210. 325. 305. 280. 230. 315. 255. FORELIMB GRIPSTRENGTH TRIAL 3: 545. 280. 375. 450. 430. 220. 245. 365. 365. HINDLIMB GRIPSTRENGTH TRIAL 3: 320. 215. 300. 260. 365. 120. 170. 270. 250. FORELIMB GRIPSTRENGTH (AVG) : 485.0 333.3 370.0 360.0 478.3 420.0 355.0 360.0 296.7 HINDLIMB GRIPSTRENGTH (AVG) : 341.7 225.0 225.0 296.7 316.7 225.0 213.3 268.3 248.3 ----------------------------------------------------------------------------------------------------------------------------------- -1015- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 95 PND 60 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 1 0 0 0 0 0 0 0 0 URINATION : 0 0 1 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 390. 410. 615. 235. 490. 280. 445. 500. 660. 465. 510. HINDLIMB GRIPSTRENGTH TRIAL 1: 365. 415. 275. 155. 350. 290. 205. 240. 325. 380. 400. FORELIMB GRIPSTRENGTH TRIAL 2: 315. 465. 425. 275. 390. 355. 555. 300. 530. 430. 370. HINDLIMB GRIPSTRENGTH TRIAL 2: 250. 375. 315. 130. 365. 280. 480. 210. 365. 320. 360. FORELIMB GRIPSTRENGTH TRIAL 3: 515. 555. 340. 270. 410. 525. 360. 325. 305. 430. 295. HINDLIMB GRIPSTRENGTH TRIAL 3: 455. 370. 255. 215. 275. 300. 415. 400. 255. 355. 220. FORELIMB GRIPSTRENGTH (AVG) : 406.7 476.7 460.0 260.0 430.0 386.7 453.3 375.0 498.3 441.7 391.7 HINDLIMB GRIPSTRENGTH (AVG) : 356.7 386.7 281.7 166.7 330.0 290.0 366.7 283.3 315.0 351.7 326.7 ----------------------------------------------------------------------------------------------------------------------------------- -1016- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 96 PND 60 GROUP: 1.0 MG/KG/DAY SEX: FEMALES ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11 ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1 1 1 1 1 1 1 1 1 GAIT : 1 1 1 1 1 1 1 1 1 CONVULSIONS-CLONIC : 1 1 1 1 1 1 1 1 1 CONVULSIONS-TONIC : 1 1 1 1 1 1 1 1 1 TREMORS : 1 1 1 1 1 1 1 1 1 AROUSAL : 3 3 3 3 3 3 3 3 3 BIZARRE/STEREOTYPIC BEHAVIOR : 1 1 1 1 1 1 1 1 1 BACKING : 0 0 0 0 0 0 0 0 0 GROOMING : 0 0 0 0 0 0 0 0 0 URINATION : 0 0 0 0 0 0 0 0 0 DEFECATION : 0 0 0 0 0 0 0 0 0 TAIL PINCH RESPONSE : 2 2 2 2 2 2 2 2 2 AIR RIGHTING REFLEX : 1 1 1 1 1 1 1 1 1 HINDLIMB EXTENSOR STRENGTH : 3 3 3 3 3 3 3 3 3 FORELIMB GRIPSTRENGTH TRIAL 1: 500. 350. 355. 305. 250. 510. 465. 450. 325. HINDLIMB GRIPSTRENGTH TRIAL 1: 245. 340. 285. 205. 250. 150. 230. 220. 380. FORELIMB GRIPSTRENGTH TRIAL 2: 390. 600. 480. 140. 270. 390. 390. 305. 315. HINDLIMB GRIPSTRENGTH TRIAL 2: 260. 365. 335. 185. 120. 260. 265. 170. 190. FORELIMB GRIPSTRENGTH TRIAL 3: 465. 390. 355. 250. 420. 305. 255. 570. 405. HINDLIMB GRIPSTRENGTH TRIAL 3: 240. 285. 370. 115. 310. 255. 260. 285. 270. FORELIMB GRIPSTRENGTH (AVG) : 451.7 446.7 396.7 231.7 313.3 401.7 370.0 441.7 348.3 HINDLIMB GRIPSTRENGTH (AVG) : 248.3 330.0 330.0 168.3 226.7 221.7 251.7 225.0 280.0 ----------------------------------------------------------------------------------------------------------------------------------- -1017- APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 97 PARAMETER SCORING CRITERIA ----------------------------------------------------------------------------------------------------------------------------------- MOBILITY : 1-NORMAL 2-SLIGHTLY IMPAIRED 3-MODERATELY IMPAIRED 4-TOTALLY IMPAIRED, NO LOCOMOTION GAIT : 1-NORMAL 4-HINDLIMBS SPLAYED 7-ATAXIA 2-TIPTOES 5-HINDLIMBS DRAGGING 3-BODY DRAGS 6-HUNCHED CONVULSIONS-CLONIC : 1-ABSENT 4-WHOLE BODY TREMORS 2-REPETITIVE MOVEMENT 5-CONVULSIONS 3-TREMORS(LIMBS) 6-WET DOG SHAKES CONVULSIONS-TONIC : 1-ABSENT 5-"POPCORN SEIZURE" 2-TONIC 6-ASPHYXIAL 3-OPISTHOTONUS 4-EMPROSTHOTONUS TREMORS : 1-ABSENT 4-MARKEDLY COARSE (4.5MM) 2-SLIGHT (1.5MM) 5-EXTREMELY COARSE (6 MM) 3-MODERATELY COARSE (3MM) AROUSAL : 1-VERY LOW 5-VERY HIGH 2-LOW 3-NORMAL 4-SOMEWHAT HIGH -1018- BIZARRE/STEREOTYPIC BEHAVIOR : 1-NONE 6-HEAD BOBBING 2-HEAD FLICK 7-WRITHING 3-HEAD SEARCH 8-RETROPULSION 4-CIRCLING 5-STRAUB TAIL BACKING (COUNTS) APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 98 PARAMETER SCORING CRITERIA ----------------------------------------------------------------------------------------------------------------------------------- GROOMING (COUNTS) URINATION (COUNTS) DEFECATION (COUNTS) TAIL PINCH RESPONSE : 1-NO REACTION 3-ENERGETIC RESPONSE 5-JUMPS OR BITES 2-TURNS SLOWLY OR WALKS AWAY 4-FREEZES AIR RIGHTING REFLEX : 1-NORMAL 2-UNCOORDINATED 3-LANDS ON SIDE 4-LANDS ON BACK HINDLIMB EXTENSOR STRENGTH : 1-HINDLIMB RESISTANCE ABSENT 3-HINDLIMB RESISTANCE PRESENT 2-REDUCED HINDLIMB RESISTANCE FORELIMB GRIPSTRENGTH TRIAL 1 (GRAMS) -1019- HINDLIMB GRIPSTRENGTH TRIAL 1 (GRAMS) FORELIMB GRIPSTRENGTH TRIAL 2 (GRAMS) HINDLIMB GRIPSTRENGTH TRIAL 2 (GRAMS) APPENDIX 27 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - OPEN FIELD OBSERVATIONS) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL DETAILED CLINICAL OBSERVATIONS SPONSOR NO.:06-128 PAGE 99 PARAMETER SCORING CRITERIA ----------------------------------------------------------------------------------------------------------------------------------- FORELIMB GRIPSTRENGTH TRIAL 3 (GRAMS) HINDLIMB GRIPSTRENGTH TRIAL 3 (GRAMS) PFOBGv1.52 10/10/2006 R:01/26/2007 -1020- PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 13 PAGE 1 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 81 12 37 3 9 2 6 4 133 21 25654-09 84 28 39 0 14 0 16 0 153 28 25632-07 224 81 175 52 458 166 8 0 865 299 25633-05 82 3 61 0 8 0 7 0 158 3 25618-08 89 6 28 0 36 0 60 0 213 6 25621-07 73 10 50 8 18 0 80 0 221 18 25687-07 105 12 5 0 124 14 0 0 234 26 25681-01 116 16 281 75 622 270 461 191 1480 552 25615-03 152 19 177 0 78 2 102 0 509 21 25637-06 11 4 13 0 1 0 31 2 56 6 25638-07 42 1 28 0 44 4 10 0 124 5 25713-02 213 56 78 11 38 4 16 2 345 73 25670-09 166 29 32 0 30 0 57 9 285 38 25657-08 129 8 35 0 30 0 160 34 354 42 25663-04 37 4 4 0 9 2 16 0 66 6 25690-01 5 1 10 2 68 4 25 0 108 7 25666-01 157 23 36 8 12 2 34 3 239 36 25692-04 130 25 70 0 64 20 28 6 292 51 25701-09 145 29 3 0 16 0 8 2 172 31 25645-06 156 50 171 64 109 30 210 82 646 226 -1021- MEAN S.D. N 110. 60.6 20 21. 20.9 67. 11. 75.0 23.2 89. 26. 160.0 68.2 67. 17. 107.9 45.3 333. 75. 336.3 135.7 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 13 PAGE 2 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 94 38 22 8 65 16 3 0 184 62 25674-02 94 13 155 46 6 0 18 0 273 59 25694-04 67 4 224 72 93 7 85 16 469 99 25631-04 760 317 250 99 28 0 7 0 1045 416 25660-01 236 64 37 0 17 0 14 0 304 64 25704-03 210 74 31 0 16 0 13 0 270 74 25665-01 252 47 246 70 39 0 16 0 553 117 25652-04 106 7 127 6 233 70 877 320 1343 403 25733-07 84 22 32 6 70 10 166 17 352 55 25748-01 259 82 235 48 20 7 1 1 515 138 25753-06 52 14 116 4 12 3 12 4 192 25 25672-06 48 19 66 12 7 0 19 0 140 31 25655-01 86 25 482 173 44 0 17 2 629 200 25727-07 35 19 1 0 0 0 144 30 180 49 25626-04 435 169 109 29 39 6 132 8 715 212 25749-04 45 1 93 20 11 0 11 3 160 24 25739-07 27 2 11 0 24 6 66 10 128 18 25756-05 182 55 251 86 11 0 71 5 515 146 25741-07 149 13 172 23 84 18 410 156 815 210 25752-09 187 8 127 18 373 141 390 142 1077 309 -1022- MEAN S.D. N 170. 172.2 20 50. 74.4 139. 36. 117.8 44.8 60. 14. 90.3 33.7 124. 36. 213.7 80.5 493. 136. 351.8 121.6 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 13 PAGE 3 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 34 6 39 11 5 0 22 0 100 17 25614-10 28 2 6 0 13 0 12 0 59 2 25698-05 191 52 163 33 110 29 288 35 752 149 25677-05 65 7 74 17 92 6 387 119 618 149 25604-04 138 30 45 0 28 4 24 0 235 34 25678-02 10 5 0 0 62 12 21 4 93 21 25609-04 892 375 1115 455 77 20 47 3 2131 853 25623-08 147 47 74 12 14 0 39 2 274 61 25653-02 106 26 354 76 31 0 146 30 637 132 25684-04 9 3 112 25 19 3 5 0 145 31 25714-02 153 9 15 0 25 4 2 0 195 13 25650-11 180 44 21 0 32 2 7 4 240 50 25735-05 113 30 9 0 481 221 790 348 1393 599 25722-01 80 16 96 1 60 8 15 0 251 25 25642-05 19 7 0 0 5 0 9 0 33 7 25628-07 80 20 0 0 29 0 26 0 135 20 25766-01 0 0 0 0 0 0 0 0 0 0 25689-02 170 33 5 0 31 0 102 0 308 33 25708-01 39 0 81 18 27 0 3 0 150 18 25743-08 105 22 8 1 94 22 0 0 207 45 -1023- MEAN S.D. N 128. 190.0 20 37. 81.3 111. 32. 250.6 101.1 62. 17. 103.8 48.9 97. 27. 192.7 80.3 398. 113. 522.2 218.5 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 13 PAGE 4 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 124 43 9 0 53 10 24 5 210 58 25686-04 84 1 24 0 66 0 133 28 307 29 25630-04 125 37 324 127 264 87 230 78 943 329 25673-09 81 22 13 0 4 0 6 0 104 22 25639-06 14 0 40 0 12 0 9 0 75 0 25658-08 0 0 152 12 40 0 11 0 203 12 25676-02 162 10 102 35 10 0 24 2 298 47 25600-02 46 0 77 4 0 0 8 0 131 4 25603-04 718 307 418 174 5 0 420 157 1561 638 25703-03 92 20 118 8 55 0 6 0 271 28 25705-07 92 10 238 61 65 20 149 60 544 151 25611-07 65 15 110 0 15 0 33 0 223 15 25619-04 235 82 16 8 1 0 24 0 276 90 25691-07 57 4 61 4 70 0 59 0 247 8 25717-04 59 3 35 0 23 0 16 0 133 3 25616-05 221 80 107 0 41 0 20 0 389 80 25715-07 135 51 5 0 4 3 18 4 162 58 25599-06 13 0 7 0 9 0 18 0 47 0 25762-01 245 102 38 0 43 0 574 230 900 332 25647-07 37 11 0 0 0 0 0 0 37 11 -1024- MEAN S.D. N 130. 155.8 20 40. 70.0 95. 22. 113.1 47.2 39. 6. 58.4 19.7 89. 28. 153.5 61.6 353. 96. 377.0 160.8 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 17 PAGE 5 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 1094 426 532 174 344 139 32 6 2002 745 25654-09 564 194 334 99 62 0 12 0 972 293 25632-07 570 211 71 4 153 37 13 0 807 252 25633-05 170 41 6 0 40 0 65 5 281 46 25618-08 355 98 372 66 40 0 15 0 782 164 25621-07 653 244 191 64 47 0 11 0 902 308 25687-07 104 25 320 119 324 113 0 0 748 257 25681-01 754 251 61 8 444 158 679 260 1938 677 25615-03 144 36 44 0 34 0 33 0 255 36 25637-06 574 169 60 14 111 0 31 2 776 185 25638-07 142 6 43 0 17 0 19 0 221 6 25713-02 816 295 236 55 680 215 523 174 2255 739 25670-09 335 74 42 0 150 0 11 0 538 74 25657-08 315 107 16 0 7 0 25 0 363 107 25663-04 187 72 11 0 3 0 51 0 252 72 25690-01 198 61 276 100 258 70 30 0 762 231 25666-01 156 42 87 0 19 0 13 4 275 46 25692-04 1181 508 685 242 661 237 522 165 3049 1152 25701-09 579 195 295 60 77 20 41 12 992 287 25645-06 521 214 487 165 207 51 29 0 1244 430 -1025- MEAN S.D. N 471. 163. 317.8 135.8 20 208. 59. 199.2 71.4 184. 52. 208.8 77.7 108. 31. 203.9 74.6 971. 305. 772.8 302.8 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 17 PAGE 6 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 707 302 393 146 541 198 611 219 2252 865 25674-02 299 110 38 0 9 0 25 0 371 110 25694-04 474 185 220 86 116 24 452 186 1262 481 25631-04 1388 603 806 325 599 231 9 0 2802 1159 25660-01 785 284 142 36 519 169 526 148 1972 637 25704-03 829 312 3 0 8 0 24 0 864 312 25665-01 410 129 437 144 425 135 522 153 1794 561 25652-04 169 27 184 34 179 30 428 135 960 226 25733-07 529 195 121 28 22 0 27 0 699 223 25748-01 373 155 44 11 78 32 112 33 607 231 25753-06 760 324 45 5 24 2 2 0 831 331 25672-06 335 88 125 30 7 0 9 0 476 118 25655-01 305 105 6 0 17 2 3 0 331 107 25727-07 666 261 246 86 54 26 456 176 1422 549 25626-04 665 227 283 93 90 24 32 2 1070 346 25749-04 273 0 102 0 18 0 12 2 405 2 25739-07 468 94 403 129 354 103 437 122 1662 448 25756-05 840 320 48 18 733 261 601 197 2222 796 25741-07 1332 592 627 227 640 218 518 205 3117 1242 25752-09 495 166 228 70 14 0 3 0 740 236 -1026- MEAN S.D. N 605. 224. 326.4 160.3 20 225. 73. 215.3 86.2 222. 73. 256.4 92.8 240. 79. 251.1 88.7 1293. 449. 832.6 345.2 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 17 PAGE 7 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 929 413 873 390 802 372 674 289 3278 1464 25614-10 605 195 426 145 416 89 373 97 1820 526 25698-05 537 223 557 209 446 194 493 185 2033 811 25677-05 606 221 720 288 533 200 460 197 2319 906 25604-04 281 117 0 0 15 2 2 0 298 119 25678-02 374 107 84 12 1 0 69 7 528 126 25609-04 862 324 482 182 563 188 471 145 2378 839 25623-08 269 64 239 41 0 0 21 0 529 105 25653-02 1361 587 303 74 294 85 132 26 2090 772 25684-04 410 128 543 131 560 145 100 0 1613 404 25714-02 472 174 2 0 1 0 11 6 486 180 25650-11 692 230 349 104 54 0 2 0 1097 334 25735-05 696 222 501 158 383 105 477 174 2057 659 25722-01 534 188 262 86 296 87 461 144 1553 505 25642-05 671 192 487 177 542 180 340 94 2040 643 25628-07 1853 851 805 337 186 56 126 35 2970 1279 25766-01 592 226 46 6 37 0 67 2 742 234 25689-02 732 260 455 133 572 220 370 124 2129 737 25708-01 912 331 292 91 590 221 19 0 1813 643 25743-08 1248 500 764 307 751 275 793 340 3556 1422 -1027- MEAN S.D. N 732. 278. 387.9 187.5 20 410. 144. 262.2 115.5 352. 121. 265.9 108.1 273. 93. 246.4 104.1 1766. 635. 932.3 413.2 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 17 PAGE 8 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 67 15 140 14 279 80 43 0 529 109 25686-04 51 15 8 0 1 0 12 0 72 15 25630-04 435 153 663 255 682 270 524 215 2304 893 25673-09 173 53 457 102 1043 409 841 334 2514 898 25639-06 383 133 77 4 1 0 0 0 461 137 25658-08 119 21 163 10 2 0 35 0 319 31 25676-02 356 113 15 0 0 0 9 0 380 113 25600-02 114 24 123 4 808 317 817 294 1862 639 25603-04 705 259 510 152 434 126 414 106 2063 643 25703-03 73 24 3 0 1 0 4 2 81 26 25705-07 342 102 855 344 836 330 454 170 2487 946 25611-07 373 125 185 0 0 0 10 0 568 125 25619-04 915 389 487 206 589 269 697 313 2688 1177 25691-07 112 10 22 0 27 0 8 0 169 10 25717-04 76 2 25 0 28 0 86 2 215 4 25616-05 733 267 812 349 801 322 784 316 3130 1254 25715-07 982 391 697 283 816 285 706 264 3201 1223 25599-06 321 77 371 116 503 181 511 202 1706 576 25762-01 973 386 862 330 632 219 583 235 3050 1170 25647-07 358 52 921 330 1054 446 541 203 2874 1031 -1028- MEAN S.D. N 383. 131. 315.0 134.6 20 370. 125. 333.9 141.5 427. 163. 393.8 158.8 354. 133. 326.4 133.1 1534. 551. 1200.5 488.1 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 21 PAGE 9 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 290 115 4 0 208 55 335 75 837 245 25654-09 398 168 36 7 33 4 2 0 469 179 25632-07 845 334 295 73 83 8 7 0 1230 415 25633-05 489 169 199 39 21 2 8 4 717 214 25618-08 441 161 18 6 53 9 57 10 569 186 25621-07 550 182 23 0 12 0 3 0 588 182 25687-07 509 176 8 0 26 0 0 0 543 176 25681-01 496 203 53 6 127 27 1 0 677 236 25615-03 319 111 39 6 76 22 11 4 445 143 25637-06 451 154 50 0 12 0 7 0 520 154 25638-07 377 96 209 47 15 0 27 0 628 143 25713-02 399 168 9 0 31 0 36 0 475 168 25670-09 535 180 40 0 170 0 67 0 812 180 25657-08 318 125 3 0 6 0 0 0 327 125 25663-04 195 70 3 0 0 0 4 2 202 72 25690-01 352 108 129 35 83 0 68 0 632 143 25666-01 402 156 4 0 8 0 35 0 449 156 25692-04 698 265 312 80 180 65 0 0 1190 410 25701-09 541 238 354 120 79 29 33 3 1007 390 25645-06 490 154 76 0 31 0 6 0 603 154 -1029- MEAN S.D. N 455. 144.9 20 167. 60.8 93. 21. 115.3 34.4 63. 11. 63.0 19.2 35. 5. 74.1 16.7 646. 263.0 204. 94.8 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 21 PAGE 10 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 483 213 4 0 29 6 7 1 523 220 25674-02 400 180 19 0 47 0 19 0 485 180 25694-04 345 143 12 0 19 0 320 65 696 208 25631-04 672 250 484 139 20 2 18 0 1194 391 25660-01 539 204 9 2 12 4 0 0 560 210 25704-03 250 89 0 0 0 0 8 0 258 89 25665-01 572 213 301 55 259 53 29 0 1161 321 25652-04 620 197 358 66 243 42 183 14 1404 319 25733-07 785 251 234 46 104 16 44 2 1167 315 25748-01 487 161 8 0 0 0 0 0 495 161 25753-06 707 274 206 73 4 0 10 0 927 347 25672-06 480 181 10 0 95 0 113 0 698 181 25655-01 407 161 12 4 6 0 54 14 479 179 25727-07 487 168 1 0 22 5 22 5 532 178 25626-04 713 317 1 0 0 0 1 0 715 317 25749-04 328 81 6 0 0 0 0 0 334 81 25739-07 638 205 316 43 16 0 11 0 981 248 25756-05 558 182 312 73 352 81 24 0 1246 336 25741-07 859 313 490 128 445 119 332 111 2126 671 25752-09 615 222 356 113 451 144 242 48 1664 527 -1030- MEAN S.D. N 547. 158.2 20 200. 61.9 157. 37. 181.0 47.6 106. 24. 154.0 43.1 72. 13. 108.1 28.9 882. 274. 483.6 142.2 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 21 PAGE 11 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 504 160 396 108 235 64 187 51 1322 383 25614-10 700 264 87 0 13 2 23 0 823 266 25698-05 798 326 177 34 20 7 13 4 1008 371 25677-05 591 223 46 0 36 0 0 0 673 223 25604-04 566 208 241 68 5 0 0 0 812 276 25678-02 439 136 19 0 1 0 0 0 459 136 25609-04 409 124 351 89 13 2 28 0 801 215 25623-08 545 195 2 0 12 2 14 0 573 197 25653-02 623 191 181 0 11 0 12 0 827 191 25684-04 275 99 1 0 29 0 0 0 305 99 25714-02 472 183 5 0 10 0 8 0 495 183 25650-11 501 175 4 0 19 0 2 0 526 175 25735-05 507 209 168 56 268 74 325 111 1268 450 25722-01 327 117 21 0 5 0 33 0 386 117 25642-05 491 154 303 96 26 4 114 2 934 256 25628-07 320 115 6 0 5 0 3 0 334 115 25766-01 353 101 24 0 20 0 3 0 400 101 25689-02 511 153 156 23 8 0 2 0 677 176 25708-01 656 264 152 36 240 54 368 91 1416 445 25743-08 663 275 234 86 0 0 17 0 914 361 -1031- MEAN S.D. N 513. 136.5 20 184. 63.2 129. 30. 126.6 39.2 49. 10. 86.4 23.4 58. 13. 109.1 32.3 748. 237. 328.7 111.9 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 21 PAGE 12 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 633 209 9 0 1 0 3 0 646 209 25686-04 259 79 178 36 52 2 21 0 510 117 25630-04 758 261 31 2 3 0 0 0 792 263 25673-09 811 323 298 78 465 126 462 143 2036 670 25639-06 632 194 168 52 9 0 29 0 838 246 25658-08 643 241 49 0 78 0 498 120 1268 361 25676-02 447 126 29 0 0 0 3 0 479 126 25600-02 505 171 10 2 2 0 19 0 536 173 25603-04 522 178 26 0 65 2 4 0 617 180 25703-03 547 195 31 2 91 26 28 4 697 227 25705-07 801 284 279 109 78 0 354 49 1512 442 25611-07 455 143 9 1 34 13 10 0 508 157 25619-04 352 149 44 0 2 0 14 0 412 149 25691-07 445 160 236 81 136 51 15 0 832 292 25717-04 465 125 52 0 19 0 9 0 545 125 25616-05 569 221 2 0 0 0 0 0 571 221 25715-07 332 135 42 7 30 0 29 0 433 142 25599-06 488 131 78 0 150 0 13 0 729 131 25762-01 729 255 71 17 7 0 27 0 834 272 25647-07 1088 441 916 340 787 280 892 322 3683 1383 -1032- MEAN S.D. N 574. 195.1 20 201. 83.6 128. 36. 207.5 78.8 100. 25. 192.6 67.0 122. 32. 239.7 79.7 924. 294. 763.6 288.3 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 61 PAGE 13 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 1456 538 1076 380 620 194 626 226 3778 1338 25654-09 1416 452 479 172 350 115 1001 404 3246 1143 25632-07 1341 598 726 288 1 0 20 1 2088 887 25633-05 1060 381 661 242 0 0 11 2 1732 625 25618-08 1007 399 237 52 23 0 0 0 1267 451 25621-07 1149 434 472 104 391 52 70 9 2082 599 25687-07 1442 535 379 134 33 7 7 0 1861 676 25681-01 1269 550 463 157 21 4 0 0 1753 711 25615-03 1424 478 778 253 713 207 142 18 3057 956 25637-06 1488 468 772 229 403 122 56 20 2719 839 25638-07 589 106 127 13 71 2 38 0 825 121 25713-02 1028 409 493 153 353 124 165 50 2039 736 25670-09 1415 589 570 236 463 190 548 244 2996 1259 25657-08 1358 493 981 366 240 74 25 7 2604 940 25663-04 1158 340 377 102 160 35 197 50 1892 527 25690-01 1437 385 654 210 331 92 105 2 2527 689 25666-01 1734 559 1135 331 579 156 422 63 3870 1109 25692-04 1410 542 803 257 545 174 551 205 3309 1178 25701-09 1424 497 722 225 432 104 226 77 2804 903 25645-06 1317 542 619 192 774 243 493 142 3203 1119 -1033- MEAN S.D. N 1296. 465. 243.7 112.3 20 626. 205. 261.6 97.3 325. 95. 248.5 80.4 235. 76. 278.3 111.5 2483. 840. 818.4 304.1 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 61 PAGE 14 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 1248 422 551 206 414 161 165 52 2378 841 25674-02 1467 524 418 141 154 37 0 0 2039 702 25694-04 1283 373 488 161 313 106 316 77 2400 717 25631-04 1157 447 472 176 562 196 322 114 2513 933 25660-01 1092 480 468 175 299 114 65 28 1924 797 25704-03 988 391 486 170 488 107 160 44 2122 712 25665-01 1357 561 895 234 804 218 417 142 3473 1155 25652-04 1150 413 167 26 12 2 8 0 1337 441 25733-07 1407 614 444 176 476 171 110 30 2437 991 25748-01 1567 567 709 305 482 198 553 225 3311 1295 25753-06 1444 618 611 155 162 31 283 80 2500 884 25672-06 1424 555 911 309 310 115 7 1 2652 980 25655-01 1778 720 609 146 344 104 575 175 3306 1145 25727-07 1287 539 509 217 496 209 311 115 2603 1080 25626-04 1683 801 802 309 800 346 629 202 3914 1658 25749-04 1779 657 697 257 690 249 387 125 3553 1288 25739-07 1154 402 559 165 213 46 331 91 2257 704 25756-05 1430 621 584 167 256 78 274 91 2544 957 25741-07 1325 482 588 205 616 249 504 194 3033 1130 25752-09 1488 608 467 162 146 57 644 243 2745 1070 -1034- MEAN S.D. N 1375. 540. 217.9 115.5 20 572. 193. 172.4 67.0 402. 140. 220.9 89.1 303. 101. 208.0 76.1 2652. 974. 624.4 271.6 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 61 PAGE 15 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 847 333 320 96 215 76 249 74 1631 579 25614-10 1746 617 475 186 541 194 357 156 3119 1153 25698-05 1377 471 231 69 40 4 1 0 1649 544 25677-05 1418 449 883 295 239 58 0 0 2540 802 25604-04 1096 405 219 20 1 0 1 0 1317 425 25678-02 1240 500 318 101 12 1 0 0 1570 602 25609-04 1279 491 537 213 335 123 289 79 2440 906 25623-08 1375 510 543 178 130 27 0 0 2048 715 25653-02 1236 423 406 95 299 86 39 2 1980 606 25684-04 1081 418 550 177 261 62 0 0 1892 657 25714-02 1488 651 652 290 581 216 599 124 3320 1281 25650-11 1654 610 757 294 604 220 277 92 3292 1216 25735-05 1974 698 689 241 756 230 432 113 3851 1282 25722-01 1650 634 747 258 486 166 699 260 3582 1318 25642-05 1755 576 1114 413 875 252 742 253 4486 1494 25628-07 893 403 473 179 271 101 362 160 1999 843 25766-01 1729 613 852 218 526 156 86 10 3193 997 25689-02 1271 502 270 86 539 207 470 182 2550 977 25708-01 1402 483 1188 498 587 184 438 112 3615 1277 25743-08 1425 569 411 116 171 61 483 159 2490 905 -1035- MEAN S.D. N 1397. 295.7 20 518. 98.8 582. 201. 277.8 118.9 373. 121. 249.8 84.0 276. 89. 250.7 86.8 2628. 929. 884.5 312.9 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS MALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 61 PAGE 16 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 1532 542 933 326 207 70 129 42 2801 980 25686-04 1103 267 305 75 667 172 630 221 2705 735 25630-04 1224 464 502 156 521 157 320 73 2567 850 25673-09 1481 639 548 143 0 0 7 3 2036 785 25639-06 1091 295 547 181 498 134 517 131 2653 741 25658-08 1177 456 360 102 189 61 358 105 2084 724 25676-02 1577 569 592 245 175 35 248 77 2592 926 25600-02 1504 544 708 258 348 99 206 66 2766 967 25603-04 874 307 447 159 336 90 190 40 1847 596 25703-03 1388 498 312 97 1 1 7 0 1708 596 25705-07 1601 509 1059 435 281 78 265 87 3206 1109 25611-07 1400 604 716 300 383 149 338 124 2837 1177 25619-04 1314 559 494 187 1091 413 386 151 3285 1310 25691-07 1186 394 315 86 121 39 117 21 1739 540 25717-04 1200 457 283 95 139 49 2 0 1624 601 25616-05 1216 474 272 75 269 77 477 150 2234 776 25715-07 1341 575 708 285 350 99 318 121 2717 1080 25599-06 1208 456 507 144 467 121 297 101 2479 822 25762-01 1448 597 805 292 321 67 381 139 2955 1095 25647-07 1246 437 1397 501 621 213 479 157 3743 1308 -1036- MEAN S.D. N 1306. 482. 186.8 104.5 20 591. 207. 291.0 120.9 349. 106. 253.4 91.0 284. 90. 175.0 60.6 2529. 886. 567.1 235.9 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 13 PAGE 17 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 388 195 178 62 40 0 16 0 622 257 25654-10 24 0 67 18 24 5 0 0 115 23 25632-09 196 57 11 2 28 6 94 24 329 89 25633-13 43 0 0 0 3 0 37 0 83 0 25618-17 5 0 60 2 110 0 15 0 190 2 25621-10 310 104 396 146 458 159 4 0 1168 409 25687-15 114 22 185 16 32 2 29 4 360 44 25681-10 48 9 20 5 11 5 127 44 206 63 25615-10 49 8 49 24 0 0 6 0 104 32 25637-17 47 13 8 0 60 0 58 8 173 21 25638-18 13 7 101 2 14 0 601 228 729 237 25713-16 236 71 86 16 8 0 22 4 352 91 25670-18 124 23 66 0 34 0 301 97 525 120 25657-10 40 15 165 10 22 2 18 2 245 29 25663-09 243 41 19 0 67 2 69 0 398 43 25690-19 118 20 162 10 0 0 72 4 352 34 25666-09 18 6 20 2 76 16 27 7 141 31 25692-07 96 22 16 2 31 0 21 0 164 24 25701-18 43 0 82 0 22 0 21 0 168 0 25645-08 143 2 140 16 134 31 23 5 440 54 -1037- MEAN S.D. N 115. 107.9 20 31. 47.3 92. 17. 94.3 33.7 59. 11. 100.6 35.5 78. 21. 140.3 53.8 343. 80. 263.0 104.6 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 13 PAGE 18 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 87 1 146 14 88 2 27 2 348 19 25674-11 304 119 285 114 367 163 307 136 1263 532 25694-13 204 27 35 4 2 0 31 3 272 34 25631-05 1020 479 802 324 583 228 91 0 2496 1031 25660-04 97 20 147 0 29 0 11 0 284 20 25704-09 93 35 133 50 274 104 816 356 1316 545 25665-07 80 6 30 2 19 0 6 0 135 8 25652-13 262 53 326 137 66 0 145 28 799 218 25733-08 44 0 18 0 4 0 19 0 85 0 25748-08 188 34 29 4 50 5 65 15 332 58 25753-15 70 29 80 0 7 0 27 0 184 29 25672-15 505 192 224 116 649 307 5 0 1383 615 25655-13 196 47 46 0 79 1 477 195 798 243 25727-16 101 14 82 1 70 5 12 0 265 20 25626-12 12 1 40 6 6 0 18 0 76 7 25749-11 74 20 47 6 21 0 10 0 152 26 25739-12 188 83 38 2 19 0 7 2 252 87 25756-13 44 2 37 0 63 0 106 22 250 24 25741-09 630 270 1085 496 766 328 902 394 3383 1488 25752-13 307 74 490 152 628 272 392 151 1817 649 -1038- MEAN S.D. N 225. 75. 244.9 117.5 20 206. 71. 284.3 129.8 190. 71. 258.1 118.1 174. 65. 271.4 120.9 795. 283. 904.3 409.2 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 13 PAGE 19 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 21 0 29 0 33 0 59 0 142 0 25614-17 89 0 29 0 22 0 17 0 157 0 25698-12 128 36 214 102 188 58 348 147 878 343 25677-08 24 7 156 35 41 10 4 0 225 52 25604-12 74 11 314 127 157 55 5 0 550 193 25678-11 202 43 5 1 222 40 150 18 579 102 25609-11 32 2 17 0 25 0 34 0 108 2 25623-15 50 7 3 0 23 0 21 0 97 7 25653-13 385 147 349 96 579 202 221 73 1534 518 25684-06 27 7 30 0 9 0 5 0 71 7 25714-13 784 258 512 151 89 2 50 2 1435 413 25650-17 232 38 31 5 310 93 52 10 625 146 25735-08 73 14 114 1 118 15 281 68 586 98 25722-15 50 8 15 5 131 10 73 26 269 49 25628-17 70 16 118 9 197 46 38 0 423 71 25766-06 0 0 40 0 14 0 23 6 77 6 25689-14 109 25 94 0 1 0 42 0 246 25 25708-15 172 48 87 24 308 74 3 0 570 146 25743-16 5 0 0 0 0 0 4 0 9 0 25642-12 52 8 7 0 51 0 43 0 153 8 -1039- MEAN S.D. N 129. 180.2 20 34. 62.3 108. 28. 139.1 48.7 126. 30. 145.7 49.8 74. 18. 98.5 37.4 437. 109. 430.9 150.2 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 13 PAGE 20 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 62 1 330 114 608 233 79 14 1079 362 25686-10 29 9 75 4 0 0 400 250 504 263 25630-09 71 1 8 0 6 0 12 0 97 1 25673-10 282 61 216 47 69 24 6 0 573 132 25639-04 30 5 0 0 14 2 0 0 44 7 25658-14 80 15 19 0 29 0 15 0 143 15 25676-15 26 8 14 0 11 0 25 0 76 8 25600-15 26 6 0 0 1 0 9 0 36 6 25603-10 105 9 47 0 368 123 581 234 1101 366 25703-10 220 76 134 44 13 0 9 0 376 120 25705-08 156 25 28 0 295 94 21 3 500 122 25611-11 35 1 15 0 8 0 8 0 66 1 25619-12 211 54 502 227 10 0 163 44 886 325 25691-11 122 27 8 1 343 108 771 360 1244 496 25717-15 33 3 0 0 1 0 1 0 35 3 25616-14 131 19 3 3 13 1 5 2 152 25 25715-10 76 22 55 0 57 12 138 26 326 60 25599-11 70 5 24 3 21 3 9 0 124 11 25762-11 148 25 36 0 30 0 3 0 217 25 25647-11 133 48 99 0 18 0 8 0 258 48 -1040- MEAN S.D. N 102. 73.1 20 21. 22.1 81. 22. 129.7 55.7 96. 30. 168.2 61.8 113. 47. 216.4 104.2 392. 120. 391.7 154.4 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 17 PAGE 21 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 1378 654 678 243 38 8 27 4 2121 909 25654-10 737 279 330 110 57 14 4 0 1128 403 25632-09 293 53 441 136 67 0 5 0 806 189 25633-13 13 0 8 0 43 0 53 6 117 6 25618-17 33 2 11 0 7 0 1 0 52 2 25621-10 380 129 16 2 25 6 2 0 423 137 25687-15 143 33 155 0 415 126 522 155 1235 314 25681-10 580 222 477 167 473 177 425 153 1955 719 25615-10 212 68 124 17 11 0 19 0 366 85 25637-17 956 420 277 127 31 8 138 55 1402 610 25638-18 571 163 595 176 246 73 36 0 1448 412 25713-16 924 328 302 115 3 0 0 0 1229 443 25670-18 382 105 9 4 1 0 18 4 410 113 25657-10 183 45 7 0 4 0 4 0 198 45 25663-09 741 278 365 113 428 177 230 73 1764 641 25690-19 668 243 560 192 483 163 38 0 1749 598 25666-09 939 391 27 5 187 66 438 157 1591 619 25692-07 465 161 133 37 0 0 1 0 599 198 25701-18 689 269 438 150 37 14 34 0 1198 433 25645-08 587 186 457 144 387 130 483 148 1914 608 -1041- MEAN S.D. N 544. 201. 351.6 164.5 20 271. 87. 224.2 79.9 147. 48. 183.4 67.3 124. 38. 185.2 62.4 1085. 374. 668.1 268.2 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 17 PAGE 22 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 832 313 263 75 552 160 728 249 2375 797 25674-11 973 464 38 15 14 0 13 4 1038 483 25694-13 225 71 49 5 221 57 266 89 761 222 25631-05 628 202 1 0 24 0 71 0 724 202 25660-04 748 294 481 130 693 262 812 317 2734 1003 25704-09 458 182 151 39 17 2 33 2 659 225 25665-07 662 275 491 180 335 102 66 0 1554 557 25652-13 602 229 721 273 741 252 650 233 2714 987 25733-08 624 176 595 202 683 247 715 252 2617 877 25748-08 562 243 6 0 13 0 10 0 591 243 25753-15 492 173 8 1 51 0 190 61 741 235 25672-15 550 171 45 0 32 0 33 6 660 177 25655-13 357 100 464 134 308 86 131 35 1260 355 25727-16 384 133 288 97 101 20 61 0 834 250 25626-12 1029 415 682 222 1019 414 778 294 3508 1345 25749-11 490 156 54 2 26 0 78 0 648 158 25739-12 608 201 232 56 27 0 8 0 875 257 25756-13 775 293 100 20 31 12 0 0 906 325 25741-09 793 309 230 66 185 28 22 0 1230 403 25752-13 348 101 39 0 12 4 47 10 446 115 -1042- MEAN S.D. N 607. 225. 208.9 102.4 20 247. 76. 241.7 86.3 254. 82. 312.4 120.8 236. 78. 304.9 116.8 1344. 461. 914.4 350.7 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 17 PAGE 23 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 218 59 18 0 13 0 28 0 277 59 25614-17 217 82 208 54 180 56 198 52 803 244 25698-12 642 270 1082 551 69 5 264 93 2057 919 25677-08 910 380 589 199 561 189 458 138 2518 906 25604-12 541 195 4 0 44 16 31 10 620 221 25678-11 923 360 450 133 424 136 414 122 2211 751 25609-11 473 150 190 44 170 55 387 90 1220 339 25623-15 106 23 12 0 16 0 9 0 143 23 25653-13 717 294 410 109 464 164 540 193 2131 760 25684-06 173 34 75 0 6 0 4 0 258 34 25714-13 653 220 538 152 389 141 559 177 2139 690 25650-17 183 45 10 4 59 21 47 15 299 85 25735-08 721 281 439 125 560 181 490 146 2210 733 25722-15 985 370 283 77 518 166 639 236 2425 849 25628-17 362 45 458 137 672 242 550 227 2042 651 25766-06 926 353 626 235 539 207 423 180 2514 975 25689-14 696 250 425 135 512 168 21 3 1654 556 25708-15 670 259 461 168 408 148 20 5 1559 580 25743-16 1120 475 501 212 695 265 702 280 3018 1232 25642-12 364 86 111 0 19 0 44 0 538 86 -1043- MEAN S.D. N 580. 212. 306.9 138.8 20 345. 117. 273.4 128.8 316. 108. 248.5 90.8 291. 98. 248.7 94.1 1532. 535. 924.5 370.3 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 17 PAGE 24 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 107 0 553 198 493 165 471 152 1624 515 25686-10 182 38 518 195 187 69 16 0 903 302 25630-09 1143 508 427 203 625 258 310 128 2505 1097 25673-10 655 205 709 261 600 224 726 269 2690 959 25639-04 304 86 280 56 197 56 27 0 808 198 25658-14 299 72 317 106 309 127 36 0 961 305 25676-15 260 83 61 0 61 0 6 0 388 83 25600-15 88 17 2 0 29 0 14 0 133 17 25603-10 171 49 98 0 303 73 325 100 897 222 25703-10 665 307 101 25 26 0 3 0 795 332 25705-08 749 332 294 134 258 59 517 181 1818 706 25611-11 268 88 26 0 12 0 11 0 317 88 25619-12 856 310 690 233 599 189 85 13 2230 745 25691-11 983 428 453 163 741 281 523 201 2700 1073 25717-15 79 4 3 0 16 0 5 0 103 4 25616-14 621 244 508 183 442 141 106 24 1677 592 25715-10 831 303 332 105 122 13 427 159 1712 580 25599-11 664 260 387 130 519 207 460 186 2030 783 25762-11 1027 410 708 201 622 207 944 357 3301 1175 25647-11 1235 507 952 317 900 298 1056 372 4143 1494 -1044- MEAN S.D. N 559. 213. 376.0 171.0 20 371. 126. 271.8 99.4 353. 118. 273.2 104.1 303. 107. 330.2 124.0 1587. 564. 1109.6 432.4 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 21 PAGE 25 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 227 89 3 0 20 0 64 0 314 89 25654-10 463 175 3 0 2 0 0 0 468 175 25632-09 518 154 10 4 20 1 1 0 549 159 25633-13 646 248 204 72 2 0 22 0 874 320 25618-17 345 78 77 2 63 0 3 0 488 80 25621-10 667 228 554 199 11 2 273 96 1505 525 25687-15 492 119 273 75 17 0 371 59 1153 253 25681-10 501 159 29 0 5 0 0 0 535 159 25615-10 578 194 96 17 24 6 37 3 735 220 25637-17 470 187 3 0 6 1 13 4 492 192 25638-18 678 254 116 24 27 0 8 0 829 278 25713-16 675 230 332 57 20 0 1 0 1028 287 25670-18 594 232 397 137 99 7 33 0 1123 376 25657-10 450 153 30 2 8 0 3 0 491 155 25663-09 288 102 3 0 15 0 115 27 421 129 25690-19 482 218 0 0 8 0 15 2 505 220 25666-09 370 141 4 0 0 0 7 4 381 145 25692-07 468 193 26 5 0 0 2 0 496 198 25701-18 539 176 23 4 14 4 278 57 854 241 25645-08 639 216 541 145 215 56 164 52 1559 469 -1045- MEAN S.D. N 505. 128.5 20 177. 52.6 136. 37. 184.1 59.3 29. 4. 49.7 12.5 71. 15. 111.9 27.9 740. 234. 367.2 117.1 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 21 PAGE 26 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 626 258 283 83 30 0 2 0 941 341 25674-11 534 146 0 0 1 0 9 0 544 146 25694-13 509 180 3 0 52 0 14 0 578 180 25631-05 368 134 381 116 270 59 152 36 1171 345 25660-04 577 229 151 36 147 17 10 0 885 282 25704-09 359 96 1 0 1 0 2 0 363 96 25665-07 545 160 189 39 163 49 289 80 1186 328 25652-13 417 143 208 50 34 8 71 8 730 209 25733-08 488 171 6 0 3 0 14 0 511 171 25748-08 367 143 12 4 137 38 10 0 526 185 25753-15 669 268 278 93 5 0 33 0 985 361 25672-15 656 196 139 17 24 0 3 0 822 213 25655-13 622 226 28 6 0 0 3 0 653 232 25727-16 369 142 221 83 143 32 10 3 743 260 25626-12 392 155 0 0 1 0 0 0 393 155 25749-11 261 95 1 0 0 0 1 0 263 95 25739-12 592 181 131 22 19 0 18 0 760 203 25756-13 445 137 288 95 144 14 9 0 886 246 25741-09 343 133 268 71 23 0 33 0 667 204 25752-13 443 172 280 88 59 18 16 2 798 280 -1046- MEAN S.D. N 479. 119.5 20 168. 47.5 143. 40. 128.3 40.8 63. 12. 76.7 18.4 35. 6. 69.2 19.1 720. 250.9 227. 78.6 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 21 PAGE 27 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 624 210 148 45 24 0 1 0 797 255 25614-17 660 254 131 24 258 74 405 108 1454 460 25698-12 669 260 33 16 28 0 36 0 766 276 25677-08 700 253 77 19 35 6 10 2 822 280 25604-12 589 223 63 0 4 0 1 0 657 223 25678-11 426 157 0 0 11 0 18 0 455 157 25609-11 438 160 230 54 312 65 74 7 1054 286 25623-15 982 395 0 0 22 0 5 0 1009 395 25653-13 539 182 13 2 35 12 20 12 607 208 25684-06 407 124 1 0 28 0 2 0 438 124 25714-13 590 206 347 83 429 124 127 19 1493 432 25650-17 366 106 14 0 132 26 45 0 557 132 25735-08 284 78 2 0 4 0 12 0 302 78 25722-15 813 262 370 111 308 73 0 0 1491 446 25628-17 314 92 70 4 222 22 78 0 684 118 25766-06 631 222 43 0 0 0 0 0 674 222 25689-14 666 240 117 20 35 0 142 16 960 276 25708-15 463 178 214 53 4 0 0 0 681 231 25743-16 561 164 66 12 57 0 16 0 700 176 25642-12 544 206 135 49 159 51 279 91 1117 397 -1047- MEAN S.D. N 563. 169.5 20 199. 72.8 104. 25. 111.1 31.6 105. 23. 130.3 35.6 64. 13. 106.0 30.4 836. 259. 345.2 115.8 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 21 PAGE 28 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 665 219 485 149 46 0 74 0 1270 368 25686-10 439 134 79 0 7 0 0 0 525 134 25630-09 425 154 191 67 2 0 349 85 967 306 25673-10 571 221 164 27 61 0 3 0 799 248 25639-04 593 231 158 53 242 36 35 0 1028 320 25658-14 787 272 476 145 610 180 586 162 2459 759 25676-15 340 129 378 121 19 2 11 0 748 252 25600-15 433 121 2 0 4 0 31 0 470 121 25603-10 412 107 23 0 82 11 35 0 552 118 25703-10 776 254 298 0 9 0 141 6 1224 260 25705-08 662 214 264 86 34 0 50 0 1010 300 25611-11 520 177 37 0 2 0 5 0 564 177 25619-12 722 250 215 83 58 22 1 0 996 355 25691-11 514 208 366 123 110 40 59 3 1049 374 25717-15 539 198 316 81 98 0 11 0 964 279 25616-14 790 303 45 8 14 0 0 0 849 311 25715-10 424 152 224 24 20 0 21 0 689 176 25599-11 565 226 502 195 27 5 4 2 1098 428 25762-11 250 69 4 0 0 0 19 0 273 69 25647-11 902 336 333 83 382 67 422 116 2039 602 -1048- MEAN S.D. N 566. 170.8 20 199. 68.4 228. 62. 164.7 60.7 91. 18. 154.0 42.2 93. 19. 163.3 45.9 979. 298. 512.3 164.7 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 61 PAGE 29 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 1262 576 892 377 418 170 483 176 3055 1299 25654-10 1401 588 556 228 581 216 850 389 3388 1421 25632-09 1102 485 647 270 328 98 343 119 2420 972 25633-13 1356 564 666 245 717 260 78 34 2817 1103 25618-17 780 272 244 61 46 2 3 0 1073 335 25621-10 1222 567 264 96 193 67 85 10 1764 740 25687-15 1188 495 618 246 62 15 153 35 2021 791 25681-10 1208 532 484 208 126 36 419 162 2237 938 25615-10 1053 495 762 345 414 160 455 217 2684 1217 25637-17 1253 490 388 115 284 83 560 158 2485 846 25638-18 967 474 404 164 425 189 389 168 2185 995 25713-16 1263 636 431 169 221 90 97 16 2012 911 25670-18 1486 701 608 234 493 212 341 91 2928 1238 25657-10 830 330 326 124 224 79 124 24 1504 557 25663-09 974 463 557 214 1 1 43 4 1575 682 25690-19 1408 688 819 364 732 299 224 57 3183 1408 25666-09 1151 464 516 174 165 58 1 0 1833 696 25692-07 1238 478 709 279 283 72 398 139 2628 968 25701-18 1176 462 147 62 521 213 47 16 1891 753 25645-08 1640 614 652 205 349 107 4 0 2645 926 -1049- MEAN S.D. N 1198. 519. 211.4 105.1 20 535. 209. 198.9 91.8 329. 121. 209.9 87.8 255. 91. 230.8 100.7 2316. 940. 612.5 283.0 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 61 PAGE 30 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 1261 612 908 438 939 430 141 44 3249 1524 25674-11 1352 537 377 129 1 0 8 0 1738 666 25694-13 1098 488 677 242 593 224 407 146 2775 1100 25631-05 975 387 329 105 478 187 66 20 1848 699 25660-04 1758 828 850 381 505 193 350 102 3463 1504 25704-09 1125 434 240 58 216 91 36 0 1617 583 25665-07 997 475 429 165 300 75 481 190 2207 905 25652-13 1185 516 476 158 209 67 0 0 1870 741 25733-08 1032 498 733 282 571 221 272 90 2608 1091 25748-08 946 450 480 197 403 196 147 46 1976 889 25753-15 945 449 444 170 206 85 339 103 1934 807 25672-15 988 439 551 204 349 135 337 122 2225 900 25655-13 1153 588 473 192 548 219 388 146 2562 1145 25727-16 1262 482 799 325 404 154 445 157 2910 1118 25626-12 1054 467 326 90 94 33 8 0 1482 590 25749-11 1356 616 448 175 193 75 468 199 2465 1065 25739-12 1422 592 836 297 576 219 549 198 3383 1306 25756-13 970 427 385 119 449 175 84 13 1888 734 25741-09 982 395 525 183 717 307 484 169 2708 1054 25752-13 1360 625 381 154 390 136 234 77 2365 992 -1050- MEAN S.D. N 1161. 515. 211.0 104.3 20 533. 203. 197.4 98.0 407. 161. 223.1 99.8 262. 91. 186.3 72.3 2364. 971. 587.9 273.0 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 61 PAGE 31 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 1112 489 596 231 271 73 75 25 2054 818 25614-17 1373 621 628 296 83 29 317 144 2401 1090 25698-12 958 454 498 184 7 1 0 0 1463 639 25677-08 1279 628 568 231 567 244 16 2 2430 1105 25604-12 1352 618 427 136 453 116 117 25 2349 895 25678-11 1330 629 167 51 4 0 53 0 1554 680 25609-11 766 350 520 182 378 143 308 103 1972 778 25623-15 1347 644 629 297 486 196 487 219 2949 1356 25653-13 1018 400 283 68 0 0 10 2 1311 470 25684-06 1172 522 164 49 11 0 143 73 1490 644 25714-13 1062 451 684 270 486 165 417 165 2649 1051 25650-17 890 377 388 121 388 114 130 33 1796 645 25735-08 1070 473 482 148 316 92 92 16 1960 729 25722-15 1375 612 480 179 518 185 228 49 2601 1025 25628-17 1544 713 845 326 756 301 518 188 3663 1528 25766-06 1505 571 406 101 2 0 96 26 2009 698 25689-14 1156 445 669 211 685 269 425 146 2935 1071 25708-15 1363 535 138 29 493 181 65 11 2059 756 25743-16 616 205 145 36 69 4 1 0 831 245 25642-12 975 370 443 176 380 148 215 86 2013 780 -1051- MEAN S.D. N 1163. 505. 246.4 127.0 20 458. 166. 199.0 92.2 318. 113. 246.7 98.1 186. 66. 169.5 70.9 2124. 850. 653.7 297.9 PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 28 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MOTOR ACTIVITY COUNTS FEMALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 61 PAGE 32 0 TO 15 MINS 16 TO 30 MINS 31 TO 45 MINS 46 TO 60 MINS COMBINED ANIMAL TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB TOTAL AMB ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 1108 478 558 224 177 73 4 0 1847 775 25686-10 1398 661 511 204 472 178 469 196 2850 1239 25630-09 1319 663 827 341 70 15 23 0 2239 1019 25673-10 1264 511 425 157 0 0 0 0 1689 668 25639-04 1387 624 522 201 514 203 402 156 2825 1184 25658-14 1159 490 596 223 493 191 113 10 2361 914 25676-15 1418 682 718 291 488 187 456 206 3080 1366 25600-15 1396 666 735 320 523 247 254 75 2908 1308 25603-10 957 354 417 157 476 157 244 83 2094 751 25703-10 928 458 514 241 157 38 66 22 1665 759 25705-08 938 343 150 39 23 5 0 0 1111 387 25611-11 1352 594 702 293 553 218 156 49 2763 1154 25619-12 1280 609 750 316 357 157 536 221 2923 1303 25691-11 1054 518 569 255 254 90 349 138 2226 1001 25717-15 1370 520 467 140 485 156 477 146 2799 962 25616-14 1232 622 617 242 178 45 229 78 2256 987 25715-10 858 346 594 213 231 79 129 42 1812 680 25599-11 1194 571 750 328 657 282 435 191 3036 1372 25762-11 1134 485 555 210 446 159 199 58 2334 912 25647-11 1601 608 729 275 671 265 427 163 3428 1311 -1052- MEAN S.D. N 1217. 540. 198.3 108.0 20 585. 234. 156.0 74.4 361. 137. 207.6 88.3 248. 92. 183.3 78.1 2412. 1003. 592.1 275.9 PMASUMv5.15 10/23/2006 APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 MALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 20 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 267.4 20.6 55.3 212.3 21.8 50.4 115.3 26.9 26.9 80.2 25.8 19.5 122.4 23.1 31.3 159.5 23.6 36.7 25654-09 195.8 22.3 43.6 192.9 24.0 42.5 175.3 21.3 38.5 186.0 22.4 41.7 192.8 21.9 51.9 188.6 22.4 43.6 25632-07 155.4 22.4 36.0 132.8 24.1 29.9 101.8 29.9 24.3 101.2 22.6 22.7 110.6 21.8 24.3 120.4 24.2 27.4 25633-05 115.3 24.8 28.3 73.1 24.5 14.2 99.4 20.9 21.6 115.5 21.6 25.3 100.4 24.6 19.8 100.7 23.3 21.8 25618-08 161.0 25.9 33.4 194.5 22.1 43.0 182.4 21.3 38.2 90.2 25.5 18.8 257.7 20.0 59.4 177.2 23.0 38.6 25621-07 225.5 21.5 54.9 208.4 20.3 49.9 182.1 20.4 45.4 80.2 25.5 19.7 52.5 36.6 12.4 149.7 24.9 36.5 25687-07 229.2 23.9 49.7 223.7 21.4 41.5 149.4 24.5 27.0 190.8 20.5 33.9 215.9 20.4 44.3 201.8 22.1 39.3 25681-01 274.6 23.2 60.4 170.0 21.6 31.7 177.5 21.4 35.9 151.7 20.8 32.7 165.4 24.7 43.0 187.8 22.3 40.7 25615-03 68.7 30.2 13.7 68.6 30.9 13.7 77.3 29.8 13.1 114.8 21.0 20.4 167.4 21.1 30.7 99.4 26.6 18.3 25637-06 169.8 25.1 38.5 113.7 26.1 19.9 110.6 21.1 26.6 79.4 30.0 16.4 199.2 19.7 40.6 134.5 24.4 28.4 25638-07 245.3 29.2 60.7 202.8 22.0 43.9 215.8 22.4 43.4 234.1 20.9 45.5 121.8 22.5 29.8 204.0 23.4 44.7 25713-02 165.9 27.6 36.0 229.7 29.7 45.0 218.7 26.8 46.4 114.7 24.1 25.1 65.5 32.1 16.1 158.9 28.1 33.7 25670-09 94.6 31.4 24.2 59.6 28.6 13.9 79.1 25.7 19.1 88.7 24.1 20.0 129.4 20.8 29.6 90.3 26.1 21.4 25657-08 82.4 35.1 16.1 44.3 31.9 9.8 75.4 35.5 17.6 31.1 27.6 6.1 40.5 40.2 10.5 54.7 34.1 12.0 25663-04 127.8 25.8 23.7 88.5 31.4 18.5 79.6 22.9 16.7 58.3 34.2 12.4 52.7 26.6 12.0 81.4 28.2 16.7 25690-01 287.2 27.0 55.1 266.8 20.9 53.3 262.2 21.3 56.1 149.5 22.5 30.9 131.4 25.0 30.9 219.4 23.3 45.3 25666-01 149.1 31.1 32.3 96.7 21.8 19.7 128.5 26.7 25.9 156.4 19.8 29.9 175.2 20.0 34.1 141.2 23.9 28.4 25692-04 251.3 23.7 48.4 238.7 20.2 47.2 206.3 21.1 48.1 166.5 23.5 40.2 178.1 28.7 49.9 208.2 23.4 46.8 25701-09 214.7 28.4 44.2 218.3 20.6 49.2 134.9 27.6 31.9 121.8 28.3 27.9 52.8 31.5 12.1 148.5 27.3 33.1 25645-06 284.8 26.2 59.0 244.2 21.7 53.9 196.3 21.7 43.2 149.9 25.6 37.9 134.2 28.3 36.5 201.9 24.7 46.1 -1053- MEAN 188.3 S.D. 69.33 N 20 26.3 40.7 3.77 14.74 164.0 71.58 24.3 34.6 4.01 15.52 148.4 55.98 24.5 32.3 4.06 12.20 123.1 49.89 24.3 26.4 3.64 10.27 133.3 61.01 25.5 31.0 5.82 14.39 151.4 48.02 25.0 33.0 2.83 10.69 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 MALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 20 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 175.7 27.6 37.7 159.9 18.9 28.1 195.5 19.7 31.0 221.7 18.6 38.2 201.7 19.5 39.8 190.9 20.9 35.0 25674-02 218.6 25.4 49.6 195.2 23.9 43.8 166.1 21.4 41.1 174.7 23.9 44.1 147.2 24.3 37.5 180.4 23.8 43.2 25694-04 167.7 26.4 39.7 130.8 23.5 24.6 139.5 21.6 29.2 106.9 24.1 21.6 65.8 24.6 15.7 122.1 24.0 26.2 25631-04 158.2 34.7 33.6 105.4 32.6 28.3 69.6 33.6 15.4 151.6 25.6 37.4 104.2 25.0 20.6 117.8 30.3 27.1 25660-01 106.4 22.2 17.8 141.8 19.3 27.0 123.1 19.5 24.9 134.6 20.6 28.2 138.1 19.4 28.7 128.8 20.2 25.3 25704-03 102.4 23.8 21.1 89.8 22.4 18.0 84.3 22.1 20.0 203.3 21.9 53.2 122.7 23.9 32.3 120.5 22.8 28.9 25665-01 134.4 22.3 27.3 199.5 20.0 28.5 185.3 20.4 32.3 188.9 21.7 35.1 176.5 20.6 37.1 176.9 21.0 32.1 25652-04 94.5 28.1 21.6 74.0 28.0 16.3 100.7 32.9 20.9 105.7 26.3 25.9 55.3 25.1 10.7 86.0 28.1 19.1 25733-07 142.6 30.1 30.8 116.8 28.1 27.5 130.7 26.8 30.6 143.8 27.9 29.3 131.1 29.4 28.1 133.0 28.5 29.3 25748-01 212.7 24.5 47.4 192.2 22.7 45.3 136.0 24.6 34.1 199.9 22.7 47.6 192.7 21.2 43.9 186.7 23.1 43.7 25753-06 115.9 25.1 23.7 130.1 20.8 25.2 131.9 22.5 24.5 149.2 20.8 32.7 169.4 22.3 35.0 139.3 22.3 28.2 25672-06 96.0 31.8 20.1 41.9 26.6 9.5 43.7 41.3 8.1 50.4 33.0 8.2 106.1 23.6 21.5 67.6 31.3 13.5 25655-01 127.8 34.7 32.4 84.0 31.3 17.2 104.0 22.6 22.2 121.3 19.2 20.1 126.0 19.4 19.8 112.6 25.4 22.3 25727-07 167.1 34.8 37.0 116.8 25.7 25.2 84.0 31.6 19.2 67.8 21.4 13.8 150.3 21.2 34.0 117.2 26.9 25.8 25626-04 251.6 21.6 49.0 166.4 19.9 35.7 83.1 27.5 20.8 149.4 29.0 42.6 150.2 22.9 43.2 160.1 24.2 38.3 25749-04 84.7 35.9 20.5 139.7 23.5 25.3 94.1 23.4 14.9 100.7 26.7 19.1 85.4 26.0 18.8 100.9 27.1 19.7 25739-07 285.9 30.9 59.0 201.3 20.6 46.0 232.2 23.3 49.8 189.3 21.0 50.0 150.9 25.4 40.9 211.9 24.2 49.1 25756-05 230.1 30.9 42.4 131.0 29.0 25.8 59.6 25.0 12.1 81.4 20.1 15.2 83.3 28.5 16.2 117.1 26.7 22.3 25741-07 211.8 22.0 48.5 224.1 20.3 59.5 215.2 20.6 58.3 97.8 31.5 24.0 26.2 35.9 5.7 155.0 26.1 39.2 25752-09 225.1 21.4 47.7 184.5 21.1 40.7 224.6 22.0 57.1 152.6 23.1 39.5 207.2 22.0 55.1 198.8 21.9 48.0 -1054- MEAN 165.5 S.D. 59.04 N 20 27.7 35.3 4.96 12.32 141.3 48.86 23.9 29.9 4.13 12.04 130.2 56.55 25.1 28.3 5.68 14.07 139.6 47.81 24.0 31.3 4.04 12.81 129.5 49.37 24.0 29.2 3.96 12.79 141.2 39.63 24.9 30.8 3.13 10.01 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 MALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 20 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 170.6 21.6 32.3 177.0 21.1 33.5 159.9 23.0 30.0 155.9 21.9 31.3 118.8 24.9 25.7 156.4 22.5 30.6 25614-10 142.3 27.6 25.2 122.2 23.3 27.5 116.9 23.7 24.5 72.9 25.0 15.2 111.9 22.5 21.0 113.2 24.4 22.7 25698-05 234.5 21.4 57.8 169.1 22.4 38.5 186.7 19.8 43.4 169.7 20.2 44.2 156.1 21.3 36.7 183.2 21.0 44.1 25677-05 216.2 21.1 42.9 102.3 23.6 22.4 21.1 33.1 2.8 54.8 26.1 10.8 70.4 25.7 15.9 93.0 25.9 19.0 25604-04 214.4 24.0 58.1 211.4 21.2 59.2 189.8 21.3 56.7 167.5 21.5 50.5 147.3 34.8 43.5 186.1 24.6 53.6 25678-02 104.3 24.3 18.0 106.9 20.0 16.1 124.8 20.7 20.9 142.7 20.2 27.8 116.5 22.0 23.9 119.0 21.4 21.3 25609-04 219.5 20.7 47.4 207.5 21.6 42.8 206.4 22.0 44.9 197.7 24.1 42.1 168.1 20.8 38.4 199.8 21.8 43.1 25623-08 108.4 28.0 24.7 76.9 25.2 13.8 127.2 20.4 26.3 137.6 20.4 36.9 159.7 21.5 38.1 122.0 23.1 28.0 25653-02 56.3 22.5 10.2 73.8 21.4 13.2 97.8 21.7 21.0 115.3 21.0 26.0 110.9 27.9 24.3 90.8 22.9 18.9 25684-04 73.0 28.4 16.1 52.1 33.7 11.4 64.2 25.5 13.0 121.5 23.4 25.2 113.2 25.0 25.3 84.8 27.2 18.2 25714-02 165.3 29.0 38.1 198.1 20.4 37.7 224.8 19.2 46.4 282.3 18.9 57.5 230.6 20.7 50.6 220.2 21.6 46.1 25650-11 153.9 32.4 27.9 134.3 25.2 25.6 170.8 22.8 28.8 188.9 20.0 36.5 246.9 20.0 52.7 179.0 24.1 34.3 25735-05 210.8 23.0 38.3 201.7 28.3 38.3 244.1 32.3 50.0 130.7 26.2 33.0 60.8 34.2 14.9 169.6 28.8 34.9 25722-01 243.5 25.3 54.2 232.6 21.8 40.8 243.5 20.1 48.7 265.7 21.5 52.3 193.3 23.3 43.5 235.7 22.4 47.9 25642-05 190.4 23.4 45.0 176.9 19.1 41.9 160.4 21.1 37.6 121.7 23.1 25.4 94.5 22.2 19.0 148.8 21.8 33.8 25628-07 95.9 31.8 21.7 87.1 31.0 21.1 123.3 19.7 26.3 149.1 21.1 31.8 150.5 20.8 33.0 121.2 24.9 26.8 25766-01 104.0 31.4 20.0 60.5 27.5 12.4 56.3 31.0 11.9 58.7 29.5 13.4 95.8 33.6 20.0 75.1 30.6 15.5 25689-02 196.7 28.6 34.4 128.4 23.6 27.4 61.4 28.7 12.2 88.1 23.6 15.0 119.8 30.5 29.6 118.9 27.0 23.7 25708-01 170.3 30.8 35.1 166.8 23.3 31.4 101.8 24.2 20.2 126.4 23.3 25.6 122.7 27.8 27.0 137.6 25.9 27.9 25743-08 156.5 28.6 33.2 169.8 20.2 33.3 131.6 24.5 30.1 115.3 28.1 24.5 159.5 19.5 33.4 146.5 24.2 30.9 -1055- MEAN 161.3 S.D. 55.70 N 20 26.2 34.0 3.90 13.89 142.8 55.56 23.7 29.4 3.84 12.68 140.6 63.72 23.7 29.8 4.29 14.84 143.1 59.29 23.0 31.3 2.86 13.17 137.4 47.86 25.0 30.8 4.93 11.10 145.0 45.67 24.3 31.1 2.61 11.05 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 MALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 20 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 127.9 23.1 27.3 111.5 24.4 22.0 157.5 20.7 30.6 77.7 24.5 15.8 63.4 23.0 11.4 107.6 23.1 21.4 25686-04 76.8 29.0 17.8 38.1 27.3 9.5 53.7 28.0 10.2 56.3 23.6 11.5 57.4 35.8 11.3 56.5 28.7 12.1 25630-04 236.0 27.2 62.5 179.4 24.8 44.8 111.1 30.2 25.6 46.1 28.2 9.7 80.3 30.4 23.7 130.6 28.2 33.3 25673-09 196.5 27.1 46.3 146.5 23.1 32.6 35.0 34.4 8.3 72.0 22.2 15.2 85.0 24.8 20.1 107.0 26.3 24.5 25639-06 136.1 21.5 28.1 62.6 30.5 16.5 81.6 25.9 15.6 104.1 23.8 20.0 119.2 19.7 25.3 100.7 24.3 21.1 25658-08 161.5 27.9 36.4 173.5 24.4 34.1 194.0 23.0 43.5 150.0 20.6 34.4 131.2 25.2 30.3 162.0 24.2 35.7 25676-02 240.6 20.6 52.2 250.6 20.3 48.1 152.4 22.7 32.1 186.8 20.5 31.2 200.3 27.4 42.2 206.1 22.3 41.2 25600-02 266.9 20.4 63.4 175.1 20.9 37.0 154.9 22.6 35.0 204.4 20.2 43.0 218.1 20.4 51.8 203.9 20.9 46.0 25603-04 188.2 23.2 29.9 217.3 19.9 33.6 225.8 20.0 39.3 237.8 22.1 37.6 206.7 22.8 38.8 215.2 21.6 35.8 25703-03 192.7 24.7 44.3 135.0 27.9 27.2 75.2 38.2 15.8 143.4 22.4 30.5 126.5 21.6 30.7 134.6 27.0 29.7 25705-07 176.5 26.0 48.4 133.9 20.0 34.3 112.9 21.1 29.1 117.6 19.6 31.0 91.8 22.4 20.6 126.5 21.8 32.7 25611-07 145.3 30.1 36.3 119.6 27.2 28.7 99.7 29.0 19.8 126.2 20.5 24.2 162.7 20.3 36.4 130.7 25.4 29.1 25619-04 21.2 36.8 4.1 15.4 35.9 3.1 13.3 32.5 2.0 17.8 21.0 2.7 12.0 30.4 1.9 15.9 31.3 2.8 25691-07 274.9 19.7 59.0 216.7 24.3 45.6 166.2 23.9 40.3 141.0 20.3 27.1 216.3 19.1 41.4 203.0 21.5 42.7 25717-04 140.1 31.2 38.4 95.5 26.1 22.4 77.6 27.2 19.0 84.9 31.5 20.5 78.6 24.0 19.0 95.3 28.0 23.9 25616-05 114.4 35.4 30.4 90.9 27.7 22.5 70.3 26.0 16.0 63.4 20.8 11.4 134.0 21.4 31.0 94.6 26.3 22.3 25715-07 249.0 20.9 57.4 273.5 19.6 61.9 294.4 19.9 72.4 240.9 21.0 61.6 201.6 24.6 47.6 251.9 21.2 60.2 25599-06 99.3 33.6 21.4 59.8 30.8 12.6 70.3 29.4 15.3 78.0 22.6 14.7 123.6 21.2 26.1 86.2 27.5 18.0 25762-01 127.5 21.7 29.0 102.9 22.2 23.3 126.7 23.3 30.8 87.1 28.5 21.1 25.7 26.7 6.1 94.0 24.5 22.1 25647-07 82.8 29.9 20.8 86.3 25.2 19.4 62.9 29.2 14.8 76.6 23.1 18.3 84.7 21.8 20.4 78.7 25.8 18.7 -1056- MEAN 162.7 S.D. 68.57 N 20 26.5 37.7 5.21 16.27 134.2 70.14 25.1 29.0 4.24 14.26 116.8 68.73 26.4 25.8 5.03 15.88 115.6 62.87 22.9 24.1 3.18 13.56 121.0 63.22 24.1 26.8 4.24 13.60 130.1 59.99 25.0 28.7 2.95 12.94 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 FEMALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 20 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 171.0 19.2 34.4 166.9 20.4 31.6 159.9 19.4 26.7 170.0 19.2 32.5 136.8 20.4 27.3 160.9 19.7 30.5 25654-10 217.6 39.8 52.5 140.4 20.3 28.8 131.5 20.3 27.3 115.2 22.8 27.4 138.7 21.7 34.5 148.7 25.0 34.1 25632-09 158.4 31.0 32.7 147.2 24.3 28.0 102.1 26.1 21.4 129.9 21.2 31.7 174.8 19.9 40.5 142.5 24.5 30.9 25633-13 212.7 37.1 49.8 153.5 27.9 40.0 150.6 26.5 38.5 137.3 21.8 37.6 145.1 36.2 41.1 159.8 29.9 41.4 25618-17 292.4 24.6 63.4 199.5 23.7 46.2 156.8 23.7 31.8 246.7 22.2 52.6 260.5 20.8 54.6 231.2 23.0 49.7 25621-10 331.8 19.9 67.9 304.8 19.6 60.5 293.1 20.0 58.0 241.0 21.0 48.8 123.4 36.5 20.8 258.8 23.4 51.2 25687-15 167.6 21.5 32.4 150.8 22.7 28.5 101.5 26.0 18.3 92.9 25.6 18.9 98.4 21.4 20.1 122.2 23.4 23.6 25681-10 205.0 19.7 46.3 218.0 19.4 52.4 204.9 19.7 47.9 69.7 25.8 17.8 100.4 20.8 18.7 159.6 21.1 36.6 25615-10 272.5 25.9 66.4 278.1 23.1 64.7 306.1 23.3 69.6 332.7 21.0 77.5 204.9 22.0 49.9 278.9 23.1 65.6 25637-17 126.1 34.4 28.5 103.8 22.5 20.9 113.4 21.0 25.2 192.5 20.3 53.5 72.0 25.8 18.7 121.6 24.8 29.4 25638-18 63.1 33.0 11.0 71.4 24.2 15.0 83.4 21.9 14.8 127.7 20.1 25.2 144.4 19.1 29.2 98.0 23.7 19.0 25713-16 188.5 19.6 42.5 161.9 19.3 37.2 167.3 21.0 43.9 159.3 22.0 44.6 73.7 30.6 21.6 150.1 22.5 38.0 25670-18 113.4 37.0 28.9 138.0 27.8 24.7 184.8 19.5 25.5 128.2 20.9 21.4 116.7 23.3 20.3 136.2 25.7 24.2 25657-10 240.1 22.0 53.7 69.2 25.8 13.5 75.0 28.0 16.8 163.0 22.8 34.2 169.2 19.7 31.7 143.3 23.7 30.0 25663-09 79.7 28.5 15.0 107.6 21.7 20.6 73.6 22.6 17.1 83.7 26.2 20.4 152.3 20.9 32.1 99.4 24.0 21.0 25690-19 125.8 21.7 24.7 132.8 22.4 26.3 101.5 23.0 21.2 142.5 21.0 32.9 87.9 26.9 20.7 118.1 23.0 25.2 25666-09 244.0 26.1 56.9 245.6 24.4 54.4 216.1 26.3 50.9 210.1 21.2 50.1 189.6 22.8 49.6 221.1 24.2 52.4 25692-07 204.4 23.0 49.3 205.3 20.2 47.2 230.4 20.1 52.0 188.4 21.2 44.3 118.4 21.9 31.2 189.4 21.3 44.8 25701-18 256.4 21.8 54.8 261.1 20.2 55.4 297.1 21.8 65.0 296.4 20.1 58.4 224.1 20.6 49.4 267.0 20.9 56.6 25645-08 346.4 23.8 79.7 310.7 23.6 70.7 117.8 21.7 27.8 143.1 24.3 35.4 216.4 22.7 49.1 226.9 23.2 52.5 -1057- MEAN 200.8 S.D. 77.89 N 20 26.5 44.5 6.62 18.30 178.3 72.32 22.7 38.3 2.61 17.13 163.3 74.00 22.6 35.0 2.69 17.04 168.5 68.86 22.0 38.3 2.00 15.43 147.4 52.11 23.7 33.1 5.11 12.35 171.7 56.34 23.5 37.8 2.12 13.32 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 FEMALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 20 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 193.4 20.5 44.7 165.2 20.6 33.2 62.1 27.2 11.3 93.3 26.9 21.4 93.0 28.9 23.1 121.4 24.8 26.7 25674-11 258.6 23.2 54.2 166.7 28.2 38.6 164.8 22.2 32.4 153.6 20.7 33.9 191.1 21.7 44.3 187.0 23.2 40.7 25694-13 204.3 28.9 43.6 134.6 21.0 26.8 176.4 21.1 36.4 48.7 27.5 10.1 83.5 24.1 20.0 129.5 24.5 27.4 25631-05 256.4 24.6 58.1 344.4 20.6 74.4 287.6 20.8 67.0 154.8 26.2 35.1 137.0 28.1 34.7 236.0 24.1 53.9 25660-04 287.3 20.8 64.0 285.2 25.2 63.3 145.0 25.6 32.2 262.7 19.4 55.9 273.3 19.1 60.2 250.7 22.0 55.1 25704-09 178.8 31.4 39.6 103.3 26.4 21.3 136.2 20.1 25.9 141.3 20.0 27.8 124.2 21.8 29.6 136.8 23.9 28.8 25665-07 156.6 29.9 32.6 185.2 22.0 37.4 114.7 21.6 22.7 149.0 25.2 31.0 154.3 23.5 35.7 152.0 24.4 31.9 25652-13 171.0 24.0 34.5 187.8 26.6 34.9 293.5 20.5 47.7 257.8 20.1 50.8 321.8 19.8 59.1 246.4 22.2 45.4 25733-08 89.2 31.2 21.1 126.8 23.0 27.7 170.3 20.2 37.1 199.5 19.9 42.8 181.0 20.0 43.1 153.4 22.9 34.4 25748-08 200.4 19.6 47.5 146.9 19.6 32.4 177.8 19.9 39.5 166.9 19.9 36.9 195.7 20.0 46.6 177.5 19.8 40.6 25753-15 188.0 24.4 37.4 133.8 21.7 27.1 59.1 23.9 10.7 86.5 30.9 18.3 77.4 23.3 15.4 109.0 24.8 21.8 25672-15 98.6 27.7 17.3 120.5 23.9 22.6 99.3 29.7 19.2 125.8 27.3 22.6 57.5 31.3 11.9 100.3 28.0 18.7 25655-13 256.1 24.1 46.9 83.0 22.8 14.8 90.0 32.5 16.6 83.4 28.3 15.4 157.8 22.9 32.5 134.1 26.1 25.2 25727-16 142.1 27.2 35.4 217.2 27.1 44.7 121.0 21.8 28.0 101.7 23.9 24.0 79.4 27.7 17.7 132.3 25.5 30.0 25626-12 113.5 31.0 26.2 111.8 23.3 27.3 70.4 23.9 15.7 136.7 24.0 26.2 103.5 24.4 21.4 107.2 25.3 23.4 25749-11 157.1 30.4 34.5 105.4 29.6 20.2 86.8 32.7 20.1 81.6 26.9 17.5 44.6 25.6 10.3 95.1 29.0 20.5 25739-12 257.8 26.2 75.6 236.7 20.9 70.3 246.6 21.5 73.8 220.1 21.8 59.9 143.2 23.3 40.1 220.9 22.7 63.9 25756-13 214.5 21.3 42.8 117.3 27.2 25.2 85.3 21.3 15.5 87.6 30.3 20.5 106.4 21.8 21.9 122.2 24.4 25.2 25741-09 102.9 31.3 20.3 89.9 24.1 17.6 114.7 21.2 26.8 110.3 24.0 26.6 100.4 26.6 26.5 103.6 25.4 23.6 25752-13 188.9 25.2 47.5 200.9 22.8 45.0 201.6 23.3 50.5 193.4 21.1 38.4 183.6 19.6 41.8 193.7 22.4 44.6 -1058- MEAN 185.8 S.D. 58.51 N 20 26.1 41.2 3.95 14.76 163.1 67.72 23.8 35.2 2.87 16.91 145.2 70.10 23.6 31.5 3.99 17.45 142.7 59.87 24.2 30.8 3.71 13.57 140.4 70.27 23.7 31.8 3.45 14.56 155.4 50.89 24.3 34.1 2.09 12.88 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 FEMALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 20 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 331.9 20.7 65.4 282.9 20.8 67.3 264.9 20.6 63.3 130.2 25.2 30.4 269.6 21.0 59.1 255.9 21.7 57.1 25614-17 111.3 26.6 22.5 95.5 22.4 19.3 97.3 20.0 20.7 99.0 20.0 22.0 98.1 19.9 21.8 100.2 21.8 21.3 25698-12 134.5 27.8 28.0 127.0 22.2 28.9 99.8 23.7 21.1 156.9 19.6 31.7 183.9 19.7 41.1 140.4 22.6 30.2 25677-08 151.3 31.3 32.8 227.1 20.4 38.4 163.6 25.2 31.1 36.1 27.0 8.5 59.5 37.2 15.9 127.5 28.2 25.3 25604-12 108.0 27.3 23.3 92.6 22.4 18.5 117.7 31.9 23.4 112.9 26.0 21.1 128.6 20.7 26.0 112.0 25.7 22.5 25678-11 176.9 22.3 39.3 206.8 20.0 47.9 146.5 23.1 36.1 186.3 20.5 47.8 129.0 20.9 34.5 169.1 21.4 41.1 25609-11 186.8 18.9 30.9 201.0 18.8 38.4 185.6 18.9 40.4 202.6 18.9 43.3 169.2 19.1 40.5 189.0 18.9 38.7 25623-15 149.6 34.1 32.6 159.3 22.7 38.5 175.1 21.4 38.8 153.3 23.5 31.4 200.7 24.5 38.5 167.6 25.2 36.0 25653-13 65.6 34.1 14.1 85.0 23.1 14.5 99.9 19.1 18.7 103.2 23.2 17.0 97.6 19.9 20.7 90.3 23.9 17.0 25684-06 233.8 21.7 46.5 227.0 27.6 46.6 336.3 22.5 72.3 275.0 20.1 65.4 153.9 23.4 38.9 245.2 23.1 53.9 25714-13 139.2 23.7 28.6 176.0 23.4 33.3 210.5 19.3 40.0 276.9 19.6 55.6 269.4 21.0 62.5 214.4 21.4 44.0 25650-17 300.2 20.6 67.7 315.7 19.9 70.6 314.0 20.0 72.2 316.6 20.2 70.1 122.2 23.2 34.7 273.7 20.8 63.1 25735-08 150.5 26.7 30.7 150.0 23.7 31.7 183.0 20.4 39.3 197.5 20.4 42.7 32.4 23.4 7.7 142.7 22.9 30.4 25722-15 94.4 31.8 24.5 71.7 29.6 14.8 57.5 37.9 10.6 56.3 27.4 13.5 82.3 25.5 16.4 72.4 30.4 16.0 25628-17 113.8 21.1 26.3 151.2 19.9 29.2 156.3 20.2 32.1 162.0 19.9 39.4 74.5 28.6 16.7 131.6 21.9 28.7 25766-06 122.2 22.4 26.6 83.6 23.7 22.6 117.4 20.4 34.7 97.0 26.7 26.7 64.8 26.3 18.4 97.0 23.9 25.8 25689-14 134.1 21.2 31.4 129.0 19.9 30.5 133.5 19.4 33.0 127.1 21.2 30.7 53.7 31.9 15.0 115.5 22.7 28.1 25708-15 225.7 20.3 43.5 153.2 21.8 33.8 111.9 30.4 25.1 79.4 20.4 13.9 55.7 26.4 9.9 125.2 23.9 25.2 25743-16 140.7 23.0 30.6 149.9 20.2 32.8 155.4 21.4 37.4 163.4 21.8 43.5 163.3 26.8 43.3 154.5 22.6 37.5 25642-12 320.3 22.5 66.4 111.3 23.3 20.6 140.5 20.6 26.4 118.1 23.6 27.1 127.1 28.8 24.5 163.5 23.8 33.0 -1059- MEAN 169.5 S.D. 75.43 N 20 24.9 35.6 4.78 15.13 159.8 66.95 22.3 33.9 2.65 15.29 163.3 71.98 22.8 35.8 5.00 16.62 152.5 73.89 22.3 34.1 2.83 16.92 126.8 67.83 24.4 29.3 4.67 15.42 154.4 56.60 23.3 33.7 2.58 12.94 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 FEMALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 20 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 86.9 27.6 19.0 48.6 25.5 9.6 78.3 26.1 15.3 43.7 25.6 7.7 123.6 19.4 23.4 76.2 24.8 15.0 25686-10 117.3 33.5 28.3 91.1 26.9 18.5 111.1 21.0 19.4 78.0 22.3 14.7 114.6 21.2 21.5 102.4 25.0 20.5 25630-09 145.7 28.4 31.9 106.9 23.8 21.2 109.8 20.6 22.9 125.3 21.7 26.6 108.4 25.4 23.8 119.2 24.0 25.3 25673-10 105.8 28.2 24.3 44.2 38.1 9.7 119.4 22.5 28.9 160.1 20.2 39.3 176.3 20.6 45.5 121.2 25.9 29.5 25639-04 109.4 27.1 21.9 32.6 35.1 6.9 39.4 38.4 6.7 52.3 36.8 9.8 60.0 32.4 10.9 58.7 34.0 11.2 25658-14 149.1 21.8 32.2 73.6 23.4 16.6 79.3 32.6 15.5 64.8 25.2 13.7 195.1 22.7 41.0 112.4 25.1 23.8 25676-15 254.3 37.0 49.7 207.3 20.7 43.0 155.5 28.5 34.1 193.8 20.2 37.7 99.1 25.0 21.4 182.0 26.3 37.2 25600-15 164.3 27.8 40.8 199.0 25.4 50.5 160.4 19.2 34.4 167.1 19.5 45.0 180.1 20.7 49.0 174.2 22.5 43.9 25603-10 188.5 27.0 42.6 153.8 25.6 37.2 73.9 21.5 14.0 94.3 24.5 23.1 83.7 30.9 17.3 118.8 25.9 26.8 25703-10 77.6 29.0 14.0 113.8 20.9 20.0 98.5 21.7 18.8 27.8 27.3 4.2 25.5 27.6 4.6 68.6 25.3 12.3 25705-08 133.9 31.6 32.4 152.3 23.4 26.0 159.1 19.3 30.2 187.2 19.5 37.0 152.3 20.4 36.2 157.0 22.8 32.4 25611-11 244.2 23.4 50.7 222.2 19.9 39.9 174.9 19.5 31.7 189.2 19.1 39.2 171.7 19.5 39.3 200.4 20.3 40.2 25619-12 101.0 30.3 28.0 87.1 27.5 24.1 57.6 28.5 16.3 52.2 27.7 12.2 57.5 27.0 12.9 71.1 28.2 18.7 25691-11 296.0 22.4 61.1 185.9 25.9 42.7 132.8 22.8 26.5 132.1 22.7 26.4 283.5 19.4 63.7 206.1 22.6 44.1 25717-15 234.3 20.2 52.0 220.4 20.0 45.2 217.5 20.0 46.8 215.4 20.4 45.3 196.6 20.4 42.4 216.8 20.2 46.3 25616-14 269.8 21.0 53.1 234.1 23.7 48.7 256.6 22.7 53.4 184.8 22.4 35.8 188.7 21.8 38.8 226.8 22.3 46.0 25715-10 255.5 22.4 54.4 188.1 20.0 39.3 61.4 24.5 12.3 93.1 30.3 24.7 108.7 28.1 28.7 141.4 25.1 31.9 25599-11 141.0 29.0 33.5 103.4 25.1 24.4 115.4 23.6 29.6 54.0 28.7 12.6 67.0 26.4 14.4 96.2 26.6 22.9 25762-11 116.2 23.5 24.0 115.2 18.8 21.0 99.6 20.0 19.6 78.9 31.4 18.9 61.4 32.8 14.0 94.3 25.3 19.5 25647-11 280.6 19.1 52.9 236.5 19.5 48.3 260.1 19.6 56.4 218.3 19.6 49.8 227.4 19.4 51.2 244.6 19.4 51.7 -1060- MEAN 173.6 S.D. 72.22 N 20 26.5 37.3 4.71 13.89 140.8 67.49 24.5 29.6 4.96 14.35 128.0 62.63 23.6 26.6 5.02 13.53 120.6 63.85 24.3 26.2 4.85 14.12 134.1 67.19 24.1 30.0 4.53 15.99 139.4 57.83 24.6 30.0 3.19 12.33 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 MALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 60 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 224.6 27.2 54.5 174.3 21.6 36.7 100.8 29.0 18.2 136.1 29.3 32.2 104.4 27.2 26.6 148.0 26.9 33.6 25654-09 414.7 31.3 112.3 351.8 23.8 72.2 180.9 23.1 37.0 225.9 31.7 48.4 221.8 32.2 52.4 279.0 28.4 64.5 25632-07 154.6 26.3 32.3 176.4 30.8 41.5 95.2 36.5 18.9 98.1 35.7 17.2 91.4 29.3 20.0 123.1 31.7 26.0 25633-05 199.5 32.4 54.5 120.6 26.6 27.7 228.4 25.7 54.4 243.7 27.0 54.0 123.5 35.5 23.8 183.1 29.4 42.9 25618-08 180.2 29.7 39.3 106.9 26.1 23.5 71.8 31.9 17.1 101.5 24.8 23.5 99.1 32.3 21.9 111.9 29.0 25.1 25621-07 115.3 29.4 22.6 110.1 37.0 18.5 179.5 29.0 34.1 101.7 33.1 17.9 40.4 45.0 9.7 109.4 34.7 20.6 25687-07 114.3 36.3 23.0 95.2 35.8 22.6 70.7 41.4 13.7 53.3 35.3 10.6 52.4 27.4 12.0 77.2 35.2 16.4 25681-01 85.4 33.6 22.0 28.4 55.0 7.5 48.8 36.3 10.9 49.5 48.4 14.1 36.8 41.8 9.7 49.8 43.0 12.8 25615-03 147.3 25.9 34.0 97.0 31.2 24.2 31.0 29.5 6.4 27.9 36.6 4.9 57.5 55.1 14.3 72.1 35.7 16.8 25637-06 164.4 26.0 38.2 58.0 31.3 12.9 152.5 31.6 34.7 32.0 40.5 8.3 25.3 42.2 5.1 86.4 34.3 19.8 25638-07 1011.6 24.1 198.9 768.6 21.0 168.9 621.6 24.3 128.3 631.6 27.1 131.2 261.9 28.1 52.9 659.1 24.9 136.0 25713-02 38.5 37.1 8.7 14.7 49.3 2.4 15.6 37.3 2.9 25.0 49.7 5.2 14.5 56.7 2.7 21.7 46.0 4.4 25670-09 60.1 46.7 12.7 51.8 45.3 13.5 100.6 29.1 20.1 62.4 27.1 10.8 52.2 25.8 8.9 65.4 34.8 13.2 25657-08 47.2 33.0 11.7 101.4 38.8 22.6 52.3 26.1 9.9 72.9 32.6 13.9 58.7 29.7 10.5 66.5 32.0 13.7 25663-04 109.4 36.0 22.2 161.2 29.6 35.1 56.9 43.4 12.2 52.4 44.0 12.4 32.2 37.7 7.1 82.4 38.1 17.8 25690-01 255.7 32.9 60.0 249.1 30.7 53.4 118.8 32.0 24.2 94.7 25.5 19.8 61.0 52.9 15.3 155.9 34.8 34.5 25666-01 83.0 45.8 16.6 114.3 31.0 22.6 36.3 25.8 7.7 29.7 40.6 6.0 65.1 26.9 13.1 65.7 34.0 13.2 25692-04 202.6 34.6 48.6 114.0 34.0 28.6 115.5 41.8 28.5 83.0 35.7 20.8 87.2 37.5 21.4 120.5 36.7 29.6 25701-09 194.2 26.6 44.0 201.2 33.9 46.2 261.1 29.5 57.3 274.2 30.3 61.9 181.1 31.3 34.7 222.4 30.3 48.8 25645-06 1123.3 25.4 200.8 799.8 21.3 146.5 1011.4 25.9 191.6 458.5 22.9 84.9 498.2 23.8 94.0 778.2 23.9 143.6 -1061- MEAN 246.3 S.D.294.08 N 20 32.0 52.8 194.7 6.30 55.42 215.91 32.7 41.4 177.5 9.10 43.10 236.83 31.5 36.4 142.7 6.08 45.93 157.72 33.9 29.9 108.2 35.9 22.8 173.9 7.68 32.11 112.74 10.06 21.78 197.06 33.2 36.7 5.52 38.06 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 MALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 60 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 581.2 22.7 123.9 379.9 26.6 76.3 179.2 31.5 35.5 272.0 25.5 49.7 494.9 20.1 84.3 381.4 25.3 73.9 25674-02 161.3 31.3 32.7 161.8 34.6 33.8 303.0 28.7 55.1 68.0 38.1 12.8 26.2 32.9 4.5 144.1 33.1 27.8 25694-04 75.5 38.6 16.7 77.0 40.1 17.8 83.0 22.6 18.8 55.5 61.2 14.1 48.7 48.4 13.8 67.9 42.2 16.2 25631-04 57.8 33.9 11.3 55.1 38.0 11.9 21.9 41.5 4.1 30.5 40.4 7.8 108.3 46.4 33.2 54.7 40.0 13.7 25660-01 380.6 24.5 78.2 286.6 27.9 60.3 261.4 28.8 56.1 282.3 28.4 59.7 178.0 29.1 36.5 277.8 27.7 58.2 25704-03 39.8 35.8 8.6 28.2 51.6 5.6 10.4 44.1 1.2 9.8 31.6 0.9 9.2 37.9 1.2 19.5 40.2 3.5 25665-01 52.3 58.3 13.9 42.1 37.1 9.3 29.1 46.3 7.6 32.5 44.8 7.2 70.1 32.9 15.1 45.2 43.9 10.6 25652-04 134.8 24.3 35.0 155.6 25.5 36.8 95.9 27.5 22.2 72.0 41.7 20.1 67.7 37.4 12.5 105.2 31.3 25.3 25733-07 73.9 41.0 21.0 67.6 45.7 15.6 63.0 40.1 12.8 58.2 36.6 14.8 51.0 31.2 11.5 62.7 38.9 15.1 25748-01 76.8 31.5 19.3 67.8 35.0 16.2 90.1 27.6 17.3 71.3 31.9 13.8 38.9 31.5 7.8 69.0 31.5 14.9 25753-06 84.1 27.9 14.5 104.2 33.7 20.0 48.5 46.1 8.7 54.3 33.6 10.5 176.3 29.4 31.2 93.5 34.1 17.0 25672-06 94.6 40.7 23.4 226.6 29.0 55.0 73.9 33.6 18.7 262.6 27.5 56.7 49.4 35.7 12.2 141.4 33.3 33.2 25655-01 207.1 24.6 45.2 133.9 22.8 28.1 224.0 24.9 51.8 275.2 23.5 59.7 252.5 22.7 52.4 218.5 23.7 47.4 25727-07 116.3 30.0 24.4 69.5 39.3 16.6 51.3 41.5 10.4 42.9 25.0 7.6 25.6 44.5 4.5 61.1 36.1 12.7 25626-04 144.9 32.5 35.1 37.9 56.5 9.4 42.2 29.2 9.6 59.4 44.5 13.1 83.8 33.9 17.3 73.6 39.3 16.9 25749-04 42.5 41.2 10.0 35.2 30.7 6.7 56.2 34.0 13.2 50.1 35.8 10.5 63.8 33.0 11.6 49.6 34.9 10.4 25739-07 78.3 42.5 20.8 118.7 30.0 25.5 91.9 29.7 27.1 56.6 42.8 15.5 88.3 39.2 21.1 86.8 36.8 22.0 25756-05 122.0 37.5 32.8 61.6 41.0 12.1 52.4 49.8 12.1 72.1 47.8 22.4 79.5 34.4 18.6 77.5 42.1 19.6 25741-07 89.2 34.1 24.2 72.3 28.2 16.5 104.4 48.9 22.1 37.4 43.0 9.0 40.4 51.4 9.1 68.7 41.1 16.2 25752-09 124.0 30.3 26.0 64.8 34.8 15.5 71.0 30.2 17.7 56.6 28.5 9.1 68.8 36.9 14.4 77.0 32.1 16.5 -1062- MEAN 136.8 S.D.129.08 N 20 34.2 30.9 8.36 26.86 112.3 91.82 35.4 24.5 8.68 19.21 97.6 80.75 35.3 21.1 8.58 16.36 96.0 92.18 36.6 20.8 101.1 9.41 18.98 110.10 35.4 20.6 7.88 19.49 108.8 88.53 35.4 23.6 5.72 17.45 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 MALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 60 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 147.7 24.4 30.2 209.6 25.7 43.5 88.9 34.0 19.6 172.5 37.0 32.9 169.4 31.5 24.6 157.6 30.5 30.2 25614-10 58.3 37.4 12.3 86.5 33.4 15.3 40.7 24.1 6.5 68.7 28.0 11.6 46.0 43.8 8.6 60.0 33.3 10.9 25698-05 156.6 34.9 29.5 65.7 38.9 15.0 70.6 34.1 13.3 223.6 25.3 48.8 207.6 24.0 49.5 144.8 31.4 31.2 25677-05 76.4 37.2 17.3 25.6 29.2 5.9 49.7 37.9 11.1 24.3 46.6 5.3 23.4 39.8 4.5 39.9 38.1 8.8 25604-04 32.2 54.1 6.8 55.8 36.4 13.8 15.9 40.7 2.2 27.8 49.3 7.0 34.5 37.1 5.1 33.2 43.5 7.0 25678-02 61.3 33.7 14.5 53.0 34.6 10.0 78.5 32.1 15.9 58.2 31.3 11.8 27.5 47.3 4.6 55.7 35.8 11.4 25609-04 185.6 21.5 36.7 103.9 28.2 20.8 150.4 21.6 30.6 95.9 23.1 19.6 101.2 25.7 19.8 127.4 24.0 25.5 25623-08 32.3 32.2 7.0 27.7 51.8 6.1 45.3 39.1 13.3 24.7 40.6 6.4 33.9 57.1 10.3 32.8 44.2 8.6 25653-02 249.9 23.6 59.5 247.4 26.9 50.5 205.1 28.6 34.7 93.3 30.4 15.3 131.0 30.2 21.2 185.3 27.9 36.2 25684-04 66.0 41.6 17.6 106.0 30.2 20.7 120.3 28.0 24.9 38.8 21.4 7.5 129.1 24.8 23.2 92.0 29.2 18.8 25714-02 206.9 25.2 43.6 191.1 24.9 37.8 146.2 23.8 30.2 119.0 26.1 24.1 81.7 42.2 18.6 149.0 28.4 30.9 25650-11 156.6 29.7 33.7 312.6 29.6 64.0 195.4 30.7 42.5 35.4 36.5 9.0 55.6 38.8 12.4 151.1 33.1 32.3 25735-05 83.4 38.0 22.5 59.0 46.7 16.6 34.8 53.9 9.3 90.8 27.2 17.9 55.1 36.2 13.0 64.6 40.4 15.9 25722-01 476.1 30.6 105.5 383.0 28.9 90.2 228.0 31.3 49.5 161.4 25.4 33.0 200.1 31.7 48.8 289.7 29.6 65.4 25642-05 314.1 28.7 70.1 415.6 23.8 77.9 379.6 23.9 70.1 212.2 23.3 39.6 362.0 21.8 71.7 336.7 24.3 65.9 25628-07 113.6 31.3 24.7 57.3 37.1 13.2 29.4 46.0 4.7 12.6 20.0 1.9 60.5 47.5 13.2 54.7 36.4 11.5 25766-01 114.2 40.3 30.2 64.1 39.7 14.6 67.1 27.7 14.9 23.5 32.3 4.9 43.1 30.2 9.2 62.4 34.0 14.8 25689-02 324.8 22.8 66.6 215.3 26.5 44.2 191.7 29.6 46.8 172.2 34.2 39.8 135.8 34.0 29.1 208.0 29.4 45.3 25708-01 178.0 35.5 38.4 221.6 27.0 45.4 186.8 26.9 39.9 102.6 28.0 20.1 271.3 27.5 49.0 192.1 29.0 38.6 25743-08 217.7 35.7 41.4 134.1 42.0 25.5 139.0 38.5 26.2 149.7 35.9 27.4 92.2 36.1 16.3 146.5 37.6 27.4 -1063- MEAN 162.6 S.D.113.35 N 20 32.9 35.4 151.7 7.78 24.49 117.82 33.1 31.6 7.70 24.36 123.2 90.15 32.6 25.3 8.15 17.76 95.4 67.05 31.1 19.2 8.04 13.70 113.0 90.60 35.4 22.6 9.12 18.35 129.2 84.79 33.0 26.8 5.73 17.42 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 MALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 60 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 203.6 29.9 45.5 97.3 21.6 18.6 90.5 30.4 19.1 45.5 34.8 9.5 56.7 31.4 12.0 98.7 29.6 20.9 25686-04 150.1 30.6 39.4 67.9 40.3 15.0 57.5 32.6 14.2 77.7 33.7 20.3 15.5 34.9 2.3 73.7 34.4 18.2 25630-04 112.1 39.2 26.3 55.0 45.7 14.1 38.0 42.6 6.2 96.9 31.9 27.1 32.7 25.8 7.4 66.9 37.0 16.2 25673-09 27.6 18.0 4.1 17.9 13.9 2.6 17.7 16.3 1.7 16.2 14.9 1.6 12.4 14.7 0.9 18.4 15.6 2.2 25639-06 383.8 27.2 65.5 317.1 20.0 50.4 291.3 24.7 50.9 245.6 36.3 40.4 269.9 34.6 46.3 301.5 28.6 50.7 25658-08 131.5 37.1 32.0 32.3 34.3 7.5 118.1 32.5 22.9 38.9 35.9 7.5 16.7 33.3 2.9 67.5 34.6 14.6 25676-02 149.0 29.4 35.3 219.5 26.0 50.5 61.5 27.1 12.8 147.6 28.5 34.2 175.2 30.5 33.8 150.6 28.3 33.3 25600-02 83.0 32.7 18.7 62.7 47.9 14.9 46.2 37.8 8.1 24.9 39.8 4.5 29.6 29.8 5.1 49.3 37.6 10.3 25603-04 103.3 31.2 23.7 68.0 40.8 14.4 39.3 43.1 9.0 37.4 46.1 9.8 95.5 31.0 20.4 68.7 38.4 15.5 25703-03 55.3 36.0 14.1 48.3 46.5 10.9 60.5 27.2 15.0 21.1 38.2 4.2 56.6 42.6 10.6 48.4 38.1 11.0 25705-07 176.0 30.3 31.0 57.1 33.0 12.6 123.6 38.2 30.4 83.9 37.1 18.8 126.8 28.4 23.7 113.5 33.4 23.3 25611-07 267.4 30.0 63.8 355.6 28.7 79.8 179.2 28.3 42.1 136.3 29.0 30.0 33.3 36.9 5.9 194.4 30.6 44.3 25619-04 19.3 42.8 4.4 15.3 57.3 2.4 14.1 52.1 2.2 10.9 60.6 1.6 30.8 59.2 7.7 18.1 54.4 3.7 25691-07 194.3 27.0 32.8 188.4 25.1 38.0 128.4 39.4 22.8 143.0 24.0 26.1 167.8 28.1 29.2 164.4 28.7 29.8 25717-04 81.1 34.3 19.2 115.2 32.4 23.2 40.8 41.7 6.8 35.5 40.0 6.7 55.1 36.2 12.5 65.5 36.9 13.7 25616-05 187.4 27.9 35.3 112.9 35.2 22.3 99.6 37.2 20.4 39.8 36.2 7.5 11.4 25.1 1.8 90.2 32.3 17.5 25715-07 237.9 28.1 46.3 162.6 27.9 31.0 42.5 50.9 11.1 110.3 41.7 22.0 25.7 48.5 6.7 115.8 39.4 23.4 25599-06 51.0 44.6 11.6 38.0 31.8 7.3 21.5 47.5 4.6 50.0 48.4 13.8 18.6 42.4 3.8 35.8 42.9 8.2 25762-01 104.7 37.3 21.4 46.0 39.4 7.9 24.6 53.5 4.2 30.2 41.6 5.1 50.3 38.9 11.1 51.2 42.1 9.9 25647-07 273.6 26.0 48.8 93.1 31.8 19.7 99.8 34.4 21.9 327.5 28.8 65.3 135.9 30.9 27.6 186.0 30.4 36.7 -1064- MEAN 149.6 S.D. 93.03 N 20 32.0 31.0 6.22 17.31 108.5 34.0 22.2 95.35 10.57 19.37 79.7 66.70 36.9 16.3 9.84 13.09 86.0 82.05 36.4 17.8 9.54 16.05 70.8 69.90 34.2 13.6 9.37 12.51 98.9 70.43 34.7 20.2 7.70 13.02 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 FEMALE GROUP: 0 MG/KG/DAY TEST PERIOD: PND 60 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 159.3 28.9 35.5 143.4 27.9 28.9 87.5 37.5 14.8 82.8 35.4 16.0 118.8 31.6 24.2 118.4 32.3 23.9 25654-10 146.7 30.5 32.0 158.5 39.7 32.6 87.5 28.3 16.8 57.9 31.1 10.5 41.1 36.2 5.9 98.3 33.2 19.6 25632-09 105.6 41.8 19.4 47.9 29.3 8.8 66.4 30.3 14.7 43.0 32.2 8.0 68.2 34.3 14.5 66.2 33.6 13.1 25633-13 103.2 28.3 19.8 82.2 28.9 17.2 62.9 37.4 12.4 137.5 25.6 26.4 84.2 28.5 15.6 94.0 29.7 18.3 25618-17 221.1 27.8 52.5 230.1 26.3 44.8 105.2 35.5 17.7 22.2 40.7 3.3 101.9 32.0 17.7 136.1 32.5 27.2 25621-10 56.4 35.5 11.9 23.4 35.2 4.2 19.6 33.9 3.1 21.3 41.1 3.3 61.5 36.7 12.0 36.4 36.5 6.9 25687-15 96.6 37.5 18.8 36.2 30.7 8.9 51.5 40.7 12.5 59.5 38.2 14.2 39.9 31.7 9.1 56.7 35.8 12.7 25681-10 179.7 35.1 34.1 40.2 34.2 7.3 28.6 32.0 4.8 56.7 25.7 10.4 38.0 31.7 6.0 68.6 31.7 12.5 25615-10 101.6 29.6 18.4 44.2 35.2 8.5 33.3 38.4 5.4 26.3 40.4 4.3 36.1 39.0 8.2 48.3 36.5 9.0 25637-17 78.4 24.5 13.0 58.2 25.9 11.1 105.7 33.5 17.0 43.2 25.5 9.2 46.7 37.5 9.9 66.4 29.4 12.0 25638-18 93.0 33.9 16.6 32.0 31.5 8.8 31.8 40.5 4.8 58.1 30.6 9.6 17.0 44.7 3.3 46.4 36.2 8.6 25713-16 35.4 41.8 7.9 64.1 46.5 14.6 31.9 41.9 8.8 25.7 29.5 5.4 18.0 38.9 3.6 35.0 39.7 8.1 25670-18 130.3 29.1 32.3 75.5 46.9 17.3 56.8 43.3 13.1 23.1 48.8 4.7 32.8 37.9 6.8 63.7 41.2 14.8 25657-10 42.6 31.3 10.2 32.4 40.2 6.0 29.9 45.5 7.1 24.4 50.8 4.8 21.2 49.3 5.5 30.1 43.4 6.7 25663-09 32.8 32.6 4.6 16.3 39.3 1.9 12.1 40.4 1.6 41.3 26.9 5.5 30.3 29.4 4.0 26.6 33.7 3.5 25690-19 79.0 26.5 20.7 73.4 46.3 20.2 71.2 45.2 18.6 48.4 35.5 12.2 35.7 42.2 6.7 61.5 39.1 15.7 25666-09 115.1 29.8 23.5 56.8 37.1 13.5 36.8 37.8 7.0 44.6 45.3 10.8 46.2 27.5 9.5 59.9 35.5 12.9 25692-07 121.5 34.5 25.9 44.3 34.8 7.5 71.4 31.3 14.1 49.4 42.8 9.8 72.3 41.8 15.4 71.8 37.0 14.5 25701-18 154.0 30.5 32.7 55.4 32.7 12.2 87.1 37.5 19.3 71.9 37.9 18.2 53.2 43.3 11.9 84.3 36.4 18.9 25645-08 286.7 22.9 55.1 147.8 26.9 24.5 111.8 31.0 16.6 87.5 27.8 16.0 86.7 26.1 14.1 144.1 26.9 25.3 -1065- MEAN 117.0 S.D. 62.93 N 20 31.6 24.2 5.06 13.54 73.1 54.88 34.8 14.9 6.70 10.72 59.4 30.86 37.1 5.04 11.5 5.66 51.2 28.27 35.6 7.86 10.1 5.87 52.5 28.25 36.0 6.27 10.2 5.46 70.6 33.29 35.0 4.09 14.2 6.44 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 FEMALE GROUP: 0.1 MG/KG/DAY TEST PERIOD: PND 60 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 70.0 32.3 13.5 98.8 27.8 18.2 68.8 25.2 12.2 46.9 34.5 8.6 51.5 43.7 8.9 67.2 32.7 12.3 25674-11 126.9 27.5 29.3 51.6 29.5 11.1 49.9 32.5 9.6 56.7 24.2 12.9 96.0 29.5 18.4 76.2 28.6 16.3 25694-13 87.8 34.6 19.1 92.9 30.4 22.9 63.8 43.2 15.2 50.2 38.8 9.0 71.7 28.7 15.7 73.3 35.1 16.4 25631-05 65.0 26.7 10.3 45.2 30.0 8.4 32.4 39.7 5.9 32.9 46.2 7.7 50.5 35.0 9.4 45.2 35.5 8.3 25660-04 88.9 39.9 16.9 60.3 26.8 10.7 78.6 27.1 13.8 52.1 39.0 9.1 32.5 45.5 5.0 62.5 35.7 11.1 25704-09 17.8 49.3 3.2 24.8 35.4 4.1 38.5 42.7 7.4 16.0 42.0 3.0 24.4 35.4 5.3 24.3 41.0 4.6 25665-07 51.1 51.0 11.7 56.9 37.1 10.8 49.7 34.0 8.0 27.5 38.8 5.9 23.3 32.2 3.7 41.7 38.6 8.0 25652-13 102.3 24.6 20.8 74.0 32.7 13.2 103.3 42.8 19.6 38.3 47.7 8.2 94.9 44.0 17.7 82.6 38.4 15.9 25733-08 95.9 32.5 18.7 67.9 34.1 14.7 31.2 30.4 5.6 18.5 32.7 3.1 14.7 38.8 2.0 45.6 33.7 8.8 25748-08 73.9 39.7 16.0 64.5 46.8 12.8 78.4 25.2 12.8 33.0 30.3 5.3 94.9 33.3 20.1 68.9 35.1 13.4 25753-15 84.9 37.0 18.5 29.3 40.0 5.9 29.5 30.9 5.9 65.6 46.5 12.1 27.8 32.7 4.4 47.4 37.4 9.4 25672-15 53.4 30.9 11.2 24.1 43.7 3.9 13.3 41.2 1.8 26.2 38.7 4.8 36.3 41.9 7.6 30.7 39.3 5.9 25655-13 75.8 38.7 16.9 33.9 43.4 7.3 78.1 33.6 16.3 71.4 29.5 10.6 20.9 58.9 4.5 56.0 40.8 11.1 25727-16 150.3 34.5 29.1 53.1 34.6 11.2 29.9 31.5 5.2 11.6 37.0 1.4 47.5 29.2 8.7 58.5 33.4 11.1 25626-12 76.2 43.1 12.4 41.0 45.3 8.7 18.3 42.5 2.3 44.3 39.8 8.0 14.3 42.0 2.3 38.8 42.5 6.7 25749-11 89.9 30.4 17.6 45.0 39.1 9.6 30.5 32.1 5.6 30.1 33.4 4.9 52.9 38.9 12.5 49.7 34.8 10.0 25739-12 61.8 29.0 13.3 59.8 37.9 12.4 20.2 30.0 4.0 32.0 45.7 6.3 51.5 35.2 9.9 45.1 35.6 9.2 25756-13 105.0 30.5 20.3 97.4 34.4 19.7 102.1 27.2 17.3 69.9 26.8 15.8 109.7 30.4 19.0 96.8 29.9 18.4 25741-09 74.1 23.3 15.7 57.7 34.5 11.7 22.6 27.9 5.5 45.0 49.0 9.1 28.6 33.6 6.7 45.6 33.7 9.7 25752-13 122.4 28.6 25.4 134.6 31.9 21.7 187.4 24.3 31.9 169.0 25.1 30.5 136.6 28.9 26.6 150.0 27.8 27.2 -1066- MEAN 83.7 S.D. 29.45 N 20 34.2 7.60 17.0 6.28 60.6 28.02 35.8 5.83 11.9 5.34 56.3 41.41 33.2 6.54 10.3 7.28 46.9 33.49 37.3 7.62 8.8 6.21 54.0 35.21 36.9 7.52 10.4 6.94 60.3 27.72 35.5 3.99 11.7 5.19 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 FEMALE GROUP: 0.3 MG/KG/DAY TEST PERIOD: PND 60 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 105.3 32.9 23.7 88.6 40.9 19.1 103.2 25.4 22.1 56.6 37.0 11.8 49.3 45.9 10.7 80.6 36.4 17.5 25614-17 23.0 60.8 4.4 10.2 45.1 1.3 12.8 39.6 1.9 11.2 61.2 1.3 8.3 43.1 1.3 13.1 50.0 2.0 25698-12 66.2 40.6 18.6 66.2 37.5 18.1 43.6 34.1 10.1 60.4 31.6 12.3 71.9 32.4 19.0 61.7 35.2 15.6 25677-08 130.1 31.7 28.4 75.7 36.6 18.3 58.6 36.7 11.5 80.9 36.7 19.5 157.4 32.0 29.4 100.5 34.7 21.4 25604-12 22.0 38.3 3.1 21.9 37.9 5.9 17.2 47.2 2.9 8.2 44.5 1.0 6.2 49.8 0.9 15.1 43.5 2.8 25678-11 90.9 31.3 24.1 51.0 45.8 13.0 130.2 23.9 32.8 57.0 28.4 11.2 46.2 31.1 10.0 75.1 32.1 18.2 25609-11 52.1 24.2 7.5 61.1 40.0 8.5 8.2 37.5 1.5 25.9 41.5 6.1 16.1 43.5 2.7 32.7 37.3 5.3 25623-15 135.8 32.9 30.7 141.7 37.9 23.0 46.8 27.4 9.0 54.4 36.5 13.7 98.5 29.3 22.1 95.4 32.8 19.7 25653-13 29.2 34.7 6.8 53.0 45.0 12.0 53.1 39.8 10.0 43.5 38.6 8.8 17.5 61.1 3.7 39.3 43.8 8.3 25684-06 76.9 34.6 11.4 91.8 29.0 17.3 91.3 36.0 14.9 105.8 26.6 19.2 186.6 23.2 32.2 110.5 29.9 19.0 25714-13 234.4 35.5 49.7 76.7 27.7 15.2 61.9 30.0 10.4 100.6 28.2 18.4 110.7 29.2 20.5 116.9 30.1 22.8 25650-17 131.3 38.8 29.0 51.2 40.0 9.6 95.3 32.8 19.8 76.6 31.5 14.9 33.6 41.1 8.0 77.6 36.8 16.3 25735-08 67.0 33.9 14.2 42.0 44.3 9.5 38.6 32.3 9.5 35.5 43.8 6.8 51.6 49.2 9.4 46.9 40.7 9.9 25722-15 63.2 25.1 10.9 86.2 26.7 16.1 34.4 39.7 6.7 15.5 34.8 3.6 76.9 30.8 16.7 55.2 31.4 10.8 25628-17 88.9 33.7 16.0 42.7 43.4 9.4 47.3 41.1 11.8 44.8 43.5 9.2 25.4 50.7 5.2 49.8 42.5 10.3 25766-06 42.4 38.6 7.6 34.4 37.0 6.6 25.1 43.0 5.6 17.0 38.3 2.8 27.0 32.5 5.0 29.2 37.9 5.5 25689-14 98.6 39.7 24.1 96.6 24.0 19.6 84.1 23.7 16.2 121.7 23.8 30.1 100.6 26.6 20.9 100.3 27.6 22.2 25708-15 170.0 26.4 27.8 69.6 24.5 12.1 52.1 35.6 9.9 72.5 29.8 13.2 58.0 35.7 10.8 84.4 30.4 14.8 25743-16 119.8 28.1 23.5 165.2 27.2 27.5 36.5 25.1 5.4 78.9 29.8 14.5 105.8 23.9 20.0 101.2 26.8 18.2 25642-12 111.8 35.9 22.4 67.9 35.0 16.1 81.5 40.0 17.4 94.3 35.2 23.7 51.8 37.6 9.4 81.5 36.7 17.8 -1067- MEAN 92.9 S.D. 52.65 N 20 34.9 19.2 7.72 11.43 69.7 36.89 36.3 7.28 13.9 6.32 56.1 32.53 34.5 6.82 11.5 7.55 58.1 33.32 36.1 8.41 12.1 7.62 65.0 37.4 49.19 10.22 12.9 9.20 68.4 31.85 35.8 6.03 13.9 6.57 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 29 (F1) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION INDIVIDUAL STARTLE RESPONSE DATA SPONSOR NO.:06-128 FEMALE GROUP: 1.0 MG/KG/DAY TEST PERIOD: PND 60 TRIALS 1 - 10 TRIALS 11 - 20 TRIALS 21 - 30 TRIALS 31 - 40 TRIALS 41 - 50 ALL TRIALS ANIMAL Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave Vmax Tmax Vave ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 26.2 31.9 3.7 9.3 8.7 0.2 17.6 17.0 1.4 17.8 17.9 1.7 12.4 13.4 0.8 16.7 17.8 1.6 25686-10 32.2 32.4 6.2 30.6 28.4 4.7 25.4 33.2 4.8 45.4 40.1 10.6 22.7 51.1 4.5 31.3 37.0 6.2 25630-09 38.9 33.0 7.0 16.3 32.8 3.2 16.4 38.5 3.2 26.1 28.5 4.2 21.3 39.4 2.6 23.8 34.4 4.0 25673-10 72.2 42.0 10.2 40.1 42.1 8.8 36.4 43.2 9.7 22.8 50.7 4.3 23.1 41.0 4.6 38.9 43.8 7.5 25639-04 42.2 38.6 9.4 42.9 39.0 7.6 50.0 37.0 7.7 27.0 46.8 6.7 38.0 30.0 7.0 40.0 38.3 7.7 25658-14 58.7 37.1 13.6 46.1 31.3 10.1 45.7 47.9 11.6 55.7 33.4 13.9 56.5 38.0 13.0 52.5 37.5 12.4 25676-15 114.0 35.4 26.7 126.2 39.1 27.5 81.2 39.7 13.5 104.7 31.2 22.9 63.5 33.7 15.8 97.9 35.8 21.3 25600-15 91.3 35.4 17.8 59.3 36.0 11.3 38.9 32.5 6.4 46.2 31.4 6.4 37.2 30.1 6.1 54.6 33.1 9.6 25603-10 85.0 28.6 15.9 30.6 49.5 7.1 23.7 48.4 3.6 28.5 47.3 5.5 58.9 38.6 12.2 45.3 42.5 8.9 25703-10 20.4 53.8 4.6 23.1 34.3 6.5 36.6 47.2 5.8 45.1 47.7 9.8 33.3 34.8 9.0 31.7 43.6 7.1 25705-08 85.5 33.6 17.9 88.7 28.9 18.1 123.8 31.3 24.6 97.4 30.8 16.7 64.9 33.1 14.5 92.1 31.5 18.4 25611-11 45.0 38.3 12.0 52.7 32.6 14.0 75.6 29.2 15.6 37.3 38.8 7.6 39.8 35.2 8.0 50.1 34.8 11.4 25619-12 60.0 40.7 14.8 44.8 33.0 10.3 26.7 32.1 5.2 46.6 36.4 10.1 25.7 52.7 8.4 40.8 39.0 9.8 25691-11 218.6 24.6 45.7 242.6 24.3 50.6 108.2 33.6 22.2 120.8 24.0 27.7 159.2 24.9 40.1 169.9 26.3 37.3 25717-15 41.3 45.3 10.2 44.6 35.3 6.9 24.6 26.8 2.8 9.0 28.6 1.1 20.4 44.7 5.4 28.0 36.1 5.3 25616-14 262.4 28.8 48.2 75.9 34.2 15.2 102.5 27.0 17.9 78.2 31.1 14.7 108.6 36.0 17.9 125.5 31.4 22.8 25715-10 40.8 31.8 8.5 21.5 44.2 3.7 12.7 32.3 1.8 12.7 52.3 1.9 10.0 43.8 1.4 19.5 40.9 3.5 25599-11 74.1 41.8 18.2 31.3 37.2 6.8 23.2 44.5 4.4 14.9 48.7 2.1 18.0 45.7 3.2 32.3 43.6 6.9 25762-11 43.0 30.2 8.4 27.5 33.9 5.7 31.9 42.7 5.0 29.3 23.7 6.3 67.2 31.6 14.4 39.8 32.4 8.0 25647-11 58.9 37.8 8.8 7.4 43.3 0.6 33.6 31.4 6.3 179.4 23.7 28.5 242.8 21.0 42.0 104.4 31.4 17.2 -1068- MEAN 75.5 S.D. 61.68 N 20 36.1 15.4 6.67 12.13 53.1 52.79 34.4 10.9 8.47 11.27 46.7 33.15 35.8 8.21 8.7 6.77 52.2 35.7 43.54 10.35 10.1 8.30 56.2 56.70 35.9 11.5 9.60 11.25 56.8 40.30 35.6 6.36 11.3 8.43 ----------------------------------------------------------------------------------------------------------------------------------Units= Vmax(millivolts), Tmax(milliseconds), Vave(millivolts) ----------------------------------------------------------------------------------------------------------------------------------- PSRSUMv5.12 10/12/2006 APPENDIX 30 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 1: 0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TRIAL NO. 1 TRIAL NO. 2 TRIAL NO. 3 TRIAL NO. 4 OVERALL PUP TIME TIME TIME TIME MEAN NO. (SEC) (SEC) (SEC) (SEC) (SEC) ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 8.97 8.96 10.46 6.15 8.64 25654-09 18.50 5.77 9.06 5.22 9.64 25632-07 12.36 9.94 9.15 9.14 10.15 25633-05 12.22 7.23 12.84 8.16 10.11 25618-08 7.43 3.70 5.95 4.44 5.38 25621-07 11.33 4.43 4.16 7.41 6.83 25687-07 10.11 6.43 4.60 7.64 7.20 25681-01 6.34 4.02 4.81 4.04 4.80 25615-03 14.07 5.81 4.95 4.28 7.28 25637-06 20.55 7.48 5.34 4.41 9.45 25638-07 39.02 8.94 5.15 7.13 15.06 25713-02 5.96 4.13 7.29 4.56 5.49 25670-09 5.54 6.34 5.61 6.23 5.93 25657-08 30.38 5.22 4.71 4.89 11.30 25663-04 15.11 7.45 7.45 6.11 9.03 25690-01 11.89 4.73 9.63 5.11 7.84 25666-01 14.03 9.30 9.34 6.15 9.71 25692-04 10.19 8.10 16.31 6.77 10.34 25701-09 16.57 12.99 6.02 7.18 10.69 25645-06 12.41 5.91 5.51 6.58 7.60 -1069- MEAN 14.15 6.84 7.42 6.08 8.62 S.D. 8.201 2.367 3.173 1.437 2.453 N 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 30 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 2: 0.1 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TRIAL NO. 1 TRIAL NO. 2 TRIAL NO. 3 TRIAL NO. 4 OVERALL PUP TIME TIME TIME TIME MEAN NO. (SEC) (SEC) (SEC) (SEC) (SEC) ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 9.19 5.74 8.70 15.70 9.83 25674-02 24.02 4.59 5.06 4.70 9.59 25694-04 26.73 9.06 6.41 4.82 11.76 25631-04 17.54 5.89 4.81 6.08 8.58 25660-01 24.01 8.46 9.02 6.99 12.12 25704-03 17.63 6.38 5.43 4.30 8.44 25665-01 14.94 10.41 5.96 10.35 10.42 25652-04 9.57 5.74 5.87 6.27 6.86 25733-07 15.13 6.27 5.07 5.44 7.98 25748-01 9.39 6.47 5.30 4.50 6.42 25753-06 12.71 5.72 5.45 4.27 7.04 25672-06 11.00 22.63 6.17 5.65 11.36 25655-01 6.37 6.09 5.72 6.57 6.19 25727-07 16.15 5.43 6.19 4.86 8.16 25626-04 7.92 4.45 5.40 3.99 5.44 25749-04 39.02 11.57 7.42 6.39 16.10 25739-07 15.81 4.58 4.16 5.70 7.56 25756-05 21.28 14.20 7.02 15.61 14.53 25741-07 8.45 9.97 7.87 6.02 8.08 25752-09 8.07 5.10 4.31 4.51 5.50 -1070- MEAN 15.75 7.94 6.07 6.64 9.10 S.D. 8.118 4.344 1.339 3.388 2.901 N 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 30 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 3: 0.3 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TRIAL NO. 1 TRIAL NO. 2 TRIAL NO. 3 TRIAL NO. 4 OVERALL PUP TIME TIME TIME TIME MEAN NO. (SEC) (SEC) (SEC) (SEC) (SEC) ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 11.81 9.70 6.95 12.61 10.27 25614-10 11.59 5.14 9.74 3.88 7.59 25698-05 16.88 6.17 5.64 8.30 9.25 25677-05 12.05 5.87 4.97 3.24 6.53 25604-04 29.66 6.71 4.08 5.55 11.50 25678-02 14.22 4.82 5.66 7.49 8.05 25609-04 13.47 13.02 9.59 5.02 10.28 25623-08 15.04 5.93 5.37 4.07 7.60 25653-02 12.14 4.45 4.52 5.33 6.61 25684-04 15.55 5.11 5.13 3.99 7.45 25714-02 15.64 7.09 5.09 7.48 8.83 25650-11 7.05 5.90 5.03 6.20 6.05 25735-05 9.44 6.84 5.79 5.00 6.77 25722-01 9.58 6.45 12.50 6.02 8.64 25642-05 11.16 5.64 5.35 9.28 7.86 25628-07 10.24 6.61 6.46 4.69 7.00 25766-01 33.55 9.48 5.28 5.73 13.51 25689-02 14.57 3.98 8.20 4.84 7.90 25708-01 16.69 5.01 4.21 5.17 7.77 25743-08 19.56 7.61 13.19 8.70 12.27 -1071- MEAN 14.99 6.58 6.64 6.13 8.58 S.D. 6.447 2.110 2.645 2.265 2.027 N 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 30 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 4: 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TRIAL NO. 1 TRIAL NO. 2 TRIAL NO. 3 TRIAL NO. 4 OVERALL PUP TIME TIME TIME TIME MEAN NO. (SEC) (SEC) (SEC) (SEC) (SEC) ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 34.32 6.39 6.25 5.60 13.14 25686-04 11.74 16.47 4.52 4.67 9.35 25630-04 30.27 4.92 5.57 4.06 11.21 25673-09 13.12 7.30 7.28 6.02 8.43 25639-06 14.86 9.49 5.33 5.70 8.85 25658-08 23.02 5.80 6.69 4.46 9.99 25676-02 27.66 6.61 4.52 4.35 10.79 25600-02 9.93 4.95 3.72 3.97 5.64 25603-04 5.46 3.20 6.51 4.81 5.00 25703-03 17.34 6.41 2.72 4.96 7.86 25705-07 28.37 26.65 10.95 8.56 18.63 25611-07 24.90 5.41 6.26 5.34 10.48 25619-04 7.63 5.84 6.40 120.00 34.97 25691-07 25.37 11.45 5.08 5.90 11.95 25717-04 19.59 9.63 7.59 10.09 11.73 25616-05 19.40 5.29 7.98 5.80 9.62 25715-07 14.27 4.45 5.04 10.21 8.49 25599-06 36.98 7.45 10.39 12.56 16.85 25762-01 11.52 5.89 6.52 5.80 7.43 25647-07 10.07 6.59 10.71 14.58 10.49 -1072- MEAN 19.29 8.01 6.50 12.37 11.54 S.D. 9.172 5.275 2.213 25.505 6.400 N 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 30 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 1: 0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TRIAL NO. 1 TRIAL NO. 2 TRIAL NO. 3 TRIAL NO. 4 OVERALL PUP TIME TIME TIME TIME MEAN NO. (SEC) (SEC) (SEC) (SEC) (SEC) ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 9.55 12.99 7.59 9.46 9.90 25654-10 20.19 8.28 8.12 14.18 12.69 25632-09 13.77 7.92 3.68 4.06 7.36 25633-13 13.49 8.24 16.33 9.54 11.90 25618-17 7.38 7.74 2.44 4.91 5.62 25621-10 7.70 4.16 4.86 7.97 6.17 25687-15 8.82 10.96 7.20 4.99 7.99 25681-10 9.44 8.40 8.34 6.51 8.17 25615-10 8.06 10.37 5.74 6.59 7.69 25637-17 12.19 9.27 6.14 5.72 8.33 25638-18 25.10 8.58 5.49 5.45 11.16 25713-16 12.38 5.49 5.71 6.13 7.43 25670-18 12.20 7.04 5.66 5.63 7.63 25657-10 11.62 11.34 5.10 4.66 8.18 25663-09 6.52 5.86 5.32 5.07 5.69 25690-19 6.24 7.18 4.78 5.06 5.82 25666-09 44.96 8.69 5.78 6.07 16.38 25692-07 10.46 7.41 4.77 4.76 6.85 25701-18 15.64 5.62 4.45 5.23 7.74 25645-08 15.06 5.62 6.27 5.28 8.06 -1073- MEAN 13.54 8.06 6.19 6.36 8.54 S.D. 8.735 2.201 2.778 2.362 2.683 N 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 30 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 2: 0.1 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TRIAL NO. 1 TRIAL NO. 2 TRIAL NO. 3 TRIAL NO. 4 OVERALL PUP TIME TIME TIME TIME MEAN NO. (SEC) (SEC) (SEC) (SEC) (SEC) ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 9.84 4.45 5.41 4.97 6.17 25674-11 28.73 7.74 8.31 5.79 12.64 25694-13 21.24 4.63 8.09 6.17 10.03 25631-05 20.24 5.04 10.59 7.79 10.92 25660-04 16.49 8.85 6.76 6.73 9.71 25704-09 20.62 5.52 5.27 5.14 9.14 25665-07 15.87 9.24 8.31 6.97 10.10 25652-13 20.92 10.08 7.77 8.02 11.70 25733-08 24.91 5.91 6.92 6.81 11.14 25748-08 5.42 9.12 5.36 4.30 6.05 25753-15 15.22 7.07 5.27 5.36 8.23 25672-15 21.31 7.20 6.29 5.43 10.06 25655-13 13.75 9.58 6.21 8.96 9.63 25727-16 30.56 7.06 4.81 5.16 11.90 25626-12 7.24 5.31 8.59 6.85 7.00 25749-11 19.78 5.50 4.79 6.34 9.10 25739-12 13.36 6.34 3.94 4.38 7.01 25756-13 12.85 17.49 6.72 4.54 10.40 25741-09 29.64 7.96 5.59 5.48 12.17 25752-13 20.98 4.05 5.41 4.31 8.69 -1074- MEAN 18.45 7.41 6.52 5.98 9.59 S.D. 6.986 2.999 1.655 1.320 1.946 N 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 30 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 3: 0.3 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TRIAL NO. 1 TRIAL NO. 2 TRIAL NO. 3 TRIAL NO. 4 OVERALL PUP TIME TIME TIME TIME MEAN NO. (SEC) (SEC) (SEC) (SEC) (SEC) ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 13.64 7.27 6.52 9.49 9.23 25614-17 22.89 6.87 8.95 5.69 11.10 25698-12 34.17 7.08 5.54 12.49 14.82 25677-08 24.16 8.89 4.99 5.83 10.97 25604-12 7.63 3.69 4.85 4.91 5.27 25678-11 15.03 4.63 6.71 5.51 7.97 25609-11 12.93 3.34 6.11 8.77 7.79 25623-15 9.41 4.96 4.87 3.96 5.80 25653-13 17.74 6.41 5.38 5.58 8.78 25684-06 12.83 5.11 3.57 4.31 6.46 25714-13 13.48 7.30 5.63 6.14 8.14 25650-17 8.88 7.66 4.77 4.24 6.39 25735-08 9.10 5.13 16.17 9.02 9.86 25722-15 9.72 4.56 4.33 6.89 6.38 25628-17 28.04 8.66 7.02 7.90 12.91 25766-06 20.50 7.40 5.09 5.31 9.58 25689-14 12.96 4.63 5.56 4.11 6.82 25708-15 13.24 5.56 5.58 6.56 7.74 25743-16 63.89 20.23 6.70 11.13 25.49 25642-12 21.77 7.48 6.26 5.59 10.28 -1075- MEAN 18.60 6.84 6.23 6.67 9.59 S.D. 12.782 3.532 2.608 2.397 4.467 N 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- APPENDIX 30 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 4: 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- TRIAL NO. 1 TRIAL NO. 2 TRIAL NO. 3 TRIAL NO. 4 OVERALL PUP TIME TIME TIME TIME MEAN NO. (SEC) (SEC) (SEC) (SEC) (SEC) ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 27.38 6.16 3.94 5.13 10.65 25686-10 17.66 6.34 5.42 5.76 8.80 25630-09 17.95 7.99 5.09 5.51 9.14 25673-10 16.07 5.08 4.42 5.63 7.80 25639-04 21.48 8.77 10.89 10.42 12.89 25658-14 9.77 7.21 5.65 5.73 7.09 25676-15 13.10 6.72 7.00 8.68 8.88 25600-15 4.95 14.38 8.46 5.19 8.25 25603-10 15.02 5.01 4.01 6.60 7.66 25703-10 9.16 10.91 3.56 7.45 7.77 25705-08 18.52 8.45 7.37 7.20 10.39 25611-11 13.68 6.38 4.86 4.47 7.35 25619-12 9.68 9.89 6.09 5.17 7.71 25691-11 8.08 4.67 3.91 4.43 5.27 25717-15 37.96 6.73 5.31 5.15 13.79 25616-14 15.83 5.32 4.63 6.38 8.04 25715-10 14.28 4.43 5.39 5.77 7.47 25599-11 14.94 4.98 7.23 4.65 7.95 25762-11 11.44 6.73 9.94 5.80 8.48 25647-11 14.49 9.54 7.16 5.13 9.08 -1076- MEAN 15.57 7.28 6.02 6.01 8.72 S.D. 7.267 2.487 2.020 1.479 1.962 N 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- MANUALv1.0 10/05/2006 R:04/30/2007 APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 1: 0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 2 - A DAY 3 - A DAY 4 - B TRIAL NUMBER 1 TRIAL NUMBER 2 TRIAL NUMBER 3 TRIAL NUMBER 