Document 6w2BBkZzLR24Gb5jBQkbyMjB4
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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
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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 Associate Director, Developmental and Reproductive Toxicology Study Director
Date
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Volume 1
Table Of Contents
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 D esign......................................................................................................21 Maternal Tissue Collection...............................................................................23 Offspring Tissue Collection..............................................................................23 R e s u lts ................................................................................................................. 24 Conclusions........................................................................................................ 26
Introduction.................................................................................................. 27
General Study Inform ation.............................................................................. 27 Key Study D a te s............................................................................................... 29
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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 AndMethods............................. 32
Test Article And V ehicle................................................................................. 32 Test Article Identification................................................................................ 32 Test Article Characterization............................................................................32 Vehicle Identification........................................................................................33 Preparation ......................................................................................................... 33 Test Article Dosage Levels and Concentration............................................. 34 Sampling And A nalysis................................................................................... 35 Test System........................................................................................................ 35 Organization Of Test Groups, Dosage Levels And Treatment Regimen........................................................................................... 36 Group Assignments - Main Study Phase (W IL-180017).............................36 Group Assignments - Toxicokinetic Phase (W IL-180017T)...................... 36 F0 Maternal Generation.....................................................................................38 Animal Receipt And Acclimation................................................................... 38 Animal H ousing.................................................................................................38 Diet, Drinking W ater And M aintenance........................................................ 39 Environmental Conditions............................................................................... 40 Assignment Of Animals To Treatment Groups And Breeding Procedures.........................................................................................40
Parameters Evaluated.................................................................................41
F 0 O b s e rv a tio n s ..................................................................................................41 Clinical Observations And Survival...............................................................41 Body W eights.....................................................................................................42
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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 F 1Litter Param eters.......................................................................................... 44 Litter Viability And D eath s.............................................................................44 Litter R eduction................................................................................................ 44 Clinical Observations........................................................................................45 Body W eights.....................................................................................................45 Sex D eterm ination............................................................................................ 46 Calculation O f Litter Param eters.................................................................... 46 Weaning And Selection................................................................................... 46 Allocation Of Pups For Behavioral Tests And Brain W eights...............................................................................................................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 W eight Measurements............................................................................52 Offspring Euthanized At Study Termination (Not Selected For Brain W eight Measurements)................................................................... 53 Offspring Selected For Brain Weight Measurements Subsets A and B .................................................................................................53 Microscopic Examinations............................................................................... 54 Neuropathology.................................................................................................. 54
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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 A ssay.................................................................... 55 Toxicokinetic Analysis And Thyroid Function A ssessm ent...................... 55 Sample Collection............................................................................................. 55 Gestation Day 20 (Toxicokinetic P h ase)....................................................... 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 M ethods............................................................................................ 58 Data R etention...................................................................................................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 W eights..................................................................................................... 62 Food Consumption............................................................................................ 63 Lactation Period.................................................................................................64 Body W eights..................................................................................................... 64 Food Consumption............................................................................................ 64 Gestation Length and Parturition.................................................................... 65 F0 Macroscopic Examinations ........................................................................ 65 F1 Litter D ata...................................................................................................... 66 PND 0 Litter Data And Postnatal Survival.................................................... 66
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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 M ortalities.................................................66 Offspring Body Weights - Pre-weaning........................................................ 67 Macroscopic Examinations - Pre-weaning....................................................67 Offspring Found D e a d ......................................................................................67 Offspring Not Selected For Behavioral Evaluations Or Brain W eight Measurements (PND 2 1 ).........................................................68 Developmental Landm arks.............................................................................. 68 Balanopreputial Separation - Subset A .......................................................... 68 Vaginal Patency - Subset A ............................................................................. 69 F 1 G eneration.....................................................................................................69 Clinical Observations and Survival................................................................69 Offspring Body Weights - Post-w eaning...................................................... 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 W eight Measurements on PND 72).............................................. 74 Animals Selected For Perfusion And Brain Weight M easurem ents....................................................................................................75 PND 21................................................................................................................75 Macroscopic Examinations.............................................................................. 75 Brain Weights/Brain M easurem ents...............................................................75 PND 72................................................................................................................76 Macroscopic Examinations.............................................................................. 76 Brain Weights/Brain M easurem ents...............................................................76 Thyroid Function Assessment..........................................................................76 Thyroid Stimulating H orm one..........................................................................76
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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 M orphom etry......................................................................................78 Thyroid Follicular Epithelial Cell Height, PND 4 ......................................... 79 Thyroid Follicular Epithelial Cell Height,PND 2 1 ........................................79 Thyroid Follicular Colloid Area, PND 4 ........................................................80 Thyroid Follicular Colloid Area, PND 2 1 ......................................................80 Toxicokinetics and rtPC R ................................................................................ 80 rtPCR Results For F0 Dams And F1Fetuses On Gestation Day 20 And F1 Male Pups Group On PND 2 1 .............................................83 Thyroid Cell Proliferation A ssay.................................................................... 83 Ki-67-Positive Follicular Epithelial Cellsin 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
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Index Of Figures
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1. Summary O f Body Weights During Gestation [G] (F0 Females)............................. 100
2. Summary O f Body Weights During Lactation [G] (F0 Females)............................. 101
3. Summary O f Offspring Weights [G] (F1Males - PND 1-21)................................. 102
4. Summary O f Offspring Weights [G] (F1Females - PND 1-21).............................. 103
5. Summary O f Body Weights [G] (F1Males - PND 28-72)........................................104
6. Summary O f Body Weights [G] (F1Females - PND 28-72).................................... 105
7. Summary O f Mean Forelimb Grip Strength [G] (F1M ales).....................................106
8. Summary O f Mean Hindlimb Grip Strength [G] (F1Males).....................................107
9. Summary O f Mean Forelimb Grip Strength [G] (F1Females)..................................108
10. Summary O f Mean Hindlimb Grip Strength [G] (F1Females).................................109
11. Summary O f Motor Activity Total Counts By Session (F1Males - PND 13, 17 And 21).................................................................................110
12. Summary O f Motor Activity Ambulatory Counts By Session (F1 Males - PND 13, 17 And 21).................................................................................111
13. Summary O f Motor Activity Total Counts By Session (F1Males - PND 61)......................................................................................................112
14. Summary O f Motor Activity Ambulatory Counts By Session (F1 Males - PND 61)......................................................................................................113
15. Summary O f Motor Activity Total Counts (F1Males - PND 13)............................ 114
16. Summary O f Motor Activity Ambulatory Counts (F1Males - PND 13).................115
17. Summary O f Motor Activity Total Counts (F1Males - PND 17)............................ 116
18. Summary O f Motor Activity Ambulatory Counts (F1Males - PND 17).................117
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19. Summary O f Motor Activity Total Counts (F1Males - PND 2 1 )............................ 118
20. Summary O f Motor Activity Ambulatory Counts (F1Males - PND 2 1 ).................119
21. Summary O f Motor Activity Total Counts (F1Males - PND 6 1 )............................ 120
22. Summary O f Motor Activity Ambulatory Counts (F1Males - PND 6 1 ).................121
23. Summary O f Motor Activity Total Counts By Session (F1Females - PND 13, 17 And 2 1 )............................................................................ 122
24. Summary O f Motor Activity Ambulatory Counts By Session (F1Females - PND 13, 17 And 2 1 )............................................................................ 123
25. Summary O f Motor Activity Total Counts By Session (F1 Females - PND 6 1 )..................................................................................................124
26. Summary O f Motor Activity Ambulatory Counts By Session (F1Females - PND 6 1 )..................................................................................................125
27. Summary O f Motor Activity Total Counts (F1Females - PND 13)......................... 126
28. Summary O f Motor Activity Ambulatory Counts (F1Females - PND 13)..............127
29. Summary O f Motor Activity Total Counts (F1Females - PND 17)......................... 128
30. Summary O f Motor Activity Ambulatory Counts (F1Females - PND 17)..............129
31. Summary O f Motor Activity Total Counts (F1Females - PND 21)......................... 130
32. Summary O f Motor Activity Ambulatory Counts (F1Females - PND 21)..............131
33. Summary O f Motor Activity Total Counts (F1Females - PND 61)......................... 132
34. Summary O f Motor Activity Ambulatory Counts (F1Females - PND 61)..............133
35. Summary O f Startle Response Data [Vmax] (F1Males - PND 2 0 )......................... 134
36. Summary O f Startle Response Data [Tmax] (F1Males - PND 20).......................... 135
37. Summary O f Startle Response Data [Vmax] (F1Females - PND 20)...................... 136
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38. Summary O f Startle Response Data [Tmax] (F1Females - PND 2 0 ).......................137
39. Summary O f Startle Response Data [Vmax] (F1Males - PND 6 0 )..........................138
40. Summary O f Startle Response Data [Tmax] (F1Males - PND 60)...........................139
41. Summary O f Startle Response Data [Vmax] (F1Females - PND 60).......................140
42. Summary O f Startle Response Data [Tmax] (F1Females - PND 6 0 ).......................141
43. Summary O f Biel Maze Data (F1Males - Time To Escape - PND 2 2 )....................142
44. Summary O f Biel Maze Data (F1Males - Mean No. O f Errors - PND 22).................................................................143
45. Summary O f Biel Maze Data (F1Females - Time To Escape - PND 22).................144
46. Summary O f Biel Maze Data (F1Females - Mean No. O f Errors - PND 2 2 )...........................................................145
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Index O f Tables
Note: Some table titles have been shortened due to software spacing constraints.
Volume 1 (continued)
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Summary Data - F0 Generation
1. Summary O f Maternal Survival And Pregnancy Status (F0) .....................................147
2. Summary O f Clinical Findings: Total Occurrence/No. O f Animals (F0 - Daily Examinations)............................................................................................. 148
3. Summary O f Clinical Findings: Total Occurrence/No. O f Animals (F0 - 1 Hour Post-Dosing)............................................................................................. 151
4. Summary O f Body Weights During Gestation [G] (F0) ............................................ 152
5. Summary O f Body Weight Changes During Gestation [G] (F0) ............................... 154
6. Summary O f Food Consumption During Gestation [G/Animal/Day] (F0).................................................................................................................................. 156
7. Summary O f Food Consumption During Gestation [G/Kg/Day] (F0).................................................................................................................................. 158
8. Summary O f Body Weights During Lactation [G] (F0) ............................................ 160
9. Summary O f Body Weight Changes During Lactation [G] (F0) ............................... 162
10. Summary O f Food Consumption During Lactation [G/Animal/Day] (F0) ..............163
11. Summary O f Food Consumption During Lactation [G/Kg/Day] (F0).................................................................................................................................. 165
12. Summary O f Gestation Lengths [Days] (F0)............................................................... 167
13. Summary O f Macroscopic Findings (F0 - Failed To Deliver)...................................168 14. Summary O f Macroscopic Findings (F0 - Lactation Day 21)....................................169
15. Summary O f Implantation Sites (F0) ............................................................................170
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Summary Data - Fi Litters 16. Summary O f PND 0 Litter Data (F1) .......................................................................... 171 17. Summary O f Postnatal Survival [% Per Litter] (F1) .................................................. 172 18. Summary O f Pup Clinical Observations (F1- Pre-Weaning)....................................174 19. Summary O f Offspring Weights [G] (F1- Pre-Weaning)..........................................175 20. Summary O f Offspring Weight Changes [G] (F1- Pre-Weaning)........................... 178 21. Summary O f Pup Necropsy Findings (F1- Found Dead Pups).................................180 22. Summary O f Pup Necropsy Findings
(F1- PND 21 Scheduled N ecropsy)............................................................................ 181 Summary D ata - F1Developmental Landm arks/F1 Generation
23. Summary O f Animal Developmental Parameters Balanopreputial Separation (F1) ...................................................................................182
24. Summary O f Animal Developmental Parameters - Vaginal Patency (F1) ...............183 25. Summary O f Clinical Findings: Total Occurrence/No. O f Animals (F1) ................184 26. Summary O f Body Weights [G] (F1- Post-Weaning)............................................... 187 27. Summary O f Body Weight Changes [G] (F1- Post-W eaning).................................191
Summary D ata - F1Neurobehavioral Testing And Brain Weights
28. Summary O f Detailed Clinical Observations (F1Functional Observational Battery - Handling Observations)............................. 195
29. Summary O f Detailed Clinical Observations (F1Functional Observational Battery - Open Field Observations)...........................227
30. Summary O f Motor Activity Counts (F1) ...................................................................257
31. Summary O f Startle Response Data (F1) ....................................................................273
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32. Summary O f Biel Maze Data (F1- PND 22).................................................................................................................283
33. Summary O f Biel Maze Swim Trials (F1- PND 22)................................................ 285
34. Summary O f Macroscopic Findings (F1- PND 72 Pups Not Selected For Brain W eights)............................................... 301
35. Summary O f Macroscopic Findings (F1- PND 21 Pups Selected For Brain W eights)...................................................... 303
36. Summary O f Brain W eights And Brain Measurements (F1- PND 21 Pups Selected For Brain W eights)...................................................... 305
37. Summary O f Brain Weights Relative To Final Body Weights (F1- PND 21 Pups Selected For Brain W eights)...................................................... 307
38. Summary O f Macroscopic Findings (F1- PND 72 Pups Selected For Brain W eights)...................................................... 309
39. Summary O f Brain W eights And Brain Measurements (F1- PND 72 Pups Selected For Brain W eights)...................................................... 311
40. Summary O f Brain Weights Relative To Final Body Weights (F1- PND 72 Pups Selected For Brain W eights)...................................................... 313
Summary Data - Thyroid Function Assessment
41. Summary O f TSH Values (F0 Dams - Gestation Day 2 0 )......................................... 315
42. Summary O f TSH Values (F1Fetuses - Gestation Day 2 0 )...................................... 316
43. Summary O f TSH Values (F0 Dams - Lactation Days 4 and 21)..............................317
44. Summary O f TSH Values (F1 Pups - PND 4 )............................................................. 318
45. Summary O f TSH Values (F1 Pups - PND 21)........................................................... 319
46. Summary O f Microscopic Findings (F1Fetuses - Gestation Day 2 0 ) ..................................................................................321
47. Summary O f Microscopic Findings (F1Pups - PND 4 ) ...........................................323
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48. Summary O f Microscopic Findings (F1Pups - PND 2 1 ).........................................325
49. Summary O f Thyroid Morphometry (F1 Pups - PND 4 )..........................................................................................................327
50. Summary O f Thyroid Morphometry (F1 Pups - PND 21)....................................................................................................... 329
51. Summary O f Ki-67 Cell Counts (F1) ..................................................................................................................................331
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Index Of Appendices
Volume 2
Page
Individual D ata - Fo G eneration 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 D eliver)...................................... 435 12. Individual Macroscopic Findings (F0 - Lactation Day 2 1 )....................................... 438 13. Individual Implantation Sites (F0) ............................................................................... 535
Individual Data - Fi 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
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18. Individual Offspring Weight Changes [G] (F1- Pre-Weaning)................................. 691
19. Individual Pup Necropsy Findings (F1- Found Dead P u p s)..................................... 766
20. Individual Pup Necropsy Findings (F1- PND 21 Scheduled N ecropsy)............................................................................ 770
Individual Data - Fi Developmental Landm arks/Fi 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-W eaning)....................................................807
25. Individual Body Weight Changes [G] (F1- Post-Weaning)...................................... 815
Individual Data - F1Neurobehavioral 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 2 2 ).................................................. 1077
Volume 4
32. Individual Macroscopic Findings (F1- PND 72 Pups Not Selected For Brain W eights)............................................. 1095
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33. Individual Macroscopic Findings (F1- PND 21 Pups Selected For Brain W eights).................................................... 1135
34. Individual Final Body And Brain Weights And Brain Measurements (F1- PND 21 Pups Selected For Brain W eights).................................................... 1255
35. Individual Brain Weights Relative To Final Body Weights (F1- PND 21 Pups Selected For Brain W eights).................................................... 1263
36. Individual Macroscopic Findings (F1- PND 72 Pups Selected For Brain W eights).................................................... 1271
37. Individual Final Body And Brain Weights And Brain Measurements (F1- PND 72 Pups Selected For Brain W eights).................................................... 1391
38. Individual Brain Weights Relative To Final Body Weights (F1- PND 72 Pups Selected For Brain W eights).................................................... 1399
Individual Data - Thyroid Function Assessment
39. Individual TSH Values (F0Dams - Gestation Day 20)............................................ 1407
40. Individual TSH Values (F1Fetuses - Gestation Day 2 0).........................................1411
41. Individual TSH Values (F0Dams - Lactation Day 4 ).............................................. 1415
42. Individual TSH Values (F1Pups - PND 4 ) ...............................................................1419
43. Individual TSH Values (F0Dams - Lactation Day 21)............................................ 1423
44. Individual TSH Values (F1Pups - PND 2 1 ).............................................................1427
Volume 5
45. Individual Microscopic Findings (F1Fetuses - Gestation Day 2 0 )........................ 1437
46. Individual Microscopic Findings (F1Pups - PND 4 )............................................... 1517
47. Individual Microscopic Findings (F1Pups - PND 21)............................................. 1597
48. Individual Thyroid Morphometry (F1 Pups - PND 4 ).......................................................................................................1677
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49. Individual Thyroid Morphometry (Fi Pups - PND 21)......................................................................................................1715
50. Individual Ki-67 Cell Counts (F1) ................................................................................................................................1755
51. Study Personnel...........................................................................................................1757
52. Study Protocol And Amendments..............................................................................1759
53. Certificate O f Analysis (Sponsor-Provided D ata)................................................... 1800
54. Analyses O f 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 R esults.............................................................................................................. 1877
59. Clinical Pathology Methods, Procedures And References
1889
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60. Statistical Analysis Report (BioSTAT Consultants, Inc.)........................................1891
61. WIL Reproductive Historical Control Data Version 2.4 [Crl:CD(SD) R ats]....... 1930
62. Developmental Neurotoxicity Method Development Studies (WIL Research Laboratories, L L C ).......................................................................... 1939
63. WIL FOB Historical Control Data Version 1.0 [Crl:CD(SD) R ats]......................2089
64. WIL Motor Activity Historical Control Data Version 2.1 [Crl:CD(SD) R ats].....2107
65. WIL Startle Response Historical Control Data Version 2.1 [Crl:CD(SD) Rats]...................................................................................................... 2128
66. WIL Biel Maze Historical ControlData Version 1.2 [Crl:CD(SD) Rats].............. 2141
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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
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(placental transfer) and through nursing during lactation. All F1pups 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 F 1selected 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.
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TT 1.
M aternal Tissue Collection
Day of No. of
Phase collection dams Blood Tissues
Analysis
Thyroid,
TK GD 20
10 Yes a Brain, MTDID 208 serum levels, rtPCR, TSH
Liver
MS LD 4
10 Yes b NA MTDID 208 serum levels, TSH
MS LD 21
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
Fetuses'3
Yesa
Thyroid, Brain, Liver
MTDID 208 serum levels, rtPCR, TSH, thyroid cell proliferation assay (1 fetus/sex/litter)
MS PND 4
10 Culled litters/groupb
Yesa
Thyroid, MTDID 208 serum levels, 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,
Liver thyroid morphometry
MSc PND 72
5/sex/group
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
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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
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and weight at attainment of balanopreputial separation and vaginal patency in the F 1males 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 F 1males or females.
Total and ambulatory motor activity counts in the 1.0 mg/kg/day group F 1males 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 F 1fetuses 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 o f F0 dams and F 1fetuses 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
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generally higher at all dosage levels during lactation than on gestation day 20, while serum concentrations for F 1fetuses/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 F 1fetuses/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 F 1pups 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 F 1generation 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 F 1 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
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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 F 1 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 F 1males on PND 17.
2 Introduction
2.1 G eneral Study Inform ation
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 F 1 litters; pups from the F 1litters were selected to constitute the F 1generation.
The following computer protocols were used for data collection during the study:
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Computer Protocol
Type of Data Collected
WIL 180017......................................................F0 maternal and F 1litter data (including F0 maternal TSH data)
WIL 180017J.................................................... F 1post-weaning body weight, clinical observation, developmental landmark and necropsy data (for animals not selected for brain weights on PND 72)
WIL 180017S.................................................... F 1 Subset A FOB (open field observations), locomotor activity, startle response and learning and memory data
WIL 180017H................................................... F 1FOB data (handling observations) WIL 180017E.................................................... F 1 Subset B PND 21 necropsy and
brain weight/measurement data WIL 180017K................................................... F 1 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................................................... F 1 PND 4 TSH data WIL 180017W .................................................. F 1gestation day 20 fetal thyroid cell proliferation assay WIL 180017V................................................... F 1 PND 21 TSH and thyroid morphometry data WIL 180017N................................................... F 1PND 4 thyroid morphometry data
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2.2 Key Study Dates Date(s)
Event(s)
18 April 2006 .................................................... Experimental starting date (animal receipt)
2 May 2 0 0 6 ..................................................... Experimental start date (initiation of F0 test article administration)
2 May 2006 - 18 June 2006............................ F0 dose administration period 22 - 25 May 2 0 0 6 .............................................Gestation day 20 euthanasia
(toxicokinetic phase) 13-19 June 2006................................................F0 lactation day 21 necropsies and
F 1PND 21 necropsies 27 May 2006 - 2 June 2006............................ F 1PND 4 necropsies 27 May 2006 - 28 July 2006...........................F 1 developmental indices and
behavioral testing 3 - 8 August 2006............................................ F 1PND 72 necropsies 21 December 2007........................................... Experimental termination/
completion date (last dosing formulation analysis)
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3 Study Design
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Study Design (continued)
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4 Experimental Procedures - M aterials And Methods
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4.1 Test A rticle A nd 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.
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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:
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TT 4.
Test A rticle Dosage Levels and Concentration
Group
Dosage Level
Number
Test Articlea
(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.
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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.
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4.3 O rganization O f Test G roups, Dosage Levels And T reatm ent 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 - M ain Study Phase (WIL-180017)
Group
Dosage Level
Number
Test Articlea
(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
Dosage Level
Number
Test Articlea
(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
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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, F 1pup 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 F 1 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
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PMI 5002 diet, it is likely that perfluorooctane sulfonate is present at low levels and as a result the F1animals 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 M aternal G eneration
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;
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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, F 1 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 fo r the Care a n d Use o f Laboratory A n im a ls [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 W ater And M aintenance
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,
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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 O f Animals To Treatm ent 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
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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 Param eters Evaluated
5.1 F0O bservations
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
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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
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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
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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 F 1 L itter Param eters
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
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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
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given animal was not weighed were designated as "NA" (Not Applicable) on the individual report table.
5.2.5
Sex D eterm ination
All pups were sexed on PND 0, 4, 11 and 21.
5.2.6
Calculation O f Litter Param eters
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)
X (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)
X (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
W eaning 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
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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 F 1 selected animals. The following table summarizes the allocation of offspring for behavioral tests and brain weights.
TT 7.
Allocation O f 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.I.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.
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5.2.8
Developmental Landm arks, Sensory Function And Neurobehavioral Testing
The various investigations described herein were used to assess the maturation and behavioral development of the selected F 1pups. 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
Fi 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.
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Fi 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 prominence Mobilitya Convulsions/tremors Groominga,b Bizarre/stereotypic behavior Pupillary responsea,b Forelimb/hindlimb gripstrengtha,b Gaita
Ease of handling animal in hand Salivation Fur appearance Respiratory rate/character Mucous membranes/skin color Eye colora,b Muscle tone Hindlimb extensionab 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 o f a 5-minute acclimation period with a 655-db broadband background white noise. The
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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).
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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 o f the Biel maze procedure. Each animal was allowed 2 trials to solve the maze in path A.
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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 O r B rain W eight M easurem ents
On PND 21, all F 1 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.
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5.2.9.2
Offspring Euthanized At Study Term ination (Not Selected For Brain W eight M easurements)
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 B rain W eight M easurem ents 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
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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.
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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.
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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 (M ain 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
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groups were used for rtPCR; all other samples were retained by the sponsor for possible future analysis.
5.3.1.4
PND 72 (M ain 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 pL o f 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.
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5.4 Statistical M ethods
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 F 1pups, 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
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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 o f 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
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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 D ata 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.
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6.1 A nalytical C hem istry
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 M aternal G eneration
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
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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.
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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.
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Lactation Period
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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
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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.
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At the lactation day 21 necropsy, no test article-related effects were observed on the number of former implantation sites and the number o f unaccounted-for sites. The differences between the control and test article-treated groups were slight and not statistically significant.
6.3 F 1 L itter D ata
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 M ortalities
Clinical observations are summarized in Table 18. Individual animal observations are tabulated in Appendix 16. The numbers of F 1pups found dead and/or missing, as well as the general physical condition of all F 1pups 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
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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 F 1generation 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
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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 O r Brain W eight M easurem ents (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 F 1 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 L andm arks
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
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group. Mean body weight at the age o f 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 o f 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 F 1 G eneration
6.5.1
Clinical Observations and Survival
Clinical observations are summarized in Table 25. Individual animal observations are tabulated in Appendix 23. All F 1males 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
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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 F 1 males or females during the functional observational battery assessments on PND 4, 11,
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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 F 1males compared to the concurrent control group; the increases in total activity were statistically significant (p<0.030). In addition, 8 males in the 1.0 mg/kg/day group had higher total activity counts during the
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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 F 1females 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 F 1males 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 (p<0.031). 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 F 1males 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.
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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 o f habituation in the 0.1 mg/kg/day groups were similar to those in the concurrent control group when the F 1 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 F 1 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 VMAXvalues in the 0.1, 0.3 and
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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 F 1male and female pups and the vehicle-treated F 1male 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
M acroscopic Examinations - Post-weaning (Not Selected For Brain W eight M easurem ents on PND 72)
Macroscopic examination data for F 1 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 F 1 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
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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 B rain W eight M easurem ents
6.6.1
PND 21
6.6.1.1
Macroscopic Examinations
Macroscopic examination data for F1pups 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 F 1animals selected for brain weights on PND 21, no gross findings were noted in the brain or spinal cord.
6.6.1.2
Brain W eights/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 F 1 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.
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6.6.2
PND 72
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6.6.2.1
Macroscopic Examinations
Macroscopic examination data for F1animals 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 F 1animals 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 W eights/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 F 1 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 T hyroid Function Assessment
6.7.1
Thyroid Stimulating Hormone
Thyroid stimulating hormone data for F0 maternal animals and F 1 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.
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On gestation day 20, TSH values of F0 dams and F 1fetuses (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 F 1pups (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 F 1 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 F1pup 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 F 1male pups in
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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 F 1female 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 F 1 pups on lactation day/PND 21.
6.7.2
Thyroid Histopathology
Thyroid histopathology data for F 1fetuses 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 M orphometry
Thyroid morphometry data for F 1fetuses 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
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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 -
-
= Number of tissues examined from each group
= micrometers
1.0 0 10 10 5.36 5.68 0.431 0.360
Females 0.1 0.3 00 ---
1.0 8 5.84 0.304
TT 9.
Thyroid Follicular Epithelial Cell H eight, PND 21
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 5.68 -
- 6.29** 6.28
Standard deviation
0.536 -
- 0.324 0.450
a = Number of tissues examinee from each group.
b = micrometers
** = Statistically significant at p<0.01 (Dunnett's test)
Females 0.1 0.3 00 ---
1.0 10 6.38 0.598
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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 00 ---
1.0 8 1969 555.1
TT 11.
Thyroid Follicular Colloid A rea, PND 21
Males
Dosage (mg/kg/day) 0 0.1 0.3 1.0
Thyroid a
10 0 0 10
Mean follicle area b 7768 - - 7267
Standard deviation
1641.1 -
- 1117.8
a = Number of tissues examined from each group.
b = micrometers
0 10 7220 1288.6
Females 0.1 0.3 00 ---
1.0 10 7677 1857.8
6.8 Toxicokinetics and rtP C R
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 Fi 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
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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 F 1fetuses 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 F 1pups 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 F 1fetuses 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 F 1 fetuses and pups, serum concentrations for dams in all test article-treated groups were lower than the fetal concentrations on gestation day 20
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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 F 1male 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.
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TT 12.
rtP C R Results F o r Fo Dams A nd Fi Fetuses O n G estation Day 20 A nd F 1 M ale Pups O n PND 21
G estation Day 20
Transcript
Group 4 Dam
Group 4 Fetus
AcylCoA
--
--
PCNA -- --
Malic Enzyme
--
--
Dio1
-- --
Por -- --
ApoA1
--
--
Cyp1a1
--
--
Cyp3a1
--
--
Cyp4a1
--
--
Cyp7a1
--
--
Cyp2b2 Ugt1A common
--
---
Ugt1a1
--
--
Ugt1a6
--
--
Ugt2b
-- --
Group 4 = 1.0 mg/ cg/day
PND 21 Group 4 Male Pup
--------
I -----
-- = Not significantly different from the control group at 95% confidence interval.
t = Significantly higher than the control group at 95% confidence interval.
I = Significantly lower than the control group at 95% confidence interval.
6.9 Thyroid Cell Proliferation Assay
Thyroid cell proliferation assay data for Fi 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.
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TT 13.
Ki-67-Positive Follicular Epithelial Cells in Thyroid Gland, G estation Day 20
Males
Females
Dosage (mg/kg/day)
0 0.1 0.3 1.0 0 0.1 0.3
Thyroid a
6 0 0 6 7 00
Ki-67-positive cells b
40 -
- 32 42 - -
Standard deviation
23.9 -
- 25.3 35.5 -
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)
-
1.0 5 88* 18.6
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 F 1males on PND 17. Total and ambulatory activity counts in these males were increased (generally statistically significant; p<0.030) 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
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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 F 1males 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 F 1animals. 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.
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This study revealed no evidence of test article-related alterations in TSH values for F0 maternal animals, F 1fetuses and F 1pups or any histologic alterations that were visible in routinely stained sections for F 1fetuses and F 1pups. 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 o f F0 dams and F 1fetuses 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 F 1 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 F 1fetuses/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 F 1pups 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 F 1generation 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
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compared to F 1fetuses 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 F 1 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 F 1males on PND 17.
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9 Key Study Personnel and Report Submission Report Submitted By:
-----( f --"_______ Donald G. Stump, PhD, DABT Associate Director, Developmental and Reproductive Toxicology Study Director
Report Prepared Bv:
(0 Date
00^
Erin E. Petruzzi, MS 0 Senior Study Analyst
ICThUCZ
Date
Kristin M. Roll, MS Study Analyst
Report Reviewed Bv:
1 1 ' ie /<'
Melissa J. Beck, PhD Assistant Director, Neurosciences
'Kfaric D. Nemec, BS, DABT Director, Developmental and Reproductive Toxicology
id
Date
\bAam QOC^
Date
I0?fii(v3-dt)8r
Date
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Key Study Personnel and Report Submission (continued)
-- ____________T Y l f A a M L ( J I h t f J i Cindy S. Roegge, PhD Staff Toxicologist, Neurosciences
O')i/QyjwA C X
Evelyn Tanenevski, BS Group Supervisor, Study Analysis and Reports
/o , W Date
Date
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10 Q uality Assurance U nit Statem ent
10.1 Phases Inspected
D ate(s) o f Inspection(s) 08-M ay-2006, 09-M ay-2006
18-M ay-2006
22-M ay-2006 08-Jun-2006
12-Jun-2006
13-Jun-2006
25-Sep-2006 25-Sep-2006 26-Sep-2006 07-N ov-2006 07-N ov-2006, 08-N ov-2006 08-N ov-2006 08-N ov-2006 20-N ov-2006, 21-N ov-2006 21-N ov-2006 21-N ov-2006
P hase Inspected
D ate(s) F indings R e p o rte d to Study D irecto r
D ate(s) F indings R e p o rte d to M anagem ent
Test A rticle Preparation/ A dm inistration
09-M ay-2006
26-Jun-2006
A nim al C are & Equipm ent
18-M ay-2006
B lood C ollection
22-M ay-2006
Functional O bservational B attery
08-Jun-2006
26-Jun-2006 26-Jun-2006
25-Jul-2006
E m bedding of Tissues
12-Jun-2006
25-Jul-2006
N ecropsy (Perfusions)
13-Jun-2006
25-Jul-2006
Study R ecords (I-8) Study R ecords (I-13) Study R ecords (I-7) Study R ecords (I-1) Study R ecords (I-3) Study R ecords (I-6) Study R ecords (I-5) Study R ecords (I-4) Study R ecords (I-10) Study R ecords (I-15)
25-Sep-2006 25-Sep-2006 26-Sep-2006 07-N ov-2006 08-N ov-2006 08-N ov-2006 08-N ov-2006 21-N ov-2006 21-N ov-2006 21-N ov-2006
18-O ct-2006 18-O ct-2006 18-O ct-2006 20-D ec-2006 20-D ec-2006 20-D ec-2006 20-D ec-2006 20-D ec-2006 20-D ec-2006 20-D ec-2006
A uditor(s)
N. Daniels; K. Dobbs
K. Dobbs K. Dobbs
A. K inney; A. Deppe K. Dobbs; T. D eV an B ooth K. M entzer; J. M uraw ski J. M u raw sk i J. M u raw sk i J. M u raw sk i J .M uraw ski J. M u raw sk i J. M u raw sk i J. M u raw sk i J. M u raw sk i J. M u raw sk i J. M u raw sk i
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D ate(s) o f Inspection(s) 27-N ov-2006
28-N ov-2006 29-N ov-2006 01-D ec-2006, 04-D ec-2006 04-D ec-2006 04-D ec-2006 06-D ec-2006 07-D ec-2006 07-D ec-2006 11-D ec-2006, 12-Dec-2006, 13-D ec-2006, 14-Dec-2006, 15- D ec-2006, 18-Dec-2006, 22-D ec-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-A pr-2007 21-A pr-2007 21-A pr-2007 22-A pr-2007, 23-A pr-2007 23-A pr-2007
25-A pr-2007
P hase Inspected Study R ecords (I-2, I-9 and I- 14) Study R ecords (I-11) Study R ecords (R x-1) Study R ecords (N -1) Study R ecords (N-2) Study R ecords (N-3) Study R ecords (C-1) Study R ecords (C-2) Study R ecords (I-12)
D ate(s) F indings R e p o rte d to Study D irecto r
D ate(s) F indings R e p o rte d to M anagem ent
27-N ov-2006 28-N ov-2006 29-N ov-2006 04-D ec-2006 04-D ec-2006 04-D ec-2006 06-D ec-2006 07-D ec-2006 07-D ec-2006
20-D ec-2006 20-D ec-2006 20-D ec-2006 30-Jan-2007 30-Jan-2007 30-Jan-2007 30-Jan-2007 30-Jan-2007 30-Jan-2007
D raft R eport (excluding Pathology R eport A ppendix)
22-Jan-2007
Study R ecords (H -1)
21-A pr-2007
Study R ecords (H -2)
21-A pr-2007
Study R ecords (H -3)
21-A pr-2007
Study R ecords (P-1)
23-A pr-2007
Study R ecords (C-2 Supplem ental, A dditional TSH D ata C ollection)
23-A pr-2007
D raft R eport (Pathology A ppendix)
25-A pr-2007
27-Feb-2007 24-M ay-2007 24-M ay-2007 24-M ay-2007 24-M ay-2007
24-M ay-2007
24-M ay-2007
A uditor(s) J. M uraw ski J. M u raw sk i J. M uraw ski J. M uraw ski J. M uraw ski J. M uraw ski J. M u raw sk i J. M u raw sk i J. M u raw sk i
J. M uraw ski J.M uraw ski J.M uraw ski J.M uraw ski J.M uraw ski
J.M uraw ski J.M uraw ski
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
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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 o f 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.
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10.2 Approval
This study was inspected according to the criteria discussed in Section 10.1.
Report Audited By:
^ U a. Jessica D. Murawski, BS, RQAP-GLP
Senior Compliance Specialist
RcportReleased By: /
n
W M 'iC ii 7 7 '! \ /' / H /U Kl
a, r //
Heather L. Johnson, BS, RQAP-GLP
Manager, Quality Assurance
\ Q W > 9 cd ' Date (j
OiACW ' 7 A-A t-X l y U , j
Date/
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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. T oxicological Sciences 2003, 74, 382-392.
4. National Research Council. G uide f o r the Care a n d Use o f L a b o ra to ry A nim als, 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]. N aunyn - Schm iedebergs A rc h iv f r E xperim entelle P athologie u n d P harm akologie 1964, 247, 367.
6. Stuckhardt, J.L.; Poppe, S.M. Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. Teratogenesis, C arcinogenesis a n d M utagenesis 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. B io lo g y o f R eproduction 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. N eurobehavioral Toxicology a n d Teratology 1985, 7, 579-586.
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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 a n d A p p lied P harm acology 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. P sychopharm acologia 1968, 13, 222-257.
11. Gad, S.C. A neuromuscular screen for use in industrial toxicology. J o u rn a l o f Toxicology a n d E nvironm ental H ealth 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. F u n d a m en ta l a n d A p p lie d T oxicology 1988, 11(2), 189-206.
13. Haggerty, G.C. Development of tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies. J o u rn a l o f the A m erica n C ollege o f T oxicology 1989, 8(1), 53-69.
14. O 'Donoghue, J.L. Screening for neurotoxicity using a neurologically based examination and neuropathology. Journal o f the A m erican College o f Toxicology 1989, 8(1), 97-115.
15. Biel, W.C. Early age differences in maze performance in the albino rat. Jo u rn a l o f G enetic P sychology 1940, 56, 439-453.
16. Snedecor, G.W.; Cochran, W.G. One Way Classifications; Analysis of Variance. In S ta tistica l M ethods, 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. B iom etrics 1964, 20, 482-491.
18. Kruskal, W.H.; Wallis, W.A. Use of ranks in one-criterion variance analysis. Jo u rn a l o f the A m erican Statistical A ssociation 1952, 47, 583-621.
19. Dunn, O.J. Multiple comparisons using rank sums. Technom etrics 1964, 6(3), 241-252.
20. Steel, R.G.D.; Torrie, J.H. P rin cip les a n d P ro ced u res o f Statistics, A B io m etrica l A p p ro a ch , 2nd ed.; McGraw-Hill Book Company: New York, NY, 1980; pp 504-506.
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21. SAS Proprietary Software, Version 8.2, SAS Institute, Inc.: Cary, NC, 1999-2001.
12 Deviations F rom 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 F1animals 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.
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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 F 1fetuses/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.
N um ber of
A nim als o r
T im e o f E u th an asia/
T est P eriod gestation day 20 gestation day 20
G eneration Fq Fq
L itters/G roup
1 1
G roup
0 m g/kg/day 0.1 m g /k g / d a y
B lo o d C ollection (hours) 0859 0859
gestation day 20 gestation day 20 gestation day 20 gestation day 20 gestation day 20 po stn atal day 4 lactation day 21 lactation day 21 lactation day 21 po stn atal day 72
Fq Fq F1 F1 F1 F1 Fq Fq Fq F1
3
0.3 m g /k g /d ay
1106 to 1153
4
1.0 m g /k g / d a y
1115 to 1148
2a
0.1 m g /k g / d a y
1052 to 1121b
3a
0.3 m g /k g /d ay
1059 to 1205 b
5a
1.0 m g /k g / d a y
1049 to 1154 b
1a
0.3 m g /k g /d ay
1056 to 1103 b
10
0.1 m g /k g / d a y
1101 to 1 1 1 6
10
0.3 m g /k g /d ay
1107 to 1125
10
1.0 m g /k g / d a y
1117 to 1132
1 0 m g/kg/day
0859
a = N u m b er o f litters.
b = B ecau se b lo o d sam ples w ere p o o led by litter, reg ard less o f sex, fo r g estatio n day 20 fetu ses and
postnatal day 4 pups, eu th an asia/b lo o d co llectio n w as co n sid ered outside the pro to co l-sp ecified
range fo r a litter if b lo o d fro m any fetu s/p u p in th at litter w as co llected after 1 1 0 0 hours.
WIL-180017 3M Corporation
-98-
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 o f the data nor the outcome of the study.
WIL-180017 3M Corporation
-99-
MTDID 208 06-128
FIGURES 1 - 46
PROJECT NO.: WIL-180017 SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 1 (F0 FEMALES) SUMMARY OF BODY WEIGHTS DURING GESTATION [G]
MEAN BODY WEIGHT [G] (SE)
-100-
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
FIGURE 2 (F0 FEMALES) SUMMARY OF BODY WEIGHTS DURING LACTATION [G]
MEAN BODY WEIGHT [G] (SE) -I0I-
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
FIGURE 3 (F1 MALES - PND 1-21) SUMMARY OF OFFSPRING WEIGHTS [G]
MEAN BODY WEIGHT [G] (SE)
-102-
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
FIGURE 4 (F1 FEMALES - PND 1-21) SUMMARY OF OFFSPRING WEIGHTS [G]
MEAN BODY WEIGHT [G] (SE)
-eoi-
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]
-104-
28 35 42 49 56 63 70
POSTNATAL DAY
-- 0 MG/KG/DAY -- --- 0.1 MG/KG/DAY - - * --0.3 MG/KG/DAY -- -O-- 1.0 MG/KG/DAY
72
PROJECT NO.: WIL-180017J SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 6 (F1 FEMALES - PND 28-72) SUMMARY OF BODY WEIGHTS [G]
-SOI-
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
FIGURE 7 (F1 MALES) SUMMARY OF MEAN FORELIMB GRIP STRENGTH [G]
MEAN FORELIMB GRIP STRENGTH [G] (SE)
-106-
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 8 (F1 MALES) SUMMARY OF MEAN HINDLIMB GRIP STRENGTH [G]
MEAN HINDLIMB GRIP STRENGTH [G] (SE)
- 0 1 -
0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY 1.0 MG/KG/DAY * = S ig n ific a n tly d iffe re n t from the co n tro l group a t 0.05 using D unnett's te s t
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 9 (F1 FEMALES) SUMMARY OF MEAN FORELIMB GRIP STRENGTH [G]
MEAN FORELIMB GRIP STRENGTH [G] (SE) - 801-
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]
MEAN HINDLIMB GRIP STRENGTH [G] (SE)
-109-
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 11 (F1 MALES - PND 13, 17 AND 21) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS BY SESSION
-on-
POSTNATAL DAY 13
POSTNATAL DAY 17
POSTNATAL DAY 21
0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY Q 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
-III-
0
POSTNATAL DAY 13
POSTNATAL DAY 17
POSTNATAL DAY 21
0 MG/KG/DAY @ 0.1 MG/KG/DAY 0.3 MG/KG/DAY D 1.0 MG/KG/DAY
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 13 (F1 MALES - PND 61) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS BY SESSION
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) -zu-
0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY Q 1.0 MG/KG/DAY
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 14 (F1 MALES - PND 61) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS BY SESSION
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) -II-
0 MG/KG/DAY 0 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 15 (F1 MALES - PND 13) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE)
-114-
TIME (MINUTES) -- 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 16 (F1 MALES - PND 13) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) -SIT-
-- 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 17 (F1 MALES - PND 17) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE)
-116-
TIME (MINUTES) ----0 MG/KG/DAY ----- 0 .1 MG/KG/DAY - - - - 0 .3 MG/KG/DAY ----- 1 .0 MG/KG/DAY
S ig n ific a n tly d iffe re n t from the co n tro l group a t ^0.031
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 18 (F1 MALES - PND 17) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE) -LU-
TIME (MINUTES) -- 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 19 (F1 MALES - PND 21) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE) - 8 1 1-
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
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 20 (F1 MALES - PND 21) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE)
-119-
-- 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 21 (F1 MALES - PND 61) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE)
-ozi-
TIME (MINUTES) -- 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 22 (F1 MALES - PND 61) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE)
-121-
TIME (MINUTES) -- 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 23 (F1 FEMALES - PND 13, 17 AND 21) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS BY SESSION
-ZZI-
POSTNATAL DAY 13
POSTNATAL DAY 17
POSTNATAL DAY 21
0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY Q 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
-123-
600
+mi m SEh
3 500
oo >EHH
EH 400
OEQh 300 >H
OEh
<i-q3 200
100
0
POSTNATAL DAY 13
POSTNATAL DAY 17
POSTNATAL DAY 21
0 MG/KG/DAY E 0 .1 MG/KG/DAY 0 .3 MG/KG/DAY 1 .0 MG/KG/DAY
* = S ig n ific a n tly d iffe re n t from the co n tro l group a t 0.05 using D unnett's te s t
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 25 (F1 FEMALES - PND 61) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS BY SESSION
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE)
-124-
0 MG/KG/DAY 0.1 MG/KG/DAY 0.3 MG/KG/DAY Q 1.0 MG/KG/DAY
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 26 (F1 FEMALES - PND 61) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS BY SESSION
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE)
-125-
0 MG/KG/DAY 0 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 27 (F1 FEMALES - PND 13) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE)
-126-
TIME (MINUTES) -- 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 28 (F1 FEMALES - PND 13) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE)
-127-
TIME (MINUTES)
0 MG/KG/DAY -- - -- 0.1 MG/KG/DAY - - Tr - -0.3 MG/KG/DAY --
- 1.0 MG/KG/DAY
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 29 (F1 FEMALES - PND 17) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE)
-128-
-- 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 30 (F1 FEMALES - PND 17) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE)
-129-
TIME (MINUTES)
0 MG/KG/DAY -- - -- 0.1 MG/KG/DAY - - Tr - -0.3 MG/KG/DAY --
- 1.0 MG/KG/DAY
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 31 (F1 FEMALES - PND 21) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE)
-130-
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
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 32 (F1 FEMALES - PND 21) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE)
-131-
TIME (MINUTES) -- 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 33 (F1 FEMALES - PND 61) SUMMARY OF MOTOR ACTIVITY TOTAL COUNTS
MEAN TOTAL MOTOR ACTIVITY COUNTS (SE)
-132-
TIME (MINUTES)
0^-- 0 MG/KG/DAY -- - -- 0.1 MG/KG/DAY - - Tr - -0.3 MG/KG/DAY --
- 1.0 MG/KG/DAY
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 34 (F1 FEMALES - PND 61) SUMMARY OF MOTOR ACTIVITY AMBULATORY COUNTS
MEAN AMBULATORY MOTOR ACTIVITY COUNTS (SE)
-133-
TIME (MINUTES) -- 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 35 (F1 MALES - PND 20) SUMMARY OF STARTLE RESPONSE DATA [Vmax]
Vmax [MILLIVOLTS] (SE)
-134-
TRIALS -- 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 36 (F1 MALES - PND 20) SUMMARY OF STARTLE RESPONSE DATA [Tmax]
Tmax [MILLISECONDS] (SE)
-135-
TRIALS -- 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 37 (F1 FEMALES - PND 20) SUMMARY OF STARTLE RESPONSE DATA [Vmax]
Vmax [MILLIVOLTS] (SE)
-136-
TRIALS -- 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 38 (F1 FEMALES - PND 20) SUMMARY OF STARTLE RESPONSE DATA [Tmax]
Tmax [MILLISECONDS] (SE)
-137-
TRIALS -- 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 39 (F1 MALES - PND 60) SUMMARY OF STARTLE RESPONSE DATA [Vmax]
Vmax [MILLIVOLTS] (SE) -8I-
TRIALS -- 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 40 (F1 MALES - PND 60) SUMMARY OF STARTLE RESPONSE DATA [Tmax]
Tmax [MILLISECONDS] (SE)
-139-
TRIALS -- 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 41 (F1 FEMALES - PND 60) SUMMARY OF STARLE RESPONSE DATA [Vmax]
Vmax [MILLIVOLTS] (SE)
-0M -
TRIALS -- 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 42 (F1 FEMALES - PND 60) SUMMARY OF STARTLE RESPONSE DATA [Tmax]
Tmax [MILLISECONDS] (SE)
-141-
TRIALS -- 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 43 (F1 MALES - TIME TO ESCAPE - PND 22) SUMMARY OF BIEL MAZE DATA
-142-
TRIAL -- 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 44 (F1 MALES - MEAN NO. OF ERRORS - PND 22) SUMMARY OF BIEL MAZE DATA
MEAN NO. OF ERRORS (SE)
-143-
1234
56789
TRIAL
10
11
-- 0 MG/KG/DAY -- --- 0.1 MG/KG/DAY -- --0.3 MG/KG/DAY -- --- 1.0 MG/KG/DAY
12
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 45 (F1 FEMALES - TIME TO ESCAPE - PND 22) SUMMARY OF BIEL MAZE DATA
-144-
SWIM
1234
56789
TRIAL
10
11
-- 0 MG/KG/DAY -- --- 0.1 MG/KG/DAY -- --0.3 MG/KG/DAY -- --- 1.0 MG/KG/DAY
12
PROJECT NO.: WIL-180017S SPONSOR: 3M CORPORATION SPONSOR NO.: 06-128
FIGURE 46 (F1 FEMALES - MEAN NO. OF ERRORS - PND 22) SUMMARY OF BIEL MAZE DATA
MEAN NO. OF ERRORS (SE)
-145-
TRIAL -- 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
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 1 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MATERNAL SURVIVAL AND PREGNANCY STATUS
DOSE GROUP :
12
FEMALES ON STUDY
NO. % 25
NO. % 25
FEMALES THAT DIED
00
FEMALES THAT WERE EUTH. IN EXTREMIS
0
0
FEMALES SCHEDULED TO DELIVER NONGRAVID GRAVID NO. THAT FAILED TO DELIVER NO. WITH TOTAL LITTER LOSS NO. WITH 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
TOTAL FEMALES GRAVID
25 100.0
23 92.0
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
4- 1.0 MG/KG/DAY
3
NO. %
25
0
0
25 0 0.0
25 100.0 0 0.0 0 0.0
25 100.0
25 100.0
PAGE
1
4
NO. %
25
0
0
25 1 4.0
24 96.0 0 0.0 0 0.0
24 100.0
24 96.0
MANUALv1.0 10/11/2006 R:10/11/2006
-147-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 2 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS
-----F E M A L E ------
TABLE RANGE: GROUP:
05-02-06 TO 06-19-06 12
NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS
773/22
846/23
DISPOSITION -SCHEDULED EUTHANASIA; POST-MATING DAY 25 -SCHEDULED EUTHANASIA; LACTATION DAY 21
0/ 0 25/25
2/ 2 23/23
BODY/INTEGUMENT -HAIR LOSS RIGHT FORELIMB -HAIR LOSS LEFT FORELIMB -HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM -HAIR LOSS DORSAL HEAD -SCABBING DORSAL HEAD -DRIED RED MATERIAL VENTRAL ABDOMINAL
AREA -HAIR LOSS VENTRAL NECK -HAIR LOSS LEFT LATERAL NECK -SCABBING LEFT LATERAL NECK -SCABBING LEFT FORELIMB -SCABBING RIGHT FORELIMB -HARD IMMOVABLE MASS LEFT LATERAL NECK
5MM X 10MM X 10MM
258/ 9 258/ 8
9/ 1
7/ 1 2/ 1 0/ 0
34/ 1 10/ 1
8/ 1 13/ 2
9/ 3 2/ 1
147/ 7 146/ 8
0/ 0
0/ 0 0/ 0 0/ 0
0/ 0 0/ 0 0/ 0 11/ 2 6/ 2 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
3
885/24
0/ 0 25/25
138/ 6 113/ 7
0/ 0
0/ 0 0/ 0 0/ 0
0/ 0 0/ 0 0/ 0 2/ 2 0/ 0 0/ 0
PAGE
1
4
899/25
1/ 1 24/24
164/ 6 148/ 7
0/ 0
0/ 0 0/ 0 1/ 1
0/ 0 0/ 0 0/ 0 2/ 1 2/ 1 0/ 0
-148-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 2 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS
-----F E M A L E ------
TABLE RANGE: GROUP:
05-02-06 TO 06-19- 06 12
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 AREA
17MM X 15MM X 15MM -SCABBING VENTRAL ABDOMINAL AREA -SCABBING FACIAL AREA -HAIR LOSS UROGENITAL AREA
17/ 1 17/ 1
3/ 1 14/ 1
9/ 1 0/ 0 5/ 1
0/ 0
0/ 0 0/ 0 1/ 1
EYES/EARS/NOSE -DRIED RED MATERIAL AROUND NOSE -DRIED RED MATERIAL AROUND LEFT EYE -DRIED RED MATERIAL AROUND RIGHT EYE -OPACITY RIGHT EYE -EXOPHTHALMUS RIGHT EYE -HAIR LOSS AROUND LEFT EYE
38/12 0/ 0 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
0/ 0 0/ 0 1/ 1 9/ 1 0/ 0 0/ 0 0/ 0
0/ 0
2/ 1 0/ 0 0/ 0
32/ 8 4/ 1 0/ 0 0/ 0 0/ 0 1/ 1
3
0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 11/ 1 0/ 0
0/ 0
0/ 0 1/ 1 0/ 0
22/10 1/ 1
16/ 3 37/ 3 11/ 2
0/ 0
PAGE
2
4
0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 2/ 1 0/ 0
1/ 1
0/ 0 4/ 1 0/ 0
22/ 9 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0
-149-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 2 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS
-----F E M A L E ------
TABLE RANGE: GROUP:
05-02-06 TO 06-19- 06 12
EYES/EARS/NOSE -HAIR LOSS AROUND RIGHT EYE -HAIR LOSS AROUND NOSE -SCABBING AROUND NOSE -WET RED MATERIAL AROUND NOSE
ORAL/DENTAL -WET YELLOW MATERIAL AROUND MOUTH
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
0/ 0 10/ 1
0/ 0 0/ 0
0/ 0 10/ 1
2/ 1 1/ 1
0/ 0
3- 0.3 MG/KG/DAY
4- 1.0 MG/KG/DAY
0/ 0
3
33/ 3 0/ 0 0/ 0 0/ 0
1/ 1
PAGE
3
4
0/ 0 0/ 0 0/ 0 1/ 1
0/ 0
PCSUv4.07 10/09/2006
-OSI-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 3 (F0 - 1 HOUR POST-DOSING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS
-----F E M A L E ------
TABLE RANGE: GROUP:
05-02-06 TO 06- 18-06 12
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
PAGE
1
34
PCSUv4.07 10/05/2006 R:10/09/2006
-1ST-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY
0
MEAN
% DIFFERENCE
S.D.
N
DAY
3
MEAN
% DIFFERENCE
S.D.
N
DAY
6
MEAN
% DIFFERENCE
S.D.
N
DAY
9
MEAN
% DIFFERENCE
S.D.
N
DAY 12 MEAN
% DIFFERENCE S.D. N
TABLE 4 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHTS DURING GESTATION [G]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
266.
12.8 25
268. 0.8
12.1 23
267. 0.4
12.4 25
284.
13.5 25
281. -1.1 14.3
23
282. -0.7 12.3
25
297.
14.8 25
294. -1.0 15.3
23
294. -1.0 12.1
25
310.
16.5 25
308. -0.6 16.1
23
306. -1.3 13.3
25
329.
17.6 25
326. -0.9 17.7
23
325. -1.2 14.7
25
None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE
1
1.0 MG/KG/DAY
266. 0.0
12.6 24
280. -1.4 12.4
24
291. -2.0 12.6
24
300. -3.2 13.3
24
317. -3.6 15.3
24
-152-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY 15 MEAN
% DIFFERENCE S.D. N
DAY 18 MEAN
% DIFFERENCE S.D. N
DAY 20 MEAN
% DIFFERENCE S.D. N
TABLE 4 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHTS DURING GESTATION [G]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
349.
20.0 25
347. -0.6 21.5
23
344. -1.4 17.5
25
388.
21.0 25
388. 0.0
23.7 23
384. -1.0 21.2
25
421.