4 TRIAL NUMBER 5 TRIAL NUMBER 6 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ------------------------------------------------------------------------------------------------------------------------------- 25597-04 180.00 E 26 41.06 4 55.01 7 53.56 10 180.00 E 43 180.00 E 34 25654-09 36.70 8 93.64 27 63.41 16 27.57 6 180.00 E 36 180.00 E 34 25632-07 136.52 29 18.42 0 35.27 10 26.05 5 54.52 13 180.00 E 41 25633-05 72.78 15 49.84 13 70.40 21 134.56 28 77.02 20 52.16 13 25618-08 165.31 29 21.74 3 22.16 3 61.23 16 51.97 9 180.00 E 48 25621-07 37.60 5 87.20 22 180.00 E 61 152.59 44 180.00 E 41 152.87 28 25687-07 24.34 4 76.13 18 58.34 18 15.56 2 180.00 E 35 133.33 33 25681-01 107.58 22 61.66 11 50.45 18 26.84 5 180.00 E 45 180.00 E 27 25615-03 63.82 13 117.37 36 22.97 5 21.80 5 97.27 27 125.20 30 25637-06 60.93 9 83.87 20 28.13 3 86.74 20 174.32 41 180.00 E 41 25638-07 77.00 18 25.03 4 35.68 9 32.02 7 180.00 E 41 180.00 E 39 25713-02 180.00 E 31 49.44 9 29.91 7 57.62 18 180.00 E 38 59.20 15 25670-09 159.91 36 48.34 10 30.72 6 11.24 0 180.00 E 42 180.00 E 44 25657-08 27.74 4 25.71 4 12.68 0 21.12 3 180.00 E 43 180.00 E 47 25663-04 18.55 1 33.72 7 15.12 0 59.61 14 76.14 13 19.42 2 25690-01 66.76 15 20.28 4 11.45 0 21.05 5 146.67 33 179.24 32 25666-01 20.43 3 20.57 3 180.00 E 38 154.46 32 62.74 11 180.00 E 34 25692-04 70.90 15 180.00 E 34 16.31 2 12.88 1 137.10 36 37.91 2 25701-09 25.68 4 65.02 14 62.45 19 24.16 4 180.00 E 42 110.99 29 25645-06 41.98 8 51.34 13 100.61 28 55.36 13 76.24 16 50.64 10 -1077- MEAN 78.73 15 58.52 13 54.05 14 52.80 12 137.70 31 136.05 29 S.D. 56.080 10.8 40.115 10.5 48.823 15.1 45.443 11.6 52.358 12.6 58.799 13.9 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 MALES ---------------------------------------------------------------------------------------------------------------------------------- GROUP 1: 0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 5 - B DAY 6 - B DAY 7 (PROBE) - A TRIAL NUMBER 7 TRIAL NUMBER 8 TRIAL NUMBER 9 TRIAL NUMBER 10 TRIAL NUMBER 11 TRIAL NUMBER 12 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 180.00 E 29 180.00 E 26 180.00 E 20 180.00 E 25 67.91 14 113.31 17 25654-09 180.00 E 31 180.00 E 38 113.02 24 180.00 E 41 42.59 8 15.79 2 25632-07 109.23 31 30.49 6 32.34 6 82.44 22 65.19 18 55.38 15 25633-05 60.88 18 41.82 10 68.70 21 34.24 9 112.59 32 114.45 38 25618-08 180.00 E 52 180.00 E 42 113.64 25 71.52 18 61.45 13 13.62 0 25621-07 180.00 E 40 94.56 23 64.86 20 22.24 5 72.98 26 27.09 4 25687-07 180.00 E 46 180.00 E 47 78.27 18 13.99 2 50.88 8 30.35 6 25681-01 180.00 E 40 152.32 28 26.13 4 46.24 11 102.52 31 22.89 5 25615-03 131.62 44 29.02 7 42.61 15 31.99 11 180.00 E 64 180.00 E 58 25637-06 57.23 14 180.00 E 32 15.69 3 44.66 10 25.12 3 17.70 1 25638-07 49.52 8 54.30 13 15.95 2 97.31 28 180.00 E 58 43.23 14 25713-02 180.00 E 33 180.00 E 34 129.68 36 10.24 1 81.27 30 12.24 1 25670-09 180.00 E 31 180.00 E 25 180.00 E 44 180.00 E 44 35.03 5 11.36 0 25657-08 180.00 E 30 22.69 7 180.00 E 47 16.20 2 25.94 6 32.89 7 25663-04 131.28 29 106.99 28 49.99 11 29.56 8 155.83 33 66.88 20 25690-01 147.44 30 11.45 1 10.80 0 68.35 16 45.88 11 31.69 9 25666-01 180.00 E 34 65.26 12 107.37 25 23.06 2 39.97 14 13.27 0 25692-04 39.63 9 50.87 11 12.54 0 10.24 0 31.25 6 33.05 4 25701-09 180.00 E 46 180.00 E 40 71.81 15 109.92 24 72.92 19 27.94 5 25645-06 178.21 40 73.93 20 180.00 E 53 17.63 3 44.73 12 24.39 6 -1078- MEAN 144.25 32 108.69 23 83.67 19 63.49 14 74.70 21 44.38 11 S.D. 51.920 12.1 67.266 13.6 60.977 15.7 58.001 13.0 48.210 16.9 43.708 14.4 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 2: 0.1 MG/KG/DAY ---------------------------------------------------------------------------------------------------------------------------------- DAY 2 - A DAY 3 - A DAY 4 - B TRIAL NUMBER 1 TRIAL NUMBER 2 TRIAL NUMBER 3 TRIAL NUMBER 4 TRIAL NUMBER 5 TRIAL NUMBER 6 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25648-07 25.76 3 107.74 30 22.33 6 29.36 5 180.00 E 36 180.00 E 36 25674-02 75.09 13 109.59 29 24.93 6 20.89 5 164.49 41 180.00 E 58 25694-04 180.00 E 27 86.47 19 19.41 2 10.91 0 59.80 15 180.00 E 31 25631-04 52.45 8 29.18 8 21.19 4 12.26 0 180.00 E 34 33.99 7 25660-01 180.00 E 26 67.96 15 13.18 0 149.73 33 180.00 E 27 180.00 E 26 25704-03 38.74 9 140.13 35 35.47 7 24.88 3 80.10 15 166.54 28 25665-01 78.96 13 37.16 5 58.56 17 12.86 0 180.00 E 38 27.51 2 25652-04 158.25 28 68.42 13 180.00 E 45 110.12 23 180.00 E 30 180.00 E 46 25733-07 180.00 E 33 103.63 23 51.56 10 16.62 1 180.00 E 35 180.00 E 27 25748-01 118.52 23 56.06 11 58.74 16 39.20 8 76.13 18 82.22 18 25753-06 31.99 7 33.87 7 96.20 29 21.16 5 180.00 E 28 177.03 40 25672.06 42.91 8 27.56 3 27.55 3 38.94 7 180.00 E 38 137.35 24 25655-01 134.63 24 77.75 21 30.45 8 18.37 4 89.81 24 155.78 32 25727-07 20.19 3 44.47 10 94.44 28 12.34 0 180.00 E 44 155.16 37 25626-04 95.63 26 13.24 1 13.24 1 36.82 10 121.04 37 108.58 32 25749-04 13.97 0 68.86 12 40.54 8 18.21 2 75.95 15 71.56 18 25739-07 21.33 3 15.18 1 85.05 15 24.77 4 140.60 28 78.41 14 25756-05 45.09 8 180.00 E 40 160.48 31 35.51 5 180.00 E 38 180.00 E 29 25741-07 39.68 7 50.66 10 25.27 3 23.42 2 180.00 E 40 180.00 E 28 25752-09 52.17 11 16.59 1 28.09 3 110.42 28 180.00 E 34 180.00 E 39 -1079- MEAN 79.27 14 66.73 15 54.33 12 38.34 7 148.40 31 140.71 29 S.D. 58.459 10.2 44.377 11.7 47.220 12.2 38.436 9.5 45.579 9.2 53.137 13.0 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 MALES ---------------------------------------------------------------------------------------------------------------------------------- GROUP 2: 0.1 MG/KG/DAY ---------------------------------------------------------------------------------------------------------------------------------- DAY 5 - B DAY 6 - B DAY 7 (PROBE) - A TRIAL NUMBER 7 TRIAL NUMBER 8 TRIAL NUMBER 9 TRIAL NUMBER 10 TRIAL NUMBER 11 TRIAL NUMBER 12 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ---------------------------------------------------------------------------------------------------------------------------------- 25648-07 180.00 E 33 180.00 E 32 180.00 E 40 180.00 E 41 69.70 20 180.00 E 38 25674-02 164.78 43 50.62 16 10.25 0 180.00 E 50 56.51 18 40.80 11 25694-04 48.23 9 180.00 E 34 47.20 9 22.59 4 69.50 21 52.70 15 25631-04 177.06 35 157.38 41 180.00 E 40 30.16 4 23.92 6 67.37 20 25660-01 180.00 E 25 180.00 E 30 144.62 43 180.00 E 41 60.56 22 17.50 2 25704-03 180.00 E 42 45.33 10 78.08 14 12.09 1 152.28 50 69.20 16 25665-01 21.43 4 48.52 8 60.87 13 69.91 14 180.00 E 57 165.56 41 25652-04 114.30 21 180.00 E 41 180.00 E 42 66.08 14 60.66 16 31.91 3 25733-07 42.14 10 171.52 27 180.00 E 53 73.05 19 41.84 6 33.73 5 25748-01 180.00 E 46 99.55 20 13.14 0 10.92 0 46.64 13 73.31 18 25753-06 180.00 E 41 33.02 10 180.00 E 43 104.20 27 72.28 24 28.45 9 25672.06 180.00 E 39 180.00 E 48 180.00 E 39 116.78 27 27.46 1 91.86 14 25655-01 118.84 29 53.88 16 25.80 8 27.16 7 30.68 6 86.79 37 25727-07 126.13 30 19.67 6 25.13 6 16.26 2 73.08 18 34.74 8 25626-04 40.95 11 180.00 E 40 22.36 3 22.90 6 71.43 25 24.91 6 25749-04 100.79 18 11.49 0 42.70 6 27.66 4 131.48 29 104.86 27 25739-07 177.02 47 141.06 30 133.17 34 54.68 12 180.00 E 46 180.00 E 43 25756-05 180.00 E 39 63.39 17 117.26 25 66.45 10 30.39 4 48.93 11 25741-07 126.02 25 169.94 27 180.00 E 28 104.09 17 21.95 2 13.90 0 25752-09 71.82 10 37.14 5 69.74 14 43.44 5 99.20 31 45.58 9 -1080- MEAN 129.48 28 109.13 23 102.52 23 70.42 15 74.98 21 69.61 17 S.D. 57.075 13.8 67.274 14.0 68.748 17.4 56.758 14.7 49.299 15.9 51.904 13.5 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 MALES ---------------------------------------------------------------------------------------------------------------------------------- GROUP 3: 0.3 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 2 - A DAY 3 - A DAY 4 - B TRIAL NUMBER 1 TRIAL NUMBER 2 TRIAL NUMBER 3 TRIAL NUMBER 4 TRIAL NUMBER 5 TRIAL NUMBER 6 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ---------------------------------------------------------------------------------------------------------------------------------- 25671-04 29.60 7 30.16 7 26.47 5 77.56 21 58.03 12 11.40 0 25614-10 63.18 13 40.14 8 74.07 18 57.83 13 180.00 E 30 117.42 19 25698-05 28.56 4 95.40 20 20.46 2 83.70 19 88.63 20 180.00 E 42 25677-05 43.55 7 82.84 21 21.88 3 15.68 3 180.00 E 47 33.09 9 25604-04 38.04 8 65.66 19 41.19 14 91.63 27 49.37 14 26.27 5 25678-02 18.12 1 23.66 3 33.81 5 63.74 16 180.00 E 44 154.01 30 25609-04 38.24 7 74.52 19 26.81 6 19.76 3 129.75 35 180.00 E 37 25623-08 180.00 E 39 22.63 3 34.81 7 27.74 5 40.27 4 180.00 E 40 25653-02 98.10 18 144.31 36 28.78 7 14.76 2 180.00 E 47 180.00 E 37 25684-04 88.64 17 12.46 0 19.84 3 52.86 16 180.00 E 39 22.47 5 25714-02 47.04 11 49.95 9 12.96 1 15.55 3 59.79 17 107.75 27 25650-11 58.46 9 36.58 4 25.15 4 10.27 0 180.00 E 32 39.41 5 25735-05 179.09 25 65.13 13 69.07 17 85.26 25 180.00 E 36 180.00 E 39 25722-01 45.59 11 46.48 12 11.09 0 15.33 2 180.00 E 35 54.49 11 25642-05 112.16 17 130.78 30 57.20 14 20.21 4 180.00 E 44 180.00 E 43 25628-07 28.85 4 19.30 3 12.39 0 23.75 3 180.00 E 37 180.00 E 38 25766-01 34.05 6 112.57 28 51.15 15 28.58 7 180.00 E 37 90.45 22 25689-02 180.00 E 43 114.71 20 87.20 24 14.89 2 180.00 E 47 137.19 21 25708-01 24.64 4 34.38 6 19.62 3 20.51 4 180.00 E 38 180.00 E 37 25743-08 94.06 16 121.16 27 20.15 2 14.66 2 134.70 30 180.00 E 36 -1081- MEAN 71.50 13 66.14 14 34.71 8 37.71 9 145.03 32 120.70 25 S.D. 53.639 11.2 41.239 10.5 21.907 6.9 28.372 8.7 53.498 12.6 66.215 14.7 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 MALES ---------------------------------------------------------------------------------------------------------------------------------- GROUP 3: 0.3 MG/KG/DAY ---------------------------------------------------------------------------------------------------------------------------------- DAY 5 - B DAY 6 - B DAY 7 (PROBE) - A TRIAL NUMBER 7 TRIAL NUMBER 8 TRIAL NUMBER 9 TRIAL NUMBER 10 TRIAL NUMBER 11 TRIAL NUMBER 12 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 8.83 0 114.83 29 54.13 13 6.78 0 142.89 38 62.66 15 25614-10 53.62 10 31.24 7 31.08 4 29.09 5 122.91 34 29.82 7 25698-05 150.09 31 23.09 4 170.63 36 163.70 33 28.14 5 16.20 2 25677-05 123.74 32 20.24 4 18.46 3 17.09 2 76.72 27 44.59 9 25604-04 100.10 36 59.74 17 12.62 2 148.38 48 131.03 44 96.56 34 25678-02 35.56 8 15.41 2 26.00 5 29.84 7 85.38 32 107.48 32 25609-04 180.00 E 43 180.00 E 43 180.00 E 48 38.44 9 22.36 7 53.65 16 25623-08 180.00 E 38 71.53 15 97.20 22 21.09 1 79.52 24 31.80 8 25653-02 180.00 E 38 23.06 2 76.45 22 180.00 E 44 35.13 8 143.78 55 25684-04 180.00 E 37 180.00 E 49 124.13 33 24.46 3 38.78 8 47.98 15 25714-02 90.01 23 13.81 2 8.46 0 9.45 0 171.31 44 16.10 2 25650-11 180.00 E 24 50.99 6 36.74 6 21.58 2 64.10 16 42.03 11 25735-05 102.90 24 13.77 2 11.59 0 110.98 23 57.85 17 10.97 0 25722-01 180.00 E 30 90.92 25 20.16 2 10.84 0 80.84 28 39.57 13 25642-05 180.00 E 45 180.00 E 41 180.00 E 50 102.43 33 122.12 31 66.54 22 25628-07 97.07 22 91.81 19 22.91 5 30.83 6 153.09 45 63.32 15 25766-01 172.93 42 92.24 26 47.66 12 180.00 E 46 64.85 21 38.06 8 25689-02 86.74 30 32.00 8 14.94 1 10.57 0 47.37 16 11.86 0 25708-01 180.00 E 58 65.78 16 45.05 7 130.45 38 41.81 9 32.57 7 25743-08 180.00 E 41 79.56 21 158.15 31 180.00 E 39 99.51 19 73.11 14 -1082- MEAN 132.08 31 71.50 17 66.82 15 72.30 17 83.29 24 51.43 14 S.D. 56.344 13.8 55.902 14.7 61.737 16.3 67.910 18.5 44.296 13.1 34.062 13.3 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 4: 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 2 - A DAY 3 - A DAY 4 - B TRIAL NUMBER 1 TRIAL NUMBER 2 TRIAL NUMBER 3 TRIAL NUMBER 4 TRIAL NUMBER 5 TRIAL NUMBER 6 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 179.05 38 64.88 15 17.84 3 19.91 3 180.00 E 53 72.83 17 25686-04 19.76 3 26.33 4 24.39 5 180.00 E 35 180.00 E 23 38.82 5 25630-04 82.18 18 17.20 2 12.06 0 18.63 2 180.00 E 46 80.16 15 25673-09 49.06 11 134.21 34 73.55 22 125.59 37 180.00 E 43 180.00 E 51 25639-06 72.17 17 124.30 41 22.62 4 25.68 6 180.00 E 39 166.03 44 25658-08 85.97 16 16.56 1 39.48 11 23.27 4 180.00 E 34 180.00 E 40 25676-02 37.91 7 169.22 34 16.55 1 24.69 4 180.00 E 48 64.90 15 25600-02 32.43 7 25.97 4 14.92 3 19.79 2 180.00 E 54 111.37 28 25603-04 32.22 6 64.64 13 31.95 6 23.25 5 180.00 E 51 43.82 8 25703-03 180.00 E 36 58.82 7 108.41 34 10.79 1 77.37 17 180.00 E 46 25705-07 101.10 18 27.31 4 17.36 2 14.77 2 180.00 E 36 71.46 19 25611-07 180.00 E 42 43.24 10 83.05 27 40.37 5 67.83 15 93.73 18 25619-04 27.26 4 46.49 10 24.84 3 20.93 4 180.00 E 29 136.49 22 25691-07 157.94 23 75.36 11 180.00 E 40 31.47 7 180.00 E 29 180.00 E 28 25717-04 14.63 1 100.31 22 17.73 1 36.47 6 180.00 E 39 180.00 E 33 25616-05 37.72 8 93.67 19 12.40 0 23.13 4 180.00 E 41 163.61 32 25715-07 180.00 E 39 180.00 E 44 96.23 30 32.26 6 18.39 3 56.35 14 25599-06 41.74 7 62.81 13 48.86 11 21.52 2 180.00 E 35 180.00 E 37 25762-01 60.27 14 29.02 4 13.42 2 C 3 28.88 5 70.55 14 25647-07 24.59 3 26.72 5 23.52 3 69.49 15 180.00 E 36 31.06 7 -1083- MEAN 79.80 16 69.35 15 43.96 10 40.11 8 153.62 34 114.06 25 S.D. 61.173 13.2 49.673 13.4 43.665 12.7 42.615 10.1 55.325 14.9 57.104 13.7 N 20 20 20 20 20 20 19 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) C = TIME NOT RECORDED; NOT INCLUDED IN CALCULATION OF MEANS E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 MALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 4: 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 5 - B DAY 6 - B DAY 7 (PROBE) - A TRIAL NUMBER 7 TRIAL NUMBER 8 TRIAL NUMBER 9 TRIAL NUMBER 10 TRIAL NUMBER 11 TRIAL NUMBER 12 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 153.50 40 14.99 1 33.94 7 25.34 3 87.07 21 26.34 5 25686-04 180.00 E 32 90.84 19 94.25 19 49.04 13 102.52 29 149.72 35 25630-04 130.87 29 16.09 1 14.29 1 12.62 0 172.09 58 34.51 8 25673-09 68.37 20 133.85 38 132.69 30 143.10 43 71.69 22 43.56 8 25639-06 180.00 E 41 86.39 17 180.00 E 51 56.51 15 55.57 15 104.34 28 25658-08 180.00 E 51 51.47 11 155.43 38 180.00 E 48 80.65 30 56.38 14 25676-02 173.09 40 115.63 24 33.45 3 44.62 10 31.21 6 49.98 12 25600-02 180.00 E 47 46.23 10 15.99 1 50.97 12 180.00 E 65 180.00 E 61 25603-04 38.77 9 47.60 9 72.04 20 30.81 7 111.82 36 22.61 5 25703-03 171.70 38 180.00 E 43 180.00 E 37 126.80 34 56.26 14 41.55 10 25705-07 39.29 12 59.66 15 54.93 14 64.13 11 41.78 16 48.36 16 25611-07 29.93 5 117.38 36 19.66 3 30.02 6 59.99 16 31.58 6 25619-04 180.00 E 30 180.00 E 34 180.00 E 36 180.00 E 39 18.63 3 54.38 16 25691-07 180.00 E 21 40.06 6 180.00 E 32 15.34 0 180.00 E 40 52.83 8 25717-04 156.87 35 15.53 1 10.58 0 25.61 4 50.46 15 180.00 E 53 25616-05 126.34 35 13.99 1 10.81 0 22.37 4 66.05 19 37.36 9 25715-07 29.17 9 78.29 23 65.98 18 39.36 10 23.74 5 19.71 3 25599-06 49.24 8 180.00 E 36 180.00 E 38 75.14 15 77.19 17 73.30 20 25762-01 180.00 E 34 179.38 43 98.80 23 66.70 5 77.71 24 14.98 2 25647-07 84.38 18 26.17 4 27.45 4 38.88 4 174.11 44 41.82 7 -1084- MEAN 125.58 28 83.68 19 87.01 19 63.87 14 85.93 25 63.17 16 S.D. 61.184 14.0 60.728 15.1 67.916 16.1 51.948 14.6 52.157 16.7 50.376 16.2 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 9 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 1: 0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 2 - A DAY 3 - A DAY 4 - B TRIAL NUMBER 1 TRIAL NUMBER 2 TRIAL NUMBER 3 TRIAL NUMBER 4 TRIAL NUMBER 5 TRIAL NUMBER 6 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ---------------------------------------------------------------------------------------------------------------------------------- 25597-17 180.00 E 41 31.81 3 88.68 17 87.99 15 180.00 E 33 113.66 18 25654-10 98.31 25 60.45 15 62.03 20 14.38 2 116.13 23 180.00 E 39 25632-09 66.99 14 59.95 15 13.88 0 12.26 0 180.00 E 51 180.00 E 39 25633-13 58.97 13 180.00 E 41 178.21 38 43.20 11 180.00 E 41 47.49 14 25618-17 31.21 4 180.00 E 44 65.04 14 11.38 0 180.00 E 44 180.00 E 39 25621-10 62.77 15 28.05 6 100.70 37 180.00 E 58 180.00 E 43 150.16 29 25687-15 61.52 15 76.32 18 10.70 0 35.88 9 95.91 28 116.74 32 25681-10 24.93 4 180.00 E 45 127.50 34 14.36 1 180.00 E 42 180.00 E 33 25615-10 44.49 10 115.58 29 24.38 2 14.41 1 180.00 E 33 180.00 E 29 25637-17 52.59 7 109.05 24 73.61 13 82.93 15 180.00 E 33 180.00 E 31 25638-18 44.62 9 14.09 0 50.71 11 11.58 0 180.00 E 41 99.20 21 25713-16 67.18 10 49.21 10 17.59 2 26.99 4 90.87 23 180.00 E 30 25670-18 35.05 8 65.00 17 15.59 1 29.43 10 61.44 12 109.20 31 25657-10 36.94 5 13.59 1 65.18 12 21.38 3 180.00 E 34 180.00 E 35 25663-09 180.00 E 38 36.08 5 85.98 20 39.63 9 180.00 E 51 180.00 E 44 25690-19 16.20 1 79.21 14 26.49 6 15.91 2 180.00 E 33 180.00 E 38 25666-09 108.09 19 76.05 11 75.87 19 54.98 10 32.37 8 180.00 E 37 25692-07 39.21 8 22.34 3 61.53 19 22.75 4 180.00 E 41 180.00 E 39 25701-18 44.17 10 13.83 1 44.62 11 46.43 11 180.00 E 28 116.45 14 25645-08 25.84 4 40.34 10 40.98 8 30.15 4 180.00 E 27 91.46 15 -1085- MEAN 63.95 13 71.55 16 61.46 14 39.80 8 154.84 33 150.22 30 S.D. 45.821 10.7 55.083 14.2 42.016 11.7 39.740 12.7 47.173 11.5 41.379 9.3 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 10 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 1: 0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 5 - B DAY 6 - B DAY 7 (PROBE) - A TRIAL NUMBER 7 TRIAL NUMBER 8 TRIAL NUMBER 9 TRIAL NUMBER 10 TRIAL NUMBER 11 TRIAL NUMBER 12 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 180.00 E 31 180.00 E 32 180.00 E 40 180.00 E 39 60.77 13 153.73 32 25654-10 180.00 E 36 54.85 9 111.81 24 24.98 5 99.01 22 26.46 5 25632-09 180.00 E 38 180.00 E 28 65.55 15 87.49 19 123.41 39 16.74 2 25633-13 87.70 23 78.64 22 180.00 E 40 180.00 E 52 41.53 11 132.48 42 25618-17 180.00 E 45 180.00 E 33 180.00 E 39 180.00 E 42 34.80 7 41.05 9 25621-10 58.09 12 26.01 1 70.47 25 33.13 6 77.26 25 18.46 3 25687-15 180.00 E 40 104.59 26 180.00 E 52 31.84 8 31.05 8 45.68 11 25681-10 68.37 21 52.88 14 54.89 20 44.02 12 45.12 12 15.24 3 25615-10 143.25 31 180.00 E 33 72.79 18 75.72 21 117.97 31 37.43 4 25637-17 180.00 E 25 180.00 E 26 180.00 E 29 137.76 20 120.45 30 59.73 13 25638-18 62.26 13 91.61 16 180.00 E 48 58.58 10 169.74 36 83.27 19 25713-16 180.00 E 21 180.00 E 33 62.98 12 14.18 1 111.40 29 12.46 0 25670-18 26.10 4 49.45 10 17.18 3 99.27 27 180.00 E 51 95.45 34 25657-10 91.48 19 24.84 4 19.54 4 13.88 2 63.87 17 21.53 4 25663-09 140.68 38 180.00 E 42 180.00 E 47 180.00 E 37 75.52 22 134.20 41 25690-19 180.00 E 34 180.00 E 35 180.00 E 32 180.00 E 34 39.42 10 32.65 6 25666-09 180.00 E 41 48.29 10 23.58 2 29.20 5 56.06 13 84.75 23 25692-07 180.00 E 44 170.33 45 126.35 31 113.65 29 121.38 32 62.99 15 25701-18 180.00 E 33 76.90 12 180.00 E 38 145.06 20 70.77 22 15.89 2 25645-08 36.51 9 71.51 17 16.95 1 11.31 0 51.97 16 16.10 3 -1086- MEAN 134.72 28 114.50 22 113.10 26 91.00 19 84.58 22 55.31 14 S.D. 57.907 12.2 62.597 12.7 67.774 16.2 65.705 15.4 43.854 11.8 44.536 13.7 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 11 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 2: 0.1 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 2 - A DAY 3 - A DAY 4 - B TRIAL NUMBER 1 TRIAL NUMBER 2 TRIAL NUMBER 3 TRIAL NUMBER 4 TRIAL NUMBER 5 TRIAL NUMBER 6 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25648-12 27.88 3 35.59 7 75.92 19 37.55 15 29.53 10 11.02 1 25674-11 34.06 8 37.45 8 86.56 26 29.44 5 126.84 28 46.16 7 25694-13 157.38 11 76.82 16 49.52 14 63.34 18 180.00 E 35 180.00 E 26 25631-05 180.00 E 20 121.50 23 13.52 0 9.06 0 180.00 E 43 51.81 9 25660-04 25.83 6 31.52 6 18.68 1 92.41 23 180.00 E 30 180.00 E 31 25704-09 94.75 25 21.36 5 15.97 2 18.89 5 180.00 E 43 128.04 26 25665-07 178.78 21 56.59 12 22.50 3 21.92 3 180.00 E 28 180.00 E 26 25652-13 35.99 6 73.28 17 30.71 7 15.34 2 155.85 31 27.72 6 25733-08 180.00 E 34 153.88 32 55.14 11 17.45 1 144.99 27 180.00 E 40 25748-08 180.00 E 42 147.06 31 57.59 14 22.91 2 180.00 E 45 34.61 7 25753-15 55.93 10 38.75 7 45.18 11 77.98 21 180.00 E 35 180.00 E 34 25672-15 180.00 E 46 142.16 31 88.56 17 44.22 9 71.69 14 180.00 E 48 25655-13 58.82 12 48.66 10 20.38 3 11.76 0 164.59 27 38.55 5 25727-16 39.05 7 180.00 E 47 67.07 12 180.00 E 45 180.00 E 37 113.49 22 25626-12 45.72 10 57.79 14 27.90 6 22.22 3 180.00 E 41 180.00 E 43 25749-11 29.83 4 180.00 E 31 180.00 E 37 95.13 12 180.00 E 33 180.00 E 38 25739-12 32.97 6 109.64 29 119.69 28 52.52 12 87.52 20 180.00 E 31 25756-13 25.12 3 163.56 22 97.52 20 17.52 0 180.00 E 35 180.00 E 29 25741-09 50.18 9 27.86 4 30.91 4 14.78 0 180.00 E 35 133.38 23 25752-13 27.23 5 19.63 4 31.06 7 18.52 3 180.00 E 40 85.29 19 -1087- MEAN 81.98 14 86.16 18 56.72 12 43.15 9 156.05 32 123.50 24 S.D. 65.243 12.9 57.290 12.3 42.111 10.0 41.878 11.2 43.725 9.3 65.560 13.9 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 12 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 2: 0.1 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 5 - B DAY 6 - B DAY 7 (PROBE) - A TRIAL NUMBER 7 TRIAL NUMBER 8 TRIAL NUMBER 9 TRIAL NUMBER 10 TRIAL NUMBER 11 TRIAL NUMBER 12 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ---------------------------------------------------------------------------------------------------------------------------------- 25648-12 180.00 E 38 45.18 9 128.61 29 45.77 15 61.77 22 14.66 2 25674-11 20.47 4 13.56 1 19.11 5 8.16 0 122.87 24 26.78 8 25694-13 180.00 E 36 180.00 E 42 180.00 E 42 48.88 7 128.30 35 52.18 13 25631-05 74.49 20 145.46 33 18.07 3 180.00 E 40 37.66 7 43.34 12 25660-04 180.00 E 29 180.00 E 25 180.00 E 44 86.24 11 80.50 22 44.25 10 25704-09 17.68 1 22.24 2 14.53 0 20.18 1 76.99 25 61.20 16 25665-07 180.00 E 38 115.14 32 26.56 7 180.00 E 42 180.00 E 51 180.00 E 61 25652-13 180.00 E 40 42.07 7 103.13 27 89.78 18 26.03 3 38.06 4 25733-08 37.02 3 79.53 9 30.99 5 11.91 0 76.91 22 107.12 29 25748-08 121.17 26 51.18 8 63.66 18 45.16 10 35.91 7 40.25 8 25753-15 180.00 E 25 180.00 E 26 34.52 5 40.20 7 74.83 18 145.41 33 25672-15 84.31 24 60.98 14 22.18 3 61.74 12 33.20 5 14.28 0 25655-13 50.84 12 60.65 18 180.00 E 51 33.80 6 25.88 6 22.43 4 25727-16 19.99 3 22.59 4 23.17 4 68.24 14 105.37 23 51.95 9 25626-12 180.00 E 40 180.00 E 45 83.70 21 109.74 28 159.95 50 44.31 10 25749-11 180.00 E 30 180.00 E 25 120.03 21 180.00 E 38 58.63 14 60.70 10 25739-12 180.00 E 39 180.00 E 37 180.00 E 30 180.00 E 32 51.94 14 31.31 6 25756-13 180.00 E 39 71.68 10 32.06 3 26.74 4 88.21 22 24.82 5 25741-09 26.38 5 19.88 1 111.62 27 12.88 0 24.27 4 23.88 2 25752-13 131.58 35 125.67 38 60.77 14 14.77 1 132.91 53 27.83 8 -1088- MEAN 119.20 24 97.79 19 80.64 18 72.21 14 79.11 21 52.74 13 S.D. 68.931 14.5 64.979 14.7 62.479 15.6 61.696 14.1 46.200 15.5 43.343 14.1 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 13 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 3: 0.3 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 2 - A DAY 3 - A DAY 4 - B TRIAL NUMBER 1 TRIAL NUMBER 2 TRIAL NUMBER 3 TRIAL NUMBER 4 TRIAL NUMBER 5 TRIAL NUMBER 6 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ---------------------------------------------------------------------------------------------------------------------------------- 25671-06 36.34 6 56.20 13 79.18 15 29.23 3 180.00 E 41 180.00 E 35 25614-17 36.27 6 15.26 1 131.13 29 22.18 3 37.67 6 180.00 E 36 25698-12 62.82 12 80.96 18 12.01 0 23.25 3 180.00 E 37 180.00 E 44 25677-08 27.90 4 27.11 6 27.30 4 19.99 2 64.86 13 21.44 4 25604-12 62.56 17 29.03 8 43.09 12 49.52 17 180.00 E 34 171.90 50 25678-11 47.34 10 116.53 37 18.20 2 20.69 4 82.06 22 20.77 3 25609-11 48.96 9 65.62 17 11.53 0 8.04 0 180.00 E 39 180.00 E 28 25623-15 38.36 10 74.93 13 70.02 22 13.37 2 180.00 E 46 180.00 E D 25653-13 85.56 21 44.55 10 19.20 2 15.61 2 180.00 E 35 68.37 11 25684-06 132.66 32 41.25 7 25.45 4 25.33 3 180.00 E 44 180.00 E 49 25714-13 48.60 8 35.06 4 35.99 11 96.77 27 180.00 E 39 59.60 12 25650-17 34.84 5 36.20 6 29.91 7 30.59 7 180.00 E 32 180.00 E 28 25735-08 28.09 4 29.01 6 28.86 4 32.59 6 180.00 E 28 61.55 8 25722-15 40.23 8 12.84 1 18.12 2 11.16 0 180.00 E 39 180.00 E 39 25628-17 33.16 7 34.41 7 51.49 13 55.01 13 180.00 E 27 180.00 E 40 25766-06 27.64 3 77.17 20 38.58 8 74.56 17 180.00 E 28 167.09 35 25689-14 14.36 1 180.00 E 30 16.75 1 32.97 6 180.00 E 41 180.00 E 36 25708-15 53.30 10 31.95 5 20.63 3 15.20 1 89.84 25 67.52 13 25743-16 21.06 1 121.52 22 49.84 12 41.13 8 180.00 E 42 180.00 E 41 25642-12 126.16 20 14.56 1 93.16 25 16.56 3 180.00 E 35 180.00 E 42 -1089- MEAN 50.31 10 56.21 12 41.02 9 31.69 6 157.72 33 139.91 29 S.D. 31.568 7.7 42.679 9.8 31.033 8.5 22.442 7.0 46.628 10.3 61.655 15.6 N 20 20 20 20 20 20 20 20 20 20 20 19 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) D = NUMBER OF ERRORS NOT RECORDED; NOT INCLUDED IN CALCULATION OF MEAN E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 14 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 3: 0.3 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 5 - B DAY 6 - B DAY 7 (PROBE) - A TRIAL NUMBER 7 TRIAL NUMBER 8 TRIAL NUMBER 9 TRIAL NUMBER 10 TRIAL NUMBER 11 TRIAL NUMBER 12 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ---------------------------------------------------------------------------------------------------------------------------------- 25671-06 180.00 E 33 180.00 E 27 125.99 28 21.60 4 44.31 8 27.89 5 25614-17 180.00 E 42 180.00 E 38 180.00 E 36 180.00 E 39 67.32 14 85.18 18 25698-12 113.04 29 41.18 20 24.44 4 103.51 25 180.00 E 67 180.00 E 53 25677-08 10.91 0 11.31 0 11.81 0 60.90 13 51.22 17 14.19 2 25604-12 23.45 5 20.76 3 28.45 4 19.13 2 79.38 25 80.80 23 25678-11 71.80 22 24.16 5 26.93 6 35.63 12 70.08 26 82.99 27 25609-11 158.91 36 48.94 11 60.89 18 25.52 5 9.65 0 9.00 0 25623-15 100.77 25 81.66 21 16.96 3 76.28 23 48.59 22 180.00 E 69 25653-13 32.38 5 49.04 9 180.00 E 43 43.26 11 46.72 9 75.41 16 25684-06 180.00 E 48 97.08 15 65.90 19 41.96 7 72.61 24 47.44 14 25714-13 180.00 E 42 177.61 37 15.63 3 25.68 6 41.91 12 89.12 33 25650-17 180.00 E 37 21.65 3 9.56 0 10.07 0 29.56 5 18.34 2 25735-08 103.62 26 67.12 15 89.04 18 50.31 13 16.28 2 125.63 37 25722-15 33.84 10 180.00 E 53 48.38 12 26.20 6 180.00 E 56 85.68 27 25628-17 50.71 13 40.52 7 34.75 6 36.33 5 81.64 28 51.56 13 25766-06 25.53 6 16.06 2 9.20 0 10.18 0 80.36 25 58.13 14 25689-14 180.00 E 42 180.00 E 44 109.13 21 180.00 E 42 19.96 3 44.43 10 25708-15 180.00 E 43 180.00 E 42 180.00 E 23 132.31 32 53.13 10 23.29 3 25743-16 180.00 E 40 180.00 E 39 108.76 22 89.70 18 62.05 16 18.33 2 25642-12 180.00 E 30 180.00 E 34 180.00 E 29 112.88 20 86.00 15 86.41 20 -1090- MEAN 117.25 27 97.85 21 75.29 15 64.07 14 66.04 19 69.19 19 S.D. 67.598 15.3 71.613 16.7 64.213 12.9 52.824 12.5 44.900 16.9 49.461 18.0 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 15 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 4: 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 2 - A DAY 3 - A DAY 4 - B TRIAL NUMBER 1 TRIAL NUMBER 2 TRIAL NUMBER 3 TRIAL NUMBER 4 TRIAL NUMBER 5 TRIAL NUMBER 6 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 26.33 4 33.67 7 40.20 9 33.23 7 44.82 8 145.49 40 25686-10 180.00 E 24 100.68 25 45.17 10 20.78 3 155.30 31 180.00 E 46 25630-09 42.67 6 127.50 28 31.18 6 37.04 7 142.49 32 180.00 E 42 25673-10 180.00 E 41 132.49 29 38.17 10 34.25 11 180.00 E 43 180.00 E 44 25639-04 30.24 5 24.21 3 38.47 5 33.02 5 62.70 8 180.00 E 39 25658-14 74.06 12 72.31 12 180.00 E 41 180.00 E 36 128.95 21 180.00 E 37 25676-15 43.69 9 180.00 E 44 172.55 60 30.39 6 109.84 28 20.24 3 25600-15 174.24 37 16.95 1 34.20 6 18.87 2 180.00 E 53 180.00 E 39 25603-10 79.59 20 45.98 7 17.97 1 14.38 1 180.00 E 43 180.00 E 38 25703-10 50.38 11 103.16 27 37.37 10 33.00 7 180.00 E 46 180.00 E 27 25705-08 59.51 13 20.86 3 18.50 3 23.62 6 180.00 E 37 174.13 43 25611-11 102.35 26 21.96 2 33.18 7 28.29 4 180.00 E 47 25.52 3 25619-12 36.34 7 132.52 23 180.00 E 39 60.09 14 180.00 E 33 180.00 E 37 25691-11 34.63 6 52.43 9 46.59 12 173.34 35 180.00 E 44 109.99 32 25717-15 32.00 4 97.09 22 88.79 21 16.83 0 180.00 E 38 180.00 E 37 25616-14 24.57 3 90.34 21 36.42 8 33.85 7 180.00 E 31 138.03 30 25715-10 29.39 7 59.16 15 16.81 4 32.56 8 180.00 E 34 180.00 E 36 25599-11 180.00 E 30 98.53 21 180.00 E 40 42.99 8 28.23 4 180.00 E 40 25762-11 41.91 8 130.06 25 78.13 19 55.99 12 82.56 19 27.78 5 25647-11 69.10 17 73.17 16 44.72 12 42.37 12 180.00 E 45 180.00 E 39 -1091- MEAN 74.55 15 80.65 17 67.92 16 47.24 10 145.74 32 149.06 33 S.D. 56.967 11.5 46.187 11.4 59.104 16.0 45.762 9.6 51.625 14.0 56.800 13.4 N 20 20 20 20 20 20 20 20 20 20 20 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS APPENDIX 31 (F1 - PND 22) PROJECT NO.:WIL-180017S ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 16 SPONSOR:3M CORPORATION INDIVIDUAL BIEL MAZE SWIM TRIALS SPONSOR NO.:06-128 FEMALES ----------------------------------------------------------------------------------------------------------------------------------- GROUP 4: 1.0 MG/KG/DAY ----------------------------------------------------------------------------------------------------------------------------------- DAY 5 - B DAY 6 - B DAY 7 (PROBE) - A TRIAL NUMBER 7 TRIAL NUMBER 8 TRIAL NUMBER 9 TRIAL NUMBER 10 TRIAL NUMBER 11 TRIAL NUMBER 12 PUP TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS TIME ERRORS NO. (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) (SEC) (NO.) ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 27.06 6 35.82 5 48.04 6 87.99 21 94.24 28 156.77 41 25686-10 103.03 23 84.49 24 13.32 0 11.87 0 42.48 14 43.01 13 25630-09 49.76 11 19.54 2 15.79 0 11.75 0 46.71 12 15.69 2 25673-10 84.21 24 19.31 3 13.33 2 39.38 11 99.74 35 100.90 27 25639-04 180.00 E 42 52.42 9 92.74 22 16.59 1 33.92 7 C 1 25658-14 180.00 E 37 180.00 E 33 36.47 6 78.87 14 26.95 6 66.48 19 25676-15 20.16 3 81.49 20 161.45 45 23.66 3 109.73 41 18.13 4 25600-15 180.00 E 26 72.43 15 39.26 10 14.55 2 95.34 34 49.89 14 25603-10 180.00 E 36 180.00 E 38 100.85 21 180.00 E 52 28.27 5 30.91 8 25703-10 132.39 34 180.00 E 43 18.99 3 13.54 2 124.09 41 81.56 26 25705-08 41.51 8 43.08 9 180.00 E 51 95.52 33 73.93 27 51.86 18 25611-11 59.68 16 31.96 5 14.27 1 8.61 0 28.81 4 13.09 0 25619-12 29.94 9 180.00 E 42 180.00 E 41 113.41 23 41.04 12 17.18 3 25691-11 180.00 E 32 180.00 E 34 180.00 E 39 180.00 E 32 118.52 37 24.92 4 25717-15 180.00 E 39 154.52 30 180.00 E 34 105.31 15 47.70 7 85.25 19 25616-14 17.92 3 24.09 4 119.32 29 17.67 4 103.18 27 49.47 18 25715-10 153.23 41 88.86 30 63.55 24 10.51 2 180.00 E 64 52.99 21 25599-11 180.00 E 43 71.07 17 176.27 38 43.88 8 81.55 13 126.03 34 25762-11 180.00 E 44 49.00 9 67.40 14 180.00 E 44 66.88 19 42.98 9 25647-11 180.00 E 38 180.00 E 50 108.35 20 38.81 4 130.95 38 49.68 14 -1092- MEAN 116.94 26 95.40 21 90.47 20 63.60 14 78.70 24 56.67 15 S.D. 67.633 14.8 64.422 15.4 65.982 16.7 60.844 15.7 42.154 16.2 38.853 11.4 N 20 20 20 20 20 20 20 20 20 20 19 20 ----------------------------------------------------------------------------------------------------------------------------------- A = ANIMALS TESTED IN PATH A DIRECTION (FORWARD ROUTE THROUGH MAZE) B = ANIMALS TESTED IN PATH B DIRECTION (REVERSE ROUTE THROUGH MAZE) C = TIME NOT RECORDED; NOT INCLUDED IN CALCULATION OF MEANS E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS MANUALv1.0 10/05/2006 R:01/24/2007 -1093- Final Report Volume 4 of 6 (Appendices 32-44) Study Title An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats Study Number WIL-180017 Data Requirement EPA OPPTS Guideline 870.6300; OECD Draft Guideline 426 Study Director Donald G. Stump, PhD, DABT Study Initiation Date 21 April 2006 Study Completion Date 10 January 2008 Performing Laboratory WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-9281 Sponsor Study Number 06-128 Sponsor 3M Corporation 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 WIL-180017 3M Corporation -1094- MTDID 208 06-128 APPENDICES 32-44 PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 1 ANIMAL NO.25654-09 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/03/06 DATE OF DEATH: 08/03/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1095- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 2 ANIMAL NO.25632-07 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1096- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 3 ANIMAL NO.25618-08 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1097- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 4 ANIMAL NO.25681-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1098- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 5 ANIMAL NO.25713-02 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1099- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 6 ANIMAL NO.25648-07 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/03/06 DATE OF DEATH: 08/03/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- KIDNEYS GROSS: DILATED PELVIS 3 RIGHT NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1100- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 7 ANIMAL NO.25674-02 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1101- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 8 ANIMAL NO.25631-04 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1102- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 9 ANIMAL NO.25733-07 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- KIDNEYS GROSS: DILATED PELVIS 3 RIGHT NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1103- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 10 ANIMAL NO.25741-07 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/08/06 DATE OF DEATH: 08/08/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1104- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 11 ANIMAL NO.25614-10 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1105- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 12 ANIMAL NO.25604-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1106- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 13 ANIMAL NO.25609-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1107- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 14 ANIMAL NO.25650-11 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1108- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 15 ANIMAL NO.25689-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1109- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 16 ANIMAL NO.25639-06 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1110- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 17 ANIMAL NO.25705-07 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- KIDNEYS GROSS: DILATED PELVIS 3 BILATERAL NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1111- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 18 ANIMAL NO.25619-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- EYES GROSS: EYE(S)- OPACITY P BILATERAL; CEO OPACITY NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1112- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 19 ANIMAL NO.25691-07 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- KIDNEYS GROSS: DILATED PELVIS 2 RIGHT NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1113- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 20 ANIMAL NO.25717-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN EPIDIDYMIDES ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND PANCREAS PITUITARY PROSTATE SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH SEMINAL VESICLES TESTES THYMUS THYROID GLANDS TRACHEA URINARY BLADDER GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1114- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 21 ANIMAL NO.25687-15 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- KIDNEYS GROSS: DILATED PELVIS 2 RIGHT THYMUS GROSS: AREA(S), DARK RED P MULTIPLE, IRREGULARLY SHAPED NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1115- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 22 ANIMAL NO.25681-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- UTERUS GROSS: CONTENTS, CLEAR FLUID P BOTH HORNS NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1116- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 23 ANIMAL NO.25713-16 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1117- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 24 ANIMAL NO.25663-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1118- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 25 ANIMAL NO.25692-07 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1119- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 26 ANIMAL NO.25648-12 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/03/06 DATE OF DEATH: 08/03/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1120- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 27 ANIMAL NO.25674-11 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1121- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 28 ANIMAL NO.25660-04 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1122- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 29 ANIMAL NO.25733-08 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- KIDNEYS GROSS: DILATED PELVIS 2 RIGHT NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1123- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 30 ANIMAL NO.25727-16 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1124- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 31 ANIMAL NO.25614-17 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1125- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 32 ANIMAL NO.25677-08 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1126- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 33 ANIMAL NO.25684-06 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1127- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 34 ANIMAL NO.25735-08 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1128- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 35 ANIMAL NO.25743-16 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1129- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 36 ANIMAL NO.25686-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- UTERUS GROSS: CONTENTS, CLEAR FLUID P BOTH HORNS NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1130- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 37 ANIMAL NO.25639-04 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1131- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 38 ANIMAL NO.25658-14 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1132- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 39 ANIMAL NO.25603-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT -1133- PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 32 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 40 ANIMAL NO.25599-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED GROSS:ADRENAL GLANDS BRAIN ESOPHAGUS EYES HEART INTESTINE KIDNEYS LIVER LYMPH NODE, MES LUNGS MAMMARY GLAND OVIDUCTS OVARIES PANCREAS PITUITARY SPINAL CORD SAL. GLAND MAND SKIN SPLEEN STOMACH THYMUS THYROID GLANDS TRACHEA URINARY BLADDER UTERUS CERVIX VAGINA GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PGRHv4.54 10/05/2006 R:01/24/2007 -1134- PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 1 ANIMAL NO.25597-07 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5342 3.934 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 39. -1135- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 2 ANIMAL NO.25654-05 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5633 3.257 NO SIGNIFICANT BRAIN LENGTH(MM) 22.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 48. -1136- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 3 ANIMAL NO.25632-06 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5922 2.793 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 57. -1137- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 4 ANIMAL NO.25633-04 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.3776 3.936 NO SIGNIFICANT BRAIN LENGTH(MM) 20.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.5 FINAL BODY WT(G) 35. -1138- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 5 ANIMAL NO.25618-07 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6450 3.046 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 54. -1139- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 6 ANIMAL NO.25621-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7036 3.042 NO SIGNIFICANT BRAIN LENGTH(MM) 22.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 56. -1140- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 7 ANIMAL NO.25687-05 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6198 3.000 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 54. -1141- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 8 ANIMAL NO.25681-06 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7520 3.074 NO SIGNIFICANT BRAIN LENGTH(MM) 22.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 57. -1142- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 9 ANIMAL NO.25615-05 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6743 3.220 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 52. -1143- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 10 ANIMAL NO.25637-11 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6787 2.845 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 59. -1144- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 11 ANIMAL NO.25638-05 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6259 2.903 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 56. -1145- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 12 ANIMAL NO.25713-08 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6503 2.895 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 57. -1146- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 13 ANIMAL NO.25670-03 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6338 2.866 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 57. -1147- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 14 ANIMAL NO.25657-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4956 2.337 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.3 FINAL BODY WT(G) 64. -1148- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 15 ANIMAL NO.25663-02 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5796 2.507 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 63. -1149- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 16 ANIMAL NO.25648-10 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5226 3.310 NO SIGNIFICANT BRAIN LENGTH(MM) 22.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 46. -1150- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 17 ANIMAL NO.25674-05 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5905 3.699 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 43. -1151- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 18 ANIMAL NO.25694-11 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7530 2.827 NO SIGNIFICANT BRAIN LENGTH(MM) 22.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 62. -1152- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 19 ANIMAL NO.25631-07 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6294 2.809 NO SIGNIFICANT BRAIN LENGTH(MM) 22.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 58. -1153- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 20 ANIMAL NO.25660-02 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6608 2.863 NO SIGNIFICANT BRAIN LENGTH(MM) 22.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 58. -1154- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 21 ANIMAL NO.25704-04 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5406 2.703 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 57. -1155- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 22 ANIMAL NO.25665-02 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6061 3.569 NO SIGNIFICANT BRAIN LENGTH(MM) 22.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 45. -1156- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 23 ANIMAL NO.25652-03 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5975 2.958 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 54. -1157- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 24 ANIMAL NO.25733-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5312 3.646 NO SIGNIFICANT BRAIN LENGTH(MM) 22.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 42. -1158- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 25 ANIMAL NO.25748-05 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6508 2.706 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 61. -1159- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 26 ANIMAL NO.25753-03 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7192 3.070 NO SIGNIFICANT BRAIN LENGTH(MM) 22.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 56. -1160- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 27 ANIMAL NO.25672-05 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5875 2.995 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 53. -1161- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 28 ANIMAL NO.25655-07 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5492 3.038 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 51. -1162- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 29 ANIMAL NO.25727-05 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5137 3.089 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 49. -1163- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 30 ANIMAL NO.25626-07 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5539 2.547 NO SIGNIFICANT BRAIN LENGTH(MM) 22.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 61. -1164- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 31 ANIMAL NO.25671-03 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5957 2.849 NO SIGNIFICANT BRAIN LENGTH(MM) 22.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 56. -1165- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 32 ANIMAL NO.25614-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4764 3.013 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 49. -1166- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 33 ANIMAL NO.25698-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5305 3.401 NO SIGNIFICANT BRAIN LENGTH(MM) 21.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 45. -1167- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 34 ANIMAL NO.25677-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5833 3.231 NO SIGNIFICANT BRAIN LENGTH(MM) 22.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 49. -1168- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 35 ANIMAL NO.25604-06 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6137 2.934 NO SIGNIFICANT BRAIN LENGTH(MM) 22.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 55. -1169- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 36 ANIMAL NO.25678-03 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4652 2.664 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 55. -1170- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 37 ANIMAL NO.25609-03 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5998 3.137 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 51. -1171- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 38 ANIMAL NO.25623-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6663 3.333 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 50. -1172- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 39 ANIMAL NO.25653-03 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5225 2.581 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 59. -1173- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 40 ANIMAL NO.25684-05 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7210 2.917 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 59. -1174- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 41 ANIMAL NO.25714-06 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6641 2.774 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 60. -1175- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 42 ANIMAL NO.25735-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6405 2.689 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 61. -1176- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 43 ANIMAL NO.25722-05 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5192 3.165 NO SIGNIFICANT BRAIN LENGTH(MM) 22.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 48. -1177- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 44 ANIMAL NO.25628-09 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5399 2.905 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 53. -1178- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 45 ANIMAL NO.25766-11 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5704 3.739 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 42. -1179- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 46 ANIMAL NO.25696-07 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6459 3.165 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 52. -1180- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 47 ANIMAL NO.25686-02 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4767 3.142 NO SIGNIFICANT BRAIN LENGTH(MM) 21.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 47. -1181- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 48 ANIMAL NO.25630-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7562 3.252 NO SIGNIFICANT BRAIN LENGTH(MM) 22.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 54. -1182- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 49 ANIMAL NO.25673-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4298 3.250 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 44. -1183- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 50 ANIMAL NO.25639-09 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5940 2.846 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 56. -1184- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 51 ANIMAL NO.25658-05 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5337 3.263 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 47. -1185- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 52 ANIMAL NO.25676-03 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7188 2.865 NO SIGNIFICANT BRAIN LENGTH(MM) 22.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 60. -1186- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 53 ANIMAL NO.25600-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7359 3.045 NO SIGNIFICANT BRAIN LENGTH(MM) 22.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 57. -1187- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 54 ANIMAL NO.25603-05 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6978 3.032 NO SIGNIFICANT BRAIN LENGTH(MM) 22.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 56. -1188- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 55 ANIMAL NO.25703-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7293 2.789 NO SIGNIFICANT BRAIN LENGTH(MM) 22.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 62. -1189- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 56 ANIMAL NO.25705-05 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5358 2.742 NO SIGNIFICANT BRAIN LENGTH(MM) 21.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 56. -1190- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 57 ANIMAL NO.25611-08 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6548 3.122 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 53. -1191- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 58 ANIMAL NO.25619-05 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5516 3.042 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 51. -1192- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 59 ANIMAL NO.25691-06 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6211 2.895 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 56. -1193- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 60 ANIMAL NO.25717-03 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6253 3.533 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 46. -1194- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 61 ANIMAL NO.25597-16 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.3884 3.752 NO SIGNIFICANT BRAIN LENGTH(MM) 21.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.4 FINAL BODY WT(G) 37. -1195- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 62 ANIMAL NO.25654-11 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5404 3.950 NO SIGNIFICANT BRAIN LENGTH(MM) 21.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.5 FINAL BODY WT(G) 39. -1196- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 63 ANIMAL NO.25632-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6386 2.825 NO SIGNIFICANT BRAIN LENGTH(MM) 22.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 58. -1197- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 64 ANIMAL NO.25633-11 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4920 4.263 NO SIGNIFICANT BRAIN LENGTH(MM) 20.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.4 FINAL BODY WT(G) 35. -1198- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 65 ANIMAL NO.25618-15 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4737 2.947 NO SIGNIFICANT BRAIN LENGTH(MM) 21.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 50. -1199- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 66 ANIMAL NO.25621-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6777 3.165 NO SIGNIFICANT BRAIN LENGTH(MM) 22.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 53. -1200- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 67 ANIMAL NO.25687-14 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6004 3.266 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 49. -1201- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 68 ANIMAL NO.25681-11 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6107 3.579 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 45. -1202- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 69 ANIMAL NO.25615-08 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5897 2.839 NO SIGNIFICANT BRAIN LENGTH(MM) 21.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 56. -1203- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 70 ANIMAL NO.25637-15 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7608 3.036 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 58. -1204- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 71 ANIMAL NO.25638-16 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7253 3.137 NO SIGNIFICANT BRAIN LENGTH(MM) 22.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 55. -1205- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 72 ANIMAL NO.25713-12 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6703 3.037 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 55. -1206- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 73 ANIMAL NO.25670-16 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6038 3.341 NO SIGNIFICANT BRAIN LENGTH(MM) 21.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 48. -1207- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 74 ANIMAL NO.25657-15 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5723 3.083 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.3 FINAL BODY WT(G) 51. -1208- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 75 ANIMAL NO.25663-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6434 2.739 NO SIGNIFICANT BRAIN LENGTH(MM) 22.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 60. -1209- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 76 ANIMAL NO.25648-14 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5386 3.345 NO SIGNIFICANT BRAIN LENGTH(MM) 21.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 46. -1210- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 77 ANIMAL NO.25674-14 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4823 4.360 NO SIGNIFICANT BRAIN LENGTH(MM) 20.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.3 FINAL BODY WT(G) 34. -1211- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 78 ANIMAL NO.25694-15 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6310 2.812 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 58. -1212- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 79 ANIMAL NO.25631-15 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5908 3.002 NO SIGNIFICANT BRAIN LENGTH(MM) 21.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 53. -1213- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 80 ANIMAL NO.25660-13 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4944 2.622 NO SIGNIFICANT BRAIN LENGTH(MM) 21.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 57. -1214- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 81 ANIMAL NO.25704-12 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5839 3.046 NO SIGNIFICANT BRAIN LENGTH(MM) 21.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 52. -1215- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 82 ANIMAL NO.25665-05 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6624 3.260 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 51. -1216- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 83 ANIMAL NO.25652-08 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6292 3.195 NO SIGNIFICANT BRAIN LENGTH(MM) 22.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 51. -1217- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 84 ANIMAL NO.25733-15 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4735 3.274 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.4 FINAL BODY WT(G) 45. -1218- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 85 ANIMAL NO.25748-10 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5158 3.032 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 50. -1219- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 86 ANIMAL NO.25753-17 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.7194 3.016 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 57. -1220- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 87 ANIMAL NO.25672-16 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5217 3.804 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 40. -1221- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 88 ANIMAL NO.25655-15 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5495 2.980 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 52. -1222- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 89 ANIMAL NO.25727-10 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5787 3.359 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 47. -1223- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 90 ANIMAL NO.25626-15 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5813 2.984 NO SIGNIFICANT BRAIN LENGTH(MM) 22.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.5 FINAL BODY WT(G) 53. -1224- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 91 ANIMAL NO.25671-09 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/13/06 DATE OF DEATH: 06/13/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5259 3.317 NO SIGNIFICANT BRAIN LENGTH(MM) 22.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.5 FINAL BODY WT(G) 46. -1225- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 92 ANIMAL NO.25614-18 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5253 3.245 NO SIGNIFICANT BRAIN LENGTH(MM) 21.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 47. -1226- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 93 ANIMAL NO.25698-04 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5141 3.292 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 46. -1227- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 94 ANIMAL NO.25677-13 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6806 3.232 NO SIGNIFICANT BRAIN LENGTH(MM) 22.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 52. -1228- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 95 ANIMAL NO.25604-10 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4340 2.927 NO SIGNIFICANT BRAIN LENGTH(MM) 21.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 49. -1229- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 96 ANIMAL NO.25678-13 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5368 3.136 NO SIGNIFICANT BRAIN LENGTH(MM) 22.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 49. -1230- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 97 ANIMAL NO.25609-12 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6100 2.825 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 57. -1231- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 98 ANIMAL NO.25623-14 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5838 3.232 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 49. -1232- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 99 ANIMAL NO.25653-05 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5506 2.628 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.4 FINAL BODY WT(G) 59. -1233- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 100 ANIMAL NO.25684-12 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6199 3.000 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 54. -1234- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 101 ANIMAL NO.25714-08 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6276 2.906 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 56. -1235- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 102 ANIMAL NO.25735-10 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5448 2.663 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 58. -1236- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 103 ANIMAL NO.25722-12 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5623 3.125 NO SIGNIFICANT BRAIN LENGTH(MM) 22.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 50. -1237- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 104 ANIMAL NO.25628-14 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5093 2.848 NO SIGNIFICANT BRAIN LENGTH(MM) 22.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.5 FINAL BODY WT(G) 53. -1238- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 105 ANIMAL NO.25766-08 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5093 3.510 NO SIGNIFICANT BRAIN LENGTH(MM) 21.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 43. -1239- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 106 ANIMAL NO.25696-16 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6080 3.034 NO SIGNIFICANT BRAIN LENGTH(MM) 22.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 53. -1240- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 107 ANIMAL NO.25686-09 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5509 3.300 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 47. -1241- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 108 ANIMAL NO.25630-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6530 3.061 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 54. -1242- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 109 ANIMAL NO.25673-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4314 3.408 NO SIGNIFICANT BRAIN LENGTH(MM) 21.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.5 FINAL BODY WT(G) 42. -1243- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 110 ANIMAL NO.25639-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4790 2.791 NO SIGNIFICANT BRAIN LENGTH(MM) 21.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 53. -1244- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 111 ANIMAL NO.25658-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5486 3.226 NO SIGNIFICANT BRAIN LENGTH(MM) 21.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 48. -1245- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 112 ANIMAL NO.25676-12 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6938 3.080 NO SIGNIFICANT BRAIN LENGTH(MM) 22.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 55. -1246- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 113 ANIMAL NO.25600-12 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6127 2.781 NO SIGNIFICANT BRAIN LENGTH(MM) 22.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 58. -1247- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 114 ANIMAL NO.25603-07 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4966 2.993 NO SIGNIFICANT BRAIN LENGTH(MM) 21.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.3 FINAL BODY WT(G) 50. -1248- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 115 ANIMAL NO.25703-08 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6146 3.105 NO SIGNIFICANT BRAIN LENGTH(MM) 22.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 52. -1249- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 116 ANIMAL NO.25705-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4230 2.587 NO SIGNIFICANT BRAIN LENGTH(MM) 21.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.4 FINAL BODY WT(G) 55. -1250- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 117 ANIMAL NO.25611-15 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.6533 3.062 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 54. -1251- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 118 ANIMAL NO.25619-14 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4748 3.073 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.4 FINAL BODY WT(G) 48. -1252- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 119 ANIMAL NO.25691-14 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.5656 2.699 NO SIGNIFICANT BRAIN LENGTH(MM) 22.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 58. -1253- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 33 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 120 ANIMAL NO.25717-13 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.4477 3.147 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 46. -1254- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PGRHv4.54 10/05/2006 R:01/26/2007 APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 MALE GROUP: 0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25597-07 39. 1.5342 22.5 14.8 25654-05 48. 1.5633 22.7 15.0 25632-06 57. 1.5922 22.4 15.1 25633-04 35. 1.3776 20.7 14.5 25618-07 54. 1.6450 22.0 15.3 25621-01 56. 1.7036 22.7 15.4 25687-05 54. 1.6198 22.5 15.3 25681-06 57. 1.7520 22.9 15.4 25615-05 52. 1.6743 22.4 15.4 25637-11 59. 1.6787 22.5 15.4 25638-05 56. 1.6259 22.4 15.2 25713-08 57. 1.6503 22.4 14.8 25670-03 57. 1.6338 22.2 14.9 25657-01 64. 1.4956 22.4 14.3 25663-02 63. 1.5796 22.4 15.0 MEAN S.D. N 54. 1.6084 7.9 0.09172 15 15 22.3 0.50 15 15.1 0.34 15 -1255- APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 MALE GROUP: 0.1 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25648-10 46. 1.5226 22.1 14.7 25674-05 43. 1.5905 22.4 14.6 25694-11 62. 1.7530 22.9 15.4 25631-07 58. 1.6294 22.9 15.0 25660-02 58. 1.6608 22.7 15.2 25704-04 57. 1.5406 22.4 14.6 25665-02 45. 1.6061 22.6 14.7 25652-03 54. 1.5975 22.5 14.6 25733-01 42. 1.5312 22.1 14.8 25748-05 61. 1.6508 22.5 15.1 25753-03 56. 1.7192 22.7 15.2 25672-05 53. 1.5875 22.2 15.2 25655-07 51. 1.5492 22.2 14.7 25727-05 49. 1.5137 22.0 14.9 25626-07 61. 1.5539 22.3 15.1 MEAN S.D. N 53. 1.6004 6.8 0.07144 15 15 22.4 0.29 15 14.9 0.27 15 -1256- APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 MALE GROUP: 0.3 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25671-03 56. 1.5957 22.9 15.1 25614-04 49. 1.4764 21.5 14.6 25698-02 45. 1.5305 21.8 15.1 25677-04 49. 1.5833 22.1 14.9 25604-06 55. 1.6137 22.3 14.9 25678-03 55. 1.4652 22.2 15.1 25609-03 51. 1.5998 22.2 14.8 25623-04 50. 1.6663 22.4 15.2 25653-03 59. 1.5225 22.0 14.8 25684-05 59. 1.7210 22.0 15.3 25714-06 60. 1.6641 22.2 14.9 25735-04 61. 1.6405 22.5 14.9 25722-05 48. 1.5192 22.1 14.6 25628-09 53. 1.5399 22.2 15.2 25766-11 42. 1.5704 22.2 14.8 MEAN S.D. N 53. 1.5806 5.7 0.07315 15 15 22.2 0.31 15 14.9 0.21 15 -1257- APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 MALE GROUP: 1.0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25696-07 52. 1.6459 22.5 15.1 25686-02 47. 1.4767 21.9 14.6 25630-01 54. 1.7562 22.7 15.4 25673-04 44. 1.4298 22.0 14.8 25639-09 56. 1.5940 22.0 15.0 25658-05 47. 1.5337 22.0 14.8 25676-03 60. 1.7188 22.9 14.9 25600-04 57. 1.7359 22.7 15.2 25603-05 56. 1.6978 22.3 15.0 25703-04 62. 1.7293 22.7 15.3 25705-05 56. 1.5358 21.8 15.0 25611-08 53. 1.6548 22.4 15.2 25619-05 51. 1.5516 22.2 14.9 25691-06 56. 1.6211 22.4 14.8 25717-03 46. 1.6253 22.2 14.9 MEAN S.D. N 53. 1.6204 5.3 0.09937 15 15 22.3 0.34 15 15.0 0.22 15 -1258- APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 FEMALE GROUP: 0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25597-16 37. 1.3884 21.3 14.4 25654-11 39. 1.5404 21.7 14.5 25632-10 58. 1.6386 22.6 15.4 25633-11 35. 1.4920 20.7 14.4 25618-15 50. 1.4737 21.7 14.6 25621-09 53. 1.6777 22.3 15.2 25687-14 49. 1.6004 22.2 15.0 25681-11 45. 1.6107 22.5 14.7 25615-08 56. 1.5897 21.4 14.7 25637-15 58. 1.7608 22.2 15.3 25638-16 55. 1.7253 22.7 15.4 25713-12 55. 1.6703 22.5 15.1 25670-16 48. 1.6038 21.9 14.6 25657-15 51. 1.5723 22.4 14.3 25663-10 60. 1.6434 22.3 15.3 MEAN S.D. N 50. 1.5992 7.9 0.09741 15 15 22.0 0.57 15 14.9 0.40 15 -1259- APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 FEMALE GROUP: 0.1 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25648-14 46. 1.5386 21.8 14.6 25674-14 34. 1.4823 20.9 14.3 25694-15 58. 1.6310 22.0 14.8 25631-15 53. 1.5908 21.8 14.8 25660-13 57. 1.4944 21.9 14.9 25704-12 52. 1.5839 21.7 14.6 25665-05 51. 1.6624 22.2 15.0 25652-08 51. 1.6292 22.1 14.6 25733-15 45. 1.4735 21.5 14.4 25748-10 50. 1.5158 22.2 14.6 25753-17 57. 1.7194 22.5 14.8 25672-16 40. 1.5217 21.5 14.7 25655-15 52. 1.5495 22.2 14.8 25727-10 47. 1.5787 22.0 15.1 25626-15 53. 1.5813 22.1 14.5 MEAN S.D. N 50. 1.5702 6.5 0.06985 15 15 21.9 0.39 15 14.7 0.22 15 -1260- APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 FEMALE GROUP: 0.3 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25671-09 46. 1.5259 22.9 14.5 25614-18 47. 1.5253 21.8 14.7 25698-04 46. 1.5141 22.0 14.7 25677-13 52. 1.6806 22.1 15.3 25604-10 49. 1.4340 21.8 14.6 25678-13 49. 1.5368 22.3 14.9 25609-12 57. 1.6100 21.5 15.1 25623-14 49. 1.5838 22.2 15.2 25653-05 59. 1.5506 22.4 14.4 25684-12 54. 1.6199 22.5 15.1 25714-08 56. 1.6276 22.2 15.1 25735-10 58. 1.5448 22.4 15.0 25722-12 50. 1.5623 22.6 15.0 25628-14 53. 1.5093 22.5 14.5 25766-08 43. 1.5093 21.9 14.7 MEAN S.D. N 51. 1.5556 4.9 0.06085 15 15 22.2 0.37 15 14.9 0.29 15 -1261- APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 FEMALE GROUP: 1.0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25696-16 53. 1.6080 22.4 15.0 25686-09 47. 1.5509 21.5 14.7 25630-11 54. 1.6530 22.0 15.2 25673-11 42. 1.4314 21.4 14.5 25639-11 53. 1.4790 21.7 14.6 25658-10 48. 1.5486 21.8 14.8 25676-12 55. 1.6938 22.9 15.1 25600-12 58. 1.6127 22.1 14.9 25603-07 50. 1.4966 21.6 14.3 25703-08 52. 1.6146 22.0 15.0 25705-10 55. 1.4230 21.8 14.4 25611-15 54. 1.6533 22.2 15.3 25619-14 48. 1.4748 21.5 14.4 25691-14 58. 1.5656 22.2 15.0 25717-13 46. 1.4477 21.5 14.6 MEAN S.D. N 52. 1.5502 4.6 0.08778 15 15 21.9 0.41 15 14.8 0.31 15 -1262- POFBWv4.14 10/05/2006 R:01/26/2007 APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 MALE GROUP: 0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25597-07 39. 3.934 25654-05 48. 3.257 25632-06 57. 2.793 25633-04 35. 3.936 25618-07 54. 3.046 25621-01 56. 3.042 25687-05 54. 3.000 25681-06 57. 3.074 25615-05 52. 3.220 25637-11 59. 2.845 25638-05 56. 2.903 25713-08 57. 2.895 25670-03 57. 2.866 25657-01 64. 2.337 25663-02 63. 2.507 MEAN S.D. N 54. 3.044 7.9 0.4336 15 15 PAGE 1 -1263- APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 MALE GROUP: 0.1 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25648-10 46. 3.310 25674-05 43. 3.699 25694-11 62. 2.827 25631-07 58. 2.809 25660-02 58. 2.863 25704-04 57. 2.703 25665-02 45. 3.569 25652-03 54. 2.958 25733-01 42. 3.646 25748-05 61. 2.706 25753-03 56. 3.070 25672-05 53. 2.995 25655-07 51. 3.038 25727-05 49. 3.089 25626-07 61. 2.547 MEAN S.D. N 53. 3.055 6.8 0.3547 15 15 PAGE 2 -1264- APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 MALE GROUP: 0.3 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25671-03 56. 2.849 25614-04 49. 3.013 25698-02 45. 3.401 25677-04 49. 3.231 25604-06 55. 2.934 25678-03 55. 2.664 25609-03 51. 3.137 25623-04 50. 3.333 25653-03 59. 2.581 25684-05 59. 2.917 25714-06 60. 2.774 25735-04 61. 2.689 25722-05 48. 3.165 25628-09 53. 2.905 25766-11 42. 3.739 MEAN S.D. N 53. 3.022 5.7 0.3150 15 15 PAGE 3 -1265- APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 MALE GROUP: 1.0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25696-07 52. 3.165 25686-02 47. 3.142 25630-01 54. 3.252 25673-04 44. 3.250 25639-09 56. 2.846 25658-05 47. 3.263 25676-03 60. 2.865 25600-04 57. 3.045 25603-05 56. 3.032 25703-04 62. 2.789 25705-05 56. 2.743 25611-08 53. 3.122 25619-05 51. 3.042 25691-06 56. 2.895 25717-03 46. 3.533 MEAN S.D. N 53. 3.066 5.3 0.2147 15 15 PAGE 4 -1266- APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 FEMALE GROUP: 0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25597-16 37. 3.752 25654-11 39. 3.950 25632-10 58. 2.825 25633-11 35. 4.263 25618-15 50. 2.947 25621-09 53. 3.165 25687-14 49. 3.266 25681-11 45. 3.579 25615-08 56. 2.839 25637-15 58. 3.036 25638-16 55. 3.137 25713-12 55. 3.037 25670-16 48. 3.341 25657-15 51. 3.083 25663-10 60. 2.739 MEAN S.D. N 50. 3.264 7.9 0.4411 15 15 PAGE 5 -1267- APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 FEMALE GROUP: 0.1 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25648-14 46. 3.345 25674-14 34. 4.360 25694-15 58. 2.812 25631-15 53. 3.002 25660-13 57. 2.622 25704-12 52. 3.046 25665-05 51. 3.260 25652-08 51. 3.195 25733-15 45. 3.274 25748-10 50. 3.032 25753-17 57. 3.016 25672-16 40. 3.804 25655-15 52. 2.980 25727-10 47. 3.359 25626-15 53. 2.984 MEAN S.D. N 50. 3.206 6.5 0.4200 15 15 PAGE 6 -1268- APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 FEMALE GROUP: 0.3 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25671-09 46. 3.317 25614-18 47. 3.245 25698-04 46. 3.292 25677-13 52. 3.232 25604-10 49. 2.927 25678-13 49. 3.136 25609-12 57. 2.825 25623-14 49. 3.232 25653-05 59. 2.628 25684-12 54. 3.000 25714-08 56. 2.906 25735-10 58. 2.663 25722-12 50. 3.125 25628-14 53. 2.848 25766-08 43. 3.510 MEAN S.D. N 51. 3.059 4.9 0.2557 15 15 PAGE 7 -1269- APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017E ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 FEMALE GROUP: 1.0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25696-16 53. 3.034 25686-09 47. 3.300 25630-11 54. 3.061 25673-11 42. 3.408 25639-11 53. 2.791 25658-10 48. 3.226 25676-12 55. 3.080 25600-12 58. 2.781 25603-07 50. 2.993 25703-08 52. 3.105 25705-10 55. 2.587 25611-15 54. 3.062 25619-14 48. 3.073 25691-14 58. 2.699 25717-13 46. 3.147 MEAN S.D. N 52. 3.023 4.6 0.2245 15 15 PAGE 8 POFBWv4.14 10/05/2006 R:01/26/2007 -1270- PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 1 ANIMAL NO.25597-04 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/03/06 DATE OF DEATH: 08/03/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.19 0.646 NO SIGNIFICANT BRAIN LENGTH(MM) 21.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 339. -1271- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 2 ANIMAL NO.25633-05 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.546 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 383. -1272- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 3 ANIMAL NO.25621-07 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.19 0.530 NO SIGNIFICANT BRAIN LENGTH(MM) 21.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.8 FINAL BODY WT(G) 413. -1273- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 4 ANIMAL NO.25687-07 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.05 0.504 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 407. -1274- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 5 ANIMAL NO.25615-03 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.505 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 414. -1275- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 6 ANIMAL NO.25637-06 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.25 0.472 NO SIGNIFICANT BRAIN LENGTH(MM) 20.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 477. -1276- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 7 ANIMAL NO.25638-07 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.16 0.535 BRAIN CYST(S) P BRAIN LENGTH(MM) 21.1 ONE, 9 X 4 X 4 MM, EXTENDS INTO RIGHT CEREBRAL HEMISPHERE BRAIN WIDTH(MM) 15.3 NO SIGNIFICANT FINAL BODY WT(G) 404. CHANGES OBSERVED GROSS:SPINAL C.-CERV. SPINAL C.-LUMB. -1277- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 8 ANIMAL NO.25670-09 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.28 0.494 NO SIGNIFICANT BRAIN LENGTH(MM) 20.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 462. -1278- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 9 ANIMAL NO.25657-08 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.26 0.467 NO SIGNIFICANT BRAIN LENGTH(MM) 21.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 484. -1279- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 10 ANIMAL NO.25663-04 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.36 0.521 NO SIGNIFICANT BRAIN LENGTH(MM) 21.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 16.0 FINAL BODY WT(G) 453. -1280- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 11 ANIMAL NO.25690-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.17 0.536 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.5 FINAL BODY WT(G) 405. -1281- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 12 ANIMAL NO.25666-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.18 0.469 NO SIGNIFICANT BRAIN LENGTH(MM) 20.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.5 FINAL BODY WT(G) 465. -1282- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 13 ANIMAL NO.25692-04 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.28 0.539 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 423. -1283- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 14 ANIMAL NO.25701-09 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.08 0.501 NO SIGNIFICANT BRAIN LENGTH(MM) 20.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 415. -1284- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 15 ANIMAL NO.25645-06 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 08/08/06 DATE OF DEATH: 08/08/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.14 0.618 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 346. -1285- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 16 ANIMAL NO.25694-04 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.29 0.470 NO SIGNIFICANT BRAIN LENGTH(MM) 21.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.5 FINAL BODY WT(G) 487. -1286- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 17 ANIMAL NO.25660-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.08 0.494 NO SIGNIFICANT BRAIN LENGTH(MM) 20.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 421. -1287- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 18 ANIMAL NO.25704-03 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.14 0.523 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 409. -1288- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 19 ANIMAL NO.25665-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.17 0.559 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.5 FINAL BODY WT(G) 388. -1289- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 20 ANIMAL NO.25652-04 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.37 0.456 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.8 FINAL BODY WT(G) 520. -1290- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 21 ANIMAL NO.25748-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.23 0.478 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 467. -1291- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 22 ANIMAL NO.25753-06 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.34 0.522 NO SIGNIFICANT BRAIN LENGTH(MM) 21.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 448. -1292- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 23 ANIMAL NO.25672-06 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.21 0.558 NO SIGNIFICANT BRAIN LENGTH(MM) 20.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 396. -1293- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 24 ANIMAL NO.25655-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.544 NO SIGNIFICANT BRAIN LENGTH(MM) 20.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 384. -1294- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 25 ANIMAL NO.25727-07 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.31 0.510 NO SIGNIFICANT BRAIN LENGTH(MM) 20.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 453. -1295- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 26 ANIMAL NO.25626-04 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.33 0.537 NO SIGNIFICANT BRAIN LENGTH(MM) 20.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 434. -1296- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 27 ANIMAL NO.25749-04 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.25 0.517 NO SIGNIFICANT BRAIN LENGTH(MM) 20.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 435. -1297- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 28 ANIMAL NO.25739-07 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.38 0.515 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 16.0 FINAL BODY WT(G) 462. -1298- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 29 ANIMAL NO.25756-05 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.23 0.432 NO SIGNIFICANT BRAIN LENGTH(MM) 21.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 516. -1299- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 30 ANIMAL NO.25752-09 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 08/08/06 DATE OF DEATH: 08/08/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.33 0.512 NO SIGNIFICANT BRAIN LENGTH(MM) 20.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.5 FINAL BODY WT(G) 455. -1300- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 31 ANIMAL NO.25671-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/03/06 DATE OF DEATH: 08/03/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.28 0.500 NO SIGNIFICANT BRAIN LENGTH(MM) 21.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 456. -1301- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 32 ANIMAL NO.25698-05 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.19 0.523 NO SIGNIFICANT BRAIN LENGTH(MM) 21.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 419. -1302- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 33 ANIMAL NO.25677-05 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.18 0.525 NO SIGNIFICANT BRAIN LENGTH(MM) 20.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 415. -1303- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 34 ANIMAL NO.25678-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.12 0.480 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 442. -1304- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 35 ANIMAL NO.25623-08 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.08 0.458 NO SIGNIFICANT BRAIN LENGTH(MM) 20.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 454. -1305- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 36 ANIMAL NO.25653-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.05 0.499 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 411. -1306- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 37 ANIMAL NO.25684-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.22 0.521 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 426. -1307- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 38 ANIMAL NO.25714-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.33 0.556 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 419. -1308- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 39 ANIMAL NO.25735-05 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.10 0.469 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 448. -1309- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 40 ANIMAL NO.25722-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.17 0.505 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 430. -1310- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 41 ANIMAL NO.25642-05 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.07 0.478 NO SIGNIFICANT BRAIN LENGTH(MM) 20.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 433. -1311- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 42 ANIMAL NO.25628-07 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.22 0.577 NO SIGNIFICANT BRAIN LENGTH(MM) 20.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.5 FINAL BODY WT(G) 385. -1312- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 43 ANIMAL NO.25766-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.571 NO SIGNIFICANT BRAIN LENGTH(MM) 20.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 366. -1313- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 44 ANIMAL NO.25708-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.18 0.536 NO SIGNIFICANT BRAIN LENGTH(MM) 20.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 407. -1314- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 45 ANIMAL NO.25743-08 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.15 0.505 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 426. -1315- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 46 ANIMAL NO.25696-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.25 0.518 NO SIGNIFICANT BRAIN LENGTH(MM) 21.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 434. -1316- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 47 ANIMAL NO.25686-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.483 NO SIGNIFICANT BRAIN LENGTH(MM) 20.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 433. -1317- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 48 ANIMAL NO.25630-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.38 0.548 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 16.0 FINAL BODY WT(G) 434. -1318- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 49 ANIMAL NO.25673-09 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.554 NO SIGNIFICANT BRAIN LENGTH(MM) 20.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 377. -1319- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 50 ANIMAL NO.25658-08 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.28 0.497 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 459. -1320- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 51 ANIMAL NO.25676-02 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.34 0.561 NO SIGNIFICANT BRAIN LENGTH(MM) 21.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 417. -1321- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 52 ANIMAL NO.25600-02 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.22 0.531 NO SIGNIFICANT BRAIN LENGTH(MM) 20.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 418. -1322- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 53 ANIMAL NO.25603-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.06 0.490 NO SIGNIFICANT BRAIN LENGTH(MM) 20.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.8 FINAL BODY WT(G) 420. -1323- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 54 ANIMAL NO.25703-03 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.16 0.536 NO SIGNIFICANT BRAIN LENGTH(MM) 20.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.7 FINAL BODY WT(G) 403. -1324- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 55 ANIMAL NO.25611-07 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.06 0.575 NO SIGNIFICANT BRAIN LENGTH(MM) 19.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 358. -1325- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 56 ANIMAL NO.25616-05 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.29 0.482 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.5 FINAL BODY WT(G) 475. -1326- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 57 ANIMAL NO.25715-07 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.483 NO SIGNIFICANT BRAIN LENGTH(MM) 20.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 433. -1327- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 58 ANIMAL NO.25599-06 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.21 0.554 NO SIGNIFICANT BRAIN LENGTH(MM) 20.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 399. -1328- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 59 ANIMAL NO.25762-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.28 0.544 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 419. -1329- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 60 ANIMAL NO.25647-07 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.21 0.612 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 361. -1330- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 61 ANIMAL NO.25597-17 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/03/06 DATE OF DEATH: 08/03/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.79 0.856 NO SIGNIFICANT BRAIN LENGTH(MM) 19.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.4 FINAL BODY WT(G) 209. -1331- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 62 ANIMAL NO.25654-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/03/06 DATE OF DEATH: 08/03/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.07 0.912 NO SIGNIFICANT BRAIN LENGTH(MM) 20.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 227. -1332- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 63 ANIMAL NO.25632-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.01 0.817 NO SIGNIFICANT BRAIN LENGTH(MM) 20.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 246. -1333- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 64 ANIMAL NO.25633-13 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.83 0.753 NO SIGNIFICANT BRAIN LENGTH(MM) 19.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.5 FINAL BODY WT(G) 243. -1334- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 65 ANIMAL NO.25618-17 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.88 0.734 NO SIGNIFICANT BRAIN LENGTH(MM) 19.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 256. -1335- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 66 ANIMAL NO.25621-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.11 0.746 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 283. -1336- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 67 ANIMAL NO.25615-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.00 0.741 NO SIGNIFICANT BRAIN LENGTH(MM) 20.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 270. -1337- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 68 ANIMAL NO.25637-17 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.14 0.773 NO SIGNIFICANT BRAIN LENGTH(MM) 19.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 277. -1338- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 69 ANIMAL NO.25638-18 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.93 0.898 NO SIGNIFICANT BRAIN LENGTH(MM) 19.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 215. -1339- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 70 ANIMAL NO.25670-18 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.07 0.770 NO SIGNIFICANT BRAIN LENGTH(MM) 19.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 269. -1340- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 71 ANIMAL NO.25657-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.05 0.751 NO SIGNIFICANT BRAIN LENGTH(MM) 20.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 273. -1341- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 72 ANIMAL NO.25690-19 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.10 0.747 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 281. -1342- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 73 ANIMAL NO.25666-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.93 0.818 NO SIGNIFICANT BRAIN LENGTH(MM) 19.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 236. -1343- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 74 ANIMAL NO.25701-18 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.00 0.816 NO SIGNIFICANT BRAIN LENGTH(MM) 19.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 245. -1344- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 75 ANIMAL NO.25645-08 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/08/06 DATE OF DEATH: 08/08/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.96 0.995 NO SIGNIFICANT BRAIN LENGTH(MM) 19.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 197. -1345- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 76 ANIMAL NO.25694-13 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.87 0.782 NO SIGNIFICANT BRAIN LENGTH(MM) 19.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.6 FINAL BODY WT(G) 239. -1346- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 77 ANIMAL NO.25631-05 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.06 0.772 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 267. -1347- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 78 ANIMAL NO.25704-09 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.04 0.758 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 269. -1348- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 79 ANIMAL NO.25665-07 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.10 0.942 NO SIGNIFICANT BRAIN LENGTH(MM) 19.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.2 FINAL BODY WT(G) 223. -1349- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 80 ANIMAL NO.25652-13 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.02 0.808 NO SIGNIFICANT BRAIN LENGTH(MM) 19.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 250. -1350- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 81 ANIMAL NO.25748-08 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.857 NO SIGNIFICANT BRAIN LENGTH(MM) 19.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 244. -1351- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 82 ANIMAL NO.25753-15 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.07 0.812 NO SIGNIFICANT BRAIN LENGTH(MM) 19.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 255. -1352- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 83 ANIMAL NO.25672-15 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.99 0.843 NO SIGNIFICANT BRAIN LENGTH(MM) 19.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 236. -1353- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 84 ANIMAL NO.25655-13 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.95 0.717 NO SIGNIFICANT BRAIN LENGTH(MM) 19.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 272. -1354- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 85 ANIMAL NO.25626-12 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.03 0.760 NO SIGNIFICANT BRAIN LENGTH(MM) 19.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 267. -1355- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 86 ANIMAL NO.25749-11 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.13 0.826 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 258. -1356- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 87 ANIMAL NO.25739-12 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.00 0.697 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 287. -1357- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 88 ANIMAL NO.25756-13 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.90 0.860 NO SIGNIFICANT BRAIN LENGTH(MM) 20.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 221. -1358- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 89 ANIMAL NO.25741-09 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/08/06 DATE OF DEATH: 08/08/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.99 0.729 NO SIGNIFICANT BRAIN LENGTH(MM) 19.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.6 FINAL BODY WT(G) 273. -1359- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 90 ANIMAL NO.25752-13 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 08/08/06 DATE OF DEATH: 08/08/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.690 NO SIGNIFICANT BRAIN LENGTH(MM) 20.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 303. -1360- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 91 ANIMAL NO.25671-06 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/03/06 DATE OF DEATH: 08/03/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.01 0.804 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 250. -1361- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 92 ANIMAL NO.25698-12 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.98 0.835 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 237. -1362- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 93 ANIMAL NO.25604-12 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.07 0.821 NO SIGNIFICANT BRAIN LENGTH(MM) 20.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 252. -1363- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 94 ANIMAL NO.25678-11 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.02 0.798 NO SIGNIFICANT BRAIN LENGTH(MM) 20.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 253. -1364- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 95 ANIMAL NO.25609-11 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.02 0.828 NO SIGNIFICANT BRAIN LENGTH(MM) 19.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 244. -1365- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 96 ANIMAL NO.25623-15 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.03 0.802 NO SIGNIFICANT BRAIN LENGTH(MM) 19.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 253. -1366- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 97 ANIMAL NO.25653-13 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.95 0.855 NO SIGNIFICANT BRAIN LENGTH(MM) 19.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 228. -1367- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 98 ANIMAL NO.25714-13 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.07 0.793 NO SIGNIFICANT BRAIN LENGTH(MM) 19.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.4 FINAL BODY WT(G) 261. -1368- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 99 ANIMAL NO.25650-17 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.03 0.728 NO SIGNIFICANT BRAIN LENGTH(MM) 19.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 279. -1369- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 100 ANIMAL NO.25722-15 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.96 0.778 NO SIGNIFICANT BRAIN LENGTH(MM) 19.7 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 252. -1370- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 101 ANIMAL NO.25628-17 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.97 0.758 NO SIGNIFICANT BRAIN LENGTH(MM) 19.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 260. -1371- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 102 ANIMAL NO.25766-06 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.97 0.883 NO SIGNIFICANT BRAIN LENGTH(MM) 19.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 223. -1372- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 103 ANIMAL NO.25689-14 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.08 0.867 NO SIGNIFICANT BRAIN LENGTH(MM) 20.2 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 240. -1373- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 104 ANIMAL NO.25708-15 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.10 0.955 NO SIGNIFICANT BRAIN LENGTH(MM) 19.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 220. -1374- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 105 ANIMAL NO.25642-12 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.96 0.688 NO SIGNIFICANT BRAIN LENGTH(MM) 19.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.1 FINAL BODY WT(G) 285. -1375- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 106 ANIMAL NO.25696-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.07 0.841 NO SIGNIFICANT BRAIN LENGTH(MM) 20.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.5 FINAL BODY WT(G) 246. -1376- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 107 ANIMAL NO.25630-09 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.90 0.864 NO SIGNIFICANT BRAIN LENGTH(MM) 19.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 220. -1377- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 108 ANIMAL NO.25673-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/04/06 DATE OF DEATH: 08/04/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.94 0.886 NO SIGNIFICANT BRAIN LENGTH(MM) 19.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 219. -1378- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 109 ANIMAL NO.25676-15 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.11 0.879 NO SIGNIFICANT BRAIN LENGTH(MM) 20.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 240. -1379- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 110 ANIMAL NO.25600-15 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.09 0.874 NO SIGNIFICANT BRAIN LENGTH(MM) 19.8 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 239. -1380- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 111 ANIMAL NO.25703-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.05 0.851 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.3 FINAL BODY WT(G) 241. -1381- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 112 ANIMAL NO.25705-08 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/05/06 DATE OF DEATH: 08/05/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.01 0.773 NO SIGNIFICANT BRAIN LENGTH(MM) 20.1 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 260. -1382- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 113 ANIMAL NO.25611-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.94 0.886 NO SIGNIFICANT BRAIN LENGTH(MM) 18.9 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 219. -1383- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 114 ANIMAL NO.25619-12 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.92 0.691 NO SIGNIFICANT BRAIN LENGTH(MM) 19.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 278. -1384- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 115 ANIMAL NO.25691-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.92 0.706 NO SIGNIFICANT BRAIN LENGTH(MM) 19.5 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 272. -1385- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 116 ANIMAL NO.25717-15 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.99 0.762 NO SIGNIFICANT BRAIN LENGTH(MM) 19.4 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.8 FINAL BODY WT(G) 261. -1386- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 117 ANIMAL NO.25616-14 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.01 0.750 NO SIGNIFICANT BRAIN LENGTH(MM) 20.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 268. -1387- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 118 ANIMAL NO.25715-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/06/06 DATE OF DEATH: 08/06/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 1.93 0.835 NO SIGNIFICANT BRAIN LENGTH(MM) 19.6 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.7 FINAL BODY WT(G) 231. -1388- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 119 ANIMAL NO.25762-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.04 1.030 NO SIGNIFICANT BRAIN LENGTH(MM) 20.3 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 14.9 FINAL BODY WT(G) 198. -1389- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 36 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MACROSCOPIC FINDINGS PAGE 120 ANIMAL NO.25647-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 08/07/06 DATE OF DEATH: 08/07/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- ORGAN WEIGHT ABS.(G) REL. PERFUSED BRAIN 2.06 0.792 NO SIGNIFICANT BRAIN LENGTH(MM) 20.0 CHANGES OBSERVED GROSS:BRAIN SPINAL C.-CERV. SPINAL C.-LUMB. BRAIN WIDTH(MM) 15.0 FINAL BODY WT(G) 260. -1390- GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT PGRHv4.54 10/05/2006 R:01/24/2007 APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 MALE GROUP: 0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25597-04 339. 2.19 21.3 15.7 25633-05 383. 2.09 20.4 15.3 25621-07 413. 2.19 21.2 15.8 25687-07 407. 2.05 20.8 15.6 25615-03 414. 2.09 20.3 15.7 25637-06 477. 2.25 20.5 15.4 25638-07 404. 2.16 21.1 15.3 25670-09 462. 2.28 20.9 15.6 25657-08 484. 2.26 21.0 15.4 25663-04 453. 2.36 21.2 16.0 25690-01 405. 2.17 20.3 15.5 25666-01 465. 2.18 20.2 15.5 25692-04 423. 2.28 20.8 15.4 25701-09 415. 2.08 20.7 15.2 25645-06 346. 2.14 20.8 15.0 MEAN S.D. N 419. 43.4 15 2.18 0.088 15 20.8 0.36 15 15.5 0.25 15 -1391- APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 MALE GROUP: 0.1 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25694-04 487. 2.29 21.0 15.5 25660-01 421. 2.08 20.0 15.6 25704-03 409. 2.14 20.4 15.4 25665-01 388. 2.17 20.4 15.5 25652-04 520. 2.37 20.8 15.8 25748-01 467. 2.23 20.8 15.4 25753-06 448. 2.34 21.9 15.6 25672-06 396. 2.21 20.5 15.4 25655-01 384. 2.09 20.1 15.4 25727-07 453. 2.31 20.7 15.7 25626-04 434. 2.33 20.9 15.7 25749-04 435. 2.25 20.6 15.4 25739-07 462. 2.38 21.5 16.0 25756-05 516. 2.23 21.1 15.6 25752-09 455. 2.33 20.9 15.5 MEAN S.D. N 445. 42.1 15 2.25 0.097 15 20.8 0.49 15 15.6 0.18 15 -1392- APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 MALE GROUP: 0.3 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25671-04 456. 2.28 21.5 15.6 25698-05 419. 2.19 21.2 15.4 25677-05 415. 2.18 20.9 15.6 25678-02 442. 2.12 20.4 15.2 25623-08 454. 2.08 20.9 15.7 25653-02 411. 2.05 20.4 15.1 25684-04 426. 2.22 20.3 15.2 25714-02 419. 2.33 20.8 15.7 25735-05 448. 2.10 20.8 15.4 25722-01 430. 2.17 20.3 15.2 25642-05 433. 2.07 20.1 15.1 25628-07 385. 2.22 20.2 15.5 25766-01 366. 2.09 20.2 14.8 25708-01 407. 2.18 20.6 15.7 25743-08 426. 2.15 20.3 15.3 MEAN S.D. N 422. 24.5 15 2.16 0.080 15 20.6 0.41 15 15.4 0.27 15 -1393- APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 MALE GROUP: 1.0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25696-04 434. 2.25 21.2 15.6 25686-04 433. 2.09 20.6 15.1 25630-04 434. 2.38 20.8 16.0 25673-09 377. 2.09 20.1 15.1 25658-08 459. 2.28 20.4 15.6 25676-02 417. 2.34 21.0 15.7 25600-02 418. 2.22 20.7 15.6 25603-04 420. 2.06 20.5 15.8 25703-03 403. 2.16 20.2 15.7 25611-07 358. 2.06 19.4 15.4 25616-05 475. 2.29 20.8 15.5 25715-07 433. 2.09 20.2 15.4 25599-06 399. 2.21 20.8 15.4 25762-01 419. 2.28 20.4 15.3 25647-07 361. 2.21 20.3 15.6 MEAN S.D. N 416. 32.7 15 2.20 0.105 15 20.5 0.44 15 15.5 0.25 15 -1394- APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 FEMALE GROUP: 0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25597-17 209. 1.79 19.9 14.4 25654-10 227. 2.07 20.5 15.1 25632-09 246. 2.01 20.1 14.6 25633-13 243. 1.83 19.2 14.5 25618-17 256. 1.88 19.5 15.1 25621-10 283. 2.11 20.4 15.3 25615-10 270. 2.00 20.2 15.1 25637-17 277. 2.14 19.6 15.4 25638-18 215. 1.93 19.4 15.0 25670-18 269. 2.07 19.9 15.1 25657-10 273. 2.05 20.0 14.7 25690-19 281. 2.10 20.4 15.2 25666-09 236. 1.93 19.0 14.7 25701-18 245. 2.00 19.5 14.8 25645-08 197. 1.96 19.5 14.6 MEAN S.D. N 248. 27.5 15 1.99 0.104 15 19.8 0.46 15 14.9 0.31 15 -1395- APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 FEMALE GROUP: 0.1 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25694-13 239. 1.87 19.9 14.6 25631-05 267. 2.06 20.4 14.8 25704-09 269. 2.04 20.4 15.2 25665-07 223. 2.10 19.9 15.2 25652-13 250. 2.02 19.9 14.9 25748-08 244. 2.09 19.9 14.9 25753-15 255. 2.07 19.6 15.1 25672-15 236. 1.99 19.5 15.1 25655-13 272. 1.95 19.3 14.8 25626-12 267. 2.03 19.6 14.9 25749-11 258. 2.13 20.4 15.3 25739-12 287. 2.00 20.4 14.8 25756-13 221. 1.90 20.0 14.8 25741-09 273. 1.99 19.9 15.6 25752-13 303. 2.09 20.4 15.4 MEAN S.D. N 258. 22.8 15 2.02 0.074 15 20.0 0.37 15 15.0 0.27 15 -1396- APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 FEMALE GROUP: 0.3 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25671-06 250. 2.01 20.3 15.1 25698-12 237. 1.98 20.3 14.9 25604-12 252. 2.07 20.5 14.9 25678-11 253. 2.02 20.2 15.4 25609-11 244. 2.02 19.8 14.9 25623-15 253. 2.03 19.6 14.9 25653-13 228. 1.95 19.7 14.8 25714-13 261. 2.07 19.6 15.4 25650-17 279. 2.03 19.6 15.1 25722-15 252. 1.96 19.7 14.9 25628-17 260. 1.97 19.4 15.1 25766-06 223. 1.97 19.4 15.0 25689-14 240. 2.08 20.2 15.1 25708-15 220. 2.10 19.8 15.0 25642-12 285. 1.96 19.6 15.1 MEAN S.D. N 249. 18.4 15 2.01 0.049 15 19.8 0.36 15 15.0 0.18 15 -1397- APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS SPONSOR NO.:06-128 FEMALE GROUP: 1.0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G) LENGTH(MM) WIDTH(MM) ----------------------------------------------------------------------------------------------------------------------------------- 25696-11 246. 2.07 20.5 15.5 25630-09 220. 1.90 19.8 14.9 25673-10 219. 1.94 19.9 15.0 25676-15 240. 2.11 20.1 15.3 25600-15 239. 2.09 19.8 15.0 25703-10 241. 2.05 20.3 15.3 25705-08 260. 2.01 20.1 14.9 25611-11 219. 1.94 18.9 14.7 25619-12 278. 1.92 19.3 14.8 25691-11 272. 1.92 19.5 14.7 25717-15 261. 1.99 19.4 14.8 25616-14 268. 2.01 20.0 14.7 25715-10 231. 1.93 19.6 14.7 25762-11 198. 2.04 20.3 14.9 25647-11 260. 2.06 20.0 15.0 MEAN S.D. N 243. 23.1 15 2.00 0.070 15 19.8 0.43 15 14.9 0.25 15 -1398- POFBWv4.14 10/05/2006 R:01/24/2007 APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 MALE GROUP: 0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25597-04 339. 0.646 25633-05 383. 0.546 25621-07 413. 0.530 25687-07 407. 0.504 25615-03 414. 0.505 25637-06 477. 0.472 25638-07 404. 0.535 25670-09 462. 0.494 25657-08 484. 0.467 25663-04 453. 0.521 25690-01 405. 0.536 25666-01 465. 0.469 25692-04 423. 0.539 25701-09 415. 0.501 25645-06 346. 0.618 MEAN S.D. N 419. 43.4 15 0.526 0.0506 15 PAGE 1 -1399- APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 MALE GROUP: 0.1 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ----------------------------------------------------------------------------------------------------------- 25694-04 487. 0.470 25660-01 421. 0.494 25704-03 409. 0.523 25665-01 388. 0.559 25652-04 520. 0.456 25748-01 467. 0.478 25753-06 448. 0.522 25672-06 396. 0.558 25655-01 384. 0.544 25727-07 453. 0.510 25626-04 434. 0.537 25749-04 435. 0.517 25739-07 462. 0.515 25756-05 516. 0.432 25752-09 455. 0.512 MEAN S.D. N 445. 42.1 15 0.508 0.0367 15 PAGE 2 -1400- APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 MALE GROUP: 0.3 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25671-04 456. 0.500 25698-05 419. 0.523 25677-05 415. 0.525 25678-02 442. 0.480 25623-08 454. 0.458 25653-02 411. 0.499 25684-04 426. 0.521 25714-02 419. 0.556 25735-05 448. 0.469 25722-01 430. 0.505 25642-05 433. 0.478 25628-07 385. 0.577 25766-01 366. 0.571 25708-01 407. 0.536 25743-08 426. 0.505 MEAN S.D. N 422. 24.5 15 0.514 0.0358 15 PAGE 3 -1401- APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 MALE GROUP: 1.0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25696-04 434. 0.518 25686-04 433. 0.483 25630-04 434. 0.548 25673-09 377. 0.554 25658-08 459. 0.497 25676-02 417. 0.561 25600-02 418. 0.531 25603-04 420. 0.490 25703-03 403. 0.536 25611-07 358. 0.575 25616-05 475. 0.482 25715-07 433. 0.483 25599-06 399. 0.554 25762-01 419. 0.544 25647-07 361. 0.612 MEAN S.D. N 416. 32.7 15 0.531 0.0387 15 PAGE 4 -1402- APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 FEMALE GROUP: 0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25597-17 209. 0.856 25654-10 227. 0.912 25632-09 246. 0.817 25633-13 243. 0.753 25618-17 256. 0.734 25621-10 283. 0.746 25615-10 270. 0.741 25637-17 277. 0.773 25638-18 215. 0.898 25670-18 269. 0.770 25657-10 273. 0.751 25690-19 281. 0.747 25666-09 236. 0.818 25701-18 245. 0.816 25645-08 197. 0.995 MEAN S.D. N 248. 27.5 15 0.808 0.0770 15 PAGE 5 -1403- APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 FEMALE GROUP: 0.1 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25694-13 239. 0.782 25631-05 267. 0.772 25704-09 269. 0.758 25665-07 223. 0.942 25652-13 250. 0.808 25748-08 244. 0.857 25753-15 255. 0.812 25672-15 236. 0.843 25655-13 272. 0.717 25626-12 267. 0.760 25749-11 258. 0.826 25739-12 287. 0.697 25756-13 221. 0.860 25741-09 273. 0.729 25752-13 303. 0.690 MEAN S.D. N 258. 22.8 15 0.790 0.0694 15 PAGE 6 -1404- APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 FEMALE GROUP: 0.3 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25671-06 250. 0.804 25698-12 237. 0.835 25604-12 252. 0.821 25678-11 253. 0.798 25609-11 244. 0.828 25623-15 253. 0.802 25653-13 228. 0.855 25714-13 261. 0.793 25650-17 279. 0.728 25722-15 252. 0.778 25628-17 260. 0.758 25766-06 223. 0.883 25689-14 240. 0.867 25708-15 220. 0.955 25642-12 285. 0.688 MEAN S.D. N 249. 18.4 15 0.813 0.0646 15 PAGE 7 -1405- APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) PROJECT NO.:WIL-180017K ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SPONSOR:3M CORPORATION INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS SPONSOR NO.:06-128 FEMALE GROUP: 1.0 MG/KG/DAY ANIMAL FBW(G) WEIGHT(G/100G) ------------------------------------------------------------------------------------------------------------ 25696-11 246. 0.841 25630-09 220. 0.864 25673-10 219. 0.886 25676-15 240. 0.879 25600-15 239. 0.874 25703-10 241. 0.851 25705-08 260. 0.773 25611-11 219. 0.886 25619-12 278. 0.691 25691-11 272. 0.706 25717-15 261. 0.762 25616-14 268. 0.750 25715-10 231. 0.835 25762-11 198. 1.030 25647-11 260. 0.792 MEAN S.D. N 243. 23.1 15 0.828 0.0857 15 PAGE 8 POFBWv4.14 10/05/2006 R:01/24/2007 -1406- APPENDIX 39 (F0 DAMS - GESTATION DAY 20) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 20 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 MG/KG/DAY FEMALES 25679 25659 25634 25620 25706 25612 25629 25718 25760 25683 13.00 9.50 18.20 11.30 11.70 9.40 11.60 11.50 15.00 18.70 -1407- MEAN 12.99 S.D. 3.292 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 39 (F0 DAMS - GESTATION DAY 20) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 20 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.1 MG/KG/DAY FEMALES 25627 25669 25613 25607 25640 25711 25682 25651 25768 25643 9.70 11.30 13.10 8.00 11.50 15.70 15.40 16.00 11.20 7.70 -1408- MEAN 11.96 S.D. 3.048 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 39 (F0 DAMS - GESTATION DAY 20) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 20 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.3 MG/KG/DAY FEMALES 25601 25644 25680 25675 25598 25667 25641 25662 25726 25596 8.40 9.50 13.60 11.70 12.80 10.50 7.80 10.10 11.70 9.10 -1409- MEAN 10.52 S.D. 1.903 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 39 (F0 DAMS - GESTATION DAY 20) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 20 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1.0 MG/KG/DAY FEMALES 25649 25608 25656 25688 25625 25699 25750 25734 25745 25693 11.30 8.00 11.00 14.90 7.70 11.50 12.60 14.40 9.10 8.80 -1410- MEAN 10.93 S.D. 2.538 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER PCHEv4.03 10/05/2006 R:10/10/2006 APPENDIX 40 (F1 FETUSES - GESTATION DAY 20) PROJECT NO.:WIL-180017C ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 20 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 MG/KG/DAY BY LITTER 25679 25659 25634 25620 25706 25612 25629 25718 25760 25683 6.60 12.60 19.90 13.20 7.90 11.20 13.90 8.80 8.60 18.10 -1411- MEAN 12.08 S.D. 4.389 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 40 (F1 FETUSES - GESTATION DAY 20) PROJECT NO.:WIL-180017C ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 20 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.1 MG/KG/DAY BY LITTER 25627 25669 25613 25607 25640 25711 25682 25651 25768 25643 7.80 8.90 10.30 14.50 12.50 6.30 12.20 13.30 11.20 8.20 -1412- MEAN 10.52 S.D. 2.667 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 40 (F1 FETUSES - GESTATION DAY 20) PROJECT NO.:WIL-180017C ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 20 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.3 MG/KG/DAY BY LITTER 25601 25680 25675 25598 25667 25641 25662 25596 6.50 11.50 7.80 9.20 6.80 12.40 10.70 9.90 MEAN 9.35 S.D. 2.175 N 8 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER -1413- APPENDIX 40 (F1 FETUSES - GESTATION DAY 20) PROJECT NO.:WIL-180017C ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 20 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1.0 MG/KG/DAY BY LITTER 25649 25608 25656 25688 25625 25750 25734 25693 7.00 7.80 8.70 10.40 12.90 11.00 11.80 8.00 MEAN 9.70 S.D. 2.125 N 8 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER PCHEv4.03 10/05/2006 R:01/23/2007 -1414- APPENDIX 41 (F0 DAMS - LACTATION DAY 4) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 4 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/mL ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 MG/KG/DAY FEMALES 25632 25618 25621 25687 25681 25615 25637 25638 25670 25657 13.80 7.20 6.00 6.90 12.20 17.10 12.80 11.60 9.40 5.10 -1415- MEAN 10.21 S.D. 3.908 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/mL = NANOGRAMS/MILLILITER APPENDIX 41 (F0 DAMS - LACTATION DAY 4) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 4 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/mL ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.1 MG/KG/DAY FEMALES 25694 25660 25674 25652 25733 25753 25672 25655 25727 25626 10.60 10.20 9.40 9.40 7.00 8.50 21.60 12.50 9.80 11.70 -1416- MEAN 11.07 S.D. 4.009 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/mL = NANOGRAMS/MILLILITER APPENDIX 41 (F0 DAMS - LACTATION DAY 4) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 4 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/mL ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.3 MG/KG/DAY FEMALES 25614 25698 25609 25623 25678 25650 25735 25722 25642 25628 7.60 9.80 7.40 10.00 7.90 8.00 9.40 9.00 9.20 7.00 -1417- MEAN 8.53 S.D. 1.073 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/mL = NANOGRAMS/MILLILITER APPENDIX 41 (F0 DAMS - LACTATION DAY 4) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 4 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/mL ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1.0 MG/KG/DAY FEMALES 25696 25686 25639 25658 25676 25630 25673 25619 25705 25616 5.00 9.60 9.10 10.70 12.80 9.20 15.10 10.80 8.40 10.90 -1418- MEAN 10.16 S.D. 2.681 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/mL = NANOGRAMS/MILLILITER PCHEv4.03 04/10/2007 R:04/10/2007 APPENDIX 42 (F1 PUPS - PND 4) PROJECT NO.:WIL-180017U ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 4 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/mL ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 MG/KG/DAY BY LITTER 25632 25618 25621 25687 25681 25615 25637 25638 25670 25657 6.40 6.70 6.40 6.10 6.50 8.20 1.00 4.10 6.20 4.20 -1419- MEAN 5.58 S.D. 2.001 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/mL = NANOGRAMS/MILLILITER APPENDIX 42 (F1 PUPS - PND 4) PROJECT NO.:WIL-180017U ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 4 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/mL ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.1 MG/KG/DAY BY LITTER 25674 25694 25660 25652 25733 25753 25672 25655 25727 25626 5.00 5.10 5.30 7.00 5.40 6.60 4.80 5.70 4.90 5.20 -1420- MEAN 5.50 S.D. 0.738 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/mL = NANOGRAMS/MILLILITER APPENDIX 42 (F1 PUPS - PND 4) PROJECT NO.:WIL-180017U ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 4 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/mL ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.3 MG/KG/DAY BY LITTER 25614 25698 25678 25609 25623 25650 25735 25722 25642 25628 1.00 4.50 5.90 6.90 7.10 1.00 5.20 5.30 6.60 4.40 -1421- MEAN 4.79 S.D. 2.203 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/mL = NANOGRAMS/MILLILITER APPENDIX 42 (F1 PUPS - PND 4) PROJECT NO.:WIL-180017U ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 4 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/mL ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1.0 MG/KG/DAY BY LITTER 25696 25686 25630 25673 25639 25658 25676 25705 25619 25616 5.90 4.60 5.10 5.10 7.00 7.00 5.50 8.40 4.70 1.00 -1422- MEAN 5.43 S.D. 1.973 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/mL = NANOGRAMS/MILLILITER PCHEv4.03 04/10/2007 R:04/10/2007 APPENDIX 43 (F0 DAMS - LACTATION DAY 21) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 MG/KG/DAY FEMALES 25632 25618 25621 25687 25681 25615 25637 25638 25670 25657 32.20 14.20 12.70 12.70 24.70 14.30 20.00 15.70 12.60 11.30 -1423- MEAN 17.04 S.D. 6.708 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 43 (F0 DAMS - LACTATION DAY 21) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.1 MG/KG/DAY FEMALES 25694 25660 25674 25652 25733 25753 25672 25655 25727 25626 19.20 21.60 14.70 12.40 8.80 18.10 28.80 15.50 16.80 19.30 -1424- MEAN 17.52 S.D. 5.426 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 43 (F0 DAMS - LACTATION DAY 21) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.3 MG/KG/DAY FEMALES 25614 25698 25609 25623 25678 25650 25735 25722 25642 25628 17.40 23.30 10.50 11.70 12.70 12.60 12.60 17.10 18.30 11.40 -1425- MEAN 14.76 S.D. 4.086 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 43 (F0 DAMS - LACTATION DAY 21) PROJECT NO.:WIL-180017 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1.0 MG/KG/DAY FEMALES 25696 25686 25639 25658 25676 25630 25673 25619 25705 25616 14.30 16.80 13.20 28.00 31.00 18.10 24.40 16.40 19.40 13.20 -1426- MEAN 19.48 S.D. 6.270 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER PCHEv4.03 10/05/2006 R:10/10/2006 APPENDIX 44 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 MG/KG/DAY MALES 25632-02 25618-09 25621-03 25687-04 25681-03 25615-06 25637-03 25638-01 25670-06 25657-07 9.90 6.50 7.00 5.10 5.30 11.00 7.00 8.30 6.80 9.40 -1427- MEAN 7.63 S.D. 1.963 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 44 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.1 MG/KG/DAY MALES 25674-04 25694-05 25660-06 25652-01 25733-06 25753-04 25672-09 25655-10 25727-06 25626-01 7.40 8.00 7.70 8.50 8.50 12.80 12.00 8.30 16.30 9.90 -1428- MEAN 9.94 S.D. 2.886 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 44 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.3 MG/KG/DAY MALES 25614-05 25698-03 25678-07 25609-06 25623-03 25650-02 25735-06 25722-10 25642-04 25628-01 7.40 10.40 8.70 5.90 11.30 7.40 12.70 7.50 13.80 9.60 -1429- MEAN 9.47 S.D. 2.565 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 44 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1.0 MG/KG/DAY MALES 25696-06 25686-01 25630-06 25673-08 25639-03 25658-04 25676-04 25705-06 25619-03 25616-02 8.40 6.80 10.00 8.40 7.30 8.50 7.60 9.60 10.40 10.90 -1430- MEAN 8.79 S.D. 1.380 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 44 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0 MG/KG/DAY FEMALES 25632-15 25618-18 25621-12 25687-10 25681-14 25615-09 25637-10 25638-11 25670-17 25657-13 10.60 11.60 7.60 7.50 8.20 11.10 7.50 8.00 6.00 9.90 -1431- MEAN 8.80 S.D. 1.863 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 44 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.1 MG/KG/DAY FEMALES 25674-13 25660-14 25652-11 25733-12 25753-09 25672-11 25655-12 25727-09 25626-08 6.90 6.70 8.60 8.40 10.60 8.40 6.50 14.40 9.30 MEAN 8.87 S.D. 2.462 N 9 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER -1432- APPENDIX 44 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 7 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 0.3 MG/KG/DAY FEMALES 25614-15 25698-14 25678-10 25609-15 25623-13 25650-01 25735-14 25722-11 25642-15 25628-16 6.30 9.40 6.50 6.20 11.70 7.50 11.00 8.80 11.60 7.70 -1433- MEAN 8.67 S.D. 2.173 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER APPENDIX 44 (F1 PUPS - PND 21) PROJECT NO.:WIL-180017V ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 8 SPONSOR:3M CORPORATION INDIVIDUAL TSH VALUES DAY 21 SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL TSH ----------------------------------------------------------------------------------------------------------------------------------- ng/ml ----------------------------------------------------------------------------------------------------------------------------------- GROUP: 1.0 MG/KG/DAY FEMALES 25696-14 25686-15 25630-13 25673-14 25639-12 25658-13 25676-08 25705-11 25619-10 25616-13 7.20 6.30 10.00 6.80 6.60 7.70 9.20 12.70 10.30 7.30 -1434- MEAN 8.41 S.D. 2.072 N 10 ----------------------------------------------------------------------------------------------------------------------------------- ng/ml = NANOGRAMS/MILLILITER PCHEv4.03 10/05/2006 R:10/10/2006 -1435- Final Report Volume 5 of 6 (Appendices 45-56) Study Title An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats Study Number WIL-180017 Data Requirement EPA OPPTS Guideline 870.6300; OECD Draft Guideline 426 Study Director Donald G. Stump, PhD, DABT Study Initiation Date 21 April 2006 Study Completion Date 10 January 2008 Performing Laboratory WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-9281 Sponsor Study Number 06-128 Sponsor 3M Corporation 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 WIL-180017 3M Corporation -1436- MTDID 208 06-128 APPENDICES 45-50 PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 1 ANIMAL NO.25679-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1437- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 2 ANIMAL NO.25659-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1438- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 3 ANIMAL NO.25634-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 2 LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1439- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 4 ANIMAL NO.25620-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1440- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 5 ANIMAL NO.25706-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1441- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 6 ANIMAL NO.25612-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1442- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 7 ANIMAL NO.25629-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1443- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 8 ANIMAL NO.25718-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1444- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 9 ANIMAL NO.25760-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1445- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 10 ANIMAL NO.25683-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1446- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 11 ANIMAL NO.25627-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1447- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 12 ANIMAL NO.25669-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1448- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 13 ANIMAL NO.25613-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1449- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 14 ANIMAL NO.25607-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1450- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 15 ANIMAL NO.25640-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1451- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 16 ANIMAL NO.25711-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1452- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 17 ANIMAL NO.25682-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1453- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 18 ANIMAL NO.25651-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1454- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 19 ANIMAL NO.25768-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1455- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 20 ANIMAL NO.25643-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1456- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 21 ANIMAL NO.25601-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1457- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 22 ANIMAL NO.25644-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1458- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 23 ANIMAL NO.25680-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1459- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 24 ANIMAL NO.25675-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1460- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 25 ANIMAL NO.25598-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1461- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 26 ANIMAL NO.25667-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1462- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 27 ANIMAL NO.25641-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1463- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 28 ANIMAL NO.25662-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1464- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 29 ANIMAL NO.25726-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1465- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 30 ANIMAL NO.25596-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1466- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 31 ANIMAL NO.25649-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1467- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 32 ANIMAL NO.25608-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1468- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 33 ANIMAL NO.25656-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED NO SIGNIFICANT CHANGES OBSERVED NOT EXAMINED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1469- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 34 ANIMAL NO.25688-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1470- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 35 ANIMAL NO.25625-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1471- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 36 ANIMAL NO.25699-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1472- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 37 ANIMAL NO.25750-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED NO SIGNIFICANT CHANGES OBSERVED NOT EXAMINED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1473- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 38 ANIMAL NO.25734-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1474- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 39 ANIMAL NO.25745-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1475- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 40 ANIMAL NO.25693-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1476- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 41 ANIMAL NO.25679-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1477- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 42 ANIMAL NO.25659-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1478- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 43 ANIMAL NO.25634-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1479- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 44 ANIMAL NO.25620-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1480- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 45 ANIMAL NO.25706-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1481- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 46 ANIMAL NO.25612-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1482- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 47 ANIMAL NO.25629-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED NO SIGNIFICANT CHANGES OBSERVED NOT EXAMINED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1483- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 48 ANIMAL NO.25718-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 CONGESTION 3 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1484- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 49 ANIMAL NO.25760-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1485- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 50 ANIMAL NO.25683-02 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1486- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 51 ANIMAL NO.25627-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1487- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 52 ANIMAL NO.25669-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1488- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 53 ANIMAL NO.25613-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1489- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 54 ANIMAL NO.25607-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1490- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 55 ANIMAL NO.25640-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1491- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 56 ANIMAL NO.25711-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1492- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 57 ANIMAL NO.25682-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1493- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 58 ANIMAL NO.25651-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1494- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 59 ANIMAL NO.25768-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1495- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 60 ANIMAL NO.25643-02 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1496- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 61 ANIMAL NO.25601-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1497- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 62 ANIMAL NO.25644-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1498- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 63 ANIMAL NO.25680-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1499- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 64 ANIMAL NO.25675-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1500- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 65 ANIMAL NO.25598-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1501- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 66 ANIMAL NO.25667-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1502- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 67 ANIMAL NO.25641-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1503- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 68 ANIMAL NO.25662-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1504- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 69 ANIMAL NO.25726-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1505- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 70 ANIMAL NO.25596-02 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1506- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 71 ANIMAL NO.25649-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1507- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 72 ANIMAL NO.25608-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/22/06 DATE OF DEATH: 05/22/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1508- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 73 ANIMAL NO.25656-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1509- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 74 ANIMAL NO.25688-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 4 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1510- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 75 ANIMAL NO.25625-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: NOT EXAMINED NOT RECEIVED AT TRIMMING NO SIGNIFICANT CHANGES OBSERVED NOT EXAMINED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1511- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 76 ANIMAL NO.25699-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/23/06 DATE OF DEATH: 05/23/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1512- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 77 ANIMAL NO.25750-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: NOT EXAMINED NOT RECEIVED AT TRIMMING NO SIGNIFICANT CHANGES OBSERVED NOT EXAMINED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1513- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 78 ANIMAL NO.25734-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/24/06 DATE OF DEATH: 05/24/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1514- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 79 ANIMAL NO.25745-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1515- PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 45 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 80 ANIMAL NO.25693-02 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/25/06 DATE OF DEATH: 05/25/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 3 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT PGRHv4.54 04/27/2007 R:04/27/2007 -1516- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 1 ANIMAL NO.25632-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1517- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 2 ANIMAL NO.25618-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1518- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 3 ANIMAL NO.25621-04 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1519- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 4 ANIMAL NO.25687-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1520- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 5 ANIMAL NO.25681-02 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1521- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 6 ANIMAL NO.25615-02 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1522- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 7 ANIMAL NO.25637-02 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1523- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 8 ANIMAL NO.25638-03 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1524- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 9 ANIMAL NO.25670-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1525- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 10 ANIMAL NO.25657-03 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 DECREASED COLLOID 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1526- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 11 ANIMAL NO.25674-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1527- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 12 ANIMAL NO.25694-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1528- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 13 ANIMAL NO.25660-03 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1529- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 14 ANIMAL NO.25652-05 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1530- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 15 ANIMAL NO.25733-02 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1531- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 16 ANIMAL NO.25753-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1532- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 17 ANIMAL NO.25672-03 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1533- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 18 ANIMAL NO.25655-02 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1534- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 19 ANIMAL NO.25727-03 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1535- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 20 ANIMAL NO.25626-02 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1536- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 21 ANIMAL NO.25614-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1537- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 22 ANIMAL NO.25698-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1538- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 23 ANIMAL NO.25678-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1539- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 24 ANIMAL NO.25609-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1540- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 25 ANIMAL NO.25623-06 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1541- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 26 ANIMAL NO.25650-03 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1542- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 27 ANIMAL NO.25735-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1543- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 28 ANIMAL NO.25722-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1544- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 29 ANIMAL NO.25642-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1545- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 30 ANIMAL NO.25628-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1546- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 31 ANIMAL NO.25696-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 DECREASED COLLOID 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1547- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 32 ANIMAL NO.25686-05 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1548- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 33 ANIMAL NO.25630-02 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1549- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 34 ANIMAL NO.25673-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1550- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 35 ANIMAL NO.25639-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1551- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 36 ANIMAL NO.25658-06 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 ONE EXAMINED P ONE THYROID LOBE IN PLANE OF SECTION, RECUT EXAMINED NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1552- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 37 ANIMAL NO.25676-05 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1553- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 38 ANIMAL NO.25705-02 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1554- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 39 ANIMAL NO.25619-02 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1555- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 40 ANIMAL NO.25616-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1556- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 41 ANIMAL NO.25632-11 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1557- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 42 ANIMAL NO.25618-12 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1558- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 43 ANIMAL NO.25621-11 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1559- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 44 ANIMAL NO.25687-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1560- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 45 ANIMAL NO.25681-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1561- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 46 ANIMAL NO.25615-07 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1562- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 47 ANIMAL NO.25637-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1563- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 48 ANIMAL NO.25638-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1564- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 49 ANIMAL NO.25670-12 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 MITOTIC FIGURES 2 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1565- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 50 ANIMAL NO.25657-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1566- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 51 ANIMAL NO.25674-10 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1567- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 52 ANIMAL NO.25694-07 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1568- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 53 ANIMAL NO.25660-11 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1569- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 54 ANIMAL NO.25652-07 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1570- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 55 ANIMAL NO.25733-09 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1571- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 56 ANIMAL NO.25753-08 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1572- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 57 ANIMAL NO.25672-10 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1573- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 58 ANIMAL NO.25655-14 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1574- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 59 ANIMAL NO.25727-11 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1575- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 60 ANIMAL NO.25626-10 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1576- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 61 ANIMAL NO.25614-14 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1577- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 62 ANIMAL NO.25698-07 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1578- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 63 ANIMAL NO.25678-09 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1579- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 64 ANIMAL NO.25609-07 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1580- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 65 ANIMAL NO.25623-10 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1581- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 66 ANIMAL NO.25650-15 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1582- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 67 ANIMAL NO.25735-09 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1583- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 68 ANIMAL NO.25722-14 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1584- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 69 ANIMAL NO.25642-09 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1585- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 70 ANIMAL NO.25628-10 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1586- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 71 ANIMAL NO.25696-12 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1587- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 72 ANIMAL NO.25686-12 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1588- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 73 ANIMAL NO.25630-08 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 ONE EXAMINED P ONE THYROID LOBE IN PLANE OF SECTION, RECUT EXAMINED NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1589- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 74 ANIMAL NO.25673-13 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/28/06 DATE OF DEATH: 05/28/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED NO SIGNIFICANT CHANGES OBSERVED NOT EXAMINED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1590- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 75 ANIMAL NO.25639-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1591- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 76 ANIMAL NO.25658-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1592- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 77 ANIMAL NO.25676-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: ONE EXAMINED P ONE THYROID LOBE IN PLANE OF SECTION, RECUT EXAMINED NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1593- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 78 ANIMAL NO.25705-12 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/29/06 DATE OF DEATH: 05/29/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1594- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 79 ANIMAL NO.25619-07 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: DECREASED COLLOID 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1595- PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 46 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 80 ANIMAL NO.25616-08 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 05/30/06 DATE OF DEATH: 05/30/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED NO SIGNIFICANT CHANGES OBSERVED NOT EXAMINED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT PGRHv4.54 04/27/2007 R:04/27/2007 -1596- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 1 ANIMAL NO.25632-02 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1597- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 2 ANIMAL NO.25618-09 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 CYST, ULTIMOBRANCHIAL P NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1598- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 3 ANIMAL NO.25621-03 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1599- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 4 ANIMAL NO.25687-04 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: CYST, ULTIMOBRANCHIAL P NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1600- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 5 ANIMAL NO.25681-03 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1601- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 6 ANIMAL NO.25615-06 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 CYST, ULTIMOBRANCHIAL P ECTOPIC THYMUS P NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1602- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 7 ANIMAL NO.25637-03 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1603- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 8 ANIMAL NO.25638-01 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1604- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 9 ANIMAL NO.25670-06 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1605- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 10 ANIMAL NO.25657-07 GROUP 1: 0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: CYST, ULTIMOBRANCHIAL P NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1606- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 11 ANIMAL NO.25674-04 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1607- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 12 ANIMAL NO.25694-05 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1608- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 13 ANIMAL NO.25660-06 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1609- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 14 ANIMAL NO.25652-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1610- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 15 ANIMAL NO.25733-06 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1611- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 16 ANIMAL NO.25753-04 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1612- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 17 ANIMAL NO.25672-09 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1613- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 18 ANIMAL NO.25655-10 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1614- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 19 ANIMAL NO.25727-06 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1615- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 20 ANIMAL NO.25626-01 GROUP 2: 0.1 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1616- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 21 ANIMAL NO.25614-05 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1617- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 22 ANIMAL NO.25698-03 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1618- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 23 ANIMAL NO.25678-07 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1619- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 24 ANIMAL NO.25609-06 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1620- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 25 ANIMAL NO.25623-03 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1621- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 26 ANIMAL NO.25650-02 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1622- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 27 ANIMAL NO.25735-06 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1623- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 28 ANIMAL NO.25722-10 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1624- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 29 ANIMAL NO.25642-04 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1625- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 30 ANIMAL NO.25628-01 GROUP 3: 0.3 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1626- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 31 ANIMAL NO.25696-06 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1627- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 32 ANIMAL NO.25686-01 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1628- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 33 ANIMAL NO.25630-06 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1629- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 34 ANIMAL NO.25673-08 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1630- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 35 ANIMAL NO.25639-03 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1631- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 36 ANIMAL NO.25658-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1632- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 37 ANIMAL NO.25676-04 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1633- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 38 ANIMAL NO.25705-06 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1634- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 39 ANIMAL NO.25619-03 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1635- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 40 ANIMAL NO.25616-02 GROUP 4: 1.0 MG/KG/DAY MALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1636- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 41 ANIMAL NO.25632-15 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1637- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 42 ANIMAL NO.25618-18 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1638- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 43 ANIMAL NO.25621-12 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1639- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 44 ANIMAL NO.25687-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1640- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 45 ANIMAL NO.25681-14 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1641- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 46 ANIMAL NO.25615-09 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1642- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 47 ANIMAL NO.25637-10 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1643- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 48 ANIMAL NO.25638-11 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1644- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 49 ANIMAL NO.25670-17 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1645- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 50 ANIMAL NO.25657-13 GROUP 1: 0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1646- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 51 ANIMAL NO.25674-13 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1647- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 52 ANIMAL NO.25694-08 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1648- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 53 ANIMAL NO.25660-14 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1649- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 54 ANIMAL NO.25652-11 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1650- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 55 ANIMAL NO.25733-12 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1651- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 56 ANIMAL NO.25753-09 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1652- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 57 ANIMAL NO.25672-11 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1653- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 58 ANIMAL NO.25655-12 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1654- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 59 ANIMAL NO.25727-09 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1655- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 60 ANIMAL NO.25626-08 GROUP 2: 0.1 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1656- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 61 ANIMAL NO.25614-15 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1657- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 62 ANIMAL NO.25698-14 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1658- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 63 ANIMAL NO.25678-10 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1659- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 64 ANIMAL NO.25609-15 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1660- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 65 ANIMAL NO.25623-13 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1661- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 66 ANIMAL NO.25650-01 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1662- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 67 ANIMAL NO.25735-14 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1663- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 68 ANIMAL NO.25722-11 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1664- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 69 ANIMAL NO.25642-15 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1665- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 70 ANIMAL NO.25628-16 GROUP 3: 0.3 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1666- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 71 ANIMAL NO.25696-14 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1667- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 72 ANIMAL NO.25686-15 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1668- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 73 ANIMAL NO.25630-13 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1669- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 74 ANIMAL NO.25673-14 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/14/06 DATE OF DEATH: 06/14/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1670- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 75 ANIMAL NO.25639-12 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1671- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 76 ANIMAL NO.25658-13 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1672- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 77 ANIMAL NO.25676-08 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CHANGES OBSERVED MICRO:THYROID GLANDS MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1673- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 78 ANIMAL NO.25705-11 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/15/06 DATE OF DEATH: 06/15/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1674- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 79 ANIMAL NO.25619-10 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: MITOTIC FIGURES 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT -1675- PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128 APPENDIX 47 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL MICROSCOPIC FINDINGS PAGE 80 ANIMAL NO.25616-13 GROUP 4: 1.0 MG/KG/DAY FEMALE SCHEDULED EUTH 06/16/06 DATE OF DEATH: 06/16/06 GRADE ----------------------------------------------------------------------------------------------------------------------------------- THYROID GLANDS MICRO: LUMINAL DEBRIS, CELLULAR 1 NO SIGNIFICANT CHANGES OBSERVED MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT PGRHv4.54 04/27/2007 R:04/27/2007 -1676- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID 25615-02 LENGTH AREA (PIXELS)(PIXELS 2) 119 93 34809 96 66 19921 91 67 19068 80 43 10912 88 56 15407 65 48 9803 77 63 15325 61 52 9922 62 47 9186 83 63 16281 MEASUREMENTS LENGTH (um) 38 30 31 21 29 22 26 14 28 18 21 15 25 20 20 17 20 15 27 20 AND AREAS AREA (um2) 3622 2073 1984 1135 1603 1020 1595 1032 956 1694 25618-01 LENGTH AREA (PIXELS)(PIXELS 2) 94 82 24332 71 47 10556 114 84 30195 76 57 13462 73 48 11025 70 56 12274 66 57 11836 68 47 10074 71 61 13657 60 44 8319 MEAN AREA SD N 16063 7652.8 10 1672 796.3 10 14573 7009.6 10 GROUP MEAN GROUP SD GROUP N 17695 3056.5 10 1841 318.1 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 1 LENGTH (um) 30 27 23 15 37 27 24 18 23 16 23 18 21 18 22 15 23 20 19 14 AREA (um2) 2532 1098 3142 1401 1147 1277 1232 1048 1421 866 1516 729.4 10 -1677- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25621-04 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 131 42 120 49346 39 5135 110 36 85 29523 27 3072 84 27 62 16465 20 1713 82 26 49 12500 16 1301 79 25 56 13852 18 1441 72 23 66 14954 21 1556 93 30 77 22391 25 2330 90 29 64 18307 21 1905 96 31 88 26583 28 2766 66 21 50 10385 16 1081 AREAS 25632-01 LENGTH AREA (PIXELS)(PIXELS 2) 69 66 14239 72 60 13487 101 73 23090 95 43 12979 70 57 12445 86 72 19420 76 64 15215 76 48 11589 72 49 10926 74 56 12992 MEAN AREA SD N 21431 11584.5 10 2230 1205.5 10 14638 3792.8 10 PAGE 2 LENGTH (um) 22 21 23 19 33 23 31 14 22 18 28 23 25 21 25 16 23 16 24 18 AREA (um2) 1482 1403 2403 1351 1295 2021 1583 1206 1137 1352 1523 394.7 10 -1678- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25637-02 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 89 29 63 17610 20 1832 95 31 74 22094 24 2299 89 29 70 19642 23 2044 118 38 79 29096 25 3028 72 23 43 9698 14 1009 77 25 45 10783 14 1122 82 27 47 12261 15 1276 73 23 42 9641 14 1003 74 24 40 9379 13 976 75 24 55 12960 18 1349 AREAS 25638-03 LENGTH AREA (PIXELS)(PIXELS 2) 97 57 17353 106 103 34430 109 82 28230 93 61 17754 77 49 11828 70 52 11443 69 45 9892 62 44 8506 70 65 14296 79 72 17887 MEAN AREA SD N 15316 6618.5 10 1594 688.7 10 17162 8291.6 10 PAGE 3 LENGTH (um) 31 18 34 33 35 27 30 20 25 16 23 17 22 15 20 14 23 21 26 23 AREA (um2) 1806 3583 2938 1847 1231 1191 1029 885 1488 1861 1786 862.8 10 -1679- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25657-03 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 133 43 97 40478 31 4212 109 35 77 26349 25 2742 82 27 53 13672 17 1423 84 27 62 16396 20 1706 104 34 96 31438 31 3271 130 42 104 42632 34 4436 96 31 67 20210 22 2103 85 28 62 16645 20 1732 74 24 54 12729 18 1325 75 24 58 13609 19 1416 AREAS 25670-01 LENGTH AREA (PIXELS)(PIXELS 2) 107 79 26576 114 78 27869 94 70 20674 86 71 19183 98 70 21495 104 77 25136 83 49 12847 71 48 10669 75 56 13095 87 71 19233 MEAN AREA SD N 23416 11274.6 10 2437 1173.2 10 19678 5966.2 10 PAGE 4 LENGTH (um) 35 26 37 25 30 23 28 23 32 23 33 25 27 16 23 16 24 18 28 23 AREA (um2) 2765 2900 2151 1996 2237 2616 1337 1110 1363 2001 2048 620.8 10 -1680- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25681-02 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 105 34 76 25027 25 2604 78 25 54 13281 17 1382 131 42 68 28223 22 2937 88 28 78 21639 25 2252 72 23 52 11696 17 1217 71 23 49 11015 16 1146 68 22 47 10060 15 1047 62 20 42 8171 13 850 82 26 56 14344 18 1493 73 24 58 13303 19 1384 AREAS 25687-01 LENGTH AREA (PIXELS)(PIXELS 2) 100 82 25672 99 74 22907 97 74 22627 83 73 19103 106 83 27619 80 64 16042 78 55 13551 67 51 10701 82 55 14192 84 67 17554 MEAN AREA SD N 15676 6823.1 10 1631 710.0 10 18997 5575.4 10 PAGE 5 LENGTH (um) 32 26 32 24 31 24 27 23 34 27 26 21 25 18 22 16 27 18 27 22 AREA (um2) 2671 2384 2355 1988 2874 1669 1410 1114 1477 1827 1977 580.2 10 -1681- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25616-01 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 134 43 92 38663 30 4023 112 36 84 29501 27 3070 115 37 60 21803 19 2269 124 40 98 37949 31 3949 92 30 55 15951 18 1660 82 26 57 14789 19 1539 70 23 56 12374 18 1288 79 26 65 16329 21 1699 74 24 47 11025 15 1147 99 32 93 29062 30 3024 AREAS 25619-02 LENGTH AREA (PIXELS)(PIXELS 2) 82 66 16817 66 43 8793 114 67 24051 77 53 12800 84 56 14683 77 53 12844 62 43 8427 64 51 10316 57 41 7425 67 66 13900 MEAN AREA SD N 22745 10363.0 10 2367 1078.4 10 13006 4913.8 10 GROUP MEAN GROUP SD GROUP N 14731 3543.6 10 1533 368.7 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 6 LENGTH (um) 26 21 21 14 37 22 25 17 27 18 25 17 20 14 21 17 18 13 22 21 AREA (um2) 1750 915 2503 1332 1528 1337 877 1073 773 1446 1353 511.3 10 -1682- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25630-02 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 94 30 76 22570 25 2349 94 30 80 23627 26 2459 68 22 51 10813 16 1125 78 25 60 14791 19 1539 97 31 45 13588 14 1414 79 26 45 11208 14 1166 70 23 44 9763 14 1016 73 23 40 9178 13 955 64 21 39 7705 12 802 66 21 36 7475 12 778 AREAS 25639-01 LENGTH AREA (PIXELS)(PIXELS 2) 104 51 16552 77 40 9597 63 29 5735 91 53 15231 64 45 9153 88 45 12301 91 39 11061 80 43 10689 85 38 10226 69 40 8732 MEAN AREA SD N 13072 5770.3 10 1360 600.4 10 10928 3150.1 10 PAGE 7 LENGTH (um) 34 16 25 13 20 9 29 17 21 15 28 14 29 13 26 14 27 12 22 13 AREA (um2) 1722 999 597 1585 952 1280 1151 1112 1064 909 1137 327.8 10 -1683- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25658-06 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 74 24 57 13301 18 1384 131 42 94 38752 30 4032 73 24 54 12291 17 1279 81 26 53 13422 17 1397 105 34 46 15076 15 1569 88 28 56 15397 18 1602 52 17 39 6404 13 666 69 22 33 7055 11 734 58 19 30 5434 10 565 52 17 36 5846 12 608 AREAS 25673-01 LENGTH AREA (PIXELS)(PIXELS 2) 101 63 20065 84 67 17749 76 64 15391 75 54 12743 83 61 15924 102 81 25769 88 85 23553 78 52 12865 56 37 6623 72 43 9735 MEAN AREA SD N 13298 9777.3 10 1384 1017.4 10 16042 5963.3 10 PAGE 8 LENGTH (um) 33 20 27 22 25 21 24 17 27 20 33 26 28 27 25 17 18 12 23 14 AREA (um2) 2088 1847 1602 1326 1657 2681 2451 1339 689 1013 1669 620.5 10 -1684- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25676-05 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 98 31 66 20082 21 2090 92 30 78 22726 25 2365 105 34 75 24884 24 2589 75 24 50 11870 16 1235 60 19 53 10038 17 1045 67 21 59 12289 19 1279 84 27 65 17173 21 1787 84 27 54 14366 17 1495 69 22 38 8325 12 866 64 21 50 9910 16 1031 AREAS 25686-05 LENGTH AREA (PIXELS)(PIXELS 2) 123 58 22561 119 96 35715 86 51 13906 94 63 18614 81 64 16162 57 50 8964 88 81 22442 62 45 8739 67 46 9612 71 56 12544 MEAN AREA SD N 15166 5776.2 10 1578 601.1 10 16926 8372.6 10 PAGE 9 LENGTH (um) 40 19 38 31 28 17 30 20 26 20 18 16 28 26 20 14 22 15 23 18 AREA (um2) 2348 3716 1447 1937 1682 933 2335 909 1000 1305 1761 871.2 10 -1685- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Males THYROID COLLOID MEASUREMENTS AND 25696-01 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 77 25 47 11423 15 1189 68 22 59 12574 19 1308 101 33 68 21607 22 2248 81 26 52 13213 17 1375 82 27 52 13553 17 1410 66 21 51 10528 16 1096 76 24 69 16397 22 1706 117 38 95 34969 31 3639 95 31 46 13777 15 1434 77 25 38 9302 12 968 AREAS 25705-02 LENGTH AREA (PIXELS)(PIXELS 2) 67 65 13612 61 51 9921 52 41 6800 70 58 12623 67 52 10870 61 45 8637 67 58 12252 67 56 11799 64 50 9978 57 42 7444 MEAN AREA SD N 15734 7578.3 10 1637 788.6 10 10394 2262.7 10 PAGE 10 LENGTH (um) 22 21 20 17 17 13 22 19 21 17 20 14 22 19 22 18 20 16 18 13 AREA (um2) 1416 1032 708 1314 1131 899 1275 1228 1038 775 1082 235.4 10 -1686- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25615-07 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 84 27 80 21027 26 2188 90 29 66 18646 21 1940 71 23 47 10551 15 1098 91 29 60 17207 19 1791 90 29 51 14469 16 1506 73 24 52 11995 17 1248 55 18 49 8559 16 891 78 25 62 15331 20 1595 60 19 60 11313 19 1177 72 23 42 9547 14 993 AREAS 25618-12 LENGTH AREA (PIXELS)(PIXELS 2) 131 77 31893 120 67 25253 86 70 19015 82 67 17361 93 59 17345 159 81 40336 130 102 41592 94 50 14808 91 62 17626 96 49 14928 MEAN AREA SD N 13864 4158.2 10 1443 432.7 10 24016 10332.3 10 GROUP MEAN GROUP SD GROUP N 20961 4256.6 10 2181 442.9 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 11 LENGTH (um) 42 25 39 22 28 23 27 22 30 19 51 26 42 33 30 16 29 20 31 16 AREA (um2) 3319 2628 1979 1807 1805 4197 4328 1541 1834 1553 2499 1075.2 10 -1687- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25621-11 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 122 39 68 26173 22 2724 113 36 75 26529 24 2761 96 31 77 23318 25 2426 91 29 59 17046 19 1774 90 29 74 20909 24 2176 82 27 54 13949 17 1452 89 29 66 18534 21 1929 83 27 72 18827 23 1959 75 24 39 9131 13 950 79 26 58 14477 19 1506 AREAS 25632-11 LENGTH AREA (PIXELS)(PIXELS 2) 110 94 32294 75 60 14152 97 89 27132 69 57 12346 82 61 15651 95 72 21387 96 82 24944 80 51 12785 75 41 9739 77 44 10659 MEAN AREA SD N 18889 5555.1 10 1966 578.1 10 18109 7809.6 10 PAGE 12 LENGTH (um) 35 30 24 19 31 29 22 18 26 20 31 23 31 27 26 16 24 13 25 14 AREA (um2) 3360 1473 2823 1285 1629 2226 2596 1330 1013 1109 1884 812.6 10 -1688- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25637-09 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 122 39 76 29079 24 3026 97 31 47 14371 15 1495 84 27 63 16497 20 1717 99 32 65 20349 21 2118 105 34 80 26402 26 2747 97 31 63 19023 20 1980 92 30 69 20029 22 2084 73 24 65 14842 21 1544 231 75 115 83884 37 8729 107 35 125 42010 40 4371 AREAS 25638-09 LENGTH AREA (PIXELS)(PIXELS 2) 107 80 26959 141 66 29063 117 53 19355 96 58 17496 91 60 17258 121 96 36636 108 52 17551 86 62 16721 100 70 22000 97 52 15825 MEAN AREA SD N 28649 21115.1 10 2981 2197.2 10 21886 6864.6 10 PAGE 13 LENGTH (um) 35 26 46 21 38 17 31 19 29 19 39 31 35 17 28 20 32 23 31 17 AREA (um2) 2805 3024 2014 1821 1796 3812 1826 1740 2289 1647 2277 714.3 10 -1689- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25657-09 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 97 31 61 18419 20 1917 128 41 84 33843 27 3522 89 29 64 18048 21 1878 106 34 65 21746 21 2263 85 28 53 14183 17 1476 98 32 58 18017 19 1875 88 28 58 15899 19 1654 76 25 55 13270 18 1381 74 24 52 12129 17 1262 119 38 115 42895 37 4464 AREAS 25670-12 LENGTH AREA (PIXELS)(PIXELS 2) 139 83 36250 157 98 48431 121 59 22507 103 57 18476 96 46 13787 107 66 22269 88 75 20781 107 57 18932 95 58 17317 89 70 19743 MEAN AREA SD N 20845 9887.5 10 2169 1028.9 10 23849 10464.6 10 PAGE 14 LENGTH (um) 45 27 50 32 39 19 33 18 31 15 34 21 28 24 34 18 31 19 29 23 AREA (um2) 3772 5040 2342 1923 1435 2317 2162 1970 1802 2054 2482 1088.9 10 -1690- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25681-09 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 115 37 62 22407 20 2332 100 32 66 20848 21 2169 88 28 57 15691 18 1633 86 28 64 17254 21 1795 79 25 53 13186 17 1372 93 30 68 19791 22 2059 76 24 73 17469 24 1818 73 24 64 14716 21 1531 74 24 58 13432 19 1398 78 25 46 11313 15 1177 AREAS 25687-09 LENGTH AREA (PIXELS)(PIXELS 2) 131 82 33731 114 66 23380 89 61 17028 123 80 31018 91 61 17395 99 77 24024 139 88 38387 88 52 14335 88 48 13399 97 53 16186 MEAN AREA SD N 16611 3607.7 10 1728 375.4 10 22888 8806.9 10 PAGE 15 LENGTH (um) 42 26 37 21 29 20 40 26 29 20 32 25 45 28 29 17 28 16 31 17 AREA (um2) 3510 2433 1772 3228 1810 2500 3994 1492 1394 1684 2382 916.4 10 -1691- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25619-07 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 171 55 80 42918 26 4466 97 31 65 19612 21 2041 98 32 65 20074 21 2089 62 20 48 9464 16 985 81 26 60 15315 20 1594 68 22 53 11298 17 1176 73 24 47 10789 15 1123 67 22 44 9265 14 964 81 26 60 15295 19 1592 74 24 45 10521 15 1095 AREAS 25630-08 LENGTH AREA (PIXELS)(PIXELS 2) 174 48 26493 118 68 25350 136 94 40392 78 43 10392 82 57 14788 76 56 13407 81 56 14084 86 56 15245 80 64 16121 82 46 11893 MEAN AREA SD N 16455 10113.0 10 1712 1052.3 10 18817 9273.1 10 GROUP MEAN GROUP SD GROUP N 18925 5334.4 8 1969 555.1 8 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 16 LENGTH (um) 56 16 38 22 44 30 25 14 27 18 25 18 26 18 28 18 26 21 27 15 AREA (um2) 2757 2638 4203 1081 1539 1395 1466 1586 1678 1238 1958 964.9 10 -1692- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25639-10 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 104 34 70 22950 23 2388 78 25 64 15657 21 1629 98 32 51 15862 17 1651 82 26 54 14028 18 1460 67 22 46 9696 15 1009 82 26 48 12188 15 1268 68 22 54 11616 17 1209 74 24 61 14188 20 1476 66 21 38 7882 12 820 56 18 38 6685 12 696 AREAS 25658-11 LENGTH AREA (PIXELS)(PIXELS 2) 90 50 14329 98 72 22126 97 65 19858 76 43 10352 89 73 20478 78 54 13120 92 50 14523 78 49 11873 86 58 15740 65 55 11260 MEAN AREA SD N 13075 4669.4 10 1361 485.9 10 15366 4125.5 10 PAGE 17 LENGTH (um) 29 16 32 23 31 21 25 14 29 24 25 17 30 16 25 16 28 19 21 18 AREA (um2) 1491 2302 2066 1077 2131 1365 1511 1236 1638 1172 1599 429.3 10 -1693- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25676-10 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 156 50 96 47110 31 4902 121 39 82 31408 27 3268 124 40 88 34441 28 3584 167 54 57 29873 18 3109 128 41 75 30189 24 3141 107 34 85 28413 27 2957 139 45 100 43624 32 4539 93 30 61 17772 20 1849 100 32 77 24297 25 2528 98 32 58 17871 19 1860 AREAS 25686-12 LENGTH AREA (PIXELS)(PIXELS 2) 126 71 28177 106 62 20736 136 73 31352 116 72 26351 89 66 18436 108 100 34104 84 53 14151 75 57 13323 86 66 17909 75 50 11876 MEAN AREA SD N 30500 9599.3 10 3174 998.9 10 21641 7889.7 10 PAGE 18 LENGTH (um) 41 23 34 20 44 24 37 23 29 21 35 32 27 17 24 18 28 21 24 16 AREA (um2) 2932 2158 3262 2742 1918 3549 1473 1386 1864 1236 2252 821.0 10 -1694- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS Females THYROID COLLOID MEASUREMENTS AND 25696-12 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 106 34 94 31556 30 3284 88 29 54 14990 17 1560 92 30 78 22472 25 2338 99 32 79 24555 25 2555 86 28 69 18739 22 1950 74 24 58 13570 19 1412 83 27 83 21507 27 2238 78 25 65 16040 21 1669 78 25 60 14664 19 1526 67 22 48 10101 16 1051 AREAS 25705-12 LENGTH AREA (PIXELS)(PIXELS 2) 121 54 20760 109 71 24309 84 55 14436 86 58 15680 115 73 26493 99 43 13235 98 43 13219 85 52 13920 91 52 14882 79 42 10363 MEAN AREA SD N 18820 6314.9 10 1958 657.1 10 16730 5289.0 10 PAGE 19 LENGTH (um) 39 18 35 23 27 18 28 19 37 24 32 14 32 14 27 17 29 17 25 14 AREA (um2) 2160 2530 1502 1632 2757 1377 1376 1448 1549 1078 1741 550.4 10 -1695- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25615-02 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 19.03 6.14 18.79 6.06 24.70 7.97 15.00 4.84 16.28 5.25 19.03 6.14 13.04 4.21 17.49 5.64 14.21 4.58 15.52 5.01 13.04 4.21 16.28 5.25 12.65 4.08 12.53 4.04 15.00 4.84 MEASUREMENTS 25618-01 CELL HEIGHT (PIXELS) 19.00 19.00 17.12 19.85 17.69 25.63 19.24 18.11 15.00 16.55 15.00 17.89 17.00 17.46 21.40 CELL HEIGHT (um) 6.13 6.13 5.52 6.40 5.71 8.27 6.20 5.84 4.84 5.34 4.84 5.77 5.48 5.63 6.90 MEAN SD N 16.17 3.272 15 5.22 1.056 15 18.40 2.628 15 5.93 0.848 15 GROUP MEAN GROUP SD GROUP N 17.02 0.805 10 5.49 0.260 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 20 -1696- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25621-04 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 15.65 5.05 16.97 5.47 16.64 5.37 16.97 5.47 16.16 5.21 18.44 5.95 13.93 4.49 19.92 6.43 13.04 4.21 19.03 6.14 24.02 7.75 21.95 7.08 15.00 4.84 19.92 6.43 13.42 4.33 MEASUREMENTS 25632-01 CELL HEIGHT (PIXELS) 19.42 16.55 19.42 18.44 12.17 15.13 13.60 16.64 15.65 11.31 18.36 12.37 13.04 16.03 19.70 CELL HEIGHT (um) 6.26 5.34 6.26 5.95 3.92 4.88 4.39 5.37 5.05 3.65 5.92 3.99 4.21 5.17 6.35 MEAN SD N 17.40 3.154 15 5.61 1.018 15 15.86 2.856 15 5.11 0.921 15 PAGE 21 -1697- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25637-02 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 19.42 6.26 17.09 5.51 22.47 7.25 23.41 7.55 16.16 5.21 21.40 6.90 11.40 3.68 19.21 6.20 19.24 6.20 17.80 5.74 14.14 4.56 14.56 4.70 12.08 3.90 13.34 4.30 17.12 5.52 MEASUREMENTS 25638-03 CELL HEIGHT (PIXELS) 18.38 14.42 18.97 18.03 19.03 20.52 14.76 14.87 9.85 19.42 17.12 25.94 12.08 15.65 20.00 CELL HEIGHT (um) 5.93 4.65 6.12 5.82 6.14 6.62 4.76 4.80 3.18 6.26 5.52 8.37 3.90 5.05 6.45 MEAN SD N 17.26 3.679 15 5.57 1.187 15 17.27 3.877 15 5.57 1.251 15 PAGE 22 -1698- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25657-03 