24.5 25
421. 0.0
28.7 23
417. -1.0 25.0
25
None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE
2
1.0 MG/KG/DAY
336. -3.7 16.8
24
374. -3.6 21.0
24
407. -3.3 22.8
24
PGBWSUv5.08 01/23/2007
-153-
PROJECT NO. :WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO. :06-128
GROUP:
DAY
0- 3 MEAN S.D. N
DAY
3- 6 MEAN S.D. N
DAY
6- 9 MEAN S.D. N
DAY
9- 12 MEAN S.D. N
DAY
12- 15 MEAN S.D. N
DAY
15- 18 MEAN S.D. N
TABLE 5 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
18. 14. 14. 6.9 6.2 5.8
25 23 25
14. 12. 12. 4.5 6.8 3.7
25 23 25
12. 14. 12. 6.8 4.4 4.8
25 23 25
19. 18. 19. 6.4 5.6 5.1
25 23 25
21. 22. 19. 10.0 6.4 6.3
25 23 25
38. 41. 40. 10.9 5.6 7.1
25 23 25
None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE
1
1.0 MG/KG/DAY
14. 5.5
24
11. 4.2
24
9. 5.1
24
17. 4.3
24
19. 5.4
24
38. 7.7
24
-154-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY 18- 20 MEAN S.D. N
DAY 0- 20 MEAN S.D. N
TABLE 5 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHT CHANGES DURING GESTATION [G]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
33. 33. 33. 8.0 8.4 6.7
25 23 25
155. 19.3
25
153. 21.7
23
150. 20.3
25
None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 2
1.0 MG/KG/DAY
33. 9.8
24
141. 17.3
24
PGBWSUv5.08 01/23/2007
-155-
PROJECT NO. :WIL-180017 SPONSOR::3M CORPORATION SPONSOR NO. :06-128
GROUP:
DAY 0- 3 MEAN S.D. N
DAY 3- 6 MEAN S.D. N
DAY 6- 9 MEAN S.D. N
DAY 9- 12 MEAN S.D. N
DAY 12- 15 MEAN S.D. N
DAY 15- 18 MEAN S.D. N
TABLE 6 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
0 MG/KG/DAY
MG/KG/DAY
0.3 MG/KG/DAY
21. 20. 20. 2.1 2.4 1.4
25 23 24
23. 22. 22. 2.5 2.1 2.1
25 22 24
24. 23. 23.* 2.0 2.2 2.1
25 23 24
25. 24. 24. 2.4 2.5 2.2
23 20 19
25. 26. 25. 2.0 2.4 2.3
22 23 23
28. 28. 28. 2.8 2.8 3.1
21 21 22
* = 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
-156-
I--1 1 O1
PAGE
1.0 MG/KG/DAY
20. 1.6
24
22. 1.5
23
22.** 1.4
24
23.** 2.4
21
24. 2.6
22
26. 2.5
20
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY 18- 20 MEAN S.D. N
DAY 0- 20 MEAN S.D. N
TABLE 6 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
28. 28. 28. 2.4 3.6 3.9
23 23 25
25. 24. 24. 1.5 1.9 1.8
23 23 24
** = Significantly different from the control group at 0.01 using Dunnett's test NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 2
1.0 MG/KG/DAY
27. 2.9
24
23. 1.4
24
PGFWSUv5.12 10/26/2006
-157-
PROJECT NO. :WIL-180017 SPONSOR::3M CORPORATION SPONSOR NO. :06-128
GROUP:
DAY 0- 3 MEAN S.D. N
DAY 3- 6 MEAN S.D. N
DAY 6- 9 MEAN S.D. N
DAY 9- 12 MEAN S.D. N
DAY 12- 15 MEAN S.D. N
DAY 15- 18 MEAN S.D. N
TABLE 7 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
75. 72. 73. 7.0 7.3 4.2
25 23 24
79. 77. 78. 7.3 5.8 5.9
25 22 24
79. 77. 76.* 4.9 4.3 5.8
25 23 24
78. 75. 76. 6.8 6.9 4.8
23 20 19
74. 77. 74. 4.9 4.9 4.3
22 23 23
76. 77. 77. 6.4 6.4 6.2
21 21 22
* = 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
PAGE
1.0 MG/KG/DAY
72. 5.8
24
77. 4.9
23
74.** 3.2
24
74. 6.9
21
73. 7.1
22
74. 5.6
20
-158-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY 18- 20 MEAN S.D. N
DAY 0- 20 MEAN S.D. N
TABLE 7 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
70. 69. 69. 7.0 6.9 8.4
23 23 25
74. 74. 73. 3.4 3.4 3.5
23 23 24
None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 2
1.0 MG/KG/DAY
69. 6.6
24
72. 3.0
24
PGFWSUv5.12 01/23/2007
-159-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY
1
MEAN
% DIFFERENCE
S.D.
N
DAY
4
MEAN
% DIFFERENCE
S.D.
N
DAY
7
MEAN
% DIFFERENCE
S.D.
N
DAY 10 MEAN
% DIFFERENCE S.D. N
DAY 14 MEAN
% DIFFERENCE S.D. N
DAY 17 MEAN
% DIFFERENCE S.D. N
TABLE 8 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHTS DURING LACTATION [G]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
317.
18.6 25
318. 0.3
20.2 23
316. -0.3 16.5
25
339.
17.1 25
339. 0.0
23.6 23
336. -0.9 16.3
25
347.
17.0 25
346. -0.3 20.9
23
340. -2.0 13.4
25
359.
17.6 25
360. 0.3
22.3 23
355. -1.1 16.1
25
370.
20.5 25
368. -0.5 20.3
23
362. -2.2 17.6
25
370.
19.8 25
374. 1.1
23.2 23
369. -0.3 20.3
25
* = 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
PAGE
1
1.0 MG/KG/DAY
306. -3.5 19.0
24
324.* -4.4 20.4
24
331.** -4.6 18.5
24
344.* -4.2 19.4
24
349.** -5.7 20.5
24
354.* -4.3 20.0
24
-160-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY
21 MEAN
DIFFERENCE S.D. N
TABLE 8 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHTS DURING LACTATION [G]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
365.
22.5 25
365. 0.0
20.5 23
363. -0.5 17.6
25
* = Significantly different from the control group at 0.05 using Dunnett's test
PAGE
2
1.0 MG/KG/DAY
351.* -3.8 17.1
24
PLBWSUv5.05 10/05/2006
-161-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY 1- 4 MEAN S.D. N
DAY 4- 7 MEAN S.D. N
DAY 7- 10 MEAN S.D. N
DAY 10- 14 MEAN S.D. N
DAY 14- 17 MEAN S.D. N
DAY 17- 21 MEAN S.D. N
DAY 1- 21 MEAN S.D. N
TABLE 9 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHT CHANGES DURING LACTATION [G]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
22. 11.6
25
21. 19. 8.4 11.3
23 25
8. 7. 4. 8.8 9.6 8.2
25 23 25
12. 14. 14. 6.6 7.5 6.6
25 23 25
11. 8. 7. 10.6 8.4 9.5
25 23 25
1. 6. 7. 8.0 10.4 10.8
25 23 25
-6. 12.3
25
-9. 14.3
23
-6. 11.8
25
48. 15.8
25
47. 17.9
23
47. 12.8
25
None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES
PAGE
1
1.0 MG/KG/DAY
18. 11.4
24
8. 10.3
24
12. 9.9
24
5. 7.2
24
5. 11.6
24
-4. 9.2
24
45. 14.8
24
PLBWSUv5.05 10/05/2006
-162-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY 1- 4 MEAN S.D. N
DAY 4- 7 MEAN S.D. N
DAY 7- 10 MEAN S.D. N
DAY 10- 14 MEAN S.D. N
DAY 14- 17 MEAN S.D. N
DAY 17- 21 MEAN S.D. N
TABLE 10 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
40. 40. 38. 7.9 6.3 5.3
20 21 20
43. 44. 42. 3.9 4.8 3.4
22 18 20
54. 56. 53. 5.0 5.4 4.4
23 20 23
62. 64. 61. 6.8 5.5 5.8
24 23 25
67. 70. 68. 8.3 6.1 5.8
25 23 25
72. 76. 73. 7.9 6.3 6.5
22 22 23
None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 1
1.0 MG/KG/DAY
36. 5.7
20
41. 4.5
20
51. 4.9
23
60. 5.5
24
65. 6.4
24
72. 6.6
24
-163-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY
1- 21 MEAN S.D. N
TABLE 10 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
57. 60. 58. 5.9 4.5 4.2
19 21 20
None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
55. 4.9
20
PLFWSUv5.07 10/05/2006
-164-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY 1- 4 MEAN S.D. N
DAY 4- 7 MEAN S.D. N
DAY 7- 10 MEAN S.D. N
DAY 10- 14 MEAN S.D. N
DAY 14- 17 MEAN S.D. N
DAY 17- 21 MEAN S.D. N
TABLE 11 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF FOOD CONSUMPTION DURING LACTATION [G/KG/DAY]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
122. 25.1
20
121. 17.9
21
116. 14.7
20
125. 11.8
22
130. 14.8
18
122. 10.6
20
153. 13.9
23
159. 14.5
20
151. 10.8
23
170. 18.3
24
177. 14.3
23
171. 14.3
25
180. 20.4
25
190. 15.8
23
185. 13.2
25
195. 20.2
22
207. 16.2
22
201. 17.7
23
None significantly different from control group NONGRAVID WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 1
1.0 MG/KG/DAY
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-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
DAY
1- 21 MEAN S.D. N
TABLE 11 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF FOOD CONSUMPTION DURING LACTATION [G/KG/DAY]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
161. 17.5
19
170. 11.9
21
165. 12.3
20
None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
165. 10.3
20
PLFWSUv5.07 10/05/2006
-166-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
GESTATION LENGTH MEAN S.D. N
(DAYS)
TABLE 12 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF GESTATION LENGTHS [DAYS]
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
21.9 0.53
25
21.7 0.47
23
21.7 0.48
25
None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
21.8 0.44
24
P G L v 5 .06 10/05/2006
-167-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS IN DOSE GROUP NUMBER OF ANIMALS EXAMINED
TABLE 13 (F0 - FAILED TO DELIVER) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MACROSCOPIC FINDINGS
SCHEDULED NECROPSY
GROUP:
- F E M A L E -- 12
25 25 02
CERVIX -ENLARGED
UTERUS -CONTENTS, THICK YELLOW -CONTENTS, CLEAR FLUID
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
0
0 0 4- 1.0 MG/KG/DAY
1
1 1
3 25
0
0
0 0
PAGE
1
4 25
1
0
0 1
PGRSI2v4.07 10/05/2006
-168-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS IN DOSE GROUP NUMBER OF ANIMALS EXAMINED
TABLE 14 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MACROSCOPIC FINDINGS
SCHEDULED NECROPSY
GROUP:
-- F E M A L E -12
25 25 25 23
KIDNEYS -ENLARGED -CYST(S)
LIVER -SWOLLEN
LUNGS -AREA(S), DARK RED
THYMUS -AREA(S), DARK RED
THYROID GLANDS -DISCOLORATION, DARK RED
UTERUS -CYST(S)
NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
1 1
1
0
1
0
0 23 4- 1.0 MG/KG/DAY
0 0
0
1
1
0
0 21
3 25 25
0 0
0
0
1
2
0 23
PAGE
1
4 25 24
0 0
0
0
3
1
1 20
PGRSI2v4.07 10/05/2006
-169-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
IMPLANTATION SITES MEAN S.D. N
NUMBER BORN MEAN S.D. N
UNACCOUNTED SITES MEAN S.D. N
TABLE 15 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF IMPLANTATION SITES
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
16.6 3.04
25
16.1 2.52
23
15.9 2.20
25
15.8 3.03
25
15.2 2.24
23
15.1 2.20
25
0.8 0.76
25
0.9 0.87
23
0.8 0.83
25
None significantly different from control group NOTE: ONLY DAMS THAT HAVE DELIVERED ONE OR MORE PUPS ARE INCLUDED IN CALCULATION OF MEAN.
PAGE 1
1.0 MG/KG/DAY
16.0 1.30
24
15.4 1.38
24
0.6 0.71
24
PISSUv5.07 10/05/2006
-0L\-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP :
TABLE 16 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF PND 0 LITTER DATA
12 3
NUMBER BORN MEAN S.D. N
15.8 3.03
25
15.2 2.24
23
15.1 2.20
25
SEX AT BIRTH MEAN S.D. N
(% MALES PER LITTER) 48.7 9.92 25
49.6 12.40
23
49.1 11.78
25
LIVE LITTER MEAN S.D. N
SIZE
(PND 0)
15.6 3.01
25
15.2 2.24
23
15.0 2.21
25
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
PAGE 1
4
15.4 1.38
24
48.9 10.44
24
15.1 1.65
24
PPVIASv5.07 10/05/2006 R:10/23/2006
-\L I -
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP :
TABLE 17 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF POSTNATAL SURVIVAL [% PER LITTER]
12 3
PND 0 (RELATIVE TO NUMBER BORN)
MEAN
99.0
S.D.
2.78
N 25
100.0 0.00 23
PND 0 TO PND MEAN S.D. N
1
98.9 2.83
25
98.4 3.41
23
PND 1 TO PND MEAN S.D. N
4 (PRE-SELECTION) 99.5 1.68 25
99.2 2.12
23
PND 4 (POST-SELECTION) MEAN S.D. N
TO PND 7 98.5 5.50 25
100.0 0.00 23
PND 7 TO PND 14 MEAN S.D. N
99.5 2.50
25
100.0 0.00 23
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
99.0 3.07
25
99.7 1.67
25
98.1 3.91
25
98.0 5.91
25
100.0 0.00 25
PAGE 1
4
98.0 4.62
24
98.7 3.20
24
99.2 3.06
24
100.0 0.00 24
100.0 0.00 24
-172-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP :
TABLE 17 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF POSTNATAL SURVIVAL [% PER LITTER]
12 3
PND 14 TO PND 21 MEAN S.D. N
100.0 0.00 25
100.0 0.00 23
100.0 0.00 25
BIRTH TO PND 4 MEAN S.D. N
(PRE-SELECTION)
97.5 4.90
25
97.6 4.01
23
PND 4 (POST-SELECTION) MEAN S.D. N
TO PND 21 98.0 5.91 25
100.0 0.00 23
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
STATISTICS PERFORMED USING DUNN'S
3- 0.3 MG/KG/DAY
4- 1.0 MG/KG/DAY
MODIFIED STATISTICS USED. None significantly different from control group
96.7 4.62
25
98.0 5.91
25
PAGE 2
4
100.0 0.00 24
95.9 6.11
24
100.0 0.00 24
PPVIASv5.07 10/05/2006 R:10/23/2006
-ZL I -
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
FINDING
TABLE 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF PUP CLINICAL OBSERVATIONS
PRE-WEANING TOTAL NUMBER OF FINDINGS/NUMBER OF PUPS WITH FINDING
GROUP :
1
2
NORMAL NO REMARKABLE OBSERVATIONS
DISPOSITION FOUND DEAD SCHEDULED EUTHANASIA (PND 21) CULLED ON SCHEDULED DAY (PND MISSING
4)
BODY/INTEGUMENT LACERATION SMALL IN SIZE SUBCUTANEOUS HEMORRHAGE(S) DISTAL PORTION OF TAIL MISSING SCABBING DRIED RED MATERIAL PALE IN COLOR HAIR LOSS
CARDIO-PULMONARY LABORED RESPIRATION
ORAL/DENTAL WET RED MATERIAL
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
1732/385
10/ 10 153/153 187/187
5/ 5
1/ 1 1/ 1 1/ 1 0/ 0 1/ 1 1/ 1 1/ 1 0/ 0
0/ 0
1/ 1
4- 1.0 MG/KG/DAY
1588/344
5/ 5 144/144 157/157
4/ 4
0/ 0 16/ 6
1/ 1 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0
1/ 1
0/ 0
PAGE
1
3
1685/372
15/ 15 156/156 166/166
1/ 1
0/ 0 12/ 2
0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 48/ 9
0/ 0
0/ 0
4
1646/356
10/ 10 152/152 163/163
5/ 5
2/ 2 20/ 7
0/ 0 3/ 1 5/ 1 0/ 0 0/ 0 0/ 0
0/ 0
0/ 0
PPOBSIv4.06 10/19/2006
-174-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 1 MALES MEAN % DIFFERENCE S.D. N
FEMALES MEAN
% DIFFERENCE S.D. N
PND 4 (BEFORE SELECTION) MALES MEAN % DIFFERENCE S.D. N
FEMALES MEAN
% DIFFERENCE S.D. N
PND 7 MALES MEAN % DIFFERENCE S.D. N
TABLE 19 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF OFFSPRING WEIGHTS [G]
0 MG/KG/DAY
(LITTER AS EXPERIMENTAL UNIT) 0.1 MG/KG/DAY
0.3 MG/KG/DAY
7.1 0.59
25
6.7 0.56
25
7.2 1.4 0.74
23
6.7 0.0 0.67
23
7.0 -1.4 0.60
25
6.7 0.0 0.55
25
9.6 1.22
25
9.1 1.17
25
10.2 6.3
1.19 23
9.6 5.5 1.17
23
9.9 3.1 0.97
25
9.3 2.2 0.91
25
15.3
2.02 25
16.3 6.5
1.88 23
15.7 2.6
1.66 25
PND = POSTNATAL DAY None significantly different from control group
PAGE
1
1.0 MG/KG/DAY
6.9 -2.8 0.67
24
6.6 -1.5 0.58
24
9.5 -1.0 1.02
24
9.1 0.0 0.87
24
15.1 -1.3 1.97
24
-175-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 7 FEMALES MEAN % DIFFERENCE S.D. N
PND 11 MALES MEAN % DIFFERENCE S.D. N
FEMALES MEAN
% DIFFERENCE S.D. N
PND 14 MALES MEAN % DIFFERENCE S.D. N
FEMALES MEAN
% DIFFERENCE S.D. N
TABLE 19 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF OFFSPRING WEIGHTS [G]
0 MG/KG/DAY
(LITTER AS EXPERIMENTAL UNIT) 0.1 MG/KG/DAY
0.3 MG/KG/DAY
14.6
2.07 25
15.3 4.8
1.97 23
14.9 2.1
1.55 25
25.3 2.97
25
24.2 3.23
25
26.0 2.8
2.78 23
24.8 2.5
2.82 23
25.5 0.8
2.40 25
24.3 0.4
2.15 25
32.9 3.47
25
31.6 3.83
25
33.6 2.1
3.11 23
32.1 1.6
3.14 23
33.2 0.9
2.89 25
31.5 -0.3 2.83
25
PND = POSTNATAL DAY None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
14.9 2.1
1.77 24
24.2 -4.3 2.65
24
24.0 -0.8 2.36
24
31.6 -4.0 3.26
24
31.3 -0.9 3.00
24
-9L\-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 17 MALES MEAN % DIFFERENCE S.D. N
FEMALES MEAN
% DIFFERENCE S.D. N
PND 21 MALES MEAN % DIFFERENCE S.D. N
FEMALES MEAN
% DIFFERENCE S.D. N
TABLE 19 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF OFFSPRING WEIGHTS [G]
0 MG/KG/DAY
(LITTER AS EXPERIMENTAL UNIT) 0.1 MG/KG/DAY
0.3 MG/KG/DAY
40.1 4.39
25
38.5 4.63
25
41.3 3.0
3.72 23
39.6 2.9
3.66 23
40.9 2.0
3.73 25
39.0 1.3
3.22 25
52.7 6.48
25
50.2 6.56
25
54.7 3.8
5.56 23
51.7 3.0
5.31 23
54.0 2.5
5.40 25
51.8 3.2
6.18 25
PND = POSTNATAL DAY None significantly different from control group
PAGE 3
1.0 MG/KG/DAY
38.5 -4.0 4.14
24
38.0 -1.3 3.62
24
50.7 -3.8 5.85
24
50.1 -0.2 4.75
24
PPWSUSNv5.11 10/23/2006 R:10/23/2006
-177-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 1 TO 4 (BEFORE SELECTION) MALES MEAN S.D. N
FEMALES
MEAN S.D.
N
PND 4 TO 7 MALES MEAN S.D. N
FEMALES
MEAN S.D.
N
PND 7 TO 11 MALES MEAN S.D. N
FEMALES
MEAN S.D.
N
TABLE 20 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF OFFSPRING WEIGHT CHANGES [G]
0 MG/KG/DAY
(LITTER AS EXPERIMENTAL UNIT) 0.1 MG/KG/DAY
0.3 MG/KG/DAY
2.6 0.75
25
2.4 0.72
25
3.0 0.54
23
2.8 0.55
23
2.8 0.52
25
2.6 0.49
25
5.7 0.99
25
5.4 1.05
25
6.1 0.97
23
5.7 1.00
23
5.9 0.90
25
5.5 0.78
25
10.0 1.39
25
9.7 1.51
25
9.7 1.18
23
9.5 1.13
23
9.8 1.19
25
9.4 1.15
25
PND = POSTNATAL DAY None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
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
-178-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 11 TO 14 MALES
MEAN S.D.
N
FEMALES
MEAN S.D.
N
PND 14 TO 17 MALES
MEAN S.D.
N
FEMALES
MEAN S.D.
N
PND 17 TO 21 MALES
MEAN S.D.
N
FEMALES
MEAN S.D.
N
TABLE 20 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF OFFSPRING WEIGHT CHANGES [G]
0 MG/KG/DAY
(LITTER AS EXPERIMENTAL UNIT) 0.1 MG/KG/DAY
0.3 MG/KG/DAY
7.6 0.91
25
7.4 0.91
25
7.7 0.71
23
7.3 0.75
23
7.8 1.00
25
7.3 1.16
25
7.2 1.42
25
7.0 1.21
25
7.7 1.19
23
7.5 1.09
23
7.6 1.18
25
7.5 0.98
25
12.6 2.38
25
11.7 2.31
25
13.5 2.48
23
12.2 2.19
23
13.1 2.36
25
12.8 4.21
25
PND = POSTNATAL DAY None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
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
PPWSUSNv5.11 10/23/2006
-179-
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
DOSE GROUP:
PU PS 12 34
NUMBER EXAMINED VISCERALLY
STOMACH MILK NOT PRESENT MILK PRESENT
MALFORMATION MANDIBULAR MICROGNATHIA SITUS INVERSUS
VARIATION RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S)
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
10 5 15 10
3 1 06 0032
0001 0001
01 00 4- 1.0 MG/KG/DAY
L ITTER S 12 3
7 3 11
310 0 02
000 000
01 0
PAGE 1
4
8
4 2
1 1
0
PPNSIv4.03 01/23/2007 R:01/23/2007
- 081-
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
DOSE GROUP:
PU PS 12 34
L ITTER S 12 3
4
NUMBER EXAMINED VISCERALLY NUMBER WITH FINDINGS
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
103 0
94 106 102 000
3- 0.3 MG/KG/DAY
4- 1.0 MG/KG/DAY
25 23 25 24 0000
PPNSIv4.03 10/05/2006 R:10/10/2006
-I8I-
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
GROUP:
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
BALANOPREPUTIAL SEPARATION MEAN S.D. N
(PND)
46.2 2.09
20
47.0 3.56
20
45.8 2.63
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
PND= POSTNATAL DAY * = Significantly different from the control group at 0.05 using Dunnett's test
PAGE 1
1.0 MG/KG/DAY
45.8 1.77
20
243.5 -1.9
21.43 20
PJTBBv1.16 10/05/2006 R:10/12/2006
-182-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
VAGINAL PATENCY (PND) MEAN S.D. N
BODY WEIGHT (GRAMS) MEAN
% DIFFERENCE S.D. N
TABLE 24 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF ANIMAL DEVELOPMENTAL PARAMETERS - VAGINAL PATENCY
0 MG/KG/DAY
0.1 MG/KG/DAY
0.3 MG/KG/DAY
31.7 1.04
20
32.7 1.45
20
32.0 1.61
20
105.8
11.23 20
118.6** 12.1
11.97 20
110.6 4.5
8.86 20
PND= POSTNATAL DAY ** = Significantly different from the control group at 0.01 using Dunnett's test
PAGE 1
1.0 MG/KG/DAY
32.3 0.72
20
110.4 4.3
9.74 20
PJTBBv1.16 10/05/2006 R:10/12/2006
-183-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 25 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS
----- M A L E -----
TABLE RANGE: GROUP:
06-17-06 TO 08-08-06 12
NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS
DISPOSITION -SCHEDULED EUTHANASIA
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
EYES/EARS/NOSE -OPACITY RIGHT EYE
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
149/20
159/20
20/20
20/20
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
0/ 0
3- 0.3 MG/KG/DAY
4- 1.0 MG/KG/DAY
0/ 0
3
150/20
20/20
5/ 2 3/ 2 1/ 1 1/ 1 0/ 0 0/ 0 0/ 0 2/ 1 1/ 1 0/ 0 0/ 0 0/ 0
0/ 0
PAGE 1
4
148/19
20/20
2/ 1 3/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 1/ 1
9/ 1
-184-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 25 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS
----- M A L E -----
TABLE RANGE: GROUP:
06-17-06 TO 08-08-06 12
EYES/EARS/NOSE -OPACITY LEFT EYE -DRIED RED MATERIAL AROUND NOSE -EXOPHTHALMUS RIGHT EYE -DRIED RED MATERIAL AROUND LEFT EYE -DRIED RED MATERIAL AROUND RIGHT EYE -APPARENT MECHANICAL INJURY RIGHT EYE
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0
3- 0.3 MG/KG/DAY
4- 1.0 MG/KG/DAY
0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0
3
0/ 0 2/ 2 0/ 0 0/ 0 0/ 0 0/ 0
PAGE 2
4
9/ 1 0/ 0 7/ 1 1/ 1 4/ 2 1/ 1
-185-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 25 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF CLINICAL FINDINGS: TOTAL OCCURRENCE/NO. OF ANIMALS
-----F E M A L E ------
TABLE RANGE: GROUP:
06-17-06 TO 08-08- 06 12
NORMAL -NO SIGNIFICANT CLINICAL OBSERVATIONS
DISPOSITION -SCHEDULED EUTHANASIA
BODY/INTEGUMENT -HAIR LOSS RIGHT FORELIMB -HAIR LOSS LEFT FORELIMB -HAIR LOSS LEFT LATERAL THORACIC AREA -SCABBING LEFT LATERAL THORACIC AREA -HAIR LOSS RIGHT HINDLIMB -HAIR LOSS LEFT HINDLIMB -HAIR LOSS RIGHT LATERAL THORACIC AREA -SCABBING RIGHT LATERAL THORACIC AREA -SCABBING LEFT FORELIMB -SCABBING RIGHT FORELIMB
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
155/20
160/20
20/20
20/20
3/ 2 3/ 2 2/ 1 2/ 1 0/ 0 0/ 0 1/ 1 1/ 1 1/ 1 1/ 1
3- 0.3 MG/KG/DAY
4- 1.0 MG/KG/DAY
0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0
3
154/20
20/20
6/ 2 6/ 2 0/ 0 0/ 0 1/ 1 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0
PAGE 3
4
160/20
20/20
0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0
PCSUv4.07 01/23/2007
-186-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 28 MEAN
% DIFFERENCE S.D. N
PND 35 MEAN
% DIFFERENCE S.D. N
PND 42 MEAN
% DIFFERENCE S.D. N
PND 49 MEAN
% DIFFERENCE S.D. N
PND 56 MEAN
% DIFFERENCE S.D. N
TABLE 26 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHTS [G]
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
88. 92. 90. 4.5 2.3
10.5 8.9 8.1 20 20 20
151.
17.9 20
160. 6.0
15.6 20
156. 3.3
12.1 20
215.
20.5 20
227. 5.6
21.6 20
222. 3.3
13.6 20
272.
24.6 20
287. 5.5
27.4 20
280. 2.9
16.7 20
325.
29.1 20
342. 5.2
30.8 20
335. 3.1
19.0 20
None significantly different from control group
PAGE
1
1.0 MG/KG/DAY
85. -3.4 10.2
20
147. -2.6 15.1
20
214. -0.5 20.0
20
271. -0.4 25.7
20
326. 0.3
26.0 20
-187-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 63 MEAN
% DIFFERENCE S.D. N
PND 70 MEAN
% DIFFERENCE S.D. N
PND 72 MEAN
% DIFFERENCE S.D. N
TABLE 26 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHTS [G]
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
364.
32.3 20
388. 6.6
38.5 20
376. 3.3
21.8 20
402.
36.1 20
428. 6.5
44.7 20
416. 3.5
24.3 20
413.
39.2 20
440. 6.5
46.9 20
428. 3.6
25.1 20
None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
365. 0.3
31.3 20
408. 1.5
34.6 20
420. 1.7
34.6 20
-188-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 28 MEAN
% DIFFERENCE S.D. N
PND 35 MEAN
% DIFFERENCE S.D. N
PND 42 MEAN
% DIFFERENCE S.D. N
PND 49 MEAN
% DIFFERENCE S.D. N
PND 56 MEAN
% DIFFERENCE S.D. N
TABLE 26 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHTS [G]
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
80. 84. 82. 5.0 2.5
9.6 9.0 7.4 20 20 20
129.
14.4 20
135. 4.7
10.6 20
132. 2.3
10.1 20
164.
15.4 20
173. 5.5
11.1 20
168. 2.4
14.1 20
188.
19.0 20
195. 3.7
16.0 20
191. 1.6
17.0 20
212.
24.2 20
218. 2.8
18.5 20
212. 0.0
20.3 20
None significantly different from control group
PAGE
3
1.0 MG/KG/DAY
80. 0.0 8.0
20
130. 0.8
11.0 20
164. 0.0
12.5 20
188. 0.0
15.9 20
210. -0.9 18.8
20
-189-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 63 MEAN
% DIFFERENCE S.D. N
PND 70 MEAN
% DIFFERENCE S.D. N
PND 72 MEAN
% DIFFERENCE S.D. N
TABLE 26 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHTS [G]
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
228.
23.5 20
237. 3.9
17.8 20
231. 1.3
22.8 20
243.
28.3 20
254. 4.5
21.1 20
244. 0.4
18.5 20
245.
25.7 20
255. 4.1
21.7 20
251. 2.4
21.6 20
None significantly different from control group
PAGE 4
1.0 MG/KG/DAY
229. 0.4
20.9 20
241. -0.8 23.6
20
246. 0.4
23.9 20
PJTBWSUv5.14 10/10/2006
-190-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 28- 35 MEAN S.D. N
PND 35- 42 MEAN S.D. N
PND 42- 49 MEAN S.D. N
PND 49- 56 MEAN S.D. N
PND 56- 63 MEAN S.D. N
PND 63- 70 MEAN S.D. N
TABLE 27 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHT CHANGES [G]
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
63. 68. 66. 8.1 7.8 5.4
20 20 20
64. 67. 66. 4.8 6.8 4.7
20 20 20
57. 60. 58. 7.0 7.8 5.1
20 20 20
52. 56. 55. 6.5 7.2 7.3
20 20 20
39.
45.*
41.
6.8 9.5 5.5
20 20 20
38. 40. 40. 7.8 8.8 5.8
20 20 20
* = Significantly different from the control group at 0.05 using Dunnett's test MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES
PAGE 1
1.0 MG/KG/DAY
62. 5.9
20
67. 7.7
20
57. 9.1
20
55. 7.0
20
39. 6.6
20
43. 6.7
20
-191-
PROJECT NO. :WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO. :06-128
GROUP:
PND 70- 72 MEAN S.D. N
PND 28- 72 MEAN S.D. N
TABLE 27 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHT CHANGES [G]
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
11. 13. 12. 5.3 4.3 4.2
20 20 20
325. 31.7
20
348. 39.7
20
338. 23.0
20
None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES
PAGE
2
1.0 MG/KG/DAY
12. 4.0
20
335. 29.2
20
-192-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 28- 35 MEAN S.D. N
PND 35- 42 MEAN S.D. N
PND 42- 49 MEAN S.D. N
PND 49- 56 MEAN S.D. N
PND 56- 63 MEAN S.D. N
PND 63- 70 MEAN S.D. N
TABLE 27 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHT CHANGES [G]
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
48. 51. 50. 6.1 3.8 4.2
20 20 20
35. 38. 36. 6.5 3.2 8.7
20 20 20
24. 22. 23. 7.2 8.1 5.8
20 20 20
24. 23. 21. 7.7 7.7 8.8
20 20 20
16. 19. 20. 7.9 7.3 6.6
20 20 20
15. 17. 13. 6.6 8.2 9.4
20 20 20
None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES
PAGE
3
1.0 MG/KG/DAY
50. 4.6
20
34. 5.5
20
24. 7.9
20
22. 6.3
20
18. 4.0
20
13. 7.2
20
-6I-
PROJECT NO. :WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO. :06-128
GROUP:
PND 70- 72 MEAN S.D. N
PND 28- 72 MEAN S.D. N
TABLE 27 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BODY WEIGHT CHANGES [G]
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
1. 1. 6. 7.1 6.8 8.7
20 20 20
164. 20.5
20
171. 17.6
20
169. 19.5
20
None significantly different from control group MEAN DIFFERENCES CALCULATED FROM INDIVIDUAL DIFFERENCES
PAGE
4
1.0 MG/KG/DAY
5. 8.9
20
166. 23.2
20
PJTBWSUv5.14 10/10/2006
-194-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 1 PND 4
-195-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
21 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
PAGE 2 PND 4
-196-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 3 PND 4
-197-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 4 PND 4
-198-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 5 PND 11
-199-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 6 PND 11
-200-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 7 PND 11
-201-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 8 PND 11
-202-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 9 PND 21
-203-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 10 PND 21
-204-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
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
PAGE 11 PND 21
-205-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 12 PND 21
-206-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 13 PND 21
-207-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
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
PAGE 14 PND 21
-208-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
EASE OF REMOVAL FROM CAGE VERY EASY EASY
20 20 19 19 --11
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
PAGE 15 PND 35
-209-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
1112 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
PAGE 16 PND 35
-210-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 17 PND 35
-uz-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 18 PND 35
-212-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV.. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE PND 35
-213-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV.. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE PND 35
-214-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 21 PND 45
-215-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 22 PND 45
-216-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 23 PND 45
-LIZ-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 24 PND 45
-218-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV.. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE PND 45
-219-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 26 PND 45
-220-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 27 PND 60
-221-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
PAGE 28 PND 60
-222-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
MALES 12 34
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
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
PAGE 29 PND 60
-223-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
EASE OF REMOVAL FROM CAGE VERY EASY EASY
20 19 19 20 -11 -
EASE OF HANDLING ANIMAL IN HAND
LOW 20 19 19 20
MODERATELY LOW
-11 -
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
PAGE 30 PND 60
-224-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 31 PND 60
-225-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 28 (F1 FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV.. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS SUMMARY OF DETAILED CLINICAL OBSERVATIONS
GROUP:
FEMALES 12 34
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
PAGE 32 PND 60
PFOBGv1.52 10/10/2006 R:01/26/2007
-226-
-227-
o o o o o o o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
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
0.00 20
0.00 20
0.00 20
0.00 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
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
PAGE PND 4
1
-228-
o o o o o o o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
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
0.00 20
0.00 20
0.00 20
0.00 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
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
PAGE PND 4
2
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
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
PAGE 3 PND 11
-229-
-230-
o o o o o o o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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 S.D. N
0.0 0.00
20
0.0 0.00
20
0.0 0.00
20
0.0 0.00
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
PAGE
4
PND 11
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
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
PAGE 5 PND 11
-231-
-232-
o o o o o o o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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 S.D. N
0.0 0.00
20
0.0 0.00
20
0.0 0.00
20
0.0 0.00
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
PAGE
6
PND 11
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
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
PAGE 7 PND 21
-233-
-234-
o o o o o o o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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 MEAN S.D. N
(AVG)
138.4 34.61
20
137.4 24.09
20
132.3 26.98
20
119.7 24.47
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
PAGE 8 PND 21
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
HINDLIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
79.8 17.51
20
82.8 12.23
20
84.8 16.30
20
66.7* 17.09
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
PAGE 9 PND 21
-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
SPONSOR:3M CORPORATION
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
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
PAGE 10 PND 21
-236-
-237-
oo oo o o o o o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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
0.00 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 MEAN S.D. N
(AVG)
142.8 32.41
20
140.5 31.10
20
132.5 28.06
20
129.3 26.98
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
PAGE 11 PND 21
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
HINDLIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
73.8 16.04
20
79.2 12.49
20
77.5 17.72
20
73.6 12.13
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
PAGE 12 PND 21
-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
SPONSOR:3M CORPORATION
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
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
PAGE 13 PND 35
-239-
-240-
o o o o o o o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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 2221
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
PAGE 14 PND 35
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
FORELIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
444.3 109.89
20
449.2 73.47
20
459.8 65.33
20
405.6 76.88
20
HINDLIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
316.8 71.99
20
354.7 100.95
20
358.7 77.92
20
337.0 87.04
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
PAGE 15 PND 35
-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
SPONSOR:3M CORPORATION
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
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
PAGE 16 PND 35
-242-
-243-
oo oo oo oo oo oo o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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
0.00 20
0.00 20
0.00 20
TAIL PINCH RESPONSE TURNS SLOWLY OR WALKS AWAY ENERGETIC RESPONSE
20 19 18 19 -12 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
PAGE 17 PND 35
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
FORELIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
434.0 77.32
20
430.8 75.65
20
424.7 70.17
20
400.6 59.28
20
HINDLIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
308.0 84.52
20
350.9 98.19
20
323.4 75.49
20
338.9 77.20
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
PAGE 18 PND 35
-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
SPONSOR:3M CORPORATION
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
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
PAGE PND 45
-245-
-246-
o o o o oo oo o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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
0.00 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
PAGE 20 PND 45
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
FORELIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
626.4 190.23
20
654.4 197.79
20
617.8 159.91
20
679.3 184.36
20
HINDLIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
434.2 162.30
20
441.8 165.65
20
425.3 159.93
20
443.4 127.66
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
PAGE 21 PND 45
-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
SPONSOR:3M CORPORATION
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
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
PAGE 22 PND 45
-248-
-249-
oo oo oo oo oo oo oo oo
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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
0.00 20
0.00 20
0.00 20
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
PAGE 23 PND 45
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
FORELIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
603.3 186.52
20
597.3 176.64
20
663.1 151.84
20
579.6 149.02
20
HINDLIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
416.6 154.75
20
427.0 144.35
20
429.1 126.17
20
427.2 140.45
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
PAGE 24 PND 45
-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
SPONSOR:3M CORPORATION
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
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
PAGE 25 PND 60
-251-
-252-
o o o o o o o o
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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 MEAN S.D. N
(AVG)
472.5 134.22
20
484.5 82.19
20
457.0 118.75
20
448.7 123.87
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
PAGE 26 PND 60
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
MALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
HINDLIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
336.0 102.60
20
310.3 68.03
20
320.8 76.45
20
315.3 81.63
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
PAGE 27 PND 60
-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
SPONSOR:3M CORPORATION
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
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
PAGE 28 PND 60
-254-
-255-
oo oo oo oo oo oo oo oo
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
BACKING COUNTS MEAN S.D. N
0.00 20
0.00 20
0.00 20
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
0.00 20
0.00 20
0.00 20
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
PAGE 29 PND 60
TABLE 29 (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
SUMMARY OF DETAILED CLINICAL OBSERVATIONS
SPONSOR NO.:06-128
FEMALES
GROUP:
12 34
NUMBER OF ANIMALS TESTED
20 20 20 20
FORELIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
408.9 78.80
20
410.2 74.18
20
441.6 133.21
20
399.1 69.26
20
HINDLIMB GRIPSTRENGTH MEAN S.D. N
(AVG)
295.9 72.64
20
297.3 93.51
20
303.6 88.82
20
286.8 63.40
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
PAGE 30 PND 60
PFOBGv1.52 10/10/2006 R:01/26/2007
-256-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period Sex Variable
PND013 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
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference S.D. N
Control
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
110 NA
60.6
67 NA 75.0
89 160.0
67 107.9
83 NA
333 NA
336.3 20
170 54.5 172.2
NT
139 107.5 117.8
NT
60 90.3
NT
124 213.7
NT
123 NA NT
493 48.0 351.8
20
128 16.4 190.0
NT
111 65.7 250.6
NT
62 103.8
NT
97 192.7
NT
99 NA NT
398 19.5 522.2
20
Statistical 1.0 Model
130 18.2 155.8
NT
95 41.8 113.1
NT
39 58.4
NT
89 153.5
NT
88 NA 0.938
353 6.0 377.0
20
0.663 0.571 0.420
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference S.D. N
Control
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
115 NA
107.9
92 NA 94.3
59 100.6
78 140.3
86 NA
343 NA
263.0 20
225 95.7 244.9
NT
206 123.9 284.3
NT
190 258.1
NT
174 271.4
NT
199 NA NT
795 131.8 904.3
20
129 12.2 180.2
NT
108 17.4 139.1
NT
126 145.7
NT
74 98.5
NT
109 NA NT
437 27.4 430.9
20
Statistical 1.0 Model
102 -11.3
73.1 NT
81 -12.0 129.7
NT
96 168.2
NT
113 216.4
NT
98 NA 0.702
392 14.3 391.7
20
0.047 0.913 0.730
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-258-
PAGE 2
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period Sex Variable
PND017 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
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference S.D. N
Control
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
471 NA
317.8
208 NA
199.2
184 208.8
108 203.9
243 NA
971 NA
772.8 20
605 28.5 326.4
NT
225 8.2 215.3 0.858
222 256.4
NT
240 251.1
NT
323 NA
0.299
1293 33.2 832.6
20
732 55.4 387.9
NT
410 97.1 262.2 0.031*
352 265.9 0.071
273 246.4 0.076
442 NA
0.012*
1766 81.9 932.3
20
Statistical 1.0 Model
383 -18.7 315.0 0.643
370 77.9 333.9 0.023*
427 393.8 0.004*
354 326.4 0.009*
383 NA
0.030*
1534 58.0 1200.5
20
0.071 <0.001*
0.002* AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference S.D. N
Control
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
544 NA
351.6
271 NA
224.2
147 183.4
124 185.2
271 NA
1085 NA
668.1 20
607 11.6 208.9
NT
247 -8.9 241.7
NT
254 312.4
NT
236 304.9
NT
336 NA NT
1344 23.9 914.4
20
580 6.6 306.9
NT
345 27.3 273.4
NT
316 248.5
NT
291 248.7
NT
383 NA NT
1532 41.2 924.5
20
Statistical 1.0 Model
559 2.8 376.0
NT
371 36.9 271.8
NT
353 273.2
NT
303 330.2
NT
397 NA
0.074
1587 46.3 1109.6
20
0.324 0.295 0.147
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-260-
PAGE 4
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period Sex Variable
PND021 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
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference S.D. N
Control
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
455 NA
144.9
93 NA 115.3
63 63.0
35 74.1
162 NA
646 NA
263.0 20
547 20.2 158.2
NT
157 68.8 181.0
NT
106 154.0
NT
72 108.1
NT
221 NA NT
882 36.5 483.6
20
513 12.7 136.5
NT
129 38.7 126.6
NT
49 86.4
NT
58 109.1
NT
187 NA NT
748 15.8 328.7
20
Statistical 1.0 Model
574 26.2 195.1
NT
128 37.6 207.5
NT
100 192.6
NT
122 239.7
NT
231 NA
0.162
924 43.0 763.6
20
0.275 0.365 0.112
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference S.D. N
Control
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
505 NA
128.5
136 NA
184.1
29 49.7
71 111.9
185 NA
740 NA
367.2 20
479 -5.1 119.5
NT
143 5.1 128.3
NT
63 76.7
NT
35 69.2
NT
180 NA NT
720 -2.7 250.9
20
563 11.5 169.5
NT
104 -23.5 111.1
NT
105 130.3
NT
64 106.0
NT
209 NA
0.413
836 13.0 345.2
20
Statistical 1.0 Model
566 12.1 170.8
NT
228 67.6 164.7
NT
91 154.0
NT
93 163.3
NT
245 NA
0.027*
979 32.3 512.3
20
0.114 0.020 0.735
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-262-
PAGE 6
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period Sex Variable
PND061 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
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference S.D. N
Control
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
1296 NA
243.7
626 NA
261.6
325 248.5
235 278.3
621 NA
2483 NA
818.4 20
1375 6.1
217.9 NT
572 -8.6 172.4
NT
402 220.9
NT
303 208.0
NT
663 NA NT
2652 6.8
624.4 20
1397 7.8
295.7 NT
582 -7.0 277.8
NT
373 249.8
NT
276 250.7
NT
657 NA NT
2628 5.8
884.5 20
Statistical 1.0 Model
1306 0.8
186.8 NT
591 -5.6 291.0
NT
349 253.4
NT
284 175.0
NT
632 NA
0.872
2529 1.9
567.1 20
0.856 0.555 0.857
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference S.D. N
Control
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
1198 NA
211.4
535 NA
198.9
329 209.9
255 230.8
579 NA
2316 NA
612.5 20
1161 -3.1 211.0
NT
533 -0.4 197.4
NT
407 223.1
NT
262 186.3
NT
591 NA NT
2364 2.1
587.9 20
1163 -2.9 246.4
NT
458 -14.4 199.0
NT
318 246.7
NT
186 169.5
NT
531 NA NT
2124 -8.3 653.7
20
Statistical 1.0 Model
1217 1.6
198.3 NT
585 9.3 156.0
NT
361 207.6
NT
248 183.3
NT
603 NA
0.937
2412 4.1
592.1 20
0.472 0.777 0.869
CS
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-264-
PAGE 8
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 13 0 TO 15 MINS AMBULATORY MEAN S.D.
16 TO 30 MINS AMBULATORY MEAN S.D.
31 TO 45 MINS AMBULATORY MEAN S.D.
46 TO 60 MINS AMBULATORY MEAN S.D.
AMBULATORY
MEAN S.D.
N
TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MOTOR ACTIVITY COUNTS
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
21. 20.9
11. 23.2
26. 68.2
17. 45.3
75. 135.7
20
50. 74.4
36. 44.8
14. 33.7
36. 80.5
136. 121.6
20
37. 81.3
32. 101.1
17. 48.9
27. 80.3
113. 218.5
20
None significantly different from control group
PAGE 9
1.0 MG/KG/DAY
40. 70.0
22. 47.2
6. 19.7
28. 61.6
96. 160.8
20
-265-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 17 0 TO 15 MINS AMBULATORY MEAN S.D.
16 TO 30 MINS AMBULATORY MEAN S.D.
31 TO 45 MINS AMBULATORY MEAN S.D.
46 TO 60 MINS AMBULATORY MEAN S.D.
AMBULATORY
MEAN S.D.
N
TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MOTOR ACTIVITY COUNTS
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
163. 135.8
59. 71.4
52. 77.7
31. 74.6
305. 302.8
20
224. 160.3
73. 86.2
73. 92.8
79. 88.7
449. 345.2
20
278. 187.5
144. 115.5
121. 108.1
93. 104.1
635. 413.2
20
None significantly different from control group
PAGE 10
1.0 MG/KG/DAY
131. 134.6
125. 141.5
163. 158.8
133. 133.1
551. 488.1
20
-266-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 21 0 TO 15 MINS AMBULATORY MEAN S.D.
16 TO 30 MINS AMBULATORY MEAN S.D.
31 TO 45 MINS AMBULATORY MEAN S.D.
46 TO 60 MINS AMBULATORY MEAN S.D.
AMBULATORY
MEAN S.D.
N
TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MOTOR ACTIVITY COUNTS
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
167. 60.8
21. 34.4
11. 19.2
5. 16.7
204. 94.8
20
200. 61.9
37. 47.6
24. 43.1
13. 28.9
274. 142.2
20
184. 63.2
30. 39.2
10. 23.4
13. 32.3
237. 111.9
20
None significantly different from control group
PAGE 11
1.0 MG/KG/DAY
201. 83.6
36. 78.8
25. 67.0
32. 79.7
294. 288.3
20
-267-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 61 0 TO 15 MINS AMBULATORY MEAN S.D.
16 TO 30 MINS AMBULATORY MEAN S.D.
31 TO 45 MINS AMBULATORY MEAN S.D.
46 TO 60 MINS AMBULATORY MEAN S.D.
AMBULATORY
MEAN S.D.
N
TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MOTOR ACTIVITY COUNTS
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
465. 112.3
205. 97.3
95. 80.4
76. 111.5
840. 304.1
20
540. 115.5
193. 67.0
140. 89.1
101. 76.1
974. 271.6
20
518. 98.8
201. 118.9
121. 84.0
89. 86.8
929. 312.9
20
None significantly different from control group
PAGE 12
1.0 MG/KG/DAY
482. 104.5
207. 120.9
106. 91.0
90. 60.6
886. 235.9
20
-268-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 13 0 TO 15 MINS AMBULATORY MEAN S.D.
16 TO 30 MINS AMBULATORY MEAN S.D.
31 TO 45 MINS AMBULATORY MEAN S.D.
46 TO 60 MINS AMBULATORY MEAN S.D.
AMBULATORY
MEAN S.D.
N
TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MOTOR ACTIVITY COUNTS
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
31. 47.3
17. 33.7
11. 35.5
21. 53.8
80. 104.6
20
75. 117.5
71. 129.8
71. 118.1
65. 120.9
283.* 409.2
20
34. 62.3
28. 48.7
30. 49.8
18. 37.4
109. 150.2
20
Significantly different from the control group at 0.05 using Dunnett's test
PAGE 13
1.0 MG/KG/DAY
21. 22.1
22. 55.7
30. 61.8
47. 104.2
120. 154.4
20
-269-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 17 0 TO 15 MINS AMBULATORY MEAN S.D.
16 TO 30 MINS AMBULATORY MEAN S.D.
31 TO 45 MINS AMBULATORY MEAN S.D.
46 TO 60 MINS AMBULATORY MEAN S.D.
AMBULATORY
MEAN S.D.
N
TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MOTOR ACTIVITY COUNTS
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
201. 164.5
87. 79.9
48. 67.3
38. 62.4
374. 268.2
20
225. 102.4
76. 86.3
82. 120.8
78. 116.8
461. 350.7
20
212. 138.8
117. 128.8
108. 90.8
98. 94.1
535. 370.3
20
None significantly different from control group
PAGE 14
1.0 MG/KG/DAY
213. 171.0
126. 99.4
118. 104.1
107. 124.0
564. 432.4
20
-270-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 21 0 TO 15 MINS AMBULATORY MEAN S.D.
16 TO 30 MINS AMBULATORY MEAN S.D.
31 TO 45 MINS AMBULATORY MEAN S.D.
46 TO 60 MINS AMBULATORY MEAN S.D.
AMBULATORY
MEAN S.D.
N
TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MOTOR ACTIVITY COUNTS
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
177. 52.6
37. 59.3
4. 12.5
15. 27.9
234. 117.1
20
168. 47.5
40. 40.8
12. 18.4
6. 19.1
227. 78.6
20
199. 72.8
25. 31.6
23. 35.6
13. 30.4
259. 115.8
20
None significantly different from control group
PAGE 15
1.0 MG/KG/DAY
199. 68.4
62. 60.7
18. 42.2
19. 45.9
298. 164.7
20
-ILZ-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
PND 61 0 TO 15 MINS AMBULATORY MEAN S.D.
16 TO 30 MINS AMBULATORY MEAN S.D.
31 TO 45 MINS AMBULATORY MEAN S.D.
46 TO 60 MINS AMBULATORY MEAN S.D.
AMBULATORY
MEAN S.D.
N
TABLE 30 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MOTOR ACTIVITY COUNTS
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
519. 105.1
209. 91.8
121. 87.8
91. 100.7
940. 283.0
20
515. 104.3
203. 98.0
161. 99.8
91. 72.3
971. 273.0
20
505. 127.0
166. 92.2
113. 98.1
66. 70.9
850. 297.9
20
None significantly different from control group
PAGE 16
1.0 MG/KG/DAY
540. 108.0
234. 74.4
137. 88.3
92. 78.1
1003. 275.9
20
PMASUMv5.15 10/23/2006 R:10/23/2006
-272-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period PND020
Variable VMAX
Sex Blocks M 1-10
11-20
21-30
31-40
41-50
Overall
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)
0 0.1
0.3
Statistical 1.0 Model
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
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
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
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
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
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. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-273-
PAGE 1
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period PND020
Variable VMAX
Sex Blocks F 1-10
11-20
21-30
31-40
41-50
Overall
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)
0 0.1
0.3
Statistical 1.0 Model
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
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
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
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
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
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. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-274-
PAGE 2
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period PND020
Variable TMAX
Sex Blocks M 1-10
11-20
21-30
31-40
41-50
Overall
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)
0 0.1
0.3
Statistical 1.0 Model
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
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
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
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
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
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. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-275-
PAGE 3
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period PND020
Variable TMAX
Sex Blocks F 1-10
11-20
21-30
31-40
41-50
Overall
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)
0 0.1
0.3
Statistical 1.0 Model
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
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
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
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
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
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. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-276-
PAGE 4
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period PND060
Variable VMAX
Sex Blocks M 1-10
11-20
21-30
31-40
41-50
Overall
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)
0 0.1
0.3
Statistical 1.0 Model
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
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
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
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
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
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. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-277-
PAGE 5
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period PND060
Variable VMAX
Sex Blocks F 1-10
11-20
21-30
31-40
41-50
Overall
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)
0 0.1
0.3
Statistical 1.0 Model
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
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
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
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
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
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. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-278-
PAGE 6
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period PND060
Variable TMAX
Sex Blocks M 1-10
11-20
21-30
31-40
41-50
Overall
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)
0 0.1
0.3
Statistical 1.0 Model
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
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
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
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
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
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. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-279-
PAGE 7
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
Period PND060
Variable TMAX
Sex Blocks F 1-10
11-20
21-30
31-40
41-50
Overall
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)
0 0.1
0.3
Statistical 1.0 Model
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
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
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
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
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
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. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
-280-
PAGE 8
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF STARTLE RESPONSE DATA
GROUP:
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
PND 20 Vave (Millivolts) ALL TRIALS MEAN S.D.
33.0 10.69
30.8 10.01
31.1 11.05
NUMBER OF ANIMALS TESTED N 20 20 20
PND 60 Vave (Millivolts) ALL TRIALS MEAN S.D.
36.7 38.06
23.6 17.45
26.8 17.42
NUMBER OF ANIMALS TESTED N 20 20 20
None significantly different from control group
PAGE 9
1.0 MG/KG/DAY
28.7 12.94
20
20.2 13.02
20
-281-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 31 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF STARTLE RESPONSE DATA
GROUP:
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
PND 20 Vave (Millivolts) ALL TRIALS MEAN S.D.
37.8 13.32
34.1 12.88
33.7 12.94
NUMBER OF ANIMALS TESTED N 20 20 20
PND 60 Vave (Millivolts) ALL TRIALS MEAN S.D.
14.2 6.44
11.7 5.19
13.9 6.57
NUMBER OF ANIMALS TESTED N 20 20 20
None significantly different from control group
PAGE 10
1.0 MG/KG/DAY
30.0 12.33
20
11.3 8.43
20 PSRSUMv5.12 10/12/2006
R:10/12/2006
-282-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 32 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BIEL MAZE DATA MALES
GROUP:
12 3
DAY 1 SWIMMING ABILITY MEAN TIME (SECONDS) S.D. N
8.62 2.453
20
9.10 2.901
20
8.58 2.027
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
PAGE 1
4
11.54 6.400
20
-283-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 32 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BIEL MAZE DATA FEMALES
GROUP:
12 3
DAY 1 SWIMMING ABILITY MEAN TIME (SECONDS) S.D. N
8.54 2.683
20
9.59 1.946
20
9.59 4.467
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
PAGE 2
4
8.72 1.962
20
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
Dose Group (mg/kg/day)
Period Sex Path Type
Variable Trial
Statistic
0 0.1
0.3
PND22 M A LEARNING ESCTIME 1
Mean % Difference Control S.D. N Linear Trend p-value#
78.73 NA
56.080 20
79.27 0.7
58.459 20 NT
71.50 -9.2
53.639 20 NT
2 Mean
58.52
66.73
66.14
% Difference Control
NA 14.0 13.0
S.D.
40.115
44.377
41.239
N 20 20 20
Linear Trend p-value#
NT NT
3 Mean
54.05
54.33
34.71
% Difference Control
NA 0.5 -35.8
S.D.
48.823
47.220
21.907
N 20 20 20
Linear Trend p-value#
NT NT
4 Mean
52.80
38.34
37.71
% Difference Control
NA -27.4 -28.6
S.D.
45.443
38.436
28.372
N 20 20 20
Linear Trend p-value#
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
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
PAGE 1
-285-
Statistical 1.0 Model
79.80 1.4
61.173 20 NT
69.35 18.5
49.673 20 NT
43.96 -18.7 43.665
20 NT
40.11 -24.0 42.615
19 NT
58.23 NA 20
0.556
0.748 0.924 0.557
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Period Sex Path Type
Variable Trial
Statistic
0 0.1
0.3
PND22 M A LEARNING ERRORS 1
Mean % Difference Control S.D. N Linear Trend p-value#
15 NA 10.8 20
14 -6.7 10.2
20 NT
13 -13.3
11.2 20 NT
2 Mean
13 15 14
% Difference Control
NA 15.4
7.7
S.D.
10.5
11.7
10.5
N 20 20 20
Linear Trend p-value#
NT NT
3 Mean
14 12
8
% Difference Control
NA -14.3 -42.9
S.D.
15.1
12.2
6.9
N 20 20 20
Linear Trend p-value#
NT NT
4 Mean
12 7 9
% Difference Control
NA -41.7 -25.0
S.D.
11.6 9.5 8.7
N 20 20 20
Linear Trend p-value#
NT NT
Overall
Mean
13 12 11
S.D.
NA NA NA
N 20 20 20
Linear Trend p-value#
NT NT
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
PAGE 2
-286-
Statistical 1.0 Model
16 6.7 13.2
20 NT
15 15.4 13.4
20 NT
10 -28.6
12.7 20 NT
8 -33.3
10.1 20 NT
12 NA 20 0.513
0.740 0.829 0.513
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Variable Trial
Statistic
0 0.1
0.3
PAGE 3
Statistical 1.0 Model
PND22 M B LEARNING ESCTIME 5
Mean % Difference Control S.D. N Linear Trend 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. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Period Sex Path Type
Variable Trial
Statistic
0 0.1
0.3
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
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
PAGE 4
___ Statistical 1.0 Model
104.64 NA 20
0.299
0.535 0.610 0.267
CS
-288-
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Variable Trial
Statistic
0 0.1
0.3
PAGE 5
Statistical 1.0 Model
PND22 M B LEARNING ERRORS 5
Mean % Difference Control S.D. N Linear Trend 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. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Period Sex Path Type
Variable Trial
Statistic
0 0.1
0.3
PND22 M B LEARNING ERRORS Overall
Mean
25 25 23
S.D.
NA NA NA
N 20 20 20
Linear Trend p-value#
NT NT
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
PAGE 6
Statistical 1.0 Model
23 NA 20 0.384
0.802 0.868 0.641
CS
-290-
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Variable Trial ESCTIME 11
12
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
74.70 NA
48.210 20
44.38 NA
43.708 20
59.54 NA 20
74.98 0.4
49.299 20 NT
69.61 56.8
51.904 20 NT
72.29 NA 20 NT
83.29 11.5
44.296 20 NT
51.43 15.9
34.062 20 NT
67.36 NA 20 NT
PAGE 7
Statistical 1.0 Model
85.93 15.0
52.157 20 NT
63.17 42.3
50.376 20 NT
74.55 NA 20
0.307
0.629 0.372 0.943
CS
-291-
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Variable Trial ERRORS 11
12
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
21 NA 16.9 20
11 NA 14.4 20
16 NA 20
21 0.0 15.9
20 NT
17 54.5 13.5
20 NT
19 NA 20 NT
24 14.3 13.1
20 NT
14 27.3 13.3
20 NT
19 NA 20 NT
PAGE 8
Statistical 1.0 Model
25 19.0 16.7
20 NT
16 45.5 16.2
20 NT
21 NA 20 0.231
0.650 0.684 0.962
CS
-292-
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Period Sex Path Type
Variable Trial
Statistic
0 0.1
0.3
PND22 F A LEARNING ESCTIME 1
Mean % Difference Control S.D. N Linear Trend p-value#
63.95 NA
45.821 20
81.98 28.2
65.243 20 NT
50.31 -21.3 31.568
20 NT
2 Mean
71.55
86.16
56.21
% Difference Control
NA
20.4
-21.4
S.D.
55.083
57.290
42.679
N 20 20 20
Linear Trend p-value#
NT NT
3 Mean
61.46
56.72
41.02
% Difference Control
NA
-7.7
-33.3
S.D.
42.016
42.111
31.033
N 20 20 20
Linear Trend p-value#
NT NT
4 Mean
39.80
43.15
31.69
% Difference Control
NA 8.4 -20.4
S.D.
39.740
41.878
22.442
N 20 20 20
Linear Trend p-value#
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
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
PAGE 9
-293-
Statistical 1.0 Model
74.55 16.6
56.967 20 NT
80.65 12.7
46.187 20 NT
67.92 10.5
59.104 20 NT
47.24 18.7
45.762 20 NT
67.59 NA 20
0.912
0.033 0.983 0.997
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Period Sex Path Type
Variable Trial
Statistic
0 0.1
0.3
PND22 F A LEARNING ERRORS 1
Mean % Difference Control S.D. N Linear Trend p-value#
13 NA 10.7 20
14 7.7 12.9
20 NT
10 -23.1
7.7 20 NT
2 Mean
16 18 12
% Difference Control
NA
12.5
-25.0
S.D.
14.2
12.3
9.8
N 20 20 20
Linear Trend p-value#
NT NT
3 Mean
14 12
9
% Difference Control
NA -14.3 -35.7
S.D.
11.7
10.0
8.5
N 20 20 20
Linear Trend p-value#
NT NT
4 Mean
8 96
% Difference Control
NA
12.5
-25.0
S.D.
12.7
11.2
7.0
N 20 20 20
Linear Trend p-value#
NT NT
Overall
Mean
13 13
9
S.D.
NA NA NA
N 20 20 20
Linear Trend p-value#
NT NT
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
PAGE 10
-294-
Statistical 1.0 Model
15 15.4 11.5
20 NT
17 6.3 11.4
20 NT
16 14.3 16.0
20 NT
10 25.0
9.6 20 NT
14 NA 20 0.967
0.065 0.990 0.992
AR1
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Variable Trial
Statistic
0 0.1
0.3
PAGE 11
Statistical 1.0 Model
PND22 F B LEARNING ESCTIME 5
Mean % Difference Control S.D. N Linear Trend 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. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Period Sex Path Type
Variable Trial
Statistic
0 0.1
0.3
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
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
PAGE 12
___ Statistical 1.0 Model
110.20 NA 20
0.171
0.296 0.945 0.866
AR1
-296-
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Variable Trial
Statistic
0 0.1
0.3
PAGE 13
Statistical 1.0 Model
PND22 F B LEARNING ERRORS 5
Mean % Difference Control S.D. N Linear Trend 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-
co o
CO
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
-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. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Dose Group (mg/kg/day)
Period Sex Path Type
Variable Trial
Statistic
0 0.1
0.3
PND22 F B LEARNING ERRORS Overall
Mean
27 22 23
S.D.
NA NA NA
N 20 20 20
Linear Trend p-value#
NT NT
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
PAGE 14
Statistical 1.0 Model
24 NA 20 0.442
0.217 0.850 0.589
AR1
-298-
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Variable Trial ESCTIME 11
12
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
84.58 NA
43.854 20
55.31 NA
44.536 20
69.94 NA 20
79.11 -6.5
46.200 20 NT
52.74 -4.6
43.343 20 NT
65.92 NA 20 NT
66.04 -21.9 44.900
20 NT
69.19 25.1
49.461 20 NT
67.61 NA 20 NT
PAGE 15
Statistical 1.0 Model
78.70 -7.0
42.154 20 NT
56.67 2.5
38.853 19 NT
67.12 NA 20
0.865
0.988 0.198 0.358
AR1
-299-
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. 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
Variable Trial ERRORS 11
12
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
Dose Group (mg/kg/day)
0 0.1
0.3
22 NA 11.8 20
14 NA 13.7 20
18 NA 20
21 -4.5 15.5
20 NT
13 -7.1 14.1
20 NT
17 NA 20 NT
19 -13.6
16.9 20 NT
19 35.7 18.0
20 NT
19 NA 20 NT
PAGE 16
Statistical 1.0 Model
24 9.1 16.2
20 NT
15 7.1 11.4
20 NT
19 NA 20 0.622
0.918 0.246 0.601
AR1
-300-
# : Level of Significance tested = .05. * : Statistically Significant.
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 34 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MACROSCOPIC FINDINGS
SCHEDULED NECROPSY
GROUP:
MA LE 12
55
--
EYES -EYE(S)- OPACITY
KIDNEYS -DILATED PELVIS
NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES
1- 0 MG/KG/DAY
2-- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
0
0 5 4- 1.0 MG/KG/DAY
0
2 3
3 5
0 0 5
PAGE
1
4 5
1 2 2
-301-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 34 (F1 - PND 72 PUPS NOT SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MACROSCOPIC FINDINGS
SCHEDULED NECROPSY
GROUP:
- F E M A L E ---12
55
KIDNEYS -DILATED PELVIS
THYMUS -AREA(S), DARK RED
UTERUS -CONTENTS , CLEAR FLUID
NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY 3- 0.3 MG/KG/DAY
1
1
1 3 4- 1.0 MG/KG/DAY
1 0 0 4
3 5
0 0 0 5
PAGE
2
4 5
0
0
1 4
PGRSI2v4.07 10/05/2006 R:01/24/2007
-302-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MACROSCOPIC FINDINGS
SCHEDULED NECROPSY
GROUP:
MA LE 12
NUMBER OF ANIMALS EXAMINED
15 15
NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES
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
--
3 15 15
PAGE
1
4 15 15
-eoe-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MACROSCOPIC FINDINGS
SCHEDULED NECROPSY
GROUP:
FEMA LE 12
NUMBER OF ANIMALS EXAMINED
15 15
NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES
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
3 15 15
PAGE
2
4 15 15
PGRSI2v4.07 10/05/2006 R:01/26/2007
-304-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
BRAIN (G) MEAN
% DIFFERENCE S.D. N
BRAIN LENGTH(MM) MEAN S.D. N
BRAIN WIDTH(MM) MEAN S.D. N
TABLE 36 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BRAIN WEIGHTS AND BRAIN MEASUREMENTS
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
1.6084
0.09172 15
1.6004 -0.5
0.07144 15
1.5806 -1.7
0.07315 15
22.3 0.50
15
22.4 0.29
15
22.2 0.31
15
15.1 0.34
15
14.9 0.27
15
14.9 0.21
15
None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
1.6204 0.7
0.09937 15
22.3 0.34
15
15.0 0.22
15
-305-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
BRAIN (G) MEAN
% DIFFERENCE S.D. N
BRAIN LENGTH(MM) MEAN S.D. N
BRAIN WIDTH(MM) MEAN S.D. N
TABLE 36 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BRAIN WEIGHTS AND BRAIN MEASUREMENTS
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
1.5992
0.09741 15
1.5702 -1.8
0.06985 15
1.5556 -2.7
0.06085 15
22.0 0.57
15
21.9 0.39
15
22.2 0.37
15
14.9 0.40
15
14.7 0.22
15
14.9 0.29
15
None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
1.5502 -3.1
0.08778 15
21.9 0.41
15
14.8 0.31
15
POFBSTv5.10 10/05/2006 R:01/26/2007
-306-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 37 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHT
GROUP:
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
FINAL BODY WT (G) MEAN S.D. N
54. 53. 53. 7.9 6.8 5.7
15 15 15
BRAIN
(G/100 G FINAL BODY WEIGHT) MEAN S.D. N
3.044 0.4336
15
3.055 0.3547
15
3.022 0.3150
15
None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
53. 5.3
15
3.066 0.2147
15
-307-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 37 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHT
GROUP:
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
FINAL BODY WT (G) MEAN S.D. N
50. 50. 51. 7.9 6.5 4.9
15 15 15
BRAIN
(G/100 G FINAL BODY WEIGHT) MEAN S.D. N
3.264 0.4411
15
3.206 0.4200
15
3.059 0.2557
15
None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
52. 4.6
15
3.023 0.2245
15
POFBSTv5.10 10/05/2006 R:01/26/2007
-308-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MACROSCOPIC FINDINGS
GROUP:
M A L E -- 12
15 15
BRAIN -CYST(S)
NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
1 14 4- 1.0 MG/KG/DAY
0 15
3 15
0 15
PAGE 1
4 15
0 15
-309-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MACROSCOPIC FINDINGS
GROUP:
FEMA LE 12
NUMBER OF ANIMALS EXAMINED
15 15
NO SIGNIFICANT CHANGES OBSERVED - ALL EXAMINED TISSUES
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
3 15 15
PAGE 2
4 15 15
PGRSI2v4.07 10/05/2006 R:01/24/2007
-oie-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
BRAIN (G) MEAN
% DIFFERENCE S.D. N
BRAIN LENGTH(MM) MEAN S.D. N
BRAIN WIDTH(MM) MEAN S.D. N
TABLE 39 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BRAIN WEIGHTS AND BRAIN MEASUREMENTS
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
2.18
0.088 15
2.25 3.2
0.097 15
2.16 -0.9 0.080
15
20.8 0.36
15
20.8 0.49
15
20.6 0.41
15
15.5 0.25
15
15.6 0.18
15
15.4 0.27
15
None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
2.20 0.9
0.105 15
20.5 0.44
15
15.5 0.25
15
-ne-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP:
BRAIN (G) MEAN
% DIFFERENCE S.D. N
BRAIN LENGTH(MM) MEAN S.D. N
BRAIN WIDTH(MM) MEAN S.D. N
TABLE 39 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BRAIN WEIGHTS AND BRAIN MEASUREMENTS
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
1.99
0.104 15
2.02 1.5
0.074 15
2.01 1.0
0.049 15
19.8 0.46
15
20.0 0.37
15
19.8 0.36
15
14.9 0.31
15
15.0 0.27
15
15.0 0.18
15
None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
2.00 0.5
0.070 15
19.8 0.43
15
14.9 0.25
15
POFBSTv5.10 10/05/2006 R:01/24/2007
-312-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 40 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHT
GROUP:
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
FINAL BODY WT (G) MEAN S.D. N
419. 43.4
15
445. 42.1
15
422. 24.5
15
BRAIN
(G/100 G FINAL BODY WEIGHT) MEAN S.D. N
0.526 0.0506
15
0.508 0.0367
15
0.514 0.0358
15
None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
416. 32.7
15
0.531 0.0387
15
-eie-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 40 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHT
GROUP:
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
FINAL BODY WT (G) MEAN S.D. N
248. 27.5
15
258. 22.8
15
249. 18.4
15
BRAIN
(G/100 G FINAL BODY WEIGHT) MEAN S.D. N
0.808 0.0770
15
0.790 0.0694
15
0.813 0.0646
15
None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
243. 23.1
15
0.828 0.0857
15
POFBSTv5.10 10/05/2006 R:01/24/2007
-314-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANALYSIS
GROUP:
TSH (ng/ml)
DAY 20
MEAN
% DIFFERENCE
S.D.
N
TABLE 41 (F0 DAMS - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF TSH VALUES
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
12.99
3.292 10
11.96 -7.9
3.048 10
10.52 -19.0 1.903
10
ng/ml = NANOGRAMS/MILLILITER None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
10.93 -15.9 2.538
10
PCPSv5.23 10/05/2006 R:10/10/2006
-315-
PROJECT NO.:WIL-180017C SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANALYSIS
GROUP:
TSH (ng/ml)
DAY 20
MEAN
% DIFFERENCE
S.D.
N
TABLE 42 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF TSH VALUES
0 MG/KG/DAY
BY LITTER 0.1 MG/KG/DAY
0.3 MG/KG/DAY
12.08
4.389 10
10.52 -12.9 2.667
10
9.35 -22.6 2.175
8
ng/ml = NANOGRAMS/MILLILITER None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
9.70 -19.7 2.125
8
PCPSv5.23 10/05/2006 R:01/23/2007
-9ie-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANALYSIS
GROUP:
TSH (ng/mL)
DAY 4
MEAN
% DIFFERENCE
S.D.
N
DAY 21
MEAN
% DIFFERENCE
S.D.
N
TABLE 43 (F0 DAMS - LACTATION DAYS 4 AND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF TSH VALUES
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
10.21
3.908 10
17.04
6.708 10
11.07 8.4
4.009 10
17.52 2.8
5.426 10
8.53 -16.5 1.073
10
14.76 -13.4 4.086
10
ng/mL = NANOGRAMS/MILLILITER None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
10.16 -0.5
2.681 10
19.48 14.3
6.270 10
PCPSv5.24 04/10/2007 R:04/10/2007
-L i e -
PROJECT NO.:WIL-180017U SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANALYSIS
GROUP:
TSH (ng/mL)
DAY 4
MEAN
% DIFFERENCE
S.D.
N
TABLE 44 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF TSH VALUES
0 MG/KG/DAY
BY LITTER 0.1 MG/KG/DAY
0.3 MG/KG/DAY
5.58
2.001 10
5.50 -1.4 0.738
10
4.79 -14.2 2.203
10
ng/mL = NANOGRAMS/MILLILITER None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
5.43 -2.7 1.973
10
PCPSv5.24 04/10/2007 R:04/10/2007
-8ie-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANALYSIS
GROUP:
TSH (ng/ml)
DAY 21
MEAN
% DIFFERENCE
S.D.
N
TABLE 45 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF TSH VALUES
0 MG/KG/DAY
MALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
7.63
1.963 10
9.94 30.3 2.886
10
9.47 24.1 2.565
10
ng/ml = NANOGRAMS/MILLILITER None significantly different from control group
PAGE 1
1.0 MG/KG/DAY
8.79 15.2 1.380
10
-6i-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANALYSIS
GROUP:
TSH (ng/ml)
DAY 21
MEAN
% DIFFERENCE
S.D.
N
TABLE 45 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF TSH VALUES
0 MG/KG/DAY
FEMALES 0.1 MG/KG/DAY
0.3 MG/KG/DAY
8.80
1.863 10
8.87 0.8
2.462 9
8.67 -1.5 2.173
10
ng/ml = NANOGRAMS/MILLILITER None significantly different from control group
PAGE 2
1.0 MG/KG/DAY
8.41 -4.4 2.072
10
PCPSv5.23 10/05/2006 R:10/10/2006
-320-
PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 4 6 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MICROSCOPIC FINDINGS
-----MALE -------
GROUP:
12
10 0
THYROID GLANDS TOTAL NUMBER EXAMINED EXAMINED, UNREMARKABLE NOT EXAMINED
-DECREASED COLLOID MODERATE SEVERE
-LUMINAL DEBRIS, CELLULAR MINIMAL
-MITOTIC FIGURES MINIMAL MILD
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
10 0 0
10 5 5 1 1 9 6 3
4- 1.0 MG/KG/DAY
0 0 0 0 NONE NONE 0 NONE 0 NONE NONE
3
0
0 0 0 0 NONE NONE 0 NONE 0 NONE NONE
PAGE
1
4
8
6 0 2 6 4 2 0 NONE 6 6 NONE
-321-
PROJECT NO.:WIL-180017W SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 46 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF1 MICROSCOPIC FINDINGS
-- FEMALE -----
GROUP:
12
10 0
THYROID GLANDS TOTAL NUMBER EXAMINED EXAMINED, UNREMARKABLE NOT EXAMINED
-DECREASED COLLOID MODERATE SEVERE
-MITOTIC FIGURES MINIMAL MILD
-CONGESTION MODERATE
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
9 0 1 9 2 7 9 4 5 1 1
4- 1.0 MG/KG/DAY
0 0 0 0 NONE NONE 0 NONE NONE 0 NONE
3
0
0 0 0 0 NONE NONE 0 NONE NONE 0 NONE
PAGE
2
4
8
6 0 2 6 3 3 6 1 5 0 NONE
PHSI2v4.24 04/27/2007 R:04/27/2007
-322-
PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 47 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MICROSCOPIC FINDINGS
-- MALE -----
GROUP:
12
10 0
THYROID GLANDS TOTAL NUMBER EXAMINED EXAMINED, UNREMARKABLE
-DECREASED COLLOID MINIMAL
-LUMINAL DEBRIS, CELLULAR MINIMAL
-MITOTIC FIGURES MINIMAL
-ONE EXAMINED PRESENT
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
10 2 4 4 3 3 5 5 0
NONE
4- 1.0 MG/KG/DAY
0 0 0 NONE 0 NONE 0 NONE 0 NONE
3
0
0 0 0 NONE 0 NONE 0 NONE 0 NONE
PAGE
1
4
10
10 5 3 3 0
NONE 4 4 1 1
-323-
PROJECT NO.:WIL-180017N SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 47 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MICROSCOPIC FINDINGS
-- FEMALE -----
GROUP:
12
10 0
THYROID GLANDS TOTAL NUMBER EXAMINED EXAMINED, UNREMARKABLE NOT EXAMINED
-DECREASED COLLOID MINIMAL
-MITOTIC FIGURES MINIMAL MILD
-ONE EXAMINED PRESENT
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
10 2 0 2 2 8 7 1 0
NONE
4- 1.0 MG/KG/DAY
0 0 0 0 NONE 0 NONE NONE 0 NONE
3
0
0 0 0 0 NONE 0 NONE NONE 0 NONE
PAGE
2
4
10
8 2 2 2 2 3 3 NONE 2 2
PHSI2v4.24 04/27/2007 R:04/27/2007
-324-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 48 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MICROSCOPIC FINDINGS
-- MALE -----
GROUP:
12
10 0
THYROID GLANDS TOTAL NUMBER EXAMINED EXAMINED, UNREMARKABLE
-MITOTIC FIGURES MINIMAL
-CYST, ULTIMOBRANCHIAL PRESENT
-ECTOPIC THYMUS PRESENT
-LUMINAL DEBRIS, CELLULAR MINIMAL
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
10 3 5 5 4 4 1 1 0
NONE
4- 1.0 MG/KG/DAY
0 0 0 NONE 0 NONE 0 NONE 0 NONE
3
0
0 0 0 NONE 0 NONE 0 NONE 0 NONE
PAGE
1
4
10
10 7 3 3 0
NONE 0
NONE 1 1
-325-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
NUMBER OF ANIMALS EXAMINED
TABLE 48 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
SUMMARY OF MICROSCOPIC FINDINGS
-----FEMALE ------
GROUP:
12
10 0
THYROID GLANDS TOTAL NUMBER EXAMINED EXAMINED, UNREMARKABLE
-MITOTIC FIGURES MINIMAL
-LUMINAL DEBRIS, CELLULAR MINIMAL
1- 0 MG/KG/DAY
2- 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
10 5 5 5 1 1
4- 1.0 MG/KG/DAY
0 0 0 NONE 0 NONE
3
0
0 0 0 NONE 0 NONE
PAGE
2
4
10
10 2 5 5 4 4
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
14
Follicle area (square pixels)
Mean
17 695
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
20 961
SD 4256.6
N 10
Follicle area (um 2) Mean SD N
2181 442.9
10
4
18 925 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
14
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
14
Follicle area (square pixels)
Mean
74 652
SD 15771.4
N 10
69838 10741.9
10
Follicle area (um 2) Mean SD N
77 68 1641.1
10
72 67 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
7 677 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
14
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 14
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-
* = S ig n ific a n tly d iffe re n t from the control group at 0.05 using Dunnett' te s t
-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
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597 F 25597 F
0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05- 02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
DISPOSITION BODY/INTEGUMENT
06-13-06 05-03-06 05-03-06 05-04-06 05-04-06 05-05-06 05-05-06 05-05-06
05-06-06 05-06-06 05-06-06
05-07-06 05-07-06 05-07-06
05-08-06 05-08-06 05-08-06
05-04-06
05-02-06 05-09-06 05-09-06 05-09-06
05-10-06
6:53 6:58 6:58 7:27 7:27 7:38 7:38 7:42
7:56 7:56 7:57
7:57 7:57 7:57
6:35 6:35 6:36
8:08
8:26 7:55 7:55 7:56
6:27
P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM 2 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE
1
-334-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-10-06 05-10-06 05-10-06
05-11-06 05-11-06 05-11-06 05-11-06
05-12-06 05-12-06 05-12-06 05-12-06
05-12-06 05-12-06 05-13-06 05-13-06 05-13-06 05-13-06 05-13-06
05-14-06 05-14-06 05-14-06
05-14-06 05-15-06 05-15-06
6:27 6:27 6:28
6:33 6:33 6:33 6:34
6:31 6:31 6:31 6:32
6:32 6:33 9:07 9:07 9:08 9:09 9:13
9:03 9:03 9:03
9:03 6:38 6:38
2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS VENTRAL NECK P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS VENTRAL NECK P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS VENTRAL NECK P HARD IMMOVABLE MASS LEFT LATERAL NECK
12MM X 13MM X 11MM 1 HAIR LOSS LEFT LATERAL NECK P SCABBING LEFT LATERAL NECK 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB P SCABBING LEFT LATERAL NECK 2 HAIR LOSS VENTRAL NECK P HARD IMMOVABLE MASS LEFT LATERAL NECK
5MM X 10MM X 10MM 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB P HARD IMMOVABLE MASS LEFT LATERAL NECK
5MM X 10MM X 10MM P SCABBING LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE
2
-335-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-15-06 05-15-06 05-15-06 05-16-06 05-16-06 05-16-06 05-16-06 05-16-06 05-17-06 05-17-06 05-17-06 05-17-06 05-17-06 05-18-06 05-18-06 05-18-06 05-18-06 05-18-06 05-19-06 05-19-06 05-19-06 05-19-06 05-19-06 05-19-06 05-20-06 05-20-06 05-20-06 05-20-06 05-21-06
6:38 6:38 6:38 8:17 8:17 8:17 8:18 8:18 6:54 6:54 6:54 6:54 6:54 6:35 6:35 6:35 6:35 6:35 6:32 6:32 6:32 6:33 6:33 6:33 6:47 6:47 6:47 6:47 6:50
1 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK P SCABBING LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK P SCABBING LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK P SCABBING LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK P SCABBING LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK P SCABBING LEFT LATERAL NECK P SCABBING RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 3
-336-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-21-06 05-21-06 05-21-06 05-22-06 05-22-06 05-22-06 05-22-06 05-23-06 05-23-06 05-23-06 05-23-06 05-24-06 05-24-06 05-24-06 05-25-06 05-25-06 05-25-06 05-26-06 05-26-06 05-26-06 05-27-06 05-27-06 05-27-06 05-28-06 05-28-06 05-28-06 05-28-06 05-28-06 05-29-06
6:50 6:50 6:50 7:05 7:05 7:05 7:05 7:47 7:47 7:47 7:47 7:07 7:07 7:07 7:04 7:05 7:05 8:22 8:22 8:23 8:40 8:40 8:40 7:17 7:17 7:17 7:18 7:18 6:45
2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT LATERAL NECK 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS VENTRAL NECK 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 2 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE
4
-337-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-29-06 05-29-06 05-29-06 05-29-06 05-30-06 05-30-06 05-30-06 05-30-06 05-30-06 05-30-06 05-31-06 05-31-06 05-31-06 05-31-06 05-31-06 05-31-06 05- 31-06 06- 01-06 06-01-06 06-01-06 06-01-06 06-01-06 06-01-06 06-01-06 06-02-06 06-02-06 06-02-06 06-02-06 06-02-06
6:45 6:46 6:46 6:46 6:12 6:12 6:12 6:13 6:13 6:14 6:16 6:16 6:16 6:16 6:16 6:17 6:17 6:13 6:13 6:13 6:13 6:13 6:13 6:14 6:19 6:19 6:20 6:20 6:20
2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB P SCABBING LEFT HINDLIMB 3 HAIR LOSS LEFT FORELIMB 3 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS RIGHT HINDLIMB P SCABBING LEFT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 3 HAIR LOSS LEFT FORELIMB 3 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS RIGHT HINDLIMB P SCABBING LEFT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 3 HAIR LOSS LEFT FORELIMB 3 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS RIGHT HINDLIMB
MODERATE 3 SEVERE P PRESENT
PAGE
5
-338-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05- 02-06 TO 06 -19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
06-02-06 06-03-06 06-03-06 06-03-06 06-03-06 06-03-06 06-03-06 06-04-06 06-04-06 06-04-06 06-04-06 06-04-06 06-04-06 06-05-06 06-05-06 06-05-06 06-05-06 06-05-06 06-05-06 06-05-06 06-06-06 06-06-06 06-06-06 06-06-06 06-06-06 06-06-06 06-06-06 06-07-06 06-07-06
6:20 6:11 6:11 6:11 6:11 6:12 6:12 6:11 6:11 6:11 6:11 6:11 6:11 6:49 6:49 6:49 6:50 6:50 6:50 6:50 6:42 6:42 6:42 6:42 6:42 6:43 6:43 6:43 6:43
1 HAIR LOSS VENTRAL ABDOMINAL AREA 3 HAIR LOSS LEFT FORELIMB 3 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 3 HAIR LOSS LEFT FORELIMB 3 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL THORACIC AREA 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL THORACIC AREA 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 6
-339-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
06-07-06 06-07-06 06-07-06 06-07-06 06-07-06 06-08-06 06-08-06 06-08-06 06-08-06 06-08-06 06-08-06 06-08-06 06-08-06
06-09-06 06-09-06 06-09-06 06-09-06 06-09-06 06-09-06 06-09-06 06-09-06
06-10-06 06-10-06 06-10-06 06-10-06 06-10-06 06-10-06
6:43 6:43 6:43 6:44 6:44 6:40 6:40 6:41 6:42 6:42 6:42 6:42 6:45
6:49 6:49 6:49 6:49 6:49 6:49 6:49 6:50
7:33 7:33 7:33 7:34 7:34 7:34
2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL THORACIC AREA 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL THORACIC AREA P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA
2 0MM X 12MM X 15MM 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL THORACIC AREA P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA
20MM X 12MM X 15MM 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS VENTRAL THORACIC AREA 2 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS RIGHT HINDLIMB
MODERATE 3 SEVERE P PRESENT
PAGE
7
-340-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
06-10-06 06-10-06
06-11-06 06-11-06 06-11-06 06-11-06 06-11-06 06-11-06 06-11-06 06-11-06
06-12-06 06-12-06 06-12-06 06-12-06 06-12-06 06-12-06 06-12-06 06-12-06
06-13-06 06-13-06 06-13-06 06-13-06 06-13-06 06-13-06 06-13-06 06-13-06
7:34 7:35
7:35 7:35 7:35 7:36 7:36 7:36 7:36 7:37
6:55 6:55 6:55 6:56 6:56 6:56 6:56 6:57
6:05 6:05 6:05 6:05 6:05 6:06 6:06 6:06
1 HAIR LOSS LEFT HINDLIMB P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA
2 0MM X 12MM X 15MM 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 2 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL THORACIC AREA 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA
20MM X 12MM X 15MM 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 2 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL THORACIC AREA P HARD MOVABLE MASS RIGHT LATERAL THORACIC AREA
20MM X 12MM X 15MM 3 HAIR LOSS RIGHT FORELIMB 3 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS VENTRAL NECK 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 2 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL THORACIC AREA 1 HAIR LOSS UROGENITAL AREA
MODERATE 3 SEVERE P PRESENT
PAGE
8
-341-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25654 F 25654 F
0 MG/KG/DAY 0 MG/KG/DAY
25632 25610 25610
F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
25618 25621 25621
F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
DISPOSITION EYES/EARS/NOSE
DISPOSITION DISPOSITION EYES/EARS/NOSE
DISPOSITION DISPOSITION BODY/INTEGUMENT
06-13-06 05-06-06 06-13-06 06-14-06 06-15-06 06-06-06 06-13-06 06-15-06 06-15-06 05-04-06 05-05-06 05-06-06 05-07-06 05-08-06 05-03-06 05-09-06 05-09-06 05-10-06 05-10-06 05-11-06 05-12-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06 05-16-06 05-17-06
6 53 7 57 6 08 6 53 6 57 6 45 6 09 6 57 6 57 7 29 7 46 7 58 7 58 6 39 9 27 7 58 7 58 6 30 6 30 6 37 6 35 9 15 9 06 9 06 6 41 6 41 8 21 8 21 6 59
P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE
9
-342-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25621 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06
6:59 6:38 6:38 6:35 6:35 6:51 6:51 6:52 6:52 7:08 7:08 7:49 7:49 7:11 7:11 7:35 7:35 8:29 8:29 8:43 8:43 7:20 7:20 6:48 6:48 6:17 6:17 6:19 6:19
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 10
-343-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25621 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06
6:16 6:16 6:23 6:23 6:13 6:13 6:14 6:14 6:51 6:51 6:45 6:45 6:46 6:46 6:47 6:47 6:53 6:53 7:42 7:42 7:41 7:41 6:58 6:58 6:10 6:10 6:07 6:07 6:06
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 11
-344-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25621 25687 25633 25633
F F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT DISPOSITION DISPOSITION BODY/INTEGUMENT
06-15-06 06-15-06 06-14-06 05-04-06 05-05-06 05-05-06 05-06-06 05-07-06 05-08-06 05-03-06 05-03-06 05-09-06 05-09-06 05-10-06 05-10-06 05-11-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06 05-16-06 05-17-06 05-17-06 05-18-06 05-18-06
6:06 6:57 6:53 7:30 7:46 7:46 7:59 7:58 6:40 9:30 9:30 7:59 7:59 6:30 6:30 6:38 6:36 9:16 9:16 9:07 9:07 6:44 6:44 8:21 8:21 7:00 7:00 6:40 6:40
1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 12
-345-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25633 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-19-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06
6:36 6:52 6:53 6:53 7:09 7:09 7:49 7:49 7:12 7:12 7:30 7:30 8:31 8:31 8:43 8:43 7:20 7:20 6:50 6:50 6:17 6:17 6:21 6:21 6:17 6:17 6:24 6:24 6:14
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 13
-346-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25633 F 0 MG/KG/DAY
25681 F 25681 F
0 MG/KG/DAY 0 MG/KG/DAY
25615 F 0 MG/KG/DAY GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
DISPOSITION EYES/EARS/NOSE DISPOSITION
06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-05-06 06-06-06 06-14-06 06-15-06
6:14 6:16 6:16 6:52 6:52 6:46 6:46 6:46 6:46 6:49 6:49 6:53 6:53 7:43 7:43 7:43 7:43 7:43 6:58 6:58 6:10 6:10 6:08 6:08 6:57 6:53 6:46 6:08 6:57
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21
MODERATE 3 SEVERE P PRESENT
PAGE 14
-347-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25637 25637 25638 25638 25713 25713
F F F F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
25670 25657 25663 25690 25690
F F F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
25666 F 25666 F
0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
DISPOSITION EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE
DISPOSITION DISPOSITION DISPOSITION DISPOSITION EYES/EARS/NOSE
DISPOSITION BODY/INTEGUMENT
06-16-06 06-09-06 06-16-06 06-06-06 06-16-06 06-05-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-10-06 06-11-06 06-12-06 06-13-06 06-14-06 06-15-06 06-16-06 06-16-06 06-16-06 06-16-06 06-16-06 06-12-06 06-13-06 06-14-06 06-16-06 05-18-06 05-19-06
6:43 6:54 6:43 6:47 6:43 6:56 6:47 6:49 6:49 6:53 6:53 6:55 7:45 7:46 7:02 6:12 6:09 6:11 6:08 6:43 6:43 6:43 6:44 7:05 6:12 6:10 6:44 7:07 6:40
P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 15
-348-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25666 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06
6:40 6:54 6:54 6:57 6:57 7:13 7:13 7:53 7:53 7:17 7:17 7:38 7:38 9:04 9:04 8:47 8:48 7:22 7:22 6:52 6:52 6:24 6:24 6:25 6:25 6:20 6:20 6:35 6:35
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 16
-349-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25666 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
06-02-06 06-03-06 06-03-06 06-03-06 06-03-06 06-04-06 06-04-06 06-04-06 06-04-06 06-05-06 06-05-06 06-05-06 06-06-06 06-06-06 06-06-06 06-07-06 06-07-06 06-07-06 06-08-06 06-08-06 06-08-06 06-09-06 06-09-06 06-09-06 06-10-06 06-10-06 06-10-06 06-10-06 06-11-06
6:35 6:17 6:17 6:17 6:17 6:21 6:21 6:21 6:21 7:00 7:00 7:00 6:49 6:49 6:49 6:51 6:51 6:51 6:56 6:56 6:56 7:00 7:00 7:00 7:47 7:47 7:47 7:47 7:48
P SCABBING RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB P SCABBING RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB P SCABBING RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB P SCABBING RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 17
-350-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25666 F 0 MG/KG/DAY
25692 F 25692 F
0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
DISPOSITION BODY/INTEGUMENT
06-11-06 06-11-06 06-11-06 06-12-06 06-12-06 06-12-06 06-13-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-17-06 05-14-06 05-15-06 05-16-06 05-17-06 05-18-06 05-19-06 05-20-06 05-21-06 05-22-06 05-23-06 05-25-06 05-26-06 05-27-06
7:48 7:48 7:48 7:07 7:07 7:07 6:13 6:13 6:13 6:11 6:11 6:14 6:14 6:12 6:12 6:31 9:10 6:48 8:26 7:05 7:08 6:41 6:54 6:58 7:14 7:53 7:39 9:05 8:18
1 HAIR LOSS LEFT FORELIMB P SCABBING RIGHT FORELIMB P SCABBING LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING :LEFT FORELIMB P SCABBING :LEFT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 18
-351-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25692 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-04-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06
7:23 7:23 6:53 6:53 6:25 6:25 6:25 6:25 6:20 6:20 6:35 6:35 6:17 6:21 6:21 6:22 7:00 7:00 6:49 6:49 6:51 6:51 6:56 6:56 7:01 7:01 7:48 7:48 7:49
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 19
-352-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25692 F 0 MG/KG/DAY
25692 F 0 MG/KG/DAY
25701 F 25701 F
25645 F 25645 F
0 MG/KG/DAY 0 MG/KG/DAY
0 MG/KG/DAY 0 MG/KG/DAY
25661 F 25661 F
0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT DISPOSITION BODY/INTEGUMENT
06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-17-06 06-17-06 06-15-06 06-16-06 06-17-06 06-17-06 06-14-06 06-15-06 06-18-06 06-03-06 06-04-06 06-05-06 06-19-06 05-07-06 05-07-06 05-08-06 05-08-06 05-09-06
7:49 7:09 7:09 6:13 6:13 6:11 6:11 6:14 6:14 6:12 6:12 6:12 6:12 6:14 6:12 6:12 6:31 6:11 6:15 6:15 6:19 6:22 7:01 7:03 8:03 8:03 6:44 6:44 8:04
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS DORSAL HEAD P SCABBING DORSAL HEAD 1 HAIR LOSS DORSAL HEAD P SCABBING DORSAL HEAD 1 HAIR LOSS DORSAL HEAD
MODERATE 3 SEVERE P PRESENT
PAGE 20
-353-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25661 F 0 MG/KG/DAY
25661 25767 25767
F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT
05-10-06 05-11-06 05-13-06 05-14-06 05-29-06 06-17-06 06-18-06 05-07-06 05-08-06 05-09-06 05-09-06 05-10-06 05-10-06 05-11-06 05-11-06 05-12-06 05-12-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06 05-16-06 05-17-06 05-17-06 05-18-06 05-18-06 05-19-06
6:36 6:43 9:22 9:12 6:38 6:14 6:15 8:03 6:45 8:04 8:04 6:36 6:36 6:44 6:44 6:42 6:42 9:23 9:14 9:14 6:50 6:50 8:27 8:27 7:07 7:07 7:09 7:09 6:42
1 HAIR LOSS DORSAL HEAD 1 HAIR LOSS DORSAL HEAD 1 HAIR LOSS DORSAL HEAD 1 HAIR LOSS DORSAL HEAD 1 HAIR LOSS RIGHT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 21
-354-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25767 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06
6:42 6:56 6:56 6:59 6:59 7:15 7:15 7:56 7:56 7:19 7:19 7:41 7:41 9:07 9:07 8:19 8:19 7:12 7:12 6:54 6:54 6:27 6:27 6:29 6:29 6:22 6:22 6:38 6:38
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 22
-355-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25767 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-17-06
6:19 6:19 6:24 6:24 7:03 7:03 6:51 6:51 6:54 6:54 6:59 6:59 7:02 7:02 7:55 7:55 7:50 7:50 7:11 7:11 6:16 6:16 6:15 6:15 6:16 6:16 6:14 6:14 6:14
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 23
-356-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25767 F 0 MG/KG/DAY
25767 F 0 MG/KG/DAY
25770 F 25770 F
0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT EYES/EARS/NOSE
DISPOSITION BODY/INTEGUMENT
06-17-06 06-18-06 06-18-06 06-07-06 06-08-06 06-09-06 06-12-06 06-13-06 06-14-06 06-15-06 06-16-06 06-17-06 06-18-06 06-19-06 05-07-06 05-09-06 05-09-06 05-10-06 05-10-06 05-11-06 05-11-06 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-15-06 05-16-06
6:14 6:06 6:06 6:54 6:59 7:02 7:11 6:16 6:15 6:16 6:14 6:14 6:06 7:03 7:53 8:05 8:05 6:37 6:37 6:44 6:44 6:42 6:42 9:23 9:23 9:14 9:14 6:50 8:27
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 24
-357-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25770 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
05-17-06 05-17-06 05-18-06 05-18-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06
7:07 7:07 7:39 7:39 6:56 7:00 7:00 7:15 7:15 7:56 7:21 7:46 7:46 9:08 9:08 8:20 7:12 6:39 6:39 6:27 6:27 6:29 6:29 6:23 6:23 6:38 6:38 6:20 6:20
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 25
-358-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25770 F 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-17-06 06-17-06 06-18-06
6:25 6:25 7:03 7:03 6:51 6:51 6:54 6:54 6:59 6:59 7:02 7:02 7:55 7:55 7:51 7:51 7:12 7:12 6:16 6:16 6:16 6:16 6:17 6:17 6:14 6:14 6:14 6:14 6:06
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE 26
-359-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25770 F 0 MG/KG/DAY
25702 25702 25702
F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
25664 F 0.1 MG/KG/DAY 25648 F 0.1 MG/KG/DAY 25694 F 0.1 MG/KG/DAY 25694 F 0.1 MG/KG/DAY 25694 F 0.1 MG/KG/DAY 25668 F 0.1 MG/KG/DAY 25631 F 0.1 MG/KG/DAY 25631 F 0.1 MG/KG/DAY 25660 F 0.1 MG/KG/DAY 25704 F 0.1 MG/KG/DAY 25695 F 0.1 MG/KG/DAY 25695 F 0.1 MG/KG/DAY
25665 F 0.1 MG/KG/DAY 25665 F 0.1 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION BODY/INTEGUMENT EYES/EARS/NOSE
DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT EYES/EARS/NOSE DISPOSITION DISPOSITION EYES/EARS/NOSE DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION BODY/INTEGUMENT
06-18-06 06-19-06 06-19-06 06-19-06 05-10-06 05-07-06 06-08-06 06-09-06 06-16-06 06-17-06 06-18-06 05-27-06 06-13-06 06-15-06 06-07-06 06-05-06 06-14-06 06-15-06 06-12-06 06-15-06 06-15-06 05-28-06 05-23-06 05-25-06 06-15-06 05-27-06 05-30-06 05-31-06 05-31-06
6:07 6:18 6:18 7:03 6:37 7:38 7:00 7:02 6:15 6:15 6:07 8:33 6:53 6:58 6:56 7:05 6:53 6:58 7:14 6:58 6:58 7:56 8:01 7:49 6:58 8:50 6:31 6:34 6:34
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; POST-MATING DAY 25 P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; POST-MATING DAY 25 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB P SCABBING RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 27
-360-
-361-
1 I-- 1 1o
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25665 F
MG/KG/DAY
25674 F 0.1 MG/KG/DAY 25674 F 0.1 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION BODY/INTEGUMENT
06-01-06 06-02-06 06-03-06 06-04-06 06-04-06 06-05-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-14-06 05-11-06 05-11-06 05-12-06 05-13-06 05-14-06 05-15-06 05-15-06 05-16-06 05-17-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06
6:27 6:45 6:23 6:29 6:29 7:07 6:54 6:58 6:58 7:05 7:05 7:06 7:06 6:53 6:48 6:48 6:49 9:31 9:18 6:57 6:57 8:31 7:12 7:46 6:49 6:49 6:59 6:59 7:07
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING :RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 28
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-27-06 05-27-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06
7:07 7:20 7:20 8:02 8:02 7:25 7:25 7:11 7:11 8:40 8:50 8:50 6:31 6:31 6:34 6:34 6:28 6:28 6:45 6:45 6:23 6:23 6:31 6:31 7:08 7:08 6:55 6:55 6:58
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 29
-362-
-363-
1 I--1 1o
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25674 F
MG/KG/DAY
25652 F 0.1 MG/KG/DAY 25733 F 0.1 MG/KG/DAY 25733 F 0.1 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION DISPOSITION BODY/INTEGUMENT
06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 05-05-06 05-05-06 05-06-06 05-06-06 05-07-06 05-07-06 05-08-06 05-08-06 05-04-06 05-04-06 05-09-06 05-09-06
6:58 7:05 7:05 7:06 7:06 8:04 8:04 7:57 7:57 7:15 7:15 6:19 6:19 6:19 6:19 6:58 6:58 7:52 7:52 8:07 8:07 8:06 8:06 6:51 6:51 9:15 9:15 8:13 8:13
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 30
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-10-06 05-11-06 05-11-06 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06 05-16-06 05-17-06 05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06
6:43 6:43 6:48 6:48 6:50 6:50 9:31 9:31 9:18 9:18 6:59 6:59 8:31 8:31 7:13 7:13 7:47 7:47 6:49 6:49 7:00 7:00 7:08 7:08 7:21 7:21 8:04 8:04 7:25
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 31
-364-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06
7:50 7:50 8:41 8:41 8:51 8:51 7:28 7:28 6:59 6:59 6:32 6:32 6:36 6:36 6:29 6:29 6:47 6:47 6:24 6:24 6:32 6:32 7:08 7:08 6:55 6:55 6:59 6:59 7:06
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 32
-365-
-366-
1 I--1 1o
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25733 F
MG/KG/DAY
25733 F 0.1 MG/KG/DAY
25748 F 0.1 MG/KG/DAY 25748 F 0.1 MG/KG/DAY
BODY/INTEGUMENT
EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT
06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-06-06 06-07-06 06-16-06 05-05-06 05-05-06 05-06-06 05-06-06 05-07-06 05-07-06 05-08-06 05-08-06 05-04-06 05-04-06 05-09-06
7:06 7:07 7:07 8:05 8:05 7:58 7:58 7:16 7:16 6:20 6:20 6:20 6:20 6:24 6:24 6:55 6:59 6:44 7:53 7:53 8:07 8:07 8:06 8:06 6:52 6:52 9:16 9:16 8:13
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 33
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-10-06 05-10-06 05-11-06 05-11-06 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06 05-16-06 05-17-06 05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06
8:13 6:43 6:43 6:49 6:49 6:50 6:50 9:32 9:32 9:19 9:19 7:00 7:00 8:32 8:32 7:13 7:13 7:48 7:48 6:50 6:50 7:00 7:00 7:08 7:08 7:22 7:22 8:04 8:04
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 34
-367-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-24-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06
7:26 7:26 7:50 9:11 9:11 8:51 8:51 7:28 7:28 7:00 6:32 6:32 6:36 6:36 6:30 6:30 6:48 6:48 6:24 6:24 6:33 6:33 7:09 7:09 6:56 6:56 7:01 7:01 7:07
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 35
-368-
-369-
i i--i 1o
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25748 F
MG/KG/DAY
25753 F 0.1 MG/KG/DAY 25753 F 0.1 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION EYES/EARS/NOSE
06-08-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-13-06 06-14-06 06-15-06 06-16-06 06-16-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-07-06 06-07-06 06-08-06 06-08-06 06-08-06 06-09-06 06-10-06
7:07 7:07 8:05 8:05 7:59 7:59 7:16 6:21 6:21 6:26 6:16 6:44 6:25 6:25 6:34 6:34 7:10 7:10 6:57 6:57 7:02 7:02 7:03 7:03 7:08 7:08 7:08 7:09 8:06
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND LEFT EYE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND LEFT EYE 2 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND LEFT EYE 2 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND LEFT EYE 2 DRIED RED MATERIAL AROUND NOSE 1 HAIR LOSS AROUND LEFT EYE 1 HAIR LOSS AROUND NOSE P SCABBING AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 HAIR LOSS AROUND NOSE P SCABBING AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 36
-370-
1 I--1 1o
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25753 F
MG/KG/DAY
25672 F 0.1 MG/KG/DAY 25672 F 0.1 MG/KG/DAY
25655 F 0.1 MG/KG/DAY 25655 F 0.1 MG/KG/DAY
EYES/EARS/NOSE
DISPOSITION EYES/EARS/NOSE
DISPOSITION BODY/INTEGUMENT
06-11-06 06-12-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-16-06 06-07-06 06-08-06 06-09-06 06-12-06 06-13-06 06-14-06 06-15-06 06-16-06 06-16-06 06-03-06 06-06-06 06-07-06 06-08-06 06-09-06 06-10-06 06-11-06 06-12-06 06-13-06 06-14-06
7:59 7:17 6:21 6:21 6:21 6:26 6:26 6:17 6:17 6:44 7:03 7:09 7:10 7:18 6:21 6:22 6:27 6:18 6:44 6:25 6:57 7:04 7:09 7:11 8:06 8:00 7:19 6:22 6:22
1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 HAIR LOSS AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 HAIR LOSS AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 37
-371-
I-- 1 1
O1
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25727 F 0.1 MG/KG/DAY 25626 F 0.1 MG/KG/DAY 25626 F 0.1 MG/KG/DAY
25739 F 0.1 MG/KG/DAY 25739 F 0.1 MG/KG/DAY 25749 F 0.1 MG/KG/DAY 25749 F 0.1 MG/KG/DAY
25756 F 0.1 MG/KG/DAY 25741 F 0.1 MG/KG/DAY 25741 F 0.1 MG/KG/DAY
25752 F 0.1 MG/KG/DAY 25752 F 0.1 MG/KG/DAY
25758 F
MG/KG/DAY
DISPOSITION DISPOSITION BODY/INTEGUMENT DISPOSITION EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE
DISPOSITION DISPOSITION EYES/EARS/NOSE
DISPOSITION BODY/INTEGUMENT
DISPOSITION
06-16-06 06-16-06 06-01-06 06-11-06 06-17-06 06-08-06 06-16-06 05-06-06 06-12-06 06-13-06 06-17-06 06-18-06 05-06-06 06-14-06 06-15-06 06-18-06 06-10-06 06-10-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-15-06 06-16-06 06-17-06 06-18-06 06-19-06
6:44 6:44 6:31 8:00 6:31 7:10 6:44 8:08 7:22 6:23 6:31 6:15 7:38 6:24 6:29 6:16 8:13 8:13 8:03 7:24 7:25 6:25 6:25 6:25 6:30 6:24 6:17 6:08 7:03
P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 WET RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS VENTRAL ABDOMINAL AREA P SCABBING LEFT HINDLIMB 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL ABDOMINAL AREA P SCABBING VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL ABDOMINAL AREA P SCABBING VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL ABDOMINAL AREA 1 HAIR LOSS VENTRAL ABDOMINAL AREA P SCHEDULED EUTHANASIA; LACTATION DAY 21
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 38
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25758 F 0.1 MG/KG/DAY 25719 F 0.1 MG/KG/DAY 25719 F 0.1 MG/KG/DAY
BODY/INTEGUMENT DISPOSITION BODY/INTEGUMENT
06-19-06 06-19-06 05-27-06 05-28-06 05-28-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 05-31-06 06-01-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-04-06 06-04-06 06-05-06 06-05-06 06-05-06 06-05-06 06-06-06 06-06-06 06-06-06
6:22 7:03 8:23 7:14 7:14 6:39 6:39 6:39 6:42 6:42 6:42 6:34 6:34 6:34 6:59 6:59 6:29 6:29 6:38 6:38 6:38 6:38 7:16 7:16 7:17 7:17 7:03 7:03 7:03
1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB P SCABBING RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB P SCABBING RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 39
-372-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25719 F 0.1 MG/KG/DAY 25719 F 0.1 MG/KG/DAY
BODY/INTEGUMENT EYES/EARS/NOSE
06-06-06 06-07-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-17-06 06-17-06 06-18-06 06-18-06 06-14-06 06-15-06 06-16-06
7:03 7:07 7:07 7:07 7:14 7:14 7:15 7:15 8:14 8:14 8:05 8:05 7:27 7:27 6:26 6:26 6:26 6:26 6:33 6:33 6:24 6:24 6:18 6:18 6:09 6:09 6:27 6:33 6:24
P SCABBING RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 40
-373-
-374-
1 I--1 1o
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25719 F
MG/KG/DAY
25606 F 0.3 MG/KG/DAY 25606 F 0.3 MG/KG/DAY
25614 F 0.3 MG/KG/DAY 25671 F 0.3 MG/KG/DAY 25671 F 0.3 MG/KG/DAY
25671 F 0.3 MG/KG/DAY
25698 F 0.3 MG/KG/DAY 25698 F 0.3 MG/KG/DAY
EYES/EARS/NOSE
DISPOSITION EYES/EARS/NOSE
DISPOSITION DISPOSITION BODY/INTEGUMENT
EYES/EARS/NOSE
DISPOSITION BODY/INTEGUMENT
06-17-06 06-18-06 06-14-06 05-13-06 06-06-06 06-06-06 06-13-06 06-14-06 06-13-06 05-16-06 05-26-06 06-09-06 06-13-06 06-14-06 05-04-06 05-05-06 05-06-06 05-07-06 05-09-06 05-10-06 05-11-06 05-12-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06 05-16-06
6:18 6:09 6:54 9:39 7:04 7:04 6:27 6:54 6:53 8:39 8:44 7:16 6:27 6:54 7:35 7:56 8:10 8:11 8:18 6:51 6:58 6:57 9:40 9:26 9:26 7:05 7:05 8:39 8:39
1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND LEFT EYE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 41
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-17-06 05-18-06 05-18-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06
7:21 7:21 7:53 7:53 7:07 7:07 7:12 7:12 7:31 7:32 8:10 8:10 7:33 7:33 7:14 7:14 8:44 8:44 8:58 8:58 7:32 7:32 7:04 7:04 6:42 6:42 6:45 6:45 6:36
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 42
-375-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25698 F 0.3 MG/KG/DAY
25609 F 0.3 MG/KG/DAY 25677 F 0.3 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION DISPOSITION
06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-14-06
6:36 7:02 7:02 6:32 6:32 6:39 6:39 7:18 7:18 7:05 7:05 7:12 7:12 7:16 7:16 7:18 7:18 8:19 8:19 8:12 8:12 7:29 7:29 6:28 6:28 6:29 6:29 6:58 6:54
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 43
-376-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25677 F 0.3 MG/KG/DAY 25623 F 0.3 MG/KG/DAY 25623 F 0.3 MG/KG/DAY 25653 F 0.3 MG/KG/DAY 25653 F 0.3 MG/KG/DAY
EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT
06-08-06 7 17 06-15-06 6 58 06-14-06 6 31 06-15-06 6 59 05-16-06 8 40 05-17-06 7 22 05-19-06 6 58 05-20-06 7 07 05-21-06 7 15 05-22-06 7 33 05-23-06 8 12 05-24-06 7 34 05-25-06 7 56 05-26-06 8 46 05-26-06 8 46 05-27-06 8 58 05-29-06 7 08 05- 30-06 6 43 06- 04-06 6 42 06-05-06 7 19 06-06-06 7 06 06-07-06 7 15 06-08-06 7 19 06-09-06 7 19 06-10-06 8 21 06-11-06 8 15 06-12-06 7 30 06-13-06 6 30 06-14-06 6 31
1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 44
-LL-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25653 F 0.3 MG/KG/DAY 25604 F 0.3 MG/KG/DAY 25604 F 0.3 MG/KG/DAY
25604 F 0.3 MG/KG/DAY
BODY/INTEGUMENT DISPOSITION BODY/INTEGUMENT
EYES/EARS/NOSE
06-15-06 06-14-06 05-20-06 05-20-06 05-21-06 05-22-06 05-22-06 05-23-06 05-24-06 05-24-06 05-25-06 05-26-06 05-30-06 06-02-06 06-02-06 06-04-06 06-05-06 06-06-06 06-07-06 06-08-06 06-09-06 06-10-06 06-11-06 06-12-06 06-13-06 06-14-06 06-14-06 06-12-06 06-14-06
6:36 6:54 7:08 7:08 7:16 7:33 7:33 8:13 7:34 7:34 7:15 8:47 6:43 7:05 7:05 6:42 7:20 7:06 7:15 7:19 7:20 8:21 8:16 7:30 6:30 6:32 6:32 7:30 6:32
1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 45
-378-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25678 F 0.3 MG/KG/DAY 25684 F 0.3 MG/KG/DAY 25684 F 0.3 MG/KG/DAY
DISPOSITION DISPOSITION BODY/INTEGUMENT
06-14-06 06-15-06 05-04-06 05-04-06 05-05-06 05-05-06 05-06-06 05-06-06 05-07-06 05-07-06 05-08-06 05-08-06 05-03-06 05-03-06 05-09-06 05-09-06 05-10-06 05-10-06 05-11-06 05-11-06 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06
6:54 6:59 7:37 7:37 7:57 7:57 8:12 8:12 8:12 8:12 7:01 7:01 9:38 9:38 8:22 8:22 6:53 6:53 7:01 7:01 7:01 7:01 9:42 9:42 9:27 9:27 7:09 7:09 8:41
P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 46
-379-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-17-06 05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06
8:41 7:24 7:24 7:59 7:59 6:59 6:59 7:08 7:08 7:17 7:17 7:17 7:34 7:34 8:14 8:14 7:35 7:35 7:56 7:56 8:48 8:48 9:00 9:00 7:36 7:36 7:10 7:10 6:43
2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 47
-380-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06
6:43 6:52 6:52 6:43 6:43 7:06 7:06 6:37 6:37 6:43 6:43 7:20 7:20 7:07 7:07 7:17 7:17 7:20 7:20 7:20 7:20 8:23 8:23 8:16 8:17 7:31 7:31 6:31 6:31
2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 48
-381-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25684 F 0.3 MG/KG/DAY
25684 F 0.3 MG/KG/DAY
25684 F 0.3 MG/KG/DAY 25714 F 0.3 MG/KG/DAY 25650 F 0.3 MG/KG/DAY 25650 F 0.3 MG/KG/DAY
BODY/INTEGUMENT
EYES/EARS/NOSE
ORAL/DENTAL DISPOSITION DISPOSITION EYES/EARS/NOSE
06-14-06 06-14-06 06-15-06 06-15-06 06-06-06 06-07-06 06-08-06 06-09-06 06-10-06 06-12-06 06-13-06 06-14-06 06-15-06 06-14-06 06-16-06 06-16-06 05-31-06 06-02-06 06-03-06 06-04-06 06-05-06 06-06-06 06-07-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06
6:33 6:33 6:37 6:37 7:07 7:17 7:20 7:20 8:23 7:31 6:31 6:33 6:37 6:34 6:45 6:45 6:54 7:08 6:38 6:44 7:22 7:08 7:18 7:21 7:21 7:21 8:24 8:24 8:18
2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 2 DRIED RED MATERIAL AROUND NOSE 2 DRIED RED MATERIAL AROUND NOSE 2 DRIED RED MATERIAL AROUND NOSE 2 DRIED RED MATERIAL AROUND NOSE 1 WET YELLOW MATERIAL AROUND MOUTH P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 2 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 49
-382-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25650 F 0.3 MG/KG/DAY
25735 F 0.3 MG/KG/DAY 25735 F 0.3 MG/KG/DAY 25722 F 0.3 MG/KG/DAY 25642 F 0.3 MG/KG/DAY 25642 F 0.3 MG/KG/DAY
25642 F 0.3 MG/KG/DAY
EYES/EARS/NOSE
DISPOSITION BODY/INTEGUMENT DISPOSITION DISPOSITION BODY/INTEGUMENT
EYES/EARS/NOSE
06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-16-06 05-17-06 05-18-06 06-16-06 06-16-06 06-06-06 06-07-06 06-08-06 06-09-06 06-10-06 06-11-06 06-12-06 06-13-06 06-14-06 06-14-06 06-15-06 06-16-06 05-31-06
8:18 7:33 7:33 6:31 6:32 6:35 6:35 6:38 6:38 6:26 6:26 6:45 7:25 8:01 6:45 6:45 7:10 7:19 7:24 7:26 8:26 8:21 7:37 6:34 6:36 6:36 6:40 6:29 6:55
1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA P SCABBING FACIAL AREA 2 HAIR LOSS FACIAL AREA 2 HAIR LOSS FACIAL AREA 3 DRIED RED MATERIAL AROUND RIGHT EYE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 50
-383-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-04-06 06-05-06 06-05-06 06-05-06 06-05-06 06-06-06 06-06-06 06-06-06 06-06-06 06-07-06 06-07-06 06-07-06 06-07-06 06-08-06 06-08-06 06-08-06 06-08-06 06-09-06 06-09-06 06-09-06 06-09-06 06-10-06
6:45 7:11 7:12 6:39 6:39 6:45 6:45 6:46 7:24 7:24 7:24 7:24 7:09 7:09 7:09 7:09 7:19 7:19 7:19 7:19 7:23 7:23 7:23 7:23 7:24 7:24 7:24 7:24 8:25
3 DRIED RED MATERIAL AROUND RIGHT EYE 2 DRIED RED MATERIAL AROUND RIGHT EYE P EXOPHTHALMUS RIGHT EYE 3 DRIED RED MATERIAL AROUND RIGHT EYE P EXOPHTHALMUS RIGHT EYE 2 DRIED RED MATERIAL AROUND RIGHT EYE P EXOPHTHALMUS RIGHT EYE 2 HAIR LOSS AROUND RIGHT EYE 3 DRIED RED MATERIAL AROUND RIGHT EYE P EXOPHTHALMUS RIGHT EYE 2 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 3 DRIED RED MATERIAL AROUND RIGHT EYE P EXOPHTHALMUS RIGHT EYE 2 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 3 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY RIGHT EYE P EXOPHTHALMUS RIGHT EYE 2 HAIR LOSS AROUND RIGHT EYE 3 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY RIGHT EYE P EXOPHTHALMUS RIGHT EYE 2 HAIR LOSS AROUND RIGHT EYE 3 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY RIGHT EYE P EXOPHTHALMUS RIGHT EYE 3 HAIR LOSS AROUND RIGHT EYE 1 DRIED RED MATERIAL AROUND RIGHT EYE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 51
-384-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25642 F 0.3 MG/KG/DAY
25628 F 0.3 MG/KG/DAY 25628 F 0.3 MG/KG/DAY
EYES/EARS/NOSE
DISPOSITION BODY/INTEGUMENT
06-10-06 06-10-06 06-10-06 06-11-06 06-11-06 06-11-06 06-11-06 06-12-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-16-06 05-14-06 05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06
8:25 8:25 8:26 8:20 8:20 8:20 8:20 7:36 7:36 7:36 6:33 6:34 6:35 6:36 6:39 6:39 6:28 6:29 6:45 9:29 7:26 8:02 8:02 7:04 7:04 7:09 7:09 7:19 7:19
P OPACITY RIGHT EYE P EXOPHTHALMUS RIGHT EYE 3 HAIR LOSS AROUND RIGHT EYE 1 DRIED RED MATERIAL AROUND RIGHT EYE P EXOPHTHALMUS RIGHT EYE P OPACITY RIGHT EYE 3 HAIR LOSS AROUND RIGHT EYE 1 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY RIGHT EYE 3 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 3 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 3 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 3 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 3 HAIR LOSS AROUND RIGHT EYE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 52
-385-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25628 F 0.3 MG/KG/DAY 25628 F 0.3 MG/KG/DAY
BODY/INTEGUMENT EYES/EARS/NOSE
05-22-06 05-22-06 05-23-06 05-23-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-30-06 05-30-06 06-06-06 06-07-06 06-08-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 05-31-06
7:38 7:38 8:15 8:15 7:57 7:57 9:21 9:21 9:04 9:04 7:38 7:38 6:48 6:48 7:11 7:20 7:25 8:21 7:40 7:40 6:34 6:34 6:37 6:37 6:40 6:40 6:30 6:30 6:56
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 DRIED RED MATERIAL AROUND RIGHT EYE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 53
-386-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25628 F 0.3 MG/KG/DAY
25763 F 0.3 MG/KG/DAY 25766 F 0.3 MG/KG/DAY 25766 F 0.3 MG/KG/DAY 25689 F 0.3 MG/KG/DAY 25708 F 0.3 MG/KG/DAY
EYES/EARS/NOSE
DISPOSITION DISPOSITION EYES/EARS/NOSE DISPOSITION DISPOSITION
06-01-06 06-02-06 06-03-06 06-04-06 06-05-06 06-06-06 06-07-06 06-08-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 05-30-06 06-17-06 06-16-06 06-12-06 06-17-06 06-17-06
6:48 7:14 6:39 6:47 7:26 7:11 7:20 7:24 7:28 8:27 8:27 8:21 8:21 7:41 7:41 6:35 6:35 6:36 6:36 6:40 6:40 6:30 6:30 10:37 6:31 6:45 7:42 6:31 6:31
2 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P OPACITY RIGHT EYE 1 HAIR LOSS AROUND RIGHT EYE P EXOPHTHALMUS RIGHT EYE P SCHEDULED EUTHANASIA; :LACTATION DAY 21 P SCHEDULED EUTHANASIA; :LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; :LACTATION DAY 21 P SCHEDULED EUTHANASIA; :LACTATION DAY 21
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 54
-387-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25743 25743 25761 25761 25712 25746 25746 25696 25686 25686 25639 25639
F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
DISPOSITION EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE DISPOSITION DISPOSITION EYES/EARS/NOSE DISPOSITION DISPOSITION EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT
06-17-06 06-15-06 06-18-06 05-06-06 06-19-06 06-19-06 06-16-06 06-14-06 06-14-06 06-08-06 06-15-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06
6:31 6:42 6:16 7:45 7:04 7:04 6:34 6:54 6:54 7:29 6:59 7:22 7:22 7:42 7:42 8:20 8:20 7:42 7:42 8:03 8:03 8:50 8:50 9:06 9:06 7:43 7:43 7:17 7:17
P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 WET RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 55
-388-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-10-06 06-11-06 06-11-06 06-11-06 06-12-06
6:53 6:53 7:05 7:05 6:55 6:55 7:24 7:24 6:45 6:45 6:50 6:50 7:32 7:32 7:16 7:17 7:25 7:25 7:30 7:30 7:32 7:32 8:33 8:33 8:33 8:25 8:25 8:25 7:46
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB P SCABBING RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB P SCABBING RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 56
-389-
-390-
1o 1 I-- 1
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25639 F
MG/KG/DAY
25658 25676 25600 25600
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-15-06 06-15-06 06-15-06 05-21-06 05-23-06 05-25-06 05-26-06 05-27-06 05-28-06 05-29-06 05-30-06 05-30-06 06-01-06 06-02-06 06-03-06 06-04-06 06-05-06 06-06-06 06-07-06 06-08-06 06-09-06 06-10-06
7:46 6:42 6:42 6:42 6:42 6:44 6:44 6:59 6:59 6:59 7:24 8:22 8:04 8:52 9:07 7:43 7:19 6:54 6:54 6:58 7:25 6:46 6:53 7:33 7:17 7:26 7:32 7:33 8:34
2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 57
-391-
1o 1 I-- 1
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25600 F
MG/KG/DAY
25600 F 1.0 MG/KG/DAY
25603 25630 25630
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
BODY/INTEGUMENT
EYES/EARS/NOSE DISPOSITION DISPOSITION BODY/INTEGUMENT
06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-05-06 06-07-06 06-08-06 06-15-06 06-14-06 05-06-06 05-06-06 05-07-06 05-07-06 05-08-06 05-08-06 05-03-06 05-03-06 05-09-06 05-09-06 05-10-06 05-10-06 05-11-06
8:34 8:28 8:28 7:47 7:47 6:44 6:44 6:42 6:42 6:47 6:47 7:33 7:26 7:32 6:59 6:54 8:17 8:17 8:18 8:18 7:10 7:10 9:29 9:29 8:31 8:31 7:04 7:04 7:08
1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 58
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06 05-16-06 05-17-06 05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06
7:08 7:11 7:11 9:52 9:52 9:35 9:35 7:25 7:25 8:51 8:51 7:35 7:35 8:11 8:11 7:10 7:10 7:14 7:14 7:26 7:26 7:43 7:43 8:23 8:23 7:43 7:43 7:18 7:18
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 59
-392-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06
8:54 8:54 9:08 9:08 7:44 7:44 7:20 7:20 6:54 6:54 7:07 7:07 7:00 7:00 7:26 7:26 6:47 6:47 6:55 6:55 7:33 7:33 7:18 7:18 7:26 7:26 7:34 7:34 7:34
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 60
-393-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25630 F 1.0 MG/KG/DAY
25703 25673 25611 25619 25705 25705
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-14-06 06-16-06 06-16-06 06-15-06 05-18-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06
7:34 8:35 8:35 8:29 8:29 7:48 7:48 6:44 6:44 6:43 6:43 6:59 6:55 6:45 6:45 7:00 8:13 7:13 7:15 7:15 7:28 7:28 7:46 7:46 8:25 8:25 7:45 7:45 8:05
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 61
-394-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-01-06 06-01-06 06-02-06 06-02-06 06-03-06 06-03-06 06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06
8:05 8:56 8:56 9:10 9:10 7:46 7:46 7:22 7:22 6:56 6:57 7:09 7:09 7:01 7:01 7:29 7:29 6:51 6:51 6:57 6:57 7:35 7:35 7:19 7:19 7:31 7:31 7:36 7:36
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 62
-395-
-396-
1o 1 I--1
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25705 F
MG/KG/DAY
25705 F 1.0 MG/KG/DAY
BODY/INTEGUMENT EYES/EARS/NOSE
06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-12-06 06-13-06 06-13-06 06-13-06 06-14-06 06-14-06 06-14-06 06-14-06 06-15-06 06-15-06 06-15-06 06-15-06 05-30-06 05-31-06 05-31-06 06-02-06 06-03-06 06-05-06 06-06-06 06-07-06 06-08-06
7:36 7:36 8:38 8:38 8:32 8:32 7:52 7:52 7:53 6:45 6:46 6:46 6:46 6:46 6:46 6:46 6:50 6:50 6:50 6:50 6:57 7:09 7:09 7:29 6:51 7:35 7:19 7:31 7:36
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING :FACIAL AREA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING FACIAL AREA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS FACIAL AREA P SCABBING FACIAL AREA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS FACIAL AREA P SCABBING FACIAL AREA 1 DRIED RED MATERIAL AROUND NOSE 2 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND RIGHT EYE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 63
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25705 F 1.0 MG/KG/DAY
25691 25691 25717 25717 25616 25616
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
25715 25757 25757
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
EYES/EARS/NOSE
DISPOSITION EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION BODY/INTEGUMENT
06-09-06 06-10-06 06-16-06 06-06-06 06-16-06 06-07-06 06-16-06 05-16-06 05-17-06 06-16-06 05-30-06 05-08-06 05-08-06 05-05-06 05-05-06 05-09-06 05-09-06 05-10-06 05-10-06 05-11-06 05-11-06 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-16-06 05-16-06
7:37 8:38 6:45 7:20 6:45 7:32 6:45 8:55 7:38 6:45 6:11 7:13 7:13 8:34 8:34 8:35 8:35 7:09 7:09 7:11 7:11 7:15 7:15 9:59 9:59 9:38 9:38 8:55 8:55
1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; POST-MATING DAY 25 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 64
-397-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-23-06 05-24-06 05-24-06 05-24-06 05-25-06 05-25-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06
7:39 7:39 8:15 8:15 7:16 7:16 7:17 7:17 7:29 7:29 7:50 7:50 8:27 8:27 8:27 7:47 7:47 7:47 8:07 8:07 9:26 9:26 8:26 8:26 7:15 7:15 6:40 6:40 6:10
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 65
-398-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25757 25762 25762 25599 25599 25647 25647 25747 25747
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
25744 25707 25707
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
BODY/INTEGUMENT DISPOSITION EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION BODY/INTEGUMENT
05-30-06 06-17-06 06-13-06 06-16-06 06-08-06 06-17-06 05-07-06 06-18-06 06-09-06
06-18-06 06-17-06 05-06-06 05-26-06 05-26-06 05-27-06 05-27-06 05-28-06 05-28-06 05-29-06 05-29-06 05-30-06 05-30-06 05-31-06 05-31-06 06-02-06 06-02-06 06-03-06 06-03-06
6:10 6:31 6:47 6:46 7:38 6:31 8:21 6:16 7:44
6:16 6:32 7:36 9:28 9:28 8:28 8:28 7:49 7:49 7:26 7:26 7:02 7:02 7:14 7:14 7:39 7:39 6:55 6:55
2 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SOFT MOVABLE MASS VENTRAL THORACIC AREA
17MM X 15MM X 15MM P SCHEDULED EUTHANASIA; LACTATION DAY 21 P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL VENTRAL ABDOMINAL AREA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 66
-399-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
1o 1 I--1
25707 F 25707 F
MG/KG/DAY MG/KG/DAY
BODY/INTEGUMENT EYES/EARS/NOSE
06-04-06 06-04-06 06-05-06 06-05-06 06-06-06 06-06-06 06-07-06 06-07-06 06-08-06 06-08-06 06-09-06 06-09-06 06-10-06 06-10-06 06-11-06 06-11-06 06-12-06 06-12-06 06-13-06 06-13-06 06-14-06 06-14-06 06-15-06 06-15-06 06-16-06 06-16-06 06-17-06 06-17-06 06-16-06
7:01 7:01 7:41 7:41 7:23 7:23 7:35 7:35 7:39 7:39 7:44 7:44 8:45 8:45 8:36 8:36 8:02 8:02 6:49 6:49 6:50 6:50 6:53 6:53 6:40 6:40 6:24 6:24 6:40
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE
O1
I--1 1
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE 67
-400-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 1 (F0 - DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 06-19-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25723 F 1.0 MG/KG/DAY 25723 F 1.0 MG/KG/DAY
DISPOSITION EYES/EARS/NOSE
06-19-06 06-08-06 06-09-06 06-12-06
7:04 7:39 7:45 8:02
P SCHEDULED EUTHANASIA; LACTATION DAY 21 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE
GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT
PAGE 68
PCRDv4.11 10/05/2006
-401-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 2 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]
PREGNANCY
STATUS
DAY 0
3
6
9 12 15 18 20 25
DAMS FROM GROUP 1:: 0 MG/KG/DAY
25597 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
G G G G G G G G G G G G G G G G G G G G G G G G G
243. 266. 275. 274. 273. 269. 267. 263. 262. 249. 238. 257. 262. 264. 280. 281. 287. 279. 263. 257. 246. 259. 277. 280. 277.