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 15.23 4.91 14.32 4.62 16.12 5.20 18.38 5.93 14.76 4.76 14.56 4.70 23.09 7.45 15.81 5.10 25.24 8.14 17.00 5.48 18.25 5.89 10.30 3.32 25.50 8.22 15.56 5.02 19.10 6.16 MEASUREMENTS 25670-01 CELL HEIGHT (PIXELS) 22.14 16.28 19.65 13.34 16.40 15.03 18.25 14.87 14.76 18.79 13.34 17.46 15.52 11.00 17.69 CELL HEIGHT (um) 7.14 5.25 6.34 4.30 5.29 4.85 5.89 4.80 4.76 6.06 4.30 5.63 5.01 3.55 5.71 MEAN SD N 17.55 4.234 15 5.66 1.366 15 16.30 2.813 15 5.26 0.907 15 PAGE 23 -1699- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25681-02 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 17.46 5.63 10.44 3.37 14.42 4.65 17.03 5.49 22.85 7.37 17.46 5.63 17.03 5.49 12.00 3.87 17.03 5.49 22.80 7.36 16.03 5.17 15.26 4.92 14.32 4.62 19.21 6.20 12.08 3.90 MEASUREMENTS 25687-01 CELL HEIGHT (PIXELS) 18.03 21.84 13.93 15.65 19.03 18.25 16.00 16.40 15.81 17.69 17.26 16.00 19.10 20.00 19.42 CELL HEIGHT (um) 5.82 7.05 4.49 5.05 6.14 5.89 5.16 5.29 5.10 5.71 5.57 5.16 6.16 6.45 6.26 MEAN SD N 16.36 3.557 15 5.28 1.147 15 17.63 2.054 15 5.69 0.663 15 PAGE 24 -1700- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25616-01 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 16.76 5.41 10.82 3.49 18.68 6.03 22.14 7.14 16.76 5.41 18.97 6.12 12.08 3.90 15.56 5.02 17.49 5.64 15.23 4.91 21.93 7.07 19.10 6.16 20.81 6.71 13.45 4.34 13.45 4.34 MEASUREMENTS 25619-02 CELL HEIGHT (PIXELS) 14.56 14.56 14.56 12.04 9.43 18.38 14.42 14.14 24.08 12.37 14.14 16.28 15.00 18.36 13.04 CELL HEIGHT (um) 4.70 4.70 4.70 3.88 3.04 5.93 4.65 4.56 7.77 3.99 4.56 5.25 4.84 5.92 4.21 MEAN SD N 16.88 3.477 15 5.45 1.122 15 15.02 3.378 15 4.85 1.090 15 GROUP MEAN GROUP SD GROUP N 16.60 1.336 10 5.36 0.431 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 25 -1701- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25630-02 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 14.32 4.62 12.53 4.04 20.25 6.53 17.46 5.63 12.37 3.99 16.12 5.20 14.32 4.62 17.46 5.63 21.40 6.90 20.22 6.52 23.02 7.43 22.20 7.16 17.80 5.74 14.87 4.80 16.12 5.20 MEASUREMENTS 25639-01 CELL HEIGHT (PIXELS) 11.00 13.04 11.18 14.87 13.00 17.89 18.38 11.70 12.37 12.37 15.81 21.40 15.00 13.89 12.37 CELL HEIGHT (um) 3.55 4.21 3.61 4.80 4.19 5.77 5.93 3.78 3.99 3.99 5.10 6.90 4.84 4.48 3.99 MEAN SD N 17.37 3.429 15 5.60 1.106 15 14.29 2.989 15 4.61 0.964 15 PAGE 26 -1702- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25658-06 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 14.42 4.65 18.03 5.82 25.00 8.06 14.56 4.70 17.03 5.49 21.10 6.80 21.26 6.86 20.62 6.65 13.93 4.49 15.00 4.84 19.24 6.20 17.89 5.77 17.26 5.57 13.00 4.19 11.18 3.61 MEASUREMENTS 25673-01 CELL HEIGHT (PIXELS) 19.24 23.54 20.00 16.28 16.00 13.89 18.03 13.00 19.00 18.25 16.64 16.76 15.52 11.05 18.25 CELL HEIGHT (um) 6.20 7.59 6.45 5.25 5.16 4.48 5.82 4.19 6.13 5.89 5.37 5.41 5.01 3.56 5.89 MEAN SD N 17.30 3.717 15 5.58 1.199 15 17.03 3.046 15 5.49 0.983 15 PAGE 27 -1703- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25676-05 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 15.00 4.84 16.28 5.25 13.15 4.24 16.55 5.34 17.00 5.48 18.44 5.95 15.03 4.85 12.53 4.04 13.42 4.33 14.87 4.80 12.21 3.94 17.12 5.52 14.32 4.62 18.03 5.82 17.03 5.49 MEASUREMENTS 25686-05 CELL HEIGHT (PIXELS) 20.10 17.46 21.59 16.55 17.00 16.03 11.05 10.20 12.53 17.00 18.38 17.49 17.03 15.23 17.03 CELL HEIGHT (um) 6.48 5.63 6.96 5.34 5.48 5.17 3.56 3.29 4.04 5.48 5.93 5.64 5.49 4.91 5.49 MEAN SD N 15.40 1.992 15 4.97 0.643 15 16.31 3.069 15 5.26 0.990 15 PAGE 28 -1704- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25696-01 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 17.69 5.71 14.76 4.76 17.46 5.63 17.26 5.57 17.72 5.72 17.00 5.48 15.26 4.92 20.00 6.45 21.10 6.80 15.00 4.84 14.87 4.80 15.03 4.85 27.20 8.78 21.38 6.90 18.60 6.00 MEASUREMENTS 25705-02 CELL HEIGHT (PIXELS) 19.85 14.76 17.09 25.00 10.00 23.43 19.65 22.36 14.87 20.88 21.40 19.24 17.03 15.81 15.00 CELL HEIGHT (um) 6.40 4.76 5.51 8.06 3.23 7.56 6.34 7.21 4.80 6.74 6.90 6.20 5.49 5.10 4.84 MEAN SD N 18.02 3.355 15 5.81 1.082 15 18.42 3.984 15 5.94 1.285 15 PAGE 29 -1705- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25615-07 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 17.26 5.57 23.26 7.50 19.10 6.16 22.00 7.10 17.03 5.49 13.42 4.33 14.14 4.56 21.54 6.95 18.60 6.00 19.42 6.26 16.00 5.16 15.56 5.02 22.85 7.37 17.00 5.48 10.44 3.37 MEASUREMENTS 25618-12 CELL HEIGHT (PIXELS) 23.43 19.70 22.09 19.10 13.60 16.28 15.00 16.28 19.70 15.52 18.03 11.40 15.81 24.60 17.20 CELL HEIGHT (um) 7.56 6.35 7.13 6.16 4.39 5.25 4.84 5.25 6.35 5.01 5.82 3.68 5.10 7.93 5.55 MEAN SD N 17.84 3.668 15 5.76 1.183 15 17.85 3.643 15 5.76 1.175 15 GROUP MEAN GROUP SD GROUP N 17.61 1.114 10 5.68 0.360 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 30 -1706- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25621-11 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 16.00 5.16 13.89 4.48 23.71 7.65 15.30 4.93 16.12 5.20 12.53 4.04 16.55 5.34 23.85 7.69 19.10 6.16 20.22 6.52 25.63 8.27 20.25 6.53 11.31 3.65 13.93 4.49 15.30 4.93 MEASUREMENTS 25632-11 CELL HEIGHT (PIXELS) 18.68 15.52 16.12 14.14 18.87 17.69 17.00 18.68 22.47 17.80 19.72 18.36 21.21 19.24 14.00 CELL HEIGHT (um) 6.03 5.01 5.20 4.56 6.09 5.71 5.48 6.03 7.25 5.74 6.36 5.92 6.84 6.20 4.52 MEAN SD N 17.58 4.359 15 5.67 1.406 15 17.97 2.365 15 5.80 0.763 15 PAGE 31 -1707- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25637-09 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 21.02 6.78 19.65 6.34 19.42 6.26 15.03 4.85 19.03 6.14 15.65 5.05 18.03 5.82 19.03 6.14 23.09 7.45 14.21 4.58 21.10 6.80 19.92 6.43 18.03 5.82 21.02 6.78 23.32 7.52 MEASUREMENTS 25638-09 CELL HEIGHT (PIXELS) 19.85 16.12 16.03 11.70 14.32 13.04 17.03 12.04 17.12 25.18 20.88 11.40 12.37 14.32 17.20 CELL HEIGHT (um) 6.40 5.20 5.17 3.78 4.62 4.21 5.49 3.88 5.52 8.12 6.74 3.68 3.99 4.62 5.55 MEAN SD N 19.17 2.683 15 6.18 0.865 15 15.91 3.868 15 5.13 1.248 15 PAGE 32 -1708- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25657-09 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 18.03 5.82 18.00 5.81 11.66 3.76 12.17 3.92 17.46 5.63 24.21 7.81 17.12 5.52 24.04 7.76 23.54 7.59 23.00 7.42 13.60 4.39 17.26 5.57 13.89 4.48 14.76 4.76 15.26 4.92 MEASUREMENTS 25670-12 CELL HEIGHT (PIXELS) 21.10 19.42 27.46 17.89 26.83 12.37 16.49 17.72 15.23 15.81 21.38 21.02 15.81 21.21 17.72 CELL HEIGHT (um) 6.80 6.26 8.86 5.77 8.66 3.99 5.32 5.72 4.91 5.10 6.90 6.78 5.10 6.84 5.72 MEAN SD N 17.60 4.295 15 5.68 1.386 15 19.16 4.149 15 6.18 1.338 15 PAGE 33 -1709- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25681-09 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 19.24 6.20 24.19 7.80 20.00 6.45 16.16 5.21 18.03 5.82 21.26 6.86 17.12 5.52 15.62 5.04 14.14 4.56 15.65 5.05 18.79 6.06 14.14 4.56 12.81 4.13 17.00 5.48 13.04 4.21 MEASUREMENTS 25687-09 CELL HEIGHT (PIXELS) 13.04 13.45 14.32 17.69 18.60 17.12 16.28 13.60 19.03 17.46 18.03 17.12 16.12 12.53 13.89 CELL HEIGHT (um) 4.21 4.34 4.62 5.71 6.00 5.52 5.25 4.39 6.14 5.63 5.82 5.52 5.20 4.04 4.48 MEAN SD N 17.14 3.183 15 5.53 1.027 15 15.89 2.200 15 5.12 0.710 15 PAGE 34 -1710- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25619-07 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 15.81 5.10 17.26 5.57 14.87 4.80 13.89 4.48 17.49 5.64 14.42 4.65 13.60 4.39 18.03 5.82 15.52 5.01 22.02 7.10 14.21 4.58 15.23 4.91 16.64 5.37 23.00 7.42 15.30 4.93 MEASUREMENTS 25630-08 CELL HEIGHT (PIXELS) 21.19 14.21 17.12 21.63 20.00 16.49 16.00 17.80 23.43 17.26 20.81 24.08 18.60 20.00 15.13 CELL HEIGHT (um) 6.84 4.58 5.52 6.98 6.45 5.32 5.16 5.74 7.56 5.57 6.71 7.77 6.00 6.45 4.88 MEAN SD N 16.49 2.785 15 5.32 0.898 15 18.92 2.972 15 6.10 0.959 15 GROUP MEAN GROUP SD GROUP N 18.11 0.942 8 5.84 0.304 8 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 35 -1711- WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25639-10 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 12.81 4.13 15.52 5.01 13.60 4.39 17.69 5.71 18.03 5.82 24.02 7.75 20.62 6.65 20.00 6.45 18.38 5.93 16.00 5.16 16.12 5.20 16.00 5.16 17.49 5.64 17.49 5.64 18.25 5.89 MEASUREMENTS 25658-11 CELL HEIGHT (PIXELS) 13.15 19.24 14.76 17.00 17.46 17.69 17.09 14.14 15.65 20.25 17.09 23.71 14.04 17.09 18.68 CELL HEIGHT (um) 4.24 6.20 4.76 5.48 5.63 5.71 5.51 4.56 5.05 6.53 5.51 7.65 4.53 5.51 6.03 MEAN SD N 17.47 2.773 15 5.64 0.894 15 17.14 2.704 15 5.53 0.872 15 PAGE 36 -1712- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25676-10 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 18.68 6.03 15.26 4.92 18.03 5.82 14.76 4.76 20.10 6.48 22.20 7.16 13.42 4.33 22.36 7.21 18.68 6.03 15.03 4.85 21.47 6.93 27.02 8.72 19.31 6.23 18.03 5.82 16.49 5.32 MEASUREMENTS 25686-12 CELL HEIGHT (PIXELS) 16.76 14.87 17.03 19.70 21.26 20.88 17.49 14.04 20.22 15.65 22.02 20.40 15.26 23.02 20.10 CELL HEIGHT (um) 5.41 4.80 5.49 6.35 6.86 6.74 5.64 4.53 6.52 5.05 7.10 6.58 4.92 7.43 6.48 MEAN SD N 18.72 3.579 15 6.04 1.154 15 18.58 2.860 15 5.99 0.923 15 PAGE 37 -1713- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017N APPENDIX 48 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25696-12 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 19.21 6.20 19.00 6.13 25.18 8.12 18.38 5.93 20.62 6.65 16.76 5.41 19.65 6.34 15.81 5.10 24.02 7.75 13.15 4.24 15.26 4.92 15.26 4.92 16.28 5.25 19.10 6.16 22.47 7.25 MEASUREMENTS 25705-12 CELL HEIGHT (PIXELS) 16.40 19.42 17.03 19.10 16.00 24.21 23.09 19.03 21.00 15.00 16.03 22.14 21.02 18.44 15.81 CELL HEIGHT (um) 5.29 6.26 5.49 6.16 5.16 7.81 7.45 6.14 6.77 4.84 5.17 7.14 6.78 5.95 5.10 MEAN SD N 18.68 3.402 15 6.03 1.097 15 18.91 2.888 15 6.10 0.932 15 PAGE 38 -1714- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25615-06 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 483 156 167 253232 54 26351 300 97 160 151442 52 15759 252 81 160 126864 52 13201 200 65 144 90626 46 9430 194 63 118 71963 38 7488 182 59 78 44849 25 4667 176 57 161 89018 52 9263 137 44 102 43879 33 4566 173 56 143 77762 46 8092 168 54 136 71927 44 7485 208 IN RATS 25618-09 LENGTH AREA (PIXELS)(PIXELS 2) 191 131 78313 195 109 66954 168 136 72106 128 98 39559 150 112 53082 144 113 51062 140 125 54979 163 79 40588 133 128 53475 128 109 43953 MEAN AREA SD N 102156 62601.0 10 10630 6514.2 10 55407 13195.2 10 GROUP MEAN GROUP SD GROUP N 74652 15771.4 10 7768 1641.1 10 PAGE 1 LENGTH (um) 62 42 63 35 54 44 41 32 49 36 46 36 45 40 53 26 43 41 41 35 AREA (um2) 8149 6967 7503 4116 5524 5313 5721 4224 5565 4574 5766 1373.1 10 -1715- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25621-03 25632-02 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 196 63 176 138 85392 45 8886 103 56950 172 55 204 168 90739 54 9442 139 89295 157 51 184 127 62770 41 6532 138 79790 181 58 278 145 82373 47 8572 136 118841 156 50 178 129 63100 42 6566 159 88621 129 42 176 102 41190 33 4286 133 73594 157 51 146 137 67500 44 7024 82 37615 162 52 203 90 45808 29 4767 172 109871 153 49 167 109 52647 35 5478 157 82301 164 53 157 124 63758 40 6635 108 53486 MEAN AREA SD N 65528 16605.3 10 6819 1727.9 10 79036 25010.0 10 PAGE 2 LENGTH (um) 57 33 66 45 59 45 90 44 57 51 57 43 47 26 65 56 54 51 51 35 AREA (um2) 5926 9292 8303 12366 9222 7658 3914 11433 8564 5566 8224 2602.5 10 -1716- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25637-03 25638-01 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 194 62 285 129 78419 42 8160 233 208815 283 91 239 180 159881 58 16637 156 117046 187 60 190 126 73830 40 7683 100 59714 170 55 214 111 59568 36 6199 151 101424 175 57 263 139 76342 45 7944 134 110457 141 45 234 101 44692 33 4651 176 129723 136 44 194 130 55615 42 5787 112 68459 128 41 164 94 37992 30 3953 152 78523 114 37 126 82 29376 26 3057 98 38966 154 50 146 104 50328 34 5237 69 31951 MEAN AREA SD N 66604 36677.4 10 6931 3816.6 10 94508 51917.9 10 PAGE 3 LENGTH (um) 92 75 77 50 61 32 69 49 85 43 76 57 63 36 53 49 41 32 47 22 AREA (um2) 21729 12180 6214 10554 11494 13499 7124 8171 4055 3325 9834 5402.5 10 -1717- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25657-07 25670-06 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 278 90 265 168 146920 54 15288 158 131471 160 52 216 128 64296 41 6691 124 84123 193 62 216 146 88343 47 9193 122 82787 177 57 174 141 78264 45 8144 105 57139 154 50 205 107 51825 35 5393 135 86802 151 49 200 107 50467 34 5251 113 70777 147 47 186 109 50333 35 5238 109 63480 137 44 170 108 46454 35 4834 116 61952 161 52 176 117 59098 38 6150 124 68309 170 55 160 166 89022 54 9263 110 55198 MEAN AREA SD N 72502 30596.3 10 7544 3183.8 10 76204 22445.9 10 PAGE 4 LENGTH (um) 86 51 70 40 70 39 56 34 66 43 64 36 60 35 55 37 57 40 52 35 AREA (um2) 13681 8754 8615 5946 9032 7365 6606 6447 7108 5744 7930 2335.7 10 -1718- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25681-03 25687-04 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 144 46 264 80 36375 26 3785 224 185689 160 52 160 151 76032 49 7912 139 69924 180 58 221 99 56117 32 5839 162 112589 158 51 163 107 53117 34 5527 105 53795 129 42 199 113 46001 37 4787 157 98097 144 46 200 95 42998 31 4474 125 78750 150 49 155 129 60821 42 6329 92 45117 142 46 165 126 55904 41 5817 119 61771 145 47 163 111 50444 36 5249 131 67085 143 46 154 106 47610 34 4954 98 47459 MEAN AREA SD N 52542 10897.1 10 5467 1133.9 10 82028 42273.2 10 PAGE 5 LENGTH (um) 85 72 52 45 71 52 53 34 64 50 65 40 50 30 53 38 53 42 50 32 AREA (um2) 19322 7276 11716 5598 10208 8195 4695 6428 6981 4938 8536 4398.9 10 -1719- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25616-02 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 239 77 195 146626 63 15258 213 69 154 102632 50 10680 195 63 130 79612 42 8284 205 66 156 100566 50 10465 196 63 183 112455 59 11702 173 56 145 78642 47 8183 155 50 115 55867 37 5813 129 42 76 30793 25 3204 163 53 133 68231 43 7100 201 65 166 104560 54 10880 208 IN RATS 25619-03 LENGTH AREA (PIXELS)(PIXELS 2) 201 136 86188 164 118 60847 231 218 158867 170 166 88814 149 101 47438 156 119 58665 152 112 53607 143 100 45062 136 99 42650 151 114 53852 MEAN AREA SD N 87999 32549.6 10 9157 3387.1 10 69599 35170.3 10 MEAN AREA GROUP SD GROUP N 69838 10741.9 10 7267 1117.8 10 PAGE 6 LENGTH (um) 65 44 53 38 75 70 55 54 48 33 50 38 49 36 46 32 44 32 49 37 AREA (um2) 8969 6332 16531 9242 4936 6105 5578 4689 4438 5604 7242 3659.8 10 -1720- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25630-06 25639-03 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 223 72 214 148 103597 48 10780 170 114662 322 104 150 196 197915 63 20595 110 51925 201 65 177 89 56503 29 5880 145 80535 132 42 190 95 39223 31 4082 138 82401 111 36 161 93 32238 30 3355 105 53389 111 36 173 70 24485 23 2548 120 65301 108 35 183 98 33263 32 3461 134 76844 141 45 176 100 44432 32 4623 112 61979 146 47 160 112 51290 36 5337 114 57086 90 29 140 70 19630 23 2043 108 47553 MEAN AREA SD N 60257 53809.6 10 6270 5599.3 10 69168 20163.5 10 PAGE 7 LENGTH (um) 69 55 49 35 57 47 61 45 52 34 56 39 59 43 57 36 52 37 45 35 AREA (um2) 11932 5403 8380 8575 5556 6795 7996 6449 5940 4948 7197 2098.2 10 -1721- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25658-04 25673-08 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 190 61 183 145 86386 47 8989 136 78024 223 72 202 149 104230 48 10846 142 89873 206 67 203 168 109091 54 11352 114 72810 233 75 199 176 128757 57 13398 144 90264 193 62 147 161 97286 52 10123 159 73661 259 83 159 122 99390 39 10342 118 59094 182 59 185 156 88968 50 9258 124 71886 153 49 143 98 46900 31 4880 98 44021 143 46 100 102 46018 33 4789 96 30242 151 49 200 104 49506 34 5152 99 62167 MEAN AREA SD N 85653 28804.5 10 8913 2997.3 10 67204 19010.2 10 PAGE 8 LENGTH (um) 59 44 65 46 65 37 64 47 48 51 51 38 60 40 46 32 32 31 64 32 AREA (um2) 8119 9352 7576 9393 7665 6149 7480 4581 3147 6469 6993 1978.2 10 -1722- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25676-04 25686-01 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 236 76 215 201 149046 65 15509 136 91617 187 60 205 126 74009 41 7701 183 117456 206 67 177 139 90246 45 9391 129 71478 185 60 253 119 69306 38 7212 198 157283 217 70 156 108 73745 35 7674 136 66802 153 49 156 98 47087 32 4900 100 49148 172 56 143 91 49053 29 5104 89 39818 181 58 143 142 80981 46 8427 107 47996 147 47 112 121 55900 39 5817 88 31231 135 44 155 99 41911 32 4361 89 43164 MEAN AREA SD N 73129 31025.1 10 7610 3228.4 10 71599 39969.0 10 PAGE 9 LENGTH (um) 69 44 66 59 57 42 82 64 50 44 50 32 46 29 46 34 36 29 50 29 AREA (um2) 9534 12222 7438 16367 6951 5114 4143 4994 3250 4492 7450 4159.1 10 -1723- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS ORAL Males APPENDIX 49 (F1 PUPS - PND 21) DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY THYROID COLLOID MEASUREMENTS AND AREAS 25696-06 25705-06 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 179 58 208 121 68272 39 7104 183 119716 207 67 203 140 90803 45 9449 167 106194 158 51 196 123 61124 40 6360 121 74810 165 53 134 125 64523 40 6714 120 50642 146 47 162 78 35677 25 3712 106 54105 167 54 140 147 77407 48 8055 88 38880 132 42 174 96 39571 31 4118 70 38343 122 39 122 99 37968 32 3951 89 34040 136 44 126 91 38976 29 4056 104 41348 115 37 113 90 32231 29 3354 93 33113 MEAN AREA SD N 54655 20449.9 10 5687 2128.0 10 59119 31079.9 10 PAGE 10 LENGTH (um) 67 59 65 54 63 39 43 39 52 34 45 29 56 23 39 29 41 34 36 30 AREA (um2) 12457 11050 7785 5270 5630 4046 3990 3542 4303 3446 6152 3234.1 10 -1724- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25615-09 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 216 70 156 105695 50 10998 160 52 88 44173 28 4597 172 55 135 72792 43 7575 164 53 119 61462 38 6396 172 55 101 54557 33 5677 163 52 113 57664 36 6000 135 43 105 44546 34 4635 147 47 113 52258 37 5438 138 44 88 37936 28 3948 174 56 106 57620 34 5996 208 IN RATS 25618-18 LENGTH AREA (PIXELS)(PIXELS 2) 203 151 96153 166 110 57743 225 195 137898 137 78 33542 188 122 72453 188 115 67728 179 157 88248 166 143 74723 162 95 48258 142 112 49821 MEAN AREA SD N 58870 19200.5 10 6126 1998.0 10 72657 29719.5 10 GROUP MEAN GROUP SD GROUP N 69382 12383.1 10 7220 1288.6 10 PAGE 11 LENGTH (um) 66 49 54 36 73 63 44 25 61 39 61 37 58 51 54 46 52 31 46 36 AREA (um2) 10005 6009 14349 3490 7539 7048 9183 7776 5022 5184 7561 3092.6 10 -1725- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25621-12 25632-15 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 210 68 221 157 104012 51 10823 159 110415 221 71 185 149 103667 48 10787 120 69807 195 63 171 123 75489 40 7855 98 52491 231 74 240 157 113673 51 11829 171 128761 213 69 201 161 107622 52 11199 164 103892 148 48 199 90 41922 29 4362 147 92311 169 55 212 101 53622 33 5580 151 100697 153 49 157 103 49592 33 5160 110 54343 144 46 165 124 56070 40 5835 144 74542 163 52 160 137 69849 44 7268 118 59231 MEAN AREA SD N 77552 27366.0 10 8070 2847.7 10 84649 26283.6 10 PAGE 12 LENGTH (um) 71 51 60 39 55 31 77 55 65 53 64 48 68 49 51 36 53 46 52 38 AREA (um2) 11490 7264 5462 13399 10811 9606 10478 5655 7757 6163 8808 2735.0 10 -1726- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25637-10 25638-11 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 180 58 183 132 74411 43 7743 146 83740 185 60 163 126 73501 41 7648 127 65073 196 63 172 128 78867 41 8207 122 66034 230 74 195 108 77705 35 8086 118 72105 239 77 169 192 144539 62 15040 132 70143 185 60 147 74 43332 24 4509 124 57154 132 42 137 88 36335 28 3781 74 31999 222 72 154 176 122999 57 12799 88 42751 141 45 134 121 53539 39 5571 106 44643 211 68 140 187 123818 60 12884 114 50255 MEAN AREA SD N 82905 36333.8 10 8627 3780.8 10 58390 15880.4 10 PAGE 13 LENGTH (um) 59 47 53 41 55 39 63 38 55 43 47 40 44 24 50 29 43 34 45 37 AREA (um2) 8714 6771 6871 7503 7299 5947 3330 4449 4645 5229 6076 1652.5 10 -1727- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25657-13 25670-17 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 204 66 252 130 83388 42 8677 183 144487 172 55 261 107 57766 35 6011 216 176602 230 74 153 104 75449 34 7851 96 45944 159 51 180 112 55954 36 5822 116 65781 137 44 194 116 50024 37 5205 145 88430 160 52 188 82 41324 27 4300 153 90337 151 49 143 88 41715 28 4341 122 55030 176 57 119 80 44417 26 4622 85 32004 115 37 110 68 24706 22 2571 87 30205 202 65 158 105 66709 34 6942 136 67426 MEAN AREA SD N 54145 17576.5 10 5634 1829.0 10 79625 47835.0 10 PAGE 14 LENGTH (um) 81 59 84 70 49 31 58 37 63 47 61 49 46 39 38 28 36 28 51 44 AREA (um2) 15035 18377 4781 6845 9202 9400 5726 3330 3143 7016 8286 4977.6 10 -1728- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 1 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25681-14 25687-10 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 179 58 184 146 82496 47 8584 138 79660 176 57 200 131 72588 42 7553 144 90619 159 51 192 89 44511 29 4632 178 107447 159 51 168 114 56787 37 5909 105 55393 165 53 234 122 63041 39 6560 97 71371 137 44 228 68 29433 22 3063 114 81870 134 43 146 118 49745 38 5176 124 56961 123 40 137 122 47115 39 4903 115 49332 111 36 152 108 37544 35 3907 112 53531 121 39 178 95 36076 31 3754 152 84789 MEAN AREA SD N 51934 16850.7 10 5404 1753.5 10 73097 19055.6 10 PAGE 15 LENGTH (um) 59 44 64 47 62 57 54 34 76 31 74 37 47 40 44 37 49 36 57 49 AREA (um2) 8289 9430 11181 5764 7427 8519 5927 5133 5570 8823 7606 1982.9 10 -1729- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25616-13 LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) 141 45 106 47149 34 4906 180 58 166 94364 54 9819 172 56 131 70871 42 7375 185 60 152 88596 49 9219 186 60 119 69498 38 7232 196 63 71 43431 23 4519 142 46 115 51253 37 5333 147 48 110 50849 35 5291 156 50 103 50754 33 5281 200 64 129 80828 42 8411 208 IN RATS 25619-10 LENGTH AREA (PIXELS)(PIXELS 2) 286 162 145160 201 106 66581 196 150 92458 216 169 114738 189 142 84171 187 98 57743 164 82 42276 185 134 78051 123 65 25040 150 121 57146 MEAN AREA SD N 64759 18558.3 10 6739 1931.1 10 76336 35176.1 10 Mean Area Group SD Group N 73774 17853.8 10 7677 1857.8 10 PAGE 16 LENGTH (um) 92 52 65 34 63 48 70 55 61 46 60 32 53 26 60 43 40 21 48 39 AREA (um2) 15105 6928 9621 11939 8759 6009 4399 8122 2606 5946 7943 3660.4 10 -1730- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25630-13 25639-12 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 245 79 201 174 133833 56 13926 109 68686 163 53 250 131 67155 42 6988 120 94451 164 53 186 122 62870 39 6542 156 91158 198 64 266 111 69272 36 7208 154 128377 173 56 180 154 83694 50 8709 102 58117 159 51 180 89 44501 29 4631 104 58738 164 53 163 157 80894 51 8418 107 54490 196 63 178 123 75626 40 7869 116 64608 175 57 184 136 75016 44 7806 148 85603 165 53 142 145 75217 47 7827 107 47500 MEAN AREA SD N 76808 22879.1 10 7992 2380.8 10 75173 24664.3 10 PAGE 17 LENGTH (um) 65 35 81 39 60 50 86 50 58 33 58 33 52 34 57 37 59 48 46 34 AREA (um2) 7147 9828 9486 13359 6048 6112 5670 6723 8908 4943 7822 2566.5 10 -1731- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25658-13 25673-14 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 351 113 234 183 201493 59 20967 185 135518 231 74 156 96 69403 31 7222 124 60481 204 66 199 171 109320 55 11376 121 75518 252 81 217 149 117826 48 12261 120 82170 204 66 120 112 71657 36 7456 93 34878 169 54 137 144 76504 47 7961 118 50774 269 87 123 226 191586 73 19936 88 34001 216 70 132 128 86563 41 9008 104 43206 158 51 152 122 60747 39 6321 90 42865 142 46 137 128 57114 41 5943 121 52141 MEAN AREA SD N 104221 52458.7 10 10845 5458.8 10 61155 30644.5 10 PAGE 18 LENGTH (um) 75 60 50 40 64 39 70 39 39 30 44 38 40 28 42 34 49 29 44 39 AREA (um2) 14102 6294 7858 8550 3629 5283 3538 4496 4460 5426 6364 3188.8 10 -1732- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25676-08 25686-15 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 224 72 261 132 93050 43 9683 157 128423 222 72 217 131 91114 42 9481 148 100758 191 61 184 108 64362 35 6697 133 76676 161 52 187 95 47987 31 4993 158 92711 201 65 178 115 72775 37 7573 148 82775 136 44 169 98 42001 32 4371 108 57448 168 54 172 143 75405 46 7846 135 73039 202 65 145 170 107832 55 11221 98 44570 161 52 166 133 67075 43 6980 106 55044 148 48 146 97 45422 31 4727 129 59377 MEAN AREA SD N 70702 21993.0 10 7357 2288.6 10 77082 25235.0 10 PAGE 19 LENGTH (um) 84 51 70 48 59 43 60 51 57 48 55 35 55 44 47 31 53 34 47 42 AREA (um2) 13363 10485 7979 9647 8613 5978 7600 4638 5728 6179 8021 2625.9 10 -1733- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V GROUP: 4 ANIMAL NUMBER: FOLLICLE NUMBER AND DESCRIPTION FOLLICLE 1, LONG AXIS FOLLICLE 1, SHORT AXIS FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS FOLLICLE 4, SHORT AXIS FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS FOLLICLE 6, SHORT AXIS FOLLICLE 7, LONG AXIS FOLLICLE 7, SHORT AXIS FOLLICLE 8, LONG AXIS FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS FOLLICLE 9, SHORT AXIS FOLLICLE 10, LONG AXIS FOLLICLE 10, SHORT AXIS APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY Females THYROID COLLOID MEASUREMENTS AND AREAS 25696-14 25705-11 LENGTH AREA LENGTH AREA LENGTH AREA (PIXELS)(PIXELS 2) (um) (um2) (PIXELS)(PIXELS 2) 174 56 229 78 42963 25 4471 178 127982 150 48 224 111 52098 36 5421 160 112860 115 37 201 84 30280 27 3151 192 121085 134 43 218 104 43684 34 4546 197 134671 174 56 201 96 52338 31 5446 97 61068 144 46 215 106 48204 34 5016 110 74211 116 38 188 90 32909 29 3424 153 90244 104 34 156 72 23715 23 2468 123 60311 96 31 156 74 22199 24 2310 118 58157 113 36 185 91 32137 29 3344 161 93916 MEAN AREA SD N 38053 11249.7 10 3960 1170.6 10 93450 29448.7 10 PAGE 20 LENGTH (um) 74 57 72 52 65 62 70 64 65 31 69 35 61 49 50 40 50 38 60 52 AREA (um2) 13318 11744 12600 14014 6355 7722 9391 6276 6052 9773 9724 3064.4 10 -1734- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25615-06 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 14.14 4.56 18.03 5.82 14.21 4.58 11.40 3.68 18.60 6.00 12.53 4.04 13.89 4.48 11.40 3.68 15.23 4.91 12.37 3.99 11.31 3.65 15.81 5.10 16.40 5.29 12.81 4.13 19.92 6.43 MEASUREMENTS 25618-09 CELL HEIGHT (PIXELS) 13.89 12.73 13.89 17.69 15.23 12.73 10.77 22.80 13.04 13.00 17.46 14.76 14.21 16.40 20.62 CELL HEIGHT (um) 4.48 4.11 4.48 5.71 4.91 4.11 3.47 7.36 4.21 4.19 5.63 4.76 4.58 5.29 6.65 MEAN SD N 14.54 2.749 15 4.69 0.887 15 15.28 3.227 15 4.93 1.041 15 GROUP MEAN GROUP SD GROUP N 17.62 1.662 10 5.68 0.536 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 21 -1735- WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25621-03 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 28.84 9.30 14.00 4.52 19.70 6.35 17.20 5.55 17.20 5.55 16.12 5.20 20.88 6.74 13.42 4.33 15.23 4.91 14.00 4.52 19.80 6.39 20.00 6.45 18.97 6.12 18.11 5.84 12.17 3.92 MEASUREMENTS 25632-02 CELL HEIGHT (PIXELS) 20.00 18.44 16.12 18.44 12.65 13.42 16.12 17.89 16.12 22.80 18.00 20.10 15.62 16.12 15.62 CELL HEIGHT (um) 6.45 5.95 5.20 5.95 4.08 4.33 5.20 5.77 5.20 7.36 5.81 6.48 5.04 5.20 5.04 MEAN SD N 17.71 4.099 15 5.71 1.322 15 17.16 2.625 15 5.54 0.847 15 PAGE 22 -1736- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25637-03 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 23.09 7.45 17.46 5.63 12.81 4.13 15.56 5.02 17.80 5.74 20.12 6.49 20.00 6.45 20.10 6.48 18.00 5.81 20.00 6.45 23.41 7.55 17.09 5.51 19.80 6.39 17.89 5.77 25.61 8.26 MEASUREMENTS 25638-01 CELL HEIGHT (PIXELS) 18.44 18.87 12.00 20.00 20.00 17.20 18.60 15.13 15.62 18.38 16.40 18.60 15.81 14.42 17.46 CELL HEIGHT (um) 5.95 6.09 3.87 6.45 6.45 5.55 6.00 4.88 5.04 5.93 5.29 6.00 5.10 4.65 5.63 MEAN SD N 19.25 3.207 15 6.21 1.034 15 17.13 2.227 15 5.53 0.718 15 PAGE 23 -1737- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25657-07 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 18.03 5.82 23.71 7.65 18.68 6.03 19.21 6.20 16.49 5.32 15.00 4.84 19.10 6.16 17.46 5.63 17.12 5.52 25.06 8.08 16.28 5.25 19.21 6.20 18.11 5.84 19.00 6.13 21.93 7.07 MEASUREMENTS 25670-06 CELL HEIGHT (PIXELS) 16.28 15.23 22.09 22.36 17.89 26.31 23.77 14.42 18.25 20.10 15.00 16.28 24.35 18.44 23.35 CELL HEIGHT (um) 5.25 4.91 7.13 7.21 5.77 8.49 7.67 4.65 5.89 6.48 4.84 5.25 7.86 5.95 7.53 MEAN SD N 18.96 2.738 15 6.12 0.883 15 19.61 3.857 15 6.32 1.244 15 PAGE 24 -1738- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25681-03 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 16.12 5.20 18.44 5.95 20.59 6.64 16.49 5.32 16.49 5.32 16.97 5.47 22.80 7.36 17.00 5.48 21.02 6.78 16.40 5.29 16.64 5.37 14.87 4.80 18.00 5.81 15.03 4.85 23.60 7.61 MEASUREMENTS 25687-04 CELL HEIGHT (PIXELS) 17.89 22.36 20.88 16.12 21.54 18.87 14.00 14.42 22.80 20.00 18.97 16.12 18.03 20.00 16.28 CELL HEIGHT (um) 5.77 7.21 6.74 5.20 6.95 6.09 4.52 4.65 7.36 6.45 6.12 5.20 5.82 6.45 5.25 MEAN SD N 18.03 2.721 15 5.82 0.878 15 18.55 2.763 15 5.98 0.891 15 PAGE 25 -1739- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25616-02 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 27.78 8.96 22.80 7.36 28.64 9.24 20.40 6.58 22.80 7.36 30.53 9.85 17.09 5.51 12.81 4.13 16.12 5.20 14.14 4.56 12.81 4.13 16.12 5.20 15.62 5.04 18.44 5.95 15.62 5.04 MEASUREMENTS 25619-03 CELL HEIGHT (PIXELS) 12.17 20.12 18.87 16.12 14.32 15.03 16.00 21.93 22.47 19.42 16.03 17.03 21.19 14.87 18.03 CELL HEIGHT (um) 3.92 6.49 6.09 5.20 4.62 4.85 5.16 7.07 7.25 6.26 5.17 5.49 6.84 4.80 5.82 MEAN SD N 19.45 5.822 15 6.27 1.878 15 17.57 3.032 15 5.67 0.978 15 GROUP MEAN GROUP SD GROUP N 19.49 1.004 10 6.29 0.324 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 26 -1740- WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25630-06 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 21.02 6.78 19.42 6.26 19.10 6.16 20.10 6.48 20.40 6.58 19.21 6.20 17.00 5.48 19.24 6.20 25.18 8.12 21.63 6.98 18.68 6.03 20.62 6.65 17.46 5.63 23.85 7.69 17.03 5.49 MEASUREMENTS 25639-03 CELL HEIGHT (PIXELS) 22.02 17.69 20.10 15.00 15.62 22.14 22.02 16.03 18.03 19.42 18.44 20.40 16.12 19.85 14.87 CELL HEIGHT (um) 7.10 5.71 6.48 4.84 5.04 7.14 7.10 5.17 5.82 6.26 5.95 6.58 5.20 6.40 4.80 MEAN SD N 20.00 2.303 15 6.45 0.743 15 18.52 2.580 15 5.97 0.832 15 PAGE 27 -1741- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25658-04 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 24.74 7.98 17.20 5.55 20.00 6.45 17.89 5.77 14.14 4.56 18.44 5.95 17.20 5.55 18.44 5.95 17.89 5.77 20.40 6.58 17.09 5.51 20.40 6.58 26.68 8.61 22.36 7.21 26.31 8.49 MEASUREMENTS 25673-08 CELL HEIGHT (PIXELS) 22.85 19.92 16.28 17.69 20.62 19.00 22.47 18.79 18.38 18.87 16.49 17.00 21.54 20.52 17.03 CELL HEIGHT (um) 7.37 6.43 5.25 5.71 6.65 6.13 7.25 6.06 5.93 6.09 5.32 5.48 6.95 6.62 5.49 MEAN SD N 19.95 3.635 15 6.43 1.172 15 19.16 2.111 15 6.18 0.681 15 PAGE 28 -1742- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25676-04 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 24.41 7.88 18.38 5.93 18.87 6.09 24.04 7.76 23.85 7.69 20.81 6.71 15.00 4.84 18.60 6.00 17.03 5.49 18.36 5.92 18.36 5.92 16.76 5.41 19.10 6.16 18.11 5.84 21.63 6.98 MEASUREMENTS 25686-01 CELL HEIGHT (PIXELS) 25.71 26.93 25.50 22.14 24.02 20.00 16.12 24.04 21.02 20.81 15.23 18.38 21.95 13.42 16.28 CELL HEIGHT (um) 8.29 8.69 8.22 7.14 7.75 6.45 5.20 7.76 6.78 6.71 4.91 5.93 7.08 4.33 5.25 MEAN SD N 19.56 2.815 15 6.31 0.908 15 20.77 4.158 15 6.70 1.341 15 PAGE 29 -1743- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Males ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25696-06 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 20.62 6.65 26.08 8.41 23.32 7.52 12.73 4.11 23.85 7.69 24.00 7.74 17.46 5.63 18.79 6.06 17.72 5.72 26.08 8.41 26.93 8.69 20.62 6.65 19.10 6.16 13.42 4.33 22.85 7.37 MEASUREMENTS 25705-06 CELL HEIGHT (PIXELS) 12.17 24.17 20.59 22.36 24.08 22.80 10.00 16.97 21.63 22.00 20.88 12.81 16.12 16.00 22.36 CELL HEIGHT (um) 3.92 7.80 6.64 7.21 7.77 7.36 3.23 5.47 6.98 7.10 6.74 4.13 5.20 5.16 7.21 MEAN SD N 20.90 4.395 15 6.74 1.418 15 19.00 4.622 15 6.13 1.491 15 PAGE 30 -1744- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25615-09 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 22.36 7.21 21.40 6.90 16.49 5.32 17.89 5.77 18.03 5.82 19.10 6.16 19.00 6.13 17.03 5.49 17.80 5.74 17.69 5.71 16.55 5.34 15.81 5.10 22.00 7.10 16.12 5.20 17.69 5.71 MEASUREMENTS 25618-18 CELL HEIGHT (PIXELS) 18.03 15.62 17.03 19.24 20.00 18.79 18.38 22.85 15.23 16.55 17.49 18.25 13.42 19.21 21.26 CELL HEIGHT (um) 5.82 5.04 5.49 6.20 6.45 6.06 5.93 7.37 4.91 5.34 5.64 5.89 4.33 6.20 6.86 MEAN SD N 18.33 2.087 15 5.91 0.673 15 18.09 2.382 15 5.84 0.768 15 GROUP MEAN GROUP SD GROUP N 19.48 1.395 10 6.28 0.450 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 31 -1745- WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25621-12 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 15.00 4.84 17.89 5.77 21.00 6.77 18.44 5.95 17.49 5.64 18.11 5.84 14.76 4.76 20.12 6.49 15.30 4.93 20.25 6.53 20.02 6.46 24.19 7.80 20.00 6.45 15.23 4.91 22.20 7.16 MEASUREMENTS 25632-15 CELL HEIGHT (PIXELS) 23.35 21.63 18.03 18.79 13.89 19.00 17.46 19.24 17.49 25.50 18.44 24.04 15.23 23.60 24.04 CELL HEIGHT (um) 7.53 6.98 5.82 6.06 4.48 6.13 5.63 6.20 5.64 8.22 5.95 7.76 4.91 7.61 7.76 MEAN SD N 18.67 2.814 15 6.02 0.908 15 19.98 3.503 15 6.45 1.130 15 PAGE 32 -1746- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25637-10 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 23.32 7.52 20.00 6.45 18.44 5.95 14.56 4.70 23.32 7.52 20.10 6.48 22.80 7.36 16.55 5.34 15.65 5.05 23.35 7.53 14.21 4.58 24.02 7.75 18.03 5.82 18.44 5.95 15.26 4.92 MEASUREMENTS 25638-11 CELL HEIGHT (PIXELS) 15.03 21.54 20.25 23.09 18.68 20.22 18.79 20.00 15.30 27.00 19.42 21.95 22.02 15.30 19.24 CELL HEIGHT (um) 4.85 6.95 6.53 7.45 6.03 6.52 6.06 6.45 4.93 8.71 6.26 7.08 7.10 4.93 6.20 MEAN SD N 19.20 3.514 15 6.19 1.134 15 19.86 3.181 15 6.40 1.026 15 PAGE 33 -1747- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25657-13 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 12.65 4.08 18.44 5.95 18.44 5.95 25.08 8.09 22.56 7.28 24.00 7.74 24.04 7.76 24.08 7.77 27.78 8.96 19.24 6.20 24.08 7.77 18.11 5.84 21.95 7.08 23.60 7.61 25.30 8.16 MEASUREMENTS 25670-17 CELL HEIGHT (PIXELS) 20.88 26.08 21.00 26.08 20.81 21.59 15.81 29.12 16.16 18.00 21.10 20.00 21.10 20.62 27.29 CELL HEIGHT (um) 6.74 8.41 6.77 8.41 6.71 6.96 5.10 9.39 5.21 5.81 6.80 6.45 6.80 6.65 8.80 MEAN SD N 21.96 3.865 15 7.08 1.247 15 21.71 3.878 15 7.00 1.251 15 PAGE 34 -1748- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 1 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25681-14 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 16.64 5.37 20.00 6.45 18.36 5.92 18.11 5.84 18.11 5.84 15.00 4.84 15.81 5.10 15.65 5.05 18.36 5.92 16.76 5.41 21.40 6.90 18.44 5.95 21.40 6.90 21.10 6.80 19.10 6.16 MEASUREMENTS 25687-10 CELL HEIGHT (PIXELS) 22.00 20.02 20.25 15.23 16.12 19.10 13.00 16.12 18.36 17.20 24.19 16.97 19.42 21.95 20.62 CELL HEIGHT (um) 7.10 6.46 6.53 4.91 5.20 6.16 4.19 5.20 5.92 5.55 7.80 5.47 6.26 7.08 6.65 MEAN SD N 18.28 2.068 15 5.90 0.667 15 18.70 2.967 15 6.03 0.957 15 PAGE 35 -1749- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25616-13 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 18.68 6.03 13.89 4.48 13.00 4.19 22.83 7.36 23.60 7.61 16.40 5.29 15.81 5.10 18.03 5.82 16.28 5.25 21.40 6.90 24.70 7.97 14.87 4.80 15.52 5.01 17.72 5.72 13.42 4.33 MEASUREMENTS 25619-10 CELL HEIGHT (PIXELS) 26.91 18.60 20.10 21.19 16.40 17.20 19.24 23.60 26.00 23.77 13.60 26.25 18.03 19.21 22.00 CELL HEIGHT (um) 8.68 6.00 6.48 6.84 5.29 5.55 6.20 7.61 8.39 7.67 4.39 8.47 5.82 6.20 7.10 MEAN SD N 17.74 3.778 15 5.72 1.219 15 20.81 3.913 15 6.71 1.262 15 GROUP MEAN GROUP SD GROUP N 19.77 1.853 10 6.38 0.598 10 PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS PAGE 36 -1750- WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25630-13 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 25.71 8.29 19.42 6.26 21.59 6.96 17.03 5.49 21.38 6.90 27.73 8.95 21.95 7.08 24.02 7.75 19.10 6.16 21.26 6.86 21.21 6.84 21.38 6.90 17.49 5.64 16.76 5.41 25.71 8.29 MEASUREMENTS 25639-12 CELL HEIGHT (PIXELS) 26.17 23.77 21.00 25.00 18.44 16.00 23.85 26.00 22.56 20.02 17.89 15.81 19.42 30.61 26.42 CELL HEIGHT (um) 8.44 7.67 6.77 8.06 5.95 5.16 7.69 8.39 7.28 6.46 5.77 5.10 6.26 9.87 8.52 MEAN SD N 21.45 3.268 15 6.92 1.054 15 22.20 4.291 15 7.16 1.384 15 PAGE 37 -1751- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25658-13 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 23.54 7.59 16.76 5.41 14.76 4.76 19.85 6.40 22.02 7.10 16.76 5.41 19.70 6.35 19.03 6.14 14.87 4.80 20.00 6.45 19.42 6.26 17.00 5.48 18.25 5.89 16.40 5.29 17.69 5.71 MEASUREMENTS 25673-14 CELL HEIGHT (PIXELS) 19.10 14.21 13.93 20.62 19.42 24.35 14.21 15.81 16.49 20.59 17.72 14.21 16.49 16.00 20.59 CELL HEIGHT (um) 6.16 4.58 4.49 6.65 6.26 7.86 4.58 5.10 5.32 6.64 5.72 4.58 5.32 5.16 6.64 MEAN SD N 18.40 2.462 15 5.94 0.794 15 17.58 3.097 15 5.67 0.999 15 PAGE 38 -1752- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25676-08 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 20.88 6.74 20.10 6.48 20.12 6.49 29.15 9.40 24.08 7.77 25.02 8.07 27.29 8.80 20.00 6.45 23.19 7.48 23.19 7.48 24.04 7.76 20.25 6.53 16.16 5.21 18.36 5.92 24.33 7.85 MEASUREMENTS 25686-15 CELL HEIGHT (PIXELS) 18.87 23.19 20.62 25.00 18.38 18.44 16.00 18.87 17.03 21.10 13.60 18.03 21.10 24.70 21.21 CELL HEIGHT (um) 6.09 7.48 6.65 8.06 5.93 5.95 5.16 6.09 5.49 6.80 4.39 5.82 6.80 7.97 6.84 MEAN SD N 22.41 3.438 15 7.23 1.109 15 19.74 3.137 15 6.37 1.012 15 PAGE 39 -1753- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017V APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL THYROID MORPHOMETRY GROUP: 4 Females ANIMAL NUMBER: CELL NUMBER 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 LINE ID L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 THYROID EPITHELIAL 25696-14 CELL HEIGHT CELL HEIGHT (PIXELS) (um) 25.71 8.29 26.63 8.59 18.38 5.93 15.03 4.85 17.00 5.48 13.89 4.48 19.72 6.36 23.77 7.67 21.19 6.84 24.02 7.75 16.12 5.20 20.25 6.53 17.80 5.74 16.00 5.16 15.30 4.93 MEASUREMENTS 25705-11 CELL HEIGHT (PIXELS) 14.32 18.03 18.38 17.09 20.40 12.53 18.60 24.04 21.02 21.02 22.09 16.28 12.17 18.00 15.62 CELL HEIGHT (um) 4.62 5.82 5.93 5.51 6.58 4.04 6.00 7.76 6.78 6.78 7.13 5.25 3.92 5.81 5.04 MEAN SD N 19.39 4.092 15 6.25 1.320 15 17.97 3.430 15 5.80 1.107 15 PAGE 40 -1754- PIXELS 2 = SQUARE PIXELS; um = MICROMETERS; um 2 = SQUARE MICROMETERS WIL-180017W APPENDIX 50 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL Ki-67 CELL COUNTS GESTATION DAY 20 FETUSES GROUP 1 MALES GROUP 4 MALES ANIMAL NUMBER 25612-01 25620-01 25629-01 25634-01 25659-01 25679-01 25683-01 25706-01 25718-01 25760-01 Ki-67 COUNT NIP 36 NIP 70 22 NIP NIP 70 25 18 ANIMAL NUMBER 25608-01 25625-01 25649-01 25656-01 25688-01 25693-01 25699-01 25734-01 25745-02 25750-01 Ki-67 COUNT NIP 36 80 NIP 14 29 NEX 24 NEX 10 MEAN SD N 40 23.9 6 MEAN SD N 32 25.3 6 NIP = NOT IN PLANE OF SECTION; NEX = TISSUE NOT RECEIVED PAGE 1 -1755- WIL-180017W APPENDIX 50 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL Ki-67 CELL COUNTS GESTATION DAY 20 FETUSES GROUP 1 FEMALES GROUP 4 FEMALES ANIMAL NUMBER 25612-02 25620-02 25629-02 25634-02 25659-02 25679-02 25683-02 25706-02 25718-02 25760-02 Ki-67 COUNT 23 4 NIP 22 NIP 34 NIP 113 39 57 ANIMAL NUMBER 25608-02 25625-02 25649-02 25656-02 25688-02 25693-02 25699-02 25734-02 25745-02 25750-02 Ki-67 COUNT 89 NIP NIP 88 64 83 NEX 116 NEX NIP MEAN SD N 42 35.5 7 MEAN SD N 88 18.6 5 NIP = NOT IN PLANE OF SECTION; NEX = TISSUE NOT RECEIVED PAGE 2 -1756- WIL-180017 3M Corporation -1757- MTDID 208 06-128 APPENDIX 51 Study Personnel WIL-180017 3M Corporation -1758- MTDID 208 06-128 Study Personnel: Susan C. Haley, BS Sally A. Keets, AS Carol A. Kopp, BS, LAT Theresa M. Rafeld Michael A. Safron, AS, HT (ASCP) Bennett J. Varsho, MPH, DABT Robert A. Wally, BS, RAC Manager, Clinical Pathology Senior Operations Manager, Vivarium Manager, Gross Pathology and Developmental Toxicology Laboratory Group Manager, Formulations Laboratory Manager, Histology Operations Manager, Developmental and Reproductive Toxicology and the Formulations Laboratory Manager, Reporting and Regulatory Technical Services WIL-180017 3M Corporation -1759- MTDID 208 06-128 APPENDIX 52 Study Protocol And Amendments -1760- Study Number: WIL-180017 PROTOCOL AMENDMENT IV 3M Study Number: 06-128 Sponsor: 3M Corporation A. Title of Study: An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats B. Protocol Modification: 1) 11.3 Organ Weight and Hormone Data: The following is added to the protocol: Thyroid morphometry and thyroid cell proliferation data will be analyzed by the parametric one-way ANOVA (Snedecor, 1980) to determine intergroup differences. If significant differences are indicated by the ANOVA, Dunnett's test (Dunnett, 1964) will be used to compare the control and treated groups. C. Reason for Protocol Modification: 1) To add statistical analysis of thyroid morphometry and thyroid cell proliferation data to the protocol. Approved By: 3M Corporation John L. Butenhoff, PhD, CIHYDABT Sponsor Representative Prepared By: WIL Research Laboratories, LLC t;A-$.( l7.W 3onald G. Stump, PhD, DABT Study Director n t 6 6 a7 Date Director, Development and Reproductive Toxicology WIL RESEARCHLABORATORIELSL,C - 1407GEORGE ROAD ASHLAND, OH 44805-9281 (419)289-8700 FAX (419)289-3650 Improving human health and protecting the environment through scientificresearchservices.@ -1761- Study Number: WIL-180017 PROTOCOL AMENDMENT I11 3M Study Number: 06-128 Sponsor: 3M Corporation A. Title of Study: An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats B. Protocol Modification: 1) 9.6 Thyroid Histopatholoey and Morphometw: ~~~ Based on the Study Director Notification dated January 11, 2007, the first sentence is changed to read: One pup/sex/litter fi-om ten randomly selected litters/group on postnatal days 4 and 21 will be prepared for thyroid microscopic examination and morphometry (thyroids for all groups will be processed; however, the control and high dose groups will be initially evaluated). Based on the Study director Notification dated January 11,2007, Section 9.7 is replaced with the following: 9.7 Thyroid Cell Proliferation Assay: One fetus/sex/litter fi-om 10 randomly selected litters/group on gestational day 20 will be prepared for thyroid microscopic examination (thyroids for all groups will be processed; however, the control and high dose groups will be initially evaluated) and have a thyroid cell proliferation assay performed using Ki67 immunohistochemicalstaining. C. Reason for Protocol Modification: 1,2) Based on the initial microscopic examination of fetal and pup thyroids, the protocol was amended to require assessment of thyroid cell proliferation for postnatal day 4 pups because of an absence of colloid. However, the boxes containing the gestation day 20 and postnatal day 4 thyroid slides were WIL RESEARCHLABORATORIELSL,C 1407GEORGE RO - AD ASHLAND,OH 44805-9281 (419)289-8700 FAX (419)289-3650 Improving human health and protecting the environment throughscientificresearchservices.@ -1762- WIL-180017 Protocol Amendment III Page 2 misidentified. The thyroids without colloid are actually from the gestation day 20 fetuses. Therefore, the cell proliferation assay will be performed on the gestation day 20 fetuses and thyroid morphometry will be performed on the postnatal day 4 pups. Approved By: 3M Corporation John L. Butenhoff, PhD, CIH, DABT Sponsor Representative Prepared By: WIL Research Laboratories, LLC n Donald G. Stump, PhD, DABT Study Director \ M a r k b & m e c , BS, DABT Director, Development and Reproductive Toxicology Date Date />72A 3 Date ..*.:::...'.....s....i..r..............:..:...::.::..t:.;i..;....:.........:a:;.......:.....:.....:A...% A.:.:;...;:........................ .-...I.. ........................ :: B : :::: : :: -1763- Study Number: WIL-180017 PROTOCOL AMENDMENT I1 3M Study Number: 06-128 Sponsor: 3M Corporation A. Title of Study: An Oral (Gavage) Developmental (eurotoxicity and Thyroid Function Study of MTDID 208 in Rats B. Protocol Modification: 1) 9.6 Thyroid Histopathology and Morphometry: The first sentence is changes to read: One fetus/sex/litter from each toxicokinetic phase female euthanized on gestation day 20 and one pup/sex/litter from 10 randomly selected litterdgroup on postnatal day 21 will be prepared for thyroid microscopic examination and morphometry (thyroids for all groups will be processed; however, the control and high dose groups will be initially evaluated). The following is added to the protocol: 9.7 Thyroid Cell Proliferation Assay: One pup/sex/litter from 10 randomly selected litters/group on postnatal day 4 will be prepared for thyroid microscopic examination (thyroids for all groups will be processed; however, the control and high dose groups will be initially evaluated) and have a thyroid cell proliferation assay performed using Ki67 immunohistochemical staining. C. Reason for Protocol Modification: 1) The client in consultation with the Study Director has elected to perform thyroid morphometry only on the toxicokinetic phase females on gestation day 20 fetuses and postnatal day 21 pups. WIL RESEARCHLABORATORIELSL,C 1407 GEORGE ROAD ASHLAND, OH 44805-9281 (419)289-8700 FAX (419)289-3650 - e - Improving human health and protecting the environment throughscientificresearchservices.@ -1764- W L - 180017 Protocol Amendment II Page 2 2) The client has elected to perform a thyroid cell proliferation assay on the postnatal day 4 animals. Approved By: 3M Corporation qLd3W John L. Butenhoff, PhD, CM, DABT Date Sponsor Representative Prepared By: WIL Research Laboratories, LLC Donald G. Stump, PhD, DABT Study Director Date Director, Development and Reproductive Toxicology -1765- Study Number: WIL-180017 PROTOCOL AMENDMENT I Sponsor: 3M Corporation A. Title of Study: An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats B. Protocol Modification: 1) 5.4 Number of Animals: The following is added to the protocol: Females not assigned to the study will be transferred to the stock colony or will be euthanized by carbon dioxide inhalation and the carcasses discarded. 2) 11.1 Maternal In-Life Data: The first sentence is changed to read: Continuous data variables [mean maternal body weights (gestation and lactation), body weight gains, and food consumption at each interval], former implantation sites, unaccounted for sites, and mean gestation length will be analyzed by a parametric one-way analysis of variance (ANOVA) (Snedecor, 1980) to determine intergroup difference. 3) 11.4.4 Learning and Memory Data: The following is added to the protocol: Time to escape the straight channel will be subjected to a parametric oneway ANOVA (Snedecor, 1980) to determine intergroup difference. If significant differences are indicated by the ANOVA, Dunnett's test (Dunnett, 1964) will be used to compare the control and treated groups. -1766- W E - 180017 Protocol Amendment I Page 2 C. Reason for Protocol Modification: 1) To provide a disposition for the surplus animals. 2 and 3) To include statistical analysis of former implantation sites, unaccounted for sites, and time to escape the straight channel to the protocol. Approved By: 3M Corporation John L. Butenhoff, PhD, CIH, DABT Sponsor Representative Prepared By: WIL Research Laboratories, LLC A 7- .$I 2006 Date Donald G. Stump, PhD, DABT Date Study Director ' Mark D. Nemec, B w m T Date Director, Development and Reproductive Toxicology -1767- Page 1 of 33 WIL-180017 April 20, 2006 PROTOCOL AN ORAL (GAVAGE) DEVELOPMENTAL NEUROTOXICITY AND THYROID FUNCTION STUDY OF MTDID 208 IN RATS (EPA OPPTS Guideline 870.6300; OECD Draft Guideline 426) 3M Study Number: 06-128 Submitted To: 3M Corporation 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-9281 -1768- Page 2 of 33 WIL-180017 April 20, 2006 1 OBJECTIVE: To determine the potential of the test article to induce functional and morphological insult to the nervous system which may arise in the offspring from exposure of the mother during pregnancy and lactation. An additional objective of this study is to determine the effects of maternal exposure to the test article on maternal and neonatal thyroid status and to establish toxicokinetic data for different compartments in the dam and offspring. This protocol has been designed in general accordance with the U.S. EPA Health Effects Test Guideline OPPTS 870.6300 Developmental Neurotoxicity Study, August 1998 and the Organisation for Economic Cooperation and Development (OECD) Revised Draft Guideline No. 426, 2003. This study will be conducted in compliance with U.S. EPA Good Laboratory Practice Standards (40 CFR 792). 2 PERSONNEL INVOLVED IN THE STUDY: 2.1 Sponsor Representatives: John L. Butenhoff, PhD, CIH, DABT (Primary) Medical Department 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 Tel: 651-733-1962 Fax: 651-733-1773 E-mail: jlbutenhoff@mmm.com Shu-Ching (Sue) Tanaka, MS (Alternate) Medical Department 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 Tel: 651-733-9073 Fax: 651-733-1773 E-mail: stanaka@mmm.com 2.2 WIL Study Director: Donald G. Stump, PhD, DABT Associate Director, Developmental, Reproductive and Neurotoxicity Tel: (419) 289-8700 Fax: (419) 289-3650 E-mail: dstump@wilresearch.com -1769- Page 3 of 33 2.3 WIL Deputy Director: Eddie D. Sloter, PhD Staff Toxicologist, Developmental and Reproductive Toxicology 2.4 WIL Departmental Responsibilities: Joseph F. Holson, PhD President, Director Mark D. Nemec, BS, DABT Director, Developmental and Reproductive Toxicology George A. Parker, DVM, PhD, DACVP, DABT Director, Pathology Melissa J. Beck, PhD Assistant Director, Neurosciences Daniel W. Sved, PhD Director, Metabolism and Analytical Chemistry Lisa T. Snyder, DVM Clinical Veterinarian Ronald E. Wilson, BS Director, Informational Systems Carol A. Kopp, BS, LAT Manager, Gross Pathology and Developmental Toxicology Laboratory Heather L. Osborn, BS, RQAP-GLP Manager, Quality Assurance Bennett J. Varsho. BS, DABT Operations Manager, Developmental, Reproductive and Neurotoxicology Robert A. Wally, BS, RAC Manager, Reporting and Regulatory Technical Services WIL-180017 April 20, 2006 -1770- Page 4 of 33 WIL-180017 April 20, 2006 2.5 Repeated Measures Analysis: Les Freshwater, MS BioSTAT Consultants, Inc. 3 STUDY SCHEDULE: Proposed Animal Receipt Date: April 18, 2006 Proposed Experimental Start Date: May 2, 2006 Proposed Experimental Termination Date: August 8, 2006 Proposed Audited Report Date: To be determined 4 TEST ARTICLE DATA: 4.1 Identification: MTDID 208 (potassium perfluorooctanoate, FC-95, Lot 217) 4.2 Lot Number: 217 4.3 Purity: 86.9 percent 4.4 Stability: The test article is considered to be stable under the storage conditions provided by the Sponsor. 4.5 Physical Description: To be documented by WIL Research Laboratories, LLC. 4.6 Storage Conditions: Room temperature. -1771- Page 5 of 33 WIL-180017 April 20, 2006 4.7 Reserve Samples: Reserve samples of the test article will be taken in accordance with WIL standard operating procedures and stored in the Archives at WIL Research Laboratories, LLC indefinitely, unless otherwise specified. 4.8 Personnel Safety Data: To be provided by the Sponsor. It is the responsibility of the Sponsor to notify the testing facility of any special handling requirements of the test article. A material safety data sheet (MSDS) should accompany the test article upon arrival at the laboratory. 5 TEST SYSTEM: 5.1 Species: Rat 5.2 Strain: Sprague Dawley Crl:CD(SD) 5.3 Source: Charles River Laboratories, Inc. (Raleigh, NC) 5.4 Number of Animals: 140 females (maximum of 175 females purchased). Resident males will be used to induce pregnancy. 5.5 Body Weight Range: Minimum of 220 g at initiation of breeding. 5.6 Approximate Age: 80 to 120 days at the start of the in-life phase. 5.7 Identification System: Each maternal animal will be uniquely identified by a Monel metal eartag displaying the animal number. Individual cage cards will be affixed to each cage and will display the animal number, group number, study number, dosage -1772- Page 6 of 33 WIL-180017 April 20, 2006 level and sex of the animal. The offspring selected to continue on study will be uniquely identified by toe tattoo after parturition and by an ear tag following weaning. 5.8 Justification for Selection and Number of Animals: This species and strain of animal is recognized as appropriate for developmental neurotoxicity studies. WIL Research Laboratories, LLC has reproductive and neurotoxicity historical control data in the Crl:CD(SD) rat. This animal model has been proven to be susceptible to the effects of developmental neurotoxicants. This number of animals is required to meet U.S. EPA guideline 870.6300 recommendations. 6 SPECIFIC MAINTENANCE SCHEDULE: 6.1 Animal Housing: The animals will be individually housed in clean suspended wire-mesh cages in an environmentally controlled room during acclimation and continuing until mating. The cages will be elevated above cage-board or other suitable material, which will be changed at least three times each week. During cohabitation, the females will be paired (1 male:1 female) with resident males in a suspended wire-mesh cage. Following successful mating, the female will be individually housed in plastic maternity cages with nesting material (Bed-O'Cobs) and will remain in these cages until euthanasia. After weaning on postnatal day (PND) 21, the offspring (F1) will be housed with litter mates in plastic cages with nesting material through PND 27. On PND 28, F1 offspring will be individually housed in wire-mesh cages and will remain in these cages until euthanasia. The cages will be subjected to routine cleaning at a frequency consistent with maintaining good animal health. The facilities at WIL Research Laboratories, LLC are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International). 6.2 Environmental Conditions: Controls will be set to maintain an average daily temperature of 71 5F (22 3C) and an average daily relative humidity of 50 20%. Temperature and relative humidity will be monitored continuously. Data for these two parameters will be scheduled for automatic collection on an hourly basis. Fluorescent lighting controlled by light timers will provide illumination for a 12-hour light (6:00 a.m. to 6:00 p.m.)/12-hour dark photoperiod. The ventilation rate will be set at a minimum of 10 room air changes per hour, 100% fresh air. -1773- Page 7 of 33 WIL-180017 April 20, 2006 6.3 Drinking Water: Reverse osmosis-purified water will be available ad libitum. Filters servicing the automatic watering system are changed regularly according to WIL standard operating procedures. The municipal water supplying the laboratory is analyzed on a routine basis according to WIL Standard Operating Procedures to assure that contaminants are not present in concentrations that would be expected to affect the outcome of the study. 6.4 Basal Diet: PMI Nutrition International, LLC Certified Rodent LabDiet 5002 will be offered ad libitum during the study. Periodic analyses of the certified feed are performed by the manufacturer to ensure that heavy metals and pesticides are not present at concentrations that would be expected to affect the outcome of the study. Results of the analyses are provided to WIL Research Laboratories, LLC by the manufacturer. Feeders will be changed and sanitized once per week. Due to the presence of fish meal in PMI 5002 diet, it is likely that perfluorooctanesulfonate (PFOS) is present at low levels that could result in exposure of control rats. Analysis of liver and sera samples for PFOS will provide information on control rat body burdens relative to potassium PFOS treatment groups. 7 EXPERIMENTAL DESIGN: 7.1 Animal Receipt and Quarantine: Each rat will be inspected by a qualified technician upon receipt. Rats judged to be in good health and suitable as test animals will be immediately placed in quarantine for a minimum of 10 days. All rats will be initially weighed and permanently identified with a metal ear tag. During the quarantine period, each rat will be observed twice daily for changes in general appearance and behavior. Prior to the start of the in-life phase, those animals judged to be suitable test subjects will be identified. 7.2 Breeding Procedure: A female will be cohabited with an untreated resident male rat of the same strain and source in a suspended wire-mesh cage for mating. Detection of mating will be confirmed by evidence of a copulatory plug or by a vaginal lavage for sperm. After confirmation of mating, the female will be placed in an individual plastic maternity cage and the day will be designated as day 0 of gestation. -1774- Page 8 of 33 WIL-180017 April 20, 2006 7.3 Randomization: At the conclusion of the quarantine period, rats judged to be suitable test subjects and meeting acceptable body weight requirements will be cohabited with an untreated resident male of the same strain and source. The mated females will be assigned daily to one control and three test article-treated groups of 25 rats each for the main study and 10 rats each for the toxicokinetic/thyroid function satellite phase using a computer program that assigns animals based on stratification of the gestation day 0 body weights in block designs. 7.4 Route and Rationale of Test Article Administration: The route of administration will be oral (gavage) since this is a possible route of exposure for humans. Historically, this route has been used extensively for studies of this nature. Appropriate-sized flexible, Teflon-shafted, stainless steel ball-tipped dosing cannulae will be used for oral administration by gavage. 7.5 Organization of Test Groups, Dosage Levels and Treatment Regimen: 7.5.1 Organization of Test Groups: The dosage levels were determined from the results of previous studies and were provided by the Sponsor Representative after consultation with the WIL Study Director. The following diagram presents the study group arrangement. Group Number 1 2 3 4 Test Article Vehicle Control MTDID 208 MTDID 208 MTDID 208 Dosage Level (mg/kg/day) 0 0.1 0.3 1.0 Dosage Concentration (mg/mL) 0 0.02 0.06 0.2 Dosage Volume (mL/kg) 5 5 5 5 Number of Females Main TK 25 10 25 10 25 10 25 10 7.5.2 Vehicle Control Article: 0.5% Tween 20 7.5.3 Treatment Regimen: The test and control articles will be administered as a single daily dose from gestation day 0 through lactation day 20, inclusively, for the main study phase or through gestation day 19 for the toxicokinetic/thyroid function satellite phase. All animals will be dosed at approximately the same time each day. F1 generation animals will be potentially exposed to the test article in utero and via the milk during the lactation period -1775- Page 9 of 33 WIL-180017 April 20, 2006 (also possibly to a minor extent through feed). No direct administration to the F1 animals will occur. 7.5.4 Adjustment of Dosages: Individual dosages will be calculated based on the most recent body weight to provide the proper mg/kg/day dosage. 7.6 Analysis of Test Article Preparation: 7.6.1 Method and Frequency of Preparation: Based on the physical characteristics of the test article, appropriate methods will be used to ensure the best possible formulations of the test article in the vehicle. The dosing formulations will be prepared and stored in plastic containers. Dosing formulations will be prepared weekly and stored under refrigeration for a period not to exceed 8 days, unless otherwise indicated based on stability. The study director or the deputy director or designee will visually inspect the formulations prior to initiation of dosing. This visual inspection will be performed to assure that the formulations are visibly homogeneous and acceptable for dosing. Any special procedures required for formulation will be documented according to Good Laboratory Practices and presented in the final report of this study. 7.6.2 Homogeneity and Stability of Test Article Formulations: Analyses to demonstrate the homogeneity and stability of the test article formulations will be conducted before the initiation of dosing, if possible. For homogeneity assessments, test article formulations of sufficient volume for dosing a group of animals will be prepared. All samples will be placed into plastic containers. Samples will be collected from the middle of the vehicle formulation and the top, middle and bottom of the test article formulations. A volume of each formulation similar in size to the amount needed for one day will be stored under refrigeration for 8 days. After remixing for a minimum of 15 minutes using a magnetic stirrer, samples will be collected from the top and bottom of each test article formulations and analyzed to assess the homogeneity after storage and resuspension and 8-day stability. The samples will be frozen at approximately -20C and shipped to the Sponsor for analysis. -1776- Page 10 of 33 WIL-180017 April 20, 2006 7.6.3 Concentration Analysis: Samples will be taken from the middle of each dosing formulation prepared for the study and placed into plastic containers. These samples will be frozen at approximately -20C. After completion of the dosing period, all of these samples will be shipped to the Sponsor and analyzed to verify the concentration of the test article in the dosing formulations. 7.6.4 Sample Shipment and Analysis: Samples collected for analysis of homogeneity, stability and concentration will be shipped on dry ice to the following individual for analysis: David Ehresman 3M Company CT&RS Laboratory 3M Center 236-1B-22 St. Paul, MN 55144 Tel: (651) 733-5070 E-mail: dijehresman@mmm.com 7.7 Maternal Observations (Main Study and Toxicokinetic/Thyroid Function Satellite Phase): 7.7.1 Maternal Appearance and Behavior: Each rat will be observed twice daily for moribundity and mortality, once in the morning and once in the afternoon from gestation day 0 through lactation day 21, inclusively for the main study animals and from gestation day 0 to 20, inclusively for the toxicokinetic phase animals. Clinical observations regarding general appearance and behavior will be recorded daily. Mortality and all signs of overt toxicity will be recorded on the day observed. The observations shall include, but are not limited to, evaluations for changes in appearance of skin and fur, eyes, mucous membranes, respiratory and circulatory systems, autonomic and central nervous systems, somatomotor activity and behavior. During the treatment period, the rats assigned to the main study will also be observed approximately one hour following dosing and the observations will be recorded. If additional observation periods are necessary, they will be documented in the study records. -1777- Page 11 of 33 WIL-180017 April 20, 2006 7.7.2 Maternal Body Weights: Individual body weights will be recorded on gestation days 0, 3, 6, 9, 12, 15, 18 and 20 and on lactation days 1, 4, 7, 10, 14, 17 and 21, if appropriate. 7.7.3 Maternal Food Consumption: Individual food consumption will be recorded on gestation days 0, 3, 6, 9, 12, 15, 18 and 20, and on lactation days 1, 4, 7, 10, 14, 17 and 21, if appropriate. 7.7.4 Parturition and Lactation: All females in each of the dose groups assigned to the main study will be allowed to deliver. The day parturition is initiated will be designated as lactation day/postnatal day 0. Any difficulties at the time of parturition will be recorded. When parturition is judged complete, litters will be sexed, examined for gross malformations and the number of stillbirths and live pups will be recorded. The dam and litter will remain together until postnatal day 21. Each litter will remain together until postnatal day 28. 7.7.5 Standardization of Litter Size and Identification: All pups will be individually identified at the completion of parturition by application of tattoo markings applied to the digits. To reduce variability among litter size, eight pups from each litter will be randomly selected on postnatal day 4. If a litter consists of less than six pups or does not meet the sex ratio criteria (at least three/sex), the litter will not be used for neurobehavioral or neuropathological evaluation, if possible. Of the eight pups selected in each litter, one male and one female pup from each litter (until N=20 pups/sex/group) will be randomly assigned to one of the following evaluation subsets. Subset A: FOB, locomotor activity, auditory startle and learning and memory assessment. Subset B: one male and/or one female pup from each litter (until N=15 pups/sex/group) will be assigned to neuropathological and brain weight evaluation on PND 21. -1778- Page 12 of 33 WIL-180017 April 20, 2006 The following table summarizes the allocation of offspring for behavioral tests, brain weights and neuropathological evaluations: ALLOCATION OF PUPS FOR BEHAVIORAL TESTS, BRAIN WEIGHTS AND NEUROPATHOLOGIC EVALUATION No. Selected Age Evaluation 15/sex/group (B) PND 21 Brain weights, neuropathological assessment, morphometry 20/sex/group (A)* PND 4, 11, 21, 35, 45 and 60 FOB 20/sex/group (A)* PND 20 and 60 Auditory startle 20/sex/group (A)* PND 13, 17, 21 and 61 Locomotor activity 20/sex/group (A)* PND 22 Learning and memory 15/sex/group (A)** PND 72 Brain weights, neuropathological assessment, morphometry * The same pup subset will be used for FOB, auditory startle, locomotor activity and learning and memory evaluation. ** Animals assigned to brain weight and neuropathological assessment and morphometry will be randomly selected from animals previously allocated to FOB, locomotor activity, auditory startle and learning and memory evaluation. 7.8 Examination of Offspring (Main Study): 7.8.1 Pup Body Weights and Sex Identification: Individual pup body weights will be recorded on postnatal days 1, 4, 7, 11, 14, 17, 21 and at weekly intervals thereafter until euthanasia (postnatal day 72). Pups will be sexed on postnatal days 0, 4, 11 and 21. 7.8.2 Appearance and Behavior: Each pup will be observed daily for moribundity and mortality from the day of parturition through weaning (PND 21). On PND 1, 4, 7, 11, 14, 17, 21 and at weekly intervals thereafter until euthanasia, offspring will be removed from the home cage and receive a detailed physical examination. Clinical observations regarding general appearance, behavior and all signs of overt toxicity will be recorded on the day observed. The observations shall include evaluations for changes in appearance of skin and fur, eyes, mucous membranes, respiratory and circulatory systems, autonomic and central nervous systems, somatomotor activity and behavior. 7.8.3 Developmental Landmarks: 7.8.3.1 Balanopreputial Separation: Each male pup assigned to Subset A will be observed for balanopreputial separation (Korenbrot, 1977) beginning on -1779- Page 13 of 33 WIL-180017 April 20, 2006 postnatal day 35. Examination of the males will continue daily until balanopreputial separation is present. The body weight of each male will be recorded on the day of demonstration of balanopreputial separation. 7.8.3.2 Vaginal Perforation: Each female pup assigned to Subset A will be observed for vaginal perforation (Adams, 1985) beginning on postnatal day 25. Examination of the females will continue daily until vaginal perforation is present. The body weight of each female will be recorded on the day of demonstration of vaginal perforation. 7.8.4 Behavioral Testing: Following standardization of litters on postnatal day 4, one male and one female pup in each litter (until N=20 pups/sex/group) will be assigned to the following tests: functional observational battery, locomotor activity, auditory startle and learning and memory. 7.8.4.1 Pup Functional Observational Battery: Twenty male and 20 female offspring from each treatment group (20 pups/sex/group assigned to Subset A) will be assigned to FOB testing on postnatal days 4, 11, 21, 35, 45 and 60. The same animals will be observed at each interval. The FOB utilized at WIL Research Laboratories, LLC is based on previously developed protocols (Moser, 1991; Irwin, 1968; Gad, 1982; Moser, 1988; Haggerty, 1989, O'Donoghue, 1989). Testing will be performed by the same trained technicians, whenever possible, who will not know the animal's group assignment. Animals will be observed for the endpoints described below. -1780- Page 14 of 33 WIL-180017 April 20, 2006 Ease of removal from cage Ease of handling animal in Lacrimation/ hand chromodacryorrhea Piloerectiona,b Palpebral closurea,b Salivation Fur appearancea,b Respiratory rate/character Red/Crusty deposits Eye prominencea,b Pupillary responsea,b Mobilitya Gaita Mucous membranes and skin color Eye colora,b Muscle tone Arousal Convulsions/tremors Urination/defecation Groominga,b Backinga Bizarre/Stereotypic behavior Tail pinch responsea,b Fore- and hindlimb grip Hindlimb extensiona,b strengtha,b Air righting reflexa,b a Parameters will not be assessed in PND 4 rat pups due to the stage of development. b Parameters will not be assessed in PND 11 rat pups due to the stage of development. 7.8.4.2 Locomotor Activity: Locomotor activity will be monitored on 20 rats/sex/group, if possible, assigned to Subset A on postnatal days 13, 17, 21 and 61. The same animals will be monitored at each interval. Locomotor activity will be measured using the SDI Photobeam Activity System (San Diego Instruments, San Diego, CA) as described by WIL standard operating procedures. Locomotor activity sessions will be performed in a room equipped with a white noise generation system set to operate at 70 10 dB. The test session will be of 60 minutes duration and will consist of twelve 5-minute intervals. Locomotor activity measures evaluated are total and ambulatory activity counts obtained for the 60-minute test session. 7.8.4.3 Auditory Startle Response: The auditory startle response will be assessed for 20 rats/sex/group, if possible, assigned to Subset A on postnatal days 20 and 60 using the SR-Lab Startle Response System (San Diego Instruments, San Diego, CA) as described by WIL standard operating procedures. Acoustic startle response testing will be performed in a room equipped with a white noise generation system set to operate at 70 10 dB. -1781- Page 15 of 33 WIL-180017 April 20, 2006 The test session will consist of a 5-minute acclimation period with a 65 5 dB broadband background white noise. The startle stimulus for each trial will be a 115 5 dB mixed frequency noise burst stimulus (approximately 20 ms in duration). Responses will be recorded during the first 100 ms following onset of the startle stimulus for each trial. The test session will consist of 50 trials with an 8 second intertrial interval. Startle response data will be analyzed in 5 blocks of 10 trials each. Startle response measures obtained are maximum response amplitude (VMAX), average response amplitude (VAVE) and latency to VMAX (TMAX). 7.8.4.4 Learning and Memory Test: Learning and memory will be assessed beginning on postnatal day 22 on 20 rats/sex/group (Subset A animals), if possible, in a water-filled Biel maze (Biel, 1940). The time to escape and number of errors (animal deviates from the correct channel with all four feet) will be recorded. Animals will be allowed three minutes to escape from the maze after which they will be removed. The minimum intertrial interval will be one hour. Animals will be tested for seven consecutive days as follows: Day 1- Each animal is given 4 trials to escape from a straight channel. Days 2 and 3- Each animal is given 2 trials per day in Path A. Days 4, 5 and 6- Each animal is given 2 trials per day in Path B (reverse of Path A). Day 7- Each animal is given 2 trials in Path A. 8 TOXICOKINETIC ANALYSIS: 8.1 Gestation Day 20 Sample Collection (Toxicokinetic/Thyroid Function Satellite Phase): On gestation day 20, rats will be euthanized between 0900 and 1100 hours as described in Section 9.1.1. Following maternal and fetal blood collection, livers and brains will be collected from the dam and each viable fetus and weighed (pooled by litter for the fetus). Thereafter, a small sample of the maternal brain and liver and a single fetal liver and brain will be placed in RNlater, stored refrigerated until shipped as specified in Section 9.2.2. Remaining brain and -1782- Page 16 of 33 WIL-180017 April 20, 2006 liver samples will be snap-frozen in liquid nitrogen and stored frozen at -70C until shipped as discussed in Section 9.2.1. 8.2 Postnatal Day 4 Sample Collection (Main Study): On postnatal day 4, culled offspring will be euthanized between 0900 and 1100 hours (prior to maternal dose administration) as specified in Section 9.1.2. Following blood collection, livers and brains will be collected from the culled offspring and weighed (pooled by litter). Thereafter, a single neonatal liver and brain will be placed in RNlater, stored refrigerated until shipped as specified in Section 9.2.2. Remaining brain and liver samples will be snap-frozen in liquid nitrogen and stored frozen at -70C until shipped as discussed in Section 9.2.1. 8.3 Postnatal Day 21 Sample Collection (Main Study): On postnatal day 21, offspring assigned to thyroid function assessment will be euthanized between 0900 and 1100 hours as specified in Section 9.1.3. Following blood collection, liver and brains will be collected from the offspring and weighed. Thereafter, a small sample of the liver and brain will be placed in RNlater, stored refrigerated until shipped as specified in Section 9.2.2. Remaining brain and liver samples will be snap-frozen in liquid nitrogen and stored frozen at -70C until shipped as discussed in Section 9.2.1. 9 NECROPSY AND PATHOLOGY: 9.1 Toxicokinetic and Thyroid Function Assessment: 9.1.1 Gestation Day 20 Sample Collection (Toxicokinetic/Thyroid Function Satellite Phase): Rats assigned to the toxicokinetic phase will be euthanized between 0900 and 1100 hours by decapitation on gestation day 20. Blood samples (at least 2 mL) will be collected via decapitation into tubes without anticoagulant. After maternal blood samples have been collected, fetal blood will be collected by decapitation of each live fetus into tubes without anticoagulant (a microcapillary tube may be used to aid in the blood collection); fetal blood will be pooled by litter regardless of sex. Following blood sample collection, maternal and fetal thyroids will be preserved in 10% neutral-buffered formalin. The thyroid of one fetus/sex/litter from the control and high dose groups will be examined microscopically. The microscopic examination will include a simple morphometric analysis as described in Section 9.6. All other fetal thyroids in each litter and all maternal thyroids will be retained for -1783- Page 17 of 33 WIL-180017 April 20, 2006 possible future histopathological assessment (with Sponsor's approval, at additional cost). 9.1.2 Lactation/Postnatal Day 4 Sample Collection (Main Study): On lactation day 4, blood samples (at least 1 mL) will be collected between 0900 and 1100 hours (prior to dose administration) from the retroorbital sinus of 10 randomly selected F0 females/group assigned to the main study into tubes without anticoagulant. Females will be anesthetized by isoflurane inhalation prior to the blood sample collection. Also, on postnatal day 4, culled offspring from the same 10 litters/group whose dams are selected for blood sample collection will be decapitated between 0900 and 1100 hours. Blood will be collected by decapitation into tubes without anticoagulant (a microcapillary tube may be used to aid in the blood collection); blood will be pooled by litter regardless of sex. Following blood sample collection, neonatal thyroids will be collected and preserved in 10% neutral-buffered formalin. The thyroid of one pup/sex/litter from the control and high dose groups will be examined microscopically. The microscopic examination will include a simple morphometric analysis as described in Section 9.6. All other neonatal thyroids in each litter will be retained for possible future histopathological assessment (with Sponsor's approval, at additional cost). 9.1.3 Lactation/Postnatal Day 21 Sample Collection (Main Study): Ten randomly selected F0 rats/group assigned to the main study will be euthanized between 0900 and 1100 hours by decapitation on lactation day 21. Blood samples (at least 2 mL) will be collected via decapitation into tubes without anticoagulant. Also, on postnatal day 21, one pup/sex/litter from the same 10 litters/group whose dams are selected for blood sample collection and that are not assigned to neurobehavioral or neuropathological assessment will be decapitated between 0900 and 1100 hours. Blood will be collected by decapitation into tubes without anticoagulant (a microcapillary tube may be used to aid in the blood collection). Following blood sample collection, maternal and neonatal thyroids will be collected and preserved in 10% neutral-buffered formalin. The thyroid of one pup/sex/litter from the control and high dose groups will be examined microscopically. The microscopic examination will include a simple morphometric analysis as described in Section 9.6. All maternal thyroids in each litter will be retained for possible future -1784- Page 18 of 33 WIL-180017 April 20, 2006 histopathological assessment (with Sponsor's approval, at additional cost). 9.2 Sample Processing and Analysis: Blood samples collected on gestation day 20, postnatal/lactation day 4 and postnatal/lactation day 21 will be centrifuged at approximately 4C. Serum samples will be harvested, separated into aliquots (one with 150 L of serum for toxicokinetic analysis and the other with the remaining volume of serum for TSH analysis). All serum, liver and brain samples will be stored in a freezer set to maintain approximately -70C. 9.2.1 Toxicokinetic Sample Analysis: Samples used for determination of test article concentrations in livers, brain and serum will be shipped to the following individual for analysis: David Ehresman 3M Company CT&RS Laboratory 3M Center 236-1B-22 St. Paul, MN 55144 Tel: (651) 733-5070 E-mail: djehresman@mmm.com 9.2.2 rtPCR Samples Analysis: Samples used for rtPCR analysis in livers and brains will be shipped to the following individual: Shu-Ching (Sue) Tanaka, MS CT&RS Laboratory 3M Center 270-3S-05 St. Paul, MN 55144 Tel: (651) 733-9073 Fax: (651) 733-1773 E-mail: stanaka@mmm.com 9.2.3 TSH Sample Analysis: Serum samples collected on gestation day 20, postnatal/lactation day 4 and postnatal/lactation day 21 will be analyzed for TSH levels using the BiotrakTM rat thyroid stimulating hormone 125I assay system (Amersham Pharmacia Biotech). -1785- Page 19 of 33 WIL-180017 April 20, 2006 9.3 Terminal Procedures for Maternal Females (Dams): 9.3.1 Premature Deliveries: Females with evidence of premature delivery will be euthanized by carbon dioxide inhalation and subjected to a gross necropsy. Intact fetuses will be examined externally, euthanized by intrathoracic injection of sodium pentobarbital, if necessary, and preserved in 10% neutral-buffered formalin. Maternal tissues will be saved for possible future histopathological examination in 10% neutral-buffered formalin only as deemed necessary by the gross findings. The carcass of each dam will be discarded. 9.3.2 Females That Deliver: On lactation day 21 (day of weaning), 10 females/group will be euthanized by decapitation as described in Section 9.1.3. The remaining females in each group will be euthanized by carbon dioxide inhalation. All females will be subjected to a gross necropsy. The number of implantation sites will be recorded. Maternal tissues will be preserved in 10% neutral-buffered formalin for histopathological examination only as deemed necessary by the gross findings and as described in Section 9.1.3. The carcass of each dam will be discarded. 9.3.3 Females That Fail to Deliver: On post-mating day 25, the females will be weighed, then euthanized by carbon dioxide inhalation and subjected to a gross necropsy. The number of implantation sites will be recorded if there is evidence of pregnancy. Nongravid uteri will be opened and placed in 10% ammonium sulfide solution as described by Salewski (Salewski, 1964) for the detection of implantation sites. Tissues will be saved for possible future histopathological examination in 10% neutral-buffered formalin only as deemed necessary by the gross findings. The carcass of each dam will be discarded. 9.3.4 Females with Total Litter Loss: Females with total litter loss will be euthanized within 24 hours by carbon dioxide inhalation and subjected to a gross necropsy. The number of former implantation sites will be recorded. Tissues will be saved for possible future histopathological examination in 10% neutralbuffered formalin only as deemed necessary by the gross findings. The carcass of each dam will be discarded. -1786- Page 20 of 33 WIL-180017 April 20, 2006 9.3.5 Females Found Dead or Euthanized In Extremis: Maternal animals found dead or euthanized in extremis (by carbon dioxide inhalation) during the study will be subjected to a gross necropsy. The necropsy will include examination of the external surface, all orifices and the cranial, thoracic, abdominal and pelvic cavities including viscera. The number and location of implantation sites and corpora lutea will be recorded as per WIL standard operating procedure. Recognizable fetuses will be examined externally and euthanized by intrathoracic injection of sodium pentobarbital, if necessary. Tissues will be saved for possible future histopathological examination in 10% neutral-buffered formalin only as deemed necessary by the gross findings. The carcass will be discarded. Offspring of dams found dead or euthanized in extremis prior to weaning will be euthanized by an intraperitoneal injection of sodium pentobarbital (if PND 0-10) or carbon dioxide inhalation (if PND 11-20) and then subjected to a gross necropsy. 9.4 Terminal Procedures for Offspring Not Scheduled for Neuropathology or Brain Weight Determinations: 9.4.1 F1 Deaths and F1 Pups Euthanized in Extremis: Stillborn pups and pups dying between birth and PND 4 will be examined by a technique described by Stuckhardt and Poppe (Stuckhardt, 1984). Pups in extremis will be euthanized by either carbon dioxide inhalation or intraperitoneal injection of sodium pentobarbital, as appropriate for the lactation day, and examined as appropriate for the age. Pups dying after PND 4 will be necropsied. Organs/tissues will be preserved for possible histopathologic examination in 10% neutral-buffered formalin only as deemed necessary by the gross findings. All carcasses will be discarded. 9.4.2 Offspring Selected for Culling on PND 4: Offspring selected for culling on PND 4 will be euthanized by decapitation and used for blood and brain sample collection as specified in section 9.1.2 then discarded without examination. Culled offspring not selected for blood sample collection will be euthanized by intraperitoneal injection of sodium pentobarbital and discarded without examination. -1787- Page 21 of 33 WIL-180017 April 20, 2006 9.4.3 Euthanasia of Offspring Not Selected for Behavioral or Thyroid Function Evaluation: On PND 21, offspring not selected for behavioral evaluations or thyroid function assessment will be euthanized by carbon dioxide inhalation and subjected to a gross necropsy. Tissues will be retained in 10% neutral-buffered formalin only as deemed necessary by the gross findings. 9.4.4 Offspring Scheduled for Euthanasia at Study Termination: Pups scheduled for euthanasia on postnatal day 72 but not allocated for neuropathology/brain weight measurements will be euthanized between 0900 to 1100 by decapitation. Blood samples (at least 2 mL) will be collected into tubes without anticoagulant. Serum will be isolated and stored at approximately -70C and shipped as described in Section 9.2.1. Following blood collection, the liver will be collected from the offspring and weighed. Thereafter, a small sample of the liver will be placed in RNlater, stored refrigerated until shipped as specified in Section 9.2.2. Remaining liver samples will be snap-frozen in liquid nitrogen and stored frozen at -70C until shipped as described in Section 9.2.1. The animals will then be subjected to a gross necropsy. The necropsy will include examination of the external surface, all orifices and the cranial, thoracic, abdominal and pelvic cavities, including viscera. Organ/tissue samples will be preserved in 10% neutral-buffered formalin as deemed necessary by the gross findings. The carcass of each pup will be discarded. 9.5 Offspring Scheduled for Neuropathology/Brain Weight Measurements: Possible future neuropathological evaluation and brain weight measurements will be conducted on postnatal day 21 and at the termination of the study (postnatal day 72). 9.5.1 Offspring Euthanized on Postnatal Day 21: 9.5.1.1 Neuropathology - Macroscopic Examination: On postnatal day 21, one male and/or one female pup will be removed from each litter (until N = 15 pups/sex/group) and macroscopically examined for neuropathology. The pups will be anesthetized by intraperitoneal injection of sodium pentobarbital and euthanized by perfusion in situ as described in Section 9.5.2.1. The brains will be removed (including olfactory -1788- Page 22 of 33 WIL-180017 April 20, 2006 bulbs), weighed and the size (length and width) will be recorded. Any abnormal coloration or lesions of the brain and spinal cord will be recorded. Brains from all animals will be retained. 9.5.1.2 Neuropathology - Microscopic Examination: The pups selected for macroscopic evaluation on PND 21 will be prepared for possible future microscopic neuropathologic examination as described in Section 9.5.2.2. Sections from all major brain regions (as specified for the brain in Section 9.5.2.2) of the first 10 rats/sex from the control and high dose groups that meet the criteria for measurement may be examined (with Sponsor's approval, at additional cost). 9.5.2 Animals Euthanized at Study Termination (Postnatal Day 72): 9.5.2.1 Neuropathology - Macroscopic Examination: At the termination of the study (postnatal day 72), one male and/or one female from each litter will be randomly selected from those pups dedicated to behavioral evaluation (until N=15 rats/sex/group). The animals will be anesthetized by intraperitoneal of sodium pentobarbital and euthanized by perfusion in situ as described in WIL standard operating procedure T3-034, as revised. The central nervous system and tissues will be dissected and preserved as described in WIL standard operating procedure T3-035, as revised. The whole brains shall be removed (including olfactory bulbs), weighed and the size (length and width) recorded. Any abnormal coloration or lesions of the brain or spinal cord will be recorded. Nervous system tissue will be retained from all animals. 9.5.2.2 Neuropathology - Microscopic Examination: Brains from all animals perfused in situ on PND 21 and 72 will be embedded in paraffin to prevent artifactual changes in brain morphology due to storage in 10% neutral-buffered formalin. The following tissues (brains only for PND 21) of the first 10 rats/sex from the control and high dose groups that meet the criteria for measurement may be microscopically examined (with Sponsor's approval, at additional cost): -1789- Page 23 of 33 WIL-180017 April 20, 2006 Brain - olfactory bulbs, cerebral cortex, hippocampus, basal ganglia, thalamus, hypothalamus, tectum, cerebral peduncles, central gray matter, cerebellum, pons and medulla oblongata. Spinal cord - at cervical swellings C3-C7 and at lumbar swellings T13-L4. Trigeminal ganglion/nerves.a Lumbar dorsal root ganglion at T13-L4.* Lumbar dorsal root fibers at T13-L4.* Lumbar ventral root fibers at T13-L4.* Cervical dorsal root ganglion at C3-C7.* Cervical dorsal root fibers at C3-C7.* Cervical ventral root fibers at C3-C7.* Sciatic nerves.(2)+ Sural nerves.(2)+ Tibial nerves.(2)+ Peroneal nerves.(2)+ Optic nerves.a Eyes.a Skeletal muscle(gastrocnemius). a Both processed. * 4-6 tissues will be collected at necropsy. + One processed for microscopic examination. (2) Indicates that two sections (one cross and one longitudinal) of the tissue will be prepared. The tissues from the left leg will be collected and preserved for possible future evaluation. The central nervous system tissues listed above will be embedded in paraffin. The peripheral nervous system tissues will be embedded in plastic. 