254. 276. 300. 282. 287. 295. 278. 286. 283. 273. 259. 276. 279. 294. 287. 297. 310. 298. 282. 284. 263. 270. 297. 283. 298.
271. 291. 324. 297. 301. 311. 284. 299. 298. 281. 270. 285. 293. 307. 310. 314. 322. 312. 293. 303. 274. 284. 308. 300. 303.
280. 304. 341. 314. 318. 327. 303. 317. 314. 295. 283. 300. 298. 319. 323. 324. 334. 318. 299. 323. 277. 296. 296. 319. 317.
295. 317. 354. 336. 337. 344. 319. 341. 327. 312. 300. 311. 312. 345. 349. 342. 356. 334. 326. 342. 296. 314. 338. 334. 335.
316. 347. 375. 346. 360. 365. 342. 365. 350. 326. 326. 337. 338. 369. 372. 362. 385. 357. 348. 365. 309. 337. 316. 358. 364.
361. 381. 412. 372. 397. 402. 382. 389. 388. 357. 372. 378. 373. 398. 414. 399. 432. 399. 378. 411. 333. 375. 396. 391. 405.
398. 410. 450. 392. 450. 435. 406. 415. 421. 388. 411. 410. 413. 447. 445. 424. 474. 423. 412. 451. 362. 399. 434. 425. 433.
NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA
MEAN S.D.
N
266. 12.8
25
284. 13.5
25
297. 14.8
25
310. 16.5
25
329. 17.6
25
349. 20.0
25
388. 21.0
25
421. 24.5
25
NA
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 1
-402-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 2 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]
PREGNANCY
STATUS
DAY 0
3
6
9 12 15 18 20 25
DAMS FROM GROUP 2:: 0.1 MG/KG/DAY
25664 25648 25694 25668 25631 25660 25704 25695 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
NG G G G G G G NG G G G G G G G G G G G G G G G G G
236. 255. 279. 277. 273. 268. 268. 266. 258. 257. 244. 257. 259. 272. 275. 281. 290. 282. 266. 257. 244. 266. 279. 278. 271.
253. 252. 299. 295. 286. 284. 274. 268. 265. 263. 262. 275. 271. 289. 290. 303. 301. 295. 288. 278. 257. 282. 286. 287. 289.
274. 283. 308. 308. 295. 293. 277. 265. 274. 270. 268. 287. 284. 306. 312. 320. 309. 305. 302. 281. 271. 301. 308. 300. 293.
278. 300. 329. 323. 315. 312. 296. 271. 287. 279. 287. 300. 298. 320. 317. 337. 323. 317. 312. 286. 282. 319. 323. 311. 305.
278. 322. 348. 349. 330. 332. 306. 278. 304. 296. 303. 316. 304. 328. 344. 354. 346. 332. 326. 302. 307. 342. 337. 331. 330.
287. 346. 378. 373. 349. 349. 331. 283. 320. 305. 322. 340. 324. 365. 360. 388. 363. 355. 353. 319. 321. 364. 363. 351. 348.
290. 391. 422. 415. 391. 395. 372. 282. 356. 351. 364. 383. 356. 407. 407. 427. 410. 392. 394. 342. 365. 410. 401. 385. 391.
295. 436. 449. 454. 420. 426. 413. 283. 379. 371. 389. 415. 377. 439. 431. 459. 457. 434. 425. 360. 403. 449. 444. 424. 425.
291. NA NA NA NA NA NA
286. NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA
MEAN S.D.
N
268. 12.1
23
281. 14.3
23
294. 15.3
23
308. 16.1
23
326. 17.7
23
347. 21.5
23
388. 23.7
23
421. 28.7
23
NA
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 2
-403-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 2 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]
PREGNANCY
STATUS
DAY 0
3
6
9 12 15 18 20 25
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25606 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
G G G G G G G G G G G G G G G G G G G G G G G G G
246. 265. 292. 277. 271. 269. 267. 265. 262. 252. 248. 259. 261. 271. 273. 290. 284. 274. 263. 262. 242. 267. 276. 277. 273.
263. 280. 308. 283. 291. 273. 277. 277. 274. 269. 263. 283. 276. 285. 281. 305. 298. 292. 287. 281. 259. 275. 281. 285. 298.
274. 296. 319. 295. 305. 288. 287. 286. 286. 279. 274. 291. 287. 296. 296. 319. 303. 301. 297. 292. 278. 293. 300. 291. 313.
281. 305. 335. 311. 320. 304. 283. 301. 297. 293. 290. 305. 298. 306. 302. 329. 310. 313. 308. 302. 295. 308. 311. 305. 332.
290. 330. 352. 339. 334. 319. 295. 320. 317. 309. 312. 327. 318. 324. 323. 345. 331. 340. 329. 327. 324. 325. 322. 322. 352.
310. 354. 372. 365. 353. 331. 308. 332. 334. 328. 316. 336. 343. 347. 342. 363. 352. 360. 343. 345. 344. 356. 352. 347. 376.
350. 405. 412. 405. 398. 370. 343. 365. 366. 372. 354. 374. 394. 376. 380. 412. 383. 402. 380. 384. 383. 402. 380. 389. 433.
379. 441. 454. 435. 423. 399. 373. 396. 391. 399. 376. 416. 432. 407. 415. 446. 420. 447. 400. 412. 418. 431. 423. 425. 473.
NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA
MEAN S.D.
N
267. 12.4
25
282. 12.3
25
294. 12.1
25
306. 13.3
25
325. 14.7
25
344. 17.5
25
384. 21.2
25
417. 25.0
25
NA
= GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 3
-404-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 2 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]
PREGNANCY
STATUS
DAY 0
3
6
9 12 15 18 20 25
DAMS FROM GROUP 4:: 1.0 MG/KG/DAY
25696 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25757 25762 25599 25647 25747 25744 25707 25723
G G G G G G G G G G G G G G G G G NG G G G G G G G
237. 254. 286. 274. 273. 268. 267. 263. 257. 250. 250. 256. 261. 267. 277. 282. 287. 273. 269. 259. 255. 267. 272. 285. 272.
259. 273. 297. 292. 285. 276. 275. 278. 268. 263. 264. 266. 278. 288. 291. 304. 304. 280. 289. 277. 269. 282. 279. 288. 275.
273. 284. 307. 298. 300. 292. 284. 287. 276. 271. 271. 276. 294. 302. 295. 313. 313. 283. 297. 289. 282. 304. 297. 299. 283.
283. 292. 325. 312. 313. 305. 291. 298. 297. 286. 273. 279. 301. 309. 302. 316. 321. 286. 308. 296. 286. 312. 302. 299. 292.
297. 300. 343. 335. 329. 323. 303. 312. 310. 302. 286. 288. 318. 325. 321. 335. 342. 300. 323. 315. 308. 326. 317. 322. 317.
316. 322. 351. 354. 345. 346. 315. 329. 329. 315. 306. 302. 337. 350. 347. 359. 367. 302. 335. 337. 326. 344. 336. 335. 349.
362. 358. 396. 387. 389. 389. 351. 369. 377. 355. 343. 311. 369. 386. 379. 397. 414. 298. 374. 373. 364. 383. 379. 375. 391.
395. 368. 428. 405. 423. 430. 373. 404. 414. 386. 374. 369. 399. 421. 413. 431. 459. 304. 415. 416. 388. 417. 401. 405. 433.
NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 315. NA NA NA NA NA NA NA
MEAN S.D.
N
266. 12.6
24
280. 12.4
24
291. 12.6
24
300. 13.3
24
317. 15.3
24
336. 16.8
24
374. 21.0
24
407. 22.8
24
NA
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 4
PGBWv4.05 01/23/2007
-405-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 3 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]
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 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
G G G G G G G G G G G G G G G G G G G G G G G G G
11. 17.
9. 15. 21. 45. 37. NA 155.
10. 15. 13. 13. 30. 34. 29. NA 144.
25. 24. 17. 13. 21. 37. 38. NA 175.
8. 15. 17. 22. 10. 26. 20. NA 118.
14. 14. 17. 19. 23. 37. 53. NA 177.
26. 16. 16. 17. 21. 37. 33. NA 166.
11. 6. 19. 16. 23. 40. 24. NA 139.
23. 13. 18. 24. 24. 24. 26. NA 152.
21. 15. 16. 13. 23. 38. 33. NA 159.
24. 8. 14. 17. 14. 31. 31. NA 139.
21. 11. 13. 17. 26. 46. 39. NA 173.
19. 9. 15. 11. 26. 41. 32. NA 153.
17. 14.
5. 14. 26. 35. 40. NA 151.
30. 13. 12. 26. 24. 29. 49. NA 183.
7. 23. 13. 26. 23. 42. 31. NA 165.
16. 17. 10. 18. 20. 37. 25. NA 143.
23. 12. 12. 22. 29. 47. 42. NA 187.
19. 14.
6. 16. 23. 42. 24. NA 144.
19. 11.
6. 27. 22. 30. 34. NA 149.
27. 19. 20. 19. 23. 46. 40. NA 194.
17. 11.
3. 19. 13. 24. 29. NA 116.
11. 14. 12. 18. 23. 38. 24. NA 140.
20. 11. -12. 42. -22. 80. 38. NA 157.
3. 17. 19. 15. 24. 33. 34. NA 145.
21. 5. 14. 18. 29. 41. 28. NA 156.
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
PAGE 1
-406-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 3 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]
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 25648 25694 25668 25631 25660 25704 25695 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
NG G G G G G G NG G G G G G G G G G G G G G G G G G
17. 21. 4. 0. 9. 3. 5. -4. 59.
-3. 31. 17. 22. 24. 45. 45. NA 181.
20. 9. 21. 19. 30. 44. 27. NA 170.
18. 13. 15. 26. 24. 42. 39. NA 177.
13. 9. 20. 15. 19. 42. 29. NA 147.
16. 9. 19. 20. 17. 46. 31. NA 158.
6. 3. 19. 10. 25. 41. 41. NA 145.
2. -3. 6. 7. 5. -1. 1. 3. 17.
7. 9. 13. 17. 16. 36. 23. NA 121.
6. 7. 9. 17. 9. 46. 20. NA 114.
18. 6. 19. 16. 19. 42. 25. NA 145.
18. 12. 13. 16. 24. 43. 32. NA 158.
12. 13. 14.
6. 20. 32. 21. NA 118.
17. 17. 14.
8. 37. 42. 32. NA 167.
15. 22.
5. 27. 16. 47. 24. NA 156.
22. 17. 17. 17. 34. 39. 32. NA 178.
11. 8. 14. 23. 17. 47. 47. NA 167.
13. 10. 12. 15. 23. 37. 42. NA 152.
22. 14. 10. 14. 27. 41. 31. NA 159.
21. 3. 5. 16. 17. 23. 18. NA 103.
13. 14. 11. 25. 14. 44. 38. NA 159.
16. 19. 18. 23. 22. 46. 39. NA 183.
7. 22. 15. 14. 26. 38. 43. NA 165.
9. 13. 11. 20. 20. 34. 39. NA 146.
18. 4. 12. 25. 18. 43. 34. NA 154.
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
PAGE 2
-407-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 3 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]
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 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
G G G G G G G G G G G G G G G G G G G G G G G G G
17. 11. 7. 9. 20. 40. 29. NA 133.
15. 16.
9. 25. 24. 51. 36. NA 176.
16. 11. 16. 17. 20. 40. 42. NA 162.
6. 12. 16. 28. 26. 40. 30. NA 158.
20. 14. 15. 14. 19. 45. 25. NA 152.
4. 15. 16. 15. 12. 39. 29. NA 130.
10. 10. -4. 12. 13. 35. 30. NA 106.
12. 9. 15. 19. 12. 33. 31. NA 131.
12. 12. 11. 20. 17. 32. 25. NA 129.
17. 10. 14. 16. 19. 44. 27. NA 147.
15. 11. 16. 22.
4. 38. 22. NA 128.
24. 8. 14. 22. 9. 38. 42. NA 157.
15. 11. 11. 20. 25. 51. 38. NA 171.
14. 11. 10. 18. 23. 29. 31. NA 136.
8. 15.
6. 21. 19. 38. 35. NA 142.
15. 14. 10. 16. 18. 49. 34. NA 156.
14. 5. 7. 21. 21. 31. 37. NA 136.
18. 9. 12. 27. 20. 42. 45. NA 173.
24. 10. 11. 21. 14. 37. 20. NA 137.
19. 11. 10. 25. 18. 39. 28. NA 150.
17. 19. 17. 29. 20. 39. 35. NA 176.
8. 18. 15. 17. 31. 46. 29. NA 164.
5. 19. 11. 11. 30. 28. 43. NA 147.
8. 6. 14. 17. 25. 42. 36. NA 148.
25. 15. 19. 20. 24. 57. 40. NA 200.
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
PAGE 3
-408-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 3 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]
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 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25757 25762 25599 25647 25747 25744 25707 25723
G G G G G G G G G G G G G G G G G NG G G G G G G G
22. 14. 10. 14. 19. 46. 33. NA 158.
19. 11. 8. 8. 22. 36. 10. NA 114.
11. 10. 18. 18.
8. 45. 32. NA 142.
18. 6. 14. 23. 19. 33. 18. NA 131.
12. 15. 13. 16. 16. 44. 34. NA 150.
8. 16. 13. 18. 23. 43. 41. NA 162.
8. 9. 7. 12. 12. 36. 22. NA 106.
15. 9. 11. 14. 17. 40. 35. NA 141.
11. 8. 21. 13. 19. 48. 37. NA 157.
13. 8. 15. 16. 13. 40. 31. NA 136.
14. 7. 2. 13. 20. 37. 31. NA 124.
10. 10. 3. 9. 14. 9. 58. NA 113.
17. 16.
7. 17. 19. 32. 30. NA 138.
21. 14.
7. 16. 25. 36. 35. NA 154.
14. 4. 7. 19. 26. 32. 34. NA 136.
22. 9. 3. 19. 24. 38. 34. NA 149.
17. 9. 8. 21. 25. 47. 45. NA 172.
7. 3. 3. 14. 2. -4. 6. 11. 31.
20. 8. 11. 15. 12. 39. 41. NA 146.
18. 12.
7. 19. 22. 36. 43. NA 157.
14. 13.
4. 22. 18. 38. 24. NA 133.
15. 22.
8. 14. 18. 39. 34. NA 150.
7. 18.
5. 15. 19. 43. 22. NA 129.
3. 11.
0. 23. 13. 40. 30. NA 120.
3. 8. 9. 25. 32. 42. 42. NA 161.
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
= GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 4
PGBWv4.05 01/23/2007
-409-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 4 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
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 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
G G G G G G G G G G G G G G G G G G G G G G G G G
19. 22. 22. 26. NA NA 29. 23.
22. 23. 25. 26. NA NA NA NA
26. 31. 28. 31. 26. 26. 30. 28.
20. 26. 27. 29. 27. 31. 34. 27.
23. 24. 24. 26. 26. 29. 33. 26.
21. 23. 23. 23. 24. 29. 29. 24.
21. 21. 23. NA
22. 26. 26. 23.
23. 25. 24. 25. 26. 25. 27. 25.
21. 23. 25. 23. 25. 28. 28. 24.
20. 24. 24. 24. 23. NA
29. 24.
17. 19. 21. 22. 23. 28. 28. 22.
19. 22. 25. 22. 27. 29. 27. 24.
21. 22. 23. 21. 22. 27. 26. 23.
20. 23. 25. 25. 27. 25. 31. 25.
18. 20. 23. 23. 25. 28. 29. 24.
18. 21. 25. 24. 28. 31. 29. 25.
21. 23. 24. 27. 28. 33. 25. 26.
23. 25. 25. 25. 26. 33. 30. 26.
22. 22. 23. 24. 25. 28. 27. 24.
22. 24. 28. 26. 26. 31. 28. 26.
19. 20. 20. NA NA 21. NA NA
19. 21. 22. 24. 26. 27. 27. 24.
21. 22. 22. 26. 22. NA
28. 23.
17. 27. 26. 29. 29. 28. 28. 26.
21. 24. 23. 23. 26. 28. 23. 24.
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
PAGE 1
-410-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 4 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
PREGNANCY STATUS DAY 0- 3
3- 6
6- 9
9-12
12-15
15-18
18-20
0-2
DAMS FROM GROUP 2:: 0.1 MG/KG/DAY
25664 25648 25694 25668 25631 25660 25704 25695 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
NG G G G G G G NG G G G G G G G G G G G G G G G G G
17. 22. 18. 22. 20. 21. 21. 20
13. 23. 22. 26. 28. NA
35. 24
23. 25. 27. 27. 30. 32. 32. 28
21. 24. 25. 20. 28. NA
32. 25
20. 23. 23. 24. 26. 30. 27. 25
20. 24. 24. 25. 24. 29. 30. 25
21. 20. 22. 23. 25. 28. 32. 24
16. 17. 18. 17. 18. 21. 18. 18
18. 20. 20. 21. 23. 25. 24. 22
18. 19. 19. 21. 21. 28. 25. 21
19. NA
22. NA
24. 27. 27. 23
22. 24. 24. NA
26. 30. 25. 25
18. 19. 21. 22. 25. 27. 23. 22
20. 22. 25. 22. 27. 27. 27. 24
20. 23. 24. 25. 26. 32. 27. 25
22. 25. 28. 29. 31. 34. 28. 28
21. 23. 24. NA
25. 28. 33. 25
22. 23. 25. 24. 28. 28. 29. 25
21. 22. 24. 21. 27. 30. 27. 25
19. 18. 20. 24. 22. 27. 23. 22
17. 21. 21. 22. 25. 25. 26. 22
21. 22. 24. 24. 26. 29. 31. 25
19. 24. 25. 24. 25. 27. 30. 25
18. 21. 22. 25. 25. 21. 21. 22
25. 25. 23. 29. 29. 30. 30. 27
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.
23 22 23 20 23 21 23 2 :
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 2
-411-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 4 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
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 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
G G G G G G G G G G G G G G G G G G G G G G G G G
19. 20. 19. 21. 21. 24. 24. 21.
19. 22. 21. 26. 26. 31. 31. 25.
23. 24. 25. 29. 26. 30. 34. 27.
20. 22. 23. 24. 28. 30. 31. 25.
23. 25. 24. 25. 26. 31. 29. 26.
18. 21. 23. 23. 24. 27. 26. 23.
19. 21. 17. 19. 22. NA
25. 20.
19. 21. 22. 23. 24. 26. 27. 23.
19. 20. 20. 23. 23. 25. 23. 22.
20. 21. 21. 21. 23. 28. 26. 23.
19. 23. 23. NA
20. NA
29. 22.
20. 22. 24. 26. 24. 28. 31. 25.
20. 22. 22. NA NA 29. 29. 24.
19. 20. 22. 23. 24. 24. 28. 23.
21. 22. 23. 24. 25. 26. 30. 24.
22. 24. 26. NA
29. 35. 32. 28.
20. 21. 22. 24. 24. 24. 16. 22.
22. NA
24. NA
25. NA
29. 25.
19. 22. 24. 26. 25. 30. 21. 24.
21. 25. 25. NA NA 29. 28. 25.
19. 21. 24. 25. 26. 28. 29. 24.
18. 21. 21. 22. 27. 26. 25. 23.
19. 24. 23. 24. 27. 27. 30. 25.
21. 24. 25. 24. 26. 27. 26. 25.
NA 29. NA NA 29. 35. 32. NA
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
PAGE 3
-412-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 4 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
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 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25757 25762 25599 25647 25747 25744 25707 25723
G G G G G G G G G G G G G G G G G NG G G G G G G G
22. 23. 22. 24. NA
27. 26. 24.
21. 22. 22. 23. 23. 23. 20. 22.
19. 21. 23. 22. 21. 28. 28. 23.
21. 24. 23. 26. 27. 27. 21. 24.
21. 23. 23. 24. 24. 26. 30. 24.
19. 22. 21. 23. 25. 28. 29. 24.
17. 22. 21. 19. 25. 26. 25. 22.
21. 22. 21. NA
24. 28. 32. 24.
19. 21. 22. 23. 24. 29. 29. 24.
19. 21. 21. 20. 21. 22. 26. 21.
18. 19. 19. 19. 20. 22. 24. 20.
18. 21. 20. 19. 19. 22. 26. 20.
20. 22. 22. 21. 26. 25. 27. 23.
18. 21. 21. 22. 26. 26. 31. 23.
21. 20. 23. 23. 26. 30. 29. 25.
23. 23. 24. 23. 23. 27. 26. 24.
22. 24. 26. 25. NA NA 30. 25.
19. 20. 21. 22. 20. 20. 21. 20.
20. 21. 21. 21. 20. 22. 30. 22.
20. 25. 22. NA
23. NA
25. 23.
18. 20. 21. 22. 26. 27. 24. 23.
21. 24. 22. NA
22. NA
27. 23.
19. NA
22. 24. 23. 28. 27. 24.
21. 23. 21. 27. 27. NA
28. 24.
17. 21. 21. 27. 29. 28. 27. 24.
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
PAGE 4
PGFWv4.08 10/26/2006
-413-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 5 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
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 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
G G G G G G G G G G G G G G G G G G G G G G G G G
76. 84. 80. 90. NA NA 76. 76.
81. 81. 84. 84. NA NA NA NA
90. 99. 84. 89. 71. 66. 70. 79.
72. 90. 88. 89. 79. 86. 89. 83.
82. 82. 77. 79. 74. 77. 78. 76.
74. 76. 72. 68. 68. 76. 69. 70.
77. 75. 78. NA
66. 72. 66. 71.
84. 85. 78. 76. 74. 66. 67. 75.
77. 79. 82. 72. 74. 76. 69. 73.
77. 87. 83. 79. 72. NA
78. 77.
68. 72. 76. 75. 73. 80. 71. 72.
71. 78. 85. 72. 83. 81. 69. 75.
77. 77. 78. 69. 68. 76. 66. 72.
72. 76. 80. 75. 76. 65. 73. 73.
63. 67. 73. 68. 69. 71. 67. 69.
62. 69. 78. 72. 80. 81. 70. 73.
70. 73. 73. 78. 75. 81. 55. 72.
80. 82. 79. 77. 75. 87. 73. 76.
81. 76. 78. 77. 74. 77. 68. 74.
81. 82. 89. 78. 73. 80. 65. 76.
75. 74. 72. NA NA 65. NA NA
72. 76. 76. 79. 80. 76. 70. 76.
73. 73. 73. 82. 67. NA
67. 69.
60. 92. 84. 89. 84. 75. 69. 77.
73. 80. 74. 71. 74. 73. 55. 70.
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
PAGE 1
-414-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 5 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
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 25648 25694 25668 25631 25660 25704 25695 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
NG G G G G G G NG G G G G G G G G G G G G G G G G G
69. 83. 65. 79. 71. 73. 72. 73.
51. 86. 75. 84. 84. NA
85. 74.
80. 82. 85. 80. 83. 80. 73. 80.
73. 79. 79. 60. 78. NA
74. 72.
71. 79. 75. 74. 76. 81. 67. 75.
72. 83. 79. 78. 70. 78. 73. 75.
77. 72. 77. 76. 78. 80. 81. 76.
60. 64. 67. 62. 64. 74. 64. 65.
69. 74. 71. 71. 74. 74. 65. 72.
69. 71. 69. 73. 70. 85. 69. 70.
75. NA
79. NA
77. 79. 72. 75.
83. 85. 82. NA
79. 83. 63. 78.
68. 68. 72. 73. 80. 79. 63. 71.
71. 74. 80. 68. 78. 70. 64. 70.
71. 76. 76. 76. 74. 83. 64. 73.
75. 80. 85. 84. 84. 83. 63. 78.
71. 75. 76. NA
70. 72. 76. 71.
76. 77. 80. 74. 81. 75. 70. 74.
76. 75. 78. 66. 79. 80. 66. 75.
71. 64. 70. 82. 71. 82. 66. 73.
68. 80. 76. 75. 80. 73. 68. 72.
77. 75. 77. 73. 74. 75. 72. 73.
67. 81. 79. 73. 71. 71. 71. 73.
64. 71. 72. 78. 73. 57. 52. 66.
89. 86. 77. 91. 86. 81. 74. 81.
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
PAGE 2
-415-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 5 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
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 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
G G G G G G G G G G G G G G G G G G G G G G G G G
75. 74. 68. 73. 70. 73. 66. 70.
70. 76. 70. 82. 76. 82. 73. 75.
77. 76. 76. 84. 72. 77. 79. 76.
71. 76. 76. 74. 80. 78. 74. 74.
82. 84. 77. 76. 76. 82. 71. 77.
66. 75. 78. 74. 74. 77. 68. 72.
70. 74. 60. 66. 73. NA
70. 66.
70. 74. 75. 74. 74. 74. 71. 72.
71. 71. 68. 75. 71. 71. 61. 70.
77. 77. 73. 70. 72. 80. 67. 73.
74. 86. 82. NA
64. NA
79. 72.
74. 77. 81. 82. 72. 79. 78. 77.
74. 78. 75. NA NA 79. 70. 74.
68. 69. 73. 73. 71. 66. 71. 70.
76. 76. 77. 77. 75. 72. 75. 73.
74. 77. 80. NA
82. 90. 75. 80.
69. 70. 72. 75. 70. 65. 40. 66.
78. NA
78. NA
71. NA
68. 73.
69. 75. 79. 82. 74. 83. 54. 74.
77. 87. 84. NA NA 79. 70. 77.
76. 78. 84. 81. 78. 77. 72. 75.
66. 74. 70. 69. 79. 69. 60. 69.
68. 82. 75. 76. 80. 74. 75. 76.
75. 83. 84. 76. 78. 73. 64. 76.
NA 95. NA NA 80. 86. 71. NA
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
PAGE 3
-416-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 5 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
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 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25757 25762 25599 25647 25747 25744 25707 25723
G G G G G G G G G G G G G G G G G NG G G G G G G G
89. 86. 79. 83. NA
80. 69. 79.
80. 79. 76. 78. 74. 68. 55. 72.
65. 70. 73. 66. 61. 75. 68. 67.
74. 81. 75. 80. 78. 73. 53. 72.
75. 78. 75. 75. 71. 71. 74. 72.
70. 77. 70. 73. 75. 76. 71. 73.
63. 79. 73. 64. 81. 78. 69. 72.
77. 78. 72. NA
75. 80. 83. 75.
72. 77. 77. 76. 75. 82. 73. 76.
74. 79. 75. 68. 68. 66. 70. 69.
70. 71. 70. 68. 68. 68. 67. 68.
69. 77. 72. 67. 64. 72. 76. 68.
74. 77. 74. 68. 79. 71. 70. 72.
65. 71. 69. 69. 77. 71. 77. 69.
74. 68. 77. 74. 78. 83. 73. 76.
78. 74. 76. 71. 66. 71. 63. 70.
74. 78. 82. 75. NA NA 69. 71.
69. 71. 74. 75. 66. 67. 70. 69.
72. 72. 69. 66. 61. 62. 76. 67.
75. 88. 75. NA
71. NA
63. 72.
69. 72. 74. 74. 82. 78. 64. 74.
76. 82. 71. NA
66. NA
68. 70.
69. NA
73. 77. 70. 78. 69. 74.
73. 78. 70. 87. 82. NA
72. 74.
62. 75. 73. 89. 87. 76. 66. 73.
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
PAGE 4
PGFWv4.08 01/23/2007
-417-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 6 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING LACTATION [G]
DAY 1
4
DAMS FROM GROUP 1: 0 MG/KG/DAY
25597 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
272. 313. 342. 332. 323. 318. 319. 315. 316. 308. 301. 290. 303. 304. 341. 356. 342. 314. 315. 318. 288. 314. 328. 331. 324.
308. 325. 353. 348. 348. 364. 345. 341. 336. 337. 324. 305. 323. 354. 354. 359. 357. 351. 332. 345. 301. 327. 343. 338. 353.
MEAN S.D.
N
317. 18.6
25
339. 17.1
25
7
318. 349. 353. 350. 350. 366. 336. 351. 346. 325. 328. 311. 341. 357. 355. 379. 365. 351. 345. 356. 315. 343. 358. 356. 369.
347. 17.0
25
10
328. 347. 362. 359. 370. 385. 350. 366. 360. 349. 336. 331. 354. 365. 358. 398. 381. 369. 348. 367. 327. 353. 379. 362. 373.
359. 17.6
25
14
350. 349. 368. 367. 377. 404. 357. 364. 378. 345. 358. 340. 349. 389. 397. 411. 387. 382. 366. 377. 329. 360. 373. 369. 395.
370. 20.5
25
17
347. 350. 361. 350. 383. 397. 360. 357. 370. 353. 369. 333. 365. 394. 396. 403. 396. 377. 376. 371. 337. 361. 381. 373. 398.
370. 19.8
25
21
350. 341. 358. 374. 379. 389. 352. 384. 360. 334. 340. 332. 358. 381. 397. 411. 394. 362. 361. 364. 318. 348. 377. 370. 382.
365. 22.5
25
PAGE 1
-418-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 6 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING LACTATION [G]
DAY 1
4
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25648 25694 25668 25631 25660 25704 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
316. 335. 315. 327. 323. 304. 290. 275. 307. 312. 316. 324. 329. 369. 345. 325. 319. 285. 300. 331. 335. 326. 308.
328. 361. 351. 354. 347. 309. 316. 291. 326. 326. 341. 336. 354. 391. 369. 350. 346. 311. 314. 363. 351. 348. 308.
MEAN S.D.
N
318. 20.2
23
339. 23.6
23
7
331. 370. 375. 351. 355. 332. 321. 306. 329. 340. 338. 346. 344. 388. 374. 344. 344. 324. 321. 376. 363. 348. 333.
346. 20.9
23
10
352. 378. 383. 368. 377. 346. 330. 316. 339. 346. 344. 366. 383. 410. 380. 357. 359. 334. 337. 383. 379. 364. 347.
360. 22.3
23
14
372. 388. 389. 370. 377. 346. 329. 325. 344. 364. 349. 375. 379. 407. 384. 378. 378. 353. 359. 382. 389. 364. 354.
368. 20.3
23
17
357. 389. 394. 374. 374. 360. 334. 317. 361. 363. 355. 379. 392. 402. 393. 398. 379. 361. 349. 406. 409. 381. 369.
374. 23.2
23
21
391. 374. 389. 374. 371. 350. 343. 320. 333. 345. 332. 370. 377. 381. 375. 375. 359. 371. 346. 391. 392. 361. 374.
365. 20.5
23
PAGE 2
-419-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 6 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING LACTATION [G]
DAY 1
4
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25606 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
285. 320. 345. 335. 325. 309. 293. 303. 305. 314. 294. 319. 313. 322. 314. 336. 291. 319. 310. 316. 334. 323. 321. 311. 353.
306. 327. 352. 339. 339. 321. 304. 338. 326. 335. 324. 348. 332. 354. 348. 365. 315. 313. 340. 352. 355. 331. 334. 338. 359.
MEAN S.D.
N
316. 16.5
25
336. 16.3
25
7
314. 342. 353. 354. 344. 328. 312. 335. 335. 334. 341. 352. 339. 348. 339. 347. 319. 322. 344. 352. 360. 351. 339. 340. 363.
340. 13.4
25
10
309. 360. 369. 375. 352. 339. 331. 347. 348. 345. 356. 362. 352. 366. 362. 355. 339. 344. 369. 369. 377. 359. 351. 346. 384.
355. 16.1
25
14
329. 369. 390. 388. 370. 341. 329. 370. 354. 356. 356. 378. 360. 366. 370. 357. 338. 350. 365. 359. 386. 348. 360. 368. 395.
362. 17.6
25
17
317. 369. 405. 391. 375. 347. 335. 370. 361. 352. 351. 374. 369. 374. 375. 376. 364. 358. 390. 381. 385. 377. 356. 368. 410.
369. 20.3
25
21
317. 354. 400. 383. 350. 364. 338. 350. 363. 362. 373. 361. 367. 377. 361. 363. 347. 362. 370. 380. 367. 372. 346. 358. 397.
363. 17.6
25
PAGE 3
-420-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 6 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING LACTATION [G]
DAY 1
4
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25696 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25762 25599 25647 25747 25744 25707 25723
281. 292. 325. 308. 335. 314. 288. 299. 312. 275. 266. 281. 313. 317. 310. 328. 341. 319. 292. 308. 307. 294. 316. 315.
293. 304. 347. 332. 339. 330. 314. 320. 319. 300. 286. 296. 328. 351. 311. 354. 366. 324. 330. 320. 350. 317. 316. 321.
MEAN S.D.
N
306. 19.0
24
324. 20.4
24
7
292. 313. 361. 336. 333. 360. 324. 324. 338. 317. 302. 302. 328. 356. 330. 345. 351. 338. 329. 321. 357. 331. 322. 339.
331. 18.5
24
10
302. 329. 362. 366. 344. 359. 331. 348. 358. 323. 312. 310. 356. 362. 348. 360. 376. 350. 349. 331. 359. 349. 336. 326.
344. 19.4
24
14
305. 329. 377. 366. 348. 369. 340. 356. 348. 329. 317. 320. 358. 364. 353. 364. 386. 358. 343. 326. 378. 345. 349. 342.
349. 20.5
24
17
319. 330. 365. 377. 354. 368. 332. 370. 349. 325. 318. 322. 349. 355. 377. 368. 378. 368. 361. 340. 373. 371. 359. 369.
354. 20.0
24
21
316. 334. 349. 387. 345. 360. 342. 355. 353. 332. 314. 329. 361. 350. 358. 371. 370. 357. 352. 338. 359. 366. 360. 354.
351. 17.1
24
PAGE 4
PLBWv4.04 10/05/2006
-421-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 7 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING LACTATION [G]
DAY 1- 4
4- 7
DAMS FROM GROUP 1:: 0 MG/KG/DAY
25597 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
36. 10. 12. 24. 11. 0. 16. 2. 25. 2. 46. 2. 26. -9. 26. 10. 20. 10. 29. -12. 23. 4. 15. 6. 20. 18. 50. 3. 13. 1.
3. 20. 15. 8. 37. 0. 17. 13. 27. 11. 13. 14. 13. 16. 15. 15.
7. 18. 29. 16.
MEAN S.D.
N
22. 11.6
25
8. 8.8
25
7-10
10. -2.
9. 9. 20. 19. 14. 15. 14. 24. 8. 20. 13. 8. 3. 19. 16. 18. 3. 11. 12. 10. 21. 6. 4.
12. 6.6
25
10-14
22. 2. 6. 8. 7.
19. 7.
-2. 18. -4. 22.
9. -5. 24. 39. 13.
6. 13. 18. 10.
2. 7. -6. 7. 22.
11. 10.6
25
14-17
-3. 1.
-7. -17.
6. -7.
3. -7. -8.
8. 11. -7. 16.
5. -1. -8.
9. -5. 10. -6.
8. 1. 8. 4. 3.
1. 8.0
25
17-21
3. -9. -3. 24. -4. -8. -8. 27. -10. -19. -29. -1. -7. -13.
1. 8. -2. -15. -15. -7. -19. -13. -4. -3. -16.
-6. 12.3
25
1-21
78. 28. 16. 42. 56. 71. 33. 69. 44. 26. 39. 42. 55. 77. 56. 55. 52. 48. 46. 46. 30. 34. 49. 39. 58.
48. 15.8
25
PAGE 1
-422-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 7 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING LACTATION [G]
DAY 1- 4
4- 7
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25648 25694 25668 25631 25660 25704 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
12. 3. 26. 9. 36. 24. 27. -3. 24. 8.
5. 23. 26. 5. 16. 15. 19. 3. 14. 14. 25. -3. 12. 10. 25. -10. 22. -3. 24. 5. 25. -6. 27. -2. 26. 13. 14. 7. 32. 13. 16. 12. 22. 0.
0. 25.
MEAN S.D.
N
21. 7. 8.4 9.6
23 23
7-10
21. 8. 8.
17. 22. 14.
9. 10. 10.
6. 6. 20. 39. 22. 6. 13. 15. 10. 16. 7. 16. 16. 14.
14. 7.5
23
10-14
20. 10.
6. 2. 0. 0. -1. 9. 5. 18. 5. 9. -4. -3. 4. 21. 19. 19. 22. -1. 10. 0. 7.
8. 8.4
23
14-17
-15. 1. 5. 4.
-3. 14.
5. -8. 17. -1.
6. 4. 13. -5. 9. 20. 1. 8. -10. 24. 20. 17. 15.
6. 10.4
23
17-21
34. -15.
-5. 0.
-3. -10.
9. 3. -28. -18. -23. -9. -15. -21. -18. -23. -20. 10. -3. -15. -17. -20. 5.
-9. 14.3
23
1-21
75. 39. 74. 47. 48. 46. 53. 45. 26. 33. 16. 46. 48. 12. 30. 50. 40. 86. 46. 60. 57. 35. 66.
47. 17.9
23
PAGE 2
-423-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 7 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING LACTATION [G]
DAY 1- 4
4- 7
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25606 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
21. 8. 7. 15. 7. 1. 4. 15.
14. 5. 12. 7. 11. 8. 35. -3. 21. 9. 21. -1. 30. 17. 29. 4. 19. 7. 32. -6. 34. -9. 29. -18. 24. 4. -6. 9. 30. 4. 36. 0. 21. 5.
8. 20. 13. 5. 27. 2.
6. 4.
MEAN S.D.
N
19. 11.3
25
4. 8.2
25
7-10
-5. 18. 16. 21.
8. 11. 19. 12. 13. 11. 15. 10. 13. 18. 23.
8. 20. 22. 25. 17. 17.
8. 12.
6. 21.
14. 6.6
25
10-14
20. 9.
21. 13. 18.
2. -2. 23.
6. 11.
0. 16.
8. 0. 8. 2. -1. 6. -4. -10. 9. -11. 9. 22. 11.
7. 9.5
25
14-17
-12. 0.
15. 3. 5. 6. 6. 0. 7.
-4. -5. -4.
9. 8. 5. 19. 26. 8. 25. 22. -1. 29. -4. 0. 15.
7. 10.8
25
17-21
0. -15.
-5. -8. -25. 17.
3. -20.
2. 10. 22. -13. -2.
3. -14. -13. -17.
4. -20.
-1. -18.
-5. -10. -10. -13.
-6. 11.8
25
1-21
32. 34. 55. 48. 25. 55. 45. 47. 58. 48. 79. 42. 54. 55. 47. 27. 56. 43. 60. 64. 33. 49. 25. 47. 44.
47. 12.8
25
PAGE 3
-424-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 7 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING LACTATION [G]
DAY 1- 4
4- 7
DAMS FROM GROUP 4:: 1.0 MG/KG/DAY
25696 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25762 25599 25647 25747 25744 25707 25723
12. -1. 12. 9. 22. 14. 24. 4.
4. -6. 16. 30. 26. 10. 21. 4.
7. 19. 25. 17. 20. 16. 15. 6. 15. 0. 34. 5.
1. 19. 26. -9. 25. -15.
5. 14. 38. -1. 12. 1. 43. 7. 23. 14.
0. 6. 6. 18.
MEAN S.D.
N
18. 11.4
24
8. 10.3
24
7-10
10. 16.
1. 30. 11. -1.
7. 24. 20.
6. 10.
8. 28.
6. 18. 15. 25. 12. 20. 10.
2. 18. 14. -13.
12. 9.9
24
10-14
3. 0. 15. 0. 4. 10. 9. 8. -10. 6. 5. 10. 2. 2. 5. 4. 10. 8. -6. -5. 19. -4. 13. 16.
5. 7.2
24
14-17
14. 1.
-12. 11. 6. -1. -8. 14. 1. -4. 1. 2. -9. -9. 24. 4. -8. 10. 18. 14. -5. 26. 10. 27.
5. 11.6
24
17-21
-3. 4.
-16. 10. -9. -8. 10.
-15. 4. 7.
-4. 7.
12. -5. -19.
3. -8. -11. -9. -2. -14. -5.
1. -15.
-4. 9.2
24
1-21
35. 42. 24. 79. 10. 46. 54. 56. 41. 57. 48. 48. 48. 33. 48. 43. 29. 38. 60. 30. 52. 72. 44. 39.
45. 14.8
24
PAGE 4
PLBWv4.04 10/05/2006
-425-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 8 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY]
DAY 1- 4
4- 7
DAMS FROM GROUP 1:: 0 MG/KG/DAY
25597 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
39. 40. 53. NA 34. 40. 26. 35. 43. 44. 40. 45. 62. NA 30. 34. 41. 41. 43. 42. 40. 46. 33. 41. NA NA 43. 44. 41. 43. 34. 47. 36. 43. 38. 40. NA 45. 45. 43. NA 44. NA 45. 40. 44. NA 46. 46. 52.
MEAN S.D.
N NA = NOT APPLICABLE
40. 7.9
20
43. 3.9
22
7-10
49. NA 52. 43. 57. 57. NA 42. 58. 56. 58. 54. 57. 55. 54. 62. 51. 57. 55. 52. 50. 52. 58. 57. 62.
54. 5.0
23
10-14
59. 52. 59. 49. 63. 63. 59. 44. 65. 64. 69. 65. 61. 66. 68. 64. 60. 66. 68. NA 56. 59. 63. 68. 75.
62. 6.8
24
14-17
58. 56. 66. 48. 70. 72. 65. 46. 69. 69. 79. 74. 71. 75. 72. 73. 74. 70. 71. 61. 58. 64. 65. 67. 74.
67. 8.3
25
17-21
64. 56. 70. 59. 78. 77. 73. 52. 71. 73. 81. 75. 74. 77. 78. 84. 75. 68. 77. 73. 68. NA 71. NA NA
72. 7.9
22
1-21
52. 54. 55. 44. 60. 60. 65. 42. 58. 59. 64. 58. NA 61. 61. 62. 58. 58. NA 56. NA NA 58. NA NA
57. 5.9
19
PAGE 1
-426-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 8 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY]
DAY 1- 4
4- 7
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25648 25694 25668 25631 25660 25704 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
35. 36. 43. 45. 35. 43. 44. 45. 46. 41. 33. 45. 34. NA 33. 38. 58. NA 34. 43. 38. 42. NA NA 39. 40. 43. 47. 40. NA 36. NA 43. 44. 33. 42. 41. 46. 49. 51. 37. 51. 42. 43. NA 56.
MEAN S.D.
N NA = NOT APPLICABLE
40. 6.3
21
44. 4.8
18
7-10
NA 59. 49. 58. 59. 57. 46. 46. NA NA 54. 55. 57. 62. 55. 55. 58. 51. 61. 59. 63. 55. 67.
56. 5.4
20
10-14
62. 72. 59. 67. 69. 63. 56. 52. 65. 63. 58. 61. 64. 64. 63. 63. 67. 59. 73. 69. 72. 66. 73.
64. 5.5
23
14-17
71. 70. 68. 73. 70. 75. 59. 57. 74. 71. 66. 60. 70. 65. 74. 73. 75. 64. 73. 75. 77. 74. 82.
70. 6.1
23
17-21
78. 79. 68. 80. 77. 76. 67. 63. 73. 66. 79. 84. 77. 77. 72. 75. 78. 79. 87. 80. 88. 76. NA
76. 6.3
22
1-21
58. 63. 54. 62. 61. 59. 53. 49. 67. 56. 58. NA 59. 61. 61. 61. 62. 56. 65. 65. 66. 60. NA
60. 4.5
21
PAGE 2
-427-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 8 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY]
DAY 1- 4
4- 7
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25606 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
35. 42. 35. 42. 41. 36. 27. 36. 39. 41. 31. NA NA NA 42. NA 31. 40. 35. 37. 38. 45. 42. 47. 41. 44. 44. 43. 43. NA 44. 39. NA NA NA 37. 32. 39. 46. 44. 43. 44. 34. 42. 38. 47. NA 45. NA 43.
MEAN S.D.
N NA = NOT APPLICABLE
38. 5.3
20
42. 3.4
20
7-10
47. 52. NA 54. 48. 48. 53. 53. 48. 49. NA 51. 54. 56. 54. 50. 57. 47. 51. 60. 57. 47. 57. 53. 63.
53. 4.4
23
10-14
59. 55. 69. 59. 59. 61. 53. 68. 58. 59. 61. 60. 67. 64. 62. 57. 58. 58. 50. 68. 67. 56. 69. 66. 74.
61. 5.8
25
14-17
60. 61. 72. 63. 64. 63. 58. 75. 64. 69. 65. 66. 74. 69. 65. 69. 72. 64. 61. 73. 70. 66. 72. 69. 84.
68. 5.8
25
17-21
67. 67. 75. 69. 66. 69. 64. 81. 79. 73. 83. 77. 76. 78. 75. 77. 72. 64. 62. 84. 80. 70. 80. NA NA
73. 6.5
23
1-21
53. 53. 60. 52. 54. 56. NA 65. 55. 55. 60. 58. 61. 60. 61. 57. NA NA 50. 64. 61. 54. 62. NA NA
58. 4.2
20
PAGE 3
-428-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 8 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/ANIMAL/DAY]
DAY 1- 4
4- 7
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25696 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25762 25599 25647 25747 25744 25707 25723
38. 37. 35. 41. 44. 51. 42. 42. 37. 41. 48. 52. 39. 40. 35. 43. 36. 44. 30. 36. 28. 43. 30. 37. 34. 37. 37. 44. 28. 42. 40. 42. 36. 39. NA NA 36. 35. 33. 37. NA NA NA NA 25. NA NA 45.
MEAN S.D.
N NA = NOT APPLICABLE
36. 5.7
20
41. 4.5
20
7-10
47. 48. 56. 59. 48. 56. 52. NA 58. 44. 48. 46. 53. 58. 51. 55. 54. 52. 47. 43. 53. 57. 54. 45.
51. 4.9
23
10-14
55. 56. 69. 64. 58. 70. 55. 67. 61. 51. 55. 56. 59. 65. 58. 67. 64. 63. 52. 52. 63. 63. 63. 59.
60. 5.5
24
14-17
60. 56. 68. 72. 61. 77. 59. 76. 68. 57. 60. 58. 58. 68. 69. 71. 69. 64. 64. 55. 66. 73. 68. 67.
65. 6.4
24
17-21
72. 72. 66. 72. 75. 77. 75. 81. 72. 60. 68. 66. 73. 73. 73. 87. 75. 69. 66. 59. 79. 84. 72. 70.
72. 6.6
24
1-21
53. 52. 60. 59. 54. 64. 54. 62. 57. 47. 51. 50. 54. 59. 55. 62. 57. NA 51. 47. NA NA 58. NA
55. 4.9
20
PAGE 4
PLFWv4.06 10/05/2006
-429-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 9 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/KG/DAY]
DAY 1- 4
4- 7
DAMS FROM GROUP 1:: 0 MG/KG/DAY
25597 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
134. 166.
98. 76. 128. 117. 187. 91. 126. 133. 128. 111. NA 131. 118. 95. 103. 114. NA 136. NA NA 119. NA 136.
128. NA
113. 100. 126. 123.
NA 98. 120. 127. 141. 133. NA 124. 121. 127. 119. 114. 133. 123. 143. 134. 125. 133. 144.
MEAN S.D.
N NA = NOT APPLICABLE
122. 25.1
20
125. 11.8
22
7-10
152. NA
145. 121. 158. 152.
NA 117. 164. 166. 175. 168. 164. 152. 151. 159. 137. 158. 159. 144. 156. 149. 157. 159. 167.
153. 13.9
23
10-14
174. 149. 162. 135. 168. 159. 167. 121. 176. 184. 199. 193. 173. 175. 180. 158. 156. 176. 190.
NA 171. 165. 168. 186. 195.
170. 18.3
24
14-17
166. 160. 181. 134. 184. 180. 181. 127. 184. 198. 217. 220. 199. 191. 181. 179. 189. 184. 191. 163. 174. 177. 172. 181. 186.
180. 20.4
25
17-21
183. 162. 194. 163. 205. 196. 205. 140. 195. 212. 228. 225. 204. 198. 196. 206. 190. 184. 209. 198. 207.
NA 187.
NA NA
195. 20.2
22
1-21
160. 159. 154. 124. 166. 160. 188. 119. 165. 176. 190. 181.
NA 168. 164. 160. 155. 162.
NA 157.
NA NA 160. NA NA
161. 17.5
19
PAGE 1
-430-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 9 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/KG/DAY]
DAY 1- 4
4- 7
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25648 25694 25668 25631 25660 25704 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
109. 124. 105. 129. 137. 107. 112. 117. 183. 107. 116.
NA 114. 113. 112. 107. 129. 111. 134. 141. 108. 125.
NA
109. 123. 118. 127. 117. 140.
NA 127.
NA 129. 124.
NA 115. 121.
NA NA 128. 132. 145. 138. 143. 124. 174.
MEAN S.D.
N NA = NOT APPLICABLE
121. 17.9
21
130. 14.8
18
7-10
NA 158. 129. 161. 161. 168. 141. 148.
NA NA 158. 154. 157. 155. 146. 157. 165. 155. 185. 155. 170. 154. 197.
159. 14.5
20
10-14
171. 188. 153. 182. 183. 182. 170. 162. 190. 177. 167. 164. 168. 156. 165. 171. 182. 172. 210. 180. 188. 181. 208.
177. 14.3
23
14-17
195. 180. 173. 196. 186. 212. 178. 178. 210. 195. 188. 159. 181. 160. 190. 188. 198. 179. 206. 190. 193. 198. 227.
190. 15.8
23
17-21
209. 207. 173. 214. 206. 214. 198. 197. 210. 186. 230. 224. 200. 196. 188. 194. 211. 216. 250. 201. 219. 205.
NA
207. 16.2
22
1-21
166. 170. 146. 172. 169. 176. 164. 160. 201. 164. 171.
NA 162. 155. 163. 169. 175. 168. 196. 173. 176. 169.
NA
170. 11.9
21
PAGE 2
-431-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 9 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/KG/DAY]
DAY 1- 4
4- 7
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25606 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
118. 108. 117.
80. 117.
98. NA 131. 98. 108. 123. 126. 127. 130. 130. 125. NA NA 98. 138. 125. 104. 116. NA NA
135. 125. 102. 104. 120.
NA NA NA 121. 110. 135. 134. 131. 123. NA 110. NA 116. 114. 125. 123. 123. 139. 133. 119.
MEAN S.D.
N NA = NOT APPLICABLE
116. 14.7
20
122. 10.6
20
7-10
151. 148.
NA 148. 138. 144. 165. 155. 140. 144.
NA 143. 156. 157. 154. 142. 173. 141. 143. 166. 154. 132. 165. 155. 168.
151. 10.8
23
10-14
185. 151. 182. 154. 163. 179. 161. 189. 165. 168. 171. 162. 188. 175. 169. 160. 171. 167. 136. 187. 175. 158. 194. 185. 190.
171. 14.3
25
14-17
186. 165. 181. 162. 172. 183. 175. 203. 179. 195. 184. 176. 203. 186. 174. 188. 205. 181. 161. 197. 181. 182. 201. 188. 208.
185. 13.2
25
17-21
211. 185. 186. 178. 182. 194. 190. 225. 218. 204. 229. 209. 207. 207. 204. 208. 202. 178. 163. 220. 213. 187. 228.
NA NA
201. 17.7
23
1-21
170. 152. 161. 142. 154. 167.
NA 188. 161. 160. 175. 163. 176. 168. 173. 160.
NA NA 141. 179. 167. 153. 180. NA NA
165. 12.3
20
PAGE 3
-432-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 9 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING LACTATION [G/KG/DAY]
DAY 1- 4
4- 7
DAMS FROM GROUP 4 : 1.0 MG/KG/DAY
25696 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25762 25599 25647 25747 25744 25707 25723
132. 117. 131. 131. 110. 149. 130. 113. 114. 104. 101. 104. 106. 111.
90. 117. 102.
NA 116. 105.
NA NA 79. NA
126. 133. 144. 126. 122. 151. 125. 134. 134. 117. 146. 124. 113. 124. 131. 120. 109.
NA 106. 115.
NA NA NA 136.
MEAN S.D.
N NA = NOT APPLICABLE
113. 16.0
20
127. 12.1
20
7-10
158. 150. 155. 168. 142. 156. 159.
NA 167. 138. 156. 150. 155. 162. 150. 156. 148. 151. 139. 132. 148. 168. 164. 135.
152. 10.3
23
10-14
181. 170. 186. 175. 168. 192. 164. 190. 173. 156. 175. 178. 165. 179. 165. 185. 168. 178. 150. 158. 171. 182. 184. 177.
174. 10.7
24
14-17
192. 170. 183. 194. 174. 209. 176. 209. 195. 174. 189. 181. 164. 189. 189. 194. 181. 176. 182. 165. 176. 204. 192. 188.
185. 12.4
24
17-21
226. 217. 185. 188. 214. 212. 223. 223. 205. 182. 215. 202. 206. 207. 198. 235. 201. 190. 185. 174. 216. 228. 200. 193.
205. 16.2
24
1-21
176. 163. 169. 167. 157. 182. 167. 183. 168. 150. 169. 162. 158. 168. 161. 174. 155.
NA 151. 144.
NA NA 172. NA
165. 10.3
20
PAGE 4
PLFWv4.06 10/05/2006
-433-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 10 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL GESTATION LENGTHS [DAYS]
GROUP:
1
2
3
4
GESTATION
GESTATION
GESTATION
GESTATION
ANIMAL LENGTH ANIMAL LENGTH ANIMAL LENGTH ANIMAL LENGTH
25597 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
21. 25648 21. 25694 22. 25668 22. 25631 22. 25660 22. 25704 22. 25665 21. 25674 22. 25652 22. 25733 22. 25748 22. 25753 22. 25672 22. 25655 22. 25727 22. 25626 21. 25739 21. 25749 22. 25756 22. 25741 23. 25752 23. 25758 22. 25719 22. 22.
21. 25606 22. 25614 21. 25671 22. 25698 22. 25609 22. 25677 22. 25623 21. 25653 22. 25604 21. 25678 22. 25684 22. 25714 22. 25650 22. 25735 21. 25722 21. 25642 22. 25628 21. 25763 22. 25766 22. 25689 22. 25708 22. 25743 22. 25761
25712 25746
22. 25696 22. 25686 21. 25639 21. 25658 22. 25676 21. 25600 22. 25603 22. 25630 21. 25703 21. 25673 22. 25611 22. 25619 22. 25705 22. 25691 22. 25717 22. 25616 21. 25715 22. 25762 21. 25599 22. 25647 22. 25747 21. 25744 22. 25707 22. 25723 22.
22. 22. 22. 22. 22. 22. 22. 21. 22. 21. 22. 22. 21. 22. 22. 22. 21. 22. 21. 22. 22. 22. 21. 22.
MEAN S.D.
N
21.9 0.53
25
21.7 0.47
23
21.7 0.48
25
21.8 0.44
24
1- 0 MG/KG/DAY
2 - 0.1 MG/KG/DAY
3- 0.3 MG/KG/DAY
4- 1.0 MG/KG/DAY
PAGE 1
P G L v 5 .06 10/05/2006
-434-
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 UTERUS
CERVIX NO SIGNIFICANT CHANGES OBSERVED
GROSS: GROSS:
GROSS:
NONGRAVID- AMMONIUM SULFIDE NEGATIVE CONTENTS, THICK YELLOW
BOTH HORNS ENLARGED
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS VAGINA
EYES LIVER OVIDUCTS SKIN THYROID GLANDS
P P
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA
MES
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 UTERUS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: NONGRAVID- AMMONIUM SULFIDE NEGATIVE GROSS: CONTENTS, CLEAR FLUID
BOTH HORNS
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS CERVIX
EYES LIVER OVIDUCTS SKIN THYROID GLANDS VAGINA
P P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA
MES
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 UTERUS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: NONGRAVID- AMMONIUM SULFIDE NEGATIVE GROSS: CONTENTS, CLEAR FLUID
BOTH HORNS
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS CERVIX
EYES LIVER OVIDUCTS SKIN THYROID GLANDS VAGINA
P P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 6,11
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo ,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
THYMUS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES 7,9
GROSS: AREA(S), DARK RED FEW, PINPOINT
(LEFT,RIGHT)
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH UTERUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYROID GLANDS CERVIX
EYES LIVER OVIDUCTS SKIN TRACHEA VAGINA
P
P
HEART LYMPH NODE, MES OVARIES SPLEEN URINARY BLADDER
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
*A !
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,9
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,8
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,8
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-444-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL NO. 25633 GROUP 1:
APPENDIX 12 (F0 - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MACROSCOPIC FINDINGS
PAGE 8
/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH:: 06/14/06
GRADE
GENERAL COMMENT GROSS: FORMER IMPLANTATION SITES (LEFT,RIGHT)
P
KIDNEYS KIDNEYS
LIVER NO SIGNIFICANT CHANGES OBSERVED
GROSS: GROSS:
GROSS:
ENLARGED BILATERAL
CYST(S) MULTIPLE, PINPOINT TO 3 MM IN DIAMETER, MEDULLA, BILATERAL
SWOLLEN ALL LOBES
IN CORTEX AND
P P
P
GROSS:ADRENAL GLANDS INTESTINE OVIDUCTS SKIN THYROID GLANDS CERVIX
ESOPHAGUS LYMPH NODE , MES OVARIES SPLEEN TRACHEA VAGINA
EYES LUNGS PANCREAS STOMACH URINARY BLADDER
HEART MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-445-
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 11,7
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 11,4
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 8,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
n-1! -n1
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 6,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 12,8
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
o ! -n1
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 8,12
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
-1n it !
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo
0,0
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 9,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo ,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,7
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 9,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 5,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 9,11
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
n-1! -n1
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,8
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 7,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 5,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo
0,0
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) n/,ro
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
r0 , 0r
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
OO 0,0
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
OO , _IT>
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
THYMUS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: AREA(S), DARK RED MULTIPLE, PINPOINT
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH UTERUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYROID GLANDS CERVIX
EYES LIVER OVIDUCTS SKIN TRACHEA VAGINA
P
HEART LYMPH NODE, MES OVARIES SPLEEN URINARY BLADDER
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
n
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 8,11
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 12,7
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
LUNGS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: GROSS:
FORMER IMPLANTATION SITES (LEFT,RIGHT) 8,9
AREA(S), DARK RED MULTIPLE, PINPOINT TO 3 MM IN DIAMETER,
GROSS:ADRENAL GLANDS INTESTINE MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
ESOPHAGUS KIDNEYS OVIDUCTS SKIN THYROID GLANDS CERVIX
EYES LIVER OVARIES SPLEEN TRACHEA VAGINA
P
ALL LOBES
P
HEART LYMPH NODE, MES PANCREAS STOMACH URINARY BLADDER
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 12,7
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 8,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,5
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) _rr),oo
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo
0,0
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 7,11
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
n-1! -n1
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo ,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 9,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) n/,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 9,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,6
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
-1n n
'!
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
THYMUS
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: GROSS: GROSS:
FORMER IMPLANTATION SITES n ,or
AREA(S), DARK RED
MULTIPLE, PINPOINT
DISCOLORATION, DARK RED BILATERAL
(LEFT, RIGHT)
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND TRACHEA VAGINA
EYES LIVER OVIDUCTS SKIN URINARY BLADDER
P P P
HEART LYMPH NODE, OVARIES SPLEEN UTERUS
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,4
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,7
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) n/,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) n ,*a
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo ,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
r0 , 0r
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo ,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 11,8
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 4,11
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
OO 0,0
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) n/,oo
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-I0S-
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
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: GROSS:
FORMER IMPLANTATION SITES 10,8
DISCOLORATION, DARK RED BILATERAL
(LEFT, RIGHT)
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH UTERUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS CERVIX
EYES LIVER OVIDUCTS SKIN TRACHEA VAGINA
P
P
HEART LYMPH NODE, MES OVARIES SPLEEN URINARY BLADDER
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
r0 , 0r
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo ,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) n ,oo
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
n-1! -n1
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) ro ,n
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 5,13
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 9,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-ois-
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) no
y /o
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA VAGINA
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-ns-
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 5,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
-1n n
'!
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
OO 0,0
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
THYMUS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: AREA(S), DARK RED MULTIPLE, PINPOINT
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH UTERUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYROID GLANDS CERVIX
EYES LIVER OVIDUCTS SKIN TRACHEA VAGINA
P
HEART LYMPH NODE, MES OVARIES SPLEEN URINARY BLADDER
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) no
y /o
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,6
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
THYMUS
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: GROSS: GROSS:
FORMER IMPLANTATION SITES _r)r,n
AREA(S), DARK RED
MULTIPLE, PINPOINT
DISCOLORATION, DARK RED
BILATERAL
(LEFT, RIGHT)
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND TRACHEA VAGINA
EYES LIVER OVIDUCTS SKIN URINARY BLADDER
P P P
HEART LYMPH NODE, OVARIES SPLEEN UTERUS
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 11,4
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT)
-1n n
'!
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,5
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,5
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 0o,0r
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,7
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 4,11
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, OVARIES SPLEEN TRACHEA VAGINA
MES
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
THYMUS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES 5,10
GROSS: AREA(S), DARK RED MULTIPLE, PINPOINT
(LEFT,RIGHT)
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH UTERUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYROID GLANDS CERVIX
EYES LIVER OVIDUCTS SKIN TRACHEA VAGINA
P
P
HEART LYMPH NODE, MES OVARIES SPLEEN URINARY BLADDER
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
UTERUS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: GROSS:
FORMER IMPLANTATION SITES (LEFT, RIGHT) no
y /o
CYST(S)
TWO, 2 MM IN DIAMETER, ON SEROSAL SURFACE,
LEFT
HORN
P P
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS CERVIX
EYES LIVER OVIDUCTS SKIN THYROID GLANDS VAGINA
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) oo ,n/
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,9
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 11,5
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 7,11
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 11,6
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 10,5
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA 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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: FORMER IMPLANTATION SITES (LEFT, RIGHT) 8,10
GROSS:ADRENAL GLANDS INTESTINE LUNGS PANCREAS STOMACH URINARY BLADDER
ESOPHAGUS KIDNEYS MAMMARY GLAND SAL. GLAND MAND THYMUS UTERUS
EYES LIVER OVIDUCTS SKIN THYROID GLANDS CERVIX
P
HEART LYMPH NODE, MES OVARIES SPLEEN TRACHEA VAGINA
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
PGRHv4.54 10/05/2006
-534-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
DAM NO.
IMPLANTATION SITES
APPENDIX 13 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL IMPLANTATION SITES
PUPS BORN
UNACCOUNTED SITES
0 MG/KG/DAY
25597 17 17 25654 15 15 25632 16 16 25610 7 5 25618 19 18 25621 18 16 25687 18 17 25633 14 14 25681 18 17 25615 15 14 25637 18 17 25638 18 18 25713 16 16 25670 20 19 25657 20 19 25663 11 11 25690 20 19 25666 14 14 25692 16 14 25701 19 19 25645 15 15 25661 17 16 25767 19 17 25770 15 14 25702 20 18
0 0 0 2 1 2 1 0 1 1 1 0 0 1 1 0 1 0 2 0 0 1 2 1 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.
PAGE
1
-535-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
DAM NO.
IMPLANTATION SITES
APPENDIX 13 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL IMPLANTATION SITES
PUPS BORN
UNACCOUNTED SITES
0.1 MG/KG/DAY
25648 18 17 25694 18 18 25668 17 17 25631 15 15 25660 16 15 25704 13 13 25665 12 12 25674 16 16 25652 13 13 25733 16 15 25748 10 10 25753 19 18 25672 19 18 25655 17 16 25727 19 17 25626 18 16 25739 15 14 25749 13 11 25756 16 16 25741 18 17 25752 18 15 25758 15 14 25719 19 17
1 0 0 0 1 0 0 0 0 1 0 1 1 1 2 2 1 2 0 1 3 1 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.
PAGE
2
-536-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
DAM NO.
IMPLANTATION SITES
APPENDIX 13 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL IMPLANTATION SITES
PUPS BORN
UNACCOUNTED SITES
0.3 MG/KG/DAY
25606 14 14 25614 19 18 25671 16 13 25698 16 15 25609 15 15 25677 14 13 25623 17 15 25653 14 14 25604 13 12 25678 15 15 25684 12 12 25714 15 13 25650 19 19 25735 15 14 25722 16 16 25642 15 15 25628 18 17 25763 20 19 25766 12 11 25689 15 15 25708 17 15 25743 18 18 25761 15 15 25712 18 17 25746 19 18
0 1 3 1 0 1 2 0 1 0 0 2 0 1 0 0 1 1 1 0 2 0 0 1 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.
PAGE
3
-537-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
DAM NO.
IMPLANTATION SITES
APPENDIX 13 (F0) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL IMPLANTATION SITES
PUPS BORN
UNACCOUNTED SITES
1.0 MG/KG/DAY
25696 17 16 25686 15 15 25639 16 16 25658 16 15 25676 17 15 25600 17 17 25603 16 15 25630 14 14 25703 15 15 25673 16 15 25611 15 15 25619 15 14 25705 14 13 25691 17 16 25717 15 15 25616 15 15 25715 17 17 25762 15 15 25599 19 19 25647 16 14 25747 18 17 25744 17 15 25707 15 14 25723 18 18
1 0 0 1 2 0 1 0 0 1 0 1 1 1 0 0 0 0 0 2 1 2 1 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.
PAGE
4
PIISv4.09 10/05/2006
-538-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 14 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL LITTER VIABILITY
LITTERS FROM GROUP 1: 0 MG/KG/DAY
NUMBER OF VIABLE PUPS
NO. DEAD DAY 0
NO. VIABLE DAY 0
DAY 1
BEFORE
AFTER
SELECTION SELECTION
DAY 4
DAY 4
DAY 7
DAM #
25597 25654 25632 25610 25618 25621 25687 25633 25681 25615 25637 25638 25713 25670 25657 25663 25690 25666 25692 25701 25645 25661 25767 25770 25702
M FU
000 000 000 000 000 000 000 000 000 000 100 000 000 000 000 000 000 000 100 000 000 000 000 000 200
M %F %
7/ 7 100 10/10 100 9/ 9 100 6/ 6 100 8/ 8 100 8/ 8 100 2/ 2 100 3/ 3 100 10/10 100 8/ 8 100 8/ 8 100 8/ 8 100 8/ 8 100 9/ 9 100 9/ 9 100 5/ 5 100 7/ 7 100 10/10 100 6/ 6 100 8/ 8 100 8/ 9 89 8/ 8 100 8/ 8 100 10/10 100 11/11 100 5/ 5 100 11/11 100 8/ 8 100 8/ 8 100 11/11 100 6/ 6 100 5/ 5 100 7/ 7 100 12/12 100 7/ 7 100 7/ 7 100 4/ 5 80 9/ 9 100 9/ 9 100 10/10 100 6/ 6 100 9/ 9 100 9/ 9 100 7/ 7 100 6/ 6 100 11/11 100 5/ 5 100 9/ 9 100 10/12 83 6/ 6 100
TOTAL
17 15 16
5 18 16 17 14 17 14 16 18 16 19 19 11 19 14 13 19 15 16 17 14 16
MF
7 10 96 88 23 10 8 88 89 95 79 68 88 88 11 5 11 8 8 10 65 7 12 77 49 9 10 69 97 6 11 59 96
MF
7 10 96 88 23 10 8 88 88 95 79 68 88 78 11 5 11 8 8 10 65 7 12 77 49 9 10 69 97 6 11 59 96
MF
44 44 44 23 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44
MF
44 43 44 23 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 24 44 44 44
TOTAL
400
189/193 202/202
391
188 198 187 197
98 99
96 98
M = MALE, F = FEMALE, U = UNDETERMINED
PAGE 1
DAY 14
MF
44 43 44 23 44 44 44 34 44 44 44 44 44 44 44 44 44 44 44 44 44 24 44 44 44
95 98
DAY 21
MF
44 43 44 23 44 44 44 34 44 44 44 44 44 44 44 44 44 44 44 44 44 24 44 44 44
95 98
-539-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 14 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL LITTER VIABILITY
LITTERS FROM GROUP 2: 0.1 MG/KG/DAY
NUMBER OF VIABLE PUPS
NO. DEAD DAY 0
NO. VIABLE DAY 0
DAY 1
BEFORE SELECTION
DAY 4
AFTER SELECTION
DAY 4
DAY 7
DAM #
25648 25694 25668 25631 25660 25704 25665 25674 25652 25733 25748 25753 25672 25655 25727 25626 25739 25749 25756 25741 25752 25758 25719
M FU
000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000
M %F %
10/10 100 8/ 8 100 4/ 4 100 5/ 5 100 8/ 8 100 7/ 7 100 4/ 4 100 9/ 9 100 6/ 6 100 7/ 7 100 7/ 7 100 7/ 7 100 8/ 8 100
10/10 100 8/ 8 100 7/ 7 100
10/10 100 6/ 6 100 7/ 7 100 7/ 7 100 9/ 9 100 6/ 6 100
12/12 100
7/ 7 100 10/10 100 13/13 100 10/10 100
7/ 7 100 6/ 6 100 8/ 8 100 7/ 7 100 7/ 7 100 8/ 8 100 3/ 3 100 11/11 100 10/10 100 6/ 6 100 9/ 9 100 9/ 9 100 4/ 4 100 5/ 5 100 9/ 9 100 10/10 100 6/ 6 100 8/ 8 100 5/ 5 100
TOTAL
17 18 17 15 15 13 12 16 13 15 10 18 18 16 17 16 14 11 16 17 15 14 17
MF
10 7 8 10 3 12 5 10 87 76 48 97 67 78 73 6 11 89
10 6 79 79
10 4 64 79 7 10 96 68
12 5
MF
10 7 8 10 3 12 5 10 87 76 48 97 67 78 73 6 10 89
10 6 79 79
10 4 64 79 7 10 86 68
11 5
MF
44 44 35 44 44 44 44 44 44 44 53 44 44 44 44 44 44 44 44 44 44 44 44
MF
44 44 35 44 44 44 44 44 44 44 53 44 44 44 44 44 44 44 44 44 44 44 44
TOTAL
000
172/172 178/178
350
169 175 167 174
92 92
92 92
M = MALE, F = FEMALE, U = UNDETERMINED
PAGE 2
DAY 14
MF
44 44 35 44 44 44 44 44 44 44 53 44 44 44 44 44 44 44 44 44 44 44 44
92 92
DAY 21
MF
44 44 35 44 44 44 44 44 44 44 53 44 44 44 44 44 44 44 44 44 44 44 44
92 92
-540-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 14 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL LITTER VIABILITY
LITTERS FROM GROUP 3: 0.3 MG/KG/DAY
NUMBER OF VIABLE PUPS
NO. DEAD DAY 0
NO. VIABLE DAY 0
DAY 1
BEFORE
AFTER
SELECTION SELECTION
DAY 4
DAY 4
DAY 7
DAM #
25606 25614 25671 25698 25609 25677 25623 25653 25604 25678 25684 25714 25650 25735 25722 25642 25628 25763 25766 25689 25708 25743 25761 25712 25746
M FU
000 000 000 000 000 000 200 000 000 000 000 000 000 000 100 000 000 000 000 000 000 000 000 01 0 000
M %F %
3/ 3 100 11/11 100 12/12 100 6/ 6 100
5/ 5 100 8/ 8 100 5/ 5 100 10/10 100 6/ 6 100 9/ 9 100 7/ 7 100 6/ 6 100 7/ 9 78 6/ 6 100 7/ 7 100 7/ 7 100 7/ 7 100 5/ 5 100 7/ 7 100 8/ 8 100 5/ 5 100 7/ 7 100 6/ 6 100 7/ 7 100 12/12 100 7/ 7 100 6/ 6 100 8/ 8 100 10/11 91 5/ 5 100 8/ 8 100 7/ 7 100 9/ 9 100 8/ 8 100 8/ 8 100 11/11 100 6/ 6 100 5/ 5 100 6/ 6 100 9/ 9 100 9/ 9 100 6/ 6 100 10/10 100 8/ 8 100 7/ 7 100 8/ 8 100 5/ 5 100 11/12 92 11/11 100 7/ 7 100
TOTAL
14 18 13 15 15 13 13 14 12 15 12 13 19 14 15 15 17 19 11 15 15 18 15 16 18
MF
3 11 12 6
58 5 10 69 76 76 77 75 78 47 67 12 7 68 10 5 87 98 8 11 65 69 96 10 8 78 5 11 11 7
MF
3 11 12 6
58 59 69 65 76 77 75 78 47 67 12 7 68 10 5 87 88 8 11 55 69 96 98 78 5 11 10 7
MF
35 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44
MF
35 44 44 44 44 44 43 44 44 44 44 44 44 44 44 43 44 33 44 44 44 44 44 44 44
TOTAL
310
184/187 190/191
374
183 190 178 188
99 101
98 98
M = MALE, F = FEMALE, U = UNDETERMINED
PAGE 3
DAY 14
MF
35 44 44 44 44 44 43 44 44 44 44 44 44 44 44 43 44 33 44 44 44 44 44 44 44
98 98
DAY 21
MF
35 44 44 44 44 44 43 44 44 44 44 44 44 44 44 43 44 33 44 44 44 44 44 44 44
98 98
-541-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 14 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL LITTER VIABILITY
LITTERS FROM GROUP 4: 1.0 MG/KG/DAY
NUMBER OF VIABLE PUPS
NO. DEAD DAY 0
NO. VIABLE DAY 0
DAY 1
BEFORE
AFTER
SELECTION SELECTION
DAY 4
DAY 4
DAY 7
DAM #
25696 25686 25639 25658 25676 25600 25603 25630 25703 25673 25611 25619 25705 25691 25717 25616 25715 25762 25599 25647 25747 25744 25707 25723
M FU
000 000 000 01 0 100 000 000 000 000 000 12 0 000 000 000 100 000 000 000 000 100 000 000 000 000
M %F %
10/10 100 6/ 6 100 8/ 8 100 7/ 7 100 8/ 8 100 8/ 8 100 7/ 7 100 7/ 8 88 6/ 7 86 8/ 8 100 4/ 4 100 13/13 100 5/ 5 100 10/10 100 7/ 7 100 7/ 7 100 5/ 5 100 10/10 100 9/ 9 100 6/ 6 100 7/ 8 88 5/ 7 71 6/ 6 100 8/ 8 100 7/ 7 100 6/ 6 100 8/ 8 100 8/ 8 100 7/ 8 88 7/ 7 100 8/ 8 100 7/ 7 100 8/ 8 100 9/ 9 100 6/ 6 100 9/ 9 100
10/10 100 9/ 9 100 7/ 8 88 6/ 6 100 7/ 7 100 10/10 100 6/ 6 100 9/ 9 100 8/ 8 100 6/ 6 100
13/13 100 5/ 5 100
TOTAL
16 15 16 14 14 17 15 14 15 15 12 14 13 16 14 15 17 15 19 13 17 15 14 18
MF
10 6 87 88 76 68 4 13 5 10 77 5 10 96 75 68 76 87 67 87 78 69
10 9 76 7 10 69 86
13 5
MF
10 6 87 88 76 68 4 13 5 10 77 5 10 96 75 68 76 87 67 87 78 69 99 76 7 10 69 84
13 5
MF
44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44
MF
44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44
TOTAL
430
177/181 186/189
363
175 183 174 181
96 96
96 96
M = MALE, F = FEMALE, U = UNDETERMINED
PAGE 4
DAY 14
MF
44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44
96 96
DAY 21
MF
44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44 44
96 96
PPLVv4.02 10/05/2006
-542-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 1: 0 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
25597 23-MAY-06
C a21 C A a21 C a21 a21 C C C a21 C C C a21 MMMMMMM FFFFFFFFF
25654 23-MAY-06
C a21 C C a21 C a21 C A A a21 C 5 a21 C MMMMMMMMM FFFFFF
25632 24-MAY-06
C a21 C a21 C a21 A C A a21 C C C C a21 a21 MMMMMMMM FFFFFFFF
25610 25-MAY-06
a21 a21 a21 a21 a21 MM FFF
25618 25-MAY-06
C a21 C C C C a21 A a21 C a21 C C C a21 C MMMMMMMMMM FFFFFF
25621 25-MAY-06
a21 a21 a21 MMM
CCCA MMMM
C a21 A C a21 C C C a21 M FFFFFFFF
25687 25-MAY-06
C C a21 a21 a21 C A C C a21 C 3 C a21 A a21 MMMMMMMM FFFFFFFF
25633 24-MAY-06
11 C C a21 A C C C a21 C a21 a21 A a21 MMMMMMMMM FFFFF
25681 25-MAY-06
A C a21 C a21 a21 a21 C C A a21 C C a21 C C MMM M FMMM FFFFFFFF
17 18 A F
A a21 FF
C F
1 F
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 1
-543-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 1: 0 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
25615 25-MAY-06 a21 C A C a21 a21 C a21 a21 A C C a21 C MMMMMM FFFFFFFF
25637 26-MAY-06
0 C a21 C C A C a21 C a21 a21 C C a21 a21 C A MMM MMMMM FFM FFFFFF
25638 26-MAY-06 a21 4 C a21 a21 C A C C C a21 1 C C a21 a21 1 A MMMMMMMM FFFFFFFFFF
25713 26-MAY-06
C A C a21 a21 C C a21 C C C a21 a21 a21 C A MMMMMMMMMMM FFFFF
25670 26-MAY-06
C C a21 a21 C a21 C C A C C C C C a21 a21 a21 A MMMMMMMMMMM FFFFFFF
25657 26-MAY-06 a21 a21 C C C C a21 A C A C a21 a21 C a21 C C 1 MMMMMMMM FFFFFFFFFF
25663 26-MAY-06
C a21 a21 A C a21 a21 a21 A a21 C MMMMMM FFFFF
25690 26-MAY-06
A C a21 C a21 C a21 C a21 C C C C C C C a21 a21 MMMMMMM FFFFFFFFFFF
25666 26-MAY-06
A a21 C C a21 C a21 a21 A C C C a21 a21 MMMMMMM FFFFFFF
19
C F C F
A F
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 2
-544-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 1: 0 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
25692 27-MAY-06
0 a21 a21 A a21 a21 A C C C C a21 C a21 MMMMM FFFFFFFFF
25701 27-MAY-06
C a21 a21 C C a21 C C A a21 a21 C C C C a21 M FM M M M M M M M 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 MMMMMM FFFFFFFFF
25661 29-MAY-06
C 7 7 a21 a21 C C C C a21 a21 a21 C a21 C C MMMMMMMMM FFFFFFF
25767 28-MAY-06 a21 C a21 C a21 a21 a21 C a21 C C a21 C C C a21 MMMMMM FFFFFFFFFF
25770 29-MAY-06
a21 a21 a21 a21 C C a21 C a21 C a21 C C a21 MMMMM FFFFFFFFF
25702 29-MAY-06
0 0 a21 a21 C C a21 C C 1 C a21 a21 C a21 a21 MMMMMMMMMMMM FFFF
17 18
CA FF
C F
C a21 FF
19
C F
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 3
-545-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 2: 0.1 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
25648 23-MAY-06
C C a21 C C C A a21 C a21 a21 A C a21 C a21 C MMMMMMMMMM FFFFFFF
25694 25-MAY-06
C C a21 A a21 C C a21 a21 C a21 C A C a21 C C C MMM MMM FFFFMM FFFFFF
25668 24-MAY-06
1 1 a21 a21 a21 a21 a21 C C a21 C a21 C C C a21 C M FM 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 MMM M FFM FFFFFFFF
25660 25-MAY-06
A a21 C A C a21 a21 C C a21 C C a21 a21 C MMM FMMMMM FFFFFF
25704 25-MAY-06 a21 C A a21 C a21 C a21 A C a21 a21 C MMMMMMM FFFFFF
25665 25-MAY-06
A a21 a21 a21 a21 a21 A C C a21 C C MMMM FFFFFFFF
25674 24-MAY-06
C A C a21 a21 C a21 C C C A C a21 a21 C a21 MMMMMMMMM FFFFFFF
25652 25-MAY-06
a21 a21 a21 MMM
ACC MMM
C a21
C a21 a21
CA
FFFFFFF
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 4
-546-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 2: 0.1 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
25733 25-MAY-06 a21 C a21 C C a21 A A C C a21 a21 C C a21 MMMMMMM FFFFFFFF
25748 26-MAY-06
A a21
C a21 a21 a21
C A a21 a21
MMMMMMM FFF
25753 26-MAY-06
C a21 a21 a21 C A 1 C a21 C C C 4 C A a21 a21 MMMMMMM FFFFFFFFFF
25672 26-MAY-06
1 a21 C C a21 A C C a21 C a21 a21 C C A a21 C FM M M M M M M M 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 MMMMMMMMMM FFFFFF
25727 26-MAY-06
1 a21 C C a21 a21 A C a21 a21 C C a21 C C A C MMMMMMMM FFFFFFFFF
25626 26-MAY-06 a21 C C A C a21 a21 a21 a21 C C A C C a21 C MMMMMMM FFFFFFFFF
25739 27-MAY-06 a21 C C C C a21 A C a21 C a21 A a21 a21 MMMMMMMMMM FFFF
25749 26-MAY-06
1 a21 a21 A C C a21 a21 a21 a21 A FM M M M M M F F F F
18
C F C F
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 5
-547-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
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 MMMMMMM FFFFFFFFF
25741 28-MAY-06
a21 a21 a21 MMM
CCCA MMMM
C A C C C C a21 a21 a21 C FFFFFFFFFF
25752 28-MAY-06 a21 C a21 C a21 2 C C A C a21 C A a21 a21 MMMMMMMMM FFFFFF
25758 29-MAY-06
a21 a21 C C a21 a21 MMMMMM
C a21 a21 a21 C a21 C C FFFFFFFF
25719 29-MAY-06
C 4 a21 a21 C C a21 C a21 C C C a21 a21 a21 C a21 MMMMMMMMMMMM FFFFF
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 6
-548-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 3: 0.3 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
25606 24-MAY-06
a21 a21 a21 a21 a21 C C a21 C C a21 a21 C C MMM FFFFFFFFFFF
25614 24-MAY-06
C C C a21 a21 C a21 C C A C C a21 C a21 C A a21 MMMMMMMMMMMM FFFFFF
25671 23-MAY-06
C a21 a21 A a21 A C a21 a21 C C C a21 MMMMM FFFFFFFF
25698 24-MAY-06
C a21 a21 a21 A a21 C C C a21 C A C a21 3 MMM FMM FFFFFFFFF
25609 25-MAY-06
C a21 a21 A C a21 C C C C A a21 C a21 a21 MMMMMM FFFFFFFFF
25677 24-MAY-06
4 a21 C a21 A C a21 A 4 a21 C a21 a21 MMMMMMM FFFFFF
25623 25-MAY-06
0 0 a21 a21 a21 C C A C C C 7 a21 a21 A MMMMMMMMM FFFFFF
25653 25-MAY-06
C A a21 C a21 a21 a21 C C C a21 a21 A C MMM M FFM FFFM FFM
25604 24-MAY-06
C a21 a21 A C a21 C a21 C a21 a21 A MMMMMMM FFFFF
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 7
-549-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 3: 0.3 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 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 MMMMMMM FFFFFFFF
25684 25-MAY-06
1 a21 a21 A a21 A C a21 C C a21 a21 MMMMM FFFFFFF
25714 26-MAY-06
C A a21 C a21 a21 C a21 a21 a21 C C A MMMMMM FFFFFFF
25650 26-MAY-06
a21 a21 C C C C C a21 FM M M M M M M
C C A C a21 a21 C C A C a21 MMMMM FFFFFF
25735 26-MAY-06 a21 C C a21 A a21 a21 A C a21 C C C a21 MMMMMM FFFFFFFF
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 FM
25642 26-MAY-06
C a21 C a21 A C C a21 C 6 C A a21 C a21 MMMMMMMM FFFFFFF
25628 26-MAY-06 a21 C C C a21 2 A C a21 C C C C a21 a21 a21 A MMMMMMMMM FFFFFFFF
25763 27-MAY-06
C a21 5 a21 C C a21 C a21 a21 C C C C a21 6 C C C MMMMMMMM FFFFFFFFFFF
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 8
-550-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 3: 0.3 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
25766 26-MAY-06
A a21 a21
3 C A a21 a21 a21
C a21
MMM M FFFFFMM
25689 27-MAY-06
C A a21 a21 C a21 a21 C C C C a21 a21 A C MMMMMM FFFFFFFFF
25708 27-MAY-06
A C C a21 C C a21 C a21 C a21 a21 C a21 A MMMMMMMMM FFFFFF
25743 27-MAY-06
C a21 C a21 C C 2 A a21 C a21 a21 C C C A C a21 MMMMMMMMMM FFFFFFFF
25761 28-MAY-06
C C C a21 a21 a21 a21 a21 a21 C C C a21 C a21 MMMMMMM FFFFFFFF
25712 29-MAY-06
0 a21 a21 C a21 a21 a21 a21 C C C C C C C a21 a21 FM 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 MMMMMMMMMMM FFFFFFF
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 9
-551-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
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 MMMMMMMMMM FFFFFF
25686 24-MAY-06
a21 a21 a21 MMM
A C C C C a21 A a21 C C C a21 MMMMM FFFFFFF
25639 25-MAY-06
C C a21 A a21 A C C a21 C a21 a21 C a21 C C MMM FMMMMM FFFFFFF
25658 25-MAY-06
0 1 a21 a21 a21 C C A C a21 C C a21 A a21 F FM 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 MMMMMMM FFFFFFFF
25600 25-MAY-06 a21 A a21 a21 a21 C C C C C a21 a21 C C A C C MMMM FFFFFFFFFFFFF
25603 25-MAY-06
a21 a21 C A a21 a21 a21 C C A C a21 C C C MMMMM FFFFFFFFFF
25630 24-MAY-06 a21 C C A a21 a21 C C A a21 a21 C a21 C MMMMMMM FFFFFFF
25703 25-MAY-06
C a21 A a21 a21 C C a21 a21 A C C C a21 C MMMMM FFFFFFFFFF
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 10
-552-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
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 MMMMMMMMM FFFFFF
25611 26-MAY-06
0 0 0 C a21 C A a21 C a21 A a21 a21 C a21 M F FM 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 MMMMMM FFFFFFFF
25705 25-MAY-06 a21 C C C a21 a21 A A a21 a21 a21 C C MMMMMMM FFFFFF
25691 26-MAY-06
C a21 C C a21 a21 A C C C A a21 1 a21 a21 C FM M M M M M M M F F F F F F F
25717 26-MAY-06
0 1 a21 A C a21 a21 C C C a21 C a21 a21 A MMMMMMMM FFFFFFF
25616 26-MAY-06
C a21 a21 C A C C C C a21 a21 a21 a21 A C MMM MMMM FFFFM FFF
25715 26-MAY-06
1 1 C a21 C a21 A a21 C A C C a21 C a21 C a21 M FM 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 MMMMMM FFFFFFFFF
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 11
-553-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 15 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP VIABILITY
LITTERS FROM GROUP 4: 1.0 MG/KG/DAY
DAY OF DAM # BIRTH PUP # i 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 MMMMMMMMMM FFFFFFFFF
25647 27-MAY-06
0 C C a21 C a21 A a21 C C A a21 a21 a21 MMM MMMM FFFFFM F
25747 28-MAY-06 a21 C a21 a21 a21 C C a21 a21 C C C a21 C a21 C C MMMMMMM FFFFFFFFFF
25744 28-MAY-06 a21 C a21 a21 C a21 C a21 C C a21 C a21 a21 C MMMMMM FFFFFFFFF
25707 27-MAY-06
C C a21 C a21 C a21 a21 a21 a21 2 a21 3 a21 MMMMMMMM FFFFFF
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 FM F
A = ALIVE, NUMBER INDICATES POSTNATAL DAY WHEN DEATH OCCURRED, C = CULLED DAY 4 M = MALE, F = FEMALE, U = UNDETERMINED a=SCHEDULED EUTHANASIA
PAGE 12
PLITRv4.02 10/05/2006
-554-
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP # SEX PUP GROSS OBSERVATION
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M LACERATION
VENTRAL ABDOMINAL AF CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY
4 21
4 21
4 21 21
4 4 4 21 4 4 4 21
4 21
4 4 21 4 21 1
4 21
4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
13 F FOUND DEAD 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 F SCHEDULED EUTHANASIA 4 F SCHEDULED EUTHANASIA 5 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY
5 21
4
4 21
4 21
4 21
4 21
4 4 4 4 21 21
21 21 21 21 21
4 21
4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 9 M SCHEDULED EUTHANASIA 10 M CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY 18 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA
4 4 4 21 21 4 21 4 4 4 21 4 21
21 21 21