9.6 Thyroid Histopathology and Morphometry: One fetus/sex/litter from each toxicokinetic phase female euthanized on gestation day 20 and one pup/sex/litter from 10 randomly selected litters/group on postnatal day 4 and 21 will be prepared for microscopic examination (thyroids for all groups will be processed; however, the control and high dose groups will be initially evaluated). The thyroids will be prepared for a qualitative and semiquantitative histopathological examination by embedding in paraffin, sectioning and staining with hematoxylin and eosin. The histopathological examination will include a simple morphometric analysis. Specific measurements taken will be determined by the pathologist after consultation with the study director and sponsor. Additional staining -1790- Page 24 of 33 WIL-180017 April 20, 2006 procedures may be required, at additional cost, depending on the nature of the semiquantitative analysis. Based on the results of the qualitative examination and the professional judgment of the pathologist, selected sites and cellular components may be further evaluated by the use of additional methods (at additional cost). If no alterations are observed in samples from the high dose group, subsequent analysis will not be performed. If a lesion is observed in the high dose group, then animals from the next lower treatment group(s) and/or from the maternal animals will be examined until no evidence of alterations are found (at additional cost). 10 DURATION OF STUDY: The gestation, lactation and behavioral assessment phases of the study will require approximately four months. 11 STATISTICAL METHODS: All analyses will be two-tailed for minimum significance levels of 5% and 1%. All means will be presented with standard deviations. All statistical tests will be performed using appropriate computing devices or programs as referenced below. The litter, rather than the neonate, will be considered as the experimental unit. 11.1 Maternal In-Life Data: Continuous data variables [mean maternal body weights (gestation and lactation), body weight gains and food consumption at each interval] and mean gestation length will be analyzed by a parametric one-way analysis of variance (ANOVA) (Snedecor, 1980) to determine intergroup difference. If the results of the ANOVA are significant (p<0.05), Dunnett's test (Dunnett, 1964) will be applied to the data compare the treated and control groups. 11.2 Litter Data: The mean litter proportions (% per litter) of males at birth and pup viability during the postnatal period will be analyzed by the Kruskal-Wallis nonparametric ANOVA test (Kruskal, 1952) to determine intergroup difference. If the results of the ANOVA are significant (p<0.05), the Dunn's test (Dunn, 1964) will be applied to the data to compare the treated and control groups. Mean numbers of pups born, live litter size, litter weights, mean day of acquisition of developmental landmarks and mean body weight at acquisition will be analyzed by the parametric ANOVA test (Snedecor, 1980) and Dunnett's test (Dunnett, 1964) as described above. -1791- Page 25 of 33 WIL-180017 April 20, 2006 11.3 Organ Weight and Hormone Data: Organ weight, brain length and width and hormone data will be analyzed by the parametric one-way ANOVA (Snedecor, 1980) to determine intergroup differences. If significant differences are indicated by the ANOVA, Dunnett's test (Dunnett, 1964) will be used to compare the control and exposed groups. 11.4 Functional Observational Battery, Locomotor Activity, Auditory Startle and Learning and Memory Data: 11.4.1 Functional Observational Battery Data: Functional Observational Battery data will be subjected to a parametric one-way analysis of variance (ANOVA) (Snedecor, 1980) to determine intergroup differences. If significant differences are indicated by the ANOVA, Dunnett's test (Dunnett, 1964) will be used to compare the control and treated groups. Functional Observational Battery parameters which yield scalar and descriptive data will be analyzed by Fisher's Exact Test (Steel, 1980). 11.4.2 Locomotor Activity Data: Each analysis endpoint (total counts) will be analyzed, by sex and session, with a repeated measure analysis of variance (RANOVA). Factors in the model will include treatment group (TRT), time interval (TIME), and the interaction of time interval and treatment group (TRT*TIME). The SAS procedure PROC MIXED will be used for analysis with the random effect of animal included as the repeated measurement. The covariance structure across time will be selected by comparing Akaike's Information Criterion (AIC) for first-order autoregressive homogeneous [AR(1)] and compound symmetric (CS) structures. The monotonic dose response relationship will be evaluated using sequential linear trend tests based on ordinal spacing of dose levels. The linear dose by time interaction (LinTrt*Time) will be evaluated and, if significant at the 0.05 level, trend tests on treatment means will be performed at the 0.05 level for each time interval. If the linear dose by time interaction is not significant, the trend test will be conducted across the pooled time intervals of the entire session only. Nonmonotonic dose responses will be evaluated whenever no significant linear trends are detected but TRT and/or TRT*TIME interaction is significant at the 0.01 level. Within the framework of the RANOVA, pairwise comparisons will be made for each individual treated group -1792- Page 26 of 33 WIL-180017 April 20, 2006 with the control group through linear contrasts. If TRT*TIME is significant, the comparisons will be conducted for each time interval. If only the TRT effect is significant, the comparisons will be conducted across the pooled time intervals of the entire session. These nonmonotonic dose response comparisons will be conducted at the 0.01 significance level. All statistical analyses will be conducted using SAS version 8.2 (SAS Institute, Inc., 1999-2002) software. Ambulatory counts will be subjected to a parametric one-way ANOVA (Snedecor, 1980) to determine intergroup difference. If significant differences are indicated by the ANOVA, Dunnett's test (Dunnett, 1964) will be used to compare the control and treated groups. 11.4.3 Startle Response Data: Each analysis endpoint (VMAX and TMAX) will be analyzed, by sex and session, with a repeated measure analysis of variance (RANOVA). Factors in the model will include treatment group (TRT), trial block (TRIAL), and the interaction of trial block and treatment group (TRT*TRIAL). The SAS procedure PROC MIXED will be used for analysis with the random effect of animal included as the repeated measurement. The covariance structure across time will be selected by comparing Akaike's Information Criterion (AIC) for first-order autoregressive homogeneous [AR(1)] and compound symmetric (CS) structures. The monotonic dose response relationship will be evaluated using sequential linear trend tests based on ordinal spacing of dose levels. The linear dose by trial interaction (LinTrt*Trial) will be evaluated and, if significant at the 0.05 level, trend tests on treatment means will be performed at the 0.05 level for each block of trials. If the linear dose by trial interaction is not significant, the trend test will be conducted across the pooled trials of the entire session only. Nonmonotonic dose responses will be evaluated whenever no significant linear trends are detected but TRT and/or TRT*TRIAL interaction is significant at the 0.01 level. Within the framework of the RANOVA, pairwise comparisons will be made for each individual treated group with the control group through linear contrasts. If TRT*TRIAL is significant, the comparisons will be conducted for each block of trials. If only the TRT effect is significant, the comparisons will be conducted across the pooled trials of the entire session. These nonmonotonic dose response comparisons will be conducted at the 0.01 significance level. -1793- Page 27 of 33 WIL-180017 April 20, 2006 All statistical analyses will be conducted using SAS version 8.2 (SAS Institute, Inc., 1999-2002) software. Average response will be subjected to a parametric one-way ANOVA (Snedecor, 1980) to determine intergroup difference. If significant differences are indicated by the ANOVA, Dunnett's test (Dunnett, 1964) will be used to compare the control and treated groups. 11.4.4 Learning and Memory Data: The analyses will be conducted individually for each sex; therefore, there will only be one pup/litter in the analysis. The time to escape for an animal that does not escape the maze in the allotted time will be considered censored and set equal to the maximum allotted time for statistical analysis. The time to escape will be analyzed, by sex, with a repeated measure analysis of variance (RANOVA). Factors in the model will include treatment group (TRT), TRIAL, and the interaction of trial and treatment group (TRT*TRIAL). The SAS procedure PROC MIXED will be used for analysis with the random effect of animal included as the repeated measurement. The covariance structure across time will be selected by comparing Akaike's Information Criterion (AIC) for first-order autoregressive homogeneous [AR(1)] and compound symmetric (CS) structures. The monotonic dose response relationship will be evaluated using sequential linear trend tests based on ordinal spacing of dose levels. The linear dose by trial interaction (LinTRT*TRIAL) will be evaluated and, if significant at the 0.05 level, trend tests on treatment means will be performed at the 0.05 level for each trial. If the linear dose by trial interaction is not significant, the trend test will be conducted across the pooled trials of the entire phase only. Nonmonotonic dose responses will be evaluated whenever no significant linear trends are detected but TRT and/or TRT*TRIAL interaction is significant at the 0.01 level. Within the framework of the RANOVA, pairwise comparisons will be made for each individual treated group with the control group through linear contrasts. If TRT*TRIAL is significant, the comparisons will be conducted for each trial. If only the TRT effect is significant, the comparisons will be conducted across the pooled trials of the entire phase. These nonmonotonic dose response comparisons will be conducted at the 0.01 significance level. Alternative methods may be considered if the proportion of censored values suggests that the methodology described above may not be appropriate. In such cases, statistical methods that take into account -1794- Page 28 of 33 WIL-180017 April 20, 2006 censored values, such as the log-rank or generalized Wilcoxon tests, will be employed for the analysis of time to escape. Any alternative methodology will be detailed and justified in the final report. The number of errors will be analyzed with the repeated measures methodology (RANOVA) described for the time to escape analysis. All statistical analyses will be conducted using SAS version 8.2 (SAS Institute, Inc., 1999) software. 12 QUALITY ASSURANCE: The study will be audited by the WIL Quality Assurance Unit while in progress to assure compliance with the study protocol, protocol amendments, WIL standard operating procedures and the appropriate provisions of the Environmental Protection Agency (EPA) Good Laboratory Practice Standards (40 CFR Part 792). The raw data and draft report will be audited by the WIL Quality Assurance Unit prior to submission to the Sponsor Representative to assure that the final report accurately describes the conduct and findings of the study. Data requiring repeated measures statistical analysis will be analyzed by BioSTAT Consultants, Inc. following the current procedural guidelines of BioSTAT Consultants, Inc. BioSTAT Consultants, Inc. will provide a statistical analysis report, which will be included as an appendix to the final report. Quality Assurance auditing of the statistical report (for internal consistency and consistency with the study report) will be conducted under the direction of the Quality Assurance Unit of WIL Research Laboratories, LLC. Test article analyses in plasma and tissue samples, and dose formulation analyses will be conducted following the Standard Operating Procedures of the performing laboratory. Quality Assurance monitoring of these analyses for SOP and possible GLP compliance is the responsibility of the performing laboratory. Inspection reports will be supplied to the Study Director. Upon completion of the prescribed activities and submission of the results to the Sponsor and Study Director, the performing laboratory will be provide a signed Quality Assurance statement to the Sponsor (copy to the Study Director). The results will be included in the final report. This is a regulated study and will be placed on the WIL master list of regulated studies. 13 RECORDS TO BE MAINTAINED: All original raw data records, as defined by WIL SOPs and the applicable GLPs, will be stored as described in Section 14 in the Archives at WIL Research Laboratories, LLC. -1795- Page 29 of 33 WIL-180017 April 20, 2006 14 WORK PRODUCT: The Sponsor will have title to all documentation records, raw data, specimens or other work product generated during the performance of the study. All work product, including raw paper data, pertinent electronic storage media, specimens and appropriate supporting documentation for statistical analyses conducted and reported by BioSTAT Consultants, Inc. will be retained for a period of five years following issuance of the final report in the Archives at WIL Research Laboratories, LLC. Thereafter, WIL Research Laboratories will charge a monthly archiving fee for retention of all work product. All work product will be stored in compliance with regulatory requirements. Any work product, including documents, specimens, and samples, that are required by this protocol, its amendments, or other written instructions of the Sponsor, to be shipped by WIL Research Laboratories, LLC to another location will be appropriately packaged and labeled as defined by WIL's SOPs and delivered to a common carrier for shipment. WIL Research Laboratories, LLC will not be responsible for shipment following delivery to the common carrier. 15 REPORTS: The final report will contain a summary, test article data, methods and procedures, maternal and fetal data and an interpretation and discussion of the study results. The final report will be comprehensive and shall define level(s) inducing toxic effects as well as "no-effect" level(s) under the conditions of this investigation. The report will contain all information necessary to conform to current OPPTS specifications. WIL Research Laboratories will provide one copy of an Audited Draft Report, submitted in a timely manner upon completion of the study prior to issuance of the final report. One revision will be permitted as part of the cost of the study, from which the Sponsor's reasonable revisions and suggestions will be incorporated into the Final Report, as appropriate. Additional changes or revisions may be made, at extra cost. It is expected that the Sponsor will review the draft report and provide comments to WIL within a two-month time frame following submission. WIL will submit the Final Report within one month following receipt of comments. Two electronic copies of the Final Report in .pdf format will be provided; requests for additional copies of the Final Report may result in additional charges. -1796- Page 30 of 33 WIL-180017 April 20, 2006 The following information will also be included in the final report: A. Historical Control Data [Charles River Crl:CD(SD) Rats] B. Positive Control Data [Charles River Crl:CD(SD) Rats] C. Graphic depiction of mean data for: a. Maternal body weights during gestation b. Maternal body weights during lactation c. Litter body weights during lactation d. Male and female body weights of postweaning Subset A animals e. Ontogeny profile of preweaning locomotor activity, by sex f. Locomotor activity interval data at each age, by sex g. Auditory startle peak and latency to peak response data by trial block at each age, by sex h. Time to escape and numbers of errors in the learning and memory test by trial at each age, by sex i. Forelimb and hindlimb grip strength values across each age tested, by sex. 16 ANIMAL WELFARE ACT COMPLIANCE: This study will comply with all applicable sections of the Final Rules of the Animal Welfare Act regulations (9 CFR Parts 1, 2 and 3). The Sponsor should make particular note of the following: The Sponsor Representative's signature on this protocol documents for the Study Director the Sponsor's assurance that the study described in this protocol does not unnecessarily duplicate previous experiments. Whenever possible, procedures used in this study have been designed to avoid or minimize discomfort, distress or pain to animals. All methods are described in this study protocol or in written laboratory standard operating procedures. Animals that experience severe or chronic pain or distress that cannot be relieved will be painlessly euthanized as deemed appropriate by the veterinary staff and Study Director. The Sponsor will be advised by the Study Director of all circumstances which could lead to this action in as timely a manner as possible. Methods of euthanasia used during this study are in conformance with the above-referenced regulation. The sponsor/study director has considered alternatives to procedures that may cause more than momentary or slight pain or distress to the animals and has provided a written narrative description (AWA covered species) of the methods and sources used to determine that alternatives are not available. -1797- Page 31 of 33 WIL-180017 April 20, 2006 17 PROTOCOL MODIFICATION: Modification of the protocol may be accomplished during the course of this investigation. However, no changes will be made in the study design without the verbal or written permission of the Sponsor. In the event that the Sponsor verbally requests or approves a change in the protocol, such changes will be made by appropriate documentation in the form of a protocol amendment. All alterations of the protocol and reasons for the modification(s) will be signed by the Study Director and the Sponsor Representative. 18 REFERENCES: Adams, J.; Buelke-Sam, J.; Kimmel, C.A.; Nelson, C.J.; Reiter, L.W.; Sobotka, T.J.; Tilson, H.A.; Nelson, B.K. Collaborative behavioral teratology study: protocol design and testing procedure. Neurobehavioral Toxicology and Teratology 1985, 7, 579-586. Biel, W.C. Early age differences in maze performance in the albino rat. Journal of Genetic Psychology 1940, 56, 439-453. Dunn, O.J. Multiple comparisons using rank sums. Technometrics, 1964 6(3):241-252. Dunnett, C.W. New tables for multiple comparisons with a control. Biometrics 1964, 20, 482-491. Gad, S.C. A neuromuscular screen for use in industrial toxicology. Journal of Toxicology and Environmental Health 1982; 9 (5-6):691-704. Haggerty, G.C. Development of Tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies. Journal of American. College of Toxicology 1989, 8, (1):53-69. Irwin, S. "Comprehensive observational assessment: Ia. A systematic quantitative procedure for assessing the behavioral physiological state of the mouse," Psychopharmacologia 1968; 13:222-257. Korenbrot, C.C.; Huhtaniemi, I.T.; Weiner, R.W. Preputial separation as an external sign of pubertal development in the male rat. Biology of Reproduction 1977, 17, 298-303. Kruskal, W.H.; Wallis, W.A. Use of ranks in one-criterion variance analysis. Journal of the American Statistical Association 1952, 47, 583-621. Moser, V.C.; McDaniel, K.L.; Phillips, P.M. Rat strain and stock comparisons using a functional observational battery: Baseline values and effects of Amitraz. Toxicology and Applied Pharmacology 1991, 108, 267-283. -1798- Page 32 of 33 WIL-180017 April 20, 2006 Moser, V.C., McCormick, J.P. Creason, J.P. and MacPhail, R.C. Comparison of chlordimeform and carbaryl using a functional observational battery. Fund. Appl. Toxicol. 1988, 11: 189-206. O'Donoghue, J.L. Screening for neurotoxicity using a neurologically based examination and neuropathology. Journal of American College of Toxicology. 1989, 8, (1) 97-116. Salewski, E. Frbemethode zum makroskopischen Nachweis von Implantationsstellen am Uterus der Ratte. [Staining method for a macroscopic test for implantation sites in the uterus of the rat]. Naunyn - Schmiedebergs Archiv fr Experimentelle Pathologie und Pharmakologie 1964, 247, 367. Snedecor, G.W.; Cochran, W.G. One Way Classifications; Analysis of Variance. In Statistical Methods, 7th ed.; The Iowa State University Press: Ames, IA, 1980; pp 215-237. Steel, R.G.D.; Torrie, J.H. Principles and Procedures of Statistics, A Biometrical Approach, 2nd ed.; McGraw-Hill Book Company: New York, NY, 1980; pp 504-506. Stuckhardt, J.L.; Poppe, S.M. Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. Teratogenesis, Carcinogenesis and Mutagenesis 1984, 4, 181-188. -1799- Page 33 of 33 WIL- 180017 April 20,2006 SAS@Proprietary Software, Version 8.2; SAS Institute, Inc., Cary, NC., 1999-2001. 19 PROTOCOL APPROVAL: Approval for this protocol was received via Date 3M Corporation John L. Butenhoff, PhDi CIH, DABT Date Sponsor Representative WIL Research Laboratories, LLC Donald G. Stump, PhD, DABT Study Director \n/T\ Mark D . \ N e w D A B T Director, Developmental and Reproductive Toxicology Date 4 b/~a-% Date ............i.......................x........i;...:..........,.....:.....:.....:......................,....,2..:..;..:;.;.................. .I....................,...........:..!....!....................*..,.....I.......... : @ ;:!b ~ WIL-180017 3M Corporation -1800- MTDID 208 06-128 APPENDIX 53 Certificate Of Analysis (Sponsor-Provided Data) -1801- C m t w Analytical Laboratories, Inc. 3048 Research Drive State College, PA 16801 www.centrelab.com (814) 231-8032 Fax: (814) 231-1253 or (814) 231-1580 INTERIM CERTIFICATE OF ANALYSIS Revhion 3 Centre Analytical Laboratories COA Reference #: 023-018A 3M Product: PFOS, Lot 217 Reference #: SD-018 Test Name Purity' Appearance Identification Specifications White CrystallinePowder Kesuit 86.9% Conforms 1 4. Potassium2 2. 0.001 wt./wt.% 3. 1.439wt./wt.% 4. 6.849wt./wt.% 1. c0.015 wt./wt.% 2. 0.59 wt./wt.% 3. <0.040 wt./wt.% 4. <0.009 wt./wt.% 5 . c0.006wt./wt.% 6. <0.007wt./wt.%o 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulhr 5. Fluorine COA023-018A 1. Theoretical Value = 17.8% 2. Theoretical Value = 0% 3. Theoretical Value = 0% 4. Theoretical Value = 5.95% 5. Theoretical Value = 60% 1. 12.48 wt./wt.% 2. 0.244 wt./wt.% 3. 1.74 wt./wt.% 4. 8.84 wt./wt.% 5. 54.1 wt./wt.% Page 1 of 3 -1802- Centre Analytical Laboratories, Inc. 3048 Research Drive State College, PA 16801 www.centrelab.com (814) 231-8032 Fax:(814) 231-1253 or (814) 231-1580 INTERIM CERTIFICATE OF ANALYSIS Revision 3 Centre Analytical Laboratories COA Reference #: 023-018A Date of Last Analysis: 08/3 1/00 Expiration Date: 0813 1/06 Storage Conditions: Frozen 5-10C Re-assessment Date: 08/3 1/06 `Purity = 100%- (sum of metal impurities, 1.45%+Lc/Msimpurities, 8.41%+horganic Fluoride, 0.59%+NMRimpurities, 1.905%+0rganicacid impurities, 0.38%+POAA, 0.33%) Total impurity from all tests = 13.07% Purity = 100% - 13.07% = 86.9% 2Potassium is expected in this salt form and is therefore not considered an impurity. 3Purityby DSC is generally not applicableto materials of low purity. No endotherm was observed for this sample. 4Sulfk in the sample appears to be converted to SO4 and hence detected using the inorganic anion method conditions. The anion result agrees well with the sulfixr determination in the elemental analysis, lending confidence to this interpretation. Based on the results, the SO4 is not considered an impurity. `TFA HFBA NFPA PFPA Trifluoroacetic acid Heptafluorobutyric acid Nonafluoropentanoic acid Pentafluoropropanoic acid 6Theoreticalvalue calculationsbased on the empirical formula, C8F17SOjK+(MW=538) This work was conducted under EPA Good Laboratory Practice Standards (40 CFR 160). COA023-0 18A Page 2 of 3 -1803- Cmtre Analytical laboratorks. Inc. 3048 Research Drive State College, PA 16801 www.centrelab.com (814) 231-8032 Fax: (814) 231-1253 or (814) 231-1580 INTERIM CERIZFICATE OF ANALYSIS Revision 3 Centre Analytical Laboratories COA Reference #: 023-018A LCMS Purity Profile: Impurity c4 cs C6 C7 Total wt./wt. Yo 1.22 1.33 4.72 1.14 8.41 Note: The C4 and C6 values were calculated using the C4 and C6 standard calibration curves, respectively. The C5 value was calculated using the average result fkom the C4 and C6 standard curves. Likewise, the C7 value was calculated using the average result fkom the C6 and C8 standard curves. Prepared By: Scientist, Centre Analytical Laboratories I&, Date Reviewed By: /&hh( 3 h . nFlaherty Da- _t-e- 'Laboratory Manager, Centre Analytical Laboratories COA023-018A Page 3 of 3 WIL-180017 3M Corporation -1804- MTDID 208 06-128 APPENDIX 54 Analyses Of Dosing Formulations And Toxicokinetics Report (3M Corporation) -1805- -1806- -1807- -1808- -1809- -1810- -1811- -1812- -1813- -1814- -1815- -1816- WIL-180017 3M Corporation -1817- MTDID 208 06-128 APPENDIX 55 Animal Room Environmental Conditions PROJECT NO.:WIL- 180017 SPONSOR: 3M CORPORATION ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY PAGE 1 -1818- STUDY SPECIFICATIONS: 180017 ROOM SPECIFICATIONS: SPECIES: B ROOM 47 RAT DATE 18-Apr-06 19-Apr-06 20-Apr-06 21-Apr-06 22-Apr-06 23-Apr-06 24-Apr-06 25-Apr-06 26-Apr-06 27-Apr-06 28-Apr-06 29-Apr-06 30-Apr-06 01-May-06 02-May-06 03-May-06 04-May-06 05-May-06 06-May-06 07-May-06 08-May-06 09-May-06 10-May-06 TEMPERATURE MEAN (F) MEAN (C) 70.5 70.5 70.5 70.4 70.5 70.6 70.4 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.6 70.5 70.5 70.5 21.4 21.4 21.4 21.3 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGE NOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES DATE IN: DATE OUT: LOW TEMPERATURE F: LOW TEMPERATURE C: 04/18/06 08/08/06 TIME IN: TIME OUT: 66.0 18.9 HIGH TEMPERATURE F: 76.0 HIGH TEMPERATURE C: 24.4 HUMIDITY MEAN (%RH) 40.9 41.1 41.6 44.9 43.6 43.3 42.2 41.0 41.3 42.5 42.9 43.0 43.4 44.8 44.9 47.0 46.6 42.6 42.7 39.8 41.7 42.3 46.3 11:00 8:00 LOW HUMIDITY: HIGH HUMIDITY: 30.0 70.0 REPORT 4 VERSION 1.09 1/26/2007 09:25 PROJECT NO.:WIL- 180017 SPONSOR: 3M CORPORATION ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY PAGE 2 -1819- STUDY SPECIFICATIONS: 180017 ROOM SPECIFICATIONS: SPECIES: B ROOM 47 RAT DATE 11-May-06 12-May-06 13-May-06 14-May-06 15-May-06 16-May-06 17-May-06 18-May-06 19-May-06 20-May-06 21-May-06 22-May-06 23-May-06 24-May-06 25-May-06 26-May-06 27-May-06 28-May-06 29-May-06 30-May-06 31-May-06 01-Jun-06 02-Jun-06 TEMPERATURE MEAN (F) MEAN (C) 70.4 70.5 70.4 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.5 70.6 70.7 70.5 70.4 70.5 70.5 70.8 70.5 21.3 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.5 21.5 21.4 21.4 21.4 21.4 21.6 21.4 NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGE NOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES DATE IN: DATE OUT: LOW TEMPERATURE F: LOW TEMPERATURE C: 04/18/06 08/08/06 TIME IN: TIME OUT: 66.0 18.9 HIGH TEMPERATURE F: 76.0 HIGH TEMPERATURE C: 24.4 HUMIDITY MEAN (%RH) 46.5 41.7 42.6 46.2 42.8 46.1 47.1 43.8 42.5 41.2 41.8 41.0 41.5 40.9 46.9 46.8 47.1 47.1 49.0 48.0 48.7 48.3 47.4 11:00 8:00 LOW HUMIDITY: HIGH HUMIDITY: 30.0 70.0 REPORT 4 VERSION 1.09 1/26/2007 09:25 PROJECT NO.:WIL- 180017 SPONSOR: 3M CORPORATION ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY PAGE 3 -1820- STUDY SPECIFICATIONS: 180017 ROOM SPECIFICATIONS: SPECIES: B ROOM 47 RAT DATE 03-Jun-06 04-Jun-06 05-Jun-06 06-Jun-06 07-Jun-06 08-Jun-06 09-Jun-06 10-Jun-06 11-Jun-06 12-Jun-06 13-Jun-06 14-Jun-06 15-Jun-06 16-Jun-06 17-Jun-06 18-Jun-06 19-Jun-06 20-Jun-06 21-Jun-06 22-Jun-06 23-Jun-06 24-Jun-06 25-Jun-06 TEMPERATURE MEAN (F) MEAN (C) 70.3 70.6 70.4 70.6 70.5 70.5 70.5 70.5 70.4 70.4 70.5 70.5 70.5 70.5 70.6 70.5 70.5 70.4 70.5 70.8 70.6 70.5 70.5 21.3 21.5 21.3 21.4 21.4 21.4 21.4 21.4 21.4 21.3 21.4 21.4 21.4 21.4 21.5 21.4 21.4 21.3 21.4 21.6 21.4 21.4 21.4 NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGE NOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES DATE IN: DATE OUT: LOW TEMPERATURE F: LOW TEMPERATURE C: 04/18/06 08/08/06 TIME IN: TIME OUT: 66.0 18.9 HIGH TEMPERATURE F: 76.0 HIGH TEMPERATURE C: 24.4 HUMIDITY MEAN (%RH) 51.0 48.5 44.2 44.9 47.3 46.2 44.1 40.5 40.8 42.4 45.4 44.4 43.7 44.4 44.7 45.5 45.4 45.1 46.2 49.5 44.8 43.7 43.4 11:00 8:00 LOW HUMIDITY: HIGH HUMIDITY: 30.0 70.0 REPORT 4 VERSION 1.09 1/26/2007 09:25 PROJECT NO.:WIL- 180017 SPONSOR: 3M CORPORATION ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY PAGE 4 -1821- STUDY SPECIFICATIONS: 180017 ROOM SPECIFICATIONS: SPECIES: B ROOM 47 RAT DATE 26-Jun-06 27-Jun-06 28-Jun-06 29-Jun-06 30-Jun-06 01-Jul-06 02-Jul-06 03-Jul-06 04-Jul-06 05-Jul-06 06-Jul-06 07-Jul-06 08-Jul-06 09-Jul-06 10-Jul-06 11-Jul-06 12-Jul-06 13-Jul-06 14-Jul-06 15-Jul-06 16-Jul-06 17-Jul-06 18-Jul-06 TEMPERATURE MEAN (F) MEAN (C) 70.5 70.5 70.7 70.5 70.4 70.5 70.5 70.4 70.5 70.5 70.5 70.5 70.5 70.6 70.6 70.5 70.5 70.5 70.5 70.5 70.5 70.4 70.5 21.4 21.4 21.5 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.3 21.4 NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGE NOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES DATE IN: DATE OUT: LOW TEMPERATURE F: LOW TEMPERATURE C: 04/18/06 08/08/06 TIME IN: TIME OUT: 66.0 18.9 HIGH TEMPERATURE F: 76.0 HIGH TEMPERATURE C: 24.4 HUMIDITY MEAN (%RH) 44.0 43.8 43.0 43.8 43.8 44.3 45.8 46.9 46.8 43.3 45.3 43.7 43.4 43.9 45.8 46.2 47.8 45.8 45.4 46.1 48.1 46.2 45.0 11:00 8:00 LOW HUMIDITY: HIGH HUMIDITY: 30.0 70.0 REPORT 4 VERSION 1.09 1/26/2007 09:25 PROJECT NO.:WIL- 180017 SPONSOR: 3M CORPORATION ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY PAGE 5 STUDY SPECIFICATIONS: 180017 ROOM SPECIFICATIONS: SPECIES: DATE 19-Jul-06 20-Jul-06 21-Jul-06 22-Jul-06 23-Jul-06 24-Jul-06 25-Jul-06 26-Jul-06 27-Jul-06 28-Jul-06 29-Jul-06 30-Jul-06 31-Jul-06 01-Aug-06 02-Aug-06 03-Aug-06 04-Aug-06 05-Aug-06 06-Aug-06 07-Aug-06 08-Aug-06 B ROOM 47 RAT TEMPERATURE MEAN (F) MEAN (C) 70.5 70.5 70.5 70.6 70.6 70.6 70.5 70.5 70.4 70.5 70.4 70.5 70.5 70.6 70.5 70.4 70.6 70.5 70.5 70.3 70.8 21.4 21.4 21.4 21.4 21.5 21.4 21.4 21.4 21.3 21.4 21.3 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.3 21.6 DATE IN: DATE OUT: LOW TEMPERATURE F: LOW TEMPERATURE C: 04/18/06 08/08/06 TIME IN: TIME OUT: 66.0 18.9 HIGH TEMPERATURE F: 76.0 HIGH TEMPERATURE C: 24.4 HUMIDITY MEAN (%RH) 44.3 50.2 51.6 51.9 51.7 51.9 52.6 52.0 52.3 52.7 55.1 54.6 55.9 56.4 54.0 55.7 52.9 52.1 51.6 51.2 51.6 11:00 8:00 LOW HUMIDITY: HIGH HUMIDITY: 30.0 70.0 -1822- NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGE NOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES REPORT 4 VERSION 1.09 1/26/2007 09:25 PROJECT NO.:WIL- 180017 SPONSOR: 3M CORPORATION ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - DAILY SUMMARY REPORT BY STUDY PAGE 6 STUDY SPECIFICATIONS: 180017 ROOM SPECIFICATIONS: SPECIES: DATE B ROOM 47 RAT TEMPERATURE MEAN (F) MEAN (C) DATE IN: DATE OUT: LOW TEMPERATURE F: LOW TEMPERATURE C: 04/18/06 08/08/06 TIME IN: TIME OUT: 66.0 18.9 HIGH TEMPERATURE F: 76.0 HIGH TEMPERATURE C: 24.4 HUMIDITY MEAN (%RH) 11:00 8:00 LOW HUMIDITY: HIGH HUMIDITY: 30.0 70.0 GRAND STATS TEMPERATURE F TEMPERATURE C HUMIDITY (%RH) N DAYS MEAN 70.5 21.4 46.0 113 MIN 70.3 21.3 39.8 MAX 70.8 21.6 56.4 -1823- NOTE: + = VALUE WAS GREATER THAN HIGH RANGE - = VALUE WAS LESS THAN LOW RANGE NOTE: MEANS REPRESENT THE MEAN OF THE DAILY VALUES REPORT 4 VERSION 1.09 1/26/2007 09:25 PROJECT NO.:WIL- 180017 SPONSOR: 3M CORPORATION ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT ROOM SPECIFICATIONS: SPECIES: LOW TEMPERATURE: HIGH TEMPERATURE: LOW HUMIDITY: HIGH HUMIDITY: B ROOM 47 RAT 66.0 76.0 30.0 70.0 DATE IN: TIME IN: DATE OUT: TIME OUT: 04/18/06 11:00 08/08/06 8:00 TEMPERATURE HUMIDITY 9:23 26-Jan-07 ROOM B ROOM 47 SUMMARY MEAN MIN MAX SD N SAMPLES FIRST DAY LAST DAY N DAYS 70.5 68.3 76.9 0.33 2685 04/18/06 08/08/06 113 46.0 16.3 73.3 4.86 2685 PAGE 1 -1824- NOTE: TEMPERATURE UNITS = DEGREES FAHRENHEIT HUMIDITY UNITS = % RELATIVE HUMIDITY NOTE: MEANS REPRESENT THE MEAN OF ALL VALUES REPORT 5 VERSION 1.10 1/26/2007 09:23 PROJECT NO.:WIL- 180017 SPONSOR: 3M CORPORATION STUDY 180017 SUMMARY ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT 9:23 26-Jan-07 MEAN MIN MAX SD N SAMPLES FIRST DAY LAST DAY N DAYS 70.5 68.3 76.9 0.33 2685 04/18/06 08/08/06 113 46.0 16.3 73.3 4.86 2685 PAGE 2 -1825- NOTE: TEMPERATURE UNITS = DEGREES FAHRENHEIT HUMIDITY UNITS = % RELATIVE HUMIDITY NOTE: MEANS REPRESENT THE MEAN OF ALL VALUES REPORT 5 VERSION 1.10 1/26/2007 09:23 WIL-180017 3M Corporation -1826- MTDID 208 06-128 APPENDIX 56 Individual Toxicokinetic Animal Data TABLE 1 (DAILY EXAMINATIONS) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 05-25-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25679 F 0 MG/KG/DAY DISPOSITION 05-22-06 6:45 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25679 F 0 MG/KG/DAY EYES/EARS/NOSE 05-11-06 6:15 1 DRIED RED MATERIAL AROUND NOSE 25659 F 0 MG/KG/DAY DISPOSITION 05-22-06 6:45 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25634 F 0 MG/KG/DAY DISPOSITION 05-23-06 6:36 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25634 F 0 MG/KG/DAY BODY/INTEGUMENT 05-04-06 7:20 1 HAIR LOSS RIGHT FORELIMB 05-04-06 7:20 1 HAIR LOSS LEFT FORELIMB 05-05-06 7:22 1 HAIR LOSS RIGHT FORELIMB 05-05-06 7:22 1 HAIR LOSS LEFT FORELIMB 05-06-06 8:23 1 HAIR LOSS RIGHT FORELIMB 05-06-06 8:23 1 HAIR LOSS LEFT FORELIMB 05-07-06 6:51 1 HAIR LOSS RIGHT FORELIMB 05-07-06 6:51 1 HAIR LOSS LEFT FORELIMB 05-08-06 6:15 1 HAIR LOSS RIGHT FORELIMB 05-08-06 6:15 1 HAIR LOSS LEFT FORELIMB 05-09-06 7:37 1 HAIR LOSS LEFT FORELIMB 05-09-06 7:37 1 HAIR LOSS RIGHT FORELIMB 05-10-06 6:09 1 HAIR LOSS LEFT FORELIMB -1827- 05-10-06 6:09 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:16 1 HAIR LOSS LEFT FORELIMB 05-11-06 6:16 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:13 1 HAIR LOSS LEFT FORELIMB 05-12-06 6:13 1 HAIR LOSS RIGHT FORELIMB 05-13-06 8:47 1 HAIR LOSS RIGHT FORELIMB 05-13-06 8:47 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:50 1 HAIR LOSS RIGHT FORELIMB 05-14-06 9:50 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:14 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:14 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:02 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT TABLE 1 (DAILY EXAMINATIONS) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 05-25-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25634 F 0 MG/KG/DAY BODY/INTEGUMENT 05-16-06 8:02 1 HAIR LOSS RIGHT FORELIMB 05-17-06 6:36 1 HAIR LOSS LEFT FORELIMB 05-17-06 6:36 1 HAIR LOSS RIGHT FORELIMB 05-18-06 6:16 1 HAIR LOSS LEFT FORELIMB 05-18-06 6:16 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:16 1 HAIR LOSS LEFT FORELIMB 05-19-06 6:16 2 HAIR LOSS RIGHT FORELIMB 05-20-06 6:34 1 HAIR LOSS LEFT FORELIMB 05-20-06 6:34 1 HAIR LOSS RIGHT FORELIMB 05-21-06 6:30 1 HAIR LOSS LEFT FORELIMB 05-21-06 6:30 1 HAIR LOSS RIGHT FORELIMB 05-22-06 6:12 1 HAIR LOSS LEFT FORELIMB 05-22-06 6:12 1 HAIR LOSS RIGHT FORELIMB 05-23-06 6:07 1 HAIR LOSS LEFT FORELIMB 05-23-06 6:07 1 HAIR LOSS RIGHT FORELIMB 25620 F 0 MG/KG/DAY DISPOSITION 05-23-06 6:37 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25706 F 0 MG/KG/DAY DISPOSITION 05-23-06 6:37 P SCHEDULED EUTHANASIA; GESTATION DAY 20 -1828- 25612 F 0 MG/KG/DAY DISPOSITION 05-24-06 6:29 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25629 F 0 MG/KG/DAY DISPOSITION 05-24-06 6:30 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25629 F 0 MG/KG/DAY BODY/INTEGUMENT 05-07-06 6:52 1 HAIR LOSS RIGHT FORELIMB 05-08-06 6:16 1 HAIR LOSS RIGHT FORELIMB 05-09-06 7:39 1 HAIR LOSS RIGHT FORELIMB 05-10-06 6:11 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:17 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:15 1 HAIR LOSS LEFT FORELIMB 05-12-06 6:15 1 HAIR LOSS RIGHT FORELIMB 05-13-06 8:49 1 HAIR LOSS RIGHT FORELIMB 05-13-06 8:49 1 HAIR LOSS LEFT FORELIMB 05-14-06 9:51 2 HAIR LOSS RIGHT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT TABLE 1 (DAILY EXAMINATIONS) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 05-25-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25629 F 0 MG/KG/DAY BODY/INTEGUMENT 05-14-06 9:51 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:17 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:17 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:03 1 HAIR LOSS LEFT FORELIMB 05-16-06 8:03 1 HAIR LOSS RIGHT FORELIMB 05-17-06 6:37 1 HAIR LOSS LEFT FORELIMB 05-17-06 6:37 1 HAIR LOSS RIGHT FORELIMB 05-18-06 6:18 1 HAIR LOSS LEFT FORELIMB 05-18-06 6:18 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:18 1 HAIR LOSS LEFT FORELIMB 05-19-06 6:18 1 HAIR LOSS RIGHT FORELIMB 05-20-06 6:35 1 HAIR LOSS LEFT FORELIMB 05-20-06 6:35 1 HAIR LOSS RIGHT FORELIMB 05-21-06 6:32 1 HAIR LOSS LEFT FORELIMB 05-21-06 6:32 1 HAIR LOSS RIGHT FORELIMB 05-22-06 6:14 1 HAIR LOSS LEFT FORELIMB 05-22-06 6:14 1 HAIR LOSS RIGHT FORELIMB -1829- 05-23-06 6:10 1 HAIR LOSS LEFT FORELIMB 05-23-06 6:10 1 HAIR LOSS RIGHT FORELIMB 05-24-06 6:15 1 HAIR LOSS LEFT FORELIMB 05-24-06 6:15 1 HAIR LOSS RIGHT FORELIMB 25718 F 0 MG/KG/DAY DISPOSITION 05-24-06 6:31 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25718 F 0 MG/KG/DAY EYES/EARS/NOSE 05-08-06 6:17 1 DRIED RED MATERIAL AROUND NOSE 25760 F 0 MG/KG/DAY DISPOSITION 05-25-06 6:26 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25760 F 0 MG/KG/DAY BODY/INTEGUMENT 05-21-06 6:33 1 HAIR LOSS LEFT FORELIMB 05-22-06 6:16 1 HAIR LOSS LEFT FORELIMB 25683 F 0 MG/KG/DAY DISPOSITION 05-25-06 6:26 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25627 F 0.1 MG/KG/DAY DISPOSITION 05-22-06 6:46 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25669 F 0.1 MG/KG/DAY DISPOSITION 05-22-06 6:47 P SCHEDULED EUTHANASIA; GESTATION DAY 20 ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT TABLE 1 (DAILY EXAMINATIONS) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 05-25-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25613 F 0.1 MG/KG/DAY DISPOSITION 05-23-06 6:38 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25607 F 0.1 MG/KG/DAY DISPOSITION 05-23-06 6:39 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25640 F 0.1 MG/KG/DAY DISPOSITION 05-23-06 6:39 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25711 F 0.1 MG/KG/DAY DISPOSITION 05-24-06 6:31 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25682 F 0.1 MG/KG/DAY DISPOSITION 05-24-06 6:32 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25682 F 0.1 MG/KG/DAY EYES/EARS/NOSE 05-06-06 8:29 1 DRIED RED MATERIAL AROUND NOSE 25651 F 0.1 MG/KG/DAY DISPOSITION 05-24-06 6:33 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25651 F 0.1 MG/KG/DAY EYES/EARS/NOSE 05-06-06 8:29 1 DRIED RED MATERIAL AROUND NOSE 05-07-06 6:55 1 DRIED RED MATERIAL AROUND NOSE 05-08-06 6:22 1 DRIED RED MATERIAL AROUND NOSE 25768 F 0.1 MG/KG/DAY DISPOSITION 05-25-06 6:27 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25643 F 0.1 MG/KG/DAY DISPOSITION 05-25-06 6:27 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25601 F 0.3 MG/KG/DAY DISPOSITION 05-22-06 6:47 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25644 F 0.3 MG/KG/DAY DISPOSITION 05-22-06 6:48 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25680 F 0.3 MG/KG/DAY DISPOSITION 05-23-06 6:40 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25675 F 0.3 MG/KG/DAY DISPOSITION 05-23-06 6:40 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25598 F 0.3 MG/KG/DAY DISPOSITION 05-23-06 6:41 P SCHEDULED EUTHANASIA; GESTATION DAY 20 -1830- 25598 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-06-06 8:31 1 HAIR LOSS RIGHT FORELIMB 05-07-06 6:57 1 HAIR LOSS RIGHT FORELIMB 05-08-06 6:25 1 HAIR LOSS RIGHT FORELIMB 05-09-06 7:45 1 HAIR LOSS RIGHT FORELIMB 05-10-06 6:19 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:24 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:23 1 HAIR LOSS RIGHT FORELIMB 05-14-06 10:00 1 HAIR LOSS RIGHT FORELIMB 05-15-06 6:24 1 HAIR LOSS RIGHT FORELIMB 05-16-06 8:10 1 HAIR LOSS RIGHT FORELIMB 05-17-06 6:44 1 HAIR LOSS RIGHT FORELIMB 05-18-06 6:25 1 HAIR LOSS LEFT FORELIMB ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT TABLE 1 (DAILY EXAMINATIONS) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 5 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 05-25-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25598 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-18-06 6:25 1 HAIR LOSS RIGHT FORELIMB 05-19-06 6:24 1 HAIR LOSS RIGHT FORELIMB 05-20-06 6:41 1 HAIR LOSS LEFT FORELIMB 05-20-06 6:41 1 HAIR LOSS RIGHT FORELIMB 05-21-06 6:39 1 HAIR LOSS RIGHT FORELIMB 05-22-06 6:23 1 HAIR LOSS LEFT FORELIMB 05-22-06 6:23 1 HAIR LOSS RIGHT FORELIMB 05-23-06 6:16 1 HAIR LOSS RIGHT FORELIMB 25667 F 0.3 MG/KG/DAY DISPOSITION 05-23-06 6:42 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25667 F 0.3 MG/KG/DAY EYES/EARS/NOSE 05-07-06 6:58 1 DRIED RED MATERIAL AROUND NOSE 25641 F 0.3 MG/KG/DAY DISPOSITION 05-24-06 6:33 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25641 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-14-06 10:00 1 HAIR LOSS RIGHT FORELIMB 05-14-06 10:00 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:25 1 HAIR LOSS LEFT FORELIMB 05-15-06 6:25 1 HAIR LOSS RIGHT FORELIMB 05-21-06 6:40 1 HAIR LOSS LEFT FORELIMB 05-23-06 6:16 1 HAIR LOSS LEFT FORELIMB -1831- 05-23-06 6:16 1 HAIR LOSS RIGHT FORELIMB 05-24-06 6:19 1 HAIR LOSS LEFT FORELIMB 05-24-06 6:19 1 HAIR LOSS RIGHT FORELIMB 25662 F 0.3 MG/KG/DAY DISPOSITION 05-24-06 6:34 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25662 F 0.3 MG/KG/DAY BODY/INTEGUMENT 05-17-06 6:45 1 HAIR LOSS RIGHT FORELIMB 25662 F 0.3 MG/KG/DAY EYES/EARS/NOSE 05-16-06 8:11 1 DRIED RED MATERIAL AROUND NOSE 25726 F 0.3 MG/KG/DAY DISPOSITION 05-25-06 6:27 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25596 F 0.3 MG/KG/DAY DISPOSITION 05-25-06 6:27 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25649 F 1.0 MG/KG/DAY DISPOSITION 05-22-06 6:49 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25608 F 1.0 MG/KG/DAY DISPOSITION 05-22-06 6:49 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25656 F 1.0 MG/KG/DAY DISPOSITION 05-23-06 6:42 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25688 F 1.0 MG/KG/DAY DISPOSITION 05-23-06 6:43 P SCHEDULED EUTHANASIA; GESTATION DAY 20 ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT TABLE 1 (DAILY EXAMINATIONS) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 6 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY] SPONSOR NO.:06-128 TABLE RANGE: 05-02-06 TO 05-25-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- 25688 F 1.0 MG/KG/DAY BODY/INTEGUMENT 05-08-06 6:29 1 HAIR LOSS LEFT FORELIMB 05-09-06 7:49 1 HAIR LOSS LEFT FORELIMB 05-09-06 7:49 1 HAIR LOSS RIGHT FORELIMB 05-10-06 6:22 P SCABBING LEFT FORELIMB 05-10-06 6:22 1 HAIR LOSS LEFT FORELIMB 05-10-06 6:22 1 HAIR LOSS RIGHT FORELIMB 05-11-06 6:28 1 HAIR LOSS LEFT FORELIMB 05-11-06 6:28 1 HAIR LOSS RIGHT FORELIMB 05-12-06 6:27 1 HAIR LOSS LEFT FORELIMB 05-12-06 6:27 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:00 1 HAIR LOSS RIGHT FORELIMB 05-13-06 9:00 1 HAIR LOSS LEFT FORELIMB 05-14-06 10:04 1 HAIR LOSS RIGHT FORELIMB 05-14-06 10:04 1 HAIR LOSS LEFT FORELIMB 05-22-06 6:28 1 HAIR LOSS LEFT FORELIMB 05-22-06 6:28 1 HAIR LOSS RIGHT FORELIMB 05-23-06 6:18 1 HAIR LOSS LEFT FORELIMB -1832- 05-23-06 6:18 1 HAIR LOSS RIGHT FORELIMB 25625 F 1.0 MG/KG/DAY DISPOSITION 05-23-06 6:44 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25699 F 1.0 MG/KG/DAY DISPOSITION 05-23-06 6:44 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25750 F 1.0 MG/KG/DAY DISPOSITION 05-24-06 6:35 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25734 F 1.0 MG/KG/DAY DISPOSITION 05-24-06 6:36 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25745 F 1.0 MG/KG/DAY DISPOSITION 05-25-06 6:27 P SCHEDULED EUTHANASIA; GESTATION DAY 20 25693 F 1.0 MG/KG/DAY DISPOSITION 05-25-06 6:27 P SCHEDULED EUTHANASIA; GESTATION DAY 20 ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT PCRDv4.11 10/05/2006 TABLE 2 (1 HOUR POST-DOSING) PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL CLINICAL OBSERVATIONS SPONSOR NO.:06-128 TABLE RANGE: 05-06-06 TO 05-07-06 ----------------------------------------------------------------------------------------------------------------------------------- ANIMAL SEX GROUP CATEGORY DATE TIME GRADE OBSERVATIONS ----------------------------------------------------------------------------------------------------------------------------------- NO SIGNIFICANT CLINICAL OBSERVATIONS 1 HOUR POST-DOSING ----------------------------------------------------------------------------------------------------------------------------------- GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT PCRDv4.11 01/23/2007 R:01/23/2007 -1833- TABLE 3 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 3 6 9 12 15 18 20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25679 G 239. 263. 280. 291. 306. 338. 366. 398. 25659 G 278. 284. 308. 321. 331. 360. 416. 447. 25634 G 275. 292. 311. 327. 343. 371. 401. 429. 25620 G 263. 281. 289. 304. 329. 347. 380. 414. 25706 G 256. 271. 279. 297. 310. 331. 376. 407. 25612 G 255. 275. 287. 293. 311. 327. 359. 395. 25629 G 256. 283. 302. 307. 327. 353. 393. 428. 25718 G 269. 288. 309. 318. 338. 361. 399. 431. 25760 G 274. 291. 304. 311. 328. 339. 362. 372. 25683 G 270. 284. 297. 309. 338. 355. 407. 439. MEAN S.D. N 264. 12.1 10 281. 9.1 10 297. 12.1 10 308. 12.0 10 326. 12.9 10 348. 14.3 10 386. 20.1 10 416. 23.1 10 -1834- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN TABLE 3 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 3 6 9 12 15 18 20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25627 G 259. 267. 283. 293. 304. 331. 379. 412. 25669 G 274. 290. 308. 314. 333. 359. 393. 425. 25613 G 268. 284. 300. 312. 337. 354. 391. 417. 25607 G 264. 280. 298. 320. 338. 366. 395. 438. 25640 G 258. 278. 296. 315. 335. 357. 396. 429. 25711 G 232. 251. 264. 282. 300. 322. 368. 404. 25682 G 256. 270. 283. 286. 304. 328. 372. 406. 25651 G 272. 295. 314. 318. 338. 372. 419. 454. 25768 G 278. 291. 306. 313. 337. 360. 411. 443. 25643 G 269. 290. 303. 316. 342. 363. 414. 448. MEAN S.D. N 263. 13.1 10 280. 13.6 10 296. 14.9 10 307. 14.2 10 327. 16.8 10 351. 17.5 10 394. 17.4 10 428. 17.8 10 -1835- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN TABLE 3 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 3 6 9 12 15 18 20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25601 G 244. 277. 286. 295. 306. 334. 372. 410. 25644 NG 262. 259. 257. 268. 272. 269. 270. 275. 25680 G 273. 286. 291. 303. 330. 351. 396. 435. 25675 G 262. 268. 281. 298. 322. 339. 388. 419. 25598 G 259. 267. 284. 299. 319. 337. 385. 420. 25667 G 251. 262. 273. 293. 310. 326. 373. 403. 25641 G 268. 286. 291. 298. 313. 340. 372. 403. 25662 G 269. 284. 295. 300. 320. 340. 385. 428. 25726 NG 283. 290. 289. 293. 305. 308. 313. 319. 25596 G 262. 281. 288. 300. 316. 331. 369. 399. MEAN S.D. N 261. 9.7 8 276. 9.5 8 286. 6.9 8 298. 3.1 8 317. 7.5 8 337. 7.4 8 380. 9.8 8 415. 13.0 8 -1836- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN TABLE 3 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHTS DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0 3 6 9 12 15 18 20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25649 G 251. 269. 283. 291. 300. 330. 373. 410. 25608 G 269. 287. 303. 302. 315. 338. 376. 405. 25656 G 267. 283. 295. 314. 336. 360. 405. 449. 25688 G 266. 277. 287. 305. 322. 345. 395. 442. 25625 G 262. 277. 296. 316. 336. 359. 412. 449. 25699 NG 250. 253. 264. 271. 270. 275. 278. 279. 25750 G 260. 273. 279. 285. 306. 331. 367. 395. 25734 G 271. 283. 294. 293. 317. 341. 376. 412. 25745 NG 289. 289. 299. 295. 310. 308. 323. 327. 25693 G 265. 288. 299. 309. 326. 348. 378. 413. MEAN S.D. N 264. 6.3 8 280. 6.7 8 292. 8.2 8 302. 11.3 8 320. 13.0 8 344. 11.4 8 385. 16.5 8 422. 21.4 8 -1837- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGBWv4.05 10/05/2006 TABLE 4 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25679 G 24. 17. 11. 15. 32. 28. 32. 159. 25659 G 6. 24. 13. 10. 29. 56. 31. 169. 25634 G 17. 19. 16. 16. 28. 30. 28. 154. 25620 G 18. 8. 15. 25. 18. 33. 34. 151. 25706 G 15. 8. 18. 13. 21. 45. 31. 151. 25612 G 20. 12. 6. 18. 16. 32. 36. 140. 25629 G 27. 19. 5. 20. 26. 40. 35. 172. 25718 G 19. 21. 9. 20. 23. 38. 32. 162. 25760 G 17. 13. 7. 17. 11. 23. 10. 98. 25683 G 14. 13. 12. 29. 17. 52. 32. 169. MEAN S.D. N 18. 15. 11. 18. 22. 38. 30. 153. 5.7 5.4 4.4 5.6 6.7 10.7 7.4 21.6 10 10 10 10 10 10 10 10 -1838- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN TABLE 4 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25627 G 8. 16. 10. 11. 27. 48. 33. 153. 25669 G 16. 18. 6. 19. 26. 34. 32. 151. 25613 G 16. 16. 12. 25. 17. 37. 26. 149. 25607 G 16. 18. 22. 18. 28. 29. 43. 174. 25640 G 20. 18. 19. 20. 22. 39. 33. 171. 25711 G 19. 13. 18. 18. 22. 46. 36. 172. 25682 G 14. 13. 3. 18. 24. 44. 34. 150. 25651 G 23. 19. 4. 20. 34. 47. 35. 182. 25768 G 13. 15. 7. 24. 23. 51. 32. 165. 25643 G 21. 13. 13. 26. 21. 51. 34. 179. MEAN S.D. N 17. 16. 11. 20. 24. 43. 34. 165. 4.4 2.3 6.6 4.4 4.6 7.5 4.2 12.8 10 10 10 10 10 10 10 10 -1839- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN TABLE 4 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25601 G 33. 9. 9. 11. 28. 38. 38. 166. 25644 NG -3. -2. 11. 4. -3. 1. 5. 13. 25680 G 13. 5. 12. 27. 21. 45. 39. 162. 25675 G 6. 13. 17. 24. 17. 49. 31. 157. 25598 G 8. 17. 15. 20. 18. 48. 35. 161. 25667 G 11. 11. 20. 17. 16. 47. 30. 152. 25641 G 18. 5. 7. 15. 27. 32. 31. 135. 25662 G 15. 11. 5. 20. 20. 45. 43. 159. 25726 NG 7. -1. 4. 12. 3. 5. 6. 36. 25596 G 19. 7. 12. 16. 15. 38. 30. 137. MEAN S.D. N 15. 10. 12. 19. 20. 43. 35. 154. 8.4 4.1 5.1 5.1 4.9 6.0 4.9 11.6 8 8 8 8 8 8 8 8 -1840- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN TABLE 4 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25649 G 18. 14. 8. 9. 30. 43. 37. 159. 25608 G 18. 16. -1. 13. 23. 38. 29. 136. 25656 G 16. 12. 19. 22. 24. 45. 44. 182. 25688 G 11. 10. 18. 17. 23. 50. 47. 176. 25625 G 15. 19. 20. 20. 23. 53. 37. 187. 25699 NG 3. 11. 7. -1. 5. 3. 1. 29. 25750 G 13. 6. 6. 21. 25. 36. 28. 135. 25734 G 12. 11. -1. 24. 24. 35. 36. 141. 25745 NG 0. 10. -4. 15. -2. 15. 4. 38. 25693 G 23. 11. 10. 17. 22. 30. 35. 148. MEAN S.D. N 16. 12. 10. 18. 24. 41. 37. 158. 3.9 4.0 8.5 5.0 2.5 7.9 6.5 21.2 8 8 8 8 8 8 8 8 -1841- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN PGBWv4.05 10/05/2006 TABLE 5 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25679 G 19. NA 21. NA NA NA NA NA 25659 G 17. 23. 25. 26. NA 32. 27. 25. 25634 G 22. 25. 23. 26. 28. 30. NA NA 25620 G 19. 20. 22. 23. 24. 28. 27. 23. 25706 G 19. 21. 22. 22. 23. 27. 24. 23. 25612 G 19. 21. 22. NA 22. 25. 27. 22. 25629 G 22. 24. NA 27. 25. 29. 28. 25. 25718 G 21. 25. 25. 26. 26. NA NA NA 25760 G 20. 23. 26. 25. 27. 28. 27. 25. 25683 G 20. 22. 27. 26. 27. 30. 28. 26. MEAN S.D. N 20. 23. 24. 25. 25. 29. 27. 24. 1.5 1.8 2.1 1.7 2.1 2.1 1.3 1.5 10 9 9 8 8 8 7 7 -1842- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE TABLE 5 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25627 G 19. 22. 21. 24. 23. 26. 28. 23. 25669 G 23. 26. 24. 25. 28. 29. 28. 26. 25613 G 19. 26. 23. 27. 25. 29. NA NA 25607 G 18. 22. 24. 25. 29. 30. NA NA 25640 G 21. 24. 23. 27. 25. 32. 28. 25. 25711 G 16. 19. 23. 24. 26. 29. 28. 23. 25682 G 20. 22. 22. NA 26. 32. 32. 25. 25651 G 22. 23. 25. 26. 27. 29. 29. 26. 25768 G 21. 23. 24. 25. 26. 30. 29. 25. 25643 G 19. 21. 24. 24. 25. 29. 31. 24. MEAN S.D. N 20. 23. 23. 25. 26. 30. 29. 25. 2.0 2.1 1.2 1.2 1.7 1.7 1.6 1.2 10 10 10 9 10 10 8 8 -1843- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE TABLE 5 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25601 G 23. 23. 21. 25. 24. 27. 30. 25. 25644 NG 15. 17. 19. 17. NA NA NA NA 25680 G 20. 20. 23. 25. 27. 31. 29. 25. 25675 G 18. 22. 22. 26. 23. 31. 28. 24. 25598 G 20. 23. 23. 24. 24. 29. 29. 24. 25667 G 20. 24. 24. 25. 25. 30. 29. 25. 25641 G 20. 19. 20. 22. 25. 30. 27. 23. 25662 G 20. 22. 22. 23. 26. 29. 31. 24. 25726 NG 19. 19. 21. 20. 20. 21. 22. 20. 25596 G 21. 20. 23. 23. 23. 25. 27. 23. MEAN S.D. N 20. 22. 22. 24. 25. 29. 29. 24. 1.4 1.8 1.3 1.4 1.4 2.1 1.4 0.8 8 8 8 8 8 8 8 8 -1844- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE TABLE 5 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25649 G 20. 20. 21. 22. 22. 28. NA NA 25608 G 22. 24. 20. 25. 24. 28. NA NA 25656 G 21. 23. 23. 25. 26. 33. 31. 26. 25688 G 19. 23. 24. 26. 29. 33. 35. 26. 25625 G 21. 24. 24. 24. 26. 31. 32. 26. 25699 NG 18. 20. 19. 18. 16. 17. NA NA 25750 G 18. 20. 20. 22. 26. 27. 27. 22. 25734 G 18. 24. 20. NA 26. NA 28. 23. 25745 NG 20. 26. 22. NA 20. 23. 24. 23. 25693 G 21. 22. 23. 22. 26. 27. 30. 24. MEAN S.D. N 20. 23. 22. 24. 26. 30. 31. 25. 1.5 1.7 1.8 1.7 2.0 2.7 2.9 1.8 8 8 8 7 8 7 6 6 -1845- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGFWv4.08 01/23/2007 TABLE 6 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY --------------------------------------- 25679 G 76. NA 73. NA NA NA NA NA 25659 G 60. 78. 79. 80. NA 82. 63. 73. 25634 G 77. 83. 72. 78. 78. 78. NA NA 25620 G 70. 70. 74. 73. 71. 77. 68. 71. 25706 G 72. 76. 76. 72. 72. 76. 61. 73. 25612 G 72. 75. 76. NA 69. 73. 72. 70. 25629 G 81. 82. NA 85. 74. 78. 68. 76. 25718 G 75. 84. 80. 79. 74. NA NA NA 25760 G 71. 77. 84. 78. 81. 80. 74. 77. 25683 G 72. 76. 89. 80. 78. 79. 66. 77. MEAN S.D. N 73. 78. 78. 78. 75. 78. 67. 74. 5.5 4.5 5.6 4.1 4.1 2.7 4.6 2.9 10 9 9 8 8 8 7 7 -1846- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE TABLE 6 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY --------------------------------------- 25627 G 72. 80. 73. 80. 72. 73. 71. 73. 25669 G 82. 87. 77. 77. 81. 77. 68. 77. 25613 G 69. 89. 75. 83. 72. 78. NA NA 25607 G 66. 76. 78. 76. 82. 79. NA NA 25640 G 78. 84. 75. 83. 72. 85. 68. 75. 25711 G 66. 74. 84. 82. 84. 84. 73. 76. 25682 G 76. 79. 77. NA 82. 91. 82. 80. 25651 G 77. 75. 79. 79. 76. 73. 66. 75. 25768 G 74. 77. 77. 77. 74. 78. 68. 73. 25643 G 68. 71. 77. 73. 71. 75. 72. 70. MEAN S.D. N 73. 79. 77. 79. 77. 79. 71. 75. 5.5 5.8 2.9 3.4 5.1 5.8 5.0 3.0 10 10 10 9 10 10 8 8 -1847- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE TABLE 6 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY --------------------------------------- 25601 G 88. 82. 72. 83. 75. 76. 77. 79. 25644 NG 57. 66. 72. 63. NA NA NA NA 25680 G 71. 69. 77. 79. 79. 83. 70. 75. 25675 G 68. 80. 76. 84. 69. 85. 69. 75. 25598 G 76. 83. 79. 78. 73. 80. 72. 75. 25667 G 78. 90. 85. 83. 79. 86. 75. 80. 25641 G 72. 66. 68. 72. 76. 84. 70. 72. 25662 G 72. 76. 74. 74. 79. 80. 76. 73. 25726 NG 66. 66. 72. 67. 65. 68. 70. 67. 25596 G 77. 70. 78. 75. 71. 71. 70. 72. MEAN S.D. N 75. 77. 76. 79. 75. 81. 72. 75. 6.2 8.2 5.1 4.6 3.9 5.1 3.2 3.0 8 8 8 8 8 8 8 8 -1848- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE TABLE 6 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY] SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- PREGNANCY STATUS DAY 0- 3 3- 6 6- 9 9-12 12-15 15-18 18-20 0-20 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY --------------------------------------- 25649 G 77. 72. 73. 74. 70. 80. NA NA 25608 G 79. 81. 66. 81. 73. 78. NA NA 25656 G 76. 80. 75. 77. 75. 86. 73. 77. 25688 G 70. 82. 81. 83. 87. 89. 84. 79. 25625 G 78. 84. 78. 74. 75. 80. 74. 77. 25699 NG 71. 77. 71. 66. 59. 61. NA NA 25750 G 67. 72. 71. 74. 82. 77. 71. 71. 25734 G 65. 83. 68. NA 79. NA 71. 71. 25745 NG 69. 88. 74. NA 65. 73. 74. 75. 25693 G 76. 75. 76. 69. 77. 74. 76. 73. MEAN S.D. N 74. 79. 74. 76. 77. 81. 75. 75. 5.4 4.9 5.0 4.8 5.4 5.2 4.9 3.4 8 8 8 7 8 7 6 6 -1849- G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE PGFWv4.08 01/23/2007 TABLE 7 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 1 SPONSOR:3M CORPORATION INDIVIDUAL PREGNANCY STATUS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 1: 0 MG/KG/DAY MATERNAL GROSS OBSERVATION ----------------------------------------------------------------------------------------------------------------------------------- 25679 GRAVID 25659 GRAVID 25634 GRAVID 25620 GRAVID 25706 GRAVID 25612 GRAVID 25629 GRAVID 25718 GRAVID 25760 GRAVID 25683 GRAVID -1850- TABLE 7 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 2 SPONSOR:3M CORPORATION INDIVIDUAL PREGNANCY STATUS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 2: 0.1 MG/KG/DAY MATERNAL GROSS OBSERVATION ----------------------------------------------------------------------------------------------------------------------------------- 25627 GRAVID 25669 GRAVID 25613 GRAVID 25607 GRAVID 25640 GRAVID 25711 GRAVID 25682 GRAVID 25651 GRAVID 25768 GRAVID 25643 GRAVID -1851- TABLE 7 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 3 SPONSOR:3M CORPORATION INDIVIDUAL PREGNANCY STATUS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 3: 0.3 MG/KG/DAY MATERNAL GROSS OBSERVATION ----------------------------------------------------------------------------------------------------------------------------------- 25601 GRAVID 25644 NONGRAVID 25680 GRAVID 25675 GRAVID 25598 GRAVID 25667 GRAVID 25641 GRAVID 25662 GRAVID 25726 NONGRAVID 25596 GRAVID -1852- TABLE 7 PROJECT NO.:WIL-180017T ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS PAGE 4 SPONSOR:3M CORPORATION INDIVIDUAL PREGNANCY STATUS SPONSOR NO.:06-128 ----------------------------------------------------------------------------------------------------------------------------------- DAMS FROM GROUP 4: 1.0 MG/KG/DAY MATERNAL GROSS OBSERVATION ----------------------------------------------------------------------------------------------------------------------------------- 25649 GRAVID 25608 GRAVID 25656 GRAVID 25688 GRAVID 25625 GRAVID 25699 NONGRAVID 25750 GRAVID 25734 GRAVID 25745 NONGRAVID 25693 GRAVID PMFGRDv4.16 10/16/2006 R:10/16/2006 -1853- -1854- Final Report Volume 6 of 6 (Appendices 57-66) Study Title An Oral (Gavage) Developmental Neurotoxicity and Thyroid Function Study of MTDID 208 in Rats Study Number WIL-180017 Data Requirement EPA OPPTS Guideline 870.6300; OECD Draft Guideline 426 Study Director Donald G. Stump, PhD, DABT Study Initiation Date 21 April 2006 Study Completion Date 10 January 2008 Performing Laboratory WIL Research Laboratories, LLC 1407 George Road Ashland, OH 44805-9281 Sponsor Study Number 06-128 Sponsor 3M Corporation 3M Center, Building 0220-06-W-08 St. Paul, Minnesota 55144-1000 WIL-180017 3M Corporation -1855- MTDID 208 06-128 APPENDIX 57 Pathology Report (WIL Research Laboratories, LLC) WIL-180017 3M Corporation -1856- MTDID 208 06-128 AN ORAL (GAVAGE) DEVELOPMENTAL NEUROTOXICITY AND THYROID FUNCTION STUDY OF MTDID 208 IN RATS PATHOLOGY REPORT Pathology Department WIL Research Laboratories, LLC -1- WIL-180017 3M Corporation -1857- MTDID 208 06-128 TABLE OF CONTENTS Page Table Of Contents ......................................................................................2 1. Introduction................................................................................................4 2. Study Design ...............................................................................................4 3. Methods.......................................................................................................5 3.1. Toxicokinetic Analysis, Necropsy And Pathology......................................5 3.1.1. GD 20 (Toxicokinetic/Thyroid Function Satellite Phase) ...........................5 3.1.2. LD/Postnatal Day (PND 4) (Main Study)....................................................5 3.1.3. LD/PND 21(Main Study).............................................................................6 3.1.4. Terminal Procedures For Maternal Females (Dams)...................................7 3.1.4.1. Females That Delivered ...............................................................................7 3.1.4.2. Females That Failed To Deliver ..................................................................7 3.1.5. Terminal Procedures For Offspring Not Scheduled For Behavioral Evaluations Or Brain Weight Determinations .............................................8 3.1.5.1. F1 Deaths......................................................................................................8 3.1.5.2. Offspring Selected For Culling On PND 4 ..................................................8 3.1.5.3. Euthanasia Of Offspring Not Selected For Behavioral Or Thyroid Function Evaluation .....................................................................................8 3.1.6. Offspring Scheduled For Euthanasia At Study Termination .......................8 3.1.7. Offspring Scheduled For Brain Weight Measurements...............................9 3.1.7.1. Offspring Euthanized On PND 21 ...............................................................9 3.1.7.1.1. Macroscopic Examination .......................................................................... 9 3.1.7.1.2. Microscopic Examination ........................................................................... 9 3.1.7.2. Animals Euthanized At Study Termination (PND 72) ..............................10 3.1.7.2.1. Macroscopic Examination ........................................................................ 10 3.1.7.2.2. Microscopic Examination ......................................................................... 10 3.1.8. Thyroid Histopathology, Cell Proliferation Assay And Morphometry .............................................................................................10 3.2. Abbreviations And Definitions ..................................................................14 -2- WIL-180017 3M Corporation -1858- MTDID 208 06-128 Page 3.3. Data Interpretation .....................................................................................14 4. Results .......................................................................................................15 4.1. Thyroid Function Assessment....................................................................15 4.2. Gross Observations ....................................................................................15 4.3. Organ Weights, Body Weights and Brain Measurements .........................15 4.4. Thyroid Histopathology And Morphometry..............................................15 5. Discussion..................................................................................................18 6. Conclusions...............................................................................................19 7. Report Submission ...................................................................................20 8. Reference ..................................................................................................21 -3- WIL-180017 3M Corporation -1859- MTDID 208 06-128 1. INTRODUCTION The purpose of this study was to determine the potential of the test article to induce functional and morphological insult to the nervous system, which may arise in the offspring from exposure of the mother during pregnancy and lactation. Additional objectives of this study were to determine the effects of maternal exposure to the test article on maternal and neonatal thyroid status and to establish toxicokinetic data for different compartments in the dam and offspring. 2. STUDY DESIGN Female Crl:CD(SD) rats were administered MTDID 208 as a single daily oral (gavage) dose from gestation day (GD) 0 through lactation day (LD) 20, inclusively, for the main study phase or through GD 19 for the toxicokinetic/thyroid function satellite phase, as indicated in the following table. All animals were dosed at approximately the same time each day. The dosage volume was 5 mL/kg for all groups. Group Number Test Article Dosage Level (mg/kg/day) 1 Vehicle Control a 0 2 MTDID 208 0.1 3 MTDID 208 0.3 4 MTDID 208 1.0 a = The vehicle control was 0.5% Tween 20. b = Toxicokinetic/thyroid function satellite phase. Number of Females Main TK b 25 10 25 10 25 10 25 10 F1 generation animals were potentially exposed to the test article in utero and via the milk during the lactation period. No direct administration to the F1 animals occurred. -4- WIL-180017 3M Corporation -1860- MTDID 208 06-128 3. METHODS 3.1. TOXICOKINETIC ANALYSIS, NECROPSY AND PATHOLOGY 3.1.1. GD 20 (TOXICOKINETIC/THYROID FUNCTION SATELLITE PHASE) On GD 20, rats were euthanized between 0859 and 1153 hours by decapitation, and blood samples (at least 2 mL) were collected via decapitation into tubes without anticoagulant. After maternal blood samples were collected, fetal blood was collected by decapitation of each live fetus into tubes without anticoagulant (microcapillary tubes were used as needed to aid in the blood collection); fetal blood were pooled by litter regardless of sex. Following maternal and fetal blood collection, livers and brains were collected from the dam and each viable fetus and weighed (pooled by litter for the fetus). Thereafter, a small sample of the maternal brain and liver and a single fetal liver and brain from each litter were placed in RNAlater, refrigerated for approximately 24 hours and stored frozen until shipped for rtPCR. Remaining brain and liver samples were snap-frozen in liquid nitrogen and stored frozen at -70C until shipped for toxicokinetic analysis. Maternal and fetal thyroids were preserved in 10% neutral-buffered formalin. The thyroid of 1 fetus/sex/litter from the control and high-dose groups were examined microscopically and used for a thyroid cell proliferation assay as described in Section 3.1.8. All other fetal thyroids in each litter and all maternal thyroids were retained for possible future histopathological assessment. 3.1.2. LD/POSTNATAL DAY (PND 4) (MAIN STUDY) On LD 4, blood samples (at least 1 mL) were collected between 0913 and 1044 hours (prior to dose administration) from the retro-orbital sinus of 10 randomly selected F0 females/group assigned to the main study into tubes without anticoagulant. Females were anesthetized by isoflurane inhalation prior to the blood sample collection. Also, on PND 4, culled offspring from the same 10 litters/group whose dams are selected for blood sample collection were decapitated between 0904 and 1103 hours. Blood was collected by decapitation into tubes without anticoagulant (microcapillary tubes were -5- WIL-180017 3M Corporation -1861- MTDID 208 06-128 used as needed to aid in the blood collection); blood was pooled by litter regardless of sex. Following blood collection, livers and brains were collected from the culled offspring and weighed (pooled by litter). Thereafter, a single neonatal liver and brain from each litter were placed in RNAlater and refrigerated until shipped for rtPCR. Remaining brain and liver samples were snap-frozen in liquid nitrogen and stored frozen at -70C until shipped for toxicokinetic analysis. Neonatal thyroids were collected and preserved in 10% neutral-buffered formalin. The thyroid of 1 pup/sex/litter from the control and high-dose groups were examined microscopically. The microscopic examination included a simple morphometric analysis as described in Section 3.1.8. All other neonatal thyroids in each litter were retained for possible future histopathological assessment. 3.1.3. LD/PND 21(MAIN STUDY) Ten randomly selected F0 rats/group assigned to the main study were euthanized between 0930 and 1132 hours by decapitation on LD 21. Blood samples (at least 2 mL) were collected via decapitation into tubes without anticoagulant. Also on PND 21, 1 pup/sex/litter from the same 10 litters/group whose dams are selected for blood sample collection and that were not assigned to neurobehavioral or brain weight measurements were decapitated between 0900 and 1104 hours. Blood was collected by decapitation into tubes without anticoagulant (microcapillary tubes were used as needed to aid in the blood collection). Following blood collection, liver and brains were collected from the offspring and weighed. Thereafter, a small sample of the liver and brain were placed in RNAlater and refrigerated until shipped for rtPCR. Remaining brain and liver samples were snap-frozen in liquid nitrogen and stored frozen at -70C until shipped for toxicokinetic analysis. -6- WIL-180017 3M Corporation -1862- MTDID 208 06-128 Maternal and neonatal thyroids were collected and preserved in 10% neutral-buffered formalin. The thyroid of 1 pup/sex/litter from the control and high-dose groups were examined microscopically. The microscopic examination included a simple morphometric analysis as described in Section 3.1.8. All thyroids in each litter (maternal and pup) were retained for possible future histopathological assessment. 3.1.4. TERMINAL PROCEDURES FOR MATERNAL FEMALES (DAMS) 3.1.4.1. FEMALES THAT DELIVERED On LD 21 (day of weaning), 10 females/group were euthanized by decapitation as described in Section 3.1.3. The remaining females in each group were euthanized by carbon dioxide inhalation. All females were subjected to a gross necropsy. The number of implantation sites was recorded. Maternal tissues were preserved in 10% neutral-buffered formalin for histopathological examination only as deemed necessary by the gross findings and as described in Section 3.1.3. The carcass of each dam was discarded. 3.1.4.2. FEMALES THAT FAILED TO DELIVER On post-mating day 25, the females were weighed, euthanized by carbon dioxide inhalation and subjected to a gross necropsy. The number of implantation sites were recorded if there was evidence of pregnancy. Nongravid uteri were opened and placed in 10% ammonium sulfide solution as described by Salewski (Salewski, 1964) for the detection of implantation sites. Tissues were saved for possible future histopathological examination in 10% neutral-buffered formalin only as deemed necessary by the gross findings. The carcass of each dam was discarded. -7- WIL-180017 3M Corporation -1863- MTDID 208 06-128 3.1.5. TERMINAL PROCEDURES FOR OFFSPRING NOT SCHEDULED FOR BEHAVIORAL EVALUATIONS OR BRAIN WEIGHT DETERMINATIONS 3.1.5.1. F1 DEATHS Stillborn pups and pups dying between birth and PND 4 were examined by a technique described by Stuckhardt and Poppe (Stuckhardt, 1984). Pups dying after PND 4 were necropsied. Organs/tissues were preserved for possible histopathologic examination in 10% neutral-buffered formalin only as deemed necessary by the gross findings. All carcasses were discarded. 3.1.5.2. OFFSPRING SELECTED FOR CULLING ON PND 4 Offspring selected for culling on PND 4 from the same 10 litters/group whose dams were used for blood collection were euthanized by decapitation, used for blood, thyroid and brain sample collection as specified in Section 3.1.2 and discarded without examination. Culled offspring not selected for blood sample collection were euthanized by intraperitoneal injection of sodium pentobarbital and discarded without examination. 3.1.5.3. EUTHANASIA OF OFFSPRING NOT SELECTED FOR BEHAVIORAL OR THYROID FUNCTION EVALUATION On PND 21, offspring not selected for behavioral evaluations or thyroid function assessment were euthanized by carbon dioxide inhalation and subjected to a gross necropsy. Tissues were retained in 10% neutral-buffered formalin only as deemed necessary by the gross findings. 3.1.6. OFFSPRING SCHEDULED FOR EUTHANASIA AT STUDY TERMINATION Pups scheduled for euthanasia on PND 72 but not allocated for brain weight measurements were euthanized between 0859 and 1043 hours by decapitation. Blood samples (at least 2 mL) were collected into tubes without anticoagulant. Serum were isolated and stored at approximately -70C. -8- WIL-180017 3M Corporation -1864- MTDID 208 06-128 Following blood collection, the livers were collected from the offspring and weighed. A small sample of the liver were placed in RNAlater and stored refrigerated until shipped for rtPCR. Remaining liver samples were snap-frozen in liquid nitrogen and stored frozen at -70C until shipped for toxicokinetic analysis. The animals were then subjected to a gross necropsy which included examination of the external surface, all orifices and the cranial, thoracic, abdominal and pelvic cavities, including viscera. Organ/tissue samples were preserved in 10% neutral-buffered formalin as deemed necessary by the gross findings. The carcass of each pup was discarded. 3.1.7. OFFSPRING SCHEDULED FOR BRAIN WEIGHT MEASUREMENTS Brain measurements (weight, length and width) were conducted on PND 21 and at the termination of the study (PND 72). The brains from these animals were retained for possible future neuropathological evaluation. 3.1.7.1. OFFSPRING EUTHANIZED ON PND 21 3.1.7.1.1. MACROSCOPIC EXAMINATION On PND 21, 1 male and/or 1 female pup were removed from each litter (until N = 15 pups/sex/group) and macroscopically examined for neuropathology. The pups were anesthetized by intraperitoneal injection of sodium pentobarbital and euthanized by perfusion in situ. The brains were removed (including olfactory bulbs), weighed and the size (length and width) were recorded. Any abnormal coloration or lesions of the brain and spinal cord were recorded. Brains from all animals were retained. 3.1.7.1.2. MICROSCOPIC EXAMINATION The brains from pups selected for macroscopic evaluation on PND 21 were prepared for possible future microscopic neuropathologic examination. -9- WIL-180017 3M Corporation -1865- MTDID 208 06-128 3.1.7.2. ANIMALS EUTHANIZED AT STUDY TERMINATION (PND 72) 3.1.7.2.1. MACROSCOPIC EXAMINATION At the termination of the study (PND 72), 1 male and/or 1 female from each litter were randomly selected from those pups dedicated to behavioral evaluation (until N = 15 rats/sex/group). The animals were anesthetized by intraperitoneal of sodium pentobarbital and euthanized by perfusion in situ. The central nervous system and tissues were dissected and preserved. The whole brains were removed (including olfactory bulbs), weighed and the size (length and width) recorded. Any abnormal coloration or lesions of the brain or spinal cord were recorded. Nervous system tissue was retained from all animals. 3.1.7.2.2. MICROSCOPIC EXAMINATION Brains from all animals perfused in situ on PND 72 were embedded in paraffin to prevent artifactual changes in brain morphology due to storage in 10% neutral-buffered formalin. 3.1.8. THYROID HISTOPATHOLOGY, CELL PROLIFERATION ASSAY AND MORPHOMETRY The thyroids from 1 fetus/sex/litter from each toxicokinetic phase female euthanized on GD 20 and 1 pup/sex/litter from 10 randomly selected litters/group on PND 4 and 21 were prepared for microscopic examination (thyroids for all groups were processed; however, only the control and high-dose groups were evaluated). The thyroids were prepared for a qualitative and semiquantitative histopathological examination by embedding in paraffin, sectioning and staining with hematoxylin and eosin. The histopathological examination of H&E-stained histologic sections for the pups euthanized on PND 4 and 21 included a basic morphometric analysis, consisting of measurement of thyroid follicular epithelial cell height and dimensions of colloid contained within thyroid follicles. The morphometric analysis of follicular cell epithelial height and colloid area was performed on a total of 10 pups/sex (representing 10 litters) from the control and 1.0 mg/kg/day groups that were collected on PND 4 and 21. Ki-67 immunohistochemical -10- WIL-180017 3M Corporation -1866- MTDID 208 06-128 staining was performed on thyroid glands from selected GD 20 fetuses to allow detection of any test article-related alteration in cellular proliferation. Ki-67 immunohistochemical staining and subsequent cell counting was intended on a total of 10 fetuses/sex (representing 10 litters) from the control and 1.0 mg/kg/day groups that were collected on GD 20, but technical limitations in slide preparation reduced the number of acceptable specimens to 6 for males in the control and 1.0 mg/kg/day groups and to 7 and 5 for females in the control and 1.0 mg/kg/day groups, respectively. Measurement of thyroid epithelial cell height: Digital images of thyroid glands from control and high-dose pups (0 and 1.0 mg/kg/day, respectively) were captured using an Olympus BX-51 photomicroscope equipped with an Olympus DP-70 digital camera. Image files were labeled with the study number, animal number, and objective magnification. Linear measurements of epithelial cell height were made using Image Pro Plus version 5.1 software (Media Cybernetics, Silver Spring, Maryland). Cell height measurement was performed on 3 cells from each of 5 follicles in each pup, resulting in a total of 15 cell measurements from each pup. Cells selected for measurement were located at approximately the 12, 4 and 8 o'clock positions in follicles. Measurements extended from the deep aspect of nuclear membranes up to the luminal surface of selected follicular epithelial cells. Epithelial cell measurements were exported to Microsoft Excel, and basic mathematical computations were used to determine group means and standard deviations. After the 15 measurement lines were placed on each digital image, the screen capture function of Image Pro was used to capture the entire image, including measurement lines and line identification markers. The original digital images plus the screen capture images with superimposed measurement lines are maintained in the study records. Review of the screen capture images allows complete tracking of the data, if desired. Measurement of thyroid follicle area: Digital images of thyroid glands from control and high-dose pups (0 and 1.0 mg/kg/day, respectively) were captured using an Olympus -11- WIL-180017 3M Corporation -1867- MTDID 208 06-128 BX-51 photomicroscope equipped with an Olympus DP-70 digital camera. Image files were labeled with the study number, animal number, and objective magnification. Measurements of were made using Image Pro Plus version 5.1 software (Media Cybernetics, Silver Spring, Maryland). Long and short axis measurements were performed on the colloid mass within the 10 largest follicles that appeared in each digital image. Colloid dimensions were exported to a Microsoft Excel spreadsheet, and basic mathematical computations were used to determine group means and standard deviations. After colloid dimensions of 10 follicles were measured, the screen capture function of Image Pro was used to capture the entire image, including measurement lines and the Image Pro data output table. The original digital images plus the screen capture images with superimposed measurement lines are maintained in the study records. Review of the screen capture images allows complete tracking of the data, if desired. Estimation of Ki-67-positive cells: Ki-67 immunohistochemical staining was performed by the following procedure, which was based on the manufacturer's procedure guide (monoclonal mouse anti-rat Ki-67 antigen, clone MIB-5, Dako catalog number M7248). General procedures for immunohistochemical staining are addressed in Biotechnics SOP 1.6.2.3. Ki-67 Immunohistochemistry Staining Procedure Step Procedure 1 Deparaffinize and rehydrate paraffin sections 2 Wash in automation buffer (Dako, Carpinteria, CA, Lot No. 00006857, expiration date Dec07) 3 HIER in a decloaker with citrate buffer (Zymed, Carlsbad, CA, Lot No.1369722, expiration date May08) 4 Wash in automation buffer (Dako, Carpinteria, CA, Lot No. 00006857, expiration date Dec07) 5 Block endogenous peroxidase activity with 0.3% H2 O2 in deionized water (Fisher Scientific Pittsburgh, PA, Lot No. 062283, expiration date Aug08) 6 Wash in automation buffer (Dako, Carpinteria, CA, Lot No. 00006857, expiration date Dec07) 7 Block with 5% horse serum (Jackson Immunoresearch, West Grove, PA, Lot No.65780, expiration date Dec07) -12- WIL-180017 3M Corporation -1868- MTDID 208 06-128 Ki-67 Immunohistochemistry Staining Procedure Step Procedure 8 Do not rinse slides. Block with Avidin (Vector Laboratories, Burlingame, CA, Lot No. S1010, expiration date Nov08) 9 Wash in automation buffer. (Dako, Carpinteria, CA, Lot No. 00006857, expiration date Dec07) 10 Buffer Block with Biotin (Vector Laboratories, Burlingame, CA, Lot No. S1010, expiration date Nov08) 11 Primary antibody (Mouse anti-rat Ki-67 (MIB-5) Dako, Carpinteria, CA, Lot No. 018085, expiration date April08) 12 Wash in automation buffer (Dako, Carpinteria, CA, Lot No. 00006857, expiration date Dec07) 13 Secondary antibody (biotinylated horse anti-mouse at 1:300 dilution, Vector Laboratories, Burlingame, CA, Lot No. R0802, expiration date Sept07) 14 Wash in automation buffer (Dako, Carpinteria, CA, Lot No. 00006857, expiration date Dec07) 15 Incubate in avidin-biotin complex (ABC) reagent (Vector Laboratories, Burlingame, CA, Vectastain ABC Kit, Catalog No. PK-6100, expiration date Nov08) 16 Wash in automation buffer (Dako, Carpinteria, CA, Lot No. 00006857, expiration date Dec07) 17 Peroxidase development- diaminobenzidine (DAKO, Carpinteria, CA, Lot No.00004233, expiration date Sept08) 18 Wash in water bath 19 Counterstain with hematoxylin (DAKO Corporation, Carpinteria, CA. Lot No. S3301, expiration date Oct07) 20 Dehydrate through 70%, 80%, 95% and 100% ethanol followed by xylene 21 Coverslip Ki-67-positive thyroid follicular epithelial cells in 3 microscopic fields at 100x objective magnification (oil objective) microscopic fields were counted. Results were recorded in a Microsoft Excel spreadsheet, and basic mathematical computations were performed to determine group means and standard deviations. -13- WIL-180017 3M Corporation -1869- MTDID 208 06-128 3.2. ABBREVIATIONS AND DEFINITIONS The following abbreviations and definitions may apply to this report: Interval - point in the study at which an animal died or was euthanized FD - found dead EE - euthanized in extremis GD - gestation day PND - postnatal day LD - lactation day SN - scheduled necropsy (end of dosing) Significant - As used in this study refers to statistical significance 3.3. DATA INTERPRETATION In the discussion of thyroid stimulating hormone (TSH) levels, values derived from the control group animals at all time points evaluated were considered as concurrent control values for purposes of constructing a `normal' range for the present study. This narrative report addresses all hormone values that were identified as statistically significantly different from control group values on the hormone data tables. In the discussion of organ weight changes, the indication of higher or lower mean organ weights refers to a statistically significant (p<0.05 or p<0.01 using Dunnett's test) difference between test article-treated versus control group animals in the present study. In addition, historical control values for this laboratory were consulted to refine data interpretation. This narrative report addresses all organ weight values that were identified as statistically significantly different from control group values on the organ weight data tables. -14- WIL-180017 3M Corporation -1870- MTDID 208 06-128 4. RESULTS 4.1. THYROID FUNCTION ASSESSMENT GD 20: TSH values of F0 dams and F1 fetuses (pooled males and females by litter) in the MTDID 208-treated groups (Note: there was no direct dosing of the pups) at 0.1, 0.3 or 1.0 mg/kg/day were lower than control group values, but the difference did not achieve statistical significance. It was noted that the pattern of TSH values in fetuses paralleled the values in the dams, suggesting maternal influence on the fetal values. LD/PND 4: TSH values of F0 dams or F1 pups (pooled males and females by litter) that received MTDID 208 at 0.1, 0.3 or 1.0 mg/kg/day were not significantly different from control group values. LD/PND 21: TSH values of F0 dams that received MTDID 208 at 0.1, 0.3 or 1.0 mg/kg/day were equivalent to control group values. TSH values of F1 male pups in the MTDID 208-treated groups were slightly higher than control group values, but the higher values did not occur in a dose-related manner and the differences did not achieve statistical significance. TSH values of F1 female pups in the MTDID 208-treated groups were equivalent to control group values. The data suggested no unequivocal test article-related effect on TSH values in F0 dams or F1 pups on LD/PND 21. 4.2. GROSS OBSERVATIONS Review of the gross necropsy observations revealed no test article-related alterations. 4.3. ORGAN WEIGHTS, BODY WEIGHTS AND BRAIN MEASUREMENTS There were no test article-related effects on PND 21 or PND 72 offspring final body weight or brain weight, length or width. 4.4. THYROID HISTOPATHOLOGY AND MORPHOMETRY There were no test article-related histologic changes in the routinely stained sections of thyroids from GD 20 fetuses, PND 4 pups or PND 21 pups. All histologic changes in the thyroid glands were considered to be incidental findings or related to some aspect of -15- WIL-180017 3M Corporation -1871- MTDID 208 06-128 experimental manipulation other than administration of the test article. There was no test article-related alteration in the incidence, severity or histologic character of those incidental and spontaneous tissue alterations. Mean thyroid follicular epithelial cell height of male pups from the 1.0 mg/kg/day group was significantly (p<0.01, Dunnett's test) higher (11%) than that of the control group on PND 21 but not on PND 4, as summarized in Text Tables 1a and 1b. Mean thyroid follicular colloid area of male and female pups from the 1.0 mg/kg/day group was similar to that of control group on PND 4 and 21, as summarized in Text Tables 2a and 2b. The mean number of Ki-67-positive thyroid follicular epithelial cells in female fetuses from the 1.0 mg/kg/day group was significantly (p<0.05) higher (2.1-fold) than that of the control group on GD 20, as summarized in Text Table 3. Text Table 1a Thyroid Follicular Epithelial Cell Height, PND 4 Males Dosage (mg/kg/day) 0 0.1 0.3 1.0 0 Thyroid a 10 0 0 10 10 Mean epithelial cell height b 5.49 - - 5.36 5.68 Standard deviation 0.260 - - 0.431 0.360 a = Number of tissues examined from each group. b = micrometers Females 0.1 0.3 0 0 - - - - 1.0 8 5.84 0.304 Dosage (mg/kg/day) Thyroid a Mean epithelial cell Standard deviation Thyroid height b Text Table 1b Follicular Epithelial Cell Males 0 0.1 0.3 10 0 0 5.68 - - 0.536 - - Height, 1.0 10 6.29** 0.324 PND 21 0 10 6.28 0.450 Females 0.1 0.3 0 0 - - - - a = Number of tissues examined from each group. b = micrometers ** = Statistically significant at p<0.01 (Dunnett's test) 1.0 10 6.38 0.598 -16- WIL-180017 3M Corporation -1872- MTDID 208 06-128 Dosage (mg/kg/day) Thyroid a Mean follicle area b Standard deviation Text Table 2a Thyroid Follicular Colloid Area , PND 4 Males 0 0.1 0.3 1.0 0 10 0 0 10 10 1841 - - 1533 2181 318.1 - - 368.7 442.9 a = Number of tissues examined from each group. b = micrometers Females 0.1 0.3 0 0 - - - - 1.0 8 1969 555.1 Dosage (mg/kg/day) Thyroida Mean follicle area b Standard deviation Text Table 2b Thyroid Follicular Colloid Area , PND 21 Males 0 0.1 0.3 1.0 0 10 0 0 10 10 7768 - - 7267 7220 1641.1 - - 1117.8 1288.6 a = Number of tissues examined from each group. b = micrometers Females 0.1 0.3 0 0 - - - - 1.0 10 7677 1857.8 Text Table 3 Ki-67-Positive Follicular Epithelial Cells in Thyroid Gland, GD20 Males Females Dosage (mg/kg/day) Thyroid a Ki-67-positive cells b 0 0.1 0.3 1.0 0 0.1 0.3 1.0 6 0 0 6 7 0 0 5 40 - - 32 42 - - 88* Standard deviation 23.9 - - 25.3 35.5 - - 18.6 a = Number of tissues examined from each group. b = Mean number of Ki-67-positive cells in 3 each 400X microscopic fields * = Statistically significant at p<0.05 (Dunnett's test) -17- WIL-180017 3M Corporation -1873- MTDID 208 06-128 5. DISCUSSION Extensive variability in the number of Ki-67-stained cells in thyroid glands from individual animals of the various treatment groups resulted in large standard deviation values. In addition, difficulties in preparing sections from these small tissues resulted in a reduced number of available samples in some dosage groups. These factors reduced confidence in the ability of this assay to detect a true test article-related effect on the thyroid gland, despite the significantly higher number of Ki-67-positive cells in the GD 20 female fetuses from the 1.0 mg/kg/day group. Mean follicular epithelial cell height of male pups from the 1.0 mg/kg/day group on PND 21 was significantly higher than concurrent control values, but it should be noted that the follicular epithelial cell height of those males was equivalent to the cell height of the control and 1.0 mg/kg/day group female pups on PND 21. The epithelial cell height of the control group males on PND 21 was extraordinarily low compared to other groups in the study, thus the higher cell height in 1.0 mg/kg/day males was a considered to be a spurious observation. -18- WIL-180017 3M Corporation -1874- MTDID 208 06-128 6. CONCLUSIONS Female Crl:CD(SD) rats were administered MTDID 208 as a single daily oral (gavage) dose from GD 0 through LD 20 or through GD 19, inclusively. The thyroids from 1 fetus/sex/litter from each toxicokinetic phase female euthanized on GD 20 and from 1 pup/sex/litter from 10 randomly selected litters/group euthanized on PND 4 and 21 were prepared for routine histopathologic examination. Morphometric analysis, consisting of measurement of thyroid follicular epithelial cell height and follicular colloid area, was performed on the H&E-stained thyroid gland sections of pups from the PND 4 and 21 necropsies. Ki-67 immunohistochemical staining was performed on thyroid gland sections of fetuses necropsied on GD 20, and cellular proliferation was estimated by counting Ki-67-positive cells. Thyroid stimulating hormone (TSH) values were determined for F0 dams and F1 fetuses/pups on GD 20, PND 4 and PND 21. This study revealed no evidence of test article-related alterations in TSH values or any histologic alterations that were visible in routinely stained sections. Morphometric analysis revealed higher mean thyroid follicular epithelial cell height in male pups from the 1.0 mg/kg/day group on PND 21, but this was suspected to be a spurious observation that was related to an extraordinarily low value in the concurrent control group. The number of Ki-67-positive proliferative cells in thyroid glands of female fetuses from the 1.0 mg/kg/day group was higher than control group values on GD 20, but the level of variability observed in this assay hindered an interpretation of the toxicologic significance of the observation. In summary, the assays performed in this study revealed no unequivocal evidence of a test article-related effect on structure or function of the thyroid gland. -19- -1875- WIL-180017 3M Corporation -1876- MTDID 208 06-128 8. REFERENCE Salewski, E. Frbemethode zum makroskopischen Nachweis von Implantationsstellen am Uterus der Ratte. [Staining method for a macroscopic test for implantation sites in the uterus of the rat]. Naunyn - Schmiedebergs Archiv fr Experimentelle Pathologie und Pharmakologie 1964, 247, 367. Stuckhardt, J.L.; Poppe, S.M. Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. Teratogenesis, Carcinogenesis and Mutagenesis 1984, 4, 181-188. -21- WIL-180017 3M Corporation -1877- MTDID 208 06-128 APPENDIX 58 rtPCR Results -1878- December 14, 2007 John L. Butenhoff, Ph.D. Medical Department 3M Center Building 220 6W 08 St. Paul, MN 55144 RE: WIL Research Study No. 180017 Dr. Butenhoff, What follows is a report of the results of transcriptional analyses performed in my laboratory concerning the above mentioned study. Rat liver samples, preserved in RNAlater, were received in our laboratory from 3M Company for quantitative determination of various gene transcripts. Individual transcript levels were quantified by real-time PCR (RT-PCR) and normalized based on the expression level of the housekeeping gene, 18s rRNA. RNA was extracted from rat liver samples which were preserved in RNAlater (Qiagen, CA) using Qiagen RNeasy spin columns. Approximately 25mg liver tissue was massed and homogenized in 600L of lysis buffer using a ground glass on glass duall tissue grinder. Sample was further homogenized by passing 5 times through a 27 gauge needle using a sterile 1mL syringe. On column DNAse digestion was carried out according to the manufactures protocol using Qiagen RNAse free DNAse set. The RNA was eluted in 35ul of RNase free water and quantified by measuring the absorbance at 260nM using the Nanodrop ND1000 spectrophotometer. Reverse transcription with the Omniscript RT kit (Qiagen, CA) was performed using random nonamer primers and 1.5 g of total RNA according to the manufacturer's protocol. Quantitative PCR was performed with the LightCycler using the Sybr Green Master Mix Kit (Roche, IN). PCR was carried out on samples, along with a 10 fold serial dilution of a target specific DNA standard, for selected transcripts using target sequence specific Primers. Target specific mRNA expression was normalized against 18s rRNA and the results were reported as transcript specific mRNA copies per 18s rRNA copies. -1879- The analyses employed the following primer sequences: Gene 18s rRNA ACoA PCNA Malic Enzym e Dio1 Por ApoA1 Cyp1a1 Cyp3a1 Cyp4a1 Cyp7a1 Cyp2b2 Ugt1A commo n Ugt1a1 Ugt1a6 Ugt2b Upper Primer CGC CGC TAG AGG TGA AAT TCT T TGG AGA GCC CTC AGC TAT GG GTG AAC CTC ACC AGC ATG TCC AAA AGG CCT CTT TAT CAG TAT CCA C TCT GCC TGA GAG GCT CTA TGT GAT AAG ACA TGG ACG TAG CCA AGG TGT GAT GAA AGC TGC AGT GTT GGC TGT TGA CCT CTT TGG AGC TGG GTT TGA TTT CGC CCA GAA AGG TTC AGC AAG ACC TCT TTC ACT CCC GTG TG TTT CTA CAT GCC CTT CGG ATC A TCC AGA CAC CTT CAA TCC TGA GCA GCC TTC CCA GTG TTA GTC ATT AGG AAG TAC CCT GTG CCA TTC CAA AAC GCG GAC ACG ACA TTG T GTG CAC TGG AGG AAG TCA TAG ACA Lower Primer CAG TCG GCA TCG TTT ATG GTC CGT TTC ACC GCC TCG TAA G ACA GCT GTA CTC CTG TTC TGG GAT CCA TCC CGT TAC AAC CAA TTT CCA GAA CAG CTC GGA CTT CTT TGA GAT GTC CAA CTA CAT GTG CAT GTT CAG CTG TTT GCC CAA AGT GGA ATG TCG GAA GGT CTC CAG GAT GAA AGA GCA AAC CTC ATG CCA ATG CAG GTG TGT GGC CAG AGC AGA GA TTC GCT TCT TCC AAC CAC GTA T GAC AAA TGC GCT TTC CTG TGG AGA CTT GGT TTG GGA ACA CAA TAG TCT TGA TCA AAG ACA CTC CGC CCA AAC TGG CAG CAA AGT GGT TGT T TAG GCT GGT CAT GGT GAA TCC TTG Lengt Gene Bank h (bp) Reference 149 M11188 338 NM_017340 198 NM_022381 140 AH002199 104 NM_021653 NM_031576. 173 1 NM_012738. 199 1 199 NM_012540 107 NM_173144 344 M57718 238 NM_012942 XM_0010623 98 35 200 U20551 80 U20551 156 U20551 XM_0010623 81 35 -1880- Table 1 describes the overall changes, if any, between treatment and control groups. Tables 2 through 16 list the data for the individual transcripts. Table 1: Overall summary ( indicates the mean values for the transcripts evaluated are significantly different than control at 95% confidence interval; -- indicates that the values are not statistically different than control). ACoA PCNA Malic Enzyme Dio1 Por ApoA1 Cyp1a1 Cyp3a1 Cyp4a1 Cyp7a1 Cyp2b2 Ugt1A common Ugt1a1 Ugt1a6 Ugt2b GD 20 Dam Fetus -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- PND 21 Dam Male pup NA NA -- NA -- NA -- NA -- NA -- NA -- NA -- NA NA NA NA -- NA -- NA -- NA -- Table 2: Acyl CoA, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 9.76E-05 4.57E-05 4.36E-05 5.31E-05 3.74E-05 5.55E-05 1.08E-05 Fetus 1.49E-05 1.88E-05 1.07E-05 1.30E-05 1.82E-05 1.51E-05 1.53E-06 5.94E-05 6.00E-05 8.21E-05 4.91E-05 6.97E-05 6.41E-05 5.57E-06 0.501 3.10E-06 8.65E-06 3.06E-05 1.47E-05 2.53E-05 1.65E-05 5.10E-06 0.802 PND 21 Dam NA NA NA NA NA NA NA Male pup 9.73E-05 5.50E-05 5.71E-05 7.53E-05 5.60E-05 6.81E-05 8.19E-06 NA 8.19E-05 NA 1.17E-04 NA 9.08E-05 NA 1.10E-04 NA 1.20E-04 NA 1.04E-04 NA 7.54E-06 NA 0.012 -1881- Table 3: PCNA, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 2.39E-06 1.59E-06 2.01E-06 2.16E-06 1.83E-06 2.00E-06 1.37E-07 Fetus 5.75E-05 4.25E-05 3.23E-05 4.10E-05 3.94E-05 4.25E-05 4.12E-06 2.29E-06 1.60E-06 2.04E-06 1.99E-06 1.92E-06 1.97E-06 1.12E-07 0.878 4.07E-05 3.50E-05 2.41E-05 4.57E-05 4.47E-05 3.80E-05 3.96E-06 0.454 PND 21 Dam NA NA NA NA NA Male pup 8.09E-06 5.74E-06 9.23E-06 8.43E-06 9.33E-06 8.16E-06 6.51E-07 NA 5.96E-06 NA 1.27E-05 NA 5.84E-06 NA 7.95E-06 NA 8.42E-06 NA 8.18E-06 NA 1.25E-06 NA 0.990 Table 4: Malic Enzyme, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 6.01E-06 3.11E-06 2.82E-06 5.28E-06 2.70E-06 3.98E-06 6.90E-07 4.46E-06 4.27E-06 4.23E-06 7.92E-06 5.22E-06 9.02E-07 0.303 Fetus 7.77E-07 4.80E-07 6.03E-07 7.58E-07 7.24E-07 6.68E-07 5.59E-08 3.23E-07 4.57E-07 1.02E-06 6.86E-07 8.66E-07 6.71E-07 1.28E-07 0.984 PND 21 Dam NA NA NA NA NA NA NA Male pup 7.13E-06 2.65E-06 3.30E-06 5.39E-06 3.41E-06 4.38E-06 8.27E-07 NA 2.86E-06 NA 5.18E-06 NA 1.69E-06 NA 1.06E-05 NA 3.08E-06 NA 4.69E-06 NA 1.59E-06 NA 0.866 -1882- Table 5: Diol 1, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 7.94E-06 2.92E-06 4.16E-06 1.68E-06 4.18E-06 1.35E-06 Fetus 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 3.09E-06 3.02E-06 6.27E-06 3.17E-06 3.89E-06 7.95E-07 0.860 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 NA PND 21 Dam NA NA NA NA NA NA NA Male pup 1.08E-05 6.94E-06 9.08E-06 8.90E-06 6.92E-06 8.52E-06 7.31E-07 NA 6.47E-06 NA 8.02E-06 NA 8.89E-06 NA 1.04E-05 NA 9.30E-06 NA 8.62E-06 NA 6.60E-07 NA 0.927 Table 6: Por, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 5.51E-06 2.89E-06 2.87E-06 3.50E-06 1.85E-06 3.32E-06 6.08E-07 Fetus 3.28E-06 1.92E-06 2.54E-06 2.96E-06 3.54E-06 2.85E-06 2.88E-07 2.79E-06 2.28E-06 4.12E-06 4.72E-06 3.45E-06 3.47E-06 4.39E-07 0.847 2.33E-06 2.11E-06 2.59E-06 3.12E-06 2.94E-06 2.62E-06 1.87E-07 0.519 PND 21 Dam NA NA NA NA NA NA NA Male pup 1.18E-05 6.40E-06 1.01E-05 1.22E-05 1.39E-05 1.09E-05 1.28E-06 NA 8.55E-06 NA 8.59E-06 NA 1.91E-05 NA 1.49E-05 NA 2.33E-05 NA 1.49E-05 NA 2.90E-06 NA 0.242 -1883- Table 7: ApoA1, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 1.10E-03 7.47E-04 1.05E-03 9.21E-04 7.17E-04 9.07E-04 7.70E-05 Fetus 7.93E-04 5.40E-04 6.27E-04 8.92E-04 8.50E-04 7.41E-04 6.74E-05 8.80E-04 6.17E-04 1.28E-03 1.19E-03 1.00E-03 9.94E-04 1.18E-04 0.550 8.31E-04 7.91E-04 6.69E-04 7.94E-04 7.27E-04 7.62E-04 2.86E-05 0.774 PND 21 Dam NA NA NA NA NA NA NA Male pup 5.51E-04 2.58E-04 6.47E-04 5.38E-04 5.83E-04 5.15E-04 6.71E-05 NA 3.84E-04 NA 3.98E-04 NA 5.47E-04 NA 4.13E-04 NA 5.93E-04 NA 4.67E-04 NA 4.29E-05 NA 0.560 Table 8: Cyp1a1, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 2.54E-05 2.00E-05 2.04E-05 2.25E-05 1.59E-05 2.09E-05 1.57E-06 Fetus 4.18E-07 2.01E-07 3.24E-07 3.62E-07 2.68E-07 3.14E-07 3.76E-08 2.50E-05 1.67E-05 1.81E-05 2.14E-05 2.17E-05 2.06E-05 1.46E-06 0.902 6.75E-07 3.20E-07 2.94E-07 3.18E-07 3.46E-07 3.91E-07 7.15E-08 0.373 PND 21 Dam NA NA NA NA NA NA NA Male pup 7.10E-05 3.66E-05 5.49E-05 5.01E-05 4.36E-05 5.12E-05 5.81E-06 NA 6.73E-05 NA 4.42E-05 NA 5.00E-05 NA 5.73E-05 NA 9.47E-05 NA 6.27E-05 NA 8.89E-06 NA 0.313 -1884- Table 9: Cyp3a1, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 2.08E-05 3.17E-05 1.39E-05 2.74E-05 1.12E-05 2.10E-05 3.89E-06 Fetus 7.01E-06 1.29E-05 0.00E+00 0.00E+00 0.00E+00 3.98E-06 2.61E-06 2.99E-05 3.58E-05 3.87E-05 2.31E-05 1.92E-05 2.94E-05 3.67E-06 0.157 0.00E+00 0.00E+00 1.07E-05 0.00E+00 1.96E-06 2.53E-06 2.07E-06 0.675 PND 21 Dam NA NA NA NA NA NA NA Male pup 1.76E-04 1.14E-04 1.50E-04 1.07E-04 1.10E-04 1.31E-04 1.36E-05 NA 1.42E-04 NA 1.65E-04 NA 1.74E-04 NA 1.72E-04 NA 2.47E-04 NA 1.80E-04 NA 1.76E-05 NA 0.060 Table 10: Cyp4a1, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 7.19E-06 3.22E-06 3.60E-06 7.31E-06 5.81E-06 5.42E-06 8.66E-07 Fetus 1.10E-07 1.65E-07 2.94E-07 1.80E-07 5.51E-07 2.60E-07 7.87E-08 8.20E-06 3.71E-06 1.12E-05 7.53E-06 8.32E-06 7.79E-06 1.20E-06 0.148 2.05E-07 4.58E-07 6.90E-07 8.52E-07 1.69E-06 7.79E-07 2.53E-07 0.086 PND 21 Dam NA NA NA NA NA NA NA Male pup 4.29E-06 3.32E-06 2.92E-06 4.06E-06 3.98E-06 3.71E-06 2.56E-07 NA 5.85E-06 NA 5.88E-06 NA 6.88E-06 NA 8.43E-06 NA 1.13E-05 NA 7.66E-06 NA 1.02E-06 NA 0.006 -1885- Table 11: Cyp7a1, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 7.15E-06 6.89E-06 3.21E-06 8.30E-06 3.57E-06 5.82E-06 1.02E-06 Fetus 1.93E-06 3.19E-06 6.33E-06 4.20E-06 7.36E-06 4.60E-06 9.97E-07 2.79E-06 5.57E-06 9.71E-06 1.71E-06 9.64E-06 5.88E-06 1.67E-06 0.977 7.86E-07 3.63E-06 8.00E-06 3.80E-06 6.01E-06 4.45E-06 1.22E-06 0.923 PND 21 Dam NA NA NA NA NA NA NA Male pup 2.48E-05 2.18E-05 3.99E-05 3.54E-05 1.76E-05 2.79E-05 4.21E-06 NA 1.06E-05 NA 1.01E-05 NA 2.46E-06 NA 1.07E-05 NA 6.45E-06 NA 8.06E-06 NA 1.61E-06 NA 0.002 Table 12: Cyp2b2, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 4.31E-06 1.49E-06 2.61E-06 3.43E-06 1.05E-06 2.58E-06 6.01E-07 Fetus 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 6.94E-06 7.07E-06 7.25E-06 7.82E-06 7.43E-06 7.30E-06 1.54E-07 0.000 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 NA PND 21 Dam NA NA NA NA NA NA NA Male pup 3.54E-05 2.18E-05 2.36E-05 1.70E-05 1.33E-05 2.22E-05 3.75E-06 NA 3.39E-05 NA 4.25E-05 NA 2.02E-05 NA 4.89E-05 NA 4.93E-05 NA 3.90E-05 NA 5.46E-06 NA 0.035 -1886- Table 13: Ugt1A common, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 1.07E-06 7.05E-07 8.03E-07 1.15E-06 1.04E-06 9.55E-07 8.54E-08 Fetus 3.13E-06 2.12E-06 6.83E-06 5.72E-06 4.25E-06 4.41E-06 8.52E-07 9.43E-07 1.77E-06 1.67E-06 1.11E-06 1.28E-06 1.36E-06 1.60E-07 0.057 2.00E-05 1.18E-05 5.78E-06 2.30E-05 4.57E-06 1.30E-05 3.70E-06 0.053 PND 21 Dam NA NA NA NA NA NA NA Male pup 4.31E-06 5.12E-06 4.83E-06 4.39E-06 3.21E-06 4.37E-06 3.25E-07 NA 3.06E-06 NA 4.37E-06 NA 4.24E-06 NA 8.42E-06 NA 6.05E-06 NA 5.23E-06 NA 9.29E-07 NA 0.410 Table 14: Ugt1a1, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 1.42E-01 2.29E-01 1.95E-01 2.94E-01 3.25E-01 2.37E-01 3.31E-02 Fetus 9.49E-02 6.96E-02 1.29E-01 3.22E-01 1.60E-01 1.55E-01 4.43E-02 1.81E-01 3.53E-01 2.39E-01 2.77E-01 2.79E-01 2.66E-01 2.82E-02 0.531 4.41E-01 2.08E-01 4.47E-02 1.22E-01 8.82E-02 1.81E-01 7.03E-02 0.767 PND 21 Dam NA NA NA NA NA NA NA Male pup 5.24E-01 5.06E-01 5.71E-01 5.95E-01 5.94E-01 5.58E-01 1.84E-02 NA 5.46E-01 NA 4.33E-01 NA 6.60E-01 NA 6.94E-01 NA 8.78E-01 NA 6.42E-01 NA 7.47E-02 NA 0.307 -1887- Table 15: Ugt1a6, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 2.40E-06 6.82E-06 2.00E-06 1.98E-06 1.66E-06 2.97E-06 9.69E-07 Fetus 5.44E-05 4.39E-05 6.97E-05 6.84E-05 8.71E-05 6.47E-05 7.34E-06 1.41E-06 1.56E-06 2.39E-06 2.05E-06 3.35E-06 2.15E-06 3.47E-07 0.448 3.23E-05 4.84E-05 7.27E-05 6.10E-05 5.70E-05 5.43E-05 6.75E-06 0.327 PND 21 Dam NA NA NA NA NA NA NA Male pup 1.05E-05 1.20E-05 1.10E-05 2.13E-05 1.73E-05 1.44E-05 2.10E-06 NA 5.94E-06 NA 9.19E-06 NA 7.17E-06 NA 2.91E-05 NA 1.18E-05 NA 1.27E-05 NA 4.24E-06 NA 0.718 Table 16: Ugt2b, GD 20 and PND 21 (copies per 18s rRNA) Control Mean SE 1 mg/kgd Mean SE p-value GD 20 Dam 1.93E-04 1.97E-04 1.09E-04 1.30E-04 6.95E-05 1.40E-04 2.46E-05 Fetus 2.06E-05 1.55E-05 3.04E-05 2.31E-05 2.06E-05 2.20E-05 2.43E-06 1.16E-04 2.02E-05 1.13E-04 1.09E-04 1.13E-04 9.45E-05 1.86E-05 0.181 2.80E-05 2.53E-05 2.20E-05 2.97E-05 2.24E-05 2.55E-05 1.51E-06 0.266 PND 21 Dam NA NA NA NA NA NA NA Male pup 7.28E-05 3.19E-05 5.24E-05 3.73E-05 3.88E-05 4.67E-05 7.36E-06 NA 4.37E-05 NA 5.39E-05 NA 5.63E-05 NA 6.12E-05 NA 5.46E-05 NA 5.39E-05 NA 2.86E-06 NA 0.385 -1888- I hope you find these data useful. Sincerely, Kendall 6 . Wallace, Ph.D. Professor WIL-180017 3M Corporation -1889- MTDID 208 06-128 APPENDIX 59 Clinical Pathology Methods, Procedures And References WIL 180017 3M Corporation -1890- MTDID 208 06 128 CLINICAL PATHOLOGY METHODS, PROCEDURES AND REFERENCES Immunoassay-GAMMA-C12 Gamma Counter Rat Thyroid Stimulating Hormone (rTSH) - 125I assay system with magnetic separation for the quantitative measurement of (rTSH). DPC GAMMA C-12 gamma counter. BiotrakTM rat thyroid stimulating hormone 125I assay system. Amersham Pharmacia Biotech. Package insert. WIL-180017 3M Corporation -1891- MTDID 208 06-128 APPENDIX 60 Statistical Analysis Report (BioSTAT Consultants, Inc.) -1892- Statistical Analysis Summary WIL Research Laboratories, LLC Study Protocol - 180017 Version 2.0 1 Statistical Methodology 1,1 Analysis Endpoints 1.2 Motor Activity Analysis Methodology 1.3 Startle Response Analysis Methodology 1.4 B i d Maze Analysis Methodology 2 Results Table 2.I : Summary of Statistically Significant Dose Group Findings 3 Statistical Analysis Srunmaries Table 3.I : Analysis Summary Table for Motor Activity Table 3.2: Analysis Summary Table for Startle Response Table 3.3: Analysis Summary Table for Biel M x ~ e Report Approval: /? 3261 Lost Pine Way Portage, MI 49024 (269) 329-7976 Date - t- -1893- 2 BioSTAT Consultants, Inc. Statement of Quality Control This report was quality checked in accordance with BioSTAT Procedural Guideline 2.1 (Quality Control Process for Tables and Reports). The statistical methodology and results of inferential statistics were verified by an independent quality control statistician. Based on these documented quality control activities, it is concluded that the statistical results incorporated in this report accurately reflect the statistical analysis of data received by BioSTAT. -1894- 3 1 Statistical Methodology 1.1 Analysis Endpoints Motor Activity o Total Count Startle Response o VMAX o TMAX Biel Maze o Errors o Escape Time 1.2 Motor Activity Analysis Methodology Total counts were analyzed, by sex and session, with a repeated measure analysis of variance (RANOVA). Factors in the model included treatment group (TRT), time interval (TIME), and the interaction of time interval and treatment group (TRT*TIME). The SAS procedure PROC MIXED was used for analysis with the random effect of animal included as the repeated measurement. The covariance structure across time was selected by comparing Akaike's Information Criterion (AIC) for first-order autoregressive homogeneous [AR(1)] and compound symmetric (CS) structures. The monotonic dose response relationship was evaluated using sequential linear trend tests based on ordinal spacing of dose levels. The linear dose by time interaction (LinTrt*Time) was evaluated and, if significant at the 0.05 level, trend tests on treatment means were performed at the 0.05 level for each time interval. If the linear dose by time interaction was not significant, the trend test was conducted across the pooled time intervals of the entire session only. Nonmonotonic dose responses were evaluated whenever no significant linear trends were detected but TRT and/or TRT*TIME interaction was significant at the 0.01 level. Within the framework of the RANOVA, pairwise comparisons were made for each individual treated group with the control group through linear contrasts. If TRT* TIME was significant, the comparisons were conducted for each time interval. If only the TRT effect was significant, the comparisons were conducted across the pooled time intervals of the entire session. These nonmonotonic dose response comparisons were conducted at the 0.01 significance level. 1.3 Startle Response Analysis Methodology Tmax and Vmax were analyzed, by sex and session, with a repeated measure analysis of variance (RANOVA). Factors in the model included treatment group (TRT), trial block (TRIAL), and the interaction of trial block and treatment group (TRT*TRIAL). The SAS procedure PROC MIXED was used for analysis with the random effect of animal included as the repeated measurement. The covariance structure across time was selected by comparing Akaike's Information Criterion (AIC) for first-order autoregressive homogeneous [AR(1)] and compound symmetric (CS) structures. -1895- 4 The monotonic dose response relationship was evaluated using sequential linear trend tests based on ordinal spacing of dose levels. The linear dose by trial interaction (LinTrt*Trial) was evaluated and, if significant at the 0.05 level, trend tests on treatment means were performed at the 0.05 level for each block of trials. If the linear dose by trial interaction was not significant, the trend test was conducted across the pooled trials of the entire session only. Nonmonotonic dose responses were evaluated whenever no significant linear trends were detected but TRT and/or TRT*TRIAL interaction was significant at the 0.01 level. Within the framework of the RANOVA, pairwise comparisons were made for each individual treated group with the control group through linear contrasts. If TRT*TRIAL was significant, the comparisons were conducted for each block of trials. If only the TRT effect was significant, the comparisons were conducted across the pooled trials of the entire session. These nonmonotonic dose response comparisons were conducted at the 0.01 significance level. 1.4 Biel Maze Analysis Methodology Time to escape and number of errors were analyzed, by sex, with a repeated measure analysis of variance (RANOVA). Factors in the model included treatment group (TRT), TRIAL, and the interaction of trial and treatment group (TRT*TRIAL). The SAS procedure PROC MIXED was used for analysis with the random effect of animal included as the repeated measurement. The covariance structure across time was selected by comparing Akaike's Information Criterion (AIC) for first-order autoregressive homogeneous [AR(1)] and compound symmetric (CS) structures. The monotonic dose response relationship was evaluated using sequential linear trend tests based on ordinal spacing of dose levels. The linear dose by trial interaction (LinTRT*TRIAL) was evaluated and, if significant at the 0.05 level, trend tests on treatment means were performed at the 0.05 level for each trial. If the linear dose by trial interaction was not significant, the trend test was conducted across the pooled trials of the entire phase only. Nonmonotonic dose responses were evaluated whenever no significant linear trends were detected but TRT and/or TRT*TRIAL interaction was significant at the 0.01 level. Within the framework of the RANOVA, pairwise comparisons were made for each individual treated group with the control group through linear contrasts. If TRT*TRIAL was significant, the comparisons were conducted for each trial. If only the TRT effect was significant, the comparisons were conducted across the pooled trials of the entire phase. These nonmonotonic dose response comparisons were conducted at the 0.01 significance level. All statistical analyses were conducted using SAS version 8.2 (SAS Institute, Inc., 19992001) software. -1896- 2 Results Results of statistical analyses are summarized in Section 3. statistically significant dose group findings. 5 Table 2.1 summarizes the Table 2.1: Summary of Statistically Significant Dose Group Findings Motor Activity Minutes Period Sex Endpoint 0-15 16-30 31-45 46-60 Overall PND013 M Total F Total PND017 M Total F Total PND021 M Total F Total PND061 M Total F Total () Dose-related increase (decrease) through 1.0 mg/kg/day ()Dose-related increase (decrease) through 0.3 mg/kg/day Startle Response No statistically significant dose group findings. Biel Maze No statistically significant dose group findings. -1897- 6 Tables Legend Motor Activity: For each analysis endpoint (study period/sex/endpoint), data are summarized by treatment group for each post-dose time interval, overall (mean across post-dose time intervals), and cumulative across post-dose time intervals. P-values for interaction terms are shown at the bottom of the table. If LinTrt*Time was not significant, sequential trend testing (described below) was conducted across the pooled time intervals only and the p-values are reported in the "Overall" row. "NT" (not tested) is reported for the p-value in the individual time interval rows. If LinTrt*Time was significant, sequential trend testing was conducted for each individual time interval as well as across the pooled time intervals. P-values are reported in the individual time interval and "Overall" rows. Startle Response, Biel Water Maze: Data are summarized as described above for motor activity with the exception that trials replace time intervals and there is no cumulative summary. Sequential trend tests: All dose groups are included in an initial trend test. If the trend test is not significant it is concluded that there is no significant dose-related trend and no further testing is conducted. If the trend test is significant, the highest dose group is flagged as significant and a trend test is conducted excluding the highest dose group. The sequence of trend tests continues until a test is not significant or the lowest nonzero dose is flagged as significant. Table Key S.D. = standard deviation N = number of animals %Difference Control = group mean percent difference from control LSMean = least squares mean Linear Trend p-value = p-value for the treatment linear trend test Trt F-test p-value = p-value for treatment group effect INTN = treatment dose by time interactions tested Trt*Time p-value = p-value for the treatment by time interaction LinTrt*Time p-value = p-value for the linear trend by time interaction Trt*Trial p-value = p-value for the treatment by trial interaction LinTrt*Trial p-value = p-value for the linear trend by trial interaction Covariance Structure: AR1=Autoregressive order 1, CS=Compound symmetric References SAS Proprietary Software, Version 8.2; SAS Institute Inc.: Cary, NC, 1999-2001. 7 3 Statistical Analysis Summaries Table 3.1: Analysis Summary Table for Motor Activity Period Sex Variable Minutes Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND013 M TOTAL 0-15 Mean % Difference Control S.D. Linear Trend p-value# 110 NA 60.6 170 54.5 172.2 NT 128 16.4 190.0 NT 130 18.2 155.8 NT 16-30 Mean % Difference Control S.D. Linear Trend p-value# 67 NA 75.0 139 107.5 117.8 NT 111 65.7 250.6 NT 95 41.8 113.1 NT 31-45 Mean S.D. Linear Trend p-value# 89 160.0 60 90.3 NT 62 103.8 NT 39 58.4 NT 46-60 Mean S.D. Linear Trend p-value# 67 107.9 124 213.7 NT 97 192.7 NT 89 153.5 NT Overall Mean S.D. Linear Trend p-value# 83 123 NA NA NT 99 88 NA NA NT 0.938 Cumulative Mean % Difference Control S.D. N 333 NA 336.3 20 493 48.0 351.8 20 398 19.5 522.2 20 353 6.0 377.0 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.663 0.571 0.420 AR1 -1898- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 8 Table 3.1: Analysis Summary Table for Motor Activity Period Sex Variable Minutes Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND013 F TOTAL 0-15 Mean % Difference Control S.D. Linear Trend p-value# 115 NA 107.9 225 95.7 244.9 NT 129 12.2 180.2 NT 102 -11.3 73.1 NT 16-30 Mean % Difference Control S.D. Linear Trend p-value# 92 NA 94.3 206 123.9 284.3 NT 108 17.4 139.1 NT 81 -12.0 129.7 NT 31-45 Mean S.D. Linear Trend p-value# 59 100.6 190 258.1 NT 126 145.7 NT 96 168.2 NT 46-60 Mean S.D. Linear Trend p-value# 78 140.3 174 271.4 NT 74 98.5 NT 113 216.4 NT Overall Mean S.D. Linear Trend p-value# 86 199 109 98 NA NA NA NA NT NT 0.702 Cumulative Mean % Difference Control S.D. N 343 NA 263.0 20 795 131.8 904.3 20 437 27.4 430.9 20 392 14.3 391.7 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.047 0.913 0.730 AR1 -1899- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 9 Table 3.1: Analysis Summary Table for Motor Activity Period Sex Variable Minutes Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND017 M TOTAL 0-15 Mean % Difference Control S.D. Linear Trend p-value# 471 NA 317.8 605 28.5 326.4 NT 732 55.4 387.9 NT 383 -18.7 315.0 0.643 16-30 Mean % Difference Control S.D. Linear Trend p-value# 208 NA 199.2 225 8.2 215.3 0.858 410 97.1 262.2 0.031* 370 77.9 333.9 0.023* 31-45 Mean S.D. Linear Trend p-value# 184 208.8 222 256.4 NT 352 265.9 0.071 427 393.8 0.004* 46-60 Mean S.D. Linear Trend p-value# 108 203.9 240 251.1 NT 273 246.4 0.076 354 326.4 0.009* Overall Mean S.D. Linear Trend p-value# 243 323 442 383 NA NA NA NA 0.299 0.012* 0.030* Cumulative Mean % Difference Control S.D. N 971 NA 772.8 20 1293 33.2 832.6 20 1766 81.9 932.3 20 1534 58.0 1200.5 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.071 <0.001* 0.002* AR1 -1900- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 10 Table 3.1: Analysis Summary Table for Motor Activity Period Sex Variable Minutes Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND017 F TOTAL 0-15 Mean % Difference Control S.D. Linear Trend p-value# 544 NA 351.6 607 11.6 208.9 NT 580 6.6 306.9 NT 559 2.8 376.0 NT 16-30 Mean % Difference Control S.D. Linear Trend p-value# 271 NA 224.2 247 -8.9 241.7 NT 345 27.3 273.4 NT 371 36.9 271.8 NT 31-45 Mean S.D. Linear Trend p-value# 147 183.4 254 312.4 NT 316 248.5 NT 353 273.2 NT 46-60 Mean S.D. Linear Trend p-value# 124 185.2 236 304.9 NT 291 248.7 NT 303 330.2 NT Overall Mean 271 336 383 397 S.D. NA NA NA NA Linear Trend p-value# NT NT 0.074 Cumulative Mean % Difference Control S.D. N 1085 NA 668.1 20 1344 23.9 914.4 20 1532 41.2 924.5 20 1587 46.3 1109.6 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.324 0.295 0.147 AR1 -1901- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 11 Table 3.1: Analysis Summary Table for Motor Activity Period Sex Variable Minutes Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND021 M TOTAL 0-15 Mean % Difference Control S.D. Linear Trend p-value# 455 NA 144.9 547 20.2 158.2 NT 513 12.7 136.5 NT 574 26.2 195.1 NT 16-30 Mean % Difference Control S.D. Linear Trend p-value# 93 NA 115.3 157 68.8 181.0 NT 129 38.7 126.6 NT 128 37.6 207.5 NT 31-45 Mean S.D. Linear Trend p-value# 63 63.0 106 154.0 NT 49 86.4 NT 100 192.6 NT 46-60 Mean S.D. Linear Trend p-value# 35 74.1 72 108.1 NT 58 109.1 NT 122 239.7 NT Overall Mean 162 221 187 231 S.D. NA NA NA NA Linear Trend p-value# NT NT 0.162 Cumulative Mean % Difference Control S.D. N 646 NA 263.0 20 882 36.5 483.6 20 748 15.8 328.7 20 924 43.0 763.6 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.275 0.365 0.112 AR1 -1902- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 12 Table 3.1: Analysis Summary Table for Motor Activity Period Sex Variable Minutes Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND021 F TOTAL 0-15 Mean % Difference Control S.D. Linear Trend p-value# 505 NA 128.5 479 -5.1 119.5 NT 563 11.5 169.5 NT 566 12.1 170.8 NT 16-30 Mean % Difference Control S.D. Linear Trend p-value# 136 NA 184.1 143 5.1 128.3 NT 104 -23.5 111.1 NT 228 67.6 164.7 NT 31-45 Mean S.D. Linear Trend p-value# 29 49.7 63 76.7 NT 105 130.3 NT 91 154.0 NT 46-60 Mean S.D. Linear Trend p-value# 71 111.9 35 69.2 NT 64 106.0 NT 93 163.3 NT Overall Mean 185 180 209 245 S.D. NA NA NA NA Linear Trend p-value# NT 0.413 0.027* Cumulative Mean % Difference Control S.D. N 740 NA 367.2 20 720 -2.7 250.9 20 836 13.0 345.2 20 979 32.3 512.3 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.114 0.020 0.735 AR1 -1903- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 13 Table 3.1: Analysis Summary Table for Motor Activity Period Sex Variable Minutes Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND061 M TOTAL 0-15 Mean % Difference Control S.D. Linear Trend p-value# 1296 NA 243.7 1375 6.1 217.9 NT 1397 7.8 295.7 NT 1306 0.8 186.8 NT 16-30 Mean % Difference Control S.D. Linear Trend p-value# 626 NA 261.6 572 -8.6 172.4 NT 582 -7.0 277.8 NT 591 -5.6 291.0 NT 31-45 Mean S.D. Linear Trend p-value# 325 248.5 402 220.9 NT 373 249.8 NT 349 253.4 NT 46-60 Mean S.D. Linear Trend p-value# 235 278.3 303 208.0 NT 276 250.7 NT 284 175.0 NT Overall Mean 621 663 657 632 S.D. NA NA NA NA Linear Trend p-value# NT NT 0.872 Cumulative Mean % Difference Control S.D. N 2483 NA 818.4 20 2652 6.8 624.4 20 2628 5.8 884.5 20 2529 1.9 567.1 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.856 0.555 0.857 AR1 -1904- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 14 Table 3.1: Analysis Summary Table for Motor Activity Period Sex Variable Minutes Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND061 F TOTAL 0-15 Mean % Difference Control S.D. Linear Trend p-value# 1198 NA 211.4 1161 -3.1 211.0 NT 1163 -2.9 246.4 NT 1217 1.6 198.3 NT 16-30 Mean % Difference Control S.D. Linear Trend p-value# 535 NA 198.9 533 -0.4 197.4 NT 458 -14.4 199.0 NT 585 9.3 156.0 NT 31-45 Mean S.D. Linear Trend p-value# 329 209.9 407 223.1 NT 318 246.7 NT 361 207.6 NT 46-60 Mean S.D. Linear Trend p-value# 255 230.8 262 186.3 NT 186 169.5 NT 248 183.3 NT Overall Mean 579 591 531 603 S.D. NA NA NA NA Linear Trend p-value# NT NT 0.937 Cumulative Mean % Difference Control S.D. N 2316 NA 612.5 20 2364 2.1 587.9 20 2124 -8.3 653.7 20 2412 4.1 592.1 20 Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure 0.472 0.777 0.869 CS -1905- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 15 Table 3.2: Analysis Summary Table for Startle Response Period Variable Sex Blocks Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND020 VMAX M 1-10 Mean % Difference Control S.D. Linear Trend p-value# 188.3 NA 69.33 165.5 -12.1 59.04 NT 161.3 -14.3 55.70 NT 162.7 -13.6 68.57 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 164.0 NA 71.58 141.3 -13.8 48.86 NT 142.8 -12.9 55.56 NT 134.2 -18.2 70.14 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 148.4 NA 55.98 130.2 -12.3 56.55 NT 140.6 -5.3 63.72 NT 116.8 -21.3 68.73 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 123.1 NA 49.89 139.6 13.4 47.81 NT 143.1 16.2 59.29 NT 115.6 -6.1 62.87 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 133.3 NA 61.01 129.5 -2.9 49.37 NT 137.4 3.1 47.86 NT 121.0 -9.2 63.22 NT Overall Mean S.D. N Linear Trend p-value# 151.4 NA 20 141.2 NA 20 NT 145.0 NA 20 NT 130.1 NA 20 0.226 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.578 0.374 0.627 AR1 -1906- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 16 Table 3.2: Analysis Summary Table for Startle Response Period Variable Sex Blocks Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND020 VMAX F 1-10 Mean % Difference Control S.D. Linear Trend p-value# 200.8 NA 77.89 185.8 -7.5 58.51 NT 169.5 -15.6 75.43 NT 173.6 -13.5 72.22 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 178.3 NA 72.32 163.1 -8.5 67.72 NT 159.8 -10.4 66.95 NT 140.8 -21.0 67.49 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 163.3 NA 74.00 145.2 -11.1 70.10 NT 163.3 0.0 71.98 NT 128.0 -21.6 62.63 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 168.5 NA 68.86 142.7 -15.3 59.87 NT 152.5 -9.5 73.89 NT 120.6 -28.4 63.85 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 147.4 NA 52.11 140.4 -4.7 70.27 NT 126.8 -14.0 67.83 NT 134.1 -9.0 67.19 NT Overall Mean S.D. N Linear Trend p-value# 171.7 NA 20 155.4 NA 20 NT 154.4 NA 20 NT 139.4 NA 20 0.073 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.314 0.511 0.530 AR1 -1907- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 17 Table 3.2: Analysis Summary Table for Startle Response Period Variable Sex Blocks Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND020 TMAX M 1-10 Mean % Difference Control S.D. Linear Trend p-value# 26.3 NA 3.77 27.7 5.3 4.96 NT 26.2 -0.4 3.90 NT 26.5 0.8 5.21 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 24.3 NA 4.01 23.9 -1.6 4.13 NT 23.7 -2.5 3.84 NT 25.1 3.3 4.24 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 24.5 NA 4.06 25.1 2.4 5.68 NT 23.7 -3.3 4.29 NT 26.4 7.8 5.03 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 24.3 NA 3.64 24.0 -1.2 4.04 NT 23.0 -5.3 2.86 NT 22.9 -5.8 3.18 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 25.5 NA 5.82 24.0 -5.9 3.96 NT 25.0 -2.0 4.93 NT 24.2 -5.1 4.24 NT Overall Mean S.D. N Linear Trend p-value# 25.0 NA 20 24.9 NA 20 NT 24.3 NA 20 NT 25.0 NA 20 0.856 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.852 0.430 0.299 AR1 -1908- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 18 Table 3.2: Analysis Summary Table for Startle Response Period Variable Sex Blocks Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND020 TMAX F 1-10 Mean % Difference Control S.D. Linear Trend p-value# 26.5 NA 6.62 26.1 -1.5 3.95 NT 24.9 -6.0 4.78 NT 26.5 0.0 4.71 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 22.7 NA 2.61 23.8 4.8 2.87 NT 22.3 -1.8 2.65 NT 24.5 7.9 4.96 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 22.6 NA 2.69 23.6 4.4 3.99 NT 22.8 0.9 5.00 NT 23.6 4.4 5.02 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 22.0 NA 2.00 24.2 10.0 3.71 NT 22.3 1.4 2.83 NT 24.3 10.5 4.85 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 23.7 NA 5.11 23.7 0.0 3.45 NT 24.4 3.0 4.67 NT 24.1 1.7 4.53 NT Overall Mean S.D. N Linear Trend p-value# 23.5 NA 20 24.3 NA 20 NT 23.3 NA 20 NT 24.6 NA 20 0.391 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.392 0.741 0.776 AR1 -1909- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 19 Table 3.2: Analysis Summary Table for Startle Response Period Variable Sex Blocks Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND060 VMAX M 1-10 Mean % Difference Control S.D. Linear Trend p-value# 246.3 NA 294.08 136.9 -44.4 129.08 NT 162.6 -34.0 113.35 NT 149.6 -39.3 93.03 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 194.7 NA 215.91 112.3 -42.3 91.82 NT 151.7 -22.1 117.82 NT 108.5 -44.3 95.35 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 177.5 NA 236.83 97.6 -45.0 80.75 NT 123.2 -30.6 90.15 NT 79.7 -55.1 66.70 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 142.7 NA 157.72 96.0 -32.7 92.18 NT 95.4 -33.1 67.05 NT 86.0 -39.7 82.05 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 108.2 NA 112.74 101.1 -6.6 110.10 NT 113.1 4.5 90.60 NT 70.8 -34.6 69.90 NT Overall Mean S.D. N Linear Trend p-value# 173.9 NA 20 108.8 NA 20 NT 129.2 NA 20 NT 98.9 NA 20 0.096 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.221 0.349 0.528 AR1 -1910- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 20 Table 3.2: Analysis Summary Table for Startle Response Period Variable Sex Blocks Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND060 VMAX F 1-10 Mean % Difference Control S.D. Linear Trend p-value# 117.0 NA 62.93 83.7 -28.5 29.45 NT 92.9 -20.6 52.65 NT 75.5 -35.5 61.68 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 73.1 NA 54.88 60.6 -17.1 28.02 NT 69.7 -4.7 36.89 NT 53.1 -27.4 52.79 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 59.5 NA 30.86 56.3 -5.4 41.41 NT 56.1 -5.7 32.53 NT 46.7 -21.5 33.15 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 51.2 NA 28.27 46.9 -8.4 33.49 NT 58.1 13.5 33.32 NT 52.2 2.0 43.54 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 52.5 NA 28.25 54.0 2.9 35.21 NT 65.0 23.8 49.19 NT 56.2 7.0 56.70 NT Overall Mean S.D. N Linear Trend p-value# 70.6 NA 20 60.3 NA 20 NT 68.4 NA 20 NT 56.8 NA 20 0.323 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.524 0.509 0.116 AR1 -1911- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 21 Table 3.2: Analysis Summary Table for Startle Response Period Variable Sex Blocks Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND060 TMAX M 1-10 Mean % Difference Control S.D. Linear Trend p-value# 32.0 NA 6.30 34.2 6.9 8.36 NT 32.9 2.8 7.78 NT 32.0 0.0 6.22 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 32.7 NA 9.10 35.4 8.3 8.68 NT 33.1 1.2 7.70 NT 34.0 4.0 10.57 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 31.5 NA 6.08 35.3 12.1 8.58 NT 32.6 3.5 8.15 NT 36.9 17.1 9.84 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 33.9 NA 7.68 36.6 8.0 9.41 NT 31.1 -8.3 8.04 NT 36.4 7.4 9.54 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 35.9 NA 10.06 35.4 -1.4 7.88 NT 35.4 -1.4 9.12 NT 34.2 -4.7 9.37 NT Overall Mean S.D. N Linear Trend p-value# 33.2 NA 20 35.4 NA 20 NT 33.0 NA 20 NT 34.7 NA 20 0.743 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.566 0.364 0.318 CS -1912- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 22 Table 3.2: Analysis Summary Table for Startle Response Period Variable Sex Blocks Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND060 TMAX F 1-10 Mean % Difference Control S.D. Linear Trend p-value# 31.6 NA 5.06 34.2 8.2 7.60 NT 34.9 10.4 7.72 NT 36.1 14.2 6.67 NT 11-20 Mean % Difference Control S.D. Linear Trend p-value# 34.8 NA 6.70 35.8 2.9 5.83 NT 36.3 4.3 7.28 NT 34.4 -1.1 8.47 NT 21-30 Mean % Difference Control S.D. Linear Trend p-value# 37.1 NA 5.04 33.2 -10.5 6.54 NT 34.5 -7.0 6.82 NT 35.8 -3.5 8.21 NT 31-40 Mean % Difference Control S.D. Linear Trend p-value# 35.6 NA 7.86 37.3 4.8 7.62 NT 36.1 1.4 8.41 NT 35.7 0.3 10.35 NT 41-50 Mean % Difference Control S.D. Linear Trend p-value# 36.0 NA 6.27 36.9 2.5 7.52 NT 37.4 3.9 10.22 NT 35.9 -0.3 9.60 NT Overall Mean S.D. N Linear Trend p-value# 35.0 NA 20 35.5 NA 20 NT 35.8 NA 20 NT 35.6 NA 20 0.702 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.968 0.460 0.314 CS -1913- --------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 23 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M A LEARNING ESCTIME 1 Mean % Difference S.D. N Linear Trend Control p-value# 78.73 NA 56.080 20 79.27 0.7 58.459 20 NT 71.50 -9.2 53.639 20 NT 79.80 1.4 61.173 20 NT 2 Mean 58.52 66.73 66.14 69.35 % Difference Control NA 14.0 13.0 18.5 S.D. 40.115 44.377 41.239 49.673 N 20 20 20 20 Linear Trend p-value# NT NT NT 3 Mean 54.05 54.33 34.71 43.96 % Difference Control NA 0.5 -35.8 -18.7 S.D. 48.823 47.220 21.907 43.665 N 20 20 20 20 Linear Trend p-value# NT NT NT 4 Mean 52.80 38.34 37.71 40.11 % Difference Control NA -27.4 -28.6 -24.0 S.D. 45.443 38.436 28.372 42.615 N 20 20 20 19 Linear Trend p-value# NT NT NT Overall Mean S.D. N Linear Trend p-value# 61.03 NA 20 59.67 NA 20 NT 52.51 NA 20 NT 58.23 NA 20 0.556 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.748 0.924 0.557 AR1 -1914- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 24 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M A LEARNING ERRORS 1 Mean % Difference S.D. N Linear Trend Control p-value# 15 NA 10.8 20 14 -6.7 10.2 20 NT 13 -13.3 11.2 20 NT 16 6.7 13.2 20 NT 2 Mean 13 15 14 15 % Difference Control NA 15.4 7.7 15.4 S.D. 10.5 11.7 10.5 13.4 N 20 20 20 20 Linear Trend p-value# NT NT NT 3 Mean 14 12 8 10 % Difference Control NA -14.3 -42.9 -28.6 S.D. 15.1 12.2 6.9 12.7 N 20 20 20 20 Linear Trend p-value# NT NT NT 4 Mean 12 7 9 8 % Difference Control NA -41.7 -25.0 -33.3 S.D. 11.6 9.5 8.7 10.1 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean 13 12 11 12 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.513 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.740 0.829 0.513 AR1 -1915- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 25 -1916- Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M B LEARNING ESCTIME 5 Mean % Difference S.D. N Linear Trend Control p-value# 137.70 NA 52.358 20 148.40 7.8 45.579 20 NT 145.03 5.3 53.498 20 NT 153.62 11.6 55.325 20 NT 6 Mean 136.05 140.71 120.70 114.06 % Difference Control NA 3.4 -11.3 -16.2 S.D. 58.799 53.137 66.215 57.104 N 20 20 20 20 Linear Trend p-value# NT NT NT 7 Mean 144.25 129.48 132.08 125.58 % Difference Control NA -10.2 -8.4 -12.9 S.D. 51.920 57.075 56.344 61.184 N 20 20 20 20 Linear Trend p-value# NT NT NT 8 Mean 108.69 109.13 71.50 83.68 % Difference Control NA 0.4 -34.2 -23.0 S.D. 67.266 67.274 55.902 60.728 N 20 20 20 20 Linear Trend p-value# NT NT NT 9 Mean 83.67 102.52 66.82 87.01 % Difference Control NA 22.5 -20.1 4.0 S.D. 60.977 68.748 61.737 67.916 N 20 20 20 20 Linear Trend p-value# NT NT NT 10 Mean 63.49 70.42 72.30 63.87 % Difference Control NA 10.9 13.9 0.6 S.D. 58.001 56.758 67.910 51.948 N 20 20 20 20 Linear Trend p-value# NT NT NT ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 26 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M B LEARNING ESCTIME Overall Mean S.D. N Linear Trend p-value# 112.31 NA 20 116.77 NA 20 NT 101.40 NA 20 NT 104.64 NA 20 0.299 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.535 0.610 0.267 CS -1917- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 27 -1918- Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M B LEARNING ERRORS 5 Mean % Difference S.D. N Linear Trend Control p-value# 31 NA 12.6 20 31 32 34 0.0 3.2 9.7 9.2 12.6 14.9 20 20 20 NT NT NT 6 Mean 29 29 25 25 % Difference Control NA 0.0 -13.8 -13.8 S.D. 13.9 13.0 14.7 13.7 N 20 20 20 20 Linear Trend p-value# NT NT NT 7 Mean 32 28 31 28 % Difference Control NA -12.5 -3.1 -12.5 S.D. 12.1 13.8 13.8 14.0 N 20 20 20 20 Linear Trend p-value# NT NT NT 8 Mean 23 23 17 19 % Difference Control NA 0.0 -26.1 -17.4 S.D. 13.6 14.0 14.7 15.1 N 20 20 20 20 Linear Trend p-value# NT NT NT 9 Mean 19 23 15 19 % Difference Control NA 21.1 -21.1 0.0 S.D. 15.7 17.4 16.3 16.1 N 20 20 20 20 Linear Trend p-value# NT NT NT 10 Mean 14 15 17 14 % Difference Control NA 7.1 21.4 0.0 S.D. 13.0 14.7 18.5 14.6 N 20 20 20 20 Linear Trend p-value# NT NT NT ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 28 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M B LEARNING ERRORS Overall Mean 25 25 23 23 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.384 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.802 0.868 0.641 CS -1919- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 29 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M A MEMORY ESCTIME 11 Mean % Difference S.D. N Linear Trend Control p-value# 74.70 NA 48.210 20 74.98 0.4 49.299 20 NT 83.29 11.5 44.296 20 NT 85.93 15.0 52.157 20 NT 12 Mean 44.38 69.61 51.43 63.17 % Difference Control NA 56.8 15.9 42.3 S.D. 43.708 51.904 34.062 50.376 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean S.D. N Linear Trend p-value# 59.54 NA 20 72.29 NA 20 NT 67.36 NA 20 NT 74.55 NA 20 0.307 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.629 0.372 0.943 CS -1920- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 30 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 M A MEMORY ERRORS 11 Mean % Difference S.D. N Linear Trend Control p-value# 21 NA 16.9 20 21 0.0 15.9 20 NT 24 14.3 13.1 20 NT 25 19.0 16.7 20 NT 12 Mean 11 17 14 16 % Difference Control NA 54.5 27.3 45.5 S.D. 14.4 13.5 13.3 16.2 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean 16 19 19 21 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.231 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.650 0.684 0.962 CS -1921- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 31 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F A LEARNING ESCTIME 1 Mean % Difference S.D. N Linear Trend Control p-value# 63.95 NA 45.821 20 81.98 28.2 65.243 20 NT 50.31 -21.3 31.568 20 NT 74.55 16.6 56.967 20 NT 2 Mean 71.55 86.16 56.21 80.65 % Difference Control NA 20.4 -21.4 12.7 S.D. 55.083 57.290 42.679 46.187 N 20 20 20 20 Linear Trend p-value# NT NT NT 3 Mean 61.46 56.72 41.02 67.92 % Difference Control NA -7.7 -33.3 10.5 S.D. 42.016 42.111 31.033 59.104 N 20 20 20 20 Linear Trend p-value# NT NT NT 4 Mean 39.80 43.15 31.69 47.24 % Difference Control NA 8.4 -20.4 18.7 S.D. 39.740 41.878 22.442 45.762 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean S.D. N Linear Trend p-value# 59.19 NA 20 67.00 NA 20 NT 44.81 NA 20 NT 67.59 NA 20 0.912 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.033 0.983 0.997 AR1 -1922- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 32 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F A LEARNING ERRORS 1 Mean % Difference S.D. N Linear Trend Control p-value# 13 NA 10.7 20 14 7.7 12.9 20 NT 10 -23.1 7.7 20 NT 15 15.4 11.5 20 NT 2 Mean 16 18 12 17 % Difference Control NA 12.5 -25.0 6.3 S.D. 14.2 12.3 9.8 11.4 N 20 20 20 20 Linear Trend p-value# NT NT NT 3 Mean 14 12 9 16 % Difference Control NA -14.3 -35.7 14.3 S.D. 11.7 10.0 8.5 16.0 N 20 20 20 20 Linear Trend p-value# NT NT NT 4 Mean 8 9 6 10 % Difference Control NA 12.5 -25.0 25.0 S.D. 12.7 11.2 7.0 9.6 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean 13 13 9 14 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.967 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.065 0.990 0.992 AR1 -1923- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 33 -1924- Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F B LEARNING ESCTIME 5 Mean % Difference S.D. N Linear Trend Control p-value# 154.84 NA 47.173 20 156.05 0.8 43.725 20 NT 157.72 1.9 46.628 20 NT 145.74 -5.9 51.625 20 NT 6 Mean 150.22 123.50 139.91 149.06 % Difference Control NA -17.8 -6.9 -0.8 S.D. 41.379 65.560 61.655 56.800 N 20 20 20 20 Linear Trend p-value# NT NT NT 7 Mean 134.72 119.20 117.25 116.94 % Difference Control NA -11.5 -13.0 -13.2 S.D. 57.907 68.931 67.598 67.633 N 20 20 20 20 Linear Trend p-value# NT NT NT 8 Mean 114.50 97.79 97.85 95.40 % Difference Control NA -14.6 -14.5 -16.7 S.D. 62.597 64.979 71.613 64.422 N 20 20 20 20 Linear Trend p-value# NT NT NT 9 Mean 113.10 80.64 75.29 90.47 % Difference Control NA -28.7 -33.4 -20.0 S.D. 67.774 62.479 64.213 65.982 N 20 20 20 20 Linear Trend p-value# NT NT NT 10 Mean 91.00 72.21 64.07 63.60 % Difference Control NA -20.6 -29.6 -30.1 S.D. 65.705 61.696 52.824 60.844 N 20 20 20 20 Linear Trend p-value# NT NT NT ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 34 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F B LEARNING ESCTIME Overall Mean S.D. N Linear Trend p-value# 126.40 NA 20 108.23 NA 20 NT 108.68 NA 20 NT 110.20 NA 20 0.171 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.296 0.945 0.866 AR1 -1925- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 35 -1926- Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F B LEARNING ERRORS 5 Mean % Difference S.D. N Linear Trend Control p-value# 33 NA 11.5 20 32 -3.0 9.3 20 NT 33 0.0 10.3 20 NT 32 -3.0 14.0 20 NT 6 Mean 30 24 29 33 % Difference Control NA -20.0 -3.3 10.0 S.D. 9.3 13.9 15.6 13.4 N 20 20 19 20 Linear Trend p-value# NT NT NT 7 Mean 28 24 27 26 % Difference Control NA -14.3 -3.6 -7.1 S.D. 12.2 14.5 15.3 14.8 N 20 20 20 20 Linear Trend p-value# NT NT NT 8 Mean 22 19 21 21 % Difference Control NA -13.6 -4.5 -4.5 S.D. 12.7 14.7 16.7 15.4 N 20 20 20 20 Linear Trend p-value# NT NT NT 9 Mean 26 18 15 20 % Difference Control NA -30.8 -42.3 -23.1 S.D. 16.2 15.6 12.9 16.7 N 20 20 20 20 Linear Trend p-value# NT NT NT 10 Mean 19 14 14 14 % Difference Control NA -26.3 -26.3 -26.3 S.D. 15.4 14.1 12.5 15.7 N 20 20 20 20 Linear Trend p-value# NT NT NT ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 36 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F B LEARNING ERRORS Overall Mean 27 22 23 24 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.442 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.217 0.850 0.589 AR1 -1927- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 37 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F A MEMORY ESCTIME 11 Mean % Difference S.D. N Linear Trend Control p-value# 84.58 NA 43.854 20 79.11 -6.5 46.200 20 NT 66.04 -21.9 44.900 20 NT 78.70 -7.0 42.154 20 NT 12 Mean 55.31 52.74 69.19 56.67 % Difference Control NA -4.6 25.1 2.5 S.D. 44.536 43.343 49.461 38.853 N 20 20 20 19 Linear Trend p-value# NT NT NT Overall Mean S.D. N Linear Trend p-value# 69.94 NA 20 65.92 NA 20 NT 67.61 NA 20 NT 67.12 NA 20 0.865 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.988 0.198 0.358 AR1 -1928- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. 38 Table 3.3: Analysis Summary Table for Biel Maze Period Sex Path Type Variable Trial Statistic Dose Group (mg/kg/day) ___________________________________________ Statistical 0 0.1 0.3 1.0 Model __________ __________ __________ __________ ____________ PND22 F A MEMORY ERRORS 11 Mean % Difference S.D. N Linear Trend Control p-value# 22 NA 11.8 20 21 -4.5 15.5 20 NT 19 -13.6 16.9 20 NT 24 9.1 16.2 20 NT 12 Mean 14 13 19 15 % Difference Control NA -7.1 35.7 7.1 S.D. 13.7 14.1 18.0 11.4 N 20 20 20 20 Linear Trend p-value# NT NT NT Overall Mean 18 17 19 19 S.D. NA NA NA NA N 20 20 20 20 Linear Trend p-value# NT NT 0.622 Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure 0.918 0.246 0.601 AR1 -1929- ------------------------------------------------------------------------------------------------------------------------------- # : Level of Significance tested = .05. ++ : Level of Significance tested = .01. * : Statistically Significant. NT : Not tested. NA : Not applicable. WIL-180017 3M Corporation -1930- MTDID 208 06-128 APPENDIX 61 WIL Reproductive Historical Control Data Version 2.4 [Crl:CD(SD) Rats] Sex: Male/Female Study Type: All WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Reproductive Performance Species: Rat Strain: Crl:CD(SD) Number of Studies/Data Sets: Range of Study Dates: 08/00 62 / 96 - 09/05 -1931- Number of Males in Control Group Male Mating Index (%) Male Fertility Index (%) Male Copulation Index (%) Number of Females in Control Group Female Mating Index (%) Female Fertility Index (%) Female Conception Index (%) Number of Females Selected to Deliver Number that Delivered Number that did not Deliver Number with Total Litter Loss Number with Dystocia Total Mean S.D. N 1600 96.8 3.69 61 89.8 6.89 61 92.7 6.08 61 2248 97.8 3.26 73 91.3 7.17 82 92.9 5.82 73 1301 1151 145 11 3 Mean -/+ 2 S.D. Mean -/+ 3 S.D. Min/Max Value 89.42 / 100.00 76.02 / 100.00 80.54 / 100.00 85.73 / 100.00 69.13 / 100.00 74.46 / 100.00 86.7 / 100.0 72.0 / 100.0 75.0 / 100.0 91.28 / 100.00 76.96 / 100.00 81.26 / 100.00 88.02 / 100.00 69.79 / 100.00 75.44 / 100.00 86.7 / 100.0 72.0 / 100.0 75.0 / 100.0 Version 2.4 23-Aug-06 Sex: Female Study Type: All WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Reproductive Performance Species: Rat Strain: Crl:CD(SD) Number of Studies/Control Groups: Range of Study Dates: 08/00 - 62 / 96 09/05 Mean S.D. N Mean Estrous Cycle Length (days) 4.5 0.41 63 Mean Pre-Coital Interval (days) 3.0 0.52 74 Mean Gestation Length (days) 21.9 0.20 46 Mean Number of Pups Born 14.3 0.91 46 Mean Viable Litter Size (PND 0) 14.1 0.94 46 Mean % Males/ Litter 50.08 2.78 58 Mean % Females/ Litter 49.92 2.78 58 Mean No. of Former Implantation Sites at Weaning 15.2 0.87 44 Mean No. of Sites Unaccounted for at Weaning 0.9 0.24 44 Mean Viable Embryos/Dam (GD 15) 14.9 0.79 25 Mean Viable Embryos (%/Litter) 95.0 1.84 25 Mean Viable Fetuses/Dam (GD 20) 14.3 0.79 16 Mean Viable Fetuses (%/Litter) 94.6 1.34 16 Mean Post-Implantation Loss/Dam 0.8 0.24 41 Mean Post-Implantation Loss (%/Litter) 5.1 1.65 41 Mean No. of Corpora Lutea/Dam 16.7 0.88 41 Mean No. of Implantation Sites/Dam 15.3 0.81 41 Mean Pre-Implantation Loss/Dam 1.4 0.41 41 Mean Pre-Implantation Loss (%/Litter) 8.2 2.42 41 Mean Fetal Body Weight (GD 20) (g) 3.6 0.16 16 Mean Primordial Follical Count of 10 Sections/Dam 115.2 31.74 11 Mean -/+ 2 S.D. 3.68 1.96 21.50 12.48 12.22 44.52 44.36 13.46 0.00 13.32 91.32 12.72 91.92 0.32 1.80 14.94 13.68 0.58 3.36 3.28 51.72 / 5.32 / 4.04 / 22.30 / 16.12 / 15.98 / 55.64 / 55.48 / 16.94 / 1.38 / 16.48 / 98.68 / 15.88 / 97.28 / 1.28 / 8.40 / 18.46 / 16.92 / 2.22 / 13.04 / 3.92 / 178.68 Mean -/+ 3 S.D. 3.27 1.44 21.30 11.57 11.28 41.74 41.58 12.59 0.18 12.53 89.48 11.93 90.58 0.08 0.15 14.06 12.87 0.17 0.94 3.12 19.98 / 5.73 / 4.56 / 22.50 / 17.03 / 16.92 / 58.42 / 58.26 / 17.81 / 1.62 / 17.27 / 100.00 / 16.67 / 98.62 / 1.52 / 10.05 / 19.34 / 17.73 / 2.63 / 15.46 / 4.08 / 210.42 Min/Max Value 4.0 / 5.8 1.8 / 4.7 21.5 / 22.3 12.2 / 16.0 12.0 / 16.0 42.7 / 58.5 41.5 / 57.3 13.2 / 17.1 0.4 / 1.4 13.5 / 16.3 90.0 / 97.1 13.0 / 15.6 91.9 / 96.8 0.4 / 1.5 2.9 / 10.0 15.3 / 18.8 13.9 / 16.8 0.5 / 2.1 2.7 / 13.8 3.3 / 3.8 50.4 / 148.8 -1932- Version 2.4 23-Aug-06 Sex: Male/Female Study Type: All WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Pup Survival Indices (%) Species: Rat Strain: Crl:CD(SD) Age Range: 0 - 21 Days Number of Studies/Data Sets: 62 / 96 Range of Study Dates: 08/00 - 09/05 Mean Number of Pups Born Survival (%) PND 0 (Relative to No. Born) PND 0 to PND 1 PND 1 to PND 4 (Before Selection) PND 4 (After Selection) to PND 7 PND 7 to PND 14 PND 14 to PND 21 Birth to PND 4 (Before Selection) PND 4 (After Selection) to PND 21 Mean S.D. N 14.3 0.91 46 98.0 1.53 46 99.1 0.89 46 98.6 1.33 45 98.9 1.76 44 99.3 1.46 41 99.5 1.11 41 95.8 2.26 43 97.8 2.50 40 Mean -/+ 2 S.D. 12.48 / 16.12 Mean -/+ 3 S.D. 11.57 / 17.03 Observed Low/High Value 12.2 / 16.0 94.94 97.32 95.94 95.38 96.38 97.28 91.28 92.80 / 100.00 / 100.00 / 100.00 / 100.00 / 100.00 / 100.00 / 100.00 / 100.00 93.41 96.43 94.61 93.62 94.92 96.17 89.02 90.30 / 100.00 / 100.00 / 100.00 / 100.00 / 100.00 / 100.00 / 100.00 / 100.00 93.3 / 100.0 95.8 / 100.0 94.1 / 100.0 91.7 / 100.0 93.5 / 100.0 94.7 / 100.0 86.6 / 98.7 91.1 / 100.0 -1933- Version 2.4 23-Aug-06 Sex: Male/Female Study Type: All Males (g) PND PND 1 PND 4 PND 7 PND 14 PND 21 PND 28 (weaned PND 28) WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Pup Body Weights (g) Species: Rat Strain: Crl:CD(SD) Age Range: 1 - 28 Days Number of Studies/Data Sets: 62 / 96 Range of Study Dates: 08/00 - 09/05 Mean S.D. N 7.1 0.25 46 10.0 0.58 45 15.3 1.22 44 30.4 3.70 36 47.5 5.18 41 82.0 6.86 15 Mean -/+ 2 S.D. 6.60 / 7.60 8.84 / 11.16 12.86 / 17.74 23.00 / 37.80 37.14 / 57.86 68.28 / 95.72 Mean -/+ 3 S.D. 6.35 8.26 11.64 19.30 31.96 61.42 / 7.85 / 11.74 / 18.96 / 41.50 / 63.04 / 102.58 Observed Low/High Value 6.7 / 7.6 9.0 / 11.4 11.9 / 17.5 20.2 / 35.3 32.8 / 56.7 69.8 / 94.0 Females (g) PND Mean S.D. N PND 1 6.7 0.25 46 PND 4 9.5 0.56 45 PND 7 14.5 1.17 44 PND 14 29.2 3.46 36 PND 21 45.6 4.76 41 PND 28 (weaned PND 28) 75.8 6.11 15 Mean -/+ 2 S.D. 6.20 / 7.20 8.38 / 10.62 12.16 / 16.84 22.28 / 36.12 36.08 / 55.12 63.58 / 88.02 Mean -/+ 3 S.D. 5.95 / 7.45 7.82 / 11.18 10.99 / 18.01 18.82 / 39.58 31.32 / 59.88 57.47 / 94.13 Observed Low/High Value 6.3 / 7.3 8.6 / 10.9 11.3 / 16.7 20.3 / 33.9 32.8 / 53.5 66.7 / 86.2 -1934- Version 2.4 23-Aug-06 Sex: Male/Female Study Type: All Males Brain (g) Spleen (g) Thymus (g) Females Brain (g) Spleen (g) Thymus (g) WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Pup Organ Weights (PND 21) Species: Rat Strain: Crl:CD(SD) Age: 21 Days Number of Studies/Number Data Sets: Range of Study Dates: 08/00 - 62 / 96 09/05 Mean S.D. N 1.4397 0.04072 21 0.2058 0.03054 21 0.1963 0.02035 21 1.3931 0.03322 21 0.2020 0.03048 21 0.1987 0.02387 21 Mean -/+ 2 S.D. 1.35826 / 1.52114 0.14472 / 0.26688 0.15560 / 0.23700 Mean -/+ 3 S.D. 1.31754 / 1.56186 0.11418 / 0.29742 0.13525 / 0.25735 Observed Low/High Value 1.3451 / 1.4899 0.1471 / 0.2480 0.1617 / 0.2330 1.32666 / 1.45954 0.14104 / 0.26296 0.15096 / 0.24644 1.29344 / 1.49276 0.11056 / 0.29344 0.12709 / 0.27031 1.3142 / 1.4378 0.1471 / 0.2448 0.1669 / 0.2547 Version 2.4 23-Aug-06 -1935- Sex: Male/Female Study Type: All WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Developmental Landmarks Species: Rat Number of Studies/Control Groups: Strain: Crl:CD(SD) Range of Study Dates: 08/00 - 62 / 96 09/05 Mean S.D. N Mean Male Anogenital Distance (PND1) (mm) 4.37 0.171 6 Mean Female Anogenital Distance (PND1) (mm) 2.38 0.175 6 Mean -/+ 2 S.D. 4.028 / 4.712 2.030 / 2.730 Mean -/+ 3 S.D. 3.857 / 4.883 1.855 / 2.905 Observed Low/High Value 4.1 / 4.7 2.1 / 2.6 Mean Day of Balanopreputial Separation Mean Body Weight at Aquisition (g) 44.8 1.30 31 42.20 / 47.40 40.90 / 48.70 225.9 9.72 31 206.46 / 245.34 196.74 / 255.06 42.0 / 49.0 203.7 / 246.8 Mean Day of Vaginal Patency Mean Body Weight at Aquisition (g) 33.6 1.05 31 111.9 6.42 31 31.50 99.06 / 35.70 / 124.74 30.45 92.64 / 36.75 / 131.16 31.7 / 37.0 99.5 / 127.4 Mean Day of Surface Righting Response Males Females Mean Day of Pinnal Detachment Males Females Mean Day of Eye Opening Males Females Mean Day of Air Drop Righting Reflex Males Females Mean Day of Hair Growth Males Females Mean Day of Incisor Eruption Males Females 5.0 0.06 3 5.2 0.10 3 4.1 0.15 4 4.1 0.10 4 16.4 1.20 4 16.4 1.20 4 14.9 NA 1 14.9 NA 1 13.5 1.43 4 13.6 1.51 4 9.9 0.41 5 9.9 0.34 5 4.88 / 5.12 5.00 / 5.40 3.80 / 4.40 3.90 / 4.30 14.00 / 18.80 14.00 / 18.80 NA / NA NA / NA 10.64 / 16.36 10.58 / 16.62 9.08 / 10.72 9.22 / 10.58 4.82 / 5.18 4.90 / 5.50 3.65 / 4.55 3.80 / 4.40 12.80 / 20.00 12.80 / 20.00 NA / NA NA / NA 9.21 / 17.79 9.07 / 18.13 8.67 / 11.13 8.88 / 10.92 5.0 / 5.1 5.1 / 5.3 4.0 / 4.3 4.0 / 4.2 15.1 / 17.8 15.1 / 17.8 14.9 / 14.9 14.9 / 14.9 11.7 / 15.0 11.8 / 15.2 9.3 / 10.4 9.3 / 10.2 -1936- Version 2.4 23-Aug-06 Sex: Male/Female Study Type: All WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Male and Female Organ Weights (Necropsy) Species: Rat Strain: Crl:CD(SD) Number of Studies/Number Data Sets: Range of Study Dates: 08/00 - 62 / 96 09/05 -1937- Males Mean Age of Males at Necropsy (weeks) Mean S.D. N 22.2 4.20 27 Mean Seminal Vesicle/Coagulating Gland Weight (g) 2.21 0.169 36 Mean Prostate Weight (g) 1.07 0.102 22 Mean Right Testis Weight (g) 1.79 0.069 48 Mean Left Testis Weight (g) 1.80 0.077 48 Mean Right Epidymis Weight (g) 0.72 0.041 48 Mean Left Epidymis Weight (g) 0.72 0.041 48 Mean Right Cauda Epidymis Weight (g) 0.3275 0.02230 48 Mean Left Cauda Epidymis Weight (g) 0.3309 0.02064 48 Females Mean Age of Females at Necropsy (weeks) Mean Combined Ovary Weight (g) 23.2 5.03 19 0.1448 0.03004 19 Mean -/+ 2 S.D. 13.80 / 30.60 1.872 / 2.548 0.866 / 1.274 1.652 / 1.928 1.646 / 1.954 0.638 / 0.802 0.638 / 0.802 0.28290 / 0.37210 0.28962 / 0.37218 Mean -/+ 3 S.D. 9.60 / 34.80 1.703 / 2.717 0.764 / 1.376 1.583 / 1.997 1.569 / 2.031 0.597 / 0.843 0.597 / 0.843 0.26060 / 0.39440 0.26898 / 0.39282 Observed Low/High Value 16.4 / 30.6 1.82 / 2.57 0.76 / 1.27 1.66 / 1.93 1.67 / 2.09 0.63 / 0.80 0.62 / 0.78 0.2629 / 0.3693 0.2714 / 0.3706 13.14 / 33.26 0.08472 / 0.20488 8.11 / 38.29 0.05468 / 0.23492 16.0 / 32.0 0.0926 / 0.1779 Version 2.4 23-Aug-06 Sex: Male/Female Study Type: All WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Sperm Concentration and Morphology Species: Rat Strain: Crl:CD(SD) Number of Studies/Control Groups: Range of Study Dates: 08/00 - 62 / 96 09/05 Mean Sperm Concentration (millions/ gram of tissue) Left Testis Left Epididymis Left Cauda Epididymis Mean S.D. N 80.9 7.33 43 454.5 49.37 37 666.2 57.99 7 Mean -/+ 2 S.D. 66.24 / 95.56 355.76 / 553.24 550.22 / 782.18 Mean -/+ 3 S.D. Observed Low/High Value 58.91 / 102.89 306.39 / 602.61 492.23 / 840.17 68.2 / 96.6 339.1 / 619.2 568.0 / 738.9 -1938- Mean Sperm Production Rate (millions/ gram of tissue/ day) Mean Sperm Motility (%) Mean Progressive Sperm Motility (%) 13.4 1.21 23 85.4 3.01 44 72.5 3.70 15 Sperm Morphology Differential Count (%) Normal 99.1 0.81 43 Normal Head Separated from Flagellum 0.4 0.40 43 Head Absent w/ Normal Flagellum 0.3 0.39 43 Head Absent w/ Abnormal Flagellum 0.0 0.00 43 Misshapen Head w/ Normal Flagellum 0.0 0.17 43 Misshapen Head w/ Abnormal Flagellum 0.0 0.06 43 Degenerative Flagellar Defects w/ Normal Head 0.0 0.00 43 Other Flagellar Defects w/ Normal Head 0.0 0.00 43 10.98 / 15.82 79.38 / 91.42 65.10 / 79.90 9.77 / 17.03 76.37 / 94.43 61.40 / 83.60 11.4 / 15.8 78.9 / 91.0 67.0 / 80.0 97.48 0.00 0.00 0.00 0.00 0.00 0.00 0.00 / 100.00 / 1.20 / 1.08 / 0.00 / 0.34 / 0.12 / 0.00 / 0.00 96.67 0.00 0.00 0.00 0.00 0.00 0.00 0.00 / 100.00 / 1.60 / 1.47 / 0.00 / 0.51 / 0.18 / 0.00 / 0.00 96.1 / 99.9 0.1 / 1.8 0.0 / 2.3 0.0 / 0.0 0.0 / 1.1 0.0 / 0.4 0.0 / 0.0 0.0 / 0.0 Version 2.4 23-Aug-06 WIL-180017 3M Corporation -1939- MTDID 208 06-128 APPENDIX 62 Developmental Neurotoxicity Method Development Studies (WIL Research Laboratories, LLC) -1940- A Validation Study for Developmental Neurotoxicity Endpoints at WIL Research Laboratories, Inc.: Effect of Propylthiouracil (PTU) on Developmental Neurotoxicity Endpoints in Crl:CD(SD)IGS BR Rats (WIL-99126) Jeffrey A. Pitt, Mark D. Nemec, Donald G. Stump, Deborah Shoup, Gordon Glenn and Kim Rhodes ABSTRACT The objective of this study was to evaluate various endpoints within the U.S. EPA OPPTS Guideline 870.6300 (Developmental Neurotoxicity). Propylthiouracil (PTU) was administered at dosage levels of 3.8, 19 and 38 mg/kg/day by oral gavage once daily from gestation day 6 through lactation day 10 to Sprague-Dawley Crl:CD(SD)IGS BR rats. Offspring were evaluated by functional observational battery, motor activity, acoustic startle response, and learning and memory in the Biel water maze. Live litter size was reduced in the 38 mg/kg/day group. Pup viability from birth to PND 4 was reduced in the 19 and 38 mg/kg/day groups. Pup weights were reduced by 10% at birth for all dosage levels, and remained reduced for the duration of the study. The observational battery demonstrated delays in pupillary response, startle reactivity, mobility and neuromuscular development on postnatal day (PND) 20. Neuromuscular measures continued to be impaired at the PND 35 and 45 observations. Motor activity was not affected. Acoustic startle response was reduced at all dosage levels when evaluated on PND 22. Latency to escape the Biel maze was increased for all dosage levels at the PND 22 evaluation; however, swimming ability was markedly reduced for all treatment groups. When assessed at PND 62 swimming ability was comparable between all groups. However, time to escape the Biel maze was increased for males and females at all dosage levels by approximately 60% although there was no dose response relationship. The experimental design used in this study demonstrated that WIL Research Laboratories, Inc. can detect effects of PTU, a known developmental neurotoxicant, and results can be considered to validate methodologies for OPPTS Guideline 870.6300 developmental neurotoxicity studies. Page 1 of 14 -1941- INTRODUCTION In 1998, the United States Environmental Protection Agency (EPA) released the Developmental Neurotoxicity Study (OPPTS 870.6300) guideline (1). The guideline required that various neurobehavioral endpoints such as motor activity, auditory startle, and learning and memory along with appearance of developmental landmarks and other standard toxicologic indices be tested to support product registration under FIFRA and TSCA. Validation of laboratory methodologies is a requirement of the guideline. We chose to evaluate potential differences in control and treated animals using an agent which produces hypothyroidism, propylthiouracil (PTU). In rats, pre- and peri-natal hypothyroidism produces behavioral deficits (2-4) and altered electrophysiology (2,5,6) along with changes in gross and microscopic measures of brain morphology (7-12). MATERIALS and METHODS Test Species and Husbandry Female Sprague-Dawley Crl:CD(SD)IGS BR rats were obtained from Charles River Breeding Laboratories (Raleigh, NC, USA). The animals were individually housed in clean suspended wire-mesh cages in an environmentally controlled room during acclimation. During cohabitation, the females were paired (1 male:1 female) with resident males in a suspended wiremesh cage. Mating was evidenced by vaginal plug and/or the presence of sperm in a vaginal smear. Following successful mating, the females were individually housed in plastic maternity cages with nesting material (Bed-O'Cobs). On postnatal day (PND) 4, pups were culled to reduce variability among litter size (3:5, 4:4 or 5:3 M:F) and dams and pups remained in these cages until the dam was euthanized on PND 21. Each litter remained housed together in plastic cages with nesting material through PND 28 whereupon they were housed 2-3/cage by sex in wire mesh cages. On PND 35 until scheduled euthanasia all animals were individually housed. Environmental controls were set to maintain temperature at 72 4 F and relative humidity between 30-70%. Air handling units provided a minimum of 10 fresh air changes per hour. Fluorescent lighting, controlled by timers, provided illumination for a 12-hour (6:00 a.m. - 6:00 p.m.) light/dark photoperiod. Temperature and relative humidity were monitored continuously. Page 2 of 14 -1942- Reverse osmosis-purified water was available ad libitum. PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 was offered ad libitum during the study. Test Material and Preparation 6-N-Propyl-2-thiouracil (PTU) was purchased from Sigma Aldrich, St. Louis, MO, (lot #76H2500). An appropriate amount of PTU was mixed with 0.5% methylcellulose (Sigma Chemical Co., St. Louis, MO, lot #97H0980) to produce dosing solutions of 0.304, 1.52 and 3.04 mg/ml. Dosing solutions were prepared weekly and daily aliquots were dispensed for dosing. Experimental Design Four groups of 25 bred rats received a daily oral gavage of 0, 3.8, 19 or 38 mg/kg PTU daily from gestation day (GD) 6 through PND 10. The dose volume was 12.5 ml/kg. Dams were examined daily for mortality, morbundity and for clinical signs of toxicity. Maternal body weight and food consumption were recorded twice weekly from GD 0 through PND 21. Pups were randomized into treatment groups and then assigned to testing groups within each treatment group. The following table summarizes the testing paradigm: Number of Animals 10/sex/group 10/sex/group 10/sex/group 10/sex/group 3-10/sex/group Age PND 20, 35, 45 and 60 PND 22 PND 13, 17, 21 and 60 PND 21 and 62 PND 4 and 28 Evaluation Functional Observational Battery (FOB) Auditory startle Locomotor Activity Learning and Memory (Biel Maze) T3, T4 and TSH levels Developmental Landmarks: Anogenital distance was measured on PND 1 for all live pups. Balanopreputial separation was observed for all male pups beginning on postnatal day 35 and continued daily until balanopreputial separation was present. The body weight of each male was recorded on the day of acquisition of balanopreputial separation. Vaginal patency was observed for all female pups beginning on postnatal day 25 and continued daily until vaginal perforation was present. The body weight of each female was recorded on the day of acquisition of vaginal patency. Page 3 of 14 -1943- Behavioral Testing Ten pups/sex/group were assigned to one of the following tests: functional observational battery (FOB), locomotor activity, auditory startle or learning and memory. The FOB utilized was based on previously developed protocols (13-16). Testing was performed by the same trained technicians, whenever possible, who did not know the animal's group assignment. Locomotor activity was monitored on postnatal days 13, 17, 21 and 60 ( 2 days). The same animals were monitored at each interval and testing of treatment groups was balanced across test times. Locomotor activity was measured using the Digiscan Micro Animal Activity System (Omnitech Electronics Inc., Columbus, Ohio) and the test session was 41 minutes duration with 1 minute test intervals for each animal. The auditory startle response test was performed on PND 22 using an automated Auditory Startle Response System (Coulbourn Instruments, Inc., Lehigh Valley, Pennsylvania). The test session consisted of a 5 minute acclimation period with a background noise level of 70 db, followed by 50 presentations of a 50-ms 120 db noise burst given at 8 second intervals. Mean amplitude on each block (1-5) of 10 trials was recorded for each animal. Learning and memory was tested on postnatal day 21 (4 days) and 62 (4 days) using a Biel maze (22). Different animals were tested at each interval. The Biel maze is a water-filled multiple T-maze with an escape ladder. The time to escape and number of errors (animal deviates from the correct channel with all four feet) was recorded and animals were allowed three minutes to escape from the maze after which they were removed. The minimum intertrial interval will be one hour. Animals will be tested for seven consecutive days as follows: Day 1: Days 2 and 3: Days 4, 5 and 6: Day 7: Each animal is given 4 trials to escape from a straight channel. Each animal is given 2 trials per day in Path A. Each animal is given 2 trials per day in Path B (reverse of Path A). Each animal is given 2 trials in Path A. Statistical Analyses All analyses were two-tailed for a significance level of 1% and 5% by a one-way analysis of variance (ANOVA; 18). If significant differences were indicated by the ANOVA, Dunnett's test (19) was used to compare the control and treated groups. Functional observational battery parameters which yield scalar and descriptive data were analyzed by Fisher's Exact Test (20). Body weights, hormone concentrations, survival, developmental landmarks, litter size, locomotor activity, Page 4 of 14 -1944- startle response and learning and memory were analyzed using a one-way ANOVA. If significant treatment effects were observed at a given time-point, then Dunnett's test was conducted to determine significant treatment differences from the control group (p<0.05). RESULTS and DISCUSSION Treatment with PTU significantly decreased maternal body weights in the 38 mg/kg/day group late in gestation (data not shown). Pup weights on PND 1 were significantly decreased in all treated groups. After the end of treatment on PND 10, body weights in all PTU-treated groups remained significantly decreased in all groups at each day measured (Figure 1). Pup weights were reduced by approximately 10% at birth for all dosage levels and remained reduced throughout the study (Figure 1). Live litter size was significantly reduced in the 38 mg/kg/day group, and pup viability was significantly reduced from birth to PND 4 in the 19 and 38 mg/kg/day groups (Table 1). The appearance of balanopreputial separation was significantly delayed (3-4 days) in the 19 and 38 mg/kg/day dose groups. Similarly, vaginal patency was also significantly delayed by 6-8 days (Table 1). These developmental landmarks are body weight dependent in the rodent and in this case are probably indicative of a body weight and not an endocrine effect. Serum T4 levels were reduced for each dose group on PND 4 for both sexes combined and on PND 28 for both sexes separately. Serum TSH levels were reduced at all dosage levels on PND 4 and serum T3 levels were reduced for each male dose group on PND 28, but not for females (data not shown). The adult rat is known to be more sensitive to perturbations of the pituitarythyroid axis than humans (21); however, the sensitivity of the neonatal rat compared to the neonatal human is less well documented. The functional observational battery demonstrated deficits in autonomic (pupillary response, palpebral closure), neuromuscular (gait, mobility, foot splay, grip strength, righting reflex, rotorod), sensorimotor (startle), CNS activity (catalepsy, rearing, grooming) and physiologic (body weight, temperature) endpoints on PND 20 in both sexes and in all dose groups. Most of these findings were no longer evident by PND 35 although deficits in grip strength and body weight were sustained through PND 60 (Table 2). Page 5 of 14 -1945- Motor activity was increased in all male dose groups on PND 21 and in females motor activity was increased, albeit not statistically nor in a dose response, on PND 17 and 21 (Figure 2), and therefore the relationship to treatment is quesitonable. The peak auditory startle response was significantly reduced and the latency to peak response was significantly increased for both sexes at all dosage levels on PND 22 (Figure 3). Swimming ability was strikingly reduced for both sexes in all treatment groups at PND 21 although only the female 19 mg/kg/day group reached statistical significance (Table 1). By PND 61 there was no difference in swimming ability across all treatment groups (Table 1). Also, while on PND 62 swimming ability was comparable between all groups, latency to escape the Biel maze was significantly increased for both sexes at all dosage levels. However, on PND 22 when swimming ability was significantly reduced, latency to escape the Biel maze was also significantly increased at all dosage levels. The mean number of errors for all was not different on PND 22, but was numerically increased across all groups on PND 62. In conclusion, Sprague Dawley Crl:CD(SD)IGS BR rats have been shown to be sensitive to the effects of pre- and peri-natal PTU exposure as assessed by developmental and behavioral assessments described by the US Environmental Protection Agency Developmental Neurotoxicity Study (OPPTS 870.6300) guidelines. REFERENCES 1. EPA Health Effects Test Guidelines (1998) OPPTS 870.6300 Developmental Neurotoxicity Study EPA 712-C-98-239. 2. Eayre, J.T. (1966) Thryoid and central nervouse system development. In: Scientific basis of medicine, annual reviews. The Athlone Press, London. 3. Essman, W.B., Mendoza, L.A. and Hamburgh, M. (1968) Critical periods of maze acquisition development in euthyroid and hypothyroid rodents. Psychol. Rep. 23:795-800. 4. Comer, C.P. and Norton, S. (1982) Effects of perinatal methimazole exposure on a developmental test battery for neurobehavioral toxicity in rats. Toxicol. Appl. Pharmacol. 63:133-141. 5. Albee, R.R., J.L. Mattsson, K.A. Johnson, Kirk, H.D. and Breslin, W.J. (1989) Neurological consequences of congenital hypothyroidism in Fisher 344 rats. Neurotoxicol. Teratol. 11:171-183. 6. Herbert, R., LeLanglois, J.M. and Dussault, J.H. (1985) Permanent defects in rat peripheral auditory function following perinatal hypothyroidism: Determination of a critical period. Dev. Brain Res. 23:161-170. Page 6 of 14 -1946- 7. Behnam-Rassoli, M., Herbert, L.C., Howard, V., Pharoah, P.O. and Stanisstreet, M. (1991) Effect of propylthiouracil treatment during prenatal and early postnatal development of the neocortex of rat pups. Neuroendocrinol. 53:321-327. 8. Mwangi, D.K. (1998) Effect of propylthiouracil induced hypothyroidism in developing rat cerebellum: comparison of cerebellar parameters in five day old normal and treated rat pups. East Afr. Med. J. 75:602-608. 9. Walker, R.F., Guerriero, F.L., Toscano, T.V. and Weideman, C.A. (1989) Relative cerebellar weight: a potential indicator of developmental neurotoxicity. Neurotoxicol Teratol. 11:251255. 10. Comer, C.P. and Norton, S. (1985) Early development in the caudate and thyroid of methimazole-treated rats. Neurotoxicol. 6:25-36. 11. Ruiz-Marcos, A. and Ipina, S.L. (1986) Hypothyroidism affects preferentially the dendritic densities on the more superficial region of pyramidal neurons of the rat cerebral cortex. Dev. Brain Res. 28:259-262. 12. Walters, S.N. and Morell, P. (1981) Effects of altered thyroid states on myelinogenesis. J. Neurochem. 36:1792-1801. 13. Irwin, S. (1968) Comprehensive observational assessment: 1a. A systematic quantitative procedure for assessing the behavioral physiological state of the mouse. Psychopharmacologia 13: 222-256. 14. Moser, V.C., McCormick, J.P. Creason, J.P. and MacPhail, R.C. (1988) Comparison of chlordimeform and carbaryl using a functional observational battery. Fund. Appl. Toxicol. 11: 189-206. 15. Haggerty, G.C. (1989) Development of Tier 1 Neurobehavioral Testing Capabilities for Incorporation into Pivotal Rodent Safety Assessment Studies. J. Amer. Coll. Toxicol. 8: 53-69. 16. O'Donoghue, (1989) J.L. Screening for Neurotoxicity Using a Neurologically Based Examination and Neuropathology. J. Amer. Coll. Toxicol. 8: 97-116. 17. Biel, W.C., (1940) Early Age Differences in Maze Performance in the Albino Rat. J. Gen. Psych. 56: 439-453. 18. Snedecor, G.W. and Cochran, W.G. (1980) One way classifications; analysis of variance. In: Statistical Methods, Seventh Edition. Iowa State University Press, Ames, IA, pp. 215-237. 19. Dunnett, C.W. (1964) New tables for multiple comparisons with a control. Biometrics 20:482491. 20. Steel, R.G.D. and Torrie, J.H. (1980) Principles and Procedures of Statistics, A Biometrical Approach, Second Edition. McGraw-Hill Book Company, New York, NY, pp. 504-506. 21. Siglin, J.C., Mattie, D.R., Dodd, D.E., Hildebrandt, P.K. and Bates, W.H. (2000) A 90-Day Drinking Water Study in Rats of the Environmental Contaminant Ammonium Perchlorate. Tox. Sciences 57: 61-74. Page 7 of 14 Table 1. Pup Viability and Physical Development Control 3.8 mg/kg/day Number Born Live Litter Size Males (Percent Per Litter) PND 1 Body Weight (grams) -Males -Females Survival (Percent Per Litter) -Birth-PND4 -PND4-weaning Developmental Landmarks -Balanopreputial separation (PND) 15.1 1.5 14.2 3.4 52.2 12.6 6.5 0.7 6.1 0.7 88.1 24.8 98.2 4.8 45.1 3.0 15.0 1.4 14.6 2.3 53.0 11.5 5.8 0.6** 5.7 0.5* 91.8 20.2 96.3 9.8 46.6 2.8 Body weight (grams) 212 16.2 188 21.9** -Vaginal patency (PND) 33.4 2.8 39.8 2.5** Body weight (grams) 101 9.0 113 15.4** Anogenital Distance Relative to Cube-Root of Body Weight (PND 1) -Male 2.71 0.6 2.58 0.5 -Female 1.63 0.5 1.54 0.4 Swimming ability (Seconds) PND 21 -Male -Female 15.8 10.7 14.3 9.2 52.6 55.5 46.3 46.8 Swimming ability (Seconds) PND 61 -Male 7.0 2.3 -Female 8.3 3.4 * = Significantly different from the control group at P<0.05. **= Significantly different from the control group at P<0.01. 