4 4 4 4 21 4 21 4 4 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
'UP # SEX PUP GROSS OBSERVATION
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F FOUND DEAD 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA 17 F CULLED ON SCHEDULED DAY
1 M MISSING 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 M SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA
4 4 21 21 21 4 4 4 21 4 3 4 21 21 4
11 4 4
21 4 4 4
21 4
21 21 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 F SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY 16 F CULLED ON SCHEDULED DAY 17 F MISSING
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY
4 21
4 21 21 21
4 4 21 4 4 21 4 4 1
21 4 4
21 21
4 21 21
4 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
JP # SEX PUP GROSS OBSERVATION
1 M FOUND DEAD 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 M SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M FOUND DEAD 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M SCABBING
FACIAL AREA DRIED RED MATERIAL
FACIAL AREA CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY
0 4 21 4 4 4 21 4 21 21 4 4 21 21 4
21 4 4
21 21
1
4
4 4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F MISSING 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA 17 F MISSING
1 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M SCHEDULED EUTHANASIA 9 M CULLED ON SCHEDULED DAY 10 M CULLED ON SCHEDULED DAY 11 M CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA
4 21
1 4 4 21 21 1
4 4 21 21 4 4 21 4 4 4 21 21 21 4
4 4 21 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 10 M CULLED ON SCHEDULED DAY 11 M CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA 17 F SCHEDULED EUTHANASIA 19 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY
4 21
4 4 4 4 4 4 4 21 21 21 4
21 21
4 4 4 4 21 4 4 21 21 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
17 F CULLED ON SCHEDULED DAY 18 F MISSING 19 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 F SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY
2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY
4 1 4
4 21 21
4 21 21 21 21
4
4 21
4 21
4 21
4 21
4 4 4 4 4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
'UP # SEX PUP GROSS OBSERVATION
16 F CULLED ON SCHEDULED DAY 17 F SCHEDULED EUTHANASIA 18 F SCHEDULED EUTHANASIA
2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA
1 M FOUND DEAD 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 F SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY
4 21 21
21 4 4
21 4
21 21
4 4 4 21 21
0 21 21 21 21
4 4 4 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
14 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 F SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 10 M SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA 17 F CULLED ON SCHEDULED DAY 19 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 7 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY
21
4 21 21
4 4 21 4 4 21 21 4 4 4 4 21 4 4
21 21
4 21
4 21
4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M SUBCUTANEOUS HEMORRHAGE(S)
VENTRAL ABDOMINAL AREA PALE IN COLOR FOUND DEAD 3 M FOUND DEAD 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F WET RED MATERIAL
AROUND MOUTH SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY 16 F CULLED ON SCHEDULED DAY
21 21
4 4 4
4 7
7 7 7 21 21 4 4 4 4 21 7
21 21
4 21
4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
'UP # SEX PUP GROSS OBSERVATION
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 F SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA 17 F SMALL IN SIZE
CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 F CULLED ON SCHEDULED DAY 7 F SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA
21 4
21 4
21 21 21
4 21
4 4 21 4 4 4 21 4 4
21 21 21 21
4 4 21 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0 MG/KG/DAY
P # SEX PUP GROSS OBSERVATION
10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA
1 M FOUND DEAD 2 M FOUND DEAD 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 M FOUND DEAD 11 M CULLED ON SCHEDULED DAY 12 M SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA 17 F CULLED ON SCHEDULED DAY 18 F SCHEDULED EUTHANASIA
4 21
4 4 21
0 0 21 21 4 4 21 4 4 1 4 21 21 4 21 21 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 8 M SCHEDULED EUTHANASIA 9 M CULLED ON SCHEDULED DAY 10 M SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA 17 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 5 M PALE IN COLOR
LABORED RESPIRATION SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 M SCHEDULED EUTHANASIA
4 4 21 4 4 4 21 4 21 21 4 21 4 21 4
4 4 21 11 11 21 4 4 21 21 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
12 M CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY 17 F CULLED ON SCHEDULED DAY 18 F CULLED ON SCHEDULED DAY
1 M FOUND DEAD 2 F FOUND DEAD 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 F SCHEDULED EUTHANASIA 7 F SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA 17 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA
4 4 21 4 4 4
1 1 21 21 21 21 21 4 4 21 4 21 4 4 4 21 4
4 21 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
6 F CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA
2 M SCHEDULED EUTHANASIA 3 M SMALL IN SIZE
CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY
4 21
4 4 21 4 4 21 4 21
21 1 4 4
21 21
4 4 21 4 4 21 21 4
21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY
2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 F SCHEDULED EUTHANASIA 6 F SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY
21 4
21 4
21 4
21 21
4
21 21 21 21 21
4 4 21 4 4
4 4 21 21 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
9 M CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F SMALL IN ;SIZE
SMALL IN ;SIZE SMALL IN SIZE SMALL IN SIZE SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY
4 4 4 21 7 11 14 17 21 4 21
21 21 21
4 4 4 21 4 21 21 4
21 4
21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA
2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA 10 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 7 M FOUND DEAD 8 F CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY
4 21
4 4 21 21 4 4 21
21 4
21 21 21
4 21 21
4 21 21 21
4 1 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
JP # SEX PUP GROSS OBSERVATION
11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F FOUND DEAD 14 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA 17 F SCHEDULED EUTHANASIA 18 F CULLED ON SCHEDULED DAY
1 F MISSING 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 M SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 16 F SMALL IN SIZE
SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SCHEDULED EUTHANASIA
4 4 4 4 21 21 4
1 21
4 4 21 4 4 21 4 21 21 4 4 1 4 7 11 14 17 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
P # SEX PUP GROSS OBSERVATION
17 F CULLED ON SCHEDULED DAY 18 F CULLED ON SCHEDULED DAY
1 M SUBCUTANEOUS HEMORRHAGE (S) AROUND MOUTH
2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 M SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY
1 M MISSING 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA
4 4
0
4 21
4 4 4 21 4 4 21 21 21 4 21 4
1 21
4 4 21 21 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 17 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY
21 4 4
21 4 4 4
21 4 4 4
21 21 21 21
4 4 4 4 21 4
21 4 4 4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
6 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M SCHEDULED EUTHANASIA 10 M CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA
1 F MISSING 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA
21 4
21 4
21 21 21
1 21 21
4 4 21 21 21 21
21 4
21 21
4 4 4 4 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
P # SEX PUP GROSS OBSERVATION
12 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 8 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA 17 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M FOUND DEAD
PARTIALLY CANNIBALIZED
4 4 21 21
21 21 21
4 4 4 4 4 4 4 4 21 21 21 4
21 4
21 4
21 2
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F SMALL IN SIZE
SMALL IN SIZE SMALL IN SIZE SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M MISSING
4 4 4 21 4 21 21
21 21
4 4 21 21 4 21 21 21 4 11 14 21 21 4 4
4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.1 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M SCHEDULED EUTHANASIA 10 M CULLED ON SCHEDULED DAY 11 M CULLED ON SCHEDULED DAY 12 M CULLED ON SCHEDULED DAY 13 F SMALL IN SIZE
SCHEDULED EUTHANASIA 14 F SMALL IN SIZE
SCHEDULED EUTHANASIA 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY 17 F SCHEDULED EUTHANASIA
21 21
4 4 21 4 21 4 4 4 21 21 21 21 21 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 F SCHEDULED EUTHANASIA 5 F SCHEDULED EUTHANASIA 6 F CULLED ON SCHEDULED DAY 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 11 M CULLED ON SCHEDULED DAY 12 M CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY
21 21 21 21 21
4 4 21 4 4 21 21 4 4
4 4 4 21 21 4 21 4 4 4 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY 18 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 F SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 F CULLED ON SCHEDULED DAY 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA
21 4
21
4 21 21 21
4 21 21
4 4 4 21
4 21 21 21 21
4 4 4 21 4 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
15 F FOUND DEAD
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 F CULLED ON SCHEDULED DAY 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F SCHEDULED EUTHANASIA
1 M FOUND DEAD 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 9 F FOUND DEAD 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA
3
4 21 21
4 21
4 4 4 4 21 4 21 21
4 21
4 21
4 21
4 21
4 21 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
1 M FOUND DEAD 2 M FOUND DEAD 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F FOUND DEAD 13 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 F SCHEDULED EUTHANASIA 6 F SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 M SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 14 M CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY
0 0 21 21 21 4 4 4 4 4 7 21 21
4 21
4 21 21 21
4 4 4 21 21 4
4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY
1 M MISSING 2 M SCHEDULED EUTHANASIA
HAIR LOSS RIGHT FORELIMB
21 21
4 21
4 21
4 21 21
4 21
4 4 21 21 21 4 21 4 21 4 4
1 21 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
2 M HAIR LOSS LEFT FORELIMB
3 M HAIR LOSS RIGHT FORELIMB
HAIR LOSS LEFT FORELIMB
HAIR LOSS RIGHT FORELIMB
HAIR LOSS RIGHT HINDLIMB
HAIR LOSS LEFT FORELIMB
HAIR LOSS LEFT HINDLIMB
SCHEDULED EUTHANASIA HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB 4 M HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB
21 14 14 17 17 17 17 21 21 21 14 14 17 17 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
4 M HAIR LOSS LEFT FORELIMB
5 M HAIR LOSS RIGHT FORELIMB
HAIR LOSS LEFT FORELIMB
HAIR LOSS RIGHT FORELIMB
HAIR LOSS LEFT FORELIMB
SCHEDULED EUTHANASIA HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB 6 F HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
RIGHT HINDLIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB
21 14 14 17 17 21 21 21 14 14 17 17 17 21 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
7 F CULLED ON SCHEDULED DAY 8 F HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB
4 14
14
17
17
21
21
21 4 4
14
14
17
17
21
21
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
25684
11 F SCHEDULED EUTHANASIA 12 F HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB HAIR LOSS
RIGHT FORELIMB HAIR LOSS
LEFT FORELIMB SCHEDULED EUTHANASIA
25714
1 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY
25650
1 F SMALL IN SIZE
PAGE 36
POSTNATAL DAY
21 14
14
17
17
21
21
21
4 21
4 21 21
4 21 21 21
4 4
0
-590-
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
1 F SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SCHEDULED EUTHANASIA
2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M SCHEDULED EUTHANASIA 9 M CULLED ON SCHEDULED DAY 10 M CULLED ON SCHEDULED DAY 12 M CULLED ON SCHEDULED DAY 13 M SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY 16 F CULLED ON SCHEDULED DAY 18 F CULLED ON SCHEDULED DAY 19 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY
1 7 4 11 14 17 21 21 21 4 4 4 4 4 21 4 4 4 21 21 4 4 4 21
21 4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
4 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA
2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 M SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 16 M FOUND DEAD
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY
21 21 21
4 21
4 4 4 21
4 4 21 21 4 4 4 4 21 21 21 21 4 0
4 21
4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
P # SEX PUP GROSS OBSERVATION
4 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F FOUND DEAD 11 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M FOUND DEAD 8 M CULLED ON SCHEDULED DAY 9 M SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA 17 F SMALL IN SIZE
SMALL IN SIZE
21 4 4
21 4 6 4
21 4
21
21 4 4 4
21 2 4
21 4 4 4 4
21 21 21
7 11
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
17 F SMALL IN SIZE SMALL IN SIZE
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M FOUND DEAD 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F FOUND DEAD 17 F CULLED ON SCHEDULED DAY 18 F CULLED ON SCHEDULED DAY 19 F CULLED ON SCHEDULED DAY
2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M FOUND DEAD 5 F CULLED ON SCHEDULED DAY 7 F SCHEDULED EUTHANASIA
14 17
4 21
5 21
4 4 21 4 21 21 4 4 4 4 21 6 4 4 4
21 21
3 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 M CULLED ON SCHEDULED DAY 11 M SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 F SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA 14 F HAIR LOSS
DORSAL HEAD 15 F CULLED ON SCHEDULED DAY
2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY
21 21
4 21
4 21 21
4 21 21
4 4 4 4 21 21 14
4
4 4 21 4 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
9 M SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M FOUND DEAD 9 M SCHEDULED EUTHANASIA 10 M CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 17 F CULLED ON SCHEDULED DAY 18 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA
21 4
21 21
4 21
4 21
4 21
4 4 2 21 4 21 21 4 4 4 4 21
4 4 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA
1 F FOUND DEAD 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 F SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA
21 21 21 21 21
4 4 4 21 4 21
0 21 21
4 21 21 21 21
4 4 4 4 4 4 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
0.3 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
17 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M FOUND DEAD 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 M CULLED ON SCHEDULED DAY 11 M SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY 17 F SCHEDULED EUTHANASIA 18 F CULLED ON SCHEDULED DAY
21
4 2 21 4 4 21 21 4 4 4 21 21 4 21 21 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M SCHEDULED EUTHANASIA 10 M CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY 16 F SCHEDULED EUTHANASIA
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 F SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA
4 4 4 4 21 21 4 21 4 4 21 21 4 21
21 21 21
4 4 4 4 21 21 4 4 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 M SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY 16 F CULLED ON SCHEDULED DAY
1 F FOUND DEAD 2 F SMALL IN SIZE
MISSING 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA
4 4 21 21 4 4 21 4 21 21 4 21 4 4
0 0 1 21 21 21 4 4 4 21 4 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
JP # SEX PUP GROSS OBSERVATION
15 F SCHEDULED EUTHANASIA
1 M FOUND DEAD 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 3 M SCABBING
DORSAL ABDOMINAL AREA SCABBING
DORSAL ABDOMINAL AREA SCABBING
DORSAL ABDOMINAL AREA SCABBING
DORSAL ABDOMINAL AREA SCHEDULED EUTHANASIA SCABBING
DORSAL ABDOMINAL AREA
21
0 21 21
4 21
4 21 21
4 4 21 4 4
21 4
7
11
17
21 14
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
4 M SCHEDULED EUTHANASIA 5 F SCHEDULED EUTHANASIA 6 F CULLED ON SCHEDULED DAY 7 F CULLED ON SCHEDULED DAY 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 16 F CULLED ON SCHEDULED DAY 17 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 F SCHEDULED EUTHANASIA 7 F SCHEDULED EUTHANASIA 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY
21 21
4 4 4 4 4 21 21 4 4 4 4
21 21
4 21 21 21
4 4 4 21 4 4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 F CULLED ON SCHEDULED DAY 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY
21 4 4
21 21
4 4 21 21 4 21 4
4 21 21 21
4 4 21 21 4 4 4 21 4
4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M LACERATION
DORSAL THORACIC AREA CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY
1 M FOUND DEAD 2 F FOUND DEAD 3 F FOUND DEAD 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 8 M SCHEDULED EUTHANASIA 9 M CULLED ON SCHEDULED DAY 10 M SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA
4 21 21
1
4 4 4 21 21 21 4 21 4
0 0 0 4 21 4 21 4 21 21 21 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA
1 M SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SCHEDULED EUTHANASIA
2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F SCHEDULED EUTHANASIA
21 4
21 21
4 4 21 4 21 4 4 21
1 4 7 11 14 17 21 21 4 4 4 21 21 21 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY
1 F CULLED ON SCHEDULED DAY 2 M SCHEDULED EUTHANASIA 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 F FOUND DEAD 14 F SCHEDULED EUTHANASIA 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY
1 M FOUND DEAD 2 M MISSING 3 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 M SCHEDULED EUTHANASIA 8 M CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY
21 4 4
4 21
4 4 21 21 4 4 4 21 1 21 21 4
0 1 21 4 21 21 4 4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA
1 M DISTAL PORTION OF TAIL MISSING DISTAL PORTION OF TAIL MISSING DISTAL PORTION OF TAIL MISSING CULLED ON SCHEDULED DAY
2 M SCHEDULED EUTHANASIA 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 F CULLED ON SCHEDULED DAY 9 F CULLED ON SCHEDULED DAY 10 F SCHEDULED EUTHANASIA 11 F SCHEDULED EUTHANASIA 12 M SCHEDULED EUTHANASIA 13 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY
1 M MISSING 2 F MISSING 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA
21 4
21 21
0 1 4 4 21 21 4 4 4 4 4 21 21 21 21 4
1 1 4 21 4 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
8 M SCHEDULED EUTHANASIA 9 M CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY 17 F SCHEDULED EUTHANASIA
2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M SCHEDULED EUTHANASIA 7 F SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F CULLED ON SCHEDULED DAY 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY
21 4 4 4
21 4
21 4
21
4 21
4 21 21 21 21
4 4 4 4 21 4
4 4 21 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
5 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 M FOUND DEAD 9 M SCHEDULED EUTHANASIA 10 M SCHEDULED EUTHANASIA 12 F SCHEDULED EUTHANASIA 13 F CULLED ON SCHEDULED DAY 14 F CULLED ON SCHEDULED DAY 15 F CULLED ON SCHEDULED DAY 16 F CULLED ON SCHEDULED DAY 17 F SCHEDULED EUTHANASIA 18 F CULLED ON SCHEDULED DAY 19 F SCHEDULED EUTHANASIA
1 M FOUND DEAD 2 M LACERATION
TAIL CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY 12 F SCHEDULED EUTHANASIA 13 M SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA
4 4 2 21 21 21 4 4 4 4 21 4 21
0 0
4 4 21 4 21 21 4 4 21 21 21
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F CULLED ON SCHEDULED DAY 11 F CULLED ON SCHEDULED DAY 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F CULLED ON SCHEDULED DAY 17 F CULLED ON SCHEDULED DAY
1 M SCHEDULED EUTHANASIA 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M SCHEDULED EUTHANASIA 5 M CULLED ON SCHEDULED DAY 6 M SCHEDULED EUTHANASIA 7 F CULLED ON SCHEDULED DAY 8 F SCHEDULED EUTHANASIA 9 F CULLED ON SCHEDULED DAY 10 F CULLED ON SCHEDULED DAY
21 4
21 21 21
4 4 21 21 4 4 4 21 4 21 4 4
21 4
21 21
4 21
4 21
4 4
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
1.0 MG/KG/DAY
'UP #
SEX
PUP GROSS OBSERVATION
11 F SCHEDULED EUTHANASIA 12 F CULLED ON SCHEDULED DAY 13 F SCHEDULED EUTHANASIA 14 F SCHEDULED EUTHANASIA 15 F CULLED ON SCHEDULED DAY
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M SCHEDULED EUTHANASIA 4 M CULLED ON SCHEDULED DAY 5 M SCHEDULED EUTHANASIA 6 M CULLED ON SCHEDULED DAY 7 M SCHEDULED EUTHANASIA 8 M SCHEDULED EUTHANASIA 9 F SCHEDULED EUTHANASIA 10 F SCHEDULED EUTHANASIA 11 F MISSING 12 F SCHEDULED EUTHANASIA 13 F FOUND DEAD 14 F SCHEDULED EUTHANASIA
1 M CULLED ON SCHEDULED DAY 2 M CULLED ON SCHEDULED DAY 3 M CULLED ON SCHEDULED DAY 4 M CULLED ON SCHEDULED DAY 5 M SMALL IN SIZE
SCHEDULED EUTHANASIA 6 M SMALL IN SIZE
21 4
21 21
4
4 4 21 4 21 4 21 21 21 21 2 21 3 21
4 4 4 4 21 21 21
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 16 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP CLINICAL OBSERVATIONS
PRE-WEANING
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
PUP #
SEX
PUP GROSS OBSERVATION
6 M SCHEDULED EUTHANASIA 7 M CULLED ON SCHEDULED DAY 8 M CULLED ON SCHEDULED DAY 9 M CULLED ON SCHEDULED DAY 10 M CULLED ON SCHEDULED DAY 11 M CULLED ON SCHEDULED DAY 12 M SCHEDULED EUTHANASIA 13 F SMALL IN SIZE
SCHEDULED EUTHANASIA 14 F CULLED ON SCHEDULED DAY 15 F SCHEDULED EUTHANASIA 16 F SCHEDULED EUTHANASIA 17 M SMALL IN SIZE
SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SCHEDULED EUTHANASIA 18 F SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SMALL IN SIZE SCHEDULED EUTHANASIA
PAGE 58
POSTNATAL DAY
21 4 4 4 4 4
21 21 21
4 21 21
7 11 14 17 21 21 11 14 17 21 21
PPOBSv4.06 10/19/2006
-612-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25597-01 25597-02 25597-03 25597-04 25597-05 25597-06 25597-07 25597-08 25597-09 25597-10 25597-11 25597-12 25597-13 25597-14 25597-15 25597-16 25597-17
M M M M M M M F F F F F F F F F F
6.5 8.0 NA NA 6.7 7.9 13.3 21.5 6.2 7.5 NA NA 6.4 8.5 14.7 23.6 5.8 7.5 12.4 20.5 5.6 7.1 NA NA 5.8 7.9 12.5 20.6 6.0 8.0 13.3 20.4 5.8 7.8 NA NA 5.8 7.8 NA NA 6.5 8.5 NA NA 5.2 6.0 9.7 15.6 6.4 8.1 NA NA 5.8 7.6 NA NA 6.2 8.2 NA NA 6.0 7.5 11.7 17.8 6.2 7.6 13.1 20.9
MALES MEAN 6.1 7.8 13.2 21.6 FEMALES MEAN 6.0 7.7 12.0 18.7
25654-01 25654-02 25654-03 25654-04 25654-05
M M M M M
6.3 7.5 NA NA 6.0 8.1 13.1 21.3 6.3 8.3 NA NA 6.2 8.4 NA NA 6.7 8.9 15.7 23.3
NA = NOT APPLICABLE
14
NA 27.6
NA 28.8 26.8
NA 26.5 26.3
NA NA NA 21.6 NA NA NA 23.6 25.3
27.4 24.2
NA 28.2
NA NA 30.6
17
NA 31.2
NA 31.8 31.0
NA 32.2 29.7
NA NA NA 25.0 NA NA NA 27.9 28.0
31.6 27.7
NA 33.4
NA NA 37.3
21
NA 40.5
NA 41.2 39.1
NA 39.2 40.0
NA NA NA 31.8 NA NA NA 36.6 35.0
40.0 35.9
NA 43.8
NA NA 47.5
PAGE 1
-613-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25654-06 25654-07 25654-08 25654-09 25654-10 25654-11 25654-12 25654-13 25654-14 25654-15
M M M M F F F F F F
6.0 7.0 NA NA 5.9 8.0 14.8 22.9 6.1 6.5 NA NA 6.1 8.0 14.5 23.0 6.2 7.6 13.3 21.2 5.9 7.6 12.8 17.9 6.0 8.5 NA NA 5.7 7.2 NA NA 5.9 7.7 12.6 20.2 6.1 7.5 NA NA
MALES MEAN 6.2 7.9 14.5 22.6 FEMALES MEAN 6.0 7.7 12.9 19.8
25632-01 25632-02 25632-03 25632-04 25632-05 25632-06 25632-07 25632-08 25632-09 25632-10 25632-11 25632-12
M M M M M M M M F F F F
8.5 11.8 NA NA 7.4 11.0 16.6 26.6 7.4 10.8 NA NA 7.5 10.9 16.7 25.3 7.5 10.7 NA NA 8.0 11.3 18.0 27.2 7.6 10.9 16.2 24.2 7.8 11.6 NA NA 7.8 11.1 17.7 26.0 8.2 11.4 18.6 28.3 7.5 10.4 NA NA 7.2 10.1 NA NA
NA = NOT APPLICABLE
14
NA 30.4
NA 29.5 27.6 25.1
NA NA 27.0 NA
29.7 26.6
NA 35.7
NA 34.0
NA 34.8 29.7
NA 32.0 36.5
NA NA
17
NA 37.1
NA 36.1 33.8 31.0
NA NA 33.1 NA
36.0 32.6
NA 41.0
NA 41.8
NA 43.2 37.7
NA 39.6 43.6
NA NA
21
NA 46.0
NA 44.1 42.0 38.7
NA NA 43.5 NA
45.4 41.4
NA 54.2
NA 56.8
NA 57.2 47.2
NA 49.2 57.7
NA NA
PAGE 2
-614-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25632-13 25632-14 25632-15 25632-16
F F F F
7.3 10.6 NA NA 6.8 10.1 NA NA 7.3 10.2 15.7 25.3 7.4 10.6 16.9 25.8
MALES MEAN FEMALES MEAN
7.7 11.1 16.9 25.8 7.4 10.6 17.2 26.4
25610-01 25610-02 25610-03 25610-04 25610-05
M M F F F
8.4 13.0 20.9 31.4 8.4 12.9 21.0 31.9 8.0 12.5 19.7 29.7 7.4 11.7 18.2 28.9 8.1 12.7 20.5 31.8
MALES MEAN FEMALES MEAN
8.4 13.0 21.0 31.7 7.8 12.3 19.5 30.1
25618-01 25618-02 25618-03 25618-04 25618-05 25618-06 25618-07 25618-08 25618-09
M M M M M M M M M
6.5 9.5 NA NA 7.1 10.0 16.0 25.4 7.8 10.4 NA NA 6.7 9.5 NA NA 7.1 10.8 NA NA 7.0 9.1 NA NA 6.8 9.5 15.1 25.4 6.8 9.6 15.1 24.4 7.4 9.5 14.5 24.8
NA = NOT APPLICABLE
14
NA NA 33.2 33.3
33.6 33.8
38.6 39.1 36.0 36.0 39.1
38.9 37.0
NA 30.5
NA NA NA NA 32.9 31.2 32.4
17
NA NA 39.6 39.9
40.9 40.7
45.1 45.4 42.8 42.3 44.7
45.3 43.3
NA 38.5
NA NA NA NA 40.2 39.2 39.4
21
NA NA 51.0 52.1
53.9 52.5
62.1 62.3 55.9 57.2 61.2
62.2 58.1
NA 52.9
NA NA NA NA 53.8 51.7 55.3
PAGE 3
-615-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25618-10 25618-11 25618-12 25618-13 25618-14 25618-15 25618-16 25618-17 25618-18
M F F F F F F F F
7.0 9.9 NA NA 7.0 10.3 16.0 27.4 7.1 10.1 NA NA 6.7 8.6 NA NA 6.6 9.1 NA NA 6.0 8.8 13.9 24.0 6.2 8.1 NA NA 6.4 8.9 13.8 23.9 7.2 9.7 15.1 24.7
MALES MEAN 7.0 9.8 15.2 25.0 FEMALES MEAN 6.7 9.2 14.7 25.0
25621-01 25621-02 25621-03 25621-04 25621-05 25621-06 25621-07 25621-08 25621-09 25621-10 25621-11 25621-12 25621-13
M M M M M M M M F F F F F
7.9 9.8 16.3 25.9 7.5 9.9 16.2 26.3 7.4 9.4 15.5 24.6 7.7 10.6 NA NA 7.7 10.1 NA NA 6.7 9.6 NA NA 7.3 9.8 16.2 26.0 7.1 9.7 NA NA 6.7 9.0 16.3 25.4 7.2 10.1 17.1 26.5 7.0 9.5 NA NA 7.2 9.6 16.0 25.7 7.3 9.8 NA NA
NA = NOT APPLICABLE
14
NA 34.1
NA NA NA 31.0 NA 29.8 32.7
31.8 31.9
33.5 33.7 33.2
NA NA NA 32.3 NA 33.6 32.7 NA 32.1 NA
17
NA 41.8
NA NA NA 37.7 NA 37.7 39.6
39.3 39.2
40.8 41.0 40.5
NA NA NA 40.5 NA 40.9 41.1 NA 39.3 NA
21
NA 57.7
NA NA NA 50.1 NA 48.5 55.0
53.4 52.8
56.4 55.2 53.4
NA NA NA 51.7 NA 53.4 52.6 NA 52.4 NA
PAGE 4
-616-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25621-14 F 25621-15 F 25621-16 F
7.0 9.2 NA NA 7.0 9.4 NA NA 7.4 9.8 16.8 26.4
MALES MEAN 7.4 9.9 16.1 25.7 FEMALES MEAN 7.1 9.6 16.6 26.0
25687-01 25687-02 25687-03 25687-04 25687-05 25687-06 25687-07 25687-08 25687-09 25687-10 25687-11 25687-12 25687-13 25687-14 25687-15 25687-16
M M M M M M M M F F F F F F F F
7.3 11.1 NA NA 7.0 10.6 NA NA 6.4 9.5 14.3 22.9 7.5 10.7 15.3 24.8 6.8 10.5 15.6 26.2 7.4 10.0 NA NA 6.9 10.4 15.0 24.6 7.1 10.7 NA NA 7.0 10.2 NA NA 6.6 9.9 14.7 23.4 7.0 10.2 NA NA 6.7 NA NA NA 6.5 10.2 NA NA 6.6 10.0 14.1 23.2 6.9 10.1 14.8 24.4 6.8 10.0 14.8 24.5
NA = NOT APPLICABLE
14
NA NA 33.9
33.2 33.1
NA NA 31.6 32.7 34.3 NA 31.4 NA NA 30.2 NA NA NA 31.1 30.5 32.2
17
NA NA 41.6
40.7 40.7
NA NA 38.6 39.8 42.1 NA 39.1 NA NA 37.1 NA NA NA 38.4 37.9 38.3
21
NA NA 53.7
54.2 53.0
NA NA 50.3 53.4 53.7 NA 50.2 NA NA 43.9 NA NA NA 48.7 46.8 48.4
PAGE 5
-617-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25687-17 F 7.0 10.5 NA NA
MALES MEAN FEMALES MEAN
7.1 10.4 15.1 24.6 6.8 10.1 14.6 23.9
25633-01 25633-02 25633-03 25633-04 25633-05 25633-06 25633-07 25633-08 25633-09 25633-10 25633-11 25633-12 25633-13 25633-14
M M M M M M M M M F F F F F
5.4 7.0 9.3
NA
5.4 6.6 NA NA
5.4 6.9 NA NA
5.3 6.8 9.3 15.2
5.5 7.3 10.2 16.8
6.1 7.8 NA NA
5.6 7.5 NA NA
5.9 7.5 NA NA
6.0 7.8 10.2 17.2
4.2 5.3 NA NA
5.5 7.0 9.7 16.0
5.2 6.1 7.7 12.8
5.0 6.4 8.4 13.9
4.9 6.5 8.6 14.5
MALES MEAN 5.6 7.2 9.8 16.4 FEMALES MEAN 5.0 6.3 8.6 14.3
25681-01 M 25681-02 M 25681-03 M
7.1 10.1 15.2 23.9 7.0 9.6 NA NA 6.1 8.3 12.3 21.2
NA = NOT APPLICABLE
14
NA
32.5 31.0
NA NA NA 22.0 22.4 NA NA NA 23.0 NA 22.6 18.3 19.2 20.0
22.5 20.0
34.4 NA
33.3
17
NA
39.9 37.9
NA NA NA 27.2 27.5 NA NA NA 28.0 NA 27.9 23.4 25.0 25.2
27.6 25.4
37.9 NA
36.5
21
NA
51.9 47.0
NA NA NA 35.3 32.3 NA NA NA 35.9 NA 34.9 29.9 30.3 32.3
34.5 31.9
43.8 NA
43.3
PAGE 6
-618-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25681-04 25681-05 25681-06 25681-07 25681-08 25681-09 25681-10 25681-11 25681-12 25681-13 25681-14 25681-15 25681-16
M F M M M F F F F F F F F
7.5 11.0 NA NA 6.3 9.1 14.5 23.4 7.9 11.1 17.1 27.1 7.4 10.5 17.2 26.9 7.5 10.5 NA NA 7.0 10.0 NA NA 6.6 9.5 15.1 24.5 6.0 8.7 13.4 22.6 6.7 9.5 NA NA 6.4 9.4 NA NA 6.6 9.4 15.6 24.7 6.8 8.9 NA NA 7.0 9.5 NA NA
MALES MEAN FEMALES MEAN
7.2 10.2 15.5 24.8 6.6 9.3 14.7 23.8
25615-01 25615-02 25615-03 25615-04 25615-05 25615-06 25615-07 25615-08 25615-09
M M M M M M F F F
8.2 11.6 17.5 26.6 7.9 11.0 NA NA 7.2 10.6 16.5 26.3 6.9 10.4 NA NA 7.7 11.3 17.9 27.1 7.5 10.3 16.5 26.1 6.4 8.8 NA NA 7.4 10.5 16.7 26.1 7.2 10.1 15.6 24.1
NA = NOT APPLICABLE
14
NA 30.6 34.8 34.7
NA NA 32.5 29.7 NA NA 32.3 NA NA
34.3 31.3
34.2 NA
31.1 NA
34.8 32.4
NA 33.1 31.9
17
NA 38.0 43.0 43.1
NA NA 37.8 36.0 NA NA 39.9 NA NA
40.1 37.9
40.3 NA
38.5 NA
38.9 40.3
NA 40.4 38.3
21
NA 46.7 57.2 55.3
NA NA 46.1 45.1 NA NA 48.6 NA NA
49.9 46.6
56.6 NA
52.7 NA
52.2 56.7
NA 56.2 52.2
PAGE 7
-619-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25615-10 25615-11 25615-12 25615-13 25615-14
F F F F F
6.7 9.4 14.9 24.2 7.1 10.2 NA NA 6.8 9.7 NA NA 6.8 10.2 15.1 25.0 6.9 10.1 NA NA
MALES MEAN FEMALES MEAN
7.6 10.9 17.1 26.5 6.9 9.9 15.6 24.9
25637-02 25637-03 25637-04 25637-05 25637-06 25637-07 25637-08 25637-09 25637-10 25637-11 25637-12 25637-13 25637-14 25637-15 25637-16
M M M M M M M F F M F F F F F
7.7 10.7 NA NA 7.9 10.9 17.2 28.7 7.5 10.9 NA NA 6.7 9.1 NA NA 7.0 9.7 15.9 27.6 6.9 9.8 NA NA 7.1 9.7 15.6 26.7 7.0 9.5 NA NA 7.3 10.1 16.6 27.9 7.6 10.5 15.8 27.8 7.3 10.3 NA NA 6.9 9.4 NA NA 7.3 10.3 15.9 27.4 7.1 10.0 16.8 29.2 6.8 9.9 NA NA
NA = NOT APPLICABLE
14
29.5 NA NA
32.8 NA
33.1 31.8
NA 36.2
NA NA 33.8 NA 34.9 NA 36.4 36.1 NA NA 35.9 37.8 NA
17
35.1 NA NA
38.2 NA
39.5 38.0
NA 44.9
NA NA 42.0 NA 44.0 NA 46.1 45.9 NA NA 44.9 43.9 NA
21
47.0 NA NA
53.4 NA
54.6 52.2
NA 60.2
NA NA 57.6 NA 62.3 NA 64.2 59.1 NA NA 61.3 61.1 NA
PAGE 8
-620-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25637-17 F
6.9 9.6 16.1 27.3
MALES MEAN FEMALES MEAN
7.3 10.2 16.1 27.7 7.1 9.9 16.4 28.0
25638-01 25638-02 25638-03 25638-04 25638-05 25638-06 25638-07 25638-08 25638-09 25638-10 25638-11 25638-13 25638-14 25638-15 25638-16 25638-18
M M M M M M M M F F F F F F F F
7.6 11.1 16.1 27.0 8.3 NA NA NA 7.2 10.4 NA NA 7.8 10.5 14.8 24.8 7.6 10.9 16.1 27.3 6.1 8.0 NA NA 7.4 10.5 15.8 25.5 7.1 10.3 NA NA 7.2 10.2 NA NA 7.6 10.0 NA NA 6.8 10.0 15.0 25.4 7.0 10.0 NA NA 7.2 10.2 NA NA 6.8 9.5 14.7 25.4 6.6 9.8 14.6 24.5 6.5 8.6 12.6 20.7
MALES MEAN FEMALES MEAN
7.4 10.2 15.7 26.2 7.0 9.8 14.2 24.0
25713-01 M 7.1 10.0 NA NA
NA = NOT APPLICABLE
14
33.3
35.3 35.9
34.7 NA NA
33.0 35.6
NA 31.3
NA NA NA 33.5 NA NA 34.2 32.9 26.5
33.7 31.8
NA
17
42.3
44.2 44.3
41.6 NA NA
40.7 41.9
NA 39.1
NA NA NA 40.0 NA NA 43.2 39.7 34.1
40.8 39.3
NA
21
55.0
59.8 60.4
57.2 NA NA
53.8 56.3
NA 48.9
NA NA NA 53.7 NA NA 55.0 54.7 41.2
54.1 51.2
NA
PAGE 9
-621-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25713-02 25713-03 25713-04 25713-05 25713-06 25713-07 25713-08 25713-09 25713-10 25713-11 25713-12 25713-13 25713-14 25713-15 25713-16
M M M M M M M M M M F F F F F
7.1 9.5 15.5 26.4 7.8 10.3 NA NA 7.0 9.0 14.2 24.5 7.5 8.7 14.4 25.6 7.5 10.0 NA NA 7.0 9.4 NA NA 7.1 9.0 14.3 25.0 7.1 9.0 NA NA 7.4 9.8 NA NA 6.8 9.2 NA NA 7.0 9.8 14.4 25.3 6.5 9.2 15.2 26.6 7.1 9.3 15.0 25.0 6.8 8.5 NA NA 7.5 9.6 15.3 26.2
MALES MEAN 7.2 9.4 14.6 25.4 FEMALES MEAN 7.0 9.3 15.0 25.8
25670-01 25670-02 25670-03 25670-04 25670-05 25670-06 25670-07
M M M M M M M
7.2 9.2 NA NA 7.6 10.2 NA NA 6.9 9.2 15.3 26.7 6.9 8.3 14.2 25.6 7.3 9.4 NA NA 6.2 7.6 11.5 21.1 7.4 10.1 NA NA
NA = NOT APPLICABLE
14
32.9 NA
30.8 33.3
NA NA 31.6 NA NA NA 32.5 33.0 31.4 NA 31.8
32.2 32.2
NA NA 37.6 33.7 NA 28.4 NA
17
40.1 NA
36.4 41.4
NA NA 39.7 NA NA NA 41.1 39.2 39.1 NA 38.7
39.4 39.5
NA NA 42.6 41.4 NA 35.4 NA
21
49.8 NA
47.2 56.2
NA NA 56.5 NA NA NA 54.6 54.2 51.3 NA 47.9
52.4 52.0
NA NA 57.1 54.5 NA 46.1 NA
PAGE 10
-622-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25670-08 25670-09 25670-10 25670-11 25670-12 25670-13 25670-14 25670-15 25670-16 25670-17 25670-18 25670-19
M M M M F F F F F F F F
6.6 8.4 NA NA 7.2 9.2 14.7 26.6 7.5 9.5 NA NA 6.9 8.9 NA NA 6.5 8.7 NA NA 6.4 7.4 NA NA 6.7 8.6 NA NA 7.1 8.5 13.3 24.1 6.0 7.4 10.7 20.4 7.0 8.7 13.8 23.9 6.9 8.8 13.3 24.4 7.2 9.1 NA NA
MALES MEAN 7.1 9.1 13.9 25.0 FEMALES MEAN 6.7 8.4 12.8 23.2
25657-01 25657-02 25657-03 25657-04 25657-05 25657-06 25657-07 25657-08 25657-09 25657-10
M M M M M M M M F F
7.4 10.2 16.6 28.2 6.9 9.6 16.2 27.0 7.0 9.7 NA NA 6.3 8.6 NA NA 7.1 9.3 NA NA 7.3 10.1 NA NA 7.0 9.5 16.5 27.4 6.2 9.4 15.4 26.3 6.4 8.7 NA NA 6.7 8.8 15.4 25.1
NA = NOT APPLICABLE
14
NA 33.9
NA NA NA NA NA 32.3 29.1 31.3 31.3 NA
33.4 31.0
37.9 35.5
NA NA NA NA 34.9 33.3 NA 31.7
17
NA 42.8
NA NA NA NA NA 40.0 36.5 38.6 40.3 NA
40.6 38.9
47.5 45.1
NA NA NA NA 45.0 44.4 NA 40.6
21
NA 53.5
NA NA NA NA NA 50.2 47.8 51.2 52.0 NA
52.8 50.3
63.8 58.1
NA NA NA NA 57.8 57.9 NA 53.0
PAGE 11
-623-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25657-11 25657-12 25657-13 25657-14 25657-15 25657-16 25657-17 25657-19
F F F F F F F F
7.0 9.9 NA NA 6.7 9.2 15.5 26.4 6.7 8.9 15.2 25.5 7.1 10.0 NA NA 5.6 8.2 13.7 22.3 6.7 9.4 NA NA 7.0 9.7 NA NA 6.2 9.0 NA NA
MALES MEAN 6.9 9.6 16.2 27.2 FEMALES MEAN 6.6 9.2 15.0 24.8
25663-01 25663-02 25663-03 25663-04 25663-05 25663-06 25663-07 25663-08 25663-09 25663-10
M M M M M M F F F F
7.9 11.1 NA NA 7.8 11.1 17.2 28.6 7.8 11.2 17.5 28.8 8.3 11.7 18.2 28.9 7.0 10.1 NA NA 8.6 12.2 18.4 29.1 7.3 10.1 15.4 26.0 7.7 11.7 18.4 29.6 6.8 9.7 14.6 24.3 7.3 10.5 16.6 26.9
NA = NOT APPLICABLE
14
NA 34.3 34.3
NA 30.2
NA NA NA
35.4 32.6
NA 36.7 36.6 35.1
NA 37.3 33.4 37.2 30.0 35.3
17
NA 43.5 42.2
NA 38.3
NA NA NA
45.5 41.2
NA 45.6 44.5 43.5
NA 46.1 41.2 45.8 38.5 43.7
21
NA 56.4 52.8
NA 50.8
NA NA NA
59.4 53.3
NA 62.8 61.7 55.0
NA 62.2 56.1 61.6 49.8 59.6
PAGE 12
-624-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25663-11 F 7.8 10.9 NA NA
MALES MEAN FEMALES MEAN
7.9 11.2 17.8 28.9 7.4 10.6 16.3 26.7
25690-01 25690-02 25690-03 25690-04 25690-05 25690-06 25690-07 25690-08 25690-09 25690-10 25690-11 25690-12 25690-13 25690-14 25690-15 25690-16 25690-17 25690-18
M M M M M M M F F F F F F F F F F F
6.7 8.4 12.9 22.8 6.7 8.6 NA NA 7.0 8.8 13.6 23.6 6.7 8.9 NA NA 6.8 9.4 14.2 25.0 7.1 8.9 NA NA 7.0 9.5 15.0 25.0 6.5 8.2 NA NA 6.1 8.1 11.4 20.2 6.5 8.4 NA NA 6.6 8.7 NA NA 6.8 8.9 NA NA 6.1 7.8 NA NA 6.7 8.8 NA NA 6.7 8.2 NA NA 6.9 8.4 NA NA 6.4 8.5 13.2 23.4 6.4 8.2 12.4 22.1
NA = NOT APPLICABLE
14
NA
36.4 34.0
29.2 NA
30.9 NA
32.4 NA
33.3 NA
28.2 NA NA NA NA NA NA NA
30.6 29.4
17
NA
44.9 42.3
38.4 NA
40.5 NA
40.8 NA
41.3 NA
35.3 NA NA NA NA NA NA NA
38.8 38.4
21
NA
60.4 56.8
50.6 NA
55.1 NA
54.0 NA
55.7 NA
47.2 NA NA NA NA NA NA NA
52.1 51.5
PAGE 13
-625-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25690-19 F
6.4 8.1 12.9 22.5
MALES MEAN 6.9 8.9 13.9 24.1 FEMALES MEAN 6.5 8.4 12.5 22.1
25666-01 25666-02 25666-03 25666-04 25666-05 25666-06 25666-07 25666-08 25666-09 25666-10 25666-11 25666-12 25666-13 25666-14
M M M M M M M F F F F F F F
7.4 10.1 15.9 26.7 6.7 9.5 13.9 23.7 7.2 10.1 NA NA 6.8 9.1 NA NA 6.9 9.7 14.6 25.2 6.8 9.7 NA NA 6.9 9.7 14.8 24.5 6.5 9.0 14.0 24.2 6.6 9.0 14.1 23.9 6.2 8.8 NA NA 6.6 8.5 NA NA 7.0 10.0 NA NA 6.5 8.5 12.5 23.0 6.5 9.1 14.2 24.5
MALES MEAN 7.0 9.7 14.8 25.0 FEMALES MEAN 6.6 9.0 13.7 23.9
25692-02 M 25692-03 M 25692-04 M
8.0 10.6 17.4 29.1 7.1 10.1 15.7 26.8 7.4 10.3 16.2 28.3
NA = NOT APPLICABLE
14
28.2
31.5 29.1
32.4 31.3
NA NA 33.7 NA 33.0 33.0 30.0 NA NA NA 30.6 31.8
32.6 31.4
37.6 33.9 36.8
17
37.9
40.3 37.6
41.2 39.9
NA NA 41.4 NA 40.6 39.9 38.6 NA NA NA 37.6 39.1
40.8 38.8
47.4 42.6 46.6
21
48.4
53.9 49.8
51.0 52.5
NA NA 51.3 NA 51.4 50.2 44.2 NA NA NA 47.3 50.3
51.6 48.0
63.5 55.7 60.3
PAGE 14
-626-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25692-05 25692-06 25692-07 25692-08 25692-09 25692-10 25692-11 25692-12 25692-13 25692-14
M F F F F F F F F F
7.5 9.7 15.0 26.8 7.2 10.4 16.3 27.2 6.8 9.1 15.0 26.0 6.8 8.9 NA NA 6.9 9.4 NA NA 7.3 9.7 NA NA 7.2 10.2 NA NA 7.3 10.0 16.0 26.5 6.7 8.5 NA NA 6.9 9.3 15.3 26.2
MALES MEAN FEMALES MEAN
7.5 10.2 16.1 27.8 7.0 9.5 15.7 26.5
25701-01 25701-02 25701-03 25701-04 25701-05 25701-06 25701-07 25701-08 25701-09 25701-10 25701-11 25701-12
M F M M M M M M M M F F
6.4 8.6 NA NA 6.4 9.1 14.3 23.1 7.0 9.6 15.4 24.0 6.5 8.9 NA NA 6.7 8.9 NA NA 6.7 9.0 14.0 21.6 6.1 8.1 NA NA 5.9 8.3 NA NA 6.8 9.1 14.2 22.8 6.4 8.8 14.0 22.1 6.5 9.1 14.5 22.5 6.3 8.9 NA NA
NA = NOT APPLICABLE
14
34.4 35.4 34.5
NA NA NA NA 33.3 NA 34.4
35.7 34.4
NA 29.9 31.1
NA NA 28.4 NA NA 29.3 28.7 29.1 NA
17
43.6 43.7 41.1
NA NA NA NA 41.3 NA 43.8
45.1 42.5
NA 36.1 38.0
NA NA 34.5 NA NA 36.0 35.6 34.7 NA
21
57.1 58.2 50.0
NA NA NA NA 54.1 NA 57.1
59.2 54.9
NA 50.8 52.5
NA NA 46.6 NA NA 49.7 45.2 48.5 NA
PAGE 15
-627-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25701-13 25701-14 25701-15 25701-16 25701-17 25701-18 25701-19
F F F F F F F
6.5 8.3 NA NA 5.7 7.1 NA NA 5.7 7.8 NA NA 6.4 8.3 13.2 21.8 6.4 8.3 NA NA 6.2 8.7 13.7 22.4 6.7 8.5 NA NA
MALES MEAN 6.5 8.8 14.4 22.6 FEMALES MEAN 6.3 8.4 13.9 22.5
25645-01 25645-02 25645-03 25645-04 25645-05 25645-06 25645-07 25645-08 25645-09 25645-10 25645-11 25645-12 25645-13 25645-14
M M M M M M F F F F F F F F
5.9 6.6 10.1 18.5 7.2 8.4 13.0 22.4 7.3 8.1 NA NA 7.2 8.6 13.8 21.1 8.1 9.7 NA NA 7.4 8.4 13.2 22.6 6.8 8.1 13.0 22.4 7.0 7.8 12.5 21.8 7.0 8.1 NA NA 7.0 7.5 NA NA 6.9 8.2 13.4 22.4 6.6 7.5 12.2 21.1 6.6 7.6 NA NA 7.3 9.2 NA NA
NA = NOT APPLICABLE
14
NA NA NA 28.8 NA 29.0 NA
29.4 29.2
26.4 30.6
NA 28.4
NA 29.2 29.0 28.1
NA NA 29.8 29.2 NA NA
17
NA NA NA 35.4 NA 36.5 NA
36.0 35.7
31.9 36.9
NA 33.8
NA 34.9 34.6 33.9
NA NA 35.6 35.3 NA NA
21
NA NA NA 49.2 NA 48.4 NA
48.5 49.2
40.2 49.9
NA 45.3
NA 44.6 45.6 44.2
NA NA 48.6 44.6 NA NA
PAGE 16
-628-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25645-15 F 6.5 7.6 NA NA
MALES MEAN 7.2 8.3 12.5 21.2 FEMALES MEAN 6.9 8.0 12.8 21.9
25661-01 25661-02 25661-03 25661-04 25661-05 25661-06 25661-07 25661-08 25661-09 25661-10 25661-11 25661-12 25661-13 25661-14 25661-15 25661-16
M M M M M M M M M F F F F F F F
7.9 9.9 NA NA
7.3 8.4 13.9
NA
7.6 9.6 NA NA
7.8 9.4 15.7 28.7
7.1 8.9 14.5 26.7
7.9 9.6 NA NA
7.6 9.2 NA NA
6.8 8.2 NA NA
7.5 9.6 NA NA
7.5 9.0 14.5 26.8
7.0 8.5 13.9 26.3
7.1 9.5 15.2 28.6
7.5 9.8 NA NA
7.1 8.7 16.0 28.3
7.5 9.4 NA NA
7.1 8.9 NA NA
MALES MEAN 7.5 9.2 14.7 27.7 FEMALES MEAN 7.3 9.1 14.9 27.5
25767-01 M
7.3 9.1 15.1 26.3
NA = NOT APPLICABLE
14
NA
28.7 29.0
NA NA NA 37.8 34.7 NA NA NA NA 36.1 36.0 38.7 NA 38.2 NA NA
36.3 37.3
34.7
17
NA
34.4 34.9
NA NA NA 46.1 42.8 NA NA NA NA 44.2 43.8 47.5 NA 45.5 NA NA
44.5 45.3
41.2
21
NA
45.0 45.8
NA NA NA 61.2 57.1 NA NA NA NA 57.2 56.7 63.2 NA 58.3 NA NA
59.2 58.9
51.9
PAGE 17
-629-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25767-02 25767-03 25767-04 25767-05 25767-06 25767-07 25767-08 25767-09 25767-10 25767-11 25767-12 25767-13 25767-14 25767-15 25767-16 25767-17
M M M M M F F F F F F F F F F F
7.2 9.4 NA NA 7.0 9.6 15.1 23.8 6.6 9.0 NA NA 7.0 10.1 15.7 27.3 7.7 10.5 15.6 26.6 6.8 8.8 14.0 24.5 7.4 9.8 NA NA 5.9 7.7 10.6 19.5 7.1 9.8 NA NA 6.5 7.9 NA NA 7.5 9.6 14.7 25.4 6.9 9.9 NA NA 5.8 7.8 NA NA 6.6 9.7 NA NA 7.7 10.6 16.2 28.0 4.5 4.8 NA NA
MALES MEAN 7.1 9.6 15.4 26.0 FEMALES MEAN 6.6 8.8 13.9 24.4
25770-01 25770-02 25770-03 25770-04 25770-05 25770-06
M M M M M F
6.3 8.8 14.7 25.1 6.7 9.5 15.9 28.6 6.7 8.9 16.0 27.3 6.4 8.2 14.1 25.1 7.1 10.0 NA NA 6.6 9.0 NA NA
NA = NOT APPLICABLE
14
NA 32.8
NA 36.5 34.6 31.2
NA 27.4
NA NA 34.2 NA NA NA 34.8 NA
34.7 31.9
32.8 34.9 36.4 32.4
NA NA
17
NA 40.4
NA 43.5 42.0 38.1
NA 33.8
NA NA 39.3 NA NA NA 41.0 NA
41.8 38.1
37.5 40.4 41.1 38.0
NA NA
21
NA 55.6
NA 52.6 52.2 50.2
NA 44.1
NA NA 51.0 NA NA NA 52.3 NA
53.1 49.4
47.7 51.1 52.0 50.2
NA NA
PAGE 18
-630-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25770-07 25770-08 25770-09 25770-10 25770-11 25770-12 25770-13 25770-14
F F F F F F F F
6.4 8.2 14.4 24.7 7.1 9.5 NA NA 6.5 8.7 15.3 26.2 6.4 8.0 NA NA 6.5 8.5 14.6 24.0 5.8 7.6 NA NA 6.3 8.7 NA NA 6.3 8.6 15.2 26.0
MALES MEAN 6.6 9.1 15.2 26.5 FEMALES MEAN 6.4 8.5 14.9 25.2
25702-03 25702-04 25702-05 25702-06 25702-07 25702-08 25702-09 25702-11 25702-12 25702-13 25702-14 25702-15 25702-16 25702-17
M M M M M M M M M F F F F F
6.7 9.3 15.9 27.6 7.3 10.0 17.2 28.6 6.6 8.9 NA NA 7.1 10.4 NA NA 7.1 9.5 16.3 26.7 6.6 9.3 NA NA 6.8 9.4 NA NA 6.3 8.3 NA NA 7.2 10.0 17.0 27.6 6.2 8.5 15.1 25.5 6.1 7.4 NA NA 7.0 9.3 15.2 26.6 6.9 9.8 16.5 26.3 6.7 8.9 NA NA
NA = NOT APPLICABLE
14
32.0 NA
34.6 NA
32.7 NA NA
34.9
34.1 33.6
38.2 38.3
NA NA 35.8 NA NA NA 36.8 34.6 NA 35.7 35.5 NA
17
37.7 NA
40.0 NA
37.8 NA NA
39.9
39.3 38.9
45.5 45.2
NA NA 42.8 NA NA NA 44.6 41.3 NA 43.6 43.2 NA
21
49.1 NA
50.1 NA
48.7 NA NA
50.3
50.3 49.6
60.3 60.5
NA NA 53.4 NA NA NA 58.3 54.7 NA 57.3 53.9 NA
PAGE 19
-631-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 1: 0 MG/KG/DAY
25702-18 F
6.5 8.8 14.6 25.4
MALES MEAN 6.9 9.5 16.6 27.6 FEMALES MEAN 6.6 8.8 15.4 26.0
14
34.4 37.3 35.1
17
42.0 44.5 42.5
21
53.6 58.1 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
PAGE 20
-632-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25648-01 25648-02 25648-03 25648-04 25648-05 25648-06 25648-07 25648-08 25648-09 25648-10 25648-11 25648-12 25648-13 25648-14 25648-15 25648-16 25648-17
M M M M M M M M M M F F F F F F F
6.2 8.2 NA NA 6.6 8.2 NA NA 6.6 8.6 15.0 23.5 6.1 8.0 NA NA 6.1 8.2 NA NA 6.5 8.1 NA NA 5.8 7.8 13.5 21.3 6.5 8.5 14.8 23.1 6.3 7.7 NA NA 6.8 8.0 13.8 21.4 5.9 7.9 12.7 20.4 6.0 8.1 14.0 22.8 5.9 7.8 NA NA 5.6 7.2 12.7 21.1 6.1 8.0 NA NA 5.5 7.3 13.3 20.3 5.8 7.6 NA NA
MALES MEAN 6.4 8.1 14.3 22.3 FEMALES MEAN 5.8 7.7 13.2 21.2
25694-01 25694-02 25694-03 25694-04 25694-05
M M M M M
6.3 9.2 NA NA 6.3 8.6 NA NA 6.1 8.2 13.5 24.3 6.6 9.5 16.1 26.3 6.4 9.5 16.6 27.5
NA = NOT APPLICABLE
14
NA NA 31.1 NA NA NA 27.9 30.3 NA 28.5 28.2 29.8 NA 28.9 NA 27.0 NA
29.5 28.5
NA NA 32.0 34.6 36.0
17
NA NA 40.5 NA NA NA 35.9 39.2 NA 36.1 36.6 37.0 NA 37.0 NA 35.1 NA
37.9 36.4
NA NA 41.1 44.0 45.2
21
NA NA 51.5 NA NA NA 46.8 49.6 NA 46.4 44.8 46.5 NA 46.0 NA 43.9 NA
48.6 45.3
NA NA 56.5 56.8 60.3
PAGE 21
-633-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25694-06 25694-07 25694-08 25694-09 25694-10 25694-11 25694-12 25694-13 25694-14 25694-15 25694-16 25694-17 25694-18
M F F F F M M F F F F F F
6.9 9.9 NA NA 6.5 9.6 NA NA 6.1 9.3 15.1 24.5 5.9 8.5 13.7 24.3 5.4 7.9 NA NA 6.6 9.5 15.7 26.0 6.4 9.4 NA NA 5.5 7.7 12.3 21.6 5.9 8.5 NA NA 6.2 8.9 15.2 25.6 5.7 7.8 NA NA 5.8 8.6 NA NA 5.4 7.5 NA NA
MALES MEAN 6.5 9.2 15.5 26.0 FEMALES MEAN 5.8 8.4 14.1 24.0
25668-03 25668-04 25668-05 25668-06 25668-07 25668-08 25668-09 25668-10 25668-11
M M M F F F F F F
6.2 9.2 13.3 21.8 7.1 9.8 14.6 22.3 6.3 9.0 13.3 21.4 6.6 9.3 13.7 21.6 6.1 8.5 12.7 20.8 5.8 8.4 NA NA 6.0 9.3 NA NA 5.5 8.3 12.4 20.0 6.3 9.5 NA NA
NA = NOT APPLICABLE
14
NA NA 32.7 33.5 NA 35.7 NA 29.2 NA 34.0 NA NA NA
34.6 32.4
29.9 29.3 29.4 29.5 28.7
NA NA 27.6 NA
17
NA NA 41.5 41.8 NA 45.7 NA 37.5 NA 42.3 NA NA NA
44.0 40.8
36.4 37.5 35.1 36.3 35.6
NA NA 33.6 NA
21
NA NA 55.2 54.6 NA 61.6 NA 48.7 NA 57.9 NA NA NA
58.8 54.1
48.6 48.7 47.5 45.8 46.3
NA NA 44.2 NA
PAGE 22
-634-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25668-12 25668-13 25668-14 25668-15 25668-16 25668-17
F F F F F F
5.6 7.6 10.9 19.0 5.8 8.9 NA NA 6.1 9.0 NA NA 7.1 10.0 NA NA 5.4 7.5 11.0 19.0 6.2 9.1 NA NA
MALES MEAN 6.5 9.3 13.7 21.8 FEMALES MEAN 6.0 8.8 12.1 20.1
25631-01 25631-02 25631-03 25631-04 25631-05 25631-06 25631-07 25631-08 25631-09 25631-10 25631-11 25631-12 25631-13 25631-14
M M M M F F M F F F F F F F
8.0 11.3 NA NA 8.0 12.1 18.4 27.7 7.6 10.6 15.5 25.5 7.7 11.3 17.8 27.2 7.1 10.5 16.5 25.6 7.3 11.3 NA NA 7.6 11.1 17.3 27.7 7.5 10.9 NA NA 6.8 10.2 NA NA 7.0 10.2 15.5 25.6 7.4 11.3 NA NA 7.5 10.5 NA NA 6.8 10.4 16.2 25.6 7.6 11.5 NA NA
NA = NOT APPLICABLE
14
26.0 NA NA NA
26.9 NA
29.5 27.7
NA 37.0 35.3 34.5 33.8
NA 35.0
NA NA 33.0 NA NA 33.4 NA
17
33.6 NA NA NA
34.3 NA
36.3 34.7
NA 42.9 42.9 42.3 41.0
NA 44.8
NA NA 42.0 NA NA 41.3 NA
21
43.4 NA NA NA
44.7 NA
48.3 44.9
NA 57.4 55.2 55.2 52.0
NA 58.1
NA NA 53.9 NA NA 54.4 NA
PAGE 23
-635-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25631-15 F
7.2 10.6 16.8 26.0
MALES MEAN FEMALES MEAN
7.8 11.3 17.3 27.0 7.2 10.7 16.3 25.7
25660-01 25660-02 25660-03 25660-04 25660-05 25660-06 25660-07 25660-08 25660-09 25660-10 25660-11 25660-12 25660-13 25660-14 25660-15
M M M F M M M M M F F F F F F
7.3 10.2 16.4 25.4 7.8 11.4 18.4 27.9 4.8 7.3 NA NA 7.8 11.4 18.8 28.8 7.8 10.7 NA NA 8.2 11.7 19.1 30.4 7.9 11.5 19.1 29.8 7.6 11.3 NA NA 7.4 10.7 NA NA 7.3 10.8 16.8 26.6 7.4 10.6 NA NA 7.1 10.5 NA NA 7.3 10.4 17.1 26.7 7.7 11.3 17.5 27.9 6.9 10.4 NA NA
MALES MEAN FEMALES MEAN
7.4 10.6 18.3 28.4 7.4 10.8 17.6 27.5
25704-01 M 25704-02 M
8.0 11.5 17.8 27.2 7.8 11.1 NA NA
NA = NOT APPLICABLE
14
33.1
35.5 33.3
31.6 36.1
NA 35.1
NA 38.8 37.9
NA NA 33.9 NA NA 35.0 35.0 NA
36.1 34.8
34.9 NA
17
40.0
43.2 41.1
38.5 42.5
NA 42.0
NA 45.9 45.6
NA NA 40.9 NA NA 42.6 41.2 NA
43.1 41.7
42.9 NA
21
52.6
56.5 53.2
52.7 57.8
NA 57.6
NA 64.0 63.0
NA NA 53.4 NA NA 57.3 58.5 NA
59.4 56.7
56.4 NA
PAGE 24
-636-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25704-03 25704-04 25704-05 25704-06 25704-07 25704-08 25704-09 25704-10 25704-11 25704-12 25704-13
M M M M M F F F F F F
8.0 11.5 18.2 27.2 7.9 11.0 17.8 26.7 8.8 11.8 NA NA 8.6 12.0 18.7 28.7 7.6 10.5 NA NA 7.5 11.0 17.8 26.7 7.7 11.3 17.8 26.8 7.5 11.7 NA NA 7.6 10.8 17.2 26.9 7.9 10.9 16.5 25.7 7.6 10.6 NA NA
MALES MEAN FEMALES MEAN
8.1 11.3 18.1 27.5 7.6 11.1 17.3 26.5
25665-01 25665-02 25665-03 25665-04 25665-05 25665-06 25665-07 25665-08 25665-09 25665-10 25665-11
M M M M F F F F F F F
6.7 10.9 16.1 23.8 6.1 9.4 13.5 20.6 6.9 10.4 15.8 24.4 6.4 9.4 13.3 20.7 6.6 10.0 15.2 24.3 6.7 9.5 14.1 21.4 5.9 8.4 12.8 21.0 6.3 9.0 NA NA 6.8 10.4 NA NA 6.3 9.5 15.0 23.1 5.7 8.4 NA NA
NA = NOT APPLICABLE
14
32.6 34.1
NA 35.9
NA 33.6 32.8
NA 33.9 31.8
NA
34.4 33.0
29.7 27.6 30.8 26.9 30.5 27.2 26.2
NA NA 32.2 NA
17
40.7 41.6
NA 44.8
NA 42.4 41.2
NA 40.4 39.3
NA
42.5 40.8
36.0 33.3 36.8 31.7 37.0 32.3 31.9
NA NA 35.1 NA
21
54.1 57.2
NA 60.4
NA 54.4 51.7
NA 53.5 51.5
NA
57.0 52.8
48.5 44.7 52.5 42.0 51.1 43.8 44.0
NA NA 49.6 NA
PAGE 25
-637-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25665-12 F 6.1 9.4 NA NA
MALES MEAN FEMALES MEAN
6.5 10.0 14.7 22.4 6.3 9.3 14.3 22.5
25674-01 25674-02 25674-03 25674-04 25674-05 25674-06 25674-07 25674-08 25674-09 25674-10 25674-11 25674-12 25674-13 25674-14 25674-15 25674-16
M M M M M M M M M F F F F F F F
5.8 8.0 NA NA 5.5 7.7 12.6 19.9 5.7 8.1 NA NA 5.9 8.7 14.4 21.7 6.2 7.8 12.1 18.7 5.8 8.7 NA NA 5.9 8.1 13.4 21.3 6.1 8.3 NA NA 6.1 7.9 NA NA 5.9 8.3 NA NA 5.6 8.2 13.6 22.2 5.6 8.3 NA NA 5.8 8.0 13.5 20.9 5.1 6.1 8.8 14.1 6.1 7.9 NA NA 5.8 8.1 13.4 21.4
MALES MEAN 5.9 8.1 13.1 20.4 FEMALES MEAN 5.7 7.8 12.3 19.7
25652-01 M
7.7 12.0 19.2 28.6
NA = NOT APPLICABLE
14
NA
28.8 29.0
NA 25.9
NA 28.7 25.7
NA 28.3
NA NA NA 27.4 NA 28.9 20.7 NA 28.5
27.2 26.4
38.0
17
NA
34.5 34.1
NA 31.7
NA 35.0 29.4
NA 34.3
NA NA NA 33.9 NA 34.8 26.4 NA 35.0
32.6 32.5
43.7
21
NA
46.9 47.1
NA 42.1
NA 48.4 43.0
NA 46.6
NA NA NA 44.3 NA 48.5 34.2 NA 48.3
45.0 43.8
58.1
PAGE 26
-638-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25652-02 25652-03 25652-04 25652-05 25652-06 25652-07 25652-08 25652-09 25652-10 25652-11 25652-12 25652-13
M M M M M F F F F F F F
7.1 10.6 17.6 25.5 7.1 11.2 17.7 27.4 8.2 12.1 19.3 28.5 7.8 11.1 NA NA 8.0 11.1 NA NA 6.9 9.9 NA NA 7.0 10.4 17.4 26.6 6.5 9.6 NA NA 7.3 11.0 17.7 27.1 7.6 10.6 16.8 25.4 7.4 11.2 NA NA 6.4 8.7 14.2 22.5
MALES MEAN FEMALES MEAN
7.7 11.4 18.5 27.5 7.0 10.2 16.5 25.4
25733-01 25733-02 25733-03 25733-04 25733-05 25733-06 25733-07 25733-08 25733-09 25733-10
M M M M M M M F F F
6.4 9.4 13.6 21.5 6.5 8.5 NA NA 6.6 9.1 13.5 21.5 6.1 7.5 NA NA 6.7 9.4 NA NA 6.9 9.6 13.4 21.5 6.7 9.1 13.7 21.3 6.4 9.4 13.2 22.1 6.9 9.7 NA NA 6.3 8.7 NA NA
NA = NOT APPLICABLE
14
33.6 35.4 36.1
NA NA NA 36.1 NA 33.2 32.2 NA 27.7
35.8 32.3
28.4 NA
30.8 NA NA
29.4 26.1 26.4
NA NA
17
40.1 40.5 42.0
NA NA NA 39.5 NA 40.5 37.6 NA 35.2
41.6 38.2
36.5 NA
36.5 NA NA
37.3 35.6 34.6
NA NA
21
51.2 54.3 52.1
NA NA NA 51.1 NA 54.0 48.0 NA 41.6
53.9 48.7
42.4 NA
45.3 NA NA
46.5 38.9 41.1
NA NA
PAGE 27
-639-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25733-11 25733-12 25733-13 25733-14 25733-15
F F F F F
6.5 9.0 13.1 20.4 6.4 9.1 13.0 21.7 6.6 8.5 NA NA 6.5 9.1 NA NA 6.3 8.0 12.2 20.6
MALES MEAN 6.6 8.9 13.6 21.5 FEMALES MEAN 6.5 8.9 12.9 21.2
25748-01 25748-02 25748-03 25748-04 25748-05 25748-06 25748-07 25748-08 25748-09 25748-10
M M M M M M M F F F
9.0 12.8 18.4 28.4 9.0 13.3 19.0 28.1 8.0 12.1 NA NA 8.3 12.2 18.3 28.5 8.6 12.7 19.1 28.0 8.5 12.8 19.0 28.7 8.9 12.7 NA NA 8.4 12.2 18.2 27.3 8.5 13.0 18.6 28.6 6.7 9.9 14.6 22.8
MALES MEAN FEMALES MEAN
8.6 12.7 18.8 28.3 7.9 11.7 17.1 26.2
25753-01 M 25753-02 M 25753-03 M
7.7 10.0 NA NA 8.3 10.6 17.0 27.1 7.2 9.6 15.5 24.5
NA = NOT APPLICABLE
14
28.2 27.8
NA NA 27.4
28.7 27.5
33.6 35.1
NA 36.4 37.4 37.1
NA 32.5 35.8 29.7
35.9 32.7
NA 33.4 31.4
17
35.2 34.2
NA NA 36.6
36.5 35.2
41.7 42.0
NA 43.2 42.9 44.9
NA 39.7 41.8 36.2
42.9 39.2
NA 40.1 38.3
21
42.4 42.9
NA NA 45.1
43.3 42.9
55.9 59.7
NA 60.5 60.8 62.2
NA 51.7 58.9 49.7
59.8 53.4
NA 58.6 56.1
PAGE 28
-640-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25753-04 25753-05 25753-06 25753-08 25753-09 25753-10 25753-11 25753-12 25753-13 25753-14 25753-15 25753-16 25753-17 25753-18
M M M F F F F F F F F F F F
7.2 9.6 16.0 26.3 7.3 9.9 NA NA 8.3 10.6 16.9 27.6 7.2 9.9 NA NA 7.8 10.5 17.0 27.0 7.9 10.6 NA NA 6.6 9.6 NA NA 7.0 10.2 NA NA 7.4 NA NA NA 7.3 10.2 NA NA 7.4 9.4 16.1 25.9 7.4 10.9 17.4 27.8 7.6 11.2 18.2 27.7 6.4 8.3 NA NA
MALES MEAN FEMALES MEAN
7.7 10.1 16.4 26.4 7.3 10.1 17.2 27.1
25672-02 25672-03 25672-04 25672-05 25672-06 25672-07 25672-08 25672-09
M M M M M M M M
7.9 10.6 16.3 26.7 7.5 10.4 NA NA 8.5 11.5 NA NA 7.4 9.8 16.2 26.3 7.2 9.5 15.6 26.2 8.5 11.5 NA NA 8.2 11.7 NA NA 7.5 11.0 16.4 26.8
NA = NOT APPLICABLE
14
32.6 NA
32.1 NA
34.3 NA NA NA NA NA
32.5 35.4 34.7
NA
32.4 34.2
35.1 NA NA
35.0 33.1
NA NA 35.0
17
40.0 NA
39.9 NA
41.1 NA NA NA NA NA
38.1 41.5 42.9
NA
39.6 40.9
42.9 NA NA
41.8 41.7
NA NA 43.4
21
55.7 NA
53.3 NA
59.1 NA NA NA NA NA
49.7 58.4 57.0
NA
55.9 56.1
58.4 NA NA
52.8 49.2
NA NA 54.2
PAGE 29
-641-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25672-10 25672-11 25672-12 25672-13 25672-14 25672-15 25672-16 25672-17 25672-18
F F F F F F F F F
6.7 8.4 NA NA 7.7 10.6 17.6 28.3 6.4 8.7 13.7 23.1 5.9 8.6 NA NA 7.2 9.6 NA NA 7.6 10.3 17.0 27.3 4.7 5.6 9.0 17.2 7.2 10.3 NA NA 7.8 10.4 NA NA
MALES MEAN FEMALES MEAN
7.8 10.8 16.1 26.5 6.8 9.2 14.3 24.0
25655-01 25655-02 25655-03 25655-04 25655-05 25655-06 25655-07 25655-08 25655-09 25655-10 25655-11 25655-12 25655-13
M M M M M M M M M M F F F
6.7 9.0 15.4 23.4 7.3 10.1 NA NA 7.6 10.8 17.6 28.3 7.2 10.5 NA NA 7.1 9.9 NA NA 6.9 9.4 NA NA 6.7 9.5 14.9 24.2 7.4 11.0 NA NA 7.7 11.4 NA NA 7.2 10.5 17.3 29.4 6.8 9.0 15.2 26.6 7.2 10.1 16.2 26.8 6.6 9.3 15.5 26.1
NA = NOT APPLICABLE
14
NA 36.4 30.7
NA NA 33.2 24.1 NA NA
34.6 31.1
29.2 NA
34.6 NA NA NA
31.9 NA NA
36.6 33.2 34.2 30.8
17
NA 44.1 38.5
NA NA 41.9 31.2 NA NA
42.5 38.9
35.6 NA
41.7 NA NA NA
37.6 NA NA
43.2 41.1 41.5 37.4
21
NA 58.6 49.7
NA NA 51.8 39.8 NA NA
53.7 50.0
44.8 NA
53.8 NA NA NA
50.8 NA NA
58.4 52.4 53.2 47.2
PAGE 30
-642-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25655-14 F 25655-15 F 25655-16 F
5.7 7.2 NA NA 7.0 9.8 15.5 27.4 6.2 8.4 NA NA
MALES MEAN FEMALES MEAN
7.2 10.2 16.3 26.3 6.6 9.0 15.6 26.7
25727-02 25727-03 25727-04 25727-05 25727-06 25727-07 25727-08 25727-09 25727-10 25727-11 25727-12 25727-13 25727-14 25727-15 25727-16
M M M M M M M F F F F F F F F
6.4 9.2 13.5 22.1 6.0 7.9 NA NA 6.4 8.7 NA NA 6.5 8.4 12.5 21.0 6.6 8.6 12.7 22.1 6.4 9.1 13.7 23.6 6.7 9.1 NA NA 6.0 7.8 11.9 20.0 6.0 8.1 11.8 21.5 6.0 8.1 NA NA 6.2 7.9 NA NA 6.1 8.7 12.7 22.1 6.5 8.4 NA NA 5.6 7.8 NA NA 5.6 7.8 11.0 18.3
NA = NOT APPLICABLE
14
NA 33.3
NA
33.1 32.9
30.5 NA NA
29.9 29.8 31.1
NA 27.7 29.0
NA NA 31.3 NA NA 24.3
17
NA 39.3
NA
39.5 39.8
38.3 NA NA
39.8 39.1 41.3
NA 36.5 37.9
NA NA 41.2 NA NA 33.9
21
NA 51.5
NA
52.0 51.1
48.5 NA NA
49.2 48.6 49.2
NA 46.6 47.3
NA NA 51.1 NA NA 38.6
PAGE 31
-643-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25727-17 F 5.6 6.9 NA NA
MALES MEAN 6.4 8.7 13.1 22.2 FEMALES MEAN 6.0 7.9 11.9 20.5
25626-01 25626-02 25626-03 25626-04 25626-05 25626-06 25626-07 25626-08 25626-09 25626-10 25626-11 25626-12 25626-13 25626-14 25626-15 25626-16
M M M M M M M F F F F F F F F F
6.0 8.0 14.0 24.6 6.5 9.0 NA NA 6.2 8.6 NA NA 6.1 8.4 14.5 25.8 6.3 8.7 NA NA 5.9 8.2 13.4 23.4 6.6 9.6 16.7 27.8 5.5 7.1 12.7 22.5 5.9 7.7 13.7 24.3 6.0 7.9 NA NA 5.8 7.7 NA NA 5.9 8.1 13.5 24.6 6.3 8.5 NA NA 5.9 8.0 NA NA 5.6 7.9 13.6 24.4 5.3 7.4 NA NA
MALES MEAN 6.2 8.6 14.7 25.4 FEMALES MEAN 5.8 7.8 13.4 24.0
25739-01 M
8.1 11.0 17.6 29.3
NA = NOT APPLICABLE
14
NA
30.3 28.1
33.3 NA NA
32.9 NA
31.3 36.8 30.6 32.3
NA NA 30.7 NA NA 32.7 NA
33.6 31.6
37.1
17
NA
39.6 37.4
41.9 NA NA
42.1 NA
39.9 46.1 37.8 40.8
NA NA 39.3 NA NA 41.1 NA
42.5 39.8
47.1
21
NA
48.9 45.9
56.8 NA NA
53.0 NA
51.9 60.7 47.2 49.8
NA NA 50.6 NA NA 52.8 NA
55.6 50.1
66.0
PAGE 32
-644-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25739-02 25739-03 25739-04 25739-05 25739-06 25739-07 25739-08 25739-09 25739-10 25739-11 25739-12 25739-13 25739-14
M M M M M M M M M F F F F
8.4 11.4 NA NA 8.5 11.2 NA NA 8.5 11.0 NA NA 8.0 10.9 NA NA 8.5 11.6 19.4 30.6 8.2 11.7 18.6 30.0 8.2 11.2 NA NA 7.9 10.6 17.5 28.7 8.4 11.2 NA NA 8.0 10.4 17.6 29.1 7.2 10.0 16.8 27.8 7.6 10.4 17.3 28.6 7.3 10.7 17.7 28.7
MALES MEAN FEMALES MEAN
8.3 11.2 18.3 29.7 7.5 10.4 17.4 28.6
25749-02 25749-03 25749-04 25749-05 25749-06 25749-07 25749-08 25749-09 25749-10
M M M M M M F F F
7.4 11.2 16.4 25.5 7.7 11.6 17.7 27.9 7.4 11.0 16.5 26.2 7.4 10.9 NA NA 7.9 11.6 NA NA 7.2 10.3 15.7 25.5 6.9 10.5 16.4 26.0 7.4 10.5 16.2 25.5 7.1 10.7 15.8 25.5
NA = NOT APPLICABLE
14
NA NA NA NA 38.7 36.5 NA 37.8 NA 38.3 35.6 37.8 37.6
37.5 37.3
34.0 36.8 32.9
NA NA 33.2 32.8 33.2 32.9
17
NA NA NA NA 48.6 47.3 NA 46.5 NA 46.9 47.0 46.8 46.6
47.4 46.8
39.9 43.3 41.4
NA NA 39.4 39.0 39.7 38.6
21
NA NA NA NA 65.0 59.9 NA 63.2 NA 61.6 60.9 60.8 61.3
63.5 61.2
54.3 58.5 51.9
NA NA 52.8 52.0 54.4 52.5
PAGE 33
-645-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25749-11 F
7.2 10.6 16.1 25.0
MALES MEAN FEMALES MEAN
7.5 11.1 16.6 26.3 7.2 10.6 16.1 25.5
25756-01 25756-02 25756-03 25756-04 25756-05 25756-06 25756-07 25756-08 25756-09 25756-10 25756-11 25756-12 25756-13 25756-14 25756-15 25756-16
M M M M M M M F F F F F F F F F
7.2 10.4 16.2 26.4 6.6 6.5 NA NA 7.5 10.2 15.9 26.4 7.2 10.4 15.7 26.3 8.2 11.4 17.9 28.6 7.8 10.8 NA NA 7.0 10.0 NA NA 6.8 10.2 NA NA 7.3 10.7 NA NA 7.7 10.9 NA NA 7.4 10.3 15.4 25.6 6.5 9.3 NA NA 7.0 9.3 15.1 25.2 7.1 10.2 NA NA 7.5 10.8 16.4 26.8 6.8 10.1 15.8 26.4
MALES MEAN FEMALES MEAN
7.4 10.0 16.4 26.9 7.1 10.2 15.7 26.0
25741-01 M
7.7 10.1 17.3 26.5
NA = NOT APPLICABLE
14
30.8
34.2 32.4
34.2 NA
34.0 34.6 36.3
NA NA NA NA NA 34.5 NA 33.4 NA 35.1 33.7
34.8 34.2
33.8
17
37.5
41.0 38.7
41.8 NA
42.5 42.2 44.0
NA NA NA NA NA 42.3 NA 41.3 NA 44.0 41.7
42.6 42.3
41.2
21
51.0
54.4 52.5
54.5 NA
61.8 56.2 57.8
NA NA NA NA NA 57.3 NA 55.5 NA 58.8 56.9
57.6 57.1
52.7
PAGE 34
-646-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25741-02 25741-03 25741-04 25741-05 25741-06 25741-07 25741-08 25741-09 25741-10 25741-11 25741-12 25741-13 25741-14 25741-15 25741-16 25741-17
M M M M M M F F F F F F F F F F
8.2 11.7 19.7 30.3 8.0 11.5 19.2 29.5 7.8 10.9 NA NA 6.9 9.9 NA NA 8.2 11.3 NA NA 8.1 10.3 17.2 28.1 8.0 11.2 NA NA 7.8 10.6 18.1 28.6 6.9 9.5 NA NA 7.8 11.1 NA NA 7.2 11.0 NA NA 6.4 8.8 NA NA 6.8 9.3 15.7 24.9 7.7 10.7 18.4 29.2 7.6 10.5 17.7 28.7 7.3 9.5 NA NA
MALES MEAN FEMALES MEAN
7.8 10.8 18.4 28.6 7.4 10.2 17.5 27.9
25752-01 25752-02 25752-03 25752-04 25752-05 25752-06
M M M M M M
7.6 11.2 18.6 30.2 8.1 11.9 NA NA 7.3 10.9 18.0 29.3 8.4 11.8 NA NA 7.4 10.3 16.6 27.1 7.1 NA NA NA
NA = NOT APPLICABLE
14
38.9 38.0
NA NA NA 34.7 NA 35.4 NA NA NA NA 33.2 36.9 36.1 NA
36.4 35.4
38.1 NA
38.9 NA
34.9 NA
17
47.4 45.3
NA NA NA 42.4 NA 42.8 NA NA NA NA 41.4 45.7 43.9 NA
44.1 43.5
48.0 NA
47.6 NA
43.4 NA
21
64.0 58.8
NA NA NA 56.2 NA 54.6 NA NA NA NA 53.8 58.5 56.6 NA
57.9 55.9
64.4 NA
63.4 NA
57.8 NA
PAGE 35
-647-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25752-07 25752-08 25752-09 25752-10 25752-11 25752-12 25752-13 25752-14 25752-15
M M M F F F F F F
7.7 11.4 NA NA 7.0 10.2 NA NA 7.6 11.6 19.2 30.6 7.0 10.5 NA NA 7.6 10.8 18.4 29.7 7.5 11.2 NA NA 7.0 11.2 18.8 31.7 7.1 10.9 18.5 30.0 7.2 10.3 17.1 28.2
MALES MEAN FEMALES MEAN
7.6 11.2 18.1 29.3 7.2 10.8 18.2 29.9
25758-01 25758-02 25758-03 25758-04 25758-05 25758-06 25758-07 25758-08 25758-09 25758-10 25758-11 25758-12 25758-13
M M M M M M F F F F F F F
7.3 10.1 17.1 27.8 6.8 9.9 15.8 26.8 7.3 9.9 NA NA 7.5 10.7 NA NA 8.1 11.4 18.5 29.3 7.4 10.6 16.8 27.7 7.4 10.7 NA NA 7.1 10.0 16.5 28.1 6.6 9.7 16.4 26.9 6.4 9.5 14.4 23.7 7.1 10.9 NA NA 6.2 8.5 12.1 19.3 6.8 9.0 NA NA
NA = NOT APPLICABLE
14
NA NA 39.3 NA 39.1 NA 39.6 39.9 36.4
37.8 38.8
35.9 34.8
NA NA 38.3 36.1 NA 35.8 34.1 31.1 NA 25.5 NA
17
NA NA 48.4 NA 48.5 NA 48.2 48.5 45.6
46.9 47.7
43.7 42.9
NA NA 46.1 44.2 NA 44.4 41.6 39.4 NA 31.7 NA
21
NA NA 63.3 NA 66.2 NA 61.5 64.3 60.3
62.2 63.1
60.6 57.9
NA NA 62.2 59.7 NA 59.0 56.6 52.0 NA 40.2 NA
PAGE 36
-648-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25758-14 F 6.8 9.2 NA NA
MALES MEAN FEMALES MEAN
7.4 10.4 17.1 27.9 6.8 9.7 14.9 24.5
25719-01 25719-02 25719-03 25719-04 25719-05 25719-06 25719-07 25719-08 25719-09 25719-10 25719-11 25719-12 25719-13 25719-14 25719-15 25719-16
M M M M M M M M M M M M F F F F
6.7 9.7 NA NA 5.5 NA NA NA 6.9 9.7 16.4 27.0 7.1 10.5 17.7 28.5 6.7 9.9 NA NA 7.2 10.3 NA NA 7.6 11.1 19.2 30.2 6.5 9.1 NA NA 6.6 10.1 17.3 28.3 6.6 9.8 NA NA 6.7 9.8 NA NA 6.5 9.6 NA NA 5.8 8.0 14.0 22.9 6.2 8.5 14.5 24.6 6.9 10.2 17.7 28.5 6.2 9.2 NA NA
NA = NOT APPLICABLE
14
NA
36.3 31.6
NA NA 34.3 36.2 NA NA 37.3 NA 36.6 NA NA NA 30.3 31.6 36.5 NA
17
NA
44.2 39.3
NA NA 41.9 42.9 NA NA 44.6 NA 46.1 NA NA NA 38.0 39.2 43.9 NA
21
NA
60.1 52.0
NA NA 55.0 56.6 NA NA 61.5 NA 62.3 NA NA NA 46.9 50.6 58.3 NA
PAGE 37
-649-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25719- 17 F
6.4 9.4 15.7 26.4
MALES MEAN FEMALES MEAN
6.7 10.0 17.7 28.5 6.3 9.1 15.5 25.6
14
33.5 36.1 33.0
17
41.3 43.9 40.6
21
52.9 58.9 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
PAGE 38
-650-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25606-01 25606-02 25606-03 25606-04 25606-05 25606-06 25606-07 25606-08 25606-09 25606-10 25606-11 25606-12 25606-13 25606-14
M M M F F F F F F F F F F F
7.3 11.1 18.4 26.3 7.7 10.9 18.8 27.3 7.2 10.7 18.3 26.9 7.5 10.7 17.6 25.4 7.1 10.2 16.7 24.3 7.2 10.4 NA NA 7.0 10.3 NA NA 7.3 11.0 17.8 25.7 6.7 9.8 NA NA 6.7 10.0 NA NA 7.3 10.4 17.4 25.1 7.4 11.2 18.0 25.3 7.5 10.8 NA NA 6.8 9.6 NA NA
MALES MEAN FEMALES MEAN
7.4 10.9 18.5 26.8 7.1 10.4 17.5 25.2
25614-01 25614-02 25614-03 25614-04 25614-05 25614-06 25614-07 25614-08
M M M M M M M M
7.2 9.7 NA NA 6.8 9.3 NA NA 6.6 8.8 NA NA 6.8 8.3 13.7 22.0 6.8 9.8 16.2 24.4 7.0 9.8 NA NA 6.3 8.2 14.0 21.8 6.8 9.5 NA NA
NA = NOT APPLICABLE
14
32.2 33.9 33.8 31.8 30.1
NA NA 31.7 NA NA 30.7 31.1 NA NA
33.3 31.1
NA NA NA 29.9 31.6 NA 29.4 NA
17
39.5 40.9 40.8 37.2 37.3
NA NA 37.0 NA NA 36.7 36.4 NA NA
40.4 36.9
NA NA NA 36.7 39.6 NA 35.0 NA
21
51.7 54.3 52.9 50.9 50.6
NA NA 50.3 NA NA 51.5 49.4 NA NA
53.0 50.5
NA NA NA 49.3 55.3 NA 47.8 NA
PAGE 39
-651-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25614-09 25614-10 25614-11 25614-12 25614-13 25614-14 25614-15 25614-16 25614-17 25614-18
M M M M F F F F F F
7.2 9.2 NA NA 7.1 9.9 16.1 24.5 7.0 9.1 NA NA 6.9 8.6 NA NA 6.2 8.3 13.9 21.4 6.7 9.0 NA NA 6.0 7.4 12.2 19.6 6.7 8.4 NA NA 5.7 7.2 12.6 20.3 6.2 7.8 13.4 20.9
MALES MEAN 6.9 9.2 15.0 23.2 FEMALES MEAN 6.3 8.0 13.0 20.6
25671-01 25671-02 25671-03 25671-04 25671-05 25671-06 25671-07 25671-08 25671-09 25671-10 25671-11 25671-12
M M M M M F F F F F F F
6.9 9.5 NA NA 6.4 9.0 15.1 24.8 7.2 9.8 16.2 27.0 6.2 8.7 14.6 24.2 7.0 9.1 14.2 23.8 6.2 8.1 13.9 23.8 6.2 8.8 NA NA 6.4 9.1 15.2 25.1 5.9 8.6 14.2 22.6 6.8 9.4 NA NA 6.4 8.9 NA NA 6.3 8.3 NA NA
NA = NOT APPLICABLE
14
NA 32.2
NA NA 27.9 NA 26.0 NA 17.2 27.9
30.8 24.8
NA 33.4 36.2 32.9 31.2 31.7
NA 33.0 29.7
NA NA NA
17
NA 38.6
NA NA 34.8 NA 32.1 NA 33.0 34.3
37.5 33.6
NA 42.7 45.8 41.6 39.6 39.9
NA 41.5 38.0
NA NA NA
21
NA 51.7
NA NA 46.9 NA 44.5 NA 42.5 47.3
51.0 45.3
NA 51.7 56.4 49.3 50.4 47.5
NA 50.8 46.4
NA NA NA
PAGE 40
-652-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25671-13 F
7.0 9.0 13.1 21.7
MALES MEAN 6.7 9.2 15.0 25.0 FEMALES MEAN 6.4 8.8 14.1 23.3
25698-01 25698-02 25698-03 25698-04 25698-05 25698-06 25698-07 25698-08 25698-09 25698-10 25698-11 25698-12 25698-13 25698-14 25698-15
M M M F M M F F F F F F F F F
6.5 8.4 NA NA 6.1 7.7 12.4 20.2 6.6 8.2 13.5 20.6 6.3 8.4 13.4 21.5 6.3 8.1 12.7 20.5 6.1 7.2 11.4 17.5 6.1 7.9 NA NA 5.6 6.1 NA NA 5.6 7.4 NA NA 6.0 8.4 13.2 21.8 6.1 8.3 NA NA 6.0 8.2 12.7 20.5 6.1 8.3 NA NA 6.5 8.6 12.7 19.5 5.8 NA NA NA
MALES MEAN 6.3 7.9 12.5 19.7 FEMALES MEAN 6.0 8.0 13.0 20.8
25609-01 M 25609-02 M
7.6 11.0 NA NA 7.1 9.4 13.6 20.5
NA = NOT APPLICABLE
14
29.1
33.4 30.9
NA 28.9 28.8 30.4 28.3 26.2
NA NA NA 30.1 NA 27.8 NA 27.5 NA
28.1 29.0
NA 25.9
17
37.3
42.4 39.2
NA 35.3 34.8 36.0 34.3 31.9
NA NA NA 36.9 NA 35.9 NA 34.0 NA
34.1 35.7
NA 32.8
21
46.1
52.0 47.7
NA 45.0 45.0 46.4 43.1 41.3
NA NA NA 47.2 NA 42.4 NA 43.6 NA
43.6 44.9
NA 42.3
PAGE 41
-653-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25609-03 25609-04 25609-05 25609-06 25609-07 25609-08 25609-09 25609-10 25609-11 25609-12 25609-13 25609-14 25609-15
M M M M F F F F F F F F F
7.4 9.4 14.6 23.6 7.5 10.6 15.8 24.5 7.9 10.5 NA NA 8.6 11.3 16.5 25.8 7.8 10.8 NA NA 7.3 10.0 NA NA 7.7 10.9 NA NA 7.7 10.8 NA NA 7.2 10.2 15.9 24.2 7.9 10.8 17.3 26.6 7.2 10.5 NA NA 7.4 10.8 15.4 23.9 7.7 11.0 17.2 26.5
MALES MEAN FEMALES MEAN
7.7 10.4 15.1 23.6 7.5 10.6 16.5 25.3
25677-01 25677-02 25677-03 25677-04 25677-05 25677-06 25677-07 25677-08 25677-09
M M M M M M M F F
7.4 NA NA NA 6.9 10.1 15.6 23.8 6.5 9.9 NA NA 6.6 10.1 15.2 23.6 6.9 10.5 16.4 24.8 6.9 10.2 NA NA 7.2 11.2 16.6 26.3 5.9 9.9 15.4 23.7 6.3 NA NA NA
NA = NOT APPLICABLE
14
29.2 28.8
NA 33.0
NA NA NA NA 28.7 33.1 NA 30.5 32.2
29.2 31.1
NA 33.0
NA 31.7 32.2
NA 34.5 31.1
NA
17
37.0 35.7
NA 40.7
NA NA NA NA 36.1 40.1 NA 37.3 39.1
36.6 38.2
NA 39.7
NA 40.5 40.4
NA 42.6 39.5
NA
21
50.8 47.7
NA 57.0
NA NA NA NA 44.7 56.5 NA 51.3 52.1
49.5 51.2
NA 50.5
NA 49.0 52.3
NA 56.8 49.5
NA
PAGE 42
-654-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25677-10 25677-11 25677-12 25677-13
F F F F
6.3 9.6 14.9 23.6 6.2 9.1 NA NA 5.9 8.1 12.8 20.9 6.8 10.6 16.0 24.4
MALES MEAN FEMALES MEAN
6.9 10.3 16.0 24.6 6.2 9.5 14.8 23.2
25623-03 25623-04 25623-05 25623-06 25623-07 25623-08 25623-09 25623-10 25623-11 25623-12 25623-13 25623-14 25623-15
M M M M M M M F F F F F F
6.6 9.8 13.4 21.8 6.8 9.9 13.8 23.2 7.3 10.5 14.6 24.8 6.9 10.4 NA NA 6.9 9.7 NA NA 6.9 10.4 14.8 23.3 6.8 9.9 NA NA 6.2 8.9 NA NA 6.6 9.5 NA NA 7.0 7.7 NA NA 6.7 9.8 13.8 23.2 6.6 9.0 12.9 22.2 5.8 8.6 12.1 19.9
MALES MEAN FEMALES MEAN
6.9 10.1 14.2 23.3 6.5 8.9 12.9 21.8
25653-01 M 7.6 10.7 NA NA
NA = NOT APPLICABLE
14
31.2 NA
29.8 32.9
32.9 31.3
29.1 30.3 31.9
NA NA 28.5 NA NA NA NA 30.2 29.4 25.1
30.0 28.2
NA
17
38.2 NA
36.7 39.7
40.8 38.5
36.0 37.0 39.5
NA NA 36.2 NA NA NA NA 36.5 36.2 31.6
37.2 34.8
NA
21
48.9 NA
45.3 52.0
52.2 48.9
47.1 49.6 52.2
NA NA 47.8 NA NA NA NA 50.6 48.8 41.3
49.2 46.9
NA
PAGE 43
-655-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25653-02 25653-03 25653-04 25653-05 25653-06 25653-07 25653-08 25653-09 25653-10 25653-11 25653-12 25653-13 25653-14
M M M F F M F F F M F F M
7.6 10.4 16.9 26.9 7.0 9.6 15.2 25.4 7.6 10.1 NA NA 7.7 10.4 15.4 25.3 7.3 9.9 15.8 25.4 7.0 9.6 15.7 25.5 6.1 8.1 NA NA 7.3 9.9 NA NA 7.1 8.9 NA NA 7.6 10.1 15.9 26.2 7.3 9.5 15.5 25.3 7.2 9.4 15.0 24.2 8.3 11.3 NA NA
MALES MEAN FEMALES MEAN
7.5 10.3 15.9 26.0 7.1 9.4 15.4 25.1
25604-01 25604-02 25604-03 25604-04 25604-05 25604-06 25604-07 25604-08 25604-09
M M M M M M M F F
7.1 11.2 NA NA 6.3 9.1 15.7 24.7 7.3 10.8 18.2 27.6 6.9 11.2 18.1 27.1 6.3 9.5 NA NA 6.7 10.4 17.1 25.5 6.5 10.3 NA NA 6.4 9.9 16.3 24.5 5.7 8.7 NA NA
NA = NOT APPLICABLE
14
34.5 35.0
NA 34.3 34.2 33.9
NA NA NA 35.4 34.7 30.6 NA
34.7 33.5
NA 31.5 36.5 35.0
NA 34.1
NA 31.7
NA
17
42.7 42.8
NA 42.3 41.6 42.9
NA NA NA 44.1 43.2 39.0 NA
43.1 41.5
NA 38.4 43.3 42.7
NA 40.3
NA 37.9
NA
21
56.0 58.5
NA 58.6 55.7 58.8
NA NA NA 57.9 55.2 50.8 NA
57.8 55.1
NA 50.5 58.9 54.8
NA 54.7
NA 51.1
NA
PAGE 44
-656-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25604-10 F 25604-11 F 25604-12 F
6.4 9.8 15.6 24.6 5.9 9.0 14.8 23.8 6.4 10.3 17.5 26.2
MALES MEAN FEMALES MEAN
6.7 10.4 17.3 26.2 6.2 9.5 16.1 24.8
25678-01 25678-02 25678-03 25678-04 25678-05 25678-06 25678-07 25678-08 25678-09 25678-10 25678-11 25678-12 25678-13 25678-14
M M M M M M M F F F F F F F
6.1 8.8 NA NA 5.5 7.9 13.9 23.4 6.2 9.4 17.0 27.1 6.3 9.2 NA NA 6.6 9.0 NA NA 6.3 9.1 15.8 26.8 5.8 8.3 15.1 25.3 6.5 9.5 16.9 26.1 6.2 9.0 NA NA 5.9 8.5 15.3 24.5 6.1 8.6 15.3 24.5 6.2 8.8 NA NA 5.5 7.6 12.9 22.5 6.2 9.2 NA NA
NA = NOT APPLICABLE
14
32.5 31.7 32.7
34.3 32.2
NA 30.6 35.0
NA NA 33.8 32.9 34.0 NA 33.2 32.0 NA 29.6 NA
17
37.8 38.6 40.0
41.2 38.6
NA 37.7 42.3
NA NA 41.2 40.2 41.7 NA 39.9 37.8 NA 37.0 NA
21
48.8 49.6 49.4
54.7 49.7
NA 49.0 54.5
NA NA 53.9 53.2 56.3 NA 52.7 48.7 NA 49.1 NA
PAGE 45
-657-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25678-15 F 4.6 7.0 NA NA
MALES MEAN 6.1 8.8 15.5 25.7 FEMALES MEAN 5.9 8.5 15.1 24.4
25684-02 25684-03 25684-04 25684-05 25684-06 25684-07 25684-08 25684-09 25684-10 25684-11 25684-12
M M M M F F F F F F F
8.0 11.5 18.6 28.5 7.3 10.6 16.0 25.3 7.3 10.2 15.4 24.2 7.7 10.6 16.4 26.2 7.3 11.0 17.1 25.8 6.8 9.7 NA NA 6.9 9.5 14.1 22.4 6.1 8.9 NA NA 7.1 10.2 NA NA 6.5 9.5 13.9 21.7 7.4 10.4 15.9 24.8
MALES MEAN FEMALES MEAN
7.6 10.7 16.6 26.1 6.9 9.9 15.3 23.7
25714-01 25714-02 25714-03 25714-04 25714-05 25714-06
M M M M M M
8.1 11.4 NA NA 7.7 11.0 17.5 28.1 7.7 11.4 17.8 29.2 8.2 11.1 NA NA 7.9 11.4 18.2 27.7 7.8 10.8 17.0 27.1
NA = NOT APPLICABLE
14
NA
33.1 32.2
36.9 33.5 30.5 35.3 31.8
NA 30.3
NA NA 29.2 31.8
34.1 30.8
NA 33.3 36.5
NA 35.3 34.6
17
NA
40.4 39.1
43.3 39.1 37.0 43.3 39.5
NA 37.6
NA NA 35.8 38.9
40.7 38.0
NA 42.6 44.4
NA 43.3 42.7
21
NA
52.7 51.7
59.5 54.6 50.1 59.2 55.2
NA 52.7
NA NA 47.4 53.6
55.9 52.2
NA 55.8 61.8
NA 57.4 60.1
PAGE 46
-658-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25714-07 25714-08 25714-09 25714-10 25714-11 25714-12 25714-13
F F F F F F F
7.6 10.8 NA NA 7.5 11.0 17.5 25.6 7.5 10.6 17.0 26.4 7.2 10.4 16.5 26.8 7.6 10.6 NA NA 7.4 10.4 NA NA 7.2 10.8 17.2 27.4
MALES MEAN FEMALES MEAN
7.9 11.2 17.6 28.0 7.4 10.7 17.1 26.6
25650-01 25650-02 25650-03 25650-04 25650-05 25650-06 25650-07 25650-08 25650-09 25650-10 25650-11 25650-12 25650-13 25650-14 25650-15
F M M M M M M M M M M M M F F
4.1 5.2 8.4 15.3 7.4 9.7 15.3 25.5 7.3 10.0 NA NA 6.8 9.3 NA NA 6.0 7.2 NA NA 7.1 9.5 NA NA 7.5 9.7 NA NA 6.7 10.4 16.9 28.0 7.1 9.5 NA NA 7.9 10.1 NA NA 6.8 9.3 15.2 25.7 7.7 10.7 NA NA 6.7 9.3 14.2 25.2 7.3 10.4 16.4 26.7 7.1 9.8 NA NA
NA = NOT APPLICABLE
14
NA 32.6 33.6 33.4
NA NA 33.4
34.9 33.3
21.8 33.3
NA NA NA NA NA 36.4 NA NA 32.2 NA 32.7 34.3 NA
17
NA 38.5 40.8 40.5
NA NA 41.4
43.3 40.3
29.4 41.6
NA NA NA NA NA 45.7 NA NA 41.7 NA 41.9 43.0 NA
21
NA 55.6 56.8 56.4
NA NA 54.4
58.8 55.8
37.9 57.2
NA NA NA NA NA 58.2 NA NA 54.8 NA 53.8 58.7 NA
PAGE 47
-659-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25650-16 25650-17 25650-18 25650-19
F F F F
7.3 9.6 NA NA 6.7 9.2 14.7 26.5 7.0 9.3 NA NA 6.4 8.6 13.5 23.8
MALES MEAN 7.1 9.6 15.4 26.1 FEMALES MEAN 6.6 8.9 13.3 23.1
25735-01 25735-02 25735-03 25735-04 25735-05 25735-06 25735-07 25735-08 25735-09 25735-10 25735-11 25735-12 25735-13
M M M M M M F F F F F F F
7.9 11.5 17.0 27.5 7.3 10.4 NA NA 7.6 11.2 NA NA 7.6 11.5 18.0 29.1 7.8 11.4 18.4 29.3 7.9 11.5 18.9 30.4 7.3 11.0 17.2 27.9 6.6 9.9 15.6 26.1 6.9 10.2 NA NA 7.6 11.5 17.9 28.6 7.1 10.6 NA NA 7.2 10.4 NA NA 6.9 10.5 NA NA
NA = NOT APPLICABLE
14
NA 33.4
NA 30.9
33.7 30.1
37.6 NA NA
39.0 36.6 40.6 37.0 32.4
NA 38.1
NA NA NA
17
NA 42.4
NA 39.3
42.7 38.5
43.5 NA NA
45.8 43.6 48.9 42.8 38.7
NA 44.9
NA NA NA
21
NA 52.8
NA 51.6
56.0 50.3
59.2 NA NA
60.6 55.2 64.6 58.0 47.4
NA 58.0
NA NA NA
PAGE 48
-660-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25735-14 F
7.0 10.4 16.3 26.8
MALES MEAN FEMALES MEAN
7.7 11.3 18.1 29.1 7.1 10.6 16.8 27.4
25722-01 25722-02 25722-03 25722-04 25722-05 25722-06 25722-07 25722-08 25722-09 25722-10 25722-11 25722-12 25722-13 25722-14 25722-15
M M M M M M M M M M F F F F F
6.6 8.1 13.2 22.1 6.3 9.0 NA NA 6.5 9.4 NA NA 6.4 8.1 12.6 20.6 6.3 8.3 13.5 21.8 6.6 8.6 NA NA 6.5 8.8 NA NA 6.7 8.8 NA NA 6.9 9.6 NA NA 6.2 9.2 13.3 22.3 6.8 9.5 14.9 23.5 6.6 9.5 14.8 23.7 6.9 9.6 14.6 23.2 6.5 9.5 NA NA 6.6 8.9 14.1 24.3
MALES MEAN 6.5 8.8 13.2 21.7 FEMALES MEAN 6.7 9.4 14.6 23.7
25642-01 M 25642-02 M
7.8 10.3 NA NA 7.4 10.3 17.3 27.3
NA = NOT APPLICABLE
14
36.1
38.5 35.9
27.9 NA NA
30.0 29.2
NA NA NA NA 30.6 31.5 31.8 31.5 NA 29.2
29.4 31.0
NA 36.6
17
43.2
45.5 42.4
33.8 NA NA
35.1 34.7
NA NA NA NA 35.7 37.1 37.5 36.5 NA 36.3
34.8 36.9
NA 46.7
21
57.9
59.9 55.3
44.6 NA NA
47.2 47.6
NA NA NA NA 47.8 47.8 49.5 52.3 NA 45.7
46.8 48.8
NA 59.7
PAGE 49
-661-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25642-03 25642-04 25642-05 25642-06 25642-07 25642-08 25642-09 25642-10 25642-11 25642-12 25642-13 25642-14 25642-15
M M M M M M F F F F F F F
7.5 9.8 NA NA 8.1 11.0 18.4 29.6 7.8 10.7 16.9 27.8 8.1 11.2 NA NA 6.7 8.7 NA NA 8.7 11.6 18.6 28.9 6.9 8.9 NA NA 6.9 9.2 NA NA 7.4 10.0 NA NA 7.5 10.2 16.7 27.7 7.6 10.1 16.4 27.3 7.7 10.2 NA NA 7.2 10.5 16.9 27.3
MALES MEAN FEMALES MEAN
7.8 10.5 17.8 28.4 7.3 9.9 16.7 27.4
25628-01 25628-02 25628-03 25628-04 25628-05 25628-06 25628-07 25628-08 25628-09
M M M M M M M M M
5.8 8.6 13.6 23.1 6.4 8.8 NA NA 6.5 8.7 NA NA 5.9 8.4 NA NA 6.7 9.3 14.3 24.9 5.5 NA NA NA 5.7 8.2 13.0 23.5 6.0 8.5 NA NA 6.3 8.7 13.8 24.3
NA = NOT APPLICABLE
14
NA 37.9 34.1
NA NA 36.1 NA NA NA 33.3 33.9 NA 35.4
36.2 34.2
30.8 NA NA NA
33.5 NA
30.3 NA
32.3
17
NA 46.3 42.8
NA NA 43.8 NA NA NA 41.8 41.4 NA 42.7
44.9 42.0
38.6 NA NA NA
41.7 NA
38.1 NA
40.1
21
NA 62.8 54.6
NA NA 63.1 NA NA NA 52.8 54.2 NA 56.5
60.1 54.5
51.6 NA NA NA
54.7 NA
49.8 NA
52.6
PAGE 50
-662-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25628-10 25628-11 25628-12 25628-13 25628-14 25628-15 25628-16 25628-17
F F F F F F F F
5.6 7.6 NA NA 6.0 8.3 NA NA 5.6 8.3 NA NA 5.7 8.5 NA NA 6.6 8.4 13.8 23.9 6.4 9.2 14.9 24.2 5.7 8.1 12.6 22.1 5.5 6.2 9.4 18.3
MALES MEAN 6.1 8.7 13.7 24.0 FEMALES MEAN 5.9 8.1 12.7 22.1
25763-01 25763-02 25763-03 25763-04 25763-05 25763-06 25763-07 25763-08 25763-09 25763-10 25763-11 25763-12 25763-13 25763-14
M M M M M M M M F F F F F F
6.2 7.9 NA NA 6.3 9.0 14.7 26.7 5.9 7.6 NA NA 6.4 8.1 13.5 24.6 6.7 9.3 NA NA 6.8 8.8 NA NA 6.4 8.3 13.0 24.5 6.6 7.7 NA NA 6.5 8.8 14.2 25.8 6.5 8.4 14.0 25.1 5.5 6.9 NA NA 5.7 8.1 NA NA 6.1 7.3 NA NA 5.8 7.2 NA NA
NA = NOT APPLICABLE
14
NA NA NA NA 33.1 32.8 30.7 24.0
31.7 30.2
NA 35.1
NA 33.3
NA NA 33.1 NA 33.5 33.2 NA NA NA NA
17
NA NA NA NA 40.4 42.3 38.2 31.7
39.6 38.2
NA 45.0
NA 42.1
NA NA 43.3 NA 42.3 42.3 NA NA NA NA
21
NA NA NA NA 52.6 55.4 50.9 40.3
52.2 49.8
NA 52.8
NA 50.4
NA NA 51.5 NA 53.1 51.4 NA NA NA NA
PAGE 51
-663-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25763-15 25763-16 25763-17 25763-18 25763-19
F F F F F
6.4 7.8 13.4 25.1 5.3 7.5 NA NA 5.8 7.5 NA NA 6.2 8.2 NA NA 6.4 7.7 NA NA
MALES MEAN 6.4 8.3 13.7 25.3 FEMALES MEAN 6.0 7.8 13.9 25.3
25766-01 25766-02 25766-03 25766-04 25766-05 25766-06 25766-07 25766-08 25766-09 25766-10 25766-11
M M M M F F F F F M M
6.9 9.6 13.1 21.7 7.2 10.1 14.7 23.3 7.0 9.3 13.8 22.7 6.8 NA NA NA 7.1 10.0 NA NA 6.3 8.6 12.7 20.6 6.5 9.4 13.6 23.0 6.7 9.3 13.9 22.0 6.4 8.7 12.6 20.1 6.9 9.5 NA NA 6.7 9.8 13.8 21.6
MALES MEAN 6.9 9.7 13.9 22.3 FEMALES MEAN 6.6 9.2 13.2 21.4
25689-01 M 25689-02 M
8.3 11.0 NA NA 7.4 10.6 17.5 28.5
NA = NOT APPLICABLE
14
33.5 NA NA NA NA
33.8 33.4
26.5 29.1 27.7
NA NA 25.0 28.5 26.7 24.8 NA 26.4
27.4 26.3
NA 37.0
17
42.8 NA NA NA NA
43.5 42.5
32.7 33.6 33.6
NA NA 30.3 34.7 32.5 30.9 NA 31.8
32.9 32.1
NA 45.1
21
54.3 NA NA NA NA
51.6 52.9
38.9 44.9 44.8
NA NA 37.2 46.2 43.4 41.4 NA 42.2
42.7 42.1
NA 62.8
PAGE 52
-664-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25689-03 25689-04 25689-05 25689-06 25689-07 25689-08 25689-09 25689-10 25689-11 25689-12 25689-13 25689-14 25689-15
M M M M F F F F F F F F F
7.9 10.9 17.7 29.8 7.6 10.3 16.4 27.9 7.7 10.7 NA NA 7.6 10.8 16.3 28.4 7.6 10.0 16.1 27.5 7.4 9.4 NA NA 7.4 10.3 NA NA 7.7 11.6 NA NA 7.7 10.6 NA NA 7.2 10.4 16.6 28.3 7.5 10.4 16.5 26.9 7.4 9.6 15.4 26.8 7.0 9.8 NA NA
MALES MEAN FEMALES MEAN
7.8 10.7 17.0 28.7 7.4 10.2 16.2 27.4
25708-01 25708-02 25708-03 25708-04 25708-05 25708-06 25708-07 25708-08 25708-09
M M M M M M M M M
7.3 10.8 17.7 28.6 7.5 10.6 NA NA 7.6 10.9 NA NA 7.8 11.4 17.6 27.5 7.7 10.3 NA NA 7.1 10.6 NA NA 7.1 10.7 15.4 26.9 7.5 11.1 NA NA 6.8 9.7 15.0 25.2
NA = NOT APPLICABLE
14
37.0 36.3
NA 37.1 34.8
NA NA NA NA 37.6 34.9 34.8 NA
36.9 35.5
36.8 NA NA
35.0 NA NA
35.6 NA
33.1
17
44.3 44.6
NA 45.1 43.4
NA NA NA NA 45.9 42.3 42.8 NA
44.8 43.6
44.5 NA NA
42.4 NA NA
43.7 NA
41.0
21
64.0 63.2
NA 60.6 58.8
NA NA NA NA 62.5 59.4 55.5 NA
62.7 59.1
56.0 NA NA
57.6 NA NA
56.1 NA
55.5
PAGE 53
-665-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25708-10 25708-11 25708-12 25708-13 25708-14 25708-15
F F F F F F
6.8 8.8 NA NA 7.0 9.8 14.8 26.3 5.9 8.1 12.0 21.3 7.1 9.6 NA NA 6.7 9.6 14.9 24.4 6.6 9.1 14.6 25.0
MALES MEAN FEMALES MEAN
7.4 10.7 16.4 27.1 6.7 9.2 14.1 24.3
25743-01 25743-02 25743-03 25743-04 25743-05 25743-06 25743-07 25743-08 25743-09 25743-10 25743-11 25743-12 25743-13 25743-14 25743-15 25743-16
M M M M M M M M M M F F F F F F
6.1 8.3 NA NA 6.4 9.0 14.8 24.8 6.3 8.7 NA NA 5.3 7.0 11.9 21.5 6.2 8.3 NA NA 5.7 7.5 NA NA 6.1 NA NA NA 5.3 7.4 12.6 21.6 6.4 8.5 15.5 26.3 6.5 8.9 NA NA 5.7 8.0 12.9 21.9 5.1 7.3 11.8 20.2 6.3 9.0 NA NA 5.5 8.2 NA NA 6.0 8.2 NA NA 5.2 7.0 11.8 20.9
NA = NOT APPLICABLE
14
NA 34.0 28.0
NA 32.0 31.1
35.1 31.3
NA 33.3
NA 28.7
NA NA NA 30.3 34.3 NA 29.5 27.7 NA NA NA 27.8
17
NA 41.4 35.7
NA 40.1 38.5
42.9 38.9
NA 39.3
NA 34.9
NA NA NA 34.8 41.4 NA 36.2 34.4 NA NA NA 34.6
21
NA 52.2 46.3
NA 52.9 49.4
56.3 50.2
NA 53.0
NA 45.8
NA NA NA 45.5 56.3 NA 47.1 45.2 NA NA NA 42.8
PAGE 54
-666-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25743-17 F 25743-18 F
5.9 8.1 NA NA 5.5 7.6 13.2 23.0
MALES MEAN 6.0 8.2 13.7 23.6 FEMALES MEAN 5.7 7.9 12.4 21.5
25761-01 25761-02 25761-03 25761-04 25761-05 25761-06 25761-07 25761-08 25761-09 25761-10 25761-11 25761-12 25761-13 25761-14 25761-15
M M M M M M M F F F F F F F F
7.8 10.4 NA NA 7.5 10.7 NA NA 8.5 11.2 NA NA 7.7 10.3 16.7 28.3 7.4 10.2 16.3 28.4 7.6 11.0 17.7 29.1 7.8 11.2 18.2 30.0 7.0 9.6 15.8 27.9 7.3 9.5 15.8 27.8 8.0 11.0 NA NA 7.5 10.5 NA NA 7.1 10.2 NA NA 7.5 10.4 16.2 28.3 7.3 10.1 NA NA 7.1 10.2 16.2 27.3
MALES MEAN FEMALES MEAN
7.8 10.7 17.2 29.0 7.4 10.2 16.0 27.8
25712-02 M
6.2 9.4 15.9 26.0
NA = NOT APPLICABLE
14
NA 28.9
31.7 28.5
NA NA NA 36.4 36.6 37.3 39.0 36.6 36.5 NA NA NA 36.6 NA 36.0
37.3 36.4
34.2
17
NA 37.3
37.6 35.6
NA NA NA 45.1 44.5 46.7 48.9 44.4 46.0 NA NA NA 44.7 NA 44.3
46.3 44.9
43.1
21
NA 50.6
50.2 46.4
NA NA NA 58.6 57.6 60.1 65.5 59.7 57.6 NA NA NA 52.2 NA 57.4
60.5 56.7
55.2
PAGE 55
-667-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25712-03 25712-04 25712-05 25712-06 25712-07 25712-08 25712-09 25712-10 25712-11 25712-12 25712-13 25712-14 25712-15 25712-16 25712-17
M M M M F F F F F F F F F F F
7.1 9.3 15.4 25.1 6.8 10.1 NA NA 7.1 9.7 15.7 25.7 7.5 10.9 18.4 29.6 7.2 10.5 16.8 27.2 6.3 9.2 14.5 22.9 7.5 10.9 NA NA 7.0 10.3 NA NA 7.0 9.3 NA NA 7.3 9.9 NA NA 7.8 11.2 NA NA 6.7 9.6 NA NA 7.5 9.9 NA NA 6.9 9.9 16.4 26.6 7.7 10.2 17.3 26.6
MALES MEAN FEMALES MEAN
6.9 9.9 16.4 26.6 7.2 10.1 16.3 25.8
25746-01 25746-02 25746-03 25746-04 25746-05 25746-06 25746-07
M M M M M M M
7.0 9.8 NA NA 7.3 NA NA NA 7.3 9.3 15.7 26.7 7.0 9.5 NA NA 6.8 9.1 NA NA 7.2 10.0 16.7 26.4 7.3 10.9 17.5 27.7
NA = NOT APPLICABLE
14
32.3 NA
33.5 37.3 34.2 30.7
NA NA NA NA NA NA NA 33.8 34.3
34.3 33.3
NA NA 36.1 NA NA 35.1 37.1
17
40.9 NA
41.3 46.8 42.4 39.2
NA NA NA NA NA NA NA 42.8 42.6
43.0 41.8
NA NA 44.9 NA NA 44.1 45.7
21
55.9 NA
56.4 61.9 50.8 51.8
NA NA NA NA NA NA NA 56.8 56.3
57.4 53.9
NA NA 64.1 NA NA 61.5 64.2
PAGE 56
-668-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25746-08 25746-09 25746-10 25746-11 25746-12 25746-13 25746-14 25746-15 25746-16 25746-17 25746-18
M M M M F F F F F F F
7.2 9.7 NA NA 6.9 9.7 NA NA 7.2 10.5 NA NA 7.5 10.2 16.6 27.5 6.5 9.3 15.2 25.2 6.7 9.3 NA NA 5.8 8.0 13.5 22.3 6.4 9.0 15.2 25.3 6.8 9.4 NA NA 7.6 10.4 17.0 28.0 6.5 8.8 NA NA
MALES MEAN 7.2 9.9 16.6 27.1 FEMALES MEAN 6.6 9.2 15.2 25.2
14
NA NA NA 36.9 33.6 NA 31.4 34.4 NA 37.0 NA
36.3 34.1
17 21
NA NA NA 45.8 41.8 NA 40.8 42.7 NA 46.2 NA
NA NA NA 60.6 54.7 NA 107.7 71.7 NA 62.6 NA
45.1 42.9
62.6 74.2
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
PAGE 57
-669-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25696-01 25696-02 25696-03 25696-04 25696-05 25696-06 25696-07 25696-08 25696-09 25696-10 25696-11 25696-12 25696-13 25696-14 25696-15 25696-16
M M M M M M M M M M F F F F F F
8.2 11.1 NA NA 7.1 9.7 NA NA 7.5 9.8 NA NA 7.9 11.0 16.7 25.5 8.2 11.2 NA NA 7.8 10.0 15.0 21.8 7.6 10.6 15.5 24.4 8.0 10.9 NA NA 7.5 9.9 15.0 22.6 8.3 10.2 NA NA 6.9 9.8 16.2 24.4 7.1 9.0 NA NA 7.2 10.1 16.6 24.5 7.5 10.1 15.2 23.1 7.3 9.9 NA NA 7.1 9.7 15.6 24.4
MALES MEAN FEMALES MEAN
7.8 10.4 15.6 23.6 7.2 9.8 15.9 24.1
25686-01 25686-02 25686-03 25686-04 25686-05 25686-06
M M M M M M
7.0 10.1 16.3 25.6 6.5 8.9 14.8 22.9 6.5 9.3 15.0 24.5 6.6 9.4 15.6 23.6 6.5 8.9 NA NA 6.1 8.3 NA NA
NA = NOT APPLICABLE
14
NA NA NA 31.5 NA 29.2 31.5 NA 30.2 NA 30.9 NA 31.3 30.1 NA 32.4
30.6 31.2
33.1 29.8 32.1 29.5
NA NA
17
NA NA NA 38.3 NA 35.6 38.1 NA 35.6 NA 37.8 NA 37.8 36.3 NA 38.9
36.9 37.7
38.1 35.6 36.8 34.7
NA NA
21
NA NA NA 52.2 NA 48.2 52.4 NA 49.3 NA 49.5 NA 52.2 49.4 NA 53.0
50.5 51.0
49.8 46.5 50.1 46.6
NA NA
PAGE 58
-670-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25686-07 25686-08 25686-09 25686-10 25686-11 25686-12 25686-13 25686-14 25686-15
M M F F F F F F F
6.3 8.9 NA NA 6.3 8.6 NA NA 6.0 8.7 14.4 22.8 5.6 7.8 12.7 20.7 6.6 9.0 15.5 23.9 6.3 8.4 NA NA 5.7 8.2 NA NA 5.8 8.2 NA NA 6.0 7.9 12.6 20.1
MALES MEAN 6.5 9.1 15.4 24.2 FEMALES MEAN 6.0 8.3 13.8 21.9
25639-01 25639-02 25639-03 25639-04 25639-05 25639-06 25639-07 25639-08 25639-09 25639-10 25639-11 25639-12 25639-13
M M M F M M M M M F F F F
7.5 10.7 NA NA 7.0 9.5 NA NA 7.4 9.5 16.3 26.0 7.0 10.0 17.6 27.3 7.0 10.6 16.0 24.6 7.6 10.6 17.8 26.6 7.6 11.3 NA NA 7.8 10.6 NA NA 7.1 10.5 18.1 28.1 5.4 7.1 NA NA 7.1 9.4 16.6 24.1 6.5 9.6 15.9 24.8 6.6 8.7 NA NA
NA = NOT APPLICABLE
14
NA NA 29.9 27.0 31.0 NA NA NA 26.5
31.1 28.6
NA NA 34.6 35.3 33.4 34.7 NA NA 36.5 NA 34.4 33.7 NA
17
NA NA 35.1 32.1 36.3 NA NA NA 32.1
36.3 33.9
NA NA 42.1 43.0 41.1 41.4 NA NA 43.8 NA 41.3 40.3 NA
21
NA NA 47.1 41.7 48.1 NA NA NA 43.2
48.3 45.0
NA NA 52.8 53.4 51.9 51.1 NA NA 55.9 NA 53.3 52.5 NA
PAGE 59
-671-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25639-14 F 25639-15 F 25639-16 F
7.3 10.2 16.1 26.0 5.6 7.3 NA NA 6.8 9.8 NA NA
MALES MEAN FEMALES MEAN
7.4 10.4 17.1 26.3 6.5 9.0 16.6 25.6
25658-03 25658-04 25658-05 25658-06 25658-07 25658-08 25658-09 25658-10 25658-11 25658-12 25658-13 25658-14 25658-15
M M M M M M M F F F F F F
7.6 8.5 13.6 22.0 7.5 8.8 13.1 20.6 7.0 8.5 13.2 21.0 7.6 8.8 NA NA 6.9 8.1 NA NA 7.6 9.6 14.7 23.2 7.0 8.1 NA NA 7.4 8.8 14.6 22.5 7.0 8.8 NA NA 7.6 8.8 NA NA 6.7 8.0 13.0 20.6 7.2 8.3 13.1 21.2 6.7 8.3 12.9 20.4
MALES MEAN 7.3 8.6 13.7 21.7 FEMALES MEAN 7.1 8.5 13.4 21.2
25676-02 M 25676-03 M
8.3 11.4 18.7 26.8 8.6 11.5 19.1 28.1
NA = NOT APPLICABLE
14
34.8 NA NA
34.8 34.6
29.7 28.5 29.3
NA NA 29.8 NA 30.4 NA NA 28.8 27.8 28.1
29.3 28.8
31.8 35.6
17
40.9 NA NA
42.1 41.4
38.2 36.2 36.8
NA NA 37.8 NA 36.7 NA NA 36.5 35.4 36.2
37.3 36.2
37.0 42.7
21
52.3 NA NA
52.9 52.9
49.1 45.3 47.0
NA NA 46.0 NA 47.7 NA NA 46.9 42.7 45.7
46.9 45.8
53.6 59.9
PAGE 60
-672-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25676-04 25676-05 25676-06 25676-07 25676-08 25676-09 25676-10 25676-11 25676-12 25676-13 25676-14 25676-15