8.9 2.7 7.8 1.5 19 mg/kg/day 14.1 3.3 12.9 4.4 50.1 16.7 5.8 0.5** 5.5 0.4** 77.4 28.8** 95.4 12.6 49.5 4.0** 194 14.3** 41.5 3.0** 111 11.6* 2.59 0.7 1.58 0.4 66.3 65.6 86.0 72.3* 8.6 3.9 7.5 1.9 38 mg/kg/day 13.5 2.3 11.4 5.2* 44.3 15.1 5.7 0.6** 5.6 0.5* 69.4 35.9** 89.9 24.6 48.1 2.4* 190 14.7** 41.4 2.4** 11015.6 2.78 0.8 1.75 0.6 56.1 68.9 60.2 71.5 9.6 5.1 8.4 2.4 -1947- Page 8 of 14 Table 2. Summary of Pup Functional Observational Battery Findings Evaluation Autonomic Neuromuscular Sensorimotor CNS Excitability CNS Activity Physiological Lacrimation Salivation Pupil Response Palpebral Closure Defecation Urination Time to First Step Gait Score Mobility Score Foot Splay Forelimb Grip Strength Hindlimb Grip Strength Air Righting Rotorod Tail Pinch Startle Response Touch Response Approach Response Olfactory Response Ease of Removal Handling Reactivity Clonic Movements Tonic Movements Arousal Vocalization Posture Catalepsy Rearing Grooming Backing Body Weight Body Temperature Appearance PND 20 Male Female PND 35 Male Female PND 45 Male Female PND 60 Male Female NR: 2,3,4 D: 2,3,4 NR: 2,3,4 D: 2,3,4 IM: 2,3,4 IM: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 4 IM: 2,3,4 IM: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 I: 4 D: 2,3,4 D: 2,3,4 I: 4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D: 2,3,4 D= Decreased F= Female I= Increased IM= Impaired M= Male NR= No Response Numbers indicate dose group(s) affected -1948- Page 9 of 14 -1949- 0 mg/kg/day 3.8 mg/kg/day 19 mg/kg/day 38 mg/kg/day 50 450 45 Male 400 Grams Grams 40 350 35 ****** **** 300 30 ****** ** **** 250 25 ** 20 **** ****** 200 ** 15 ** ****** 150 ** 10 ** **** 100 ** 5 ** 0 **** ****** 50 ****** 0 1 4 4 7 11 17 21 28 35 42 49 56 63 70 77 BC AC Postnatal Day 50 Female 450 45 400 Grams Grams 40 350 35 300 30 ****** 25 ** 20 **** 15 **** ** 10 5 **** 0 1 4 4 7 11 17 21 250 *** -*--* 200 ** ****** * 150 **** ****** 100 ****** ****** 50 ****** 0 28 35 42 49 56 63 70 77 BC AC Postnatal Day FIGURE 1. Mean SD body weight of Control and PTU-treated rat pups. Significance between the control and treated groups is indicated by * (p<0.05) and ** (p<0.01). The row of */** indicates which groups is different from control with top, middle and bottoms rows corresponding to 3.8, 19 and 38 mg/kg/day, respectively. BC= Before culling AC= After culling Page 10 of 14 Percent of Control -1950- 0 mg/kg/day 3.8 mg/kg/day 300 * 250 MALE 200 150 100 50 0 PND 13 PND 17 PND 21 PND 60 19 mg/kg/day 38 mg/kg/day FEMALE PND 13 PND 17 PND 21 PND 60 FIGURE 2. FIGURE 2. Locomotor activity expressed as a percentage of control in male (left) and female (right) pups. Significance is indicated by an * (p<0.05). Page 11 of 14 -1951- Grams 125 100 75 50 25 0 Control Peak Response Male Female ** ** ** ** ** ** 3.8 mg/kg 19 mg/kg 38 mg/kg Latency to Peak Response 75 *** ** ** ** **** ** 50 Milliseconds 25 0 Control 3.8 mg/kg 19 mg/kg 38 mg/kg FIGURE 3. Mean SD auditory startle response on PND 22. Significance between the control and treated groups is indicated by * (p<0.05) and ** (p<0.01). Page 12 of 14 -1952- (A) Latency to Escape 200 180 160 140 * ** Latency (seconds) 120 100 80 60 40 20 0 0 mg/kg 3.8 mg/kg Male ** ** 19 mg/kg Group Female ** ** 38 mg/kg Number of Errors (B) Number of Errors 30 25 20 15 10 5 0 0 mg/kg 3.8 mg/kg 19 mg/kg 38 mg/kg Group FIGURE 4. Mean SD Biel maze response on PND 22. Significance between the control and treated groups is indicated by * (p<0.05) and ** (p<0.01). No statistical analysis was performed on the mean total number of errors. Page 13 of 14 -1953- Latency (seconds) (A) Latency to Escape 140 120 ** ** Male ** ** 100 80 60 40 20 0 0 mg/kg 3.8 mg/kg 19 mg/kg Group Female ** ** 38 mg/kg Number of Errors (B) Number of Errors 30 25 20 15 10 5 0 0 mg/kg 3.8 mg/kg 19 mg/kg 38 mg/kg Group FIGURE 5. Mean SD Biel maze response on PND 62. Significance between the control and treated groups is indicated by * (p<0.05) and ** (p<0.01). No statistical analysis was performed on the mean total number of errors. Page 14 of 14 -1954- WIL-99140 Date Range: April 12-13, 1999 Determination of Test Session Duration and Test Interval for the San Diego Photobeam Activation System Using Untreated Rats Study Objective: Regulatory guidelines require that the length of the locomotor activity monitoring session be long enough to allow untreated rats to approach normal activity levels by the last 20% of the session following their placement into a novel environment habituation). The primary objective of this study was to determine the appropriate test session duration for the locomotor activity measuring apparatus (San Diego Instruments - Photobeam Activity System [SDI-PAS]). A secondary objective was to collect data that could be used to determine an appropriate interval length (epoch) within the test session for the capturing and reporting of locomotor activity data. Test System: Juvenile (approximately six-week old) Sprague-Dawley Crl:CD(SD)IGS BR rats weighing approximately 225 + 75 grams (males) and 135 + 25 grams (females) were used on the study. The rats were arbitrarily selected from available stock. Environmental Conditions: The rats were acclimated to laboratory conditions for five days prior to monitoring locomotor activity. Animals were housed and maintained under conditions consistent with maintaining good health and as per WIL Standard Operating Procedures. Temperature and humidity were maintained at 72 + 4 F and 50 + 20%, respectively, in a room with a 12 hours light/12 hours dark (0600-1800 hrs) photoperiod. The facilities at WIL Research Laboratories, Inc. are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. Locomotor Activity Monitoring Methods: Locomotor activity of 24 untreated rats (12 per sex) was monitored to determine the acceptable test session duration and test interval to be used on subsequent studies. (The test interval is the frequency at which activity counts are captured.) For this testing, the duration of the test session was 120 minutes. The test interval was one minute. That is, total activity (photobeam interruptions) was recorded at one-minute intervals for 120 minutes. Monitoring commenced one minute after placement of the rats into the monitoring units. -1955- WIL-99140 Locomotor activity monitoring was performed using the SDI Photobeam Activity System (San Diego Instruments, Inc., San Diego, CA), which includes Photobeam Activity System (PAS) software, analyzer and 24 activity monitors. A local personal computer linked to the laboratory's mainframe computer controls the SDI PAS. Each locomotor activity monitoring unit consists of seven photobeam emitting/detecting units attached to a mounting frame. A clear acrylic shoe box -style cage (18.5"L x 9.5"W x 8"H) fits into the mounting frame to contain a single animal during the test session. Activity is measured as interruptions of the photobeams. Photobeam diagnostic checks were performed prior to and following completion of the test session. Confirmation that the software-driven procedure was operating correctly was obtained by manually blocking the photobeams with pre-cut pieces of cardboard. Monitoring was performed in a sound-attenuated room equipped with a white-noise generator set to operate at approximately 70 db. Results: Mean total locomotor activity data are presented graphically as both one-minute and five-minute test intervals (epochs) for the entire 120-minute test session in Figures 1 and 2, respectively. Corresponding numerical data are presented in Tables 1 and 2. Mean total activity counts per minute were calculated using all 24 animals at each time point. Five-minute epochal data represent grand mean activity counts for each five-minute interval. Discussion: Following their placement into the monitoring units, untreated rats returned to normal locomotor activity levels after 36 minutes. Therefore, although a 45-minute test session would be adequate to allow rats to fully habituate to a novel environment, a 60-minute test session was selected for future studies. A test session of 60 minutes duration would comfortably meet the criterion for approaching normal locomotor activity levels by the last 20% of the test session, while providing a slightly extended session that may allow for detection of delayed effects. No differences in locomotor activity levels were apparent when the data were examined in one-minute versus five-minute test intervals (epochs). Therefore, collection and reporting of locomotor activity with the SDI-PAS using a five-minute test interval was judged to be adequate to detect alterations in locomotor activity. -1956- WIL-99140 Alternative locomotor activity monitoring paradigms can be employed as appropriate, necessary or requested, but the above conditions (60-minute test session with fiveminute epochs) are considered to be acceptable standards for this laboratory and equipment. WIL-99140 Figure 1 Mean Total Activity Count -1957- Habituation Locomotor Activity in One-Minute Epochs 80 70 60 50 40 30 20 10 0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93 97 101 105 109 113 117 Interval (Minutes) Page 1 WIL-99140 Figure 2 Mean Total Activity Count -1958- Habituation Locomotor Activity in Five-Minute Epochs 80 70 60 50 40 30 20 10 0 2.5 7.5 12.5 17.5 22.5 27.5 32.5 37.5 42.5 47.5 52.5 57.5 62.5 67.5 72.5 77.5 82.5 87.5 92.5 97.5 102.5 107.5 112.5 117.5 Interval (Minutes) Page 1 WIL-99140 Interval 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 MAC 71.95833 48.625 45.45833 42.0833 40.95833 29.70833 37.70833 21.58333 27.16667 20.83333 14.95833 13.16667 10.91667 11.45833 10.45833 11.125 12.70833 10.70833 8.625 9.458333 11.45833 9.541667 9.458333 9.833333 Interval 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 Table 1 Locomotor Activity Data in 1-Minute Epochs MAC Interval MAC Interval 10.41667 49 3.083333 73 11.04167 50 3.375 74 8.041667 51 4.125 75 12.25 52 0.5 76 8.083333 53 0.583333 77 3.541667 54 0.625 78 7.25 55 0.75 79 5.291667 56 2.416667 80 3.083333 57 1.083333 81 2.125 58 1.708333 82 3.791667 59 2.666667 83 3.416667 60 1 84 1.208333 61 2.125 85 0.416667 62 3.625 86 0.375 63 4.875 87 0.458333 64 4.291667 88 0.5 65 3.458333 89 1.916667 66 1.583333 90 0.791667 67 2.333333 91 0.958333 68 1.333333 92 0 69 1.666667 93 0.708333 70 1.75 94 0.625 71 2.5 95 1.083333 72 1.666667 96 MAC 2.5 0.541667 1 1.375 2.541667 1.875 2.833333 1.041667 0.5 1.333333 3.625 0.708333 0.791667 1.416667 0.791667 0.5 0.375 0.25 1.291667 0.083333 0.75 1.625 1.75 0.375 Interval 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 MAC 1.208333 0.458333 0.333333 0.25 1.583333 3.708333 1.416667 2.625 6.333333 2.416667 0.333333 0.875 0.625 1.125 2.208333 0.708333 0.208333 0.791667 0.125 0 0.333333 0 0.166667 0.541667 -1959- MAC = Mean Activity Count Page 1 WIL-99140 Interval 5 10 15 20 25 30 35 40 MAC 49.81667 27.4 12.19167 10.525 10.14167 8.591667 4.308333 1.175 Table 2 Mean Total Activity Counts in 5-Minute Epochs Interval 45 50 55 60 65 70 75 80 MAC 0.833334 1.775 1.316667 1.775 3.675 1.733333 1.641667 1.933333 Interval 85 90 95 100 105 110 115 120 MAC 1.391667 0.666667 1.1 0.525 3.133333 1.075 0.808333 0.208333 -1960- MAC = Mean Activity Counts Page 1 -1961- WIL-99144 DEMONSTRATION OF THE SENSITIVITY OF THE SR-LAB STARTLE RESPONSE SYSTEM TO DETECT CHEMICAL-INDUCED ALTERATIONS IN ACOUSTIC STARTLE RESPONSE IN RATS Study Objective: Regulatory guidelines require that the testing laboratory demonstrate the ability to detect chemical-induced alterations in startle response. Therefore, the objective of this study was to demonstrate that the acoustic startle response measuring apparatus (San Diego Instruments SRLAB Startle Response System) is able to detect chemical-induced alterations in startle response with each of the following testing paradigms (Figure 1): A. Habituation of the Acoustic Startle Response The acoustic startle response is a centrally mediated reflex. This reflex is evaluated in an apparatus in which the test subject is placed in an acrylic cylinder that is mounted on a platform that is enclosed in a sound-attenuating chamber. There is a piezoelectric force-transducer mounted on the underside of the platform to which the acrylic cylinder is affixed. When the animal reacts to the startle stimulus, the animal's movement produces a deflection of the platform, which induces a voltage change in the piezoelectric force-transducer. This signal is amplified and converted to a digital signal for analysis. Startle response measures obtained are maximum response amplitude (Vmax), average response amplitude (Vave) and latency to Vmax (Tmax). B. Prepulse inhibition of the Acoustic Startle Response Prepulse inhibition is when a weaker stimulus is presented prior to the startle stimulus. In this case, the prepulse inhibits the strength of the startle response. By varying the amplitude of the prepulse stimulus, one can obtain an inhibition curve where the degree of suppression of the startle response increases as the magnitude of the prepulse signal is increased. Test and Control Articles: One test article was employed to elicit changes in the auditory startle response, 3'-3' Iminodipropionitrile (IDPN; Aldrich, Milwaukee, WI, lot no. 90906AT). Physiological saline (Baxter Healthcare Corporation, Deerfield, IL) was used as the vehicle control. Page 1 of 24 -1962- WIL-99144 Test System: Juvenile (approximately 4-5 weeks old) Sprague-Dawley Crl:CD(SD)IGS BR rats weighing approximately 154 g (males) and 129 g (females) at randomization were used in this study. The rats were assigned to three treatment groups using a computer-based randomization procedure which ensures homogeneity of group means and variances for body weight. Eight male and eight female rats will be randomized into each study group. Following the group randomization procedure, the 8 rats/sex/group were randomized into study replicates as described in WIL Standard Operating Procedure No. T1-126 (as revised). Each dose group and sex were equally represented in each study replicate to avoid the introduction of bias into the recorded observations related to these variables. Environmental Conditions: Weanling animals were housed three per cage, by sex in suspended wire-mesh cages in an environmentally controlled room, for approximately three days following receipt. Thereafter, all animals were housed individually. The animals were housed and maintained under conditions consistent with maintaining good health and as per WIL standard operating procedures. Temperature and relative humidity at approximately were maintain at 72 4F and 30-70%, respectively in a room with a 12 hour light/dark photoperiod (6 a.m. to 6 p.m.). Temperature and relative humidity will be recorded once per day. The facilities at WIL Research Laboratories, Inc. are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International). Treatment Regimen: Animals were assigned to treatment groups as follows: Group Number 1 2 3 Test Article Physiological Saline IDPN IDPN Dosage Level (mg/kg/day) 0 200 400 Dosage Concentration (mg/ml) 0 40 80 Dosage Volume (ml/kg) 5 5 5 Number of Animals Males Females 8 8 8 8 8 8 The test and control articles were administered by intraperitoneal injection (ip) for three consecutive days. Individual doses were calculated based upon the animal's body weight taken just before administration of the test article. Startle Response Assessment: All startle response measurements were made using the SR-Lab Startle Response System (San Diego Instruments, San Diego, CA). The apparatus consisted of a slotted acrylic cylinder (6" long by 2.25" in diameter) mounted in a horizontal orientation on a platform and Page 2 of 24 -1963- WIL-99144 enclosed in a sound-attenuating chamber. A piezoelectric force transducer is mounted on the under side of the platform. When an animal placed inside the cylinder reacts to the startle stimulus, the movement produces a deflection of the platform, which induces a voltage change in the piezoelectric force transducer. This voltage signal is amplified and converted to a digital signal for analysis. Startle response measures obtained are maximum response amplitude (Vmax), latency or time to Vmax (Tmax) and average response amplitude (Vave). Startle response evaluations were performed in a sound-attenuated room equipped with a white-noise generator set to operate at approximately 70 db. The transducers were calibrated to provide the correct average output and sound checks were performed on the chamber and room white noise generators prior to data collection. Testing was controlled and data are captured/converted via a local PC (486DX2 or better). Data were transferred to the mainframe computer system for subsequent presentation and evaluation. A. Habituation of the Acoustic Startle Response: Habituation of the acoustic startle response was evaluated for all animals four and 11 days following dose administration using an automated startle response-measuring device (SR-LAB Startle Response System, San Diego Instruments, San Diego, CA). The test session consisted of a five-minute acclimation period with a 65-db broadband background white noise. The startle stimulus for each trial was a 115-db, mixed frequency noise burst stimulus (20 ms in duration). Responses were recorded during the first 100 ms following startle signal onset for each trial. The test session consisted of 50 trials with an eight-second inter-trial-interval. Startle response data was analyzed in five blocks of 10 trials each plus all 50 trials combined.1,2 B. Prepulse Inhibition of the Acoustic Startle Response: Prepulse inhibition of the acoustic startle response was evaluated for all animals 12 days following dose administration. Prepulse trials were identical to habituation trials except that the prepulse trial startle signal was preceded by a less intense, but otherwise identical signal of 20-ms in duration (measured from prepulse signal onset to startle signal onset). Five prepulse intensities were used (70-, 75-, 80-, 85- and 90-db). These five, plus no-prepulse trials, constituted the six trial types. Each trial type was presented eight times for a total of 48 trials. Trial order for prepulse trials was balanced using a Latin-square design with the provision that the first trial was a no-prepulse trial.1,2 Prepulse inhibition response was analyzed in six trial blocks by prepulse intensity (0-, 70-, 75-, 80-, 85- and 90-db). Page 3 of 24 -1964- WIL-99144 Statistical Methods: Startle Response activity data was analyzed using a two-way repeated measure analysis of variance with trial as the within-subject factor. Significant (p<0.05) treatment or treatment-time interactions were subjected to a one-way ANOVA at each time-point. Significant treatment effects at a given time-point were then subjected to Dunnett's test to determine significant treatment differences from the control group. Quality Assurance: The raw data and draft report will be audited by the WIL Quality Assurance Unit prior to assure that the final report accurately describes the conduct and the findings of the study. Results: Group mean values of Vmax, Tmax and Vave for Acoustic Startle Inhibition, four days after termination of dosing, are presented by sex and interval in Figures 1-6. Group mean values of Vmax, Tmax and Vave for Acoustic Startle Inhibition, 11 days after termination of dosing, are presented by sex and interval in Figures 7-12. Group mean values of Vmax, Tmax and Vave for Pre-pulse Inhibition of the Acoustic Startle Inhibition, 12 days after termination of dosing, are presented by sex and interval in Figures 13-18. A. Habituation of the Acoustic Startle Response: Habituation of the acoustic startle response was demonstrated for all 400 mg/kg treated animals four and 11 days following termination of dose administration. At the four day post-dose interval, Vmax in the male 400 mg/kg dose group was decreased by 711-994% across all trial blocks and Vave was decreased by 6471054% across all trial blocks. Tmax was increased in the 400 mg/kg dose group by 57-68% across all trial blocks. Similar effects were observed in the male 400 mg/kg dose group 11 days after termination of dosing. There were no apparent differences between the 200 mg/kg dose group and the control in any endpoint four or 11 days after termination of dosing. In females, Vmax in the 400 mg/kg dose group was decreased by 72-247% across all trial blocks and Vave was decreased by 74-282% across all trial blocks. Tmax was increased in the 400 mg/kg dose group by 75-100% across all trial blocks. Similar effects were observed in the male 400 mg/kg dose group 11 days after termination of dosing. There were no apparent differences between the 200 mg/kg dose group and the control in any endpoint four or 11 days after termination of dosing. Page 4 of 24 -1965- WIL-99144 B. Prepulse Inhibition of the Acoustic Startle Response: Prepulse inhibition of the acoustic startle response was demonstrated for all animals 12 days following dose administration. In the control and 200 mg/kg groups, Vmax and Vave in both male and females decreased with increasing prepulse stimulus (Figures 13-14, 17-18). There was no apparent change in the Vmax or Vave response in the 400 mg/kg dose group in response to increasing prepulse stimulus (Figures 15-16). Vmax or Vave was increased in males of the 400 mg/kg dose group over 0-, 70- and 75-db compared to the control group, while Tmax was similar in all female groups across the range of prepulse stimuli. Discussion: The data indicate that the SR-LAB Startle Response System is capable of detecting test articleinduced changes in changes in the Vmax, Vave and Tmax of the acoustic startle response. The ability to detect prepulse inhibition of the acoustic startle response was demonstrated in the control and 200 mg/kg dose group. The inability of the 400 mg/kg dose group to respond to the prepulse inhibition of the acoustic startle response indicates that the SR-LAB Startle Response System is capable of detecting test article-induced changes in prepulse inhibition. References: 1. CYP2D1 polymorphism in methamphetamine-treated rats: Genetic differences in neonatal mortality and effects on spatial learning and acoustic startle. (1998) Vorhees, C.V., Reed, T.M., Schilling, M.A., Fisher, J.E., Moran, M.S., Cappon, G.D., Nebert, D.W. Neurotox. Teratol. 20:265-273. 2. Methods for detecting long-term CNS dysfunction after prenatal exposure to neurotoxins. (1997) Drug and Chem. Toxicol. 20:387-399. Page 5 of 24 WIL-99144 Figure 1. Graphic Depiction of the Acoustic Startle and Prepulse Inhibition Responses. Startle Habituation Trial 1,Trial 2,Trial 3, etc... Startle stimulus Startle Response TPriraelp1u,lTseriSalti2m,uTlurisal 3, etc... Startle stimulus Prepulse Inhibition -1966- Startle Response Page 6 of 24 WIL-99144 Figure 2. Male Startle Habituation (Vmax) Four Days Following Termination of Dosing 275 250 225 200 175 150 125 100 75 50 25 0 Trial 1-50 Control 200 mg/kg 400 mg/kg Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Trial 41-50 Vmax (mV) -1967- Page 7 of 24 WIL-99144 Vmax (mV) -1968- Figure 3. Female Startle Habituation (Vmax) Four Days Following Termination of Dosing Control 200 mg/kg 400 mg/kg 275 250 225 200 175 150 125 100 75 50 25 0 Trial 1-50 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Trial 41-50 Page 8 of 24 WIL-99144 Tmax (mSec) -1969- Figure 4. Male Startle Habituation (Tmax) Four Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 60.0 50.0 40.0 30.0 20.0 10.0 0.0 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Page 9 of 24 Trial 41-50 Trial 1-50 WIL-99144 Tmax (mSec) -1970- Figure 5. Female Startle Habituation (Tmax) Four Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 60.0 50.0 40.0 30.0 20.0 10.0 0.0 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Page 10 of 24 Trial 41-50 Trial 1-50 WIL-99144 60.0 Figure 6. Male Startle Habituation (Vave) Four Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 50.0 40.0 Vaverage (mV) -1971- 30.0 20.0 10.0 0.0 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Page 11 of 24 Trial 41-50 Trial 1-50 WIL-99144 Figure 7. Female Startle Habituation (Vave) Four Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 60.0 50.0 40.0 Vaverage (mV) -1972- 30.0 20.0 10.0 0.0 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Page 12 of 24 Trial 41-50 Trial 1-50 WIL-99144 Figure 8. Male Startle Habituation (Vmax) 11 Days Following Termination of Dosing Vmax (mV) -1973- 300 275 250 225 200 175 150 125 100 75 50 25 0 Trial 1-50 Control 200 mg/kg 400 mg/kg Trial 1-10 Trial 11-20 Trial 21-30 Page 13 of 24 Trial 31-40 Trial 41-50 WIL-99144 Vmax (mV) -1974- Figure 9. Female Startle Habituation (Vmax) 11 Days Following Termination of Dosing Control 200 mg/kg 400 mg/kg 300 275 250 225 200 175 150 125 100 75 50 25 0 Trial 1-50 Trial 1-10 Trial 11-20 Page 14 of 24 Trial 21-30 Trial 31-40 Trial 41-50 WIL-99144 60.0 Figure 10. Male Startle Habituation (Tmax) 11 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 50.0 40.0 Tmax (mSec) -1975- 30.0 20.0 10.0 0.0 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Page 15 of 24 Trial 41-50 Trial 1-50 WIL-99144 Tmax (mSec) -1976- Figure 11. Female Startle Habituation (Tmax) 11 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 60.0 50.0 40.0 30.0 20.0 10.0 0.0 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Page 16 of 24 Trial 41-50 Trial 1-50 WIL-99144 Figure 12. Male Startle Habituation (Vave) 11 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 70.0 60.0 50.0 Vaverage (mV) -1977- 40.0 30.0 20.0 10.0 0.0 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Page 17 of 24 Trial 41-50 Trial 1-50 WIL-99144 Figure 13. Female Startle Habituation (Vave) 11 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 70.0 60.0 50.0 Vaverage (mV) -1978- 40.0 30.0 20.0 10.0 0.0 Trial 1-10 Trial 11-20 Trial 21-30 Trial 31-40 Page 18 of 24 Trial 41-50 Trial 1-50 Vmax (mV) WIL-99144 200.0 180.0 160.0 140.0 120.0 100.0 80.0 60.0 40.0 20.0 0.0 Figure 14. Male Prepulse Inhibition (Vmax) of the Acoustic Startle Response 12 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 0 db 70 db 75 db 80 db 85 db 90db Page 19 of 24 -1979- WIL-99144 Vmax (mV) -1980- 200.0 180.0 160.0 140.0 120.0 100.0 80.0 60.0 40.0 20.0 0.0 Figure 15. Female Prepulse Inhibition (Vmax) of the Acoustic Startle Response 12 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 0 db 70 db 75 db 80 db 85 db 90db Page 20 of 24 WIL-99144 Figure 16. Male Pre-pulse Inhibition (Tmax) of the Acoustic Startle Response 12 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 60.0 50.0 40.0 Tmax (mSec) -1981- 30.0 20.0 10.0 0.0 0 db 70 db 75 db 80 db Pre-Ppauglsee2s1tiomfu2l4us (db) 85 db 90db WIL-99144 60.0 Figure 17. Female Pre-pulse Inhibition (Tmax) of the Acoustic Startle Response 12 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 50.0 40.0 Tmax (mSec) -1982- 30.0 20.0 10.0 0.0 0 db 70 db 75 db 80 db Pre-pulse stimulus (db) Page 22 of 24 85 db 90db Vaverage (mV) WIL-99144 45.0 40.0 35.0 30.0 25.0 20.0 15.0 10.0 5.0 0.0 Figure 18. Male Prepulse Inhibition (Vave) of the Acoustic Startle Response 12 Days Following Termination of Dosing 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 0 db 70 db 75 db 80 db 85 db 90db Pre-pulse stimulus (db) Page 23 of 24 -1983- WIL-99144 Figure 19. Female Pre-pulse Inhibition (Vave) of the Acoustic Startle Response 12 Days Following Termination of Dosing 45.0 0 mg/kg/day 200 mg/kg/day 400 mg/kg/day 40.0 35.0 30.0 Vaverage (mV) 25.0 -1984- 20.0 15.0 10.0 5.0 0.0 0 db 70 db 75 db 80 db Pre-pulse stimulus (db) Page 24 of 24 85 db 90db -1985- WIL-99149 Date Range: May 17-21, 1999 Demonstration of the Sensitivity of the SDI-PAS to Detect Alterations in Locomotor Activity in Rats Study Objective: Regulatory guidelines require that the testing laboratory demonstrate that the devices and systems used for measuring locomotor activity be able to detect chemicallyinduced increases and decreases in locomotor activity. The objective of this study was to demonstrate that the locomotor activity measuring apparatus (San Diego Instruments - Photobeam Activity System [SDI-PAS]) and the testing paradigm used by WIL Research Laboratories, Inc., met this criterion. Test And Control Articles: Two test articles were employed, one to elicit increases in motor activity (d-amphetamine sulfate, Research Biochemicals International, Natick, MA, Lot. No. BS-111-100) and one to elicit decreases in motor activity (chlorpromazine hydrochloride, Sigma Chemical Company, St. Louis, MO, Lot No. 48 H 1403). Physiological saline was used as the vehicle and for treatment of the concurrent negative control group. Test System: Juvenile (approximately six-week old) Sprague-Dawley Crl:CD(SD)IGS BR rats weighing 175 + 27 grams (males) and 146 + 20 grams (females) at the time of randomization were used on the study. The rats were randomly assigned to treatment groups by body weight stratification in a block design, and subsequently allocated to group- and sex-uniform replicates for the locomotor activity evaluations. Dosing and locomotor activity evaluations occurred on the day after randomization (Day 0). Environmental Conditions: The rats were acclimated to laboratory conditions for 13 days prior to dosing. Animals were housed and maintained under conditions consistent with maintaining good health and as per WIL Standard Operating Procedures. Temperature and humidity were maintained at 72 + 4 F and 50 + 20%, respectively, in a room with a 12 hours light/12 hours dark (0600-1800 hrs) photoperiod. The facilities at WIL Research Laboratories, Inc. are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. -1986- WIL-99149 Treatment Regimen: Animals were assigned to treatment groups as follows: Group Number Test Article Dosage Level (mg/kg) Dosage Concentration (mg/ml) Dosage Volume (mg/kg) Number of Animals Male Female 1 PS 0 2 AMP 2 3 AMP 4 4 CPZ 5 5 CPZ 10 0 1.0 12 12 2 1.0 12 12 4 1.0 12 12 5 1.0 12 12 10 1.0 12 12 PS = Physiological Saline AMP = d-Amphetamine Sulfate CPZ = Chlorpromazine Hydrochloride The test and control articles were administered as a single intraperitoneal injection (Day 0). Individual doses were calculated based on the animals' body weights recorded on the day of dose administration. Locomotor Activity Monitoring Methods: Locomotor activity was monitored once 4-5 days prior to dose administration (pretest) and on the day of dose administration. The duration of each test session was 60 minutes. The test interval was five minutes. Monitoring following dosing commenced 15 minutes after test or control article administration. The duration of the test session and length of the test interval were selected based on results of a previous study (WIL-99140). Locomotor activity monitoring was performed using the SDI Photobeam Activity System (San Diego Instruments, Inc., San Diego, CA), which includes Photobeam Activity System (PAS) software, analyzer and 24 activity monitors. A local personal computer linked to the laboratory's mainframe computer controls the SDI-PAS. Each locomotor activity monitoring unit consists of seven photobeam emitting/detecting units attached to a mounting frame. A clear acrylic shoe box -style cage (18.5"L x 9.5"W x 8"H) fits into the mounting frame to contain a single animal during the test session. Activity is measured as interruptions of the photobeams. Photobeam diagnostic checks were performed prior to and following completion of the test session. Confirmation that the software-driven procedure was operating correctly was obtained by manually blocking the photobeams with pre-cut pieces of cardboard or other appropriate devices. After completion of the test session, motor -1987- WIL-99149 activity and photobeam files are transferred electronically to the mainframe computer for subsequent manipulation and presentation of the collected information, i.e., generation of tables, including statistical analysis. Activity counts are presented as Total Activity Counts (ambulatory plus stereotypic counts) and Ambulatory Activity Counts. Sequential interruption of 2 or more photobeams, i.e., gross motor movement, is recorded as one ambulatory activity count. Repeated beam breaks of the same photobeam, i.e., fine motor movement, is recorded as one stereotypic count. Monitoring was performed in a sound-attenuated room equipped with a white-noise generator set to operate at approximately 70 db. Statisical Analysis: Locomotor activity data were analyzed by analysis of variance. A one-way ANOVA followed by Dunnett's test was conducted to determine significant treatment differences from the control group at significance levels of p < 0.05 and p < 0.01. Quality Assurance: The raw data and draft report were audited by the WIL Quality Assurance Unit to assure that the final report accurately describes the conduct and findings of the study. Results: Group mean locomotor activity counts are presented in Table 1. The data are presented graphically by sex, interval and activity type in Figures 1-8. Discussion: There were no differences in either total or ambulatory activity counts for either sex during the pretest evaluations. Dose-dependent increases in both total and ambulatory activity counts were observed for both males and females following administration of d-amphetamine sulfate (AMP). For males, over the entire 60-minute test session, total (ambulatory) counts were increased 103 (135)% at 2 mg/kg AMP and 166 (193)% at 4 mg/kg AMP. For females, over the entire 60-minute test session, total (ambulatory) activity counts were increased 37 (46)% at 2 mg/kg AMP and 146 (184)% at 4 mg/kg AMP. With the exception of the 2 mg/kg AMP females, all differences from the vehicle control group were statistically significant (p < 0.01). -1988- WIL-99149 Dose-dependent decreases in both total and ambulatory activity counts were observed for both males and females following administration of chlorpromazine hydrochloride (CPZ). For males, over the entire 60-minute test session, total (ambulatory) counts were decreased 77 (85)% at 5 mg/kg CPZ and 96 (98)% at 10 mg/kg CPZ. For females, over the entire 60-minute test session, total (ambulatory) activity counts were decreased 88 (92)% at 5 mg/kg CPZ and 97 (99)% at 10 mg/kg CPZ. All differences from the vehicle control group were statistically significant (p < 0.01). Based on the results obtained, the SDI-PAS is sufficiently sensitive to detect doserelated increases and decreases in locomotor activity under the testing paradigm that was used. PROJECT NO.:WIL-99149 SPONSOR:WIL RESEARCH LABS TABLE 1 SENSITIVITY OF THE SDI-PAS TO DETECT LOCOMOTOR ACTIVITY IN RATS GROUP MEAN MOTOR ACTIVITY COUNTS PAGE 1 ----------------------------------------------------------------------------------------------------------------------------------- ----- M A L E ----- GROUP: 0 MG/KG 2 MG/KG AMP 4 MG/KG AMP 5 MG/KG CPZ 10 MG/KG CPZ ----------------------------------------------------------------------------------------------------------------------------------- PRETEST TOTAL MEAN 1019. 934. 1246. 1163. 1221. S.D. 398.2 447.5 735.0 377.1 444.6 N 12 12 12 12 12 AMBULATORY MEAN 309. 281. 391. 376. 366. S.D. 139.5 177.0 280.9 154.3 194.8 N 12 12 12 12 12 DAY 0 TOTAL MEAN 794. 1609.** 2110.** 184.** 33.** S.D. 293.6 655.8 638.9 195.6 25.6 N 12 12 12 12 12 AMBULATORY MEAN 234. 549.** 686.** 34.** 5.** S.D. 114.9 254.8 330.0 71.3 6.0 N 12 12 12 12 12 ----------------------------------------------------------------------------------------------------------------------------------- For statistical analyses, control group 1 was compared to groups 2 and 3; control group 1 was compared to groups 4 and 5. ** = Significantly different from control group 1 at 0.01 using Dunnett's test -1989- PROJECT NO.:WIL-99149 SPONSOR:WIL RESEARCH LABS TABLE 1 SENSITIVITY OF THE SDI-PAS TO DETECT LOCOMOTOR ACTIVITY IN RATS GROUP MEAN MOTOR ACTIVITY COUNTS PAGE 2 ----------------------------------------------------------------------------------------------------------------------------------- ----- F E M A L E ----- GROUP: 0 MG/KG 2 MG/KG AMP 4 MG/KG AMP 5 MG/KG CPZ 10 MG/KG CPZ ----------------------------------------------------------------------------------------------------------------------------------- PRETEST TOTAL MEAN 1033. 1190. 974. 853. 1347. S.D. 463.6 543.2 343.2 231.6 695.0 N 12 12 12 12 12 AMBULATORY MEAN 357. 399. 312. 277. 480. S.D. 193.8 204.5 128.3 105.3 309.4 N 12 12 12 12 12 DAY 0 TOTAL MEAN 1223. 1672. 3005.** 142.** 31.** S.D. 676.1 759.8 773.4 116.9 45.4 N 12 12 12 12 12 AMBULATORY MEAN 442. 646. 1255.** 36.** 4.** S.D. 251.0 348.5 451.5 39.5 5.2 N 12 12 12 12 12 ----------------------------------------------------------------------------------------------------------------------------------- For statistical analyses, control group 1 was compared to groups 2 and 3; control group 1 was compared to groups 4 and 5. ** = Significantly different from control group 1 at 0.01 using Dunnett's test PMASUMv4.13 03/30/2000 -1990- Mean Acivity Count WIL-99149 1400 1200 1000 800 600 400 200 0 0 mg/kg Figure 1 Male Pretest Total Activity 2 mg/kg AMP 4 mg/kg AMP Treatment 5 mg/kg CPZ 10 mg/kg CPZ Page 1 -1991- Mean Activity Count WIL-99149 450 400 350 300 250 200 150 100 50 0 0 mg/kg Figure 2 Male Pretest Ambulatory Activity 2 mg/kg AMP 4 mg/kg AMP Treatment 5 mg/kg CPZ 10 mg/kg CPZ Page 1 -1992- Mean Activity Count WIL-99149 1600 1400 1200 1000 800 600 400 200 0 0 mg/kg Figure 3 Female Pretest Total Activity 2 mg/kg AMP 4 mg/kg AMP Treatment 5 mg/kg CPZ 10 mg/kg CPZ Page 1 -1993- Mean Activity Count WIL-99149 600 500 400 300 200 100 0 0 mg/kg Figure 4 Female Pretest Ambulatory Activity 2 mg/kg AMP 4 mg/kg AMP Treatment 5 mg/kg CPZ 10 mg/kg CPZ Page 1 -1994- WIL-99149 2500 2000 1500 Figure 5 Male Day 0 Total Activity * * * * Mean Activity Count 1000 500 0 0 mg/kg 2 mg/kg AMP 4 mg/kg AMP Treatment ** = Significantly different from control group 1 at 0.01 using Dunnett's test * * 5 mg/kg CPZ * * 10 mg/kg CPZ Page 1 -1995- WIL-99149 Figure 6 Male Day 0 Ambulatory Activity 800 700 * * 600 * * 500 Mean Activity Count 400 300 200 100 0 0 mg/kg 2 mg/kg AMP 4 mg/kg AMP Treatment ** = Significantly different from control group 1 at 0.01 using Dunnett's test * * 5 mg/kg CPZ * * 10 mg/kg CPZ Page 1 -1996- WIL-99149 Figure 7 Female Day 0 Total Activity 3500 3000 * * 2500 Mean Activity Count 2000 1500 1000 500 0 0 mg/kg 2 mg/kg AMP 4 mg/kg AMP Treatment ** = Significantly different from control group 1 at 0.01 using Dunnett's test * * 5 mg/kg CPZ * * 10 mg/kg CPZ Page 1 -1997- WIL-99149 Figure 8 Female Day 0 Ambulatory Activity 1400 * * 1200 1000 Mean Activity Count 800 600 400 200 0 0 mg/kg 2 mg/kg AMP 4 mg/kg AMP Treatment ** = Significantly different from control group 1 at 0.01 using Dunnett's test * * 5 mg/kg CPZ * * 10 mg/kg CPZ Page 1 -1998- -1999- WIL-99168 A STUDY WITH UNTREATED STOCK RATS TO EXPAND THE WIL DEVELOPMENTAL NEUROTOXICITY HISTORICAL CONTROL DATABASE Study Objective: The objective of this study was to generate historical control data for developmental neurotoxicity studies focusing on postnatal day 11 rat brain morphometrics, locomotor activity and acoustic startle response. This draft report includes the acoustic startle response data collected from the SR Lab Startle Response System (San Diego Instruments, San Diego, CA) and brain morphometry. Test and Control Articles: No test or control article was employed to elicit changes in the auditory startle response as this study is designed to produce historical control data. Test System: Ten male and ten female neonatal (20 day old) rats weighing 47 + 9 grams (males) and 40 + 10 grams (females) at the time of the startle response evaluations were used on the study. The neonates were born of dams bred at WIL Research Laboratories, Inc. using standard procedures. The parental animals were Sprague-Dawley Crl:CD(SD)IGS BR strain rats. Two neonates per sex were selected from the litters of five different dams based on health and apparent normal development. Environmental Conditions: The animals were housed and maintained under conditions consistent with maintaining good health and as per WIL standard operating procedures. Temperature and relative humidity at approximately were maintain at 72 4F and 30-70%, respectively in a room with a 12 hour light/dark photoperiod (6 a.m. to 6 p.m.). Temperature and relative humidity will be recorded once per day. The facilities at WIL Research Laboratories, Inc. are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International). Viability Observations: The rats were observed for mortality/moribundity and general condition twice daily, in the morning and in the afternoon. Page 1 of 19 -2000- WIL-99168 Body Weights: Body weights were recorded on PND 17, PND 20 (the day of evaluation) and PND 21. Startle Response Assessment: All startle response measurements were made using the SR-Lab Startle Response System (San Diego Instruments, San Diego, CA). The apparatus consisted of a slotted acrylic cylinder (6" long by 2.25" in diameter) mounted in a horizontal orientation on a platform and enclosed in a sound-attenuating chamber. A piezoelectric force transducer is mounted on the under side of the platform. When an animal placed inside the cylinder reacts to the startle stimulus, the movement produces a deflection of the platform, which induces a voltage change in the piezoelectric force transducer. This voltage signal is amplified and converted to a digital signal for analysis. Startle response measures obtained are maximum response amplitude (Vmax), latency or time to Vmax (Tmax) and average response amplitude (Vave). Startle response evaluations were performed in a sound-attenuated room equipped with a white-noise generator set to operate at approximately 70 db. The transducers were calibrated to provide the correct average output and sound checks were performed on the chamber and room white noise generators prior to data collection. Testing was controlled and data are captured/converted via a local PC (486DX2 or better). Data were transferred to the mainframe computer system for subsequent presentation and evaluation. A. Habituation of the Acoustic Startle Response: Habituation of the acoustic startle response was evaluated for two rats/sex from five different litters (N=10). The test session consisted of a 5-minute acclimation period with a 65-db broadband background white noise. The startle stimulus for each trial was a 115-db, mixed frequency noise burst stimulus (20 ms in duration). Responses were recorded during the first 100 ms following startle signal onset for each trial. The test session consisted of 50 trials with an eight-second inter-trial-interval. Startle response data was analyzed in five blocks of 10 trials each plus all 50 trial combined.1,2 B. Prepulse Inhibition of the Acoustic Startle Response: Prepulse inhibition of the acoustic startle response was evaluated for all animals 12 days following dose administration. Prepulse trials were identical to habituation trials except that the prepulse trial startle signal was preceded by a less intense, but otherwise identical signal of 20-ms in duration (measured from prepulse signal onset to startle signal onset). Five prepulse intensities were used (70-, 75-, 80-, 85- and 90-db). These five, plus no-prepulse trials, constituted the six trial types. Each trial Page 2 of 19 -2001- WIL-99168 type was presented eight times for a total of 48 trials. Trial order for prepulse trials was balanced using a Latin-square design with the provision that the first trial was a no-prepulse trial.1,2 Prepulse inhibition response was analyzed in six trial blocks by prepulse intensity (0-, 70-, 75-, 80-, 85- and 90-db). Morphometry: On postnatal day 11, one pup/sex from six litters was euthanized by carbon dioxide inhalation and perfused in situ. The brains were processed for morphometric evaluation as per WIL standard operating procedures (T4-035, as revised). Ten linear measurements (based on those of Rodier and Gramann, 1979) were made on four coronal sections of cerebrum and midbrain and one sagittal section of cerebellum and brainstem from each pup. Images were captured using the Pax-ItTM Computer System as per WIL standard operating procedures (T8-005, as revised). The following brain areas were measured: R1 Width of hemisphere, perpendicular to height and adjacent to top of dorsal white matter tract. R2 Height of hemisphere, immediately adjacent to medial margin of lateral ventricle. R3 Vertical thickness of the frontoparietal cortex, parallel to height measurement. R4 Width of caudoputtamen of hemisphere. R5 One-half the width of the base of the forrix. R6 Vertical Height from the base of the brain to the anterior commissure. R7 Vertical thickness of the frontoparietal cortex measured at the highest point of the corpus callosum. R8 Radial thickness of the parietal cortex (approximately 10 o'clock position). R9 Thickness of the piriform cortex (measured at surface indentation). R10 Thickness of the corpus callosum at the midline. R34 Height of the cerebellum (highest dimension), parallel to thickness of pons, Quality Assurance: The raw data and draft report will be audited by the WIL Quality Assurance Unit prior to assure that the final report accurately describes the conduct and the findings of the study. Results: A. Viability: No deaths or overt signs of clinical illness occurred on the study. Page 3 of 19 -2002- WIL-99168 B. Body Weights: There were no remarkable differences in body weight or changes in body weight gain (Table 1). C. Habituation: Startle response, as measured by Vmax and Vave, decreased over time for both males and females (Figures 1-6). Compared to the initial trials (trial block 1-10), Vmax decreased 14.9%, 22.3%, 26.0% and 26.1% (males) and 22.8%, 32.3%, 34.7% and 50.3% (females) for trial blocks 11-20, 21-30, 31-40 and 41-50, respectively. Compared to the initial trials (trial block 1-10), Vave was decreased 12.1%, 20.6%, 23.1% and 22.2% (males) and 17.7%, 26.5%, 30.4% and 44.0% (females) for trial blocks 11-20, 21-30, 31-40 and 41-50, respectively. No effect on Tmax was apparent for either sex. D. Prepulse Inhibition: Startle response, as measured by Vmax and Vave, decreased with increasing prepulse signal intensity for both males and females (Figures 7-12). Compared to the no-prepulse trials, Vmax was decreased 7.8%, 15.0%, 32.5%, 38.5% and 54.4% (males) and 3.1%, 8.0%, 18.5%, 38.3% and 55.1% (females) for the 70-, 75-, 80-, 85- and 90-decibel prepulse signal intensities, respectively. Compared to the no-prepulse trials, Vave was decreased 12.3%, 16.6%, 32.8%, 39.0% and 50.4% (males) and 5.7%, 10.1%, 22.7%, 40.3% and 56.4% (females) for the 70-, 75-, 80-, 85- and 90-decibel prepulse signal intensities, respectively. No effect on Tmax was apparent for either sex. E. Morphometry: All measurements provided robust measurements (Table 2). Measurements were repeatable across hemispheres (data not shown). Page 4 of 19 -2003- WIL-99168 Discussion: The expected habituation over time to repeated auditory stimuli of the same intensity was observed, as was the expected decrease in auditory startle response associated with increasing prepulse signal intensity. Both Vmax and Vave data showed clear time- (habituation) or signal- (prepulse inhibition) related decreases in startle response. The results of this investigation demonstrate that the equipment and testing paradigms used are capable of detecting changes in startle response in young (PND 20) rats. References: 1. CYP2D1 polymorphism in methamphetamine-treated rats: Genetic differences in neonatal mortality and effects on spatial learning and acoustic startle. (1998) Vorhees, C.V., Reed, T.M., Schilling, M.A., Fisher, J.E., Moran, M.S., Cappon, G.D., Nebert, D.W. Neurotox. Teratol. 20:265-273. 2. Methods for detecting long-term CNS dysfunction after prenatal exposure to neurotoxins. (1997) Drug and Chem. Toxicol. 20:387-399. Page 5 of 19 -2004- WIL-99168 Animal No. 29796-01 29796-02 29775-03 29775-04 29797-05 29797-06 29784-07 29784-08 29800-09 29800-10 Mean S.D. N 29796-11 29796-12 29775-13 29775-14 29797-15 29797-16 29784-17 29784-18 29800-19 29800-20 Mean S.D. N Table 1. Individual Body Weights. Sex PND 17 M 37 M 35 M 36 M 37 M 38 M 40 M 36 M 30 M 36 M 36 36.1 2.56 10 F 37 F 34 F 34 F 25 F 36 F 38 F 30 F 34 F 34 F 36 33.8 3.79 10 PND 20 42 43 44 45 54 55 45 38 48 47 46.1 5.22 10 43 42 41 30 49 50 38 42 42 46 42.3 5.68 10 PND 21 45 49 47 48 57 59 48 42 51 50 49.6 5.13 10 47 46 46 34 49 50 38 42 42 46 44 5.01 10 Page 6 of 19 -2005- WIL-99168 Table 2. Summary of Data Means and Standard Deviations MEASUREMENT R1 Mean SD n R2 Mean SD n R3 Mean SD n R4 Mean SD n R5 Mean SD n R6 Mean SD n R7 Mean SD n R8 Mean SD n R9 Mean SD n R10 Mean SD n R34 Mean SD n MALE 0.77432 0.05060 6 0.21684 0.04163 6 0.15563 0.01343 5 1.72302 2.83884 5 0.11062 0.00958 6 0.05612 0.00826 6 0.13064 0.02023 6 0.29491 0.05562 6 2.11685 3.36504 6 3.82729 1.98242 6 0.38703 0.07017 6 FEMALE 0.78033 0.05858 6 0.21348 0.02186 6 0.15244 0.00668 6 2.05304 3.41895 6 0.09825 0.01312 6 0.04579 0.00636 6 0.14496 0.03126 6 0.31876 0.04145 6 2.12007 3.36298 6 3.82768 1.98127 6 0.36064 0.05789 6 Page 7 of 19 WIL-99168 Figure 1: Habituation to Acoustic Startle Response (Vmax) in Untreated PND 20 Male Rats Trials 1-10 300 Trials 11-20 Trials 21-30 Trials 31-40 Trials 41-50 Trials 1-50 250 200 Vmax (mV) -2006- 150 100 50 0 Trial Blocks Page 8 of 19 WIL-99168 Figure 2: Habituation to Acoustic Startle Response (Vmax) in Untreated PND 20 Female Rats Trials 1-10 250 Trials 11-20 Trials 21-30 Trials 31-40 Trials 41-50 Trials 1-50 200 Vmax (mV) -2007- 150 100 50 0 Trial Blocks Page 9 of 19 WIL-99168 Figure 3: Habituation to Acoustic Startle Response (Tmax) in Untreated PND 20 Male Rats Trials 1-10 30 Trials 11-20 Trials 21-30 Trials 31-40 Trials 41-50 Trials 1-50 25 20 Tmax (mSec) -2008- 15 10 5 0 Trial Blocks Page 10 of 19 WIL-99168 Figure 4: Habituation to Acoustic Startle Response (Tmax) in PND 20 Female Rats Trials 1-10 26.5 Trials 11-20 Trials 21-30 Trials 31-40 Trials 41-50 Trials 1-50 26 25.5 Tmax (mSec) -2009- 25 24.5 24 23.5 23 Trial Blocks Page 11 of 19 WIL-99168 Figure 5: Habitutation to Acoustic Startle Response (Vave) in Untreated PND 20 Male Rats Trials 1-10 60 Trials 11-20 Trials 21-30 Trials 31-40 Trials 41-50 Trials 1-50 50 40 Vave (mV) -2010- 30 20 10 0 Trial Blocks Page 12 of 19 WIL-99168 Vave (mV) -2011- Figure 6: Habituation to Acoustic Startle Response (Vave) in Untreated PND 20 Female Rats Trials 1-10 50 Trials 11-20 Trials 21-30 Trials 31-40 Trials 41-50 Trials 1-50 45 40 35 30 25 20 15 10 5 0 Trial Blocks Page 13 of 19 WIL-99168 Figure 7: Prepulse Inhibition of Acoustic Startle Response (Vmax) in Untreated PND 20 Male Rats 250.0 0 dB 70 dB 75 dB 80 dB 85 dB 90 dB 200.0 Vmax (mV) -2012- 150.0 100.0 50.0 0.0 Prepulse Intensity Page 14 of 19 Vmax (mV) WIL-99168 180.0 160.0 140.0 120.0 100.0 80.0 60.0 40.0 20.0 0.0 Figure 8: Prepulse Inhibition of Acoustic Startle Response (Vmax) in Untreated PND 20 Female Rats 0 dB 70 dB 75 dB 80 dB 85 dB 90 dB Prepulse Intensity Page 15 of 19 -2013- WIL-99168 Figure 9: Prepulse Inhibition of Acoustic Startle Response (Tmax) in Untreated PND 20 Male Rats 0 dB 70 dB 75 dB 80 dB 85 dB 90 dB 30.0 25.0 20.0 Tmax (mSec) -2014- 15.0 10.0 5.0 0.0 Prepulse Intensity Page 16 of 19 WIL-99168 Figure 10: Prepulse Inhibition of Acoustic Startle Response (Tmax) in Untreated PND 20 Female Rats 0 dB 70 dB 75 dB 80 dB 85 dB 90 dB 25.5 25.0 24.5 Tmax (mSec) -2015- 24.0 23.5 23.0 22.5 22.0 21.5 Prepulse Intensity Page 17 of 19 WIL-99168 Vave (mV) -2016- Figure 11: Prepulse Inhibition of Acoustic Startle Response (Vave) in Untreated PND 20 Male Rats 0 dB 70 dB 75 dB 80 dB 85 dB 90 dB 50.0 45.0 40.0 35.0 30.0 25.0 20.0 15.0 10.0 5.0 0.0 Prepulse Intensity Page 18 of 19 WIL-99168 Figure 12: Prepulse Inhibition of Acoustic Startle Response (Vave) in Untreated PND 20 Female Rats 0 dB 70 dB 75 dB 80 dB 85 dB 90 dB 40.0 35.0 30.0 Vave (mV) -2017- 25.0 20.0 15.0 10.0 5.0 0.0 Prepulse Intensity Page 19 of 19 -2018- Validation Of Developmental Neurotoxicity Endpoints In Rats Administered Methimazole In Drinking Water G.J. Schaefer, M.D. Nemec, M.T. Herberth, J.A. Pitt, A.E. Radovsky and J.F. Knapp. WIL Research Laboratories, Inc., Ashland, OH. The purpose of this study was to validate procedures outlined in the U.S. EPA OPPTS 870.6300 guideline for developmental neurotoxicity (DNT) studies. Pregnant Sprague-Dawley rats (N=25/group) were administered either 0, 10, 30 or 100 ppm methimazole (used to treat human hyperthyroidism) in drinking water from gestation day 6 through postnatal day (PND) 21. Endpoints evaluated in the dams included a modified functional observational battery (mFOB), body weights, and food and water consumption. In the pups, brain weights, qualitative neuropathology and quantitative brain morphometry were evaluated at PND 11, 22 and 72. Auditory startle, locomotor activity, learning and memory (Biel Maze) and mFOB were assessed in the offspring repeatedly throughout their development. During lactation, the dams in all three exposure groups weighed significantly less, and consumed less food and water than controls. Locomotor activity was reduced on PND 13 and increased on PND 21 for 30 and 100 ppm offspring relative to controls. Auditory startle response endpoints (Vmax, Tmax and Vave) were affected in the 30 and 100 ppm offspring at PND 20 and 60. Pup body weights were reduced from PND 1-70 for both sexes in all exposure groups relative to controls. Delayed sexual maturation (balanopreputial separation and vaginal patency) was readily apparent in all three exposure groups, except for vaginal patency at 10 ppm. In addition, on PND 11 and 22 both male and female offspring mean brain weights (100 ppm) were reduced relative to controls. Brain weights were reduced on PND 72 for 100 ppm male offspring only. No dam or offspring exposure-related deficits were noted in the mFOB at any time point. Qualitative neuropathology and quantitative morphometry at PND 11 (comparing immersion and perfusion fixation at PND 11), 22 and 72, along with learning and memory data, will be presented. The data analyzed thus far are being used to assess the appropriateness of methimazole as a positive control agent for DNT studies. INTRODUCTION In humans, hypothyroidism causes irreversible mental retardation and various neuromotor disabilities. Methimazole administration to pregnant rats is a commonly used experimental model of human congenital hypothyroidism. The objective of this study was to evaluate the sensitivity of the experimental design described by U.S. EPA OPPTS Guideline 870.6300 (Developmental Neurotoxicity) to predict the adverse effects in rats of a known human developmental neurotoxicant. MATERIALS AND METHODS Methimazole was administered to groups of 25 bred female Crl:CD(SD) IGS BR SpragueDawley (Charles River) at dosage levels of 0, 10, 30 or 100 ppm in drinking water from gestation day 6 through postnatal day (PND) 21. Offspring were evaluated by use of a modified -2019- functional observational battery (PND 4, 11, 21, 35, 45 and 60) and evaluated for motor activity (PND 13, 17, 21 and 61), auditory startle response (PND 20 and 60) and learning and memory in the Biel water maze (PND 22 and 62). Qualitative neuropathology and quantitative morphometry evaluations were conducted at PND 11 (comparing immersion and perfusion fixation at PND 11), 22 and 72. For quantitative morphometry, 10 measurements were made on 3 levels. All data are presented in tables and figures as mean standard deviation. RESULTS Maternal body weights, food consumption and water consumption were reduced in all methimazole-treated groups throughout the entire lactation period. Live litter size was unaffected in any of the treated groups; however, pup viability was reduced from birth (PND 0) to PND 4 in the 10 and 100 ppm groups (data not shown). Pup weights were reduced at birth for all exposure levels and remained reduced throughout the study. Markers of sexual maturation were delayed in all methimazole-treated groups with the exception of vaginal patency in the 10 ppm group. The modified functional observational battery detected no differences in dam or offspring findings when comparing the treated groups to the concurrent control group. Motor activity was reduced on PND 13 and increased on PND 21 for pups in the 30 and 100 ppm groups. Auditory startle response was affected for both sexes at the 30 and 100 ppm dosage levels on PND 20 and 60. Swimming ability was markedly reduced for both sexes at 30 and 100 ppm, and latency to escape the Biel maze was increased at the 30 and 100 ppm dosage levels on PND 22. On PND 62, swimming ability was comparable between all groups, but latency to escape the Biel maze was still increased for both sexes at the 30 and 100 ppm dosage levels. The mean number of errors committed during the swimming trials, however, was comparable among all groups on both PND 22 and 62. On PND 11 and 22 both male and female pup brain weights in the 100 ppm group were reduced relative to the control group. On PND 72 brain weights were reduced for 100 ppm male pups only, but gross brain lengths were reduced in both sexes. Coronal sections of the cerebrum and a mid-sagittal section of the cerebellum and brainstem of the 100 ppm pups had significantly reduced measurements at all time points. There were qualitative histopathologic abnormalities in the brains of 100 ppm pups at all time points. On PND 11 there were an increased number of undifferentiated cells under the ependyma of the roof of the lateral ventricle, and a disproportionately short ventral limb of the dentate hilus in the hippocampus in 100 ppm pups of both sexes in both the perfused and immersion-fixed groups. On PND 22, 100 ppm pups had persistence of the external granule cell layer of the cerebellum which had disappeared in control groups at this timepoint. On PND 72, there were increased malalignments of the pyramidal neurons of the hippocampus in 100 ppm pups of both sexes and males had instances of abnormal foliation in cerebellar lobules 8 and/or 9. -2020- CONCLUSIONS Based on the endpoints affected (e.g., pup body weight, locomotor activity, auditory startle response, learning and memory, brain weight and length, qualitative and quantitative neuropathology), methimazole altered multiple functional domains in the F1 generation demonstrating that this compound is acceptable for use as a positive control agent in DNT studies. Both immersion and perfusion fixation of the PND 11 pup brains provided adequate tissue samples for quantitative morphometrics and qualitative histopathology. ACKNOWLEDGEMENTS The authors wish to acknowledge the following WIL Research Laboratories, Inc. personnel for their assistance in the conduct of this project and preparation of materials for this poster. Kim Collings, Lorelei Watson, Roxanne Phillips and Ron Wilson -2021- MATERNAL WATER AND COMPOUND CONSUMPTION DURING GESTATION AND LACTATION 0 PPM 10 PPM 30 PPM 100 PPM Gestation Day 6-20 Water Compound (ml/kg) (mg/kg/day) 38 5.2 NA 36 4.5 1 0.0 36 6.1 3 0.5 34 4.3* 10 1.3 Lactation Day 0-21 Water Compound (ml/kg) (mg/kg/day) 75 9.5 NA 59 7.2** 2 0.2 54 6.5** 5 0.8 48 5.9** 16 2.0 * = Significantly different from the control group at p<0.05 ** = Significantly different from the control group at p<0.01 Pup Body Weight (Grams) Adult Body Weight (Grams) F1 BODY WEIGHTS Male 70 0 PPM 10 PPM 30 PPM 60 50 40 30 ** ** ** 20 ** ** ** ** ** 10 ** 0 ** ** ** ** **** ** ** ** ** ** ** ** ** ** * ** ** * ** ** ** 100 PPM 450 400 350 300 ** ** ** 250 ** ** 200 ** 150 100 50 0 -2022- PNDPND 1 4 (BS) PN D PN 7 D 11 PN D PN 13 D 17 PN D 2 1 W 4 W 5 W 6 W 7 W 8 W 9 W 10 * = Significantly different from the control group at p<0.05 **= Significantly different from the control group at p<0.01 Pup Body Weight (Grams) Adult Body Weight (Grams) 0 PPM 60 50 40 ** ** 30 ** ** ** 20 ** ** ** ** ** ** 10 ** 0 F1 BODY WEIGHTS Female 10 PPM 30 PPM 100 PPM 450 400 350 ** ** ** ** ** ** ** ** ** ** ** ** ** 300 ** ** ** 250 * **** ** 200 ** ** ** ** 150 ** 100 50 0 -2023- PNDPND 1 4 (BS) PND PN 7 D 11 PND PND 13 PND 17 2 1 W 4 W 5 W 6 W 7 W 8 W 9 W 10 * = Significantly different from the control group at p<0.05 ** = Significantly different from the control group at p<0.01 Total Activity Counts for PND 13 Male Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 250 200 Counts 150 -2024- 100 50 0 0-15 15-30 31-45 Interval (min) 46-60 Total Activity Counts for PND 17 Male Rats Exposed to Methimazole Counts -2025- 0 ppm 10 ppm 30 ppm 100 ppm 450 400 350 300 250 200 150 100 50 0 0-15 15-30 31-45 Interval (min) 46-60 Total Activity Counts for PND 21 Male Rats Exposed to Methimazole Counts -2026- 0 ppm MMZ 10 ppm MMZ 30 ppm MMZ 100 ppm MMZ 600 500 400 300 ** ** 200 100 0 0-15 16-30 31-45 Interval (min) 46-60 Total Activity Counts in PND 61 Male Rats Exposed to Methimazole 1200 0 ppm 10 ppm 30 ppm 100 ppm 1000 800 Counts -2027- 600 400 200 0 0-15 16-30 31-45 Interval (min) 46-60 Total Activity Counts for PND 13 Female Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 250 200 Counts 150 -2028- 100 50 0 0-15 16-30 31-45 Interval (min) 46-60 Total Activity Counts in PND 17 Female Rats Exposed to Methimazole Counts -2029- 0 ppm 10 ppm 30 ppm 100 ppm 450 400 350 * 300 ** ** 250 ** 200 ** 150 100 50 0 0-15 16-30 31-45 Interval (min) 46-60 Total Activity Counts in PND 21 Female Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 600 500 Total Counts -2030- 400 ** **** ** 300 ** 200 100 0 0-15 16-30 31-45 Interval (min) 46-60 Total Activity Counts in PND 61 Female Rats Exposed to Methimazole 1200 0 ppm 10 ppm 30 ppm 100 ppm 1000 800 Counts -2031- 600 400 200 0 0-15 16-30 31-45 Interval (min) 46-60 Preweaning Total Activity Counts in Male Rats Exposed to Methimazole Counts -2032- 1800 1600 1400 1200 1000 800 600 400 200 0 0 ppm MMZ 10 ppm MMZ 30 ppm MMZ 100 ppm MMZ ** PND 13 PND 17 Age at Testing PND 21 Preweaning Total Activity Counts in Female Rats Exposed to Methimazole Counts -2033- 1800 1600 1400 1200 1000 800 600 400 200 0 0 ppm 10 ppm 30 ppm 100 ppm * PND 13 PND 17 Age at Testing PND 21 Peak Response in PND 20 Male Rats Exposed to Methimazole 0 ppm MMZ 10 ppm MMZ 30 ppm MMZ 100 ppm MMZ 250 200 Vmax (mV) 150 -2034- 100 ++ 50 ++ 0 1-10 ++ ++ 11-20 ++ ++ 21-30 Trial Block ++ ++ 31-40 ++ ++ 41-50 Peak Response in PND 60 Male Rats Exposed to Methimazole 0 ppm MMZ 10 ppm MMZ 30 ppm MMZ 100 ppm MMZ 600 Vmax (mV) 500 ++++ 400 ++++ ++ ++++ ++ ++ 300 -2035- 200 100 0 1-10 11-20 21-30 Trial Block 31-40 41-50 Latency to Peak Response in PND 20 Male Rats Exposed to Methimazole Tmax (msec) -2036- 40 35 ** * 30 25 20 15 10 5 0 1-10 0 ppm 10 ppm 30 ppm 100 ppm ** ** ** * * 11-20 21-30 Trial Block 31-40 41-50 Latency to Peak Response in PND 60 Male Rats Exposed to Methimazole Tmax (msec) -2037- 0 ppm 10 ppm 30 ppm 100 ppm 50 45 40 35 30 + 25 ++++ 20 15 10 5 0 1-10 + + + ++ ++++ ++++ 11-20 21-30 Trial Block 31-40 + ++ 41-50 Peak Response in PND 20 Female Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 250 200 Vmax (mV) 150 -2038- 100 ++ 50 ++ 0 1-10 ++ ++ 11-20 ++ ++ 21-30 Trial Block ++ ++ 31-40 ++ ++ 41-50 Peak Response in PND 60 Female Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 600 500 Vmax (mV) -2039- 400 ++ ++ ++ ++ 300 ++ ++ ++ ++ ++ ++ 200 100 0 1-10 11-20 21-30 Trial Block 31-40 41-50 Latency to Peak Response in PND 20 Female Rats Exposed to Methimazole Tmax (msec) -2040- 0 ppm 10 ppm 30 ppm 100 ppm 40 35 + ++ ++ 30 +++ + ++ ++ 25 + 20 15 10 5 0 1-10 11-20 21-30 Trial Block 31-40 41-50 Latency to Peak Response in PND 60 Female Rats Exposed to Methimazole Tmax (msec) -2041- 50 45 40 35 30 25 ++ ++ 20 15 10 5 0 1-10 0 ppm 10 ppm 30 ppm 100 ppm ++ ++ ++ ++ ++ ++ ++ ++ 11-20 21-30 Trial Block 31-40 41-50 Time to Escape in PND 22 Male Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm Time (sec) 180 160 140 120 100 80 ** 60 ++ ++ ++ ++ ++ ++ ++ ** ** ** ** * ++ ++ ++ ++ -2042- 40 20 0 S 1234 5 6 7 8 9 10 Trial 11 12 Number of Errors in PND 22 Male Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 35 30 25 Errors 20 -2043- 15 ** 10 5 0 1234 5 6 7 8 9 10 Trial 11 12 Time to Escape in PND 22 Female Rats Exposed to Methimazole Time (sec) -2044- 180 160 140 120 100 80 60 40 ** 20 0 S 0 ppm 10 ppm ++ ++ ++ ++ ++ ++ ++ ++ 30 ppm 100 ppm * * ** ** ** ++ +++ + 1234 5 6 7 8 9 10 Trial 11 12 Number of Errors in PND 22 Female Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 35 30 25 20 * Errors -2045- 15 10 5 0 1234 5 6 7 8 9 10 Trial 11 12 Time to Escape in PND 62 Male Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 180 Time (sec) 160 140 + 120 + +++ **** 100 + + + + + 80 ++++ 60 + + 40 -2046- 20 0 S 1234 5 6 7 8 9 10 11 12 Trial Number of Errors in PND 62 Male Rats Exposed to Methimazole 0 ppm 10 ppm 30 ppm 100 ppm 40 35 30 ** 25 ** * 20 Errors -2047- 15 10 5 0 1234 5 6 7 8 9 10 Trial 11 12 Time to Escape in PND 62 Female Rats Exposed to Methimazole Time (sec) -2048- 180 160 140 120 100 80 60 40 20 0 S 0 ppm 10 ppm 30 ppm 100 ppm ++ ++ ++ ++ ++ ++++ ++ ++ ++ ++ ++ ++ ++ ++ 1234 5 6 7 8 9 10 Trial 11 12 Number of Errors in PND 62 Female Rats Exposed to Methimazole Errors -2049- 0 ppm 40 35 30 25 + + 20 ++ 15 10 5 0 1234 10 ppm 30 ppm 100 ppm +++ ++ ++ ++ + ++ +++ ++ + 5 6 7 8 9 10 Trial ++ ++ 11 12 LEVEL 1 - CORONAL SECTION (Midway between olfactory bulbs and optic chiasm) Line B - Vertical thickness of cortex PND 11 Males Females Line P I P I A NS * ** ** B NS * ** ** -2050- Line A - Height of hemisphere PND 22 PND 72 Line M F M F A NS * NS ** B NS NS NS ** PND = Postnatal Day P = Perfusion, I = Immersion NS = Not significant when compared to control brains * p<0.05, ** p<0.01 when compared to control brains M = Male, F = Female LEVEL 3 - CORONAL SECTION (Just rostral to pituitary recess) -2051- Line D Line E Line F Line C Line C - Vertical height between layers of pyramidal neurons of the hippocampus Line D - Distance between the limbs of the dentate gyrus of the hippocampus Line E - Length of the ventral limb of the dentate gyrus of the hippocampus Line F - Radial thickness of the cortex PND 11 Males Females Line P I P I C NS NS NS NS D NS * NS NS E * ** ** ** F NS NS ** NS PND 22 PND 72 Line M F M F C NS NS NS NS D NS NS NS NS E ** * NS NS F NS NS NS ** PND = Postnatal Day P = Perfusion, I = Immersion NS = Not significant when compared to control brains * p<0.05, ** p<0.01 when compared to control brains M = Male, F = Female LEVEL 5 - MID-SAGITTAL SECTION (cerebellum and brain stem) Line H - Distance across base of lobule #9 PND 11 Males Females Line P I P I G NS * NS NS H * * NS ** -2052- Line G - Vertical thickness of the pons (perpendicular to the caudal spinal cord) PND 22 PND 72 Line M F M F G NS NS NS NS H NS NS NS NS PND = Postnatal Day P = Perfusion, I = Immersion NS = Not significant when compared to control brains * p<0.05, ** p<0.01 when compared to control brains M = Male, F = Female -2053- F1 BRAIN WEIGHTS AND LENGTHS Brains either immersion fixed or perfusion fixed for PND 11 pups. Brains perfusion fixed on PND 22 and 72. Brain lengths measured after fixation. 0 PPM 100 PPM 0 PPM 100 PPM PND 11 Immersion Weight Length (g) (mm) 1.29 16.6 0.075 0.51 1.08 15.2 0.188** 1.23** PND 11 Immersion Weight Length (g) (mm) 1.26 16.3 (0.077) 0.63 1.07 15.5 0.153** 1.04* MALE PND 11 Perfusion Weight Length (g) (mm) 1.23 16.0 0.121 0.67 1.06 15.1 0.173* 1.05* FEMALE PND 11 Perfusion Weight Length (g) (mm) 1.23 16.4 0.082 0.48 0.99 14.8 0.127** 0.90** PND 22 Perfusion Weight Length (g) (mm) 1.71 18.5 0.072 0.50 1.56 17.5 0.117** 0.49** PND 22 Perfusion Weight Length (g) (mm) 1.65 18.3 0.828 0.36 1.49 17.5 0.128** 0.51** PND 72 Perfusion Weight Length (g) (mm) 1.97 20.5 0.154 0.91 1.79 19.4 0.134** 1.05* PND 72 Perfusion Weight Length (g) (mm) 1.75 20.6 0.130 1.52 1.69 19.3 0.104 0.86* * = Significantly different from the control group at p<0.05 ** = Significantly different from the control group at p<0.01 -2054- -2055- WIL-99263 AN INTER-OBSERVER RELIABILITY STUDY OF TECHNICIANS ASSIGNED TO PERFORM FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENTS IN RATS Study Date Range: December 14, 2001 - October 9, 2002 STUDY OBJECTIVE: The objective of this study was to train personnel to conduct the Functional Observational Battery (FOB) and to assess inter-observer reliability of the same technicians. FOB. inter-observer reliability studies serve as training for new employees, as well as on-going training for current employees. CONTROL ARTICLES: Deionized water was used as the negative control article. Two positive control articles, 3,3-Iminodipropionitrile (IDPN) and Parathion, were used to elicit behavioral changes in the animals. IDPN was administered orally at 2000 mg/kg, and Parathion was administered orally at 4 mg/kg. All control articles were administered as a single dose. TEST SYSTEM: All animals used on the study were female Sprague-Dawley Crl:CD (SD)IGS BR rats obtained from the WIL Research Laboratories, Inc. stock colony. Animals were randomly assigned to treatment groups using a computer program. The study was conducted according the protocol and WIL standard operating procedures. ENVIRONMENTAL CONDITIONS: The animals were housed and maintained under conditions consistent with maintaining good health. Temperature and relative humidity were set to maintain at 71 5 C and 30-70%, respectively, in a room with a 12 hour light (6 a.m. to 6 p.m.)/dark photoperiod. Temperature and relative humidity were recorded once daily. The facilities at WIL Research Laboratories, Inc. are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International). VIABILITY OBSERVATIONS: The rats were observed for mortality/moribundity and general condition twice daily, in the morning and in the afternoon. BODY WEIGHTS: Body weights were recorded on days of dosing for calculation of doses only. -2056- WIL-99263 FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENTS: The Functional Observational Battery used at WIL Research Laboratories, Inc. is based on previously developed protocols (Moser et al., 1999; Irwin, 1968; Gad, 1982; Moser et al., 1988; Haggerty, 1989; O'Donoghue, 1989). Testing for Phase III (described below) was performed by trained technicians who did not know the animal's group assignment. The time of testing was determined by the Study Director based on the appearance of the expected behavioral signs following dosing. Animals were observed for the following parameters as described below (see WIL standard operating procedure No. T1-112, as revised, for a description of scoring criteria): HOME CAGE OBSERVATIONS: Posture Convulsions/Tremors Feces consistency Biting Palpebral (eyelid) closure HANDLING OBSERVATIONS: Ease of removal from cage Lacrimation/chromodacryorrhea Piloerection Palpebral closure Red/crusty deposits Eye prominence Ease of handling animal in hand Salivation Fur appearance Respiratory rate/character Mucous membranes/eye/skin color Muscle tone OPEN FIELD OBSERVATIONS: (evaluated over a 2-minute observation period) Mobility Rearing Convulsions/tremors Grooming Bizarre/stereotypic behavior Time to first step (seconds) Gait Arousal Urination/defecation Gait score Backing SENSORY OBSERVATIONS: Approach response Startle response Pupil response Forelimb extension Air righting reflex Touch response Tail pinch Eyeblink response Hindlimb extension Olfactory orientation The study design consisted of three distinct phases to ensure the most adequate training and reliability among the technicians. Phases were designed as a progression to allow for -2057- WIL-99263 training and discussion prior to the final phase, which evaluated the inter-observer reliability. The phases of testing are described as follows: PHASE I: Phase I testing consisted of FOB assessments on naive stock animals. Each technician observed up to 60 rats through the entire FOB assessment. The purpose of Phase I testing was to ensure consistent and accurate use of all equipment and to gain a strong knowledge of the stereotypic behavior of naive animals. All rats used in Phase I testing were returned to stock following FOB assessments. PHASE II: Phase II testing consisted of an open discussion of each animal's observations conducted in a group setting. Two animals per group were dosed with Parathion, IDPN or deionized water and evaluated by the observers once the effects were apparent. Phase II allowed for open discussion of observations and interpretation of the findings. All animals used in Phase II testing were euthanized by carbon dioxide inhalation and carcasses discarded following testing. PHASE III: Phase III testing consisted of three animals per group dosed with a single dose of Parathion, IDPN or deionized water and observed at a time determined by the Study Director. Each technician individually recorded observations for each animal to evaluate the inter-observer reliability. All animals used in Phase III testing were euthanized by carbon dioxide inhalation and carcasses discarded following testing. CRITERIA FOR EVALUATION OF TECHNICIANS: The following criteria were used to evaluate the ability of technicians to reliably distinguish signs of neurotoxicity. 1. No omission of findings within the categories of Home Cage Observations, Handling Observations, Open Field Observations and Sensory Observations. 2. A difference of no more than two grades (severity) for a given finding in each category. RESULTS: VIABILITY: All animals survived until scheduled euthanasia. -2058- WIL-99263 FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENTS: Technicians were consistent in the findings reported when deionized water, IDPN or Parathion was administered (Table 1). There were no obvious or gross inconsistencies among the calls. It was determined that the previously established criteria for evaluation were fulfilled to a degree deemed acceptable by the Study Director. It should be noted that there were a few apparent omissions of findings (Table 2) which upon further review were found to be of no practical significance. CONCLUSIONS: It was determined that the technicians fulfilled the criteria for reliably observing FOB parameters to assess behavioral changes in rats in a manner consistent with good science and WIL Research Laboratories, Inc. standard operating procedures. REFERENCES: Gad, S.C. A neuromuscular screen for use in industrial toxicology. Toxicology and Environmental Health 1982, 9(5-6), 691-704. Journal of Haggerty, G.C. Development of tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies. Journal of the American College of Toxicology 1989, 8(1), 53-69. Irwin, S. Comprehensive observational assessment: Ia. a systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia 1968, 13, 222-257. Moser, V.C.; McCormick, J.P.; Creason, J.P.; MacPhail, R.C. Comparison of chlordimeform and carbaryl using a functional observational battery. Fundamentals of Applied Toxicology 1988, 11(2), 189-206. Moser, V.C.; McDaniel, K.L.; Phillips, P.M. Rat strain and stock comparisons using a functional observational battery: baseline values and effects of amitraz. Toxicology and Applied Pharmacology 1991, 108(2), 267-283. O'Donoghue, J.L. (1989) Screening for neurotoxicity using a neurologically based examination and neuropathology. J. Amer. Coll. Toxicol. 8:97-116. WIL-99263 TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 1 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ POSTURE 1 - SITTING OR STANDING NORMALLY 1 2 12 3 2 32 2 - ASLEEP, LYING ON SIDE OR CURLED UP 2 1 21 3 3 33 3 - ALERT, ORIENTED TOWARD OBSERVER 1 1 4 - SITTING, HEAD HELD LOW 5 - FLATTENED, LIMBS MAY BE EXTENDED 6 - LYING ON SIDE, LIMBS IN AIR 7 - IMMOBILE 8 - REARING 9 - SPLAYED HINDLEGS 10 - PROSTRATION CONVULSIONS - CLONIC 1 - ABSENT 3 3 33 3 3 33 2 3 33 2 - TWITCHES (BACK MUSCLES) 3 - IRREGULAR JERKING MOVEMENTS OF THE LIMBS 4 - CLONIC WHOLE-BODY CONVULSIONS 5 - HEAD AND/OR BODY TWITCHES (MYOCLONUS) 6 - MUSCLE FASICULATIONS 7 - REPETITIVE MOVEMENT OF MOUTH AND JAWS (CHEWING) CONVULSIONS - TONIC 1 - ABSENT 3 3 33 3 3 33 3 3 33 2 - TONIC: CONTRACTION OF EXTENSORS SUCH THAT LIMBS ARE RIGID AND EXTENDED 3 - OPISTHOTONUS: HEAD, BODY AND LIMBS RIGIDLY ARCHED BACKWARDS 4 - EMPROSTHOTONUS: HEAD, BODY AND LIMBS EXTENDED FORWARD 5 - 'POPCORN SEIZURE': ANIMAL REPEATEDLY JUMPS OR BOUNCES IN AIR 6 - ASPHYXIAL: BOUTS OF SEVERE CLONIC-TONIC CONVULSIONS TREMORS 1 - NONE 3 3 33 3 3 33 3 3 33 2 - SLIGHT (1.5mm) 3 - MODERATELY COARSE (3 mm) 4 - MARKEDLY COARSE (4.5mm) 5 - EXTREMELY COARSE (6 mm) -2059- Counts indicate the number of animals observed with a particular finding. WIL-99263 TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 2 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ BITING 1 - NONE 2 - BITING OF CAGE 3 - BITING OF SELF PALPEBRAL CLOSURE 1 - EYELIDS WIDE OPEN 2 - EYELIDS SLIGHTLY DROOPING 3 - DROOPING EYELIDS (HALF-CLOSED) 4 - EYELIDS COMPLETELY SHUT FECES CONSISTENCY 1 - PELLETS 2 - PELLETS, PARTIALLY FORMED 3 - UNFORMED, DIARRHEA 4 - PELLETS ABSENT EASE OF REMOVAL 1 - VERY EASY: ANIMAL SITS QUIETLY, ALLOWS INVESTIGATOR TO PICK IT UP 2 - EASY: WITH/WITHOUT VOCALIZATION, WITHOUT RESISTANCE OR SLIGHT RESISTANCE 3 - MODERATELY DIFFICULT: ANIMAL REARS, OFTEN FOLLOWING THE INVESTIGATOR'S HAND 4 - FREEZES: WITH/WITHOUT VOCALIZATION 5 - DIFFICULT: RUNS AROUND CAGE, IS HARD TO GRAB, WITH/WITHOUT VOCALIZATION 6 - VERY DIFFICULT: TAIL AND THROAT RATTLES WITH/WITHOUT VOCALIZATION; MAY ATTACK EASE OF HANDLING IN HAND 1 - LOW: NO RESISTANCE, ANIMAL IS EASY TO HANDLE 2 - MODERATELY LOW: SLIGHT RESISTANCE TO BEING HANDLED, WITH/WITHOUT VOCALIZATION 3 - MODERATELY HIGH: MAY FREEZE, BE TENSE OR RIGID, WITH/WITHOUT VOCALIZATION 4 - HIGH: SQUIRMS, TWISTS, ATTEMPTS TO BITE, WITH/WITHOUT VOCALIZATION LACRIMATION 1 - NONE 2 - SLIGHT 3 - SEVERE CHROMODACRYORRHEA 1 - ABSENT 2 - PRESENT 3 3 33 3 3 33 3 2 33 1 2 12 2 3 33 1 2 1 21 3 3 33 2 2 22 1 1 11 3 3 33 3 3 33 2 2 21 3 3 33 2 2 21 1 1 1 11 1 1 11 2 1 21 11 1 1 2 12 2 2 22 2 2 32 1 1 11 3 3 33 2 2 22 3 3 33 1 1 11 3 3 33 3 3 33 3 3 33 -2060- Counts indicate the number of animals observed with a particular finding. WIL-99263 TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 3 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ SALIVATION 1 - NONE 2 - SLIGHT 3 - SEVERE PILOERECTION 1 - NONE 2 - SLIGHT 3 - SEVERE FUR APPEARANCE 1 - NORMAL: CLEAN AND GROOMED 2 - SLIGHTLY SOILED 3 - VERY SOILED, CRUSTY PALPEBRAL CLOSURE 1 - EYELIDS WIDE OPEN 2 - EYELIDS SLIGHTLY DROOPING 3 - DROOPING EYELIDS (HALF-CLOSED) 4 - EYELIDS COMPLETELY SHUT RESPIRATORY RATE 1 - NORMAL: BY OBSERVATION (80-110/MIN.) 2 - DECREASED: BELOW 80/MIN. 3 - INCREASED: ABOVE 110/MIN. RESPIRATORY CHARACTER 1 - NORMAL 2 - RALES: ABNORMAL SOUND ACCOMPANYING BREATHING 3 - RETCHING 4 - DYSPNEIC: SHORT OF BREATH 5 - GASPING 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 2 2 22 1 1 11 3 3 33 2 2 22 3 3 33 1 1 11 3 3 33 3 3 33 3 3 33 3 3 33 3 3 23 3 3 33 RED DEPOSITS - eyes 1 - PRESENT 2 - ABSENT RED DEPOSITS - nose 1 - PRESENT 2 - ABSENT 3 3 33 3 3 33 3 3 33 1 1 11 3 3 33 3 3 33 2 2 22 -2061- Counts indicate the number of animals observed with a particular finding. WIL-99263 RED DEPOSITS - mouth 1 - PRESENT 2 - ABSENT CRUSTY DEPOSITS - eyes 1 - PRESENT 2 - ABSENT CRUSTY DEPOSITS - nose 1 - PRESENT 2 - ABSENT CRUSTY DEPOSITS - mouth 1 - PRESENT 2 - ABSENT MUCOUS MEMBRANES - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH EYES - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH SKIN - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 4 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 -2062- Counts indicate the number of animals observed with a particular finding. WIL-99263 TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 5 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ EYE PROMINENCE 1 - NORMAL 2 - EXOPHTHALMUS 3 - ENOPHTHALMUS MUSCLE TONE 1 - MUSCLE IS FIRM BUT NOT HARD (NORMAL) 2 - MUSCLE IS SOFT AND FLABBY 3 - MUSCLE IS TENSE AND HARD TIME TO FIRST STEP (seconds) REQUIRES NUMERICAL INPUT 3 3 33 3 3 33 3 3 33 2 2 22 3 3 33 1 1 11 1 1 11 1 1 11 1 1 11 MOBILITY 1 - NORMAL 2 - SLIGHTLY IMPAIRED 3 - MODERATELY IMPAIRED 4 - TOTALLY IMPAIRED, LOCOMOTION IMPOSSIBLE GAIT 1 - NORMAL 2 - WALKS ON TIPTOES 3 - BODY DRAGS, ABDOMEN CONTACTS SURFACE, BODY SWAYS 4 - HINDLIMBS SPLAYED OR DRAGGING, UNABLE TO SUPPORT WEIGHT 5 - HUNCHED BODY 6 - ATAXIA, EXCESSIVE SWAY, ROCKS OR LURCHES AS PROCEEDS FORWARD 7 - WALKS ON METATARSUS CONVULSIONS - CLONIC 1 - ABSENT 2- TWITCHES (BACK MUSCLES) 3 - REPETITIVE MOVEMENT OF MOUTH AND JAWS 4 - CLONIC TREMORS OF THE LIMBS 5 - WHOLE BODY TREMORS 6 - CLONIC CONVULSIONS 7 - WET DOG SHAKES 3 3 33 3 3 33 3 3 33 3 3 33 2 2 11 1 1 21 2 3 33 1 2 3 33 1 1 11 3 2 23 3 3 33 2 2 12 3 3 33 1 1 21 -2063- Counts indicate the number of animals observed with a particular finding. WIL-99263 TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 6 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ CONVULSIONS - TONIC 1 - ABSENT 2 - TONIC: CONTRACTION OF EXTENSORS SUCH THAT LIMBS ARE RIGID AND EXTENDED 3 - OPISTHOTONUS: HEAD, BODY AND LIMBS RIGIDLY ARCHED BACKWARDS 4 - EMPROSTHOTONUS: HEAD, BODY AND LIMBS EXTENDED FORWARD 5 - 'POPCORN SEIZURE': ANIMAL REPEATEDLY JUMPS OR BOUNCES IN AIR 6 - ASPHYXIAL: BOUTS OF SEVERE CLONIC-TONIC CONVULSIONS TREMORS 1 - NONE 2 - SLIGHT (1.5mm) 3 - MODERATELY COARSE (3 mm), SLIGHT IMPAIRMENT OF LOCOMOTION 4 - MARKEDLY COARSE (4.5mm), MODERATE/MARKED IMPAIRMENT OF LOCOMOTION 5 - EXTREMELY COARSE (6 mm), LOCOMOTION IMPOSSIBLE GAIT SCORE 1 - NORMAL 2 - SLIGHT IMPAIRMENT, BUT DEFINITE 3 - CONSIDERABLE IMPAIRMENT, WITHOUT FALLING 4 - MARKED IMPAIRMENT, FALLS EVERY 4 TO 6 STEPS 5 - SEVERE IMPAIRMENT, CANNOT WALK WITHOUT FALLING AROUSAL 1 - VERY LOW: STUPOR, COMA, LITTLE OR NO RESPONSIVENESS 2 - LOW: SOMEWHAT STUPOROUS 3 - NORMAL: ALERT, EXPLORATORY MOVEMENTS 4 - SOMEWHAT HIGH: SLIGHT EXCITEMENT, TENSE, SUDDEN DARTING OR FREEZING 5 - VERY HIGH: HYPERALERT, EXCITED, SUDDEN BOUTS OF RUNNING OR BODY MOVEMENTS 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 2 2 22 3 3 33 1 1 11 1 3 3 33 3 2 23 3 3 33 1 -2064- Counts indicate the number of animals observed with a particular finding. WIL-99263 TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 7 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ BIZARRE/STEREOTYPIC BEHAVIOR 1 - NONE 3 3 33 2 2 22 2 - HEAD FLICK: HEAD SHAKING OR BACKWARD FLIP OF HEAD 3 3 23 3 - HEAD SEARCH: STEREOTYPED, REPETITIVE TURNING OF HEAD FROM SIDE TO SIDE 3 3 33 4 - HALLUCINATORY: APPEARS TO BE RESPONDING TO OBJECTS NOT PRESENT 5 - COMPULSIVE LICKING OR BITING 6 - PRANCING: RESTLESS SHIFTING FROM ONE FORELIMB TO THE OTHER 7 - UPRIGHT WALKING: ON HINDLIMBS ONLY 8 - AIMLESS WANDERING: PROGRESSIVE, SLOW, PLODDING MOVEMENTS, NO APPARENT PURPOSE 9 - CIRCLING: TENDENCY TO MOVE IN CIRCLES AROUND OBJECTS, OR IN AN OPEN ENVIRONMENT 2 2 22 10 - WALTZING: RAPID TURNING IN CIRCLES 11 - RETROPULSION: ANIMAL WALKS BACKWARDS 1 2 22 1 1 11 12 - SPATIAL DISORIENTATION: WALKING OR STUMBLING INTO OBJECTS 13 - SIDE TO SIDE ROCKING 14 - STRAUB TAIL: INCREASED TAIL ELEVATION 15 - VERTICAL JUMPING 16 - PACING WITHOUT PURPOSE 17 - HEAD BOBBING 18 - WRITHING: LYING DOWN, WAVELIKE MOVEMENTS OF ABDOMEN, ALTERNATING LIMB MOVEMENTS REARING REQUIRES NUMERICAL INPUT 17 17 17 17 1 1 1 1 13 13 13 13 BACKING REQUIRES NUMERICAL INPUT 0 0 00 4 4 44 2 2 22 GROOMING REQUIRES NUMERICAL INPUT 3 3 33 1 1 11 2 2 22 URINATION REQUIRES NUMERICAL INPUT 0 0 00 1 1 11 1 1 11 DEFECATION REQUIRES NUMERICAL INPUT 1 1 11 0 0 00 0 0 00 -2065- Counts indicate the number of animals observed with a particular finding. WIL-99263 TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 8 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ APPROACH RESPONSE 1 - NO REACTION 2 - SLOW APPROACH, SNIFFING OR TURNING AWAY 3 - MORE ENERGETIC RESPONSE THAN (2), WITH/WITHOUT VOCALIZATION 4 - FREEZES, ACTUAL MUSCLE CONTRACTION 5 - BIZARRE REACTION: JUMPS, BITES OR ATTACKS TOUCH RESPONSE 1 - NO REACTION 2 - ANIMAL MAY SLOWLY TURN, WALK AWAY 3 - MORE ENERGETIC RESPONSE THAN (2), WITH/WITHOUT VOCALIZATION 4 - FREEZES, ACTUAL MUSCLE CONTRACTION 5 - BIZARRE REACTION: JUMPS, BITES OR ATTACKS STARTLE RESPONSE 1 - NO REACTION 2 - SLIGHT REACTION, EAR FLICK OR SOME EVIDENCE THAT SNAP WAS HEARD 3 - MORE ENERGETIC RESPONSE THAN (2), WITH/WITHOUT VOCALIZATION 4 - FREEZES, ACTUAL MUSCLE CONTRACTION 5 - BIZARRE REACTION: JUMPS, BITES OR ATTACKS 1 1 11 2 2 22 3 3 33 3 3 23 1 2 2 22 3 3 33 3 3 33 1 1 11 3 3 33 3 3 23 1 2 12 1 2 1 21 TAIL PINCH RESPONSE 1 - NO REACTION 2 - ANIMAL MAY SLOWLY TURN, WALK AWAY 3 - MORE ENERGETIC RESPONSE THAN (2), WITH/WITHOUT VOCALIZATION 4 - FREEZES, ACTUAL MUSCLE CONTRACTION 5 - BIZARRE REACTION: JUMPS, BITES OR ATTACKS OLFACTORY ORIENTATION 1 - NO REACTION PRESENT 2 - REACTION PRESENT: ANIMAL APPROACHES SWAB MAKING SNIFFING MOVEMENTS WITH NOSE PUPIL RESPONSE 1 - NO PUPIL RESPONSE 2 - PUPIL RESPONSE PRESENT EYEBLINK RESPONSE 1 - NO EYEBLINK RESPONSE 2 - EYEBLINK RESPONSE PRESENT 2 2 22 3 3 33 2 2 22 1 1 11 1 1 11 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 3 3 33 -2066- Counts indicate the number of animals observed with a particular finding. WIL-99263 FORELIMB EXTENSION 1 - NO FORELIMB EXTENSION 2 - FORELIMB EXTENSION PRESENT HINDLIMB EXTENSION 1 - NO HINDLIMB EXTENSION 2 - HINDLIMB EXTENSION PRESENT AIR RIGHTING REFLEX 1 - NORMAL 2 - SLIGHTLY UNCOORDINATED 3 - LANDS ON SIDE 4 - LANDS ON BACK TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS PAGE 9 TREATMENT: CONTROL IDPN Parathion TECHNICIAN GRG MJM TAP AZ GRG MJM TAP AZ GRG MJM TAP AZ 2 2 22 3 3 33 1 1 11 3 3 33 3 3 33 2 2 11 3 3 33 1 1 22 3 3 33 3 3 33 1 1 11 1 1 11 1 1 11 -2067- Counts indicate the number of animals observed with a particular finding. -2068- WIL-99263 TABLE 2 FOB OBSERVATIONS - FINDINGS OMITTED PAGE 1 TECHNICIAN TAP AZ GRG MJM TREATMENT IDPN IDPN PARATHION PARATHION CATEGORY OMITTED RESPIRATORY CHARACTER EASE OF REMOVAL CONVULSIONS - CLONIC BITING -2069- WIL-99310 AN INTER-OBSERVER RELIABILITY STUDY OF INDIVIDUALS ASSIGNED TO PERFORM FUNCTIONAL OBSERVATIONAL BATTERY OBSERVATIONS FOR NEUROTOXICITY STUDIES Study Date Range: April 13-29, 2004 STUDY OBJECTIVE: The objective of this study was to train personnel to conduct the Functional Observational Battery (FOB) and to assess inter-observer reliability of the same individuals. The inter-observer reliability also included one individual that had been previously trained to further demonstrate inter-observer reliability of the newly trained individuals with those currently approved to conduct neurotoxicity studies. FOB inter-observer reliability studies serve as training for new employees, as well as on-going training for current employees. CONTROL ARTICLES: Mazola corn oil was used as the negative control article. Three positive control articles, 3,3-Iminodipropionitrile (IDPN), Parathion and d-Amphetamine, were used to elicit behavioral changes in the animals. IDPN was administered orally (gavage) at 2000 mg/kg, Parathion was administered orally (gavage) at 4 mg/kg, and d-Amphetamine was administered by intraperitoneal injection at 2 mg/kg. All positive and negative control articles were administered as a single dose. TEST SYSTEM: All animals used on the study were female Sprague-Dawley Crl:CD (SD)IGS BR rats obtained from the WIL Research Laboratories, Inc. stock colony. Animals were randomly assigned to treatment groups using a computer program. The study was conducted according the protocol and WIL standard operating procedures. ENVIRONMENTAL CONDITIONS: The animals were housed and maintained under conditions consistent with maintaining good health. Temperature and relative humidity were set to maintain at 71 5 C and 30-70%, respectively, in a room with a 12 hour light (6 a.m. to 6 p.m.)/dark photoperiod. Temperature and relative humidity were recorded once daily. The ventilation rate was set at a minimum of 10 room air changes per hour using 100% fresh air. The facilities at WIL Research Laboratories, Inc. are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International). -2070- WIL-99310 VIABILITY OBSERVATIONS: The rats were observed for mortality/moribundity and general condition twice daily, in the morning and in the afternoon. BODY WEIGHTS: Body weights were recorded on days of dose administration for calculation of doses only. FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENTS: The Functional Observational Battery used at WIL Research Laboratories, Inc. is based on previously developed protocols (Moser et al., 1999; Irwin, 1968; Gad, 1982; Moser et al., 1988; Haggerty, 1989; O'Donoghue, 1989). Testing for the Inter-observer Reliability testing (described below) was performed by trained technicians who did not know the animal's group assignment. The time of testing was determined by the Study Director based on the appearance of the expected behavioral signs following dosing. Animals were observed for the following parameters as described below (see WIL standard operating procedure No. T1-112, as revised, for a description of scoring criteria): HOME CAGE OBSERVATIONS: Posture Convulsions/Tremors Feces consistency Biting Palpebral (eyelid) closure HANDLING OBSERVATIONS: Ease of removal from cage Lacrimation/chromodacryorrhea Piloerection Palpebral closure Red/crusty deposits Eye prominence Ease of handling animal in hand Salivation Fur appearance Respiratory rate/character Mucous membranes/eye/skin color Muscle tone OPEN FIELD OBSERVATIONS: (evaluated over a 2-minute observation period) Mobility Rearing Convulsions/tremors Grooming Bizarre/stereotypic behavior Time to first step (seconds) Gait Arousal Urination/defecation Gait score Backing -2071- WIL-99310 SENSORY OBSERVATIONS: Approach response Startle response Pupil response Forelimb extension Air righting reflex Touch response Tail pinch Eyeblink response Hindlimb extension Olfactory orientation The study design consisted of three distinct phases to ensure the most adequate training and reliability among the technicians. Phases were designed as a progression to allow for training and discussion prior to the final phase, which evaluated the inter-observer reliability. The phases of testing are described as follows: PHASE I: Phase I testing consisted of FOB assessments on naive stock animals. Each technician observed up to 60 rats through the entire FOB assessment. The purpose of Phase I testing was to ensure consistent and accurate use of all equipment and to gain a strong knowledge of the stereotypic behavior of naive animals. All rats used in Phase I testing were returned to stock following FOB assessments. PHASE II: Phase II testing consisted of an open discussion of each animal's observations conducted in a group setting. Two animals per group were dosed with IDPN, Parathion, d-Amphetamine or corn oil and evaluated by the observers once the effects were apparent. Phase II allowed for open discussion of observations and interpretation of the findings. All animals used in Phase II testing were euthanized by carbon dioxide inhalation and carcasses discarded following testing. PHASE III: Inter-observer Reliability testing consisted of three animals per group dosed with a single dose of Parathion, IDPN, d-Amphetamine or corn oil and observed at a time determined by the Study Director or designee. Each observer individually recorded observations for each animal to evaluate the inter-observer reliability. All animals used in Inter-observer Reliability testing were euthanized by carbon dioxide inhalation and carcasses discarded following testing. CRITERIA FOR EVALUATION OF TECHNICIANS: The following criteria were used to evaluate the ability of technicians to reliably distinguish signs of neurotoxicity. 1. No omission of findings within the categories of Home Cage Observations, Handling Observations, Open Field Observations and Sensory Observations. -2072- WIL-99310 2. A difference of no more than two grades (severity) for a given finding in each category. RESULTS: VIABILITY: All animals survived until scheduled euthanasia. FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENTS: Observers B, C, D and E were consistent in the findings reported when corn oil, IDPN, Parathion or d-Amphetamine was administered (Table 1). There were no obvious or gross inconsistencies among the calls with the exception of observer E who differed consistently when evaluating pupillary response. Therefore, these four observers were considered to have met acceptable for performing the functional observational battery on neurotoxicity studies. However, prior to working independently on studies, observer E will undergo additional training and demonstrate proficiency in the evaluation of pupillary response. Observer A differed significantly from the common response of the other observers in several categories. Therefore, observer A was not considered to have met acceptable criteria for performing functional observational battery testing on neurotoxicity studies. It should be noted there were six apparent omissions of observations (Table 2) which upon further review were found to be of no consequence. REFERENCES: Gad, S.C. A neuromuscular screen for use in industrial toxicology. Toxicology and Environmental Health 1982, 9(5-6), 691-704. Journal of Haggerty, G.C. Development of tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies. Journal of the American College of Toxicology 1989, 8(1), 53-69. Irwin, S. Comprehensive observational assessment: Ia. a systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia 1968, 13, 222-257. Moser, V.C.; McCormick, J.P.; Creason, J.P.; MacPhail, R.C. Comparison of chlordimeform and carbaryl using a functional observational battery. Fundamentals of Applied Toxicology 1988, 11(2), 189-206. -2073- WIL-99310 Moser, V.C.; McDaniel, K.L.; Phillips, P.M. Rat strain and stock comparisons using a functional observational battery: baseline values and effects of amitraz. Toxicology and Applied Pharmacology 1991, 108(2), 267-283. O'Donoghue, J.L. (1989) Screening for neurotoxicity using a neurologically based examination and neuropathology. J. Amer. Coll. Toxicol. 8:97-116. WIL-99310 TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS Observer: POSTURE 1 - SITTING OR STANDING NORMALLY 2 - ASLEEP, LYING ON SIDE OR CURLED UP 3 - ALERT, ORIENTED TOWARD OBSERVER 4 - SITTING, HEAD HELD LOW 5 - FLATTENED, LIMBS MAY BE EXTENDED 6 - LYING ON SIDE, LIMBS IN AIR 7 - IMMOBILE 8 - REARING 9 - SPLAYED HINDLEGS 10 - PROSTRATION CONVULSIONS - CLONIC 1 - ABSENT 2 - TWITCHES (BACK MUSCLES) 3 - IRREGULAR JERKING MOVEMENTS OF THE LIMBS 4 - CLONIC WHOLE-BODY CONVULSIONS 5 - HEAD AND/OR BODY TWITCHES (MYOCLONUS) 6 - MUSCLE FASICULATIONS (CHEWING) CONVULSIONS - TONIC 1 - ABSENT 2 - TONIC: CONTRACTION OF EXTENSORS SUCH THAT LIMBS ARE RIGID AND EXTENDED ARCHED BACKWARDS EXTENDED FORWARD 5 - 'POPCORN SEIZURE': ANIMAL REPEATEDLY JUMPS OR BOUNCES IN AIR 6 - ASPHYXIAL: BOUTS OF SEVERE CLONIC-TONIC CONVULSIONS Animal #52298 AEDCB X XX X X X XXXXX XXXXX Animal #52277 AEDCB XX XX X XXXXX XXXXX Animal #52222 AEDCB X XX X X XXXXX XXXXX Animal #52210 AEDCB XXXXX XXXX X XXXXX Animal #52321 AEDCB X XXXX XXXXX XXXXX Animal #52315 AEDCB XXXXX X XXXXX XXXXX -2074- WIL-99310 TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS POSTURE TREMORS 1 - ABSENT 2 - SLIGHT (1.5mm) 3 - MODERATELY COARSE (3 mm) 4 - MARKEDLY COARSE (4.5mm) 5 - EXTREMELY COARSE (6 mm) BITING 1 - NONE 2 - BITING OF CAGE 3 - BITING OF SELF PALPEBRAL CLOSURE 1 - EYELIDS WIDE OPEN 2 - EYELIDS SLIGHTLY DROOPING 3 - DROOPING EYELIDS (HALF-CLOSED) 4 - EYELIDS COMPLETELY SHUT FECES CONSISTENCY 1 - PELLETS 2 - PELLETS, PARTIALLY FORMED 3 - UNFORMED, DIARRHEA 4 - PELLETS ABSENT Observer: A E D C B A E D C B A E D C B A E D C B A E D C B A E D C B XXXXXXXXXXXXXXX XXXXXXXXX XXXX X X XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XX XXXXXXXXXXXXXXXXXXXXXXXXX X XX XXXXXXXXXXXXXXXXXXXXXXXXX XXXX EASE OF HANDLING IN HAND 1 - LOW: NO RESISTANCE, ANIMAL IS EASY TO HANDLE 2 - MODERATELY LOW: SLIGHT RESISTANCE TO BEING HANDLED, WITH/WITHOUT VOCALIZATION 3 - MODERATELY HIGH: MAY FREEZE, BE TENSE OR RIGID, WITH/WITHOUT VOCALIZATION XXXXXXX XXXXXX XXXXXXXXXXXXXXX X X 4 - HIGH: SQUIRMS, TWISTS, ATTEMPTS TO BITE, WITH/WITHOUT VOCALIZATION LACRIMATION 1 - NONE 2 - SLIGHT 3 - SEVERE CHROMODACRYORRHEA 1 - ABSENT 2 - PRESENT XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX -2075- WIL-99310 TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS Observer: A E D C B A E D C B A E D C B A E D C B A E D C B A E D C B POSTURE SALIVATION 1 - NONE XXXXXXXXXXXXXXX XXXXXXXXXXXXXX 2 - SLIGHT X 3 - SEVERE PILOERECTION 1 - NONE XXXXXXXXXX XXX XXXXXXXXXX XX 2 - SLIGHT X X X XX 3 - SEVERE FUR APPEARANCE 1 - NORMAL: CLEAN AND GROOMED XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 2 - SLIGHTLY SOILED 3 - VERY SOILED, CRUSTY PALPEBRAL CLOSURE 1 - EYELIDS WIDE OPEN XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 2 - EYELIDS SLIGHTLY DROOPING 3 - DROOPING EYELIDS (HALF-CLOSED) 4 - EYELIDS COMPLETELY SHUT RESPIRATORY RATE 1 - NORMAL: BY OBSERVATION (80-110/MIN.) XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 2 - DECREASED: BELOW 80/MIN. 3 - INCREASED: ABOVE 110/MIN. RESPIRATORY CHARACTER 1 - NORMAL 2 - RALES: ABNORMAL SOUND ACCOMPANYING BREATHING 3 - RETCHING 4 - DYSPNEIC: SHORT OF BREATH 5 - GASPING RED DEPOSITS - eyes 1 - PRESENT 2 - ABSENT RED DEPOSITS - nose 1 - PRESENT 2 - ABSENT XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX X XXXXXXXXXXXXXXXXXXXXXXXXXX XXX -2076- WIL-99310 POSTURE RED DEPOSITS - mouth 1 - PRESENT 2 - ABSENT CRUSTY DEPOSITS - eyes 1 - PRESENT 2 - ABSENT CRUSTY DEPOSITS - nose 1 - PRESENT 2 - ABSENT CRUSTY DEPOSITS - mouth 1 - PRESENT 2 - ABSENT MUCOUS MEMBRANES - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH EYES - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH SKIN - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH EYE PROMINENCE 1 - NORMAL 2 - EXOPHTHALMUS 3 - ENOPHTHALMUS TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS Observer: A E D C B A E D C B A E D C B A E D C B A E D C B A E D C B XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXX XX XXXXXXXXXXX X X -2077- WIL-99310 TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS Observer: A E D C B A E D C B A E D C B A E D C B A E D C B A E D C B POSTURE MUSCLE TONE 1 - MUSCLE IS FIRM BUT NOT HARD (NORMAL) XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 2 - MUSCLE IS SOFT AND FLABBY 3 - MUSCLE IS TENSE AND HARD MOBILITY 1 - NORMAL XXXXXXXXXXX XXXXXXXXXXXX 2 - SLIGHTLY IMPAIRED XXXXX 3 - MODERATELY IMPAIRED 4 - TOTALLY IMPAIRED, LOCOMOTION IMPOSSIBLE GAIT 1 - NORMAL XXXX XXXXXXXXXXXXXX XX 2 - WALKS ON TIPTOES X X 3 - BODY DRAGS, ABDOMEN CONTACTS SURFACE, BODY SWAYS 4 - HINDLIMBS SPLAYED OR DRAGGING, UNABLE TO SUPPORT WEIGHT 5 - HUNCHED BODY 6 - ATAXIA, EXCESSIVE SWAY, ROCKS OR LURCHES AS PROCEEDS FORWARD 7 - WALKS ON METATARSUS CONVULSIONS - CLONIC 1 - ABSENT 2- TWITCHES (BACK MUSCLES) 3 - REPETITIVE MOVEMENT OF MOUTH AND JAWS 4 - CLONIC TREMORS OF THE LIMBS 5 - WHOLE BODY TREMORS 6 - CLONIC CONVULSIONS 7 - WET DOG SHAKES XX X XX X XXXX XXXX XXXXXXXXXXX X XX XX XXXXXXXXXXXXX CONVULSIONS - TONIC 1 - ABSENT XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX -2078- 2 - TONIC: CONTRACTION OF EXTENSORS SUCH THAT LIMBS ARE RIGID AND EXTENDED 3 - OPISTHOTONUS: HEAD, BODY AND LIMBS RIGIDLY ARCHED BACKWARDS 4 - EMPROSTHOTONUS: HEAD, BODY AND LIMBS EXTENDED FORWARD WIL-99310 TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS Observer: A E D C B A E D C B A E D C B A E D C B A E D C B A E D C B POSTURE 5 - 'POPCORN SEIZURE': ANIMAL REPEATEDLY JUMPS OR BOUNCES IN AIR 6 - ASPHYXIAL: BOUTS OF SEVERE CLONIC-TONIC CONVULSIONS TREMORS 1 - NONE XXXXXXXXXXXXXXXXXXXXXXXXX XXXX 2 - SLIGHT (1.5mm) X 3 - MODERATELY COARSE (3 mm), SLIGHT IMPAIRMENT OF LOCOMOTION 4 - MARKEDLY COARSE (4.5mm), MODERATE/MARKED IMPAIRMENT OF LOCOMOTION 5 - EXTREMELY COARSE (6 mm), LOCOMOTION IMPOSSIBLE GAIT SCORE 1 - NORMAL XXXXXXXXXXXXXXXXXXXXXXXXX 2 - SLIGHT IMPAIRMENT, BUT DEFINITE XXXX 3 - CONSIDERABLE IMPAIRMENT, WITHOUT FALLING X -2079- 4 - MARKED IMPAIRMENT, FALLS EVERY 4 TO 6 STEPS 5 - SEVERE IMPAIRMENT, CANNOT WALK WITHOUT FALLING AROUSAL 1 - VERY LOW: STUPOR, COMA, LITTLE OR NO RESPONSIVENESS 2 - LOW: SOMEWHAT STUPOROUS X 3 - NORMAL: ALERT, EXPLORATORY MOVEMENTS XXXXXXXXXXXXXXXXXXXXXXXX XXXXX 4 - SOMEWHAT HIGH: SLIGHT EXCITEMENT, TENSE, SUDDEN DARTING OR FREEZING 5 - VERY HIGH: HYPERALERT, EXCITED, SUDDEN BOUTS OF RUNNING OR BODY MOVEMENTS WIL-99310 TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS Observer: A E D C B A E D C B A E D C B A E D C B A E D C B A E D C B POSTURE BIZARRE/STEREOTYPIC BEHAVIOR 1 - NONE XXXXXXXXXXXXXXXXXX XXXXXX 2 - HEAD FLICK: HEAD SHAKING OR BACKWARD FLIP OF HEAD XXXXX X 3 - HEAD SEARCH: STEREOTYPED, REPETITIVE TURNING OF HEAD FROM SIDE TO SIDE 4 - HALLUCINATORY: APPEARS TO BE RESPONDING TO OBJECTS NOT PRESENT 5 - COMPULSIVE LICKING OR BITING 6 - PRANCING: RESTLESS SHIFTING FROM ONE FORELIMB TO THE OTHER 7 - UPRIGHT WALKING: ON HINDLIMBS ONLY 8 - AIMLESS WANDERING: PROGRESSIVE, SLOW, PLODDING MOVEMENTS, NO APPARENT PURPOSE BIZARRE/STEREOTYPIC BEHAVIOR (Continued) X XX -2080- 9 - CIRCLING: TENDENCY TO MOVE IN CIRCLES AROUND OBJECTS, OR IN AN OPEN ENVIRONMENT X X X 10 - WALTZING: RAPID TURNING IN CIRCLES 11 - RETROPULSION: ANIMAL WALKS BACKWARDS X 12 - SPATIAL DISORIENTATION: WALKING OR STUMBLING INTO OBJECTS X 13 - SIDE TO SIDE ROCKING 14 - STRAUB TAIL: INCREASED TAIL ELEVATION 15 - VERTICAL JUMPING 16 - PACING WITHOUT PURPOSE 17 - HEAD BOBBING X X 18 - WRITHING: LYING DOWN, WAVELIKE MOVEMENTS OF ABDOMEN, ALTERNATING LIMB MOVEMENTS PUPIL RESPONSE 1 - NO PUPIL RESPONSE XXXXX X X 2 - PUPIL RESPONSE PRESENT XXXXXXXXXXX XXXXXXXXX XXX AIR RIGHTING REFLEX 1 - NORMAL XXXXXXXXXXXXXXXXXXXXXXXXX 2 - SLIGHTLY UNCOORDINATED 3 - LANDS ON SIDE 4 - LANDS ON BACK X X XX X WIL-99310 TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS -2081- Observer: POSTURE 1 - SITTING OR STANDING NORMALLY 2 - ASLEEP, LYING ON SIDE OR CURLED UP 3 - ALERT, ORIENTED TOWARD OBSERVER 4 - SITTING, HEAD HELD LOW 5 - FLATTENED, LIMBS MAY BE EXTENDED 6 - LYING ON SIDE, LIMBS IN AIR 7 - IMMOBILE 8 - REARING 9 - SPLAYED HINDLEGS 10 - PROSTRATION CONVULSIONS - CLONIC 1 - ABSENT 2 - TWITCHES (BACK MUSCLES) 3 - IRREGULAR JERKING MOVEMENTS OF THE LIMBS 4 - CLONIC WHOLE-BODY CONVULSIONS 5 - HEAD AND/OR BODY TWITCHES (MYOCLONUS) 6 - MUSCLE FASICULATIONS 7 - REPETITIVE MOVEMENT OF MOUTH AND JAWS (CHEWING) CONVULSIONS - TONIC 1 - ABSENT 2 - TONIC: CONTRACTION OF EXTENSORS SUCH THAT LIMBS ARE RIGID AND EXTENDED 3 - OPISTHOTONUS: HEAD, BODY AND LIMBS RIGIDLY ARCHED BACKWARDS 4 - EMPROSTHOTONUS: HEAD, BODY AND LIMBS EXTENDED FORWARD 5 - 'POPCORN SEIZURE': ANIMAL REPEATEDLY JUMPS OR BOUNCES IN AIR 6 - ASPHYXIAL: BOUTS OF SEVERE CLONIC-TONIC CONVULSIONS TREMORS 1 - ABSENT 2 - SLIGHT (1.5mm) 3 - MODERATELY COARSE (3 mm) Animal #52247 AEDCB XX XX X XXXXX XXXXX XXXXX Animal #52225 AEDCB XXXXX XXXXX XXXXX XXXXX Animal #52216 AEDCB XXXXX XXXXX XXXXX XXXX X Animal #51868 AEDCB XXXXX XXX X X XXXXX XXXXX Animal #52254 AEDCB XXXXX XXXXX XXXXX XXXXX Animal #52338 AEDCB XXXXX XXXXX XXXXX XXX X X WIL-99310 TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS -2082- 4 - MARKEDLY COARSE (4.5mm) 5 - EXTREMELY COARSE (6 mm) BITING 1 - NONE 2 - BITING OF CAGE 3 - BITING OF SELF PALPEBRAL CLOSURE 1 - EYELIDS WIDE OPEN 2 - EYELIDS SLIGHTLY DROOPING 3 - DROOPING EYELIDS (HALF-CLOSED) 4 - EYELIDS COMPLETELY SHUT FECES CONSISTENCY 1 - PELLETS 2 - PELLETS, PARTIALLY FORMED 3 - UNFORMED, DIARRHEA 4 - PELLETS ABSENT Observer: EASE OF HANDLING IN HAND 1 - LOW: NO RESISTANCE, ANIMAL IS EASY TO HANDLE 2 - MODERATELY LOW: SLIGHT RESISTANCE TO BEING HANDLED, WITH/WITHOUT VOCALIZATION 3 - MODERATELY HIGH: MAY FREEZE, BE TENSE OR RIGID, WITH/WITHOUT VOCALIZATION 4 - HIGH: SQUIRMS, TWISTS, ATTEMPTS TO BITE, WITH/WITHOUT VOCALIZATION LACRIMATION 1 - NONE 2 - SLIGHT 3 - SEVERE CHROMODACRYORRHEA 1 - ABSENT 2 - PRESENT SALIVATION 1 - NONE 2 - SLIGHT 3 - SEVERE Animal #52247 AEDCB XXXXX XXXXX X XX X X X XXXXX XXXXX XXXXX XXXXX Animal #52225 AEDCB XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX Animal #52216 AEDCB XXXXX XXXXX XXXX X XXXX X X X XXX XXXXX XXXXX Animal #51868 AEDCB XXXXX X X X XX XXXX X XXXXX XXXX X XXXXX XXXXX Animal #52254 AEDCB XXXXX X XX XX XX X X X XXXXX X XX X X XXXXX XXXXX Animal #52338 AEDCB XXXXX XXXXX XXX X X X XXXXX XXXX X XXXXX XXXXX WIL-99310 TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS -2083- Observer: PILOERECTION 1 - NONE 2 - SLIGHT 3 - SEVERE FUR APPEARANCE 1 - NORMAL: CLEAN AND GROOMED 2 - SLIGHTLY SOILED 3 - VERY SOILED, CRUSTY PALPEBRAL CLOSURE 1 - EYELIDS WIDE OPEN 2 - EYELIDS SLIGHTLY DROOPING 3 - DROOPING EYELIDS (HALF-CLOSED) 4 - EYELIDS COMPLETELY SHUT RESPIRATORY RATE 1 - NORMAL: BY OBSERVATION (80-110/MIN.) 2 - DECREASED: BELOW 80/MIN. 3 - INCREASED: ABOVE 110/MIN. RESPIRATORY CHARACTER 1 - NORMAL 2 - RALES: ABNORMAL SOUND ACCOMPANYING BREATHING 3 - RETCHING 4 - DYSPNEIC: SHORT OF BREATH 5 - GASPING RED DEPOSITS - eyes 1 - PRESENT 2 - ABSENT RED DEPOSITS - nose 1 - PRESENT 2 - ABSENT RED DEPOSITS - mouth 1 - PRESENT 2 - ABSENT CRUSTY DEPOSITS - eyes 1 - PRESENT 2 - ABSENT Animal #52247 AEDCB XXXX X XXXXX XXXXX XXXXX XXXXX XXXXX X X XXX XXXXX XXXXX Animal #52225 AEDCB XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX Animal #52216 AEDCB XXXXX XXXX X XXXXX XXXXX XXXXX X XXXX XXXXX XXXXX XXXXX Animal #51868 AEDCB XXXXX XXXX X XXXX X XXXXX XXXXX X X XXX XX XXX X X XXX XXXXX Animal #52254 AEDCB XXXXX XXX X X X XX X X XXXXX XXXXX X X XXX X X XXX XXXXX XXXXX Animal #52338 AEDCB XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX WIL-99310 TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS CRUSTY DEPOSITS - nose 1 - PRESENT 2 - ABSENT CRUSTY DEPOSITS - mouth 1 - PRESENT 2 - ABSENT MUCOUS MEMBRANES - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH EYES - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH Observer: SKIN - color 1 - PINK 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BRIGHT, DEEP RED FLUSH EYE PROMINENCE 1 - NORMAL 2 - EXOPHTHALMUS 3 - ENOPHTHALMUS MUSCLE TONE 1 - MUSCLE IS FIRM BUT NOT HARD (NORMAL) 2 - MUSCLE IS SOFT AND FLABBY 3 - MUSCLE IS TENSE AND HARD Animal #52247 AEDCB XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXX X Animal #52225 AEDCB XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX Animal #52216 AEDCB XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX Animal #51868 AEDCB XXXXX XXXXX XXXXX XXXXX XXXX X XXXXX X X XX X Animal #52254 AEDCB XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XX XX X Animal #52338 AEDCB XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX -2084- WIL-99310 TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS -2085- Observer: MOBILITY 1 - NORMAL 2 - SLIGHTLY IMPAIRED 3 - MODERATELY IMPAIRED 4 - TOTALLY IMPAIRED, LOCOMOTION IMPOSSIBLE GAIT 1 - NORMAL 2 - WALKS ON TIPTOES 3 - BODY DRAGS, ABDOMEN CONTACTS SURFACE, BODY SWAYS 4 - HINDLIMBS SPLAYED OR DRAGGING, UNABLE TO SUPPORT WEIGHT 5 - HUNCHED BODY 6 - ATAXIA, EXCESSIVE SWAY, ROCKS OR LURCHES AS PROCEEDS FORWARD 7 - WALKS ON METATARSUS CONVULSIONS - CLONIC 1 - ABSENT 2- TWITCHES (BACK MUSCLES) 3 - REPETITIVE MOVEMENT OF MOUTH AND JAWS 4 - CLONIC TREMORS OF THE LIMBS 5 - WHOLE BODY TREMORS 6 - CLONIC CONVULSIONS 7 - WET DOG SHAKES CONVULSIONS - TONIC 1 - ABSENT 2 - TONIC: CONTRACTION OF EXTENSORS SUCH THAT LIMBS ARE RIGID AND EXTENDED 3 - OPISTHOTONUS: HEAD, BODY AND LIMBS RIGIDLY ARCHED BACKWARDS 4 - EMPROSTHOTONUS: HEAD, BODY AND LIMBS EXTENDED FORWARD 5 - 'POPCORN SEIZURE': ANIMAL REPEATEDLY JUMPS OR BOUNCES IN AIR 6 - ASPHYXIAL: BOUTS OF SEVERE CLONIC-TONIC CONVULSIONS Animal #52247 AEDCB XXXXX XXX X X X XXXXX XXXXX Animal #52225 AEDCB XXXXX XXXXX XXXXX XXXXX Animal #52216 AEDCB XXXXX XXXX X XXXXX XXXXX Animal #51868 AEDCB XXX XX XX XX XX X XXX XXXX X XXXXX Animal #52254 AEDCB XXXXX X X XX XXXXX XXXX XXX X X XXXXX Animal #52338 AEDCB XXXXX XXX XX XXXXX XXXXX WIL-99310 TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS -2086- Observer: TREMORS 1 - NONE 2 - SLIGHT (1.5mm) 3 - MODERATELY COARSE (3 mm), SLIGHT IMPAIRMENT OF LOCOMOTION 4 - MARKEDLY COARSE (4.5mm), MODERATE/MARKED IMPAIRMENT OF LOCOMOTION 5 - EXTREMELY COARSE (6 mm), LOCOMOTION IMPOSSIBLE GAIT SCORE 1 - NORMAL 2 - SLIGHT IMPAIRMENT, BUT DEFINITE 3 - CONSIDERABLE IMPAIRMENT, WITHOUT FALLING 4 - MARKED IMPAIRMENT, FALLS EVERY 4 TO 6 STEPS 5 - SEVERE IMPAIRMENT, CANNOT WALK WITHOUT FALLING AROUSAL 1 - VERY LOW: STUPOR, COMA, LITTLE OR NO RESPONSIVENESS 2 - LOW: SOMEWHAT STUPOROUS 3 - NORMAL: ALERT, EXPLORATORY MOVEMENTS 4 - SOMEWHAT HIGH: SLIGHT EXCITEMENT, TENSE, SUDDEN DARTING OR FREEZING 5 - VERY HIGH: HYPERALERT, EXCITED, SUDDEN BOUTS OF RUNNING OR BODY MOVEMENTS BIZARRE/STEREOTYPIC BEHAVIOR 1 - NONE 2 - HEAD FLICK: HEAD SHAKING OR BACKWARD FLIP OF HEAD 3 - HEAD SEARCH: STEREOTYPED, REPETITIVE TURNING OF HEAD FROM SIDE TO SIDE 4 - HALLUCINATORY: APPEARS TO BE RESPONDING TO OBJECTS NOT PRESENT 5 - COMPULSIVE LICKING OR BITING 6 - PRANCING: RESTLESS SHIFTING FROM ONE FORELIMB TO THE OTHER 7 - UPRIGHT WALKING: ON HINDLIMBS ONLY 8 - AIMLESS WANDERING: PROGRESSIVE, SLOW, PLODDING MOVEMENTS, NO APPARENT PURPOSE Animal #52247 AEDCB XXXXX XXXXX XXXXX XXXXX Animal #52225 AEDCB XXXXX XXXXX XXXXX XXXXX Animal #52216 AEDCB XX X X X XXXXX XXXXX XXXXX Animal #51868 AEDCB XXXXX X X X X X XXXXX X XX XXXX Animal #52254 AEDCB XXXXX X X XX X X XX X X XXXXX XXXX X Animal #52338 AEDCB XXX X X XXXXX X X X X X X XXX WIL-99310 TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS Observer: BIZARRE/STEREOTYPIC BEHAVIOR (Continued) 9 - CIRCLING: TENDENCY TO MOVE IN CIRCLES AROUND OBJECTS, OR IN AN OPEN ENVIRONMENT 10 - WALTZING: RAPID TURNING IN CIRCLES 11 - RETROPULSION: ANIMAL WALKS BACKWARDS 12 - SPATIAL DISORIENTATION: WALKING OR STUMBLING INTO OBJECTS 13 - SIDE TO SIDE ROCKING 14 - STRAUB TAIL: INCREASED TAIL ELEVATION 15 - VERTICAL JUMPING 16 - PACING WITHOUT PURPOSE 17 - HEAD BOBBING Animal #52247 AEDCB Animal #52225 AEDCB Animal #52216 AEDCB Animal #51868 AEDCB XX X XXXXX X X Animal #52254 AEDCB X X XX XX X X Animal #52338 AEDCB -2087- 18 - WRITHING: LYING DOWN, WAVELIKE MOVEMENTS OF ABDOMEN, ALTERNATING LIMB MOVEMENTS PUPIL RESPONSE 1 - NO PUPIL RESPONSE X X X X XXXXXXXXX X 2 - PUPIL RESPONSE PRESENT X XXXX XXXX X XX X XXX AIR RIGHTING REFLEX 1 - NORMAL XXXXXXXXXXXXXXX XXXX 2 - SLIGHTLY UNCOORDINATED X 3 - LANDS ON SIDE XXX X 4 - LANDS ON BACK X XXX XX -2088- WIL-99310 TABLE 2 FOB OBSERVATIONS - FINDINGS OMITTED PAGE 1 OBSERVER E D E D A E OBSERVATION MOBILITY MOBILITY CONVULSIONS- CLONIC FECES CONSISTENCY FECES CONSISTENCY BIZARRE/STEREOTYPIC BEHAVIOR NUMBER OMITTED 1 1 1 1 1 1 WIL-180017 3M Corporation -2089- MTDID 208 06-128 APPENDIX 63 WIL FOB Historical Control Data Version 1.0 [Crl:CD(SD) Rats] WIL Historical Control Data Crl:CD(SD) Rat Timepoint (PND) Number of Studies Total Number of Animals Tested Test DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Male 4 11 21 8 8 7 119 118 98 AROUSAL 1 VERY LOW STUPOR, COMA, LITTLE OR NO RESPONSIVENESS 2 LOW SOMEWHAT STUPOROUS 3 ALERT, EXPLORATORY MOVEMENTS 4 SOMEWHAT HIGH, SLIGHT EXCITEMENT 5 VERY HIGH HYPERALERT BACKING** NUMBER OF TIMES ANIMAL TAKES 3 OR MORE STEPS BACKWARD IN 2 MINUTES MEAN S.D. MAX MIN N BIZARRE/STEREOTYPIC BEHAVIOR 1 NONE BODY CONDITION (EMACIATION/DEHYDRATION) 1 ABSENT CHROMODACRYORRHEA 1 ABSENT CONVULSIONS CLONIC 1 ABSENT PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 10 2 0 9 15 2 98 101 94 1 0 2 1 0 0 0.03 0.18 1 0 119 119 10 109 119 0.06 0.37 3 0 118 118 10 108 118 0.00 0.00 0 0 98 98 10 98 98 22 1 20 0 0 20 0 0 0.00 0.00 0 0 20 20 0 20 20 35 7 98 0 1 97 0 0 0.01 0.10 1 0 98 98 10 98 98 1 of 17 45 60 8 8 118 118 0 0 2 2 113 115 3 1 0 0 0.00 0.00 0 0 118 0.00 0.00 0 0 118 118 118 10 10 118 118 118 118 IGS DNT FOB v1.0 -2090- WIL Historical Control Data Crl:CD(SD) Rat Timepoint (PND) Number of Studies Total Number of Animals Tested Test CONVULSIONS TONIC 1 ABSENT CRUSTY_DEPOSITS EYES 2 ABSENT CRUSTY_DEPOSITS MOUTH 1 PRESENT 2 ABSENT CRUSTY_DEPOSITS NOSE 1 PRESENT 2 ABSENT DEFECATION** NUMBER OF FECAL BOLI IN OPEN FIELD MEAN S.D. MAX MIN N DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Male 4 11 21 22 8 8 7 1 119 118 98 20 119 118 98 20 109 108 98 20 3 0 0 0 116 118 98 20 3 3 0 0 116 115 98 20 0.00 0.00 0 0 119 0.03 0.16 1 0 118 0.20 0.62 3 0 98 0.00 0.00 0 0 20 35 7 98 98 98 1 97 1 97 0.12 0.59 5 0 98 45 8 118 118 118 0 118 7 111 0.03 0.21 2 0 118 2 of 17 60 8 118 118 118 0 118 0 118 0.03 0.26 2 0 118 -2091- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Male Timepoint (PND) 4 11 21 Number of Studies 8 8 7 Total Number of Animals Tested Test 119 118 98 EASE OF HANDLING 1 VERY EASY 2 2W EASY WITH VOCALIZATION 2W/O EASY WITHOUT VOCALIZATION 3W/O MODERATELY DIFFICULT WITHOUT 4W FREEZES WITH VOCALIZATION VOCALIZATION 116 116 98 0 0 0 1 2 0 2 0 0 2 0 0 0 0 0 EASE OF REMOVAL 1 VERY EASY 2 2W EASY WITH VOCALIZATION 2W/O EASY WITHOUT VOCALIZATION 3W MODERATELY DIFFICULT WITH VOCALIZATION 3W/O MODERATELY DIFFICULT WITHOUT VOCALIZATION 109 115 98 3 0 0 7 1 0 2 0 0 0 0 0 0 0 0 EYE COLOR* 1 PINK 0 0 98 EYE PROMINENCE* 1 NORMAL 0 0 98 FORELIMB MEAN S.D. MAX MIN N GRIPSTRENGTH* PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 0 0 140 0 0 51.43 0 0 300 0 0 17 237 234 174 22 1 20 20 0 0 0 0 0 20 0 0 0 0 0 20 20 109 35.79 210 50 60 3 of 17 35 45 60 7 8 8 98 118 118 97 114 112 0 2 2 0 0 1 0 2 2 0 2 2 0 0 1 78 101 97 16 17 14 2 0 3 0 2 2 1 0 1 1 0 0 98 118 118 98 118 118 295 133.87 670 70 174 592 257.36 1500 190 234 776 331.49 1750 225 234 IGS DNT FOB v1.0 -2092- WIL Historical Control Data Crl:CD(SD) Rat Timepoint (PND) Number of Studies Total Number of Animals Tested Test DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Male 4 11 21 8 8 7 119 118 98 FUR APPEARANCE** 1 NORMAL CLEANED AND GROOMED 2 SLIGHTLY SOILED GAIT 1 NORMAL 3 WALKS ON TIPTOES 4 HINDLIMBS SPLAYED, DRAGGING 5 HUNCHED BODY, ARCHED BACK CANNOT SUPPORT WEIGHT GENERAL BODY POSTURE 1 SITTING OR STANDING NORMALLY 2 ASLEEP, LYING ON SIDE OR CURLED UP 3 ALERT, OREIENTED TOWARD OBSERVER GROOMING MEAN S.D. MAX MIN N 0 107 98 0 1 0 10 98 98 0 8 0 0 1 0 0 1 0 12 20 0 8 0 0 0 0 0 0.00 0.00 0.00 0.00 119.00 0.05 0.21 1.00 0.00 118.00 0.29 0.61 3.00 0.00 98.00 22 1 20 20 0 20 0 0 0 20 0 0 0.45 0.69 2.00 0.00 20.00 4 of 17 35 45 60 7 8 8 98 118 118 98 118 117 0 0 1 98 118 118 0 0 0 0 0 0 0 0 0 0 9 16 0 1 0 0 10 4 0.12 0.44 3.00 0.00 98.00 0.07 0.31 2.00 0.00 118.00 0.03 0.16 1.00 0.00 118.00 -2093- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat Timepoint (PND) Number of Studies Total Number of Animals Tested Test HINDLIMB MEAN S.D. MAX MIN N GRIPSTRENGTH TRIAL* DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Male 4 11 21 22 8 8 7 1 119 118 98 20 0 0 70 54 0 0 26 14 0 0 130 100 0 0 20 30 237 234 174 60 LACRIMATION 1 NONE 109 108 98 20 MOBILITY SCORE BASED ON FIRST 30 SECONDS IN OPEN FIELD ARENA 1 NORMAL 2 SLIGHTLY IMPARED 20 110 98 20 0 8 0 0 MUCOUS MEMBRANES COLOR 1 PINK 119 118 98 20 MUSCLE TONE 1 MUSCLE IS FIRM BUT NOT HARD (NORMAL) 2 MUSCLE IS SOFT AND FLABBY 3 MUSCLE IS TENSE AND HARD 107 117 98 20 12 0 0 0 0 0 0 0 PALPEBRAL CLOSURE* 1 EYELIDS WIDE OPEN 0 0 98 20 5 of 17 35 45 60 7 8 8 98 118 118 128 317 483 54 149 218 270 800 1375 30 50 100 174 234 234 98 118 118 98 118 118 0 0 0 98 118 118 98 118 117 0 0 0 0 0 1 98 118 118 -2094- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Male Timepoint (PND) 4 11 21 22 Number of Studies 8 8 7 1 Total Number of Animals Tested Test 119 118 98 20 PILOERECTION** 1 NONE 2 SLIGHT 0 108 98 20 0 0 0 0 PUPIL RESPONSE* 1 NO PUPIL RESPONSE 2 PUPIL RESPONSE PRESENT 0 0 2 0 0 0 66 20 RED_DEPOSITS EYES 1 PRESENT 2 ABSENT 2 0 0 0 107 108 98 20 RED_DEPOSITS MOUTH 1 PRESENT 2 ABSENT 1 0 0 0 118 118 98 20 RED_DEPOSITS NOSE 1 PRESENT 2 ABSENT 1 0 1 0 118 118 97 20 REPIRATORY CHARACTER 1 NORMAL 119 118 98 20 REPIRATORY RATE 1 NORMAL 119 117 98 20 6 of 17 35 45 60 7 8 8 98 118 118 98 118 116 0 0 2 1 0 1 67 88 87 0 1 3 98 117 115 0 1 1 98 117 117 7 11 5 91 107 113 98 118 118 98 118 118 -2095- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat Timepoint (PND) Number of Studies Total Number of Animals Tested Test SALIVATION 1 NONE SKIN COLOR 1 PINK 2 PALE TREMORS 1 NONE URINATION MEAN S.D. MAX MIN N DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Male 4 11 21 22 8 8 7 1 119 118 98 20 119 119 0 119 0.03 0.18 1 0 119 118 117 1 118 0.19 0.43 2 0 118 98 98 0 98 0.02 0.14 1 0 98 20 20 0 20 0.00 0.00 0 0 20 35 7 98 98 98 0 98 0.13 0.37 2 0 98 45 8 118 118 118 0 118 0.27 0.73 4 0 118 7 of 17 60 8 118 118 118 0 118 0.74 1.06 5 0 118 -2096- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female 8 of 17 -2097- Timepoint (PND) Number of Studies Total Number of Animals Tested Test AROUSAL 1 VERY LOW STUPOR, COMA, LITTLE OR NO RESPONSIVENESS 2 LOW SOMEWHAT STUPOROUS 3 ALERT, EXPLORATORY MOVEMENTS 4 SOMEWHAT HIGH, SLIGHT EXCITEMENT BACKING** NUMBER OF TIMES ANIMAL TAKES 3 OR MORE STEPS BACKWARD IN 2 MINUTES MEAN S.D. MAX MIN N BIZARRE/STEREOTYPIC BEHAVIOR 1 NONE 6 UPRIGHT WALKING BODY CONDITION (EMACIATION/DEHYDRATION) 1 ABSENT PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 4 11 21 22 35 45 60 8 8 7 1 7 8 8 119 118 98 19 98 117 117 11 3 1 0 0 0 1 6 14 0 0 0 1 0 97 100 95 19 95 107 110 5 1 2 0 3 9 6 0.00 0.00 0 0 119 0.03 0.17 1 0 118 0.00 0.00 0 0 98 0.00 0.00 0 0 19 0.00 0.00 0 0 98 0.00 0.00 0 0 117 0.00 0.00 0 0 117 119 117 98 19 98 117 117 0 1 0 0 0 0 0 10 10 10 0 10 10 10 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female Timepoint (PND) Number of Studies Total Number of Animals Tested Test CHROMODACRYORRHEA 1 ABSENT CONVULSIONS CLONIC 1 ABSENT 5 CLONIC CONVULSIONIS CONVULSIONS TONIC 1 ABSENT 5 'POPCORN SEIZURE' CRUSTY_DEPOSITS EYES 1 PRESENT 2 ABSENT CRUSTY_DEPOSITS MOUTH 2 ABSENT CRUSTY_DEPOSITS NOSE 1 PRESENT 2 ABSENT PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 4 11 21 22 8 8 7 1 119 118 98 19 108 108 98 19 119 117 98 19 0 1 0 0 119 117 98 19 0 1 0 0 0 0 0 0 108 108 98 19 119 118 98 19 3 2 0 0 116 116 98 19 9 of 17 35 45 60 7 8 8 98 117 117 98 117 117 98 117 117 0 0 0 98 117 117 0 0 0 0 2 0 98 115 117 98 117 117 1 2 0 97 115 117 IGS DNT FOB v1.0 -2098- WIL Historical Control Data Crl:CD(SD) Rat Timepoint (PND) Number of Studies Total Number of Animals Tested Test DEFECATION** NUMBER OF FECAL BOLI IN OPEN FIELD MEAN S.D. MAX MIN N EASE OF HANDLING 1 VERY EASY 2 2W EASY WITH VOCALIZATION 2W/O EASY WITHOUT VOCALIZATION 3 DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female 4 11 21 22 8 8 7 1 119 118 98 19 10 of 17 35 45 60 7 8 8 98 117 117 0.00 0.00 0 0 119 0.02 0.13 1 0 118 0.12 0.46 3 0 98 0.05 0.23 1 0 19 0.00 0.00 0 0 98 0.00 0.00 0 0 117 0.00 0.00 0 0 117 116 0 2 1 0 118 0 0 0 0 98 0 0 0 0 19 0 0 0 0 96 2 0 0 0 108 3 1 4 1 112 1 0 4 0 -2099- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female 11 of 17 Timepoint (PND) Number of Studies Total Number of Animals Tested Test EASE OF REMOVAL 1 VERY EASY 2 2W EASY WITH VOCALIZATION 2W/O EASY WITHOUT VOCALIZATION 3 3W/O MODERATELY DIFFICULT WITHOUT VOCALIZATION 5 EYE COLOR* 1 PINK EYE PROMINENCE* 1 NORMAL 4 11 21 22 35 45 60 8 8 7 1 7 8 8 119 118 98 19 98 117 117 115 116 97 19 80 93 102 2 0 1 0 15 19 9 2 1 0 0 1 1 3 0 1 0 0 2 1 3 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 98 19 98 117 117 0 0 98 19 98 117 117 -2100- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female 12 of 17 Timepoint (PND) Number of Studies Total Number of Animals Tested Test FORELIMB GRIPSTRENGTH* MEAN S.D. MAX MIN N FUR APPEARANCE** 1 NORMAL CLEANED AND GROOMED GAIT 1 NORMAL 3 WALKS ON TIPTOES 4 HINDLIMBS SPLAYED, DRAGGING CANNOT SUPPORT WEIGHT GENERAL BODY POSTURE 1 SITTING OR STANDING NORMALLY 2 ASLEEP, LYING ON SIDE OR CURLED UP 3 ALERT, OREIENTED TOWARD OBSERVER 4 11 21 22 35 45 60 8 8 7 1 7 8 8 119 118 98 19 98 117 117 0 0 143 108 278 506 637 0 0 49 31 124 222 289 0 0 300 190 640 1075 1425 0 0 50 50 60 180 150 234 234 174 57 174 231 231 0 108 98 19 98 117 117 10 101 98 19 98 117 117 0 5 0 0 0 0 0 0 2 0 0 0 0 0 13 20 7 0 0 0 0 19 0 0 0 0 0 5 13 0 0 0 0 14 6 -2101- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat Timepoint (PND) Number of Studies Total Number of Animals Tested Test GROOMING MEAN S.D. MAX MIN N HINDLIMB GRIPSTRENGTH TRIAL* MEAN S.D. MAX MIN N LACRIMATION 1 NONE 2 SLIGHT DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female 4 11 21 22 8 8 7 1 119 118 98 19 0.00 0.00 0 0 119 0 0 0 0 0 234 0.03 0.21 2 0 118 0 0 0 0 0 234 0.31 0.65 3 0 98 72 25 150 20 174 0.47 0.51 1 0 19 49 14 80 20 57 108 108 98 19 0 0 0 0 35 7 98 0.04 0.25 2 0 98 117 53 290 30 174 98 0 13 of 17 45 60 8 8 117 117 0.07 0.29 2 0 117 0.05 0.32 3 0 117 270 413 137 155 900 900 50 125 231 231 117 116 0 1 -2102- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female Timepoint (PND) Number of Studies Total Number of Animals Tested Test MOBILITY SCORE BASED ON FIRST 30 SECONDS IN OPEN FIELD ARENA 1 NORMAL 2 SLIGHTLY IMPARED MUCOUS MEMBRANES COLOR 1 PINK MUSCLE TONE 1 MUSCLE IS FIRM BUT NOT HARD (NORMAL) 2 MUSCLE IS SOFT AND FLABBY PALPEBRAL CLOSURE* 1 EYELIDS WIDE OPEN PILOERECTION** 1 NONE PUPIL RESPONSE* 1 NO PUPIL RESPONSE 2 PUPIL RESPONSE PRESENT PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 4 11 21 22 8 8 7 1 119 118 98 19 20 111 98 19 0 7 0 0 119 118 98 19 109 118 98 19 10 0 0 0 0 0 98 19 0 108 98 19 0 0 3 0 0 0 65 19 14 of 17 35 45 60 7 8 8 98 117 117 98 117 117 0 0 0 98 117 117 98 117 117 0 0 0 98 117 117 98 117 117 0 0 0 68 87 87 IGS DNT FOB v1.0 -2103- WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female Timepoint (PND) Number of Studies Total Number of Animals Tested Test RED_DEPOSITS EYES 1 PRESENT 2 ABSENT RED_DEPOSITS MOUTH 1 PRESENT 2 ABSENT RED_DEPOSITS NOSE 1 PRESENT 2 ABSENT REPIRATORY CHARACTER 1 NORMAL 2 RALES ABNORMAL SOUND ACCOMPANYING BREATHING REPIRATORY RATE 1 NORMAL SALIVATION 1 NONE PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 4 11 21 22 8 8 7 1 119 118 98 19 0 0 1 0 108 108 97 19 1 0 0 0 118 118 98 19 5 0 0 0 114 118 98 19 119 118 98 19 0 0 0 0 119 118 98 19 119 118 98 19 15 of 17 35 45 60 7 8 8 98 117 117 0 1 4 98 116 113 0 0 0 98 117 117 0 5 0 98 112 117 98 117 116 0 0 1 98 117 117 98 117 117 IGS DNT FOB v1.0 -2104- WIL Historical Control Data Crl:CD(SD) Rat Timepoint (PND) Number of Studies Total Number of Animals Tested Test SKIN COLOR 1 PINK TREMORS 1 NONE 2 SLIGHT (1.5MM) URINATION MEAN S.D. MAX MIN N DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04 Female 4 11 21 22 8 8 7 1 119 118 98 19 119 118 98 19 119 117 98 19 0 1 0 0 0.02 0.13 1 0 119 0.14 0.46 3 0 118 0.04 0.20 1 0 98 0.00 0.00 0 0 19 35 7 98 98 98 0 0.08 0.37 3 0 98 16 of 17 45 60 8 8 117 117 117 117 117 117 0 0 0.00 0.00 0 0 117 0.04 0.24 2 0 117 -2105- PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11 IGS DNT FOB v1.0 WIL Historical Control Data Crl:CD(SD) Rat DNT Functional Observational Battery Study Information Study Number 1 2 3 4 5 6 7 8 Vehicle 1% Methylcellulose 5% gum arabic and 0.01% Tween 80. PMI Nutrition Diet Virgin Olive Oil Deionized Water 1% Methylcellulose 1% Methylcellulose Certified Rodent LabDiet Route Oral Gavage Oral Gavage Oral Inhalation Oral Gavage Oral Gavage Oral Gavage Diet Start Date 07/13/1999 11/02/1999 03/26/2002 06/24/2001 02/21/2001 10/14/2003 10/14/2003 06/27/2000 End Date 08/02/2000 10/21/2000 06/04/2003 09/17/2002 07/01/2001 06/10/2004 06/10/2004 03/02/2001 17 of 17 -2106- IGS Rat DNT FOB v1.0.xls WIL-180017 3M Corporation -2107- MTDID 208 06-128 APPENDIX 64 WIL Motor Activity Historical Control Data Version 2.1 [Crl:CD(SD) Rats] WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 1 of 10 -2108- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 122 99 147 97 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Males - PND 13 16-30 MIN 100 107 139 84 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 31-45 MIN 52 39 156 158 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 46-60 MIN 62 48 138 108 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Combined 336 169 580 396 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Ambulatory 49 52 190 323 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 2 of 10 Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 276 207 NA NA 129 85 NA NA NA NA NA NA 131 125 234 223 Grand Mean S.D. S.E.M. Count Minimum Maximum 173 65.2 26.6 6 122 276 Males - PND 13 16-30 MIN 362 317 NA NA 115 123 NA NA NA NA NA NA 110 197 315 393 31-45 MIN 327 378 NA NA 98 109 NA NA NA NA NA NA 113 227 251 435 46-60 MIN 389 413 NA NA 126 136 NA NA NA NA NA NA 72 100 125 210 190 116.6 47.6 6 100 362 166 103.8 42.4 6 52 327 152 120.3 49.1 6 62 389 Combined 1354 1101 NA NA 468 406 NA NA NA NA NA NA 427 525 925 1049 682 388.0 158.4 6 336 1354 Ambulatory 514 506 NA NA 174 278 NA NA NA NA NA NA 134 231 327 448 231 165.6 67.6 6 49 514 -2109- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 3 of 10 -2110- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 187 76 273 184 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Males - PND 17 16-30 MIN 121 87 110 129 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 31-45 MIN 67 113 47 60 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 46-60 MIN 50 124 13 21 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Combined 425 283 442 332 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Ambulatory 146 154 167 130 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 4 of 10 Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 675 262 NA NA 386 227 NA NA NA NA NA NA 482 340 372 165 Grand Mean S.D. S.E.M. Count Minimum Maximum 396 170.3 69.5 6 187 675 Males - PND 17 16-30 MIN 452 230 NA NA 207 152 NA NA NA NA NA NA 282 393 218 224 31-45 MIN 381 283 NA NA 47 44 NA NA NA NA NA NA 250 444 170 226 46-60 MIN 364 277 NA NA 29 20 NA NA NA NA NA NA 181 288 160 206 231 125.5 51.3 6 110 452 160 135.1 55.2 6 47 381 133 133.0 54.3 6 13 364 Combined 1872 833 NA NA 668 385 NA NA NA NA NA NA 1195 1307 920 670 920 551.0 224.9 6 425 1872 Ambulatory 731 377 NA NA 222 154 NA NA NA NA NA NA 419 590 254 225 323 221.8 90.6 6 146 731 -2111- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 5 of 10 -2112- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 398 123 301 118 252 101 366 159 205 120 230 114 321 179 228 95 192 77 NA NA 327 192 270 162 NA NA Males - PND 21 16-30 MIN 140 121 79 79 32 45 86 102 25 26 64 93 59 61 34 59 24 19 NA NA 80 123 22 35 NA NA 31-45 MIN 97 112 26 31 25 43 55 101 22 19 60 116 9 10 20 31 26 25 NA NA 67 120 22 51 NA NA 46-60 MIN 47 65 10 8 38 64 28 57 24 23 47 77 17 32 41 91 26 24 NA NA 24 50 8 9 NA NA Combined 682 308 416 180 347 110 535 334 276 128 401 355 406 227 323 160 267 129 NA NA 498 323 321 212 NA NA Ambulatory 239 129 143 78 107 38 166 112 78 56 126 128 122 95 113 74 89 38 NA NA 166 126 110 78 NA NA NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 6 of 10 Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 472 126 382 85 288 151 513 93 449 198 463 166 496 195 399 117 Grand Mean S.D. S.E.M. Count Minimum Maximum 345 102.8 23.6 19 192 513 Males - PND 21 16-30 MIN 164 124 217 159 113 100 185 122 186 206 172 90 232 191 100 110 31-45 MIN 114 130 201 227 48 79 142 148 114 171 79 102 159 175 80 109 46-60 MIN 147 177 123 177 65 80 87 135 104 144 41 42 124 129 50 75 106 69.4 15.9 19 22 232 72 54.1 12.4 19 9 201 55 41.8 9.6 19 8 147 Combined 896 436 923 606 513 307 928 360 854 616 755 294 1010 561 628 223 578 249.7 57.3 19 267 1010 Ambulatory 273 184 416 395 115 115 265 115 250 236 215 99 275 198 173 67 181 86.8 19.9 19 78 416 -2113- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 7 of 10 -2114- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 408 164 NA NA NA NA 401 156 Males - PND 23 16-30 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 85 108 NA NA NA NA 100 138 31-45 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 32 46 NA NA NA NA 40 103 46-60 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 25 48 NA NA NA NA 40 92 Combined NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 550 257 NA NA NA NA 581 356 Ambulatory NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 181 88 NA NA NA NA 187 131 NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 8 of 10 Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Grand Mean 404 S.D. 5.1 S.E.M. 3.6 Count 2 Minimum 401 Maximum 408 Males - PND 23 16-30 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 31-45 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 46-60 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 92 36 33 10.3 5.6 10.8 7.3 3.9 7.6 2 2 2 85 32 25 100 40 40 Combined NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 565 21.6 15.3 2 550 581 Ambulatory NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 184 4.2 3.0 2 181 187 -2115- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 9 of 10 -2116- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 692 207 807 130 809 190 850 154 799 192 759 127 739 204 952 172 908 127 892 265 835 194 825 193 732 247 Males - PND 60 & 61 16-30 MIN 322 199 471 247 376 158 496 199 375 209 329 164 371 293 400 212 420 193 256 215 333 125 333 217 356 162 31-45 MIN 267 174 274 277 247 202 156 130 260 189 246 129 278 215 239 206 160 111 51 91 350 246 210 212 251 126 46-60 MIN 253 175 159 167 76 79 150 216 195 206 118 98 187 175 183 199 134 143 32 64 152 164 123 176 183 156 Combined 1534 607 1710 636 1508 500 1652 262 1629 462 1452 341 1575 690 1774 642 1622 397 1232 441 1669 569 1491 636 1522 451 Ambulatory 411 222 501 276 454 165 478 71 442 204 373 95 456 245 545 222 481 144 392 174 514 209 441 209 432 195 NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 10 of 10 Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 1105 157 791 205 731 106 1064 232 1088 149 988 160 1087 137 1089 206 Grand Mean S.D. S.E.M. Count Minimum Maximum 883 137.2 29.9 21 692 1105 Males - PND 60 & 61 16-30 MIN 501 176 378 209 363 155 497 243 492 236 401 215 639 221 620 160 31-45 MIN 345 200 329 254 292 236 328 263 325 290 230 202 473 237 305 180 46-60 MIN 371 241 178 178 207 100 210 167 131 189 160 150 328 189 243 228 416 97.4 21.3 21 256 639 267 85.2 18.6 21 51 473 180 76.2 16.6 21 32 371 Combined 2322 543 1676 624 1593 405 2098 701 2035 664 1779 458 2527 624 2257 514 1745 322.7 70.4 21 1232 2527 Ambulatory 818 253 496 235 417 151 752 261 704 276 608 177 920 270 828 207 546 161.0 35.1 21 373 920 -2117- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 1 of 10 -2118- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 54 52 87 72 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Females - PND 13 16-30 MIN 41 49 46 41 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 31-45 MIN 70 45 64 55 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 46-60 MIN 82 63 91 120 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Combined 247 83 288 222 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Ambulatory 46 57 65 117 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 313 241 NA NA 99 81 NA NA NA NA NA NA 233 205 207 219 Grand Mean S.D. S.E.M. Count Minimum Maximum 166 101.0 41.25 6 54 313 Females - PND 13 16-30 MIN 367 334 NA NA 167 218 NA NA NA NA NA NA 165 207 239 317 31-45 MIN 292 405 NA NA 312 548 NA NA NA NA NA NA 97 162 205 373 46-60 MIN 252 430 NA NA 252 558 NA NA NA NA NA NA 80 142 143 223 171 123.0 50.20 6 41 367 173 111.8 45.66 6 64 312 150 82.4 33.62 6 80 252 Combined 1224 1172 NA NA 829 1300 NA NA NA NA NA NA 574 552 794 1051 659 369.1 150.69 6 247 1224 Ambulatory 492 617 NA NA 389 813 NA NA NA NA NA NA 182 255 264 484 240 177.4 72.43 6 46 492 Page 2 of 10 -2119- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 3 of 10 -2120- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 106 60 348 160 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Females - PND 17 16-30 MIN 20 20 240 178 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 31-45 MIN 34 45 121 160 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 46-60 MIN 30 28 107 158 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Combined 190 108 815 530 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Ambulatory 38 34 326 253 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 716 314 NA NA 404 315 NA NA NA NA NA NA 562 264 542 287 Grand Mean S.D. S.E.M. Count Minimum Maximum 446 211.2 86.20 6 106 716 Females - PND 17 16-30 MIN 564 408 NA NA 301 302 NA NA NA NA NA NA 391 395 348 230 31-45 MIN 534 420 NA NA 237 399 NA NA NA NA NA NA 311 389 241 237 46-60 MIN 442 328 NA NA 227 356 NA NA NA NA NA NA 284 455 237 262 310 179.8 73.42 6 20 564 246 171.8 70.14 6 34 534 221 143.4 58.54 6 30 442 Combined 2256 1348 NA NA 1170 1299 NA NA NA NA NA NA 1549 1284 1368 795 1224 697.3 284.65 6 190 2256 Ambulatory 934 686 NA NA 474 644 NA NA NA NA NA NA 555 559 422 310 458 293.9 119.98 6 38 934 Page 4 of 10 -2121- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 5 of 10 -2122- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 319 84 210 149 269 142 312 148 282 78 200 90 262 116 241 146 260 146 NA NA 364 151 185 88 NA NA Females - PND 21 16-30 MIN 43 69 106 117 69 85 126 122 100 97 12 25 63 91 60 80 48 104 NA NA 99 136 50 74 NA NA 31-45 MIN 35 55 71 102 41 58 56 85 52 51 39 64 19 26 19 22 76 131 NA NA 74 125 26 42 NA NA 46-60 MIN 11 14 36 56 31 49 80 138 31 49 40 67 11 6 51 72 59 118 NA NA 76 95 18 35 NA NA Combined 408 137 423 249 410 266 573 437 464 179 291 139 354 213 372 218 443 371 NA NA 612 373 279 191 NA NA Ambulatory 131 52 119 101 125 78 186 185 136 82 92 50 111 77 119 79 146 143 NA NA 178 128 84 60 NA NA NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 416 124 259 150 420 168 432 161 425 164 549 130 526 160 471 159 Grand Mean S.D. S.E.M. Count Minimum Maximum 337 111.1 25.50 19 185 549 Females - PND 21 16-30 MIN 100 97 84 88 144 143 195 160 168 161 184 203 229 174 154 129 31-45 MIN 84 106 161 127 151 192 87 122 165 184 83 135 150 176 133 180 46-60 MIN 99 130 96 95 143 222 82 131 93 144 89 145 114 153 108 138 107 58.8 13.49 19 12 229 80 49.3 11.31 19 19 165 67 38.4 8.81 19 11 143 Combined 699 257 600 305 857 655 795 475 852 598 905 517 1018 516 865 438 591 232.5 53.35 19 279 1018 Ambulatory 183 73 209 133 294 292 241 158 250 209 278 177 302 181 259 143 181 71.1 16.31 19 84 302 Page 6 of 10 -2123- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 7 of 10 -2124- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 425 183 NA NA NA NA 411 190 Females - PND 23 16-30 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 97 101 NA NA NA NA 74 112 31-45 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 45 78 NA NA NA NA 58 103 46-60 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 26 34 NA NA NA NA 32 55 Combined NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 593 280 NA NA NA NA 576 364 Ambulatory NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 201 123 NA NA NA NA 191 135 NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Grand Mean S.D. S.E.M. Count Minimum Maximum 418 9.8 6.93 2 411 425 Females - PND 23 16-30 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 31-45 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 46-60 MIN NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Combined NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Ambulatory NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 86 16.2 11.43 2 74 97 52 9.8 6.93 2 45 58 29 3.8 2.72 2 26 32 584 12.3 8.72 2 576 593 196 6.7 4.75 2 191 201 Page 8 of 10 -2125- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 9 of 10 -2126- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 862 143 827 136 870 190 830 214 918 144 798 293 875 220 958 165 970 114 834 160 894 272 966 196 797 263 Females - PND 60 & 61 16-30 MIN 246 135 351 193 425 203 440 220 407 170 351 277 434 267 432 196 357 255 221 177 370 219 485 189 284 211 31-45 MIN 134 149 323 255 245 128 312 187 340 239 139 178 241 186 324 228 279 242 45 61 251 255 222 218 140 141 46-60 MIN 161 264 283 205 166 220 142 147 301 280 121 134 92 106 165 184 278 215 36 81 245 140 155 158 217 167 Combined 1403 451 1784 625 1706 590 1724 407 1966 524 1410 757 1642 575 1879 552 1885 453 1136 271 1760 631 1828 509 1438 498 Ambulatory 509 201 608 221 626 256 601 173 690 227 513 314 593 225 694 267 722 214 409 119 630 314 653 239 503 239 NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Summary of Motor Activity SDI Photobeam Activity System Page 10 of 10 Study Number 14 15 16 17 18 19 20 21 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 0-15 MIN 1047 212 801 227 800 142 1024 168 1035 72 1035 130 1028 141 1003 168 Grand Mean S.D. S.E.M. Count Minimum Maximum 913 91.7 20.01 21 797 1047 Females - PND 60 & 61 16-30 MIN 498 174 421 129 295 169 479 188 555 217 512 232 586 181 535 195 31-45 MIN 326 190 301 183 228 219 301 208 396 275 280 263 352 247 351 214 46-60 MIN 281 197 190 192 198 167 236 224 218 172 111 175 351 226 252 188 414 100.3 21.89 21 221 586 263 88.0 19.20 21 45 396 200 77.8 16.98 21 36 351 Combined 2152 467 1712 471 1521 463 2040 569 2203 588 1938 602 2316 537 2141 600 1790 299.6 65.37 21 1136 2316 Ambulatory 863 199 568 189 460 164 800 223 891 258 743 283 969 242 858 259 662 150.8 32.91 21 409 969 -2127- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Motor Activity v2.1 WIL-180017 3M Corporation -2128- MTDID 208 06-128 APPENDIX 65 WIL Startle Response Historical Control DataVersion 2.1 [Crl:CD(SD) Rats] WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Males - PND 20 Page 1 of 6 -2129- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 1-10 213.5 82.8 248.1 99.6 159.9 95.4 214.5 96.0 163.2 93.0 209.9 91.8 177.7 85.0 NA NA 192.6 87.7 209.1 89.6 216.6 66.1 264.5 123.8 Vmax 11-20 21-30 161.2 137.8 63.6 77.6 232.3 180.6 136.7 81.3 130.6 130.0 75.6 93.5 188.2 177.8 87.1 88.1 149.2 134.1 70.1 72.2 160.8 159.1 87.1 102.3 144.1 167.9 75.0 68.2 NA NA NA NA 149.8 134.4 71.2 74.2 169.9 145.9 89.3 66.1 172.1 139.3 80.3 63.0 232.7 206.9 124.5 92.7 31-40 144.8 69.6 203.8 106.7 136.9 86.6 191.7 86.6 125.8 78.2 140.4 99.6 160.7 63.5 NA NA 137.2 75.7 132.7 69.4 151.2 44.4 189.2 110.0 41-50 151.1 70.7 206.6 113.9 123.7 59.3 200.2 89.9 135.8 55.6 117.6 98.6 143.7 45.4 NA NA 123.7 85.9 105.2 65.6 155.2 63.9 161.2 134.6 All Trials 161.7 68.0 214.3 94.9 136.2 77.3 194.5 82.8 141.6 67.7 157.6 90.6 158.8 61.9 NA NA 147.5 73.0 152.6 64.2 166.9 53.7 210.9 102.0 1-10 28.8 4.3 26.6 4.4 30.0 9.2 25.6 4.1 26.5 5.4 26.7 5.3 25.8 2.5 NA NA 27.1 3.7 24.8 3.8 24.8 4.1 24.5 3.1 11-20 25.6 4.7 24.8 3.1 27.1 8.0 23.6 4.4 22.7 2.1 24.6 3.9 24.8 4.1 NA NA 26.4 5.4 24.3 4.8 26.3 3.4 22.8 3.8 Tmax 21-30 31-40 26.3 26.3 6.8 4.4 25.4 23.8 6.1 5.1 26.8 24.9 7.6 4.5 22.4 22.8 3.1 2.5 22.7 24.9 3.2 6.6 25.2 23.3 5.9 2.8 22.8 23.0 2.7 3.4 NA NA NA NA 23.8 25.2 2.9 5.7 24.1 24.9 3.4 4.2 25.6 25.4 4.0 5.5 23.7 24.3 5.3 4.7 41-50 25.5 6.9 23.8 4.5 25.7 7.1 21.2 1.6 22.4 4.2 25.4 4.4 23.5 3.3 NA NA 25.2 4.5 25.1 3.6 23.9 3.2 25.7 6.0 All Trials 26.5 4.7 24.9 3.6 26.9 6.9 23.1 2.0 23.8 2.8 25.0 3.4 24.0 2.1 NA NA 25.6 3.0 24.6 2.4 25.2 2.7 24.2 2.6 Vave 35.4 12.5 45.6 18.6 30.8 17.0 39.7 16.9 30.8 12.6 33.4 18.1 34.8 14.0 NA NA 33.6 17.4 29.9 14.0 34.1 11.4 45.0 20.1 NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Males - PND 20 Page 2 of 6 Study Number 13 14 15 16 17 18 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 1-10 213.5 120.3 211.1 111.3 179.9 109.0 213.9 92.7 NA NA NA NA Vmax 11-20 21-30 203.0 170.6 121.9 110.1 172.0 137.1 85.4 73.6 150.5 120.1 82.6 64.4 171.1 160.6 65.1 70.2 NA NA NA NA NA NA NA NA 31-40 159.3 116.1 126.3 75.1 118.5 62.9 155.7 72.1 NA NA NA NA 41-50 159.9 121.0 138.9 120.6 108.6 95.2 144.1 71.5 NA NA NA NA Grand Mean S.D. S.E.M. Count Minimum Maximum 205.9 46.21 11.93 15 82.8 264.5 172.5 40.02 10.33 15 63.6 232.7 153.5 28.02 7.23 15 77.6 206.9 151.6 29.63 7.65 15 69.6 203.8 145.0 31.58 8.15 15 70.7 206.6 All Trials 181.3 114.4 157.1 73.2 135.5 72.5 169.1 67.6 NA NA NA NA 165.7 34.00 8.78 15 68.0 214.3 1-10 24.7 2.9 28.8 10.7 26.0 6.3 25.8 3.8 NA NA NA NA 11-20 23.3 1.3 27.6 10.2 24.0 4.5 23.4 3.6 NA NA NA NA Tmax 21-30 31-40 23.2 23.5 3.3 4.7 27.0 27.6 7.0 8.5 24.2 24.6 4.3 7.0 25.3 24.6 6.1 4.7 NA NA NA NA NA NA NA NA 41-50 23.2 3.5 29.0 7.6 24.3 5.4 23.9 4.1 NA NA NA NA 26.4 7.19 1.86 15 4.3 30.0 24.8 7.08 1.83 15 4.7 27.6 24.6 6.36 1.64 15 6.8 27.0 24.6 7.33 1.89 15 4.4 27.6 24.5 6.87 1.78 15 6.9 29.0 All Trials 23.6 2.3 28.0 7.4 24.6 4.0 24.6 2.8 NA NA NA NA 25.0 7.26 1.87 15 4.7 28.0 Vave 37.9 24.9 30.0 14.4 26.3 15.5 32.6 14.5 NA NA NA NA 34.7 7.49 1.93 15 12.5 45.6 -2130- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Males - PND 21 Page 3 of 6 -2131- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 1-10 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 258.7 102.3 NA NA NA NA Vmax 11-20 21-30 31-40 41-50 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 224.4 217.1 217.8 200.3 94.4 95.5 100.9 97.6 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA All Trials NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 223.7 91.8 NA NA NA NA Tmax 1-10 11-20 21-30 31-40 41-50 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 23.1 22.3 22.5 21.7 22.0 2.6 2.5 4.9 3.4 2.3 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA All Trials NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 22.3 2.4 NA NA NA NA Vave NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 47.2 19.2 NA NA NA NA NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Males - PND 21 Page 4 of 6 Study Number 13 14 15 16 17 18 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 1-10 NA NA NA NA NA NA NA NA NA NA NA NA Vmax 11-20 21-30 31-40 41-50 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Grand Mean NA S.D. NA S.E.M. NA Count NA Minimum NA Maximum NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA All Trials NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Tmax 1-10 11-20 21-30 31-40 41-50 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA All Trials NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Vave NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA -2132- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Males - PND 60 Page 5 of 6 -2133- Study Vmax All Number 1-10 11-20 21-30 31-40 41-50 Trials 1-10 11-20 1 Mean 290.2 238.6 157.6 135.6 155.4 195.5 28.5 27.6 S.D. 167.9 135.5 77.9 65.1 123.1 90.9 3.1 3.1 2 Mean 329.7 237.5 175.9 176.0 130.4 209.9 31.8 34.6 S.D. 206.8 179.9 122.6 111.2 88.1 129.0 7.4 8.0 3 Mean 207.7 152.1 124.2 110.6 95.2 138.0 29.5 28.7 S.D. 124.4 102.6 68.4 63.5 67.7 64.3 4.3 1.5 4 Mean 341.0 272.6 253.2 195.5 173.2 247.1 30.8 32.7 S.D. 161.3 198.7 257.3 146.5 143.2 162.7 5.6 7.5 5 Mean 295.0 258.0 193.0 214.7 188.3 229.8 30.7 32.3 S.D. 292.0 326.5 297.3 361.5 243.5 299.3 8.8 10.8 6 Mean 126.7 109.5 93.0 79.0 72.0 96.0 33.2 32.4 S.D. 90.7 111.0 74.1 63.9 56.8 58.2 5.2 5.8 7 Mean 127.2 107.7 73.5 70.2 57.3 87.2 34.8 36.4 S.D. 71.4 98.8 39.8 47.9 37.2 48.0 5.6 7.2 8 Mean 198.4 141.2 128.9 93.0 90.4 130.4 30.3 30.7 S.D. 106.8 91.4 102.0 69.6 66.4 68.1 7.1 5.5 9 Mean 141.8 96.4 58.6 75.5 72.0 88.8 32.7 32.4 S.D. 134.9 81.2 50.0 57.6 70.4 73.8 8.9 5.4 10 Mean 316.6 241.8 198.8 154.9 168.8 216.2 30.3 31.4 S.D. 315.1 219.9 176.5 149.5 155.4 183.8 8.5 8.1 11 Mean 184.9 189.0 133.6 98.7 149.6 151.1 31.2 32.6 S.D. 113.5 161.3 122.7 75.5 162.0 112.0 5.2 9.4 12 Mean 308.1 206.6 141.2 147.6 154.2 191.5 31.5 32.1 S.D. 235.1 173.4 88.0 144.1 189.9 128.6 8.6 7.1 13 Mean 177.0 136.7 131.2 154.6 118.1 143.5 32.4 31.4 NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Tmax 21-30 31-40 41-50 29.3 32.5 33.8 6.3 6.2 7.3 31.9 29.8 29.6 7.0 3.0 5.0 32.2 33.5 37.0 5.3 4.2 7.5 34.3 35.6 34.5 8.0 7.1 9.4 35.4 32.2 34.7 9.3 6.5 8.6 38.7 37.8 37.7 8.6 7.1 10.0 40.4 39.0 44.2 6.5 10.2 13.5 32.4 34.7 32.7 6.7 5.9 6.6 33.7 37.0 36.5 7.8 10.2 10.5 32.0 28.3 26.6 7.5 10.8 6.7 36.8 32.2 36.8 12.1 8.6 9.2 31.0 31.5 36.0 4.9 5.4 11.5 29.8 28.5 27.2 All Trials 30.4 4.4 31.5 4.8 32.2 2.7 33.6 5.9 33.1 7.0 36.0 5.1 39.0 5.5 32.2 3.9 34.5 5.8 29.7 5.7 33.9 7.1 32.4 5.1 29.9 Vave 42.7 18.8 46.5 28.0 29.3 12.8 53.0 33.5 46.6 57.0 21.2 12.2 21.2 12.7 28.7 14.0 20.0 16.3 42.7 38.1 33.1 21.5 39.7 23.0 28.5 IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Males - PND 60 Page 6 of 6 Study Number 14 15 16 17 18 S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 1-10 165.9 197.5 123.3 205.2 184.1 254.7 202.5 240.9 156.1 283.1 177.3 Vmax 11-20 21-30 31-40 41-50 147.2 143.2 152.8 125.5 155.4 138.1 117.8 120.7 119.5 142.6 110.9 146.8 182.3 170.3 139.8 156.6 151.9 169.4 138.9 189.4 202.8 183.6 153.3 132.1 209.0 180.5 144.5 107.5 156.0 166.3 149.9 133.3 156.7 201.2 212.9 152.8 204.0 152.5 132.3 151.7 160.7 120.6 98.3 125.5 Grand Mean S.D. S.E.M. Count Minimum Maximum 234.8 79.86 18.82 18 126.7 341.0 182.7 55.61 13.11 18 96.4 272.6 148.5 49.61 11.69 18 58.6 253.2 133.3 43.95 10.36 18 65.1 214.7 128.8 42.26 9.96 18 57.3 188.3 All Trials 142.2 145.9 120.1 170.8 153.5 185.3 162.0 169.3 162.2 184.7 112.0 165.6 55.44 13.07 18 87.2 247.1 Tmax 1-10 11-20 21-30 31-40 41-50 8.2 8.8 6.2 6.9 12.9 31.3 31.3 33.1 31.5 34.7 5.3 5.3 9.3 6.3 8.0 33.9 35.5 34.2 34.7 32.7 6.4 9.6 9.4 8.9 8.9 29.9 32.3 32.0 32.0 31.9 4.3 6.2 6.0 6.7 9.7 28.6 28.1 30.1 30.9 31.5 4.6 5.4 5.5 5.1 9.2 30.1 30.5 32.2 32.9 31.4 5.5 4.7 5.4 6.8 5.4 31.2 8.16 1.92 18 3.1 34.8 31.8 8.30 1.96 18 3.1 36.4 33.3 8.11 1.91 18 6.3 40.4 33.0 8.48 2.00 18 6.2 39.0 33.9 8.29 1.95 18 7.3 44.2 All Trials 5.5 32.4 4.7 34.2 6.8 31.6 4.3 29.9 3.5 31.4 3.2 32.6 8.75 2.06 18 4.4 39.0 Vave 28.5 28.5 23.6 34.9 37.8 36.7 34.8 30.8 30.8 39.8 22.3 34.7 11.34 2.67 18 18.8 53.0 -2134- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Females - PND 20 Page 1 of 6 -2135- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 1-10 232.4 68.7 230.5 59.6 179.3 72.5 208.6 62.0 226.5 91.1 184.3 68.2 174.4 120.3 NA NA 135.4 72.0 198.5 89.4 241.9 130.5 219.4 93.0 Vmax 11-20 21-30 31-40 41-50 189.4 186.2 188.8 194.7 51.3 39.6 36.1 30.1 186.6 171.5 150.2 167.1 65.2 57.0 63.5 61.2 173.1 154.3 133.7 159.5 71.3 69.4 52.4 71.6 204.6 157.2 181.8 160.2 73.8 40.7 70.4 89.0 184.3 178.3 187.5 192.0 88.7 67.5 58.9 68.3 140.6 150.6 142.3 127.5 67.5 62.0 55.7 54.2 171.3 133.4 132.6 136.9 69.9 53.8 41.5 36.0 NA NA NA NA NA NA NA NA 138.9 109.0 110.9 119.4 59.9 45.9 40.7 61.7 153.1 139.6 132.6 116.9 79.6 76.9 71.6 57.3 192.8 191.3 183.9 192.1 87.9 83.1 62.8 97.8 200.2 183.6 187.6 182.2 102.3 118.7 101.7 89.3 All Trials 198.3 37.7 181.2 50.8 160.0 60.9 182.5 56.4 193.7 70.0 149.0 54.5 149.7 53.5 NA NA 122.7 43.8 148.2 64.7 200.4 78.9 194.6 94.4 Tmax 1-10 11-20 21-30 31-40 41-50 26.7 23.3 21.4 22.0 22.5 6.5 3.3 1.3 2.2 1.7 23.3 22.3 22.1 23.3 22.4 4.2 3.1 2.7 4.7 3.7 28.7 27.2 25.1 26.4 24.6 5.9 7.0 5.2 5.2 4.5 24.6 22.7 21.9 22.3 24.3 3.3 2.9 1.6 2.6 5.1 24.4 21.9 20.8 22.3 21.8 6.1 2.6 2.7 3.2 4.5 23.8 22.4 22.9 22.2 24.2 2.9 3.0 3.5 2.5 6.6 26.0 24.1 22.9 23.1 23.3 6.2 5.4 2.5 3.2 3.0 NA NA NA NA NA NA NA NA NA NA 24.6 23.4 25.4 23.2 22.4 4.6 3.1 6.3 4.3 3.9 25.3 23.2 24.0 23.9 24.1 6.7 4.4 5.1 5.4 5.9 26.3 24.2 23.3 23.9 24.1 4.8 4.2 3.0 4.4 4.0 23.6 22.6 23.0 22.1 24.0 2.8 5.0 4.9 4.7 6.2 All Trials 23.2 2.0 22.7 2.6 26.4 4.7 23.2 1.7 22.3 2.9 23.1 2.6 23.9 2.8 NA NA 23.8 3.6 24.1 3.9 24.4 2.9 23.1 4.1 Vave 44.4 8.1 39.5 10.0 35.3 12.0 37.1 9.7 38.7 12.6 31.4 12.2 32.4 14.5 NA NA 27.3 10.0 27.3 12.3 42.3 15.8 41.4 19.0 NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Females - PND 20 Page 2 of 6 Study Number 13 14 15 16 17 18 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. 1-10 168.0 69.7 163.5 79.1 165.6 67.7 181.2 83.5 NA NA NA NA Vmax 11-20 21-30 31-40 41-50 132.5 110.7 110.9 106.7 79.3 40.1 44.7 31.1 141.5 111.6 111.8 110.9 64.5 52.9 65.9 55.5 122.4 121.6 112.5 103.0 53.8 64.4 69.9 57.0 161.8 163.7 158.3 138.6 76.0 81.4 97.3 96.3 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Grand Mean S.D. S.E.M. Count Minimum Maximum 194.0 31.32 8.09 15 135.4 241.9 166.2 26.66 6.88 15 122.4 204.6 150.8 28.71 7.41 15 109.0 191.3 148.3 30.90 7.98 15 110.9 188.8 147.2 33.14 8.56 15 103.0 194.7 All Trials 125.8 46.1 127.8 51.5 125.0 49.2 160.7 78.7 NA NA NA NA 161.3 28.72 7.41 15 122.7 200.4 Tmax 1-10 11-20 21-30 31-40 41-50 25.9 24.7 23.8 25.5 26.3 4.0 3.6 3.1 4.5 4.8 31.5 26.0 26.7 27.3 25.0 9.6 4.9 5.5 7.1 4.7 25.3 24.8 25.8 23.2 23.9 7.1 6.8 6.5 5.6 2.9 29.4 24.3 23.2 24.2 27.1 6.8 3.2 3.6 4.8 8.2 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 26.0 2.32 0.60 15 23.3 31.5 23.8 1.46 0.38 15 21.9 27.2 23.5 1.68 0.43 15 20.8 26.7 23.7 1.61 0.42 15 22.0 27.3 24.0 1.45 0.37 15 21.8 27.1 All Trials 25.2 2.4 27.3 4.7 24.6 4.5 25.6 3.4 NA NA NA NA 24.2 1.44 0.37 15 22.3 27.3 Vave 24.2 9.6 24.2 10.4 24.3 10.5 30.0 15.0 NA NA NA NA 33.3 7.02 1.81 15 24.2 44.4 -2136- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Females - PND 21 Page 3 of 6 -2137- Study Number 1 2 3 4 5 6 7 8 9 10 11 12 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Vmax 1-10 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 11-20 21-30 31-40 41-50 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA All Trials NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Tmax 1-10 11-20 21-30 31-40 41-50 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA All Trials NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Vave NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Females - PND 21 Page 4 of 6 Study Number 13 14 15 16 17 18 Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Vmax 1-10 NA NA NA NA NA NA NA NA NA NA 258.0 74.4 11-20 21-30 31-40 41-50 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 246.4 228.6 229.5 217.6 91.5 90.1 87.8 82.8 Grand Mean NA NA NA NA NA S.D. NA NA NA NA NA S.E.M. NA NA NA NA NA Count NA NA NA NA NA Minimum NA NA NA NA NA Maximum NA NA NA NA NA All Trials NA NA NA NA NA NA NA NA NA NA 236.0 76.7 NA NA NA NA NA NA Tmax 1-10 11-20 21-30 31-40 41-50 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 23.4 21.5 21.2 21.9 21.2 4.3 3.0 2.9 4.0 2.9 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA All Trials NA NA NA NA NA NA NA NA NA NA 21.8 2.8 NA NA NA NA NA NA Vave NA NA NA NA NA NA NA NA NA NA 49.0 15.4 NA NA NA NA NA NA -2138- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Females - PND 60 Page 5 of 6 -2139- Study Vmax All Number 1-10 11-20 21-30 31-40 41-50 Trials 1-10 11-20 1 Mean 144.7 98.1 100.5 111.5 79.4 106.8 32.8 32.6 S.D. 92.6 77.5 68.5 88.9 58.2 56.0 5.3 7.9 2 Mean 116.8 81.3 72.3 61.8 58.8 78.2 33.5 32.0 S.D. 53.1 47.2 40.7 45.9 33.2 36.1 5.4 5.3 3 Mean 163.1 83.4 71.2 76.6 62.1 91.3 29.6 33.7 S.D. 105.8 56.5 55.0 41.8 40.6 53.7 4.9 6.4 4 Mean 167.6 139.7 93.3 90.8 110.4 120.3 29.3 31.4 S.D. 91.1 98.5 52.3 66.3 111.7 73.6 4.4 6.6 5 Mean 177.5 176.7 146.6 122.1 114.7 147.5 29.1 30.8 S.D. 131.5 184.5 168.2 125.6 120.0 140.0 6.3 6.7 6 Mean 87.8 59.9 68.5 51.9 44.2 62.5 33.4 35.8 S.D. 45.0 43.3 43.8 20.8 20.6 24.7 8.5 11.4 7 Mean 102.1 91.6 89.9 64.1 65.6 82.6 37.4 36.2 S.D. 61.0 66.9 55.8 41.2 55.2 41.3 6.3 11.8 8 Mean 111.9 80.7 68.4 74.0 69.9 81.0 30.4 31.6 S.D. 87.3 64.2 64.5 71.5 79.6 70.6 5.5 6.1 9 Mean 72.4 51.2 42.6 39.5 37.1 48.6 35.3 36.2 S.D. 44.3 31.5 24.2 27.6 20.9 24.4 8.3 6.6 10 Mean 147.9 109.2 101.9 94.4 70.0 104.3 31.2 29.5 S.D. 71.6 58.1 61.1 62.9 41.6 48.4 6.9 4.9 11 Mean 163.7 121.4 88.3 109.3 67.1 109.9 31.0 35.3 S.D. 117.4 110.1 66.3 58.7 43.9 61.6 9.2 11.2 12 Mean 146.0 101.2 81.7 137.6 116.0 116.5 29.9 35.5 S.D. 100.3 41.0 46.0 171.5 152.1 75.0 3.9 8.3 13 Mean 96.3 68.9 53.1 65.3 39.3 64.6 34.9 36.4 NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Tmax 21-30 31-40 41-50 35.5 34.9 32.1 6.5 8.6 4.2 36.7 33.9 35.2 6.3 7.1 4.5 33.8 35.0 33.3 7.4 6.7 6.3 31.1 30.0 31.9 4.6 5.0 6.2 34.3 34.9 33.5 9.3 9.1 6.0 38.7 39.9 38.5 11.8 6.6 6.8 34.7 39.7 37.6 6.8 7.5 9.8 33.7 32.6 34.8 8.1 8.5 7.9 38.5 37.3 36.1 6.1 8.5 6.9 30.9 30.7 30.4 7.9 8.1 6.9 35.3 31.1 39.3 9.2 7.3 9.8 30.5 30.9 32.2 5.1 8.5 5.9 34.8 37.8 36.1 All Trials 33.6 4.5 34.3 4.4 33.1 4.7 30.8 3.4 32.5 6.8 37.2 5.7 37.1 5.8 32.6 5.1 36.7 5.1 30.6 5.0 34.4 6.3 31.8 4.2 36.0 Vave 21.5 11.0 16.8 7.6 18.6 11.7 23.5 15.9 29.1 25.6 12.4 4.7 18.1 9.0 16.0 13.3 11.0 5.9 16.5 8.3 22.9 12.1 24.6 14.4 10.0 IGS Rat DNT Auditory Startle Response v2.1 WIL Research Laboratories, LLC Crl:CD(SD) Rat* Historical Control Data Pup Auditory Startle Response Females - PND 60 Page 6 of 6 Study Number 14 15 16 17 18 S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Mean S.D. Vmax 1-10 59.1 147.4 119.4 125.7 83.5 188.4 200.6 118.6 69.3 167.8 93.3 11-20 21-30 31-40 41-50 66.6 39.3 59.0 17.8 113.3 97.0 71.2 72.2 107.0 87.1 58.3 66.3 101.9 101.2 61.4 68.3 110.6 103.5 45.6 63.0 145.3 123.1 99.2 114.7 228.7 152.4 108.1 155.5 78.8 74.1 63.4 66.2 51.5 75.2 39.5 55.6 137.0 105.5 101.8 90.6 115.7 92.7 93.8 81.6 Grand Mean S.D. S.E.M. Count Minimum Maximum 129.2 33.33 7.86 18 72.4 188.4 97.1 32.53 7.67 18 51.2 176.7 86.5 24.75 5.83 18 42.6 146.6 78.7 26.46 6.24 18 39.5 137.6 72.9 25.17 5.93 18 37.1 116.0 All Trials 41.4 100.2 83.1 91.7 73.3 134.1 161.9 80.2 49.8 120.5 85.4 92.0 25.99 6.13 18 48.6 147.5 Tmax 1-10 11-20 21-30 31-40 41-50 5.6 11.2 6.6 10.2 7.1 35.7 32.7 33.9 34.9 35.9 10.2 6.9 5.3 6.7 5.4 34.3 32.7 34.3 35.6 34.5 6.4 6.1 10.4 8.9 9.6 32.4 34.8 33.6 32.0 32.5 4.5 8.0 7.7 5.0 5.2 31.4 32.4 33.8 29.7 30.8 6.2 7.7 10.4 7.5 6.5 30.7 33.0 32.5 36.0 33.8 6.2 8.8 6.1 7.0 8.1 29.7 2.45 0.58 18 29.1 37.4 30.9 2.10 0.49 18 29.5 36.4 31.9 2.25 0.53 18 30.5 38.7 31.6 3.17 0.75 18 29.7 39.9 31.6 2.55 0.60 18 30.4 39.3 All Trials 6.1 34.6 4.5 34.3 6.1 33.1 3.6 31.6 5.2 33.2 5.2 30.9 2.04 0.48 18 30.6 37.2 Vave 6.7 17.7 15.7 16.0 14.3 24.4 36.3 12.4 8.6 25.3 16.1 17.7 5.46 1.29 18 10.0 29.1 -2140- NA = Not applicable * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat DNT Auditory Startle Response v2.1 WIL-180017 3M Corporation -2141- MTDID 208 06-128 APPENDIX 66 WIL Biel Maze Historical Control Data Version 1.2 [Crl:CD(SD) Rats] WIL Historical Control Data Crl:CD(SD) Rat* Male PND 22 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Female PND 22 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Swimming Ability All 11.2 2.7 0.6 9.0 17.1 NA NA NA NA NA 11.7 2.8 0.7 7.5 19.4 NA NA NA NA NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 86.4 11.9 2.9 58.6 103.2 15.2 2.6 0.6 9.9 20.2 74.4 19.2 4.7 52.6 115.6 13.7 3.8 0.9 9.3 21.6 62.5 19.2 4.7 31.9 104.9 12.4 4.1 1.0 5.4 18.9 50.0 12.6 3.1 25.1 72.5 9.4 3.0 0.7 3.6 14.3 Path B Trials (Learning) 5 6 7 8 9 137.7 13.0 3.2 113.3 158.5 26.4 4.9 1.2 16.1 33.3 116.4 20.5 5.0 86.7 152.5 21.6 5.2 1.3 15.3 31.0 108.2 15.6 3.8 87.3 148.5 20.7 5.0 1.2 13.5 34.0 89.6 21.2 5.1 56.6 117.5 17.2 5.4 1.3 8.6 28.2 75.8 16.6 4.0 37.5 113.6 14.0 2.6 0.6 9.1 19.4 1 of 27 Path A Trials (Memory) 10 11 12 60.7 15.5 3.8 40.6 96.1 11.3 2.7 0.7 6.5 15.5 76.7 19.0 4.6 38.3 127.5 19.7 4.1 1.0 9.2 25.6 59.7 25.4 6.2 40.3 152.5 14.3 4.5 1.1 9.1 27.0 83.4 17.6 4.3 55.5 110.5 15.3 3.5 0.8 9.5 20.7 74.3 15.5 3.8 48.2 114.6 13.6 3.1 0.8 6.7 19.1 63.1 14.0 3.4 43.4 95.2 12.3 3.4 0.8 6.7 19.7 46.7 8.8 2.1 29.3 65.0 9.0 2.3 0.6 5.8 14.2 145.9 16.9 4.1 115.7 168.6 26.5 5.0 1.2 13.7 34.3 114.4 15.9 3.9 82.5 147.5 21.2 2.9 0.7 15.8 26.0 99.4 19.4 4.7 63.6 133.6 18.8 5.4 1.3 6.0 26.8 79.5 18.0 4.4 46.6 106.9 14.5 4.0 1.0 8.4 21.4 74.8 21.6 5.2 51.9 125.0 14.6 5.2 1.3 8.1 25.6 56.0 12.1 2.9 33.6 82.2 10.2 3.2 0.8 5.2 15.2 73.0 14.2 3.4 50.8 97.2 19.0 5.1 1.2 11.4 28.8 58.2 11.3 2.7 39.9 82.2 13.7 3.9 0.9 7.3 21.8 -2142- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Note: PND 22 data compiled from 17 datasets (212 males and 213 females tested) SEC = Seconds PND = Postnatal day IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 24 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Female PND 24 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Swimming Ability All 7.5 NA NA NA NA NA NA NA NA NA 7.8 NA NA NA NA NA NA NA NA NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 66.4 NA NA NA NA 11.9 NA NA NA NA 47.8 NA NA NA NA 9.3 NA NA NA NA 48.3 NA NA NA NA 11.8 NA NA NA NA 33.5 NA NA NA NA 6.5 NA NA NA NA Path B Trials (Learning) 5 6 7 8 9 144.5 NA NA NA NA 25.9 NA NA NA NA 100.3 NA NA NA NA 17.3 NA NA NA NA 81.6 NA NA NA NA 15.0 NA NA NA NA 67.8 NA NA NA NA 12.5 NA NA NA NA 61.0 NA NA NA NA 14.5 NA NA NA NA 2 of 27 Path A Trials (Memory) 10 11 12 49.8 NA NA NA NA 9.0 NA NA NA NA 59.0 NA NA NA NA 15.6 NA NA NA NA 49.5 NA NA NA NA 11.3 NA NA NA NA 71.5 NA NA NA NA 12.8 NA NA NA NA 62.7 NA NA NA NA 12.8 NA NA NA NA 35.9 NA NA NA NA 8.1 NA NA NA NA 32.1 NA NA NA NA 6.1 NA NA NA NA 133.5 NA NA NA NA 23.1 NA NA NA NA 131.6 NA NA NA NA 24.3 NA NA NA NA 106.6 NA NA NA NA 18.9 NA NA NA NA 75.9 NA NA NA NA 13.1 NA NA NA NA 86.1 NA NA NA NA 16.2 NA NA NA NA 68.4 NA NA NA NA 12.8 NA NA NA NA 59.6 NA NA NA NA 14.9 NA NA NA NA 41.2 NA NA NA NA 9.0 NA NA NA NA -2143- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Note: PND 24 data compiled from 1 dataset (20 males and 20 females tested) SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 26 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Female PND 26 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Swimming Ability All 8.4 NA NA NA NA NA NA NA NA NA 9.3 NA NA NA NA NA NA NA NA NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 88.7 NA NA NA NA 19.8 NA NA NA NA 70.9 NA NA NA NA 16.1 NA NA NA NA 78.4 NA NA NA NA 19.6 NA NA NA NA 47.7 NA NA NA NA 11.0 NA NA NA NA Path B Trials (Learning) 5 6 7 8 9 136.0 NA NA NA NA 30.2 NA NA NA NA 101.0 NA NA NA NA 20.0 NA NA NA NA 89.2 NA NA NA NA 18.4 NA NA NA NA 56.8 NA NA NA NA 11.1 NA NA NA NA 60.2 NA NA NA NA 11.4 NA NA NA NA 3 of 27 Path A Trials (Memory) 10 11 12 53.8 NA NA NA NA 9.0 NA NA NA NA 81.1 NA NA NA NA 20.7 NA NA NA NA 46.2 NA NA NA NA 10.3 NA NA NA NA 83.4 NA NA NA NA 17.7 NA NA NA NA 67.6 NA NA NA NA 16.3 NA NA NA NA 54.3 NA NA NA NA 12.1 NA NA NA NA 45.7 NA NA NA NA 10.7 NA NA NA NA 134.8 NA NA NA NA 31.0 NA NA NA NA 106.4 NA NA NA NA 24.4 NA NA NA NA 89.0 NA NA NA NA 19.4 NA NA NA NA 43.9 NA NA NA NA 9.4 NA NA NA NA 50.5 NA NA NA NA 10.7 NA NA NA NA 39.3 NA NA NA NA 7.3 NA NA NA NA 78.3 NA NA NA NA 20.6 NA NA NA NA 50.1 NA NA NA NA 12.3 NA NA NA NA -2144- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Note: PND 26 data compiled from 1 dataset (19 males and 20 females tested) SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 60 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Female PND 60 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Swimming Ability All 6.9 NA NA NA NA NA NA NA NA NA 6.9 NA NA NA NA NA NA NA NA NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 39.0 NA NA NA NA 8.0 NA NA NA NA 37.2 NA NA NA NA 8.5 NA NA NA NA 28.8 NA NA NA NA 6.5 NA NA NA NA 27.9 NA NA NA NA 5.7 NA NA NA NA Path B Trials (Learning) 5 6 7 8 9 139.1 NA NA NA NA 34.0 NA NA NA NA 80.1 NA NA NA NA 16.1 NA NA NA NA 69.8 NA NA NA NA 14.9 NA NA NA NA 59.4 NA NA NA NA 12.5 NA NA NA NA 32.1 NA NA NA NA 5.6 NA NA NA NA 4 of 27 Path A Trials (Memory) 10 11 12 25.2 NA NA NA NA 4.0 NA NA NA NA 77.0 NA NA NA NA 16.9 NA NA NA NA 42.1 NA NA NA NA 10.3 NA NA NA NA 109.0 NA NA NA NA 22.1 NA NA NA NA 44.2 NA NA NA NA 8.4 NA NA NA NA 49.0 NA NA NA NA 11.1 NA NA NA NA 42.4 NA NA NA NA 7.5 NA NA NA NA 116.2 NA NA NA NA 21.6 NA NA NA NA 122.5 NA NA NA NA 24.7 NA NA NA NA 68.5 NA NA NA NA 14.0 NA NA NA NA 39.9 NA NA NA NA 7.5 NA NA NA NA 20.3 NA NA NA NA 2.5 NA NA NA NA 15.6 NA NA NA NA 1.0 NA NA NA NA 72.1 NA NA NA NA 11.9 NA NA NA NA 30.9 NA NA NA NA 4.9 NA NA NA NA -2145- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Note: PND 60 data compiled from 1 dataset (10 males and 10 females tested) SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 62 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Female PND 62 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Swimming Ability All 6.7 1.0 0.2 4.9 9.1 NA NA NA NA NA 7.3 0.9 0.2 6.0 8.5 NA NA NA NA NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 76.4 20.7 4.4 45.5 129.1 14.3 3.5 0.8 8.4 21.3 54.2 14.2 3.0 35.1 94.2 11.2 2.5 0.5 7.1 18.5 45.1 13.3 2.8 25.7 70.2 9.8 3.4 0.7 4.8 16.8 31.6 10.7 2.3 15.4 57.5 6.5 2.3 0.5 2.8 11.4 Path B Trials (Learning) 5 6 7 8 9 131.1 17.9 3.8 82.9 164.4 24.6 4.5 1.0 16.5 32.0 93.4 14.9 3.2 71.1 122.4 17.6 3.3 0.7 12.2 24.6 67.7 16.4 3.5 30.2 91.3 12.3 3.4 0.7 5.5 18.8 45.8 13.4 2.8 26.0 73.3 8.3 2.9 0.6 4.1 13.6 43.1 18.0 3.8 18.0 93.2 7.3 3.9 0.8 1.8 17.1 5 of 27 Path A Trials (Memory) 10 11 12 30.2 10.4 2.2 13.7 51.8 4.9 2.2 0.5 1.2 8.9 76.5 20.9 4.5 45.9 113.2 17.0 4.4 0.9 9.4 26.0 50.7 12.6 2.7 30.7 84.0 10.6 3.0 0.6 6.1 17.6 72.6 16.5 3.5 40.2 98.4 14.4 3.9 0.8 5.6 21.8 56.6 11.7 2.5 37.1 80.4 12.1 2.9 0.6 7.8 16.3 43.8 14.8 3.2 22.1 97.7 8.9 3.4 0.7 4.8 21.5 34.0 8.7 1.8 19.7 54.9 6.3 2.1 0.4 2.3 10.3 127.7 17.4 3.7 89.7 165.3 25.6 4.5 1.0 16.0 36.1 91.0 17.4 3.7 61.2 136.8 18.1 3.7 0.8 11.8 24.0 72.1 18.5 3.9 44.7 110.1 13.7 3.8 0.8 6.9 20.7 46.4 15.3 3.3 26.7 74.5 7.9 2.5 0.5 3.1 12.8 40.3 13.5 2.9 19.2 65.0 6.7 2.9 0.6 1.8 11.5 34.8 8.3 1.8 23.4 49.2 5.9 1.8 0.4 3.5 11.4 72.3 20.0 4.3 41.8 126.3 16.6 4.9 1.0 8.3 28.5 53.2 12.8 2.7 37.2 89.9 10.6 3.0 0.6 5.8 18.9 -2146- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Note: PND 62 data compiled from 22 datasets (337 males and 337 females tested) SEC = Seconds PND = Postnatal day IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male Mean S.D. S.E. Min. Max. PND 63 Time (SEC) Mean No. Errors S.D. S.E. Min. Max. Female PND 63 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Swimming Ability All 7.2 NA NA NA NA NA NA NA NA NA 9.9 NA NA NA NA NA NA NA NA NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 55.5 NA NA NA NA 8.4 NA NA NA NA 44.7 NA NA NA NA 7.1 NA NA NA NA 30.4 NA NA NA NA 6.1 NA NA NA NA 20.8 NA NA NA NA 4.0 NA NA NA NA Path B Trials (Learning) 5 6 7 8 9 110.2 NA NA NA NA 21.3 NA NA NA NA 89.5 NA NA NA NA 17.7 NA NA NA NA 77.2 NA NA NA NA 12.8 NA NA NA NA 53.8 NA NA NA NA 11.0 NA NA NA NA 31.3 NA NA NA NA 4.9 NA NA NA NA 6 of 27 Path A Trials (Memory) 10 11 12 20.2 NA NA NA NA 2.7 NA NA NA NA 82.6 NA NA NA NA 19.6 NA NA NA NA 70.4 NA NA NA NA 15.4 NA NA NA NA 68.1 NA NA NA NA 10.7 NA NA NA NA 51.5 NA NA NA NA 8.6 NA NA NA NA 48.4 NA NA NA NA 8.9 NA NA NA NA 37.0 NA NA NA NA 5.4 NA NA NA NA 129.4 NA NA NA NA 24.6 NA NA NA NA 97.3 NA NA NA NA 18.4 NA NA NA NA 66.1 NA NA NA NA 11.3 NA NA NA NA 63.1 NA NA NA NA 9.3 NA NA NA NA 32.8 NA NA NA NA 3.3 NA NA NA NA 40.2 NA NA NA NA 6.3 NA NA NA NA 86.4 NA NA NA NA 20.7 NA NA NA NA 59.1 NA NA NA NA 9.2 NA NA NA NA * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. -2147- Note: PND 63 data compiled from 1 datasests (10 males and 9 females tested) SEC = Seconds PND = Postnatal day IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 70 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Female PND 70 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Swimming Ability All 6.3 0.5 0.4 5.9 6.6 NA NA NA NA NA 6.3 0.5 0.4 5.9 6.7 NA NA NA NA NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 77.3 6.1 4.3 73.0 81.6 16.0 0.9 0.6 15.4 16.7 47.3 6.0 4.2 43.1 51.6 10.9 2.2 1.6 9.4 12.5 38.2 5.4 3.8 34.4 42.1 8.3 1.9 1.3 7.0 9.7 26.1 4.9 3.4 22.7 29.5 5.9 1.4 1.0 4.9 6.9 Path B Trials (Learning) 5 6 7 8 9 131.3 16.6 11.7 119.6 143.0 29.3 2.5 1.8 27.5 31.1 95.3 26.6 18.8 76.5 114.1 20.4 3.3 2.3 18.0 22.7 77.2 9.4 6.6 70.5 83.8 16.5 1.5 1.1 15.4 17.6 62.2 17.4 12.3 50.0 74.5 12.6 3.1 2.2 10.4 14.8 45.1 13.8 9.8 35.3 54.9 10.2 2.5 1.8 8.4 12.0 7 of 27 Path A Trials (Memory) 10 11 12 28.4 12.4 8.8 19.6 37.2 4.9 2.5 1.8 3.1 6.6 67.6 5.0 3.5 64.0 71.1 18.1 0.6 0.5 17.7 18.6 41.0 6.2 4.4 36.6 45.4 10.7 3.1 2.2 8.5 12.9 62.4 1.3 0.9 61.5 63.4 13.9 1.4 1.0 12.9 15.0 56.2 4.4 3.1 53.1 59.3 14.2 1.3 0.9 13.3 15.1 39.1 4.2 3.0 36.1 42.1 9.2 2.1 1.5 7.8 10.7 28.0 9.6 6.8 21.2 34.8 6.7 3.0 2.1 4.6 8.8 115.0 29.2 20.7 94.4 135.7 28.6 6.2 4.4 24.2 33.0 76.0 7.9 5.6 70.5 81.6 17.4 1.8 1.3 16.2 18.7 64.9 5.3 3.8 61.1 68.6 15.1 0.3 0.2 14.9 15.3 32.0 3.0 2.1 29.9 34.1 6.1 0.8 0.6 5.5 6.7 27.2 2.3 1.7 25.5 28.8 5.2 0.4 0.3 5.0 5.5 22.9 2.2 1.6 21.3 24.5 3.7 0.1 0.1 3.6 3.7 62.5 2.2 1.6 60.9 64.1 17.7 0.1 0.1 17.7 17.8 39.6 13.2 9.4 30.2 48.9 9.1 3.6 2.6 6.6 11.7 -2148- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Note: PND 70 data compiled from 2 datasests (48 males and 50 females tested) SEC = Seconds PND = Postnatal day IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 107 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Female PND 107 Mean Time (SEC) S.D. S.E. Min. Max. Mean No. Errors S.D. S.E. Min. Max. Swimming Ability All 5.6 NA NA NA NA NA NA NA NA NA 6.7 NA NA NA NA NA NA NA NA NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 75.8 NA NA NA NA 14.3 NA NA NA NA 42.7 NA NA NA NA 7.9 NA NA NA NA 34.4 NA NA NA NA 6.9 NA NA NA NA 23.5 NA NA NA NA 5.9 NA NA NA NA Path B Trials (Learning) 5 6 7 8 9 146.6 NA NA NA NA 27.3 NA NA NA NA 99.4 NA NA NA NA 17.2 NA NA NA NA 76.4 NA NA NA NA 13.8 NA NA NA NA 43.7 NA NA NA NA 9.8 NA NA NA NA 29.9 NA NA NA NA 6.2 NA NA NA NA 8 of 27 Path A Trials (Memory) 10 11 12 37.4 NA NA NA NA 6.7 NA NA NA NA 87.6 NA NA NA NA 19.4 NA NA NA NA 36.0 NA NA NA NA 6.9 NA NA NA NA 60.4 NA NA NA NA 10.6 NA NA NA NA 38.0 NA NA NA NA 8.3 NA NA NA NA 37.0 NA NA NA NA 8.0 NA NA NA NA 28.5 NA NA NA NA 7.2 NA NA NA NA 105.6 NA NA NA NA 26.5 NA NA NA NA 103.4 NA NA NA NA 18.9 NA NA NA NA 61.6 NA NA NA NA 11.3 NA NA NA NA 41.9 NA NA NA NA 5.6 NA NA NA NA 42.7 NA NA NA NA 7.1 NA NA NA NA 31.6 NA NA NA NA 4.4 NA NA NA NA 74.3 NA NA NA NA 14.9 NA NA NA NA 54.7 NA NA NA NA 9.7 NA NA NA NA -2149- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. Note: PND 107 data compiled from 1 datasest (18 males and 20 females tested) SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 22 Study 2 Mean Time (SEC) Mean No. Errors Study 4 Mean Time (SEC) Mean No. Errors Study 5 Mean Time (SEC) Mean No. Errors Study 6 Mean Time (SEC) Mean No. Errors Study 8 Mean Time (SEC) Mean No. Errors Study 9 Mean Time (SEC) Mean No. Errors Study 10 Mean Time (SEC) Mean No. Errors Study 11 Mean Time (SEC) Mean No. Errors Swimming Ability All 11.5 NA 9.0 NA 12.8 NA 9.7 NA 9.7 NA 9.1 NA 9.3 NA 12.3 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 9 of 27 Path A Trials (Memory) 10 11 12 103.2 17.6 77.4 16.3 99.8 15.5 90.7 15.0 98.6 17.8 73.3 13.0 75.4 12.2 86.4 14.3 78.5 12.5 65.8 13.6 60.9 11.4 61.6 9.9 77.3 13.9 73.2 12.8 95.8 18.9 83.3 18.3 90.1 18.9 73.9 18.0 39.1 5.6 57.8 9.9 31.9 5.4 64.4 13.4 50.6 10.7 41.8 7.5 51.1 10.1 50.9 8.8 66.2 14.3 30.7 4.5 25.1 3.6 55.0 9.2 46.5 9.7 48.4 6.5 117.1 21.9 110.3 16.6 116.2 19.8 97.0 15.5 113.6 19.4 130.3 28.9 87.3 16.2 97.8 23.0 103.1 22.5 83.0 17.8 155.1 28.8 110.6 17.4 116.2 18.6 86.0 15.3 64.7 10.3 122.6 25.2 150.2 31.0 90.0 15.9 114.3 28.2 78.7 13.8 113.3 20.8 97.0 16.3 90.6 15.5 86.5 15.8 70.8 12.9 136.4 25.5 103.6 19.0 108.3 19.0 59.9 8.6 69.3 12.4 158.5 32.1 115.3 22.6 104.9 22.9 84.3 15.6 69.2 13.2 144.5 31.5 109.7 20.7 87.3 18.8 79.3 14.9 69.2 13.6 42.7 6.5 50.0 12.2 67.6 11.4 63.1 11.5 62.1 10.0 40.6 6.7 71.3 12.2 49.7 10.5 90.7 22.6 54.1 15.4 85.7 23.2 72.5 17.2 57.3 15.3 80.7 22.2 80.7 20.6 62.9 17.4 61.5 13.4 49.9 13.0 50.3 13.1 43.1 10.0 52.9 14.3 46.8 10.3 55.6 12.1 46.3 13.8 -2150- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 22 Study 13 Mean Time (SEC) Mean No. Errors Study 14 Mean Time (SEC) Mean No. Errors Study 17 Mean Time (SEC) Mean No. Errors Study 19 Mean Time (SEC) Mean No. Errors Study 20 Mean Time (SEC) Mean No. Errors Study 21 Mean Time (SEC) Mean No. Errors Study 22 Mean Time (SEC) Mean No. Errors Swimming Ability All 11.0 NA 15.9 NA 9.0 NA 11.3 NA 10.9 NA 13.4 NA 6.2 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 10 of 27 Path A Trials (Memory) 10 11 12 58.6 9.9 53.1 9.3 68.3 12.4 93.5 13.3 73.4 12.7 104.9 17.3 78.9 16.6 100.4 20.6 56.2 13.2 88.7 19.2 62.8 13.1 43.2 8.3 78.4 13.8 52.6 10.9 66.3 13.8 79.4 12.9 54.4 9.3 68.1 14.4 98.9 20.2 55.3 10.8 54.3 11.9 45.3 7.2 72.5 13.4 54.0 11.9 32.0 6.7 46.0 9.5 52.7 9.9 49.5 11.0 152.2 32.0 92.4 18.5 116.7 24.6 62.5 13.9 134.4 19.8 128.3 17.7 124.2 13.5 117.1 15.0 151.3 33.3 86.7 15.3 148.5 34.0 115.7 24.0 133.8 26.0 136.7 29.7 121.1 25.4 117.5 26.0 147.2 27.8 138.3 29.1 111.5 23.5 77.8 16.1 141.9 27.1 107.5 21.1 95.6 19.7 71.7 13.5 136.6 29.3 128.1 26.9 108.8 25.5 78.7 14.8 63.2 14.7 90.3 10.6 88.2 15.6 82.1 15.7 87.0 16.5 65.8 14.3 37.5 9.1 44.4 9.4 96.1 12.4 75.5 14.1 67.4 15.5 44.8 8.6 74.0 15.4 42.3 8.8 76.4 21.5 88.3 19.4 38.3 9.2 86.9 25.6 80.7 22.2 75.7 22.3 72.6 23.1 67.2 17.3 50.3 12.0 40.3 9.1 57.3 13.8 58.1 16.4 55.4 14.0 74.5 22.1 -2151- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 22 Study 26 Mean Time (SEC) Mean No. Errors Study 27 Mean Time (SEC) Mean No. Errors Swimming Ability All 17.1 NA 11.5 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 11 of 27 Path A Trials (Memory) 10 11 12 96.6 16.0 101.4 14.1 90.8 15.8 115.6 21.6 86.8 16.6 64.7 13.3 56.4 10.5 68.0 13.5 137.8 22.2 124.5 22.0 110.9 17.3 56.6 10.6 127.5 16.1 152.5 27.0 90.8 15.8 115.6 21.6 92.0 14.1 64.7 13.3 72.0 13.0 68.0 13.5 72.9 21.7 52.3 11.9 127.5 16.1 152.5 27.0 -2152- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Female PND 22 Study 2 Mean Time (SEC) Mean No. Errors Study 4 Mean Time (SEC) Mean No. Errors Study 5 Mean Time (SEC) Mean No. Errors Study 6 Mean Time (SEC) Mean No. Errors Study 8 Mean Time (SEC) Mean No. Errors Study 9 Mean Time (SEC) Mean No. Errors Study 10 Mean Time (SEC) Mean No. Errors Study 11 Mean Time (SEC) Mean No. Errors Swimming Ability All 19.4 NA 11.5 NA 12.3 NA 12.5 NA 10.6 NA 9.4 NA 11.1 NA 9.6 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 12 of 27 Path A Trials (Memory) 10 11 12 94.0 14.6 48.2 8.2 66.5 11.3 73.6 16.5 66.8 11.9 52.3 6.7 64.2 9.5 84.4 15.0 99.2 17.6 114.6 17.1 55.5 11.3 69.4 14.2 76.5 13.6 78.0 12.5 69.3 14.6 72.2 15.8 63.6 12.5 74.3 15.9 43.4 6.7 74.5 13.5 58.1 11.3 72.3 15.0 64.5 13.1 63.6 11.8 39.6 5.8 58.6 12.0 48.1 8.5 46.1 7.8 65.0 14.2 38.7 6.2 50.3 8.8 29.3 7.2 166.5 30.1 102.1 19.4 87.5 14.6 46.6 8.4 51.9 8.5 164.3 31.1 112.4 19.8 100.3 22.3 73.0 13.3 71.0 14.8 115.7 13.7 109.8 19.6 63.6 6.0 77.8 9.6 55.5 16.9 168.6 29.5 116.3 20.9 120.9 21.1 106.5 21.4 125.0 24.2 116.4 21.8 119.7 22.1 111.0 19.3 99.0 17.6 72.3 14.9 147.7 23.0 147.5 22.2 101.3 16.2 61.1 8.9 99.9 16.5 123.2 24.8 128.9 24.9 102.3 21.3 80.6 14.4 86.8 15.7 147.1 25.3 106.4 17.2 109.0 23.1 60.7 10.7 63.2 13.1 33.6 5.2 43.5 11.7 72.5 13.3 52.3 8.7 54.7 9.2 61.8 12.2 47.6 6.5 55.3 7.4 66.3 14.1 58.7 15.0 63.5 11.4 59.4 14.7 61.7 16.0 92.1 23.8 72.0 16.6 58.3 14.3 48.0 9.1 53.1 12.4 39.9 7.3 72.4 15.8 44.4 10.6 73.8 17.9 69.1 14.5 49.8 7.6 -2153- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Female PND 22 Study 13 Mean Time (SEC) Mean No. Errors Study 14 Mean Time (SEC) Mean No. Errors Study 17 Mean Time (SEC) Mean No. Errors Study 19 Mean Time (SEC) Mean No. Errors Study 20 Mean Time (SEC) Mean No. Errors Study 21 Mean Time (SEC) Mean No. Errors Study 22 Mean Time (SEC) Mean No. Errors Swimming Ability All 11.5 NA 13.0 NA 7.5 NA 11.6 NA 11.1 NA 13.2 NA 7.7 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 13 of 27 Path A Trials (Memory) 10 11 12 110.5 20.6 105.1 20.7 89.0 18.5 83.7 17.4 70.5 13.5 100.7 18.1 90.5 17.9 68.2 11.1 96.4 19.1 77.9 15.2 61.9 12.9 79.9 16.6 73.6 12.1 61.9 13.1 47.2 8.7 95.2 19.7 67.6 15.9 43.8 9.0 80.3 15.0 67.7 13.9 46.6 9.2 36.9 7.0 52.9 10.6 49.0 11.0 37.7 8.0 46.0 6.5 57.0 11.8 46.5 9.7 131.6 26.5 82.5 15.8 108.8 21.7 98.4 19.5 111.3 25.6 158.4 24.0 134.5 24.3 133.6 22.1 106.9 15.3 71.6 10.8 150.2 34.3 92.8 18.0 106.4 22.5 91.0 19.4 96.3 20.3 164.9 32.8 123.0 25.9 69.5 13.2 64.6 14.7 59.5 10.6 147.9 26.5 108.9 22.1 110.9 23.3 90.4 17.4 54.3 9.2 131.5 26.5 106.3 22.4 114.7 26.8 81.5 16.9 55.8 12.4 145.5 32.3 131.8 26.0 94.2 20.3 77.0 15.6 72.1 16.3 56.1 10.7 82.2 15.0 57.4 10.8 63.8 12.9 69.5 15.2 61.3 13.2 53.5 9.6 69.1 17.3 91.7 26.2 50.8 13.5 82.3 23.0 91.9 28.8 69.0 21.7 79.3 24.3 49.5 10.2 57.4 13.5 60.2 15.3 59.5 14.5 82.2 21.8 58.8 17.1 52.0 14.8 -2154- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Female PND 22 Study 26 Mean Time (SEC) Mean No. Errors Study 27 Mean Time (SEC) Mean No. Errors Swimming Ability All 11.9 NA 15.7 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 14 of 27 Path A Trials (Memory) 10 11 12 108.2 17.4 67.4 11.9 70.4 12.5 80.3 13.2 54.7 8.5 55.5 9.2 46.5 8.9 46.0 8.7 148.0 25.0 104.7 19.2 152.7 22.7 117.6 21.2 91.9 17.0 63.8 9.3 53.8 9.6 82.1 14.6 59.8 9.6 66.0 8.1 40.0 6.4 47.2 6.3 78.5 19.9 97.2 22.7 64.8 17.3 54.9 12.6 -2155- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 24 Study 18 Mean Time (SEC) Mean No. Errors Female PND 24 Study 18 Mean Time (SEC) Mean No. Errors Swimming Ability All 7.5 NA 7.8 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 15 of 27 Path A Trials (Memory) 10 11 12 66.4 11.9 47.8 9.3 48.3 11.8 33.5 6.5 144.5 25.9 100.3 17.3 81.6 15.0 67.8 12.5 61.0 14.5 49.8 9.0 59.0 15.6 49.5 11.3 71.5 12.8 62.7 12.8 35.9 8.1 32.1 6.1 133.5 23.1 131.6 24.3 106.6 18.9 75.9 13.1 86.1 16.2 68.4 12.8 59.6 14.9 41.2 9.0 -2156- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 26 Study 12 Mean Time (SEC) Mean No. Errors Female PND 26 Study 12 Mean Time (SEC) Mean No. Errors Swimming Ability All 8.4 NA 9.3 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 16 of 27 Path A Trials (Memory) 10 11 12 88.7 19.8 70.9 16.1 78.4 19.6 47.7 11.0 136.0 30.2 101.0 20.0 89.2 18.4 56.8 11.1 60.2 11.4 53.8 9.0 81.1 20.7 46.2 10.3 83.4 17.7 67.6 16.3 54.3 12.1 45.7 10.7 134.8 31.0 106.4 24.4 89.0 19.4 43.9 9.4 50.5 10.7 39.3 7.3 78.3 20.6 50.1 12.3 -2157- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 60 Study 17 Mean Time (SEC) Mean No. Errors Female PND 60 Study 17 Mean Time (SEC) Mean No. Errors Swimming Ability All 6.9 NA 7.5 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 17 of 27 Path A Trials (Memory) 10 11 12 39.0 8.0 37.2 8.5 28.8 6.5 27.9 5.7 139.1 34.0 80.1 16.1 69.8 14.9 59.4 12.5 32.1 5.6 25.2 4.0 77.0 16.9 42.1 10.3 109.0 22.1 44.2 8.4 49.0 11.1 42.4 7.5 116.2 21.6 122.5 24.7 68.5 14.0 39.9 7.5 20.3 2.5 15.6 1.0 72.1 11.9 30.9 4.9 -2158- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 62 Study 1 Mean Time (SEC) Mean No. Errors Study 2 Mean Time (SEC) Mean No. Errors Study 3 Mean Time (SEC) Mean No. Errors Study 4 Mean Time (SEC) Mean No. Errors Study 5 Mean Time (SEC) Mean No. Errors Study 7 Mean Time (SEC) Mean No. Errors Study 8 Mean Time (SEC) Mean No. Errors Swimming Ability All 7.4 NA 7.5 NA 6.3 NA 5.5 NA 8.6 NA 6.1 NA 6.1 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 18 of 27 Path A Trials (Memory) 10 11 12 108.8 21.3 77.1 14.2 77.7 13.0 65.1 11.6 86.1 13.4 75.9 13.5 100.8 19.8 81.3 16.0 52.1 11.1 60.1 12.0 63.3 13.7 38.7 9.4 43.0 9.4 60.1 11.1 54.9 12.2 53.6 9.9 35.9 7.0 53.3 13.3 44.5 8.0 39.2 9.2 26.0 6.4 50.9 11.4 26.2 4.4 29.0 6.1 19.8 3.8 41.4 7.6 23.1 4.0 33.8 5.8 120.1 23.6 78.4 14.0 131.4 21.3 122.4 22.9 142.4 22.0 86.2 12.2 101.2 20.1 119.8 24.6 137.0 24.7 105.7 18.3 140.7 25.8 107.9 20.8 157.4 19.4 79.9 12.6 91.3 15.5 71.1 9.6 85.4 13.3 80.1 18.8 81.3 17.5 71.9 12.6 34.6 5.5 48.1 9.2 37.5 7.3 55.8 9.3 35.6 8.3 33.3 5.7 30.0 4.8 34.2 6.2 65.6 10.8 93.2 17.1 25.3 2.6 23.3 4.2 39.1 7.3 34.8 6.7 27.1 3.2 49.4 8.9 51.8 8.6 23.2 3.0 24.6 4.2 43.9 8.9 20.4 3.2 23.0 3.9 66.5 15.6 85.5 17.6 87.7 16.8 47.2 14.1 64.3 13.3 84.4 20.4 100.2 22.1 50.2 12.5 37.1 6.1 59.7 11.0 43.6 12.0 51.1 11.8 44.1 7.9 69.1 13.3 -2159- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 62 Study 9 Mean Time (SEC) Mean No. Errors Study 10 Mean Time (SEC) Mean No. Errors Study 11 Mean Time (SEC) Mean No. Errors Study 12 Mean Time (SEC) Mean No. Errors Study 13 Mean Time (SEC) Mean No. Errors Study 14 Mean Time (SEC) Mean No. Errors Study 15 Mean Time (SEC) Mean No. Errors Study 18 Mean Time (SEC) Mean No. Errors Swimming Ability All 7.2 NA 6.2 NA 6.4 NA 6.1 NA 6.7 NA 7.1 NA 6.4 NA 8.0 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 19 of 27 Path A Trials (Memory) 10 11 12 76.1 14.8 77.6 15.1 95.3 17.7 59.1 12.2 61.0 10.8 63.2 14.6 54.9 10.7 78.9 15.3 35.1 8.0 44.7 9.0 94.2 18.5 52.2 11.1 54.6 11.9 45.8 10.5 55.7 11.9 51.2 10.5 66.0 14.3 26.9 4.8 54.5 13.7 62.6 16.8 44.4 8.7 57.6 15.1 40.6 8.5 57.5 10.0 22.0 3.7 28.3 5.3 27.5 6.5 39.0 8.0 48.7 10.5 33.6 7.3 29.7 6.6 25.3 4.9 164.4 32.0 109.0 17.7 108.4 20.6 89.1 15.4 145.5 30.9 95.2 19.3 82.9 16.5 78.0 17.3 147.4 27.5 98.1 18.6 127.9 24.5 76.3 15.0 128.4 29.0 99.2 21.5 133.5 22.7 91.5 17.8 47.8 8.2 74.9 10.6 67.3 11.9 30.2 7.0 75.0 15.9 49.4 9.8 85.2 16.7 81.7 13.5 39.0 5.7 45.4 6.0 27.2 4.1 26.0 4.2 41.9 8.9 32.2 6.9 59.8 10.4 55.3 9.6 47.7 5.7 42.1 6.7 31.9 5.9 26.5 4.5 18.0 1.8 59.3 11.4 39.7 6.4 60.6 9.8 34.9 4.2 24.9 4.1 26.3 6.9 13.7 1.2 16.5 2.0 37.7 7.5 28.9 4.7 27.5 4.1 48.5 11.9 54.3 10.4 109.4 21.8 62.7 15.3 107.6 26.0 62.3 16.0 78.7 16.4 80.9 14.8 48.6 11.4 45.3 8.8 43.2 10.0 30.7 6.4 59.8 14.8 42.2 10.1 46.7 8.7 50.4 9.7 -2160- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 62 Study 19 Mean Time (SEC) Mean No. Errors Study 20 Mean Time (SEC) Mean No. Errors Study 21 Mean Time (SEC) Mean No. Errors Study 22 Mean Time (SEC) Mean No. Errors Study 23 Mean Time (SEC) Mean No. Errors Study 26 Mean Time (SEC) Mean No. Errors Study 27 Mean Time (SEC) Mean No. Errors Swimming Ability All 5.7 NA 6.7 NA 7.3 NA 6.2 NA 9.1 NA 5.8 NA 4.9 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 20 of 27 Path A Trials (Memory) 10 11 12 61.8 11.9 45.5 9.8 76.6 14.2 60.4 14.2 129.1 20.5 109.8 20.7 59.6 12.6 56.7 13.3 41.6 9.5 58.1 11.2 47.8 9.8 74.5 12.0 54.2 12.3 36.4 9.5 36.4 7.5 25.8 5.5 45.0 11.0 40.0 8.5 70.2 13.2 47.3 9.3 25.7 5.6 32.3 8.9 15.4 2.8 42.3 9.6 28.1 5.8 57.5 8.9 20.4 5.7 32.3 8.1 129.8 28.6 81.0 16.8 139.0 29.0 92.8 19.1 142.5 31.9 108.5 22.1 134.8 30.1 86.1 17.3 130.6 22.1 109.9 16.6 130.9 19.2 71.1 13.2 128.5 23.5 71.7 14.5 68.7 12.2 72.5 14.4 82.9 14.8 63.9 12.5 53.4 9.3 60.2 10.9 52.3 9.6 61.7 11.3 49.4 10.5 55.8 11.9 33.8 4.5 60.7 9.1 73.3 12.9 62.7 13.6 52.9 7.9 46.8 9.5 43.8 8.4 29.6 4.5 35.0 5.3 44.9 6.4 73.0 16.8 38.0 5.2 27.8 5.4 35.7 6.2 23.5 3.5 30.4 3.7 26.5 4.2 46.8 6.6 70.8 13.4 67.0 19.2 59.9 12.7 110.7 24.7 113.2 21.8 45.9 9.4 68.6 17.9 54.2 11.1 41.8 10.5 46.2 7.8 84.0 17.6 54.0 8.0 31.6 6.5 61.9 13.8 -2161- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Female PND 62 Study 1 Mean Time (SEC) Mean No. Errors Study 2 Mean Time (SEC) Mean No. Errors Study 3 Mean Time (SEC) Mean No. Errors Study 4 Mean Time (SEC) Mean No. Errors Study 5 Mean Time (SEC) Mean No. Errors Study 7 Mean Time (SEC) Mean No. Errors Study 8 Mean Time (SEC) Mean No. Errors Swimming Ability All 7.0 NA 8.5 NA 6.0 NA 6.1 NA 8.5 NA 7.3 NA 7.7 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 21 of 27 Path A Trials (Memory) 10 11 12 82.3 16.8 97.5 17.5 81.0 15.5 71.4 13.1 40.2 5.6 81.0 15.0 72.0 11.8 51.7 10.7 53.6 10.8 66.6 12.6 44.9 9.2 46.7 7.8 59.8 13.3 72.0 16.3 60.6 13.0 36.4 6.3 42.7 7.7 38.6 8.1 40.4 7.0 37.2 8.5 34.0 6.0 43.4 9.5 39.4 7.3 30.3 5.6 28.9 6.3 30.9 4.5 36.2 8.5 26.9 4.0 113.7 23.1 99.5 16.4 136.7 23.5 113.5 24.6 128.8 25.0 139.5 27.8 89.7 16.0 79.1 14.8 78.6 15.0 66.3 11.8 104.5 16.5 96.3 15.0 66.5 11.2 82.5 19.1 48.8 10.7 70.5 15.0 66.3 14.6 94.5 19.3 74.7 14.6 68.9 12.9 44.7 6.9 50.1 9.3 34.7 5.6 59.2 10.0 30.0 5.9 41.7 7.5 65.5 12.8 30.3 5.3 61.6 11.5 65.0 11.1 51.6 7.7 26.8 5.0 19.2 2.6 49.6 8.9 24.2 2.8 33.6 5.7 41.1 8.1 38.9 5.1 33.1 5.8 27.8 4.4 32.6 5.6 27.0 4.6 56.1 13.3 52.6 10.6 60.8 12.7 66.2 18.2 60.4 17.9 58.3 13.8 74.1 14.8 43.1 8.3 54.0 14.4 63.9 11.7 41.0 10.8 59.2 11.0 47.0 10.0 37.2 7.8 -2162- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Female PND 62 Study 9 Mean Time (SEC) Mean No. Errors Study 10 Mean Time (SEC) Mean No. Errors Study 11 Mean Time (SEC) Mean No. Errors Study 12 Mean Time (SEC) Mean No. Errors Study 13 Mean Time (SEC) Mean No. Errors Study 14 Mean Time (SEC) Mean No. Errors Study 15 Mean Time (SEC) Mean No. Errors Study 18 Mean Time (SEC) Mean No. Errors Swimming Ability All 7.7 NA 7.3 NA 6.3 NA 6.5 NA 6.4 NA 7.5 NA 6.1 NA 8.1 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 22 of 27 Path A Trials (Memory) 10 11 12 45.3 9.3 59.6 14.5 68.5 13.5 59.1 21.8 80.7 16.9 58.1 12.7 87.6 16.5 71.2 14.8 51.6 11.2 38.0 8.3 49.2 9.7 52.2 15.7 59.3 12.6 73.0 15.2 61.5 14.5 54.7 11.3 43.8 9.0 31.0 6.4 62.1 14.8 62.6 12.9 39.0 7.8 97.7 21.5 39.4 9.0 37.7 7.3 28.7 5.4 19.7 2.3 22.1 4.8 40.8 5.0 48.9 10.3 54.9 8.7 25.1 3.7 29.7 5.8 162.4 31.0 92.0 19.3 121.2 24.7 72.2 13.9 116.2 27.3 112.0 21.0 110.3 23.3 61.2 13.6 116.3 23.6 99.0 17.8 126.4 21.8 98.2 17.5 137.8 31.6 104.4 23.8 141.7 25.1 100.4 20.8 64.4 8.9 80.7 13.8 98.8 20.7 56.6 13.3 62.2 11.1 71.8 11.8 50.2 9.5 89.0 15.9 68.0 11.8 39.5 6.1 73.5 10.8 28.2 5.1 47.5 7.9 51.0 7.4 39.1 6.1 47.7 8.0 54.0 8.7 43.2 7.7 57.2 10.8 22.9 4.1 21.5 1.8 41.3 6.0 42.8 7.1 39.3 7.1 36.2 4.9 23.4 3.5 49.2 7.8 27.7 5.4 30.4 5.2 46.7 7.4 28.7 4.4 25.6 4.3 76.6 15.7 41.8 8.3 92.5 21.8 60.0 13.3 87.6 21.0 126.3 28.5 68.4 13.0 71.5 15.2 46.0 8.0 39.7 7.8 44.4 5.8 46.4 9.1 49.0 10.1 75.9 13.3 56.1 11.2 41.4 8.5 -2163- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Female PND 62 Study 19 Mean Time (SEC) Mean No. Errors Study 20 Mean Time (SEC) Mean No. Errors Study 21 Mean Time (SEC) Mean No. Errors Study 22 Mean Time (SEC) Mean No. Errors Study 23 Mean Time (SEC) Mean No. Errors Study 26 Mean Time (SEC) Mean No. Errors Study 27 Mean Time (SEC) Mean No. Errors Swimming Ability All 6.3 NA 8.5 NA 7.2 NA 7.7 NA 8.2 NA 8.2 NA 7.0 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 23 of 27 Path A Trials (Memory) 10 11 12 71.6 15.8 92.9 19.8 87.1 17.3 51.6 9.3 86.6 12.6 77.9 15.0 98.4 20.1 43.6 9.7 41.2 8.3 67.1 15.1 67.4 15.6 80.4 15.3 65.3 13.1 37.1 8.3 39.2 8.4 50.4 11.5 45.1 10.4 34.7 7.7 47.5 8.3 45.8 8.0 32.7 7.1 32.1 7.2 22.5 3.7 27.5 5.3 36.6 8.2 44.7 8.4 31.4 6.3 32.7 7.8 125.0 29.8 103.6 24.0 90.7 18.2 165.3 36.1 80.5 15.2 59.5 13.7 126.8 27.9 92.0 19.7 96.0 20.4 127.5 28.7 109.1 23.8 64.1 14.9 131.3 23.8 136.8 23.0 110.1 19.7 139.5 24.4 92.4 16.3 60.6 8.6 139.6 27.9 82.8 19.6 53.1 13.3 43.9 9.4 30.5 5.8 58.2 11.7 30.7 6.4 74.5 9.6 26.7 3.1 33.4 6.6 31.1 5.2 43.4 9.1 55.2 10.6 29.9 5.3 48.8 8.0 27.4 3.4 37.6 6.8 26.6 3.6 33.8 7.5 44.0 8.2 25.3 4.7 48.3 7.2 32.4 5.6 48.8 11.4 100.2 20.2 58.9 16.7 60.1 13.1 92.5 23.3 93.8 20.1 43.9 9.4 72.8 20.4 89.9 18.9 58.8 14.1 45.3 9.6 72.1 16.0 55.8 7.8 46.2 10.2 51.3 9.6 -2164- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 63 Study 6 Mean Time (SEC) Mean No. Errors Female PND 63 Study 6 Mean Time (SEC) Mean No. Errors Swimming Ability All 7.2 NA 9.9 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 24 of 27 Path A Trials (Memory) 10 11 12 55.5 8.4 44.7 7.1 30.4 6.1 20.8 4.0 110.2 21.3 89.5 17.7 77.2 12.8 53.8 11.0 31.3 4.9 20.2 2.7 82.6 19.6 70.4 15.4 68.1 10.7 51.5 8.6 48.4 8.9 37.0 5.4 129.4 24.6 97.3 18.4 66.1 11.3 63.1 9.3 32.8 3.3 40.2 6.3 86.4 20.7 59.1 9.2 -2165- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 70 Study 24 Mean Time (SEC) Mean No. Errors Study 25 Mean Time (SEC) Mean No. Errors Female PND 70 Study 24 Mean Time (SEC) Mean No. Errors Study 25 Mean Time (SEC) Mean No. Errors Swimming Ability All 6.6 NA 5.9 NA 6.7 NA 5.9 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 25 of 27 Path A Trials (Memory) 10 11 12 81.6 16.7 73.0 15.4 51.6 12.5 43.1 9.4 42.1 9.7 34.4 7.0 29.5 6.9 22.7 4.9 119.6 27.5 76.5 18.0 143.0 31.1 114.1 22.7 70.5 15.4 83.8 17.6 50.0 10.4 74.5 14.8 35.3 8.4 54.9 12.0 19.6 3.1 37.2 6.6 64.0 17.7 71.1 18.6 45.4 12.9 36.6 8.5 61.5 12.9 63.4 15.0 59.3 15.1 53.1 13.3 36.1 7.8 42.1 10.7 21.2 4.6 34.8 8.8 135.7 33.0 94.4 24.2 81.6 18.7 70.5 16.2 68.6 14.9 61.1 15.3 34.1 5.5 29.9 6.7 28.8 5.0 25.5 5.5 24.5 3.6 21.3 3.7 64.1 17.8 60.9 17.7 48.9 11.7 30.2 6.6 -2166- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Male PND 107 Study 16 Mean Time (SEC) Mean No. Errors Female PND 107 Study 16 Mean Time (SEC) Mean No. Errors Swimming Ability All 5.6 NA 6.7 NA Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) Path A Trials (Learning) 1 2 3 4 Path B Trials (Learning) 5 6 7 8 9 26 of 27 Path A Trials (Memory) 10 11 12 75.8 14.3 42.7 7.9 34.4 6.9 23.5 5.9 146.6 27.3 99.4 17.2 76.4 13.8 43.7 9.8 29.9 6.2 37.4 6.7 87.6 19.4 36.0 6.9 60.4 10.6 38.0 8.3 37.0 8.0 28.5 7.2 105.6 26.5 103.4 18.9 61.6 11.3 41.9 5.6 42.7 7.1 31.6 4.4 74.3 14.9 54.7 9.7 -2167- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. SEC = Seconds PND = Postnatal day NA = Not applicable IGS Rat Biel Maze HC v1.2 WIL Historical Control Data Crl:CD(SD) Rat* Biel Maze - Grand Mean Data (27 Studies Conducted Between 6/14/99 and 6/28/04) HC Study Number 1 2 3 4 5 6 7 8 9 10 11 12 13 No. of Animals Evaluated (per sex) 24 10 23 10 10 10 20 10 10 18-20 10 19 10 14 10 15 20-21 16 18-20 17 10 18 20 19 20 20 13 21 19-20 22 19-20 23 20 24 23-25 25 25 26 10 27 10 Vehicle 10% Aqueous Acacia 0.5% Aqueous Carboxymethylcellulose 10% Aqueous Acacia Deionized Water 10 mM Lactic Acid in Deionized Water 5% Aqueous Acacia Deionized Water 0.5% Aqueous Carboxymethylcellulose 5% Gum Arabic with 0.01% Tween 80 (aqueous) Diet Drinking Water Filtered Air 2.5% Aqueous Hydroxypropylmethylcellulose in 50 mM Sodium Acetate Deionized Water 0.5% Aqueous Methylcellulose Sterile Water for Injection, USP 0.1 M Sodium Phosphate Buffer Filtered Air Deionized Water Deionized Water 1% Aqueous Methylcellulose 1% Aqueous Methylcellulose 0.5% Aqueous Hydroxypropylmethylcellulose with 0.1% Tween 80 1% Aqueous Methylcellulose Distilled Water 1% Aqueous Methylcellulose Methylcellulose Matrix Route Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Dietary Drinking Water Inhalation Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Inhalation Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Oral Gavage Intranasal Start Date 09/20/99 05/15/00 07/03/00 02/09/01 08/21/00 06/14/99 01/18/01 02/07/00 11/02/99 03/26/02 NA 04/08/03 10/08/02 11/26/01 11/18/02 08/11/03 09/02/99 07/24/01 07/08/03 10/01/02 10/14/03 11/18/03 02/04/03 05/20/03 12/18/03 07/13/99 08/09/99 End Date 03/09/00 10/12/00 12/21/01 02/20/02 01/23/01 01/25/00 07/02/01 07/11/00 10/21/00 06/04/03 NA 06/28/04 06/24/03 04/24/02 05/08/03 01/12/04 08/18/00 09/17/02 12/17/03 06/13/03 06/10/04 06/10/04 07/24/03 12/02/03 06/10/04 08/02/00 01/11/00 27 of 27 -2168- * = Prior to January 1, 2005, this strain of rat was designated the Crl:CD(SD)IGS BR rat. IGS Rat Biel Maze HC v1.2