M M M M F F F F F F F F
7.7 10.4 17.9 25.8 7.5 10.3 NA NA 8.6 11.5 19.2 27.8 8.1 10.8 NA NA 7.7 10.0 17.1 25.9 8.0 10.8 18.3 26.3 7.3 9.5 NA NA 7.7 9.6 NA NA 8.2 10.8 18.5 27.2 7.2 9.6 NA NA 7.8 10.3 NA NA 8.1 10.5 18.0 25.7
MALES MEAN FEMALES MEAN
8.1 11.0 18.7 27.1 7.8 10.1 18.0 26.3
25600-01 25600-02 25600-03 25600-04 25600-05 25600-06 25600-07 25600-08 25600-09 25600-10
M M M M F F F F F F
7.2 10.1 17.1 26.6 7.3 11.1 17.6 26.4 7.7 10.6 17.0 26.4 7.2 10.4 16.8 27.2 6.7 9.9 16.2 25.2 6.5 9.6 NA NA 6.9 10.5 NA NA 7.0 10.0 NA NA 6.8 9.4 NA NA 7.2 10.2 NA NA
NA = NOT APPLICABLE
14
32.8 NA
35.7 NA
32.3 33.3
NA NA 34.8 NA NA 32.5
34.0 33.2
34.9 35.1 36.0 34.9 33.2
NA NA NA NA NA
17
38.1 NA
42.2 NA
38.7 38.7
NA NA 40.5 NA NA 38.0
40.0 39.0
43.3 43.5 44.8 43.0 41.6
NA NA NA NA NA
21
55.4 NA
58.4 NA
53.9 54.8
NA NA 54.5 NA NA 51.6
56.8 53.7
58.9 57.7 59.0 57.3 54.9
NA NA NA NA NA
PAGE 61
-673-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25600-11 25600-12 25600-13 25600-14 25600-15 25600-16 25600-17
F F F F F F F
7.2 11.0 18.3 28.8 6.7 10.4 17.0 27.4 7.2 10.8 NA NA 7.1 9.6 NA NA 7.1 11.0 18.7 28.1 7.0 9.4 NA NA 7.0 11.0 NA NA
MALES MEAN FEMALES MEAN
7.4 10.6 17.1 26.7 7.0 10.2 17.6 27.4
25603-01 25603-02 25603-03 25603-04 25603-05 25603-06 25603-07 25603-08 25603-09 25603-10 25603-11 25603-12 25603-13 25603-14
M M M M M F F F F F F F F F
7.2 10.2 16.1 24.2 6.4 8.1 13.9 21.4 7.0 9.9 NA NA 7.1 10.7 16.7 24.6 6.7 9.3 15.5 24.0 6.6 9.6 15.4 23.4 6.2 9.2 14.7 22.0 6.8 8.6 NA NA 6.2 8.2 NA NA 6.9 10.1 15.7 24.3 6.3 8.2 NA NA 6.8 9.5 15.5 24.7 7.0 10.2 NA NA 6.9 10.1 NA NA
NA = NOT APPLICABLE
14
36.7 35.3
NA NA 35.9 NA NA
35.2 35.3
31.5 28.2
NA 30.1 30.9 29.7 28.4
NA NA 29.1 NA 30.6 NA NA
17
44.5 43.9
NA NA 44.7 NA NA
43.7 43.7
37.8 34.0
NA 36.6 37.3 35.4 33.5
NA NA 36.3 NA 36.6 NA NA
21
62.1 58.0
NA NA 58.7 NA NA
58.2 58.4
55.7 49.8
NA 51.2 55.6 53.6 49.6
NA NA 51.8 NA 52.8 NA NA
PAGE 62
-674-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25603-15 F 6.9 10.0 NA NA
MALES MEAN 6.9 9.6 15.6 23.6 FEMALES MEAN 6.7 9.4 15.3 23.6
25630-01 25630-02 25630-03 25630-04 25630-05 25630-06 25630-07 25630-08 25630-09 25630-10 25630-11 25630-12 25630-13 25630-14
M M M M M M M F F F F F F F
6.4 9.4 15.4 24.6 6.4 9.8 NA NA 6.7 9.4 NA NA 6.7 10.4 16.6 25.6 6.3 9.5 15.5 24.1 6.6 9.7 15.9 25.1 6.3 9.8 NA NA 6.3 9.3 NA NA 6.3 9.0 14.6 23.2 6.1 9.0 14.6 22.1 6.2 9.4 15.8 24.9 6.1 8.9 NA NA 5.9 9.0 14.8 23.5 6.9 10.4 NA NA
MALES MEAN 6.5 9.7 15.9 24.9 FEMALES MEAN 6.3 9.3 15.0 23.4
25703-01 M 25703-02 M 25703-03 M
7.4 9.7 NA NA 7.5 10.7 18.6 28.7 7.5 10.2 17.6 27.4
NA = NOT APPLICABLE
14
NA
30.2 29.5
32.6 NA NA
33.2 32.3 33.5
NA NA 31.0 30.9 33.0 NA 31.9 NA
32.9 31.7
NA 36.7 34.1
17
NA
36.4 35.5
41.0 NA NA
42.8 41.8 43.7
NA NA 38.6 38.7 41.8 NA 39.2 NA
42.3 39.6
NA 44.4 42.0
21
NA
53.1 52.0
53.9 NA NA
54.0 53.8 54.2
NA NA 47.4 50.3 53.7 NA 50.8 NA
54.0 50.6
NA 58.3 54.7
PAGE 63
-675-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25703-04 25703-05 25703-06 25703-07 25703-08 25703-09 25703-10 25703-11 25703-12 25703-13 25703-14 25703-15
M M F F F F F F F F F F
7.7 10.7 18.5 29.3 7.3 9.7 17.2 26.4 7.6 10.0 NA NA 6.8 9.0 NA NA 6.6 8.4 15.5 24.6 6.7 9.3 16.3 26.0 6.7 8.9 16.2 25.4 6.5 8.0 NA NA 7.5 9.8 NA NA 7.2 9.5 NA NA 7.2 10.0 18.1 27.5 7.1 9.0 NA NA
MALES MEAN FEMALES MEAN
7.5 10.2 18.0 28.0 7.0 9.2 16.5 25.9
25673-01 25673-02 25673-03 25673-04 25673-05 25673-06 25673-07 25673-08 25673-09 25673-10
M M M M M M M M M F
6.5 8.8 NA NA 5.7 8.1 NA NA 6.3 8.3 13.3 19.7 6.3 8.9 13.8 21.6 6.1 7.9 NA NA 6.5 8.4 NA NA 6.8 9.6 NA NA 6.3 8.3 12.9 20.0 6.4 9.1 13.7 21.4 5.7 8.5 13.2 19.6
NA = NOT APPLICABLE
14
37.3 34.6
NA NA 31.9 33.7 31.6 NA NA NA 35.7 NA
35.7 33.2
NA NA 25.7 28.3 NA NA NA 25.2 26.4 24.0
17
44.7 43.6
NA NA 38.7 40.8 39.1 NA NA NA 42.3 NA
43.7 40.2
NA NA 32.0 34.3 NA NA NA 31.2 32.3 29.6
21
61.7 59.6
NA NA 52.4 54.4 50.1 NA NA NA 56.3 NA
58.6 53.3
NA NA 41.1 44.4 NA NA NA 39.4 39.9 37.7
PAGE 64
-676-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25673-11 25673-12 25673-13 25673-14 25673-15
F F F F F
6.0 8.1 13.2 19.9 6.2 8.7 13.9 22.1 6.1 8.6 NA NA 6.1 8.3 12.7 19.1 6.0 8.3 NA NA
MALES MEAN 6.3 8.6 13.4 20.7 FEMALES MEAN 6.0 8.4 13.3 20.2
25611-04 25611-05 25611-06 25611-07 25611-08 25611-09 25611-10 25611-11 25611-12 25611-13 25611-14 25611-15
M M M M M M M F F F F F
7.8 11.1 NA NA 8.1 11.0 16.3 23.7 8.0 11.0 NA NA 7.7 10.6 16.6 24.6 7.8 10.9 16.5 24.5 7.5 10.7 NA NA 7.3 10.7 16.2 23.8 7.2 10.1 15.5 24.1 7.9 10.7 15.4 23.4 7.7 10.7 16.8 24.2 7.8 10.1 NA NA 8.5 11.4 17.4 25.3
MALES MEAN FEMALES MEAN
7.7 10.9 16.4 24.2 7.8 10.6 16.3 24.3
25619-01 M
6.8 9.5 14.6 22.7
NA = NOT APPLICABLE
14
26.5 28.7
NA 25.2
NA
26.4 26.1
NA 31.1
NA 31.1 33.1
NA 32.3 29.0 32.3 32.7
NA 34.1
31.9 32.0
29.7
17
32.6 34.4
NA 31.0
NA
32.5 31.9
NA 37.9
NA 38.4 39.9
NA 38.0 36.4 38.5 38.5
NA 40.4
38.6 38.5
33.3
21
41.7 44.6
NA 40.0
NA
41.2 41.0
NA 51.5
NA 50.4 52.6
NA 50.5 46.7 49.6 50.5
NA 53.7
51.3 50.1
45.8
PAGE 65
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25619-02 25619-03 25619-04 25619-05 25619-06 25619-07 25619-08 25619-09 25619-10 25619-11 25619-12 25619-13 25619-14
M M M M M F F F F F F F F
5.8 8.3 NA NA 7.0 10.0 16.0 24.9 6.0 8.1 11.9 18.4 7.0 9.9 15.3 25.4 6.4 8.8 NA NA 6.9 9.1 NA NA 6.7 9.0 14.2 23.7 6.0 8.2 NA NA 6.2 8.4 12.7 21.6 6.2 8.5 NA NA 6.5 9.1 14.4 23.7 6.0 8.0 NA NA 6.0 8.5 13.5 22.2
MALES MEAN 6.5 9.1 14.5 22.9 FEMALES MEAN 6.3 8.6 13.7 22.8
25705-01 25705-02 25705-03 25705-04 25705-05 25705-06 25705-07 25705-08 25705-09
M M M M M M M F F
4.3 5.8 9.9 17.0 6.5 10.0 NA NA 7.2 10.5 NA NA 6.6 10.2 NA NA 6.7 10.3 17.2 27.3 6.4 9.6 16.0 24.5 6.5 10.0 16.8 26.3 6.8 11.1 18.1 27.8 6.5 9.9 16.5 25.7
NA = NOT APPLICABLE
14
NA 33.2 24.1 32.8
NA NA 30.7 NA 27.6 NA 27.7 NA 29.3
30.0 28.8
23.5 NA NA NA
36.0 32.3 33.8 34.8 34.7
17
NA 37.6 28.4 37.5
NA NA 36.2 NA 31.6 NA 32.5 NA 34.0
34.2 33.6
26.3 NA NA NA
42.1 36.6 41.2 40.7 39.6
21
NA 49.8 35.3 50.8
NA NA 48.4 NA 39.5 NA 40.8 NA 47.5
45.4 44.1
33.2 NA NA NA
55.7 49.7 50.5 50.8 52.3
PAGE 66
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25705-10 25705-11 25705-12 25705-13
F F F F
6.4 9.8 17.0 26.3 6.5 10.0 17.0 26.9 6.9 10.5 NA NA 6.6 9.8 NA NA
MALES MEAN FEMALES MEAN
6.3 9.5 15.0 23.8 6.6 10.2 17.2 26.7
25691-01 25691-02 25691-03 25691-04 25691-05 25691-06 25691-07 25691-08 25691-09 25691-10 25691-11 25691-12 25691-14 25691-15
F M M M M M M M M F F F F F
6.6 8.9 NA NA 6.7 9.0 14.4 25.1 6.1 8.9 NA NA 6.9 9.2 NA NA 7.0 9.8 15.8 26.7 7.1 10.2 16.1 26.8 6.6 9.8 16.7 27.8 7.0 10.4 NA NA 7.1 10.3 NA NA 6.0 8.5 NA NA 7.0 10.1 17.4 29.2 6.7 9.6 15.9 27.8 6.8 9.9 17.4 27.7 7.2 10.3 17.2 28.9
NA = NOT APPLICABLE
14
35.4 36.3
NA NA
31.4 35.3
NA 35.5
NA NA 35.4 36.9 37.2 NA NA NA 36.0 38.1 37.6 37.4
17
41.0 41.6
NA NA
36.6 40.7
NA 41.3
NA NA 40.4 44.6 43.1 NA NA NA 45.2 45.7 45.0 46.3
21
55.4 55.0
NA NA
47.3 53.4
NA 56.0
NA NA 51.7 56.4 50.8 NA NA NA 53.3 58.0 57.8 61.1
PAGE 67
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-680-
co
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25691-16 F
6.1
NA NA
MALES MEAN 6.8 9.7 15.8 26.6 FEMALES MEAN 6.6 9.4 17.0 28.4
25717-03 25717-04 25717-05 25717-06 25717-07 25717-08 25717-09 25717-10 25717-11 25717-12 25717-13 25717-14 25717-15
M M M M M M F F F F F F F
6.2 7.6 12.2 20.8 6.2 7.6 12.0 21.0 5.9 7.6 NA NA 6.7 8.2 13.5 22.8 6.2 8.0 13.1 21.7 5.5 7.0 NA NA 6.5 8.1 NA NA 4.5 5.8 NA NA 5.9 7.2 11.1 19.6 5.5 7.0 NA NA 6.3 8.2 12.2 20.9 6.1 7.2 11.9 20.5 6.4 7.9 12.3 21.0
MALES MEAN 6.1 7.7 12.7 21.6 FEMALES MEAN 5.9 7.3 11.9 20.5
25616-01 M 25616-02 M 25616-03 M 25616-04 M
6.3 9.8 NA NA 6.3 9.8 15.8 26.6 7.2 11.3 18.5 29.8 6.9 10.5 NA NA
NA = NOT APPLICABLE
14
NA
36.3 37.3
26.7 26.4
NA 29.0 27.9
NA NA NA 25.6 NA 26.7 28.1 26.8
27.5 26.8
NA 34.8 37.3
NA
17
NA
42.4 45.6
34.9 33.9
NA 35.6 35.8
NA NA NA 33.4 NA 34.7 35.1 33.8
35.1 34.3
NA 43.7 45.9
NA
21
NA
53.7 57.6
46.4 45.0
NA 49.5 46.6
NA NA NA 44.8 NA 45.6 46.5 42.3
46.9 44.8
NA 56.1 62.9
NA
PAGE 68
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25616-05 25616-06 25616-07 25616-08 25616-09 25616-10 25616-11 25616-12 25616-13 25616-14 25616-15
M M M F F F F M F F F
6.9 10.5 16.2 27.4 7.2 11.1 NA NA 7.1 11.4 NA NA 7.2 11.1 NA NA 6.7 9.8 NA NA 6.5 9.5 14.9 24.8 7.0 10.5 16.9 27.7 7.3 11.0 17.1 28.7 5.8 8.4 13.1 23.7 6.2 9.2 14.7 26.0 6.6 9.7 NA NA
MALES MEAN FEMALES MEAN
6.9 10.7 16.9 28.1 6.6 9.7 14.9 25.6
25715-03 25715-04 25715-05 25715-06 25715-07 25715-08 25715-09 25715-10 25715-11 25715-12 25715-13
M M M M M M M F F F F
6.0 8.3 NA NA 6.5 9.1 15.9 25.8 6.8 9.8 NA NA 6.5 8.9 15.1 25.4 6.5 9.2 14.6 25.0 7.1 9.2 15.8 25.4 6.6 8.8 NA NA 5.9 8.0 13.7 23.2 6.4 9.2 NA NA 6.2 9.1 NA NA 6.3 9.2 14.9 24.8
NA = NOT APPLICABLE
14
33.7 NA NA NA NA
33.2 35.8 35.7 31.7 32.6
NA
35.4 33.3
NA 34.8
NA 33.7 32.2 34.1
NA 29.7
NA NA 33.9
17
43.5 NA NA NA NA
41.5 45.1 46.2 39.7 42.3
NA
44.8 42.2
NA 43.2
NA 41.3 40.0 42.4
NA 38.0
NA NA 41.9
21
51.6 NA NA NA NA
54.4 56.4 61.3 52.4 52.4
NA
58.0 53.9
NA 55.3
NA 55.4 49.3 57.1
NA 47.6
NA NA 54.5
PAGE 69
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25715-14 25715-15 25715-16 25715-17
F F F F
6.4 8.7 NA NA 6.4 9.3 15.4 26.0 6.6 9.2 NA NA 6.0 8.3 13.9 24.0
MALES MEAN 6.6 9.0 15.4 25.4 FEMALES MEAN 6.3 8.9 14.5 24.5
25762-01 25762-02 25762-03 25762-04 25762-05 25762-06 25762-07 25762-08 25762-09 25762-10 25762-11 25762-12 25762-13 25762-14
M M M M M M F F F F F F F F
6.8 9.1 13.6 23.7 6.5 8.6 NA NA 7.2 10.2 15.5 26.9 6.6 9.0 NA NA 6.6 8.9 13.5 24.9 7.4 10.0 14.5 25.7 5.9 7.7 12.2 22.0 6.8 9.8 14.5 24.5 6.6 9.2 NA NA 6.4 8.3 NA NA 6.5 8.8 13.7 23.0 6.6 8.8 NA NA 6.0 8.1 NA NA 6.7 9.6 14.3 25.3
NA = NOT APPLICABLE
14
NA 34.9
NA 31.8
33.7 32.6
31.5 NA
35.7 NA
32.6 33.3 29.9 32.3
NA NA 30.6 NA NA 32.6
17
NA 42.5
NA 38.6
41.7 40.3
38.4 NA
42.7 NA
39.3 40.6 36.7 38.9
NA NA 36.2 NA NA 39.4
21
NA 55.8
NA 50.2
54.3 52.0
48.0 NA
58.5 NA
52.2 53.9 48.0 50.9
NA NA 46.9 NA NA 52.9
PAGE 70
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25762-15 F 6.3 9.2 NA NA
MALES MEAN 6.9 9.3 14.3 25.3 FEMALES MEAN 6.4 8.8 13.7 23.7
25599-01 25599-02 25599-03 25599-04 25599-05 25599-06 25599-07 25599-08 25599-09 25599-10 25599-11 25599-12 25599-13 25599-14 25599-15 25599-16 25599-17 25599-18
M M M M M M M M M M F F F F F F F F
5.5 7.1 NA NA 5.4 7.2 NA NA 5.7 6.7 9.6 17.6 6.2 7.9 NA NA 5.7 7.1 NA NA 5.9 7.7 11.5 20.7 6.2 8.6 NA NA 5.4 NA NA NA 5.4 6.9 10.3 18.7 5.9 8.0 12.3 20.9 6.1 7.8 12.1 20.4 6.1 8.4 12.3 22.3 5.8 7.9 NA NA 5.2 6.3 NA NA 5.1 6.3 NA NA 5.9 7.9 NA NA 5.7 7.6 11.0 20.1 5.5 7.2 NA NA
NA = NOT APPLICABLE
14
NA
33.3 31.4
NA NA 24.6 NA NA 26.9 NA NA 25.4 28.3 25.8 29.9 NA NA NA NA 27.1 NA
17
NA
40.3 37.8
NA NA 31.3 NA NA 34.9 NA NA 33.1 36.2 32.8 37.0 NA NA NA NA 34.5 NA
21
NA
53.2 49.7
NA NA 40.1 NA NA 44.3 NA NA 42.1 45.8 41.0 49.2 NA NA NA NA 43.2 NA
PAGE 71
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25599-19 F
5.7 7.4 11.2 20.6
MALES MEAN 5.7 7.5 10.9 19.5 FEMALES MEAN 5.7 7.4 11.7 20.9
25647-02 25647-03 25647-04 25647-05 25647-06 25647-07 25647-08 25647-09 25647-10 25647-11 25647-12 25647-13 25647-14
M M M M M M F F F F F M F
6.3 8.6 NA NA 5.5 7.8 NA NA 6.3 8.5 12.2 20.5 6.1 8.8 NA NA 5.2 6.8 9.4 15.7 5.4 6.8 10.0 16.8 5.8 8.0 12.6 20.6 6.6 8.8 NA NA 5.7 7.7 NA NA 7.0 9.7 14.5 23.4 6.8 9.8 14.2 23.3 6.4 9.1 12.8 20.8 6.2 8.9 13.3 21.8
MALES MEAN 5.9 8.1 11.1 18.5 FEMALES MEAN 6.4 8.8 13.7 22.3
25747-01 M 25747-02 M 25747-03 M 25747-04 M
6.5 8.1 13.0 21.4 7.2 9.3 NA NA 7.3 8.9 14.7 24.9 7.8 10.2 16.0 25.7
NA = NOT APPLICABLE
14
29.1
26.3 28.0
NA NA 27.0 NA 22.0 23.0 26.9 NA NA 28.3 29.9 27.5 29.1
24.9 28.6
26.5 NA
30.9 31.6
17
34.5
33.9 34.7
NA NA 32.2 NA 25.6 26.4 31.5 NA NA 34.5 34.2 31.8 34.7
29.0 33.7
33.1 NA
39.0 40.5
21
44.4
43.1 44.5
NA NA 42.2 NA 33.1 30.3 42.6 NA NA 44.6 45.8 39.8 44.4
36.4 44.4
43.6 NA
53.9 57.1
PAGE 72
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25747-05 25747-06 25747-07 25747-08 25747-09 25747-10 25747-11 25747-12 25747-13 25747-14 25747-15 25747-16 25747-17
M M M F F F F F F F F F F
7.2 9.3 16.3 26.8 7.4 9.9 NA NA 7.7 10.5 NA NA 7.5 10.0 15.9 26.0 6.3 8.4 13.8 22.5 6.5 8.1 NA NA 6.5 8.6 NA NA 6.7 8.6 NA NA 6.8 8.9 15.6 26.7 6.7 9.0 NA NA 6.9 9.0 14.8 24.5 6.7 8.9 NA NA 6.9 9.5 NA NA
MALES MEAN 7.3 9.5 15.0 24.7 FEMALES MEAN 6.8 8.9 15.0 24.9
25744-01 25744-02 25744-03 25744-04 25744-05 25744-06 25744-07 25744-08 25744-09
M M M M M M F F F
7.9 11.1 16.7 26.9 7.5 9.7 NA NA 8.6 11.4 18.4 29.0 7.7 11.0 17.0 27.3 8.1 10.5 NA NA 7.9 10.6 16.8 27.7 7.0 9.8 NA NA 7.1 9.2 14.6 25.0 7.2 9.4 NA NA
NA = NOT APPLICABLE
14
32.9 NA NA
32.0 28.6
NA NA NA 31.9 NA 30.9 NA NA
30.5 30.9
35.7 NA
37.3 34.2
NA 36.0
NA 32.0
NA
17
41.7 NA NA
39.8 35.2
NA NA NA 39.2 NA 37.2 NA NA
38.6 37.9
42.8 NA
45.0 42.0
NA 44.5
NA 38.6
NA
21
55.6 NA NA
56.1 49.4
NA NA NA 55.0 NA 50.9 NA NA
52.6 52.9
58.1 NA
62.9 57.4
NA 58.8
NA 53.7
NA
PAGE 73
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25744-10 25744-11 25744-12 25744-13 25744-14 25744-15
F F F F F F
7.3 9.4 NA NA 7.9 11.1 17.6 28.4 7.4 10.2 NA NA 7.2 10.5 16.4 26.9 7.4 10.1 16.1 26.7 7.7 10.4 NA NA
MALES MEAN FEMALES MEAN
8.0 10.7 17.2 27.7 7.4 10.0 16.2 26.8
25707-01 25707-02 25707-03 25707-04 25707-05 25707-06 25707-07 25707-08 25707-09 25707-10 25707-11 25707-12 25707-13
M M M M M M M M F F F F F
6.6 8.5 NA NA 6.2 7.8 NA NA 5.8 8.1 13.9 23.2 6.5 8.6 NA NA 6.4 8.6 14.0 24.9 6.0 8.5 NA NA 6.1 8.4 14.7 25.0 6.6 8.9 14.5 25.1 6.1 8.6 13.8 23.9 5.5 7.9 12.8 22.9 5.9 NA NA NA 6.3 8.4 14.4 24.4 5.5 NA NA NA
NA = NOT APPLICABLE
14
NA 36.4
NA 35.1 35.4
NA
35.8 34.7
NA NA 30.7 NA 32.1 NA 31.7 32.5 32.2 29.5 NA 30.7 NA
17
NA 44.1
NA 41.3 41.9
NA
43.6 41.5
NA NA 36.9 NA 40.5 NA 39.0 39.5 39.1 37.0 NA 37.4 NA
21
NA 58.8
NA 55.1 57.4
NA
59.3 56.3
NA NA 46.5 NA 50.9 NA 48.4 50.0 50.1 46.9 NA 47.8 NA
PAGE 74
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25707-14 F
6.2 8.5 15.4 25.6
MALES MEAN 6.3 8.4 14.3 24.6 FEMALES MEAN 5.9 8.4 14.1 24.2
25723-01 25723-02 25723-03 25723-04 25723-05 25723-06 25723-07 25723-08 25723-09 25723-10 25723-11 25723-12 25723-13 25723-14 25723-15 25723-16 25723-17
M M M M M M M M M M M M F F F F M
6.2 8.0 NA NA 6.3 9.3 NA NA 6.2 8.7 NA NA 6.0 7.8 NA NA 6.2 8.6 13.8 21.7 6.1 8.6 12.9 21.1 6.5 9.0 NA NA 6.8 9.9 NA NA 6.9 9.5 NA NA 6.1 7.9 NA NA 6.4 8.8 NA NA 7.2 10.4 17.0 27.2 5.3 7.1 11.2 19.1 6.1 8.5 NA NA 6.4 9.0 15.0 23.2 6.1 8.4 13.8 21.7 5.5 6.4 9.4 14.9
NA = NOT APPLICABLE
14
33.2
31.8 31.4
NA NA NA NA 29.2 28.8 NA NA NA NA NA 36.3 26.0 NA 30.4 30.2 21.6
17
41.3
39.0 38.7
NA NA NA NA 35.0 33.2 NA NA NA NA NA 41.3 31.8 NA 37.2 35.9 25.5
21
49.8
49.0 48.7
NA NA NA NA 48.2 41.6 NA NA NA NA NA 60.1 41.8 NA 51.3 49.3 35.3
PAGE 75
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 17 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHTS [G]
POSTNATAL DAY
PUP NUMBER SEX
1
4
7 11
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25723- 18 F
5.5 7.0 10.9 17.3
MALES MEAN 6.3 8.7 13.3 21.2 FEMALES MEAN 5.9 8.0 12.7 20.3
14
23.6 29.0 27.6
17
28.3 33.8 33.3
21
37.9 46.3 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
PAGE 76
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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
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25597-02 25597-03 25597-04 25597-05 25597-06 25597-07 25597-08 25597-09 25597-10 25597-11 25597-12 25597-13 25597-14 25597-15 25597-16 25597-17
M M M M M M M F F F F F F F F F F
1.5 NA NA NA NA NA 1.2 5.4 8.2 6.1 3.6 9.3 1.3 NA NA NA NA NA 2.1 6.2 8.9 5.2 3.0 9.4 1.7 4.9 8.1 6.3 4.2 8.1 1.5 NA NA NA NA NA 2.1 4.6 8.1 5.9 5.7 7.0 2.0 5.3 7.1 5.9 3.4 10.3 2.0 NA NA NA NA NA 2.0 NA NA NA NA NA 2.0 NA NA NA NA NA 0.8 3.7 5.9 6.0 3.4 6.8 1.7 NA NA NA NA NA 1.8 NA NA NA NA NA 2.0 NA NA NA NA NA 1.5 4.2 6.1 5.8 4.3 8.7 1.4 5.5 7.8 4.4 2.7 7.0
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 25654-02 25654-03 25654-04 25654-05
M M M M 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
PAGE 1
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PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP NUMBER SEX 1- 4 4- 7
7-11 11-14 14-17 17-21
DAMS FROM GROUP 1: 0 MG/KG/DAY
25654-06 25654-07 25654-08 25654-09 25654-10 25654-11 25654-12 25654-13 25654-14 25654-15
M M M M F F F F F F
1.0 NA NA NA NA NA 2.1 6.8 8.1 7.5 6.7 8.9 0.4 NA NA NA NA NA 1.9 6.5 8.5 6.5 6.6 8.0 1.4 5.7 7.9 6.4 6.2 8.2 1.7 5.2 5.1 7.2 5.9 7.7 2.5 NA NA NA NA NA 1.5 NA NA NA NA NA 1.8 4.9 7.6 6.8 6.1 10.4 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
25632-01 25632-02 25632-03 25632-04 25632-05 25632-06 25632-07 25632-08 25632-09 25632-10 25632-11 25632-12
M M M M M M M M F F F 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
PAGE 2
-692-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25632-14 25632-15 25632-16
F F F F
3.3 NA NA NA NA NA 3.3 NA NA NA NA NA 2.9 5.5 9.6 7.9 6.4 11.4 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 25610-02 25610-03 25610-04 25610-05
M M F F 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
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 25618-02 25618-03 25618-04 25618-05 25618-06 25618-07 25618-08 25618-09
M M M M M M M M 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
PAGE 3
-693-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP NUMBER SEX 1- 4 4- 7
7-11 11-14 14-17 17-21
DAMS FROM GROUP 1: 0 MG/KG/DAY
25618-10 25618-11 25618-12 25618-13 25618-14 25618-15 25618-16 25618-17 25618-18
M F F F F F F F F
2.9 NA NA NA NA NA 3.3 5.7 11.4 6.7 7.7 15.9 3.0 NA NA NA NA NA 1.9 NA NA NA NA NA 2.5 NA NA NA NA NA 2.8 5.1 10.1 7.0 6.7 12.4 1.9 NA NA NA NA NA 2.5 4.9 10.1 5.9 7.9 10.8 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
25621-01 25621-02 25621-03 25621-04 25621-05 25621-06 25621-07 25621-08 25621-09 25621-10 25621-11 25621-12 25621-13
M M M M M M M M F F F F 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
PAGE 4
-694-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25621-15 F 25621-16 F
2.2 NA NA NA NA NA 2.4 NA NA NA NA NA 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
25687-01 25687-02 25687-03 25687-04 25687-05 25687-06 25687-07 25687-08 25687-09 25687-10 25687-11 25687-13 25687-14 25687-15 25687-16
M M M M M M M M F F F F F F 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
PAGE 5
-695-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25633-02 25633-03 25633-04 25633-05 25633-06 25633-07 25633-08 25633-09 25633-10 25633-11 25633-12 25633-13 25633-14
M M M M M M M M M F F F F 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
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
PAGE 6
-696-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP NUMBER SEX 1- 4 4- 7
7-11 11-14 14-17 17-21
DAMS FROM GROUP 1: 0 MG/KG/DAY
25681-04 25681-05 25681-06 25681-07 25681-08 25681-09 25681-10 25681-11 25681-12 25681-13 25681-14 25681-15 25681-16
M F M M M F F F F F F F F
3.5 NA NA NA NA NA 2.8 5.4 8.9 7.2 7.4 8.7 3.2 6.0 10.0 7.7 8.2 14.2 3.1 6.7 9.7 7.8 8.4 12.2 3.0 NA NA NA NA NA 3.0 NA NA NA NA NA 2.9 5.6 9.4 8.0 5.3 8.3 2.7 4.7 9.2 7.1 6.3 9.1 2.8 NA NA NA NA NA 3.0 NA NA NA NA NA 2.8 6.2 9.1 7.6 7.6 8.7 2.1 NA NA NA NA NA 2.5 NA NA NA NA NA
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 25615-02 25615-03 25615-04 25615-05 25615-06 25615-07 25615-08 25615-09
M M M M M M F F 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
PAGE 7
-697-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP NUMBER SEX 1- 4 4- 7
7-11 11-14 14-17 17-21
DAMS FROM GROUP 1: 0 MG/KG/DAY
25615-10 25615-11 25615-12 25615-13 25615-14
F F F F F
2.7 5.5 9.3 5.3 5.6 11.9 3.1 NA NA NA NA NA 2.9 NA NA NA NA NA 3.4 4.9 9.9 7.8 5.4 15.2 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
25637-02 25637-03 25637-04 25637-05 25637-06 25637-07 25637-08 25637-09 25637-10 25637-11 25637-12 25637-13 25637-14 25637-15 25637-16
M M M M M M M F F M F F F F 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
PAGE 8
-698-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25638-03 25638-04 25638-05 25638-06 25638-07 25638-08 25638-09 25638-10 25638-11 25638-13 25638-14 25638-15 25638-16 25638-18
M M M M M M M F F F F F F F 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
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
PAGE 9
-699-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25713-04 25713-05 25713-06 25713-07 25713-08 25713-09 25713-10 25713-11 25713-12 25713-13 25713-14 25713-15 25713-16
M M M M M M M M M F F F F F
2.5 NA NA NA NA NA 2.0 5.2 10.3 6.3 5.6 10.8 1.2 5.7 11.2 7.7 8.1 14.8 2.5 NA NA NA NA NA 2.4 NA NA NA NA NA 1.9 5.3 10.7 6.6 8.1 16.8 1.9 NA NA NA NA NA 2.4 NA NA NA NA NA 2.4 NA NA NA NA NA 2.8 4.6 10.9 7.2 8.6 13.5 2.7 6.0 11.4 6.4 6.2 15.0 2.2 5.7 10.0 6.4 7.7 12.2 1.7 NA NA NA NA NA 2.1 5.7 10.9 5.6 6.9 9.2
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 25670-02 25670-03 25670-04 25670-05 25670-06 25670-07 25670-08
M M M M M M M 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
PAGE 10
-700-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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
2 56 7 0--09 M 2 56 7 0- 10 M 2 56 7 0- 11 M 2 56 7 0- 12 F 2 56 7 0--13 F 2 56 7 0- 14 F 2 56 7 0- 15 F 2 56 7 0- 16 F 2 56 7 0- 17 F 2 56 7 0--18 F 2 56 7 0- 19 F
2.0 5.5 11.9 7.3 8.9 10.7 2.0 NA NA NA NA NA 2.0 NA NA NA NA NA 2.2 NA NA NA NA NA 1.0 NA NA NA NA NA 1.9 NA NA NA NA NA 1.4 4.8 10.8 8.2 7.7 10.2 1.4 3.3 9.7 8.7 7.4 11.3 1.7 5.1 10.1 7.4 7.3 12.6 1.9 4.5 11.1 6.9 9.0 11.7 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
2 56 57- 01 M 2 56 57- 02 M 2 56 57- 03 M 2 56 57- 04 M 2 56 57- 05 M 2 56 57- 06 M 2 56 57- 07 M 2 56 57- 08 M 2 56 57- 09 F 2 56 57- 10 F 2 56 57- 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
PAGE 11
-701-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25657-13 25657-14 25657-15 25657-16 25657-17 25657-19
F F F F F F F
2.5 6.3 10.9 7.9 9.2 12.9 2.2 6.3 10.3 8.8 7.9 10.6 2.9 NA NA NA NA NA 2.6 5.5 8.6 7.9 8.1 12.5 2.7 NA NA NA NA NA 2.7 NA NA NA NA NA 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
25663-01 25663-02 25663-03 25663-04 25663-05 25663-06 25663-07 25663-08 25663-09 25663-10
M M M M M M F F F 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
PAGE 12
-702-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25690-02 25690-03 25690-04 25690-05 25690-06 25690-07 25690-08 25690-09 25690-10 25690-11 25690-12 25690-13 25690-14 25690-15 25690-16 25690-17 25690-18
M M M M M M M F F F F F F F F F F 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
NA = NOT APPLICABLE
PAGE 13
-703-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25666-02 25666-03 25666-04 25666-05 25666-06 25666-07 25666-08 25666-09 25666-10 25666-11 25666-12 25666-13 25666-14
M M M M M M M F F F F F F 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
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
PAGE 14
-704-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25692-06 25692-07 25692-08 25692-09 25692-10 25692-11 25692-12 25692-13 25692-14
M F F F F F F F F F
2.2 5.3 11.8 7.6 9.2 13.5 3.2 5.9 10.9 8.2 8.3 14.5 2.3 5.9 11.0 8.5 6.6 8.9 2.1 NA NA NA NA NA 2.5 NA NA NA NA NA 2.4 NA NA NA NA NA 3.0 NA NA NA NA NA 2.7 6.0 10.5 6.8 8.0 12.8 1.8 NA NA NA NA NA 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
25701-01 25701-02 25701-03 25701-04 25701-05 25701-06 25701-07 25701-08 25701-09 25701-10 25701-11 25701-12
M F M M M M M M M M F 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
PAGE 15
-705-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25701-14 25701-15 25701-16 25701-17 25701-18 25701-19
F F F F F F F
1.8 NA NA NA NA NA 1.4 NA NA NA NA NA 2.1 NA NA NA NA NA 1.9 4.9 8.6 7.0 6.6 13.8 1.9 NA NA NA NA NA 2.5 5.0 8.7 6.6 7.5 11.9 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
25645-01 25645-02 25645-03 25645-04 25645-05 25645-06 25645-07 25645-08 25645-09 25645-10 25645-11 25645-12 25645-13 25645-14
M M M M M M F F F F F F F 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
PAGE 16
-706-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25661-02 25661-03 25661-04 25661-05 25661-06 25661-07 25661-08 25661-09 25661-10 25661-11 25661-12 25661-13 25661-14 25661-15 25661-16
M M M M M M M M M F F F F F F 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
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
PAGE 17
-L0L-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25767-03 25767-04 25767-05 25767-06 25767-07 25767-08 25767-09 25767-10 25767-11 25767-12 25767-13 25767-14 25767-15 25767-16 25767-17
M M M M M F F F F F F F F F F F
2.2 NA NA NA NA NA 2.6 5.5 8.7 9.0 7.6 15.2 2.4 NA NA NA NA NA 3.1 5.6 11.6 9.2 7.0 9.1 2.8 5.1 11.0 8.0 7.4 10.2 2.0 5.2 10.5 6.7 6.9 12.1 2.4 NA NA NA NA NA 1.8 2.9 8.9 7.9 6.4 10.3 2.7 NA NA NA NA NA 1.4 NA NA NA NA NA 2.1 5.1 10.7 8.8 5.1 11.7 3.0 NA NA NA NA NA 2.0 NA NA NA NA NA 3.1 NA NA NA NA NA 2.9 5.6 11.8 6.8 6.2 11.3 0.3 NA NA NA NA NA
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 25770-02 25770-03 25770-04 25770-05 25770-06
M M M M M 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
PAGE 18
-708-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25770-08 25770-09 25770-10 25770-11 25770-12 25770-13 25770-14
F F F F F F F F
1.8 6.2 10.3 7.3 5.7 11.4 2.4 NA NA NA NA NA 2.2 6.6 10.9 8.4 5.4 10.1 1.6 NA NA NA NA NA 2.0 6.1 9.4 8.7 5.1 10.9 1.8 NA NA NA NA NA 2.4 NA NA NA NA NA 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
25702-03 25702-04 25702-05 25702-06 25702-07 25702-08 25702-09 25702-11 25702-12 25702-13 25702-14 25702-15 25702-16 25702-17
M M M M M M M M M F F F F 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
PAGE 19
-709-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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
co
LD
25702-18 F
2.3
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
PAGE 20
-ou-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25648-02 25648-03 25648-04 25648-05 25648-06 25648-07 25648-08 25648-09 25648-10 25648-11 25648-12 25648-13 25648-14 25648-15 25648-16 25648-17
M M M M M M M M M M F F F F F F F
2.0 NA NA NA NA NA 1.6 NA NA NA NA NA 2.0 6.4 8.5 7.6 9.4 11.0 1.9 NA NA NA NA NA 2.1 NA NA NA NA NA 1.6 NA NA NA NA NA 2.0 5.7 7.8 6.6 8.0 10.9 2.0 6.3 8.3 7.2 8.9 10.4 1.4 NA NA NA NA NA 1.2 5.8 7.6 7.1 7.6 10.3 2.0 4.8 7.7 7.8 8.4 8.2 2.1 5.9 8.8 7.0 7.2 9.5 1.9 NA NA NA NA NA 1.6 5.5 8.4 7.8 8.1 9.0 1.9 NA NA NA NA NA 1.8 6.0 7.0 6.7 8.1 8.8 1.8 NA NA NA NA NA
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 25694-02 25694-03 25694-04 25694-05
M M M M 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
PAGE 21
-ML-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25694-07 25694-08 25694-09 25694-10 25694-11 25694-12 25694-13 25694-14 25694-15 25694-16 25694-17 25694-18
M F F F F M M F F F F F F
3.0 NA NA NA NA NA 3.1 NA NA NA NA NA 3.2 5.8 9.4 8.2 8.8 13.7 2.6 5.2 10.6 9.2 8.3 12.8 2.5 NA NA NA NA NA 2.9 6.2 10.3 9.7 10.0 15.9 3.0 NA NA NA NA NA 2.2 4.6 9.3 7.6 8.3 11.2 2.6 NA NA NA NA NA 2.7 6.3 10.4 8.4 8.3 15.6 2.1 NA NA NA NA NA 2.8 NA NA NA NA NA 2.1 NA NA NA NA NA
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 25668-04 25668-05 25668-06 25668-07 25668-08 25668-09 25668-10 25668-11
M M M F F F F F 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
PAGE 22
-712-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25668-13 25668-14 25668-15 25668-16 25668-17
F F F F F F
2.0 3.3 8.1 7.0 7.6 9.8 3.1 NA NA NA NA NA 2.9 NA NA NA NA NA 2.9 NA NA NA NA NA 2.1 3.5 8.0 7.9 7.4 10.4 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
25631-01 25631-02 25631-03 25631-04 25631-05 25631-06 25631-07 25631-08 25631-09 25631-10 25631-11 25631-12 25631-13 25631-14
M M M M F F M F F F F F F 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
PAGE 23
-713-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25660-02 25660-03 25660-04 25660-05 25660-06 25660-07 25660-08 25660-09 25660-10 25660-11 25660-12 25660-13 25660-14 25660-15
M M M F M M M M M F F F F F 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
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
PAGE 24
-714-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25704-04 25704-05 25704-06 25704-07 25704-08 25704-09 25704-10 25704-11 25704-12 25704-13
M M M M M F F F F F F
3.5 6.7 9.0 5.4 8.1 13.4 3.1 6.8 8.9 7.4 7.5 15.6 3.0 NA NA NA NA NA 3.4 6.7 10.0 7.2 8.9 15.6 2.9 NA NA NA NA NA 3.5 6.8 8.9 6.9 8.8 12.0 3.6 6.5 9.0 6.0 8.4 10.5 4.2 NA NA NA NA NA 3.2 6.4 9.7 7.0 6.5 13.1 3.0 5.6 9.2 6.1 7.5 12.2 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
25665-01 25665-02 25665-03 25665-04 25665-05 25665-06 25665-07 25665-08 25665-09 25665-10 25665-11
M M M M F F F F F F 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
PAGE 25
-715-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25674-02 25674-03 25674-04 25674-05 25674-06 25674-07 25674-08 25674-09 25674-10 25674-11 25674-12 25674-13 25674-14 25674-15 25674-16
M M M M M M M M M F F F F F F 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
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
PAGE 26
-716-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25652-03 25652-04 25652-05 25652-06 25652-07 25652-08 25652-09 25652-10 25652-11 25652-12 25652-13
M M M M M F F F F F F F
3.5 7.0 7.9 8.1 6.5 11.1 4.1 6.5 9.7 8.0 5.1 13.8 3.9 7.2 9.2 7.6 5.9 10.1 3.3 NA NA NA NA NA 3.1 NA NA NA NA NA 3.0 NA NA NA NA NA 3.4 7.0 9.2 9.5 3.4 11.6 3.1 NA NA NA NA NA 3.7 6.7 9.4 6.1 7.3 13.5 3.0 6.2 8.6 6.8 5.4 10.4 3.8 NA NA NA NA NA 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
25733-01 25733-02 25733-03 25733-04 25733-05 25733-06 25733-07 25733-08 25733-09 25733-10
M M M M M M M F F 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
PAGE 27
-717-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25733-12 25733-13 25733-14 25733-15
F F F F F
2.5 4.1 7.3 7.8 7.0 7.2 2.7 3.9 8.7 6.1 6.4 8.7 1.9 NA NA NA NA NA 2.6 NA NA NA NA NA 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 25748-02 25748-03 25748-04 25748-05 25748-06 25748-07 25748-08 25748-09 25748-10
M M M M M M M F F 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
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
PAGE 28
-718-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25753-05 25753-06 25753-08 25753-09 25753-10 25753-11 25753-12 25753-14 25753-15 25753-16 25753-17 25753-18
M M M F F F F F F F F F F
2.4 6.4 10.3 6.3 7.4 15.7 2.6 NA NA NA NA NA 2.3 6.3 10.7 4.5 7.8 13.4 2.7 NA NA NA NA NA 2.7 6.5 10.0 7.3 6.8 18.0 2.7 NA NA NA NA NA 3.0 NA NA NA NA NA 3.2 NA NA NA NA NA 2.9 NA NA NA NA NA 2.0 6.7 9.8 6.6 5.6 11.6 3.5 6.5 10.4 7.6 6.1 16.9 3.6 7.0 9.5 7.0 8.2 14.1 1.9 NA NA NA NA NA
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 25672-03 25672-04 25672-05 25672-06 25672-07 25672-08 25672-09 25672-10
M M M M M M M M 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
PAGE 29
-719-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25672-12 25672-13 25672-14 25672-15 25672-16 25672-17 25672-18
F F F F F F F F
2.9 7.0 10.7 8.1 7.7 14.5 2.3 5.0 9.4 7.6 7.8 11.2 2.7 NA NA NA NA NA 2.4 NA NA NA NA NA 2.7 6.7 10.3 5.9 8.7 9.9 0.9 3.4 8.2 6.9 7.1 8.6 3.1 NA NA NA NA NA 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
25655-01 25655-02 25655-03 25655-04 25655-05 25655-06 25655-07 25655-08 25655-09 25655-10 25655-11 25655-12 25655-13 25655-14
M M M M M M M M M M F F F 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
PAGE 30
-720-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25655-16 F
2.8 5.7 11.9 5.9 6.0 12.2 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 25727-03 25727-04 25727-05 25727-06 25727-07 25727-08 25727-09 25727-10 25727-11 25727-12 25727-13 25727-14 25727-15 25727-16
M M M M M M M F F F F F F F 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
NA = NOT APPLICABLE
PAGE 31
-721-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25626-02 25626-03 25626-04 25626-05 25626-06 25626-07 25626-08 25626-09 25626-10 25626-11 25626-12 25626-13 25626-14 25626-15 25626-16
M M M M M M M F F F F F F F F 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
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
PAGE 32
-722-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25739-03 25739-04 25739-05 25739-06 25739-07 25739-08 25739-09 25739-10 25739-11 25739-12 25739-13 25739-14
M M M M M M M M M F F F F
3.0 NA NA NA NA NA 2.7 NA NA NA NA NA 2.5 NA NA NA NA NA 2.9 NA NA NA NA NA 3.1 7.8 11.2 8.1 9.9 16.4 3.5 6.9 11.4 6.5 10.8 12.6 3.0 NA NA NA NA NA 2.7 6.9 11.2 9.1 8.7 16.7 2.8 NA NA NA NA NA 2.4 7.2 11.5 9.2 8.6 14.7 2.8 6.8 11.0 7.8 11.4 13.9 2.8 6.9 11.3 9.2 9.0 14.0 3.4 7.0 11.0 8.9 9.0 14.7
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 25749-03 25749-04 25749-05 25749-06 25749-07 25749-08 25749-09 25749-10
M M M M M M F F 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
PAGE 33
-723-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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
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
PAGE 34
-724-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25741-03 25741-04 25741-05 25741-06 25741-07 25741-08 25741-09 25741-10 25741-11 25741-12 25741-13 25741-14 25741-15 25741-16 25741-17
M M M M M M F F F F F F F F F F
3.5 8.0 10.6 8.6 8.5 16.6 3.5 7.7 10.3 8.5 7.3 13.5 3.1 NA NA NA NA NA 3.0 NA NA NA NA NA 3.1 NA NA NA NA NA 2.2 6.9 10.9 6.6 7.7 13.8 3.2 NA NA NA NA NA 2.8 7.5 10.5 6.8 7.4 11.8 2.6 NA NA NA NA NA 3.3 NA NA NA NA NA 3.8 NA NA NA NA NA 2.4 NA NA NA NA NA 2.5 6.4 9.2 8.3 8.2 12.4 3.0 7.7 10.8 7.7 8.8 12.8 2.9 7.2 11.0 7.4 7.8 12.7 2.2 NA NA NA NA NA
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 25752-02 25752-03 25752-04 25752-05 25752-07
M M M M M 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
PAGE 35
-725-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25752-09 25752-10 25752-11 25752-12 25752-13 25752-14 25752-15
M M F F F F F F
3.2 NA NA NA NA NA 4.0 7.6 11.4 8.7 9.1 14.9 3.5 NA NA NA NA NA 3.2 7.6 11.3 9.4 9.4 17.7 3.7 NA NA NA NA NA 4.2 7.6 12.9 7.9 8.6 13.3 3.8 7.6 11.5 9.9 8.6 15.8 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
25758-01 25758-02 25758-03 25758-04 25758-05 25758-06 25758-07 25758-08 25758-09 25758-10 25758-11 25758-12 25758-13
M M M M M M F F F F F F 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
PAGE 36
-726-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25719-03 25719-04 25719-05 25719-06 25719-07 25719-08 25719-09 25719-10 25719-11 25719-12 25719-13 25719-14 25719-15 25719-16 25719-17
M M M M M M M M M M M F F F F 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
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
PAGE 37
-727-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25606-02 25606-03 25606-04 25606-05 25606-06 25606-07 25606-08 25606-09 25606-10 25606-11 25606-12 25606-13 25606-14
M M M F F F F F F F F F F F
3.8 7.3 7.9 5.9 7.3 12.2 3.2 7.9 8.5 6.6 7.0 13.4 3.5 7.6 8.6 6.9 7.0 12.1 3.2 6.9 7.8 6.4 5.4 13.7 3.1 6.5 7.6 5.8 7.2 13.3 3.2 NA NA NA NA NA 3.3 NA NA NA NA NA 3.7 6.8 7.9 6.0 5.3 13.3 3.1 NA NA NA NA NA 3.3 NA NA NA NA NA 3.1 7.0 7.7 5.6 6.0 14.8 3.8 6.8 7.3 5.8 5.3 13.0 3.3 NA NA NA NA NA 2.8 NA NA NA NA NA
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 25614-02 25614-03 25614-04 25614-05 25614-06 25614-07 25614-08
M M M M M M M 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
PAGE 38
-728-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25614-10 25614-11 25614-12 25614-13 25614-14 25614-15 25614-16 25614-17 25614-18
M M M M F F F F F F
2.0 NA NA NA NA NA 2.8 6.2 8.4 7.7 6.4 13.1 2.1 NA NA NA NA NA 1.7 NA NA NA NA NA 2.1 5.6 7.5 6.5 6.9 12.1 2.3 NA NA NA NA NA 1.4 4.8 7.4 6.4 6.1 12.4 1.7 NA NA NA NA NA 1.5 5.4 7.7 -3.1 15.8 9.5 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
25671-01 25671-02 25671-03 25671-04 25671-05 25671-06 25671-07 25671-08 25671-09 25671-10 25671-11 25671-12
M M M M M F F F F F F 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
PAGE 39
-729-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25698-02 25698-03 25698-04 25698-05 25698-06 25698-07 25698-08 25698-09 25698-10 25698-11 25698-12 25698-13 25698-14
M M M F M M F F F F F F F 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
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
PAGE 40
-730-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25609-05 25609-06 25609-07 25609-08 25609-09 25609-10 25609-11 25609-12 25609-13 25609-14 25609-15
M M M F F F F F F F F F
3.1 5.2 8.7 4.3 6.9 12.0 2.6 NA NA NA NA NA 2.7 5.2 9.3 7.2 7.7 16.3 3.0 NA NA NA NA NA 2.7 NA NA NA NA NA 3.2 NA NA NA NA NA 3.1 NA NA NA NA NA 3.0 5.7 8.3 4.5 7.4 8.6 2.9 6.5 9.3 6.5 7.0 16.4 3.3 NA NA NA NA NA 3.4 4.6 8.5 6.6 6.8 14.0 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
25677-02 25677-03 25677-04 25677-05 25677-06 25677-07 25677-08 25677-10 25677-11 25677-12
M M M M M M F F F 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
PAGE 41
-731-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25623-04 25623-05 25623-06 25623-07 25623-08 25623-09 25623-10 25623-11 25623-12 25623-13 25623-14 25623-15
M M M M M M M F F F F F 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
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
PAGE 42
-732-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25653-06 25653-07 25653-08 25653-09 25653-10 25653-11 25653-12 25653-13 25653-14
F F M F F F M F F M
2.7 5.0 9.9 9.0 8.0 16.3 2.6 5.9 9.6 8.8 7.4 14.1 2.6 6.1 9.8 8.4 9.0 15.9 2.0 NA NA NA NA NA 2.6 NA NA NA NA NA 1.8 NA NA NA NA NA 2.5 5.8 10.3 9.2 8.7 13.8 2.2 6.0 9.8 9.4 8.5 12.0 2.2 5.6 9.2 6.4 8.4 11.8 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
25604-01 25604-02 25604-03 25604-04 25604-05 25604-06 25604-07 25604-08 25604-09 25604-10 25604-11
M M M M M M M F F F 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
PAGE 43
-733-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25678-02 25678-03 25678-04 25678-05 25678-06 25678-07 25678-08 25678-09 25678-10 25678-11 25678-12 25678-13 25678-14 25678-15
M M M M M M M F F F F F F F 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
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
PAGE 44
-734-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25684-05 25684-06 25684-07 25684-08 25684-09 25684-10 25684-11 25684-12
M M F F F F F F F
2.9 5.2 8.8 6.3 6.5 13.1 2.9 5.8 9.8 9.1 8.0 15.9 3.7 6.1 8.7 6.0 7.7 15.7 2.9 NA NA NA NA NA 2.6 4.6 8.3 7.9 7.3 15.1 2.8 NA NA NA NA NA 3.1 NA NA NA NA NA 3.0 4.4 7.8 7.5 6.6 11.6 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
25714-01 25714-02 25714-03 25714-04 25714-05 25714-06 25714-07 25714-08 25714-09 25714-10 25714-11 25714-12
M M M M M M F F F F F 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
PAGE 45
-735-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25650-02 25650-03 25650-04 25650-05 25650-06 25650-07 25650-08 25650-09 25650-10 25650-11 25650-12 25650-13 25650-14 25650-15 25650-16 25650-17 25650-18
F M M M M M M M M M M M M F F F F 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
NA = NOT APPLICABLE
PAGE 46
-736-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25735-02 25735-03 25735-04 25735-05 25735-06 25735-07 25735-08 25735-09 25735-10 25735-11 25735-12 25735-13 25735-14
M M M M M M F F F F F F F 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
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
PAGE 47
-737-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25722-05 25722-06 25722-07 25722-08 25722-09 25722-10 25722-11 25722-12 25722-13 25722-14 25722-15
M M M M M M M F F F F F
1.7 4.5 8.0 9.4 5.1 12.1 2.0 5.2 8.3 7.4 5.5 12.9 2.0 NA NA NA NA NA 2.3 NA NA NA NA NA 2.1 NA NA NA NA NA 2.7 NA NA NA NA NA 3.0 4.1 9.0 8.3 5.1 12.1 2.7 5.4 8.6 8.0 5.6 10.7 2.9 5.3 8.9 8.1 5.7 12.0 2.7 5.0 8.6 8.3 5.0 15.8 3.0 NA NA NA NA NA 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
25642-01 25642-02 25642-03 25642-04 25642-05 25642-06 25642-07 25642-08 25642-09 25642-10
M M M M M M M M F 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
PAGE 48
-738-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25642-12 25642-13 25642-14 25642-15
F F F F F
2.6 NA NA NA NA NA 2.7 6.5 11.0 5.6 8.5 11.0 2.5 6.3 10.9 6.6 7.5 12.8 2.5 NA NA NA NA NA 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
25628-01 25628-02 25628-03 25628-04 25628-05 25628-07 25628-08 25628-09 25628-10 25628-11 25628-12 25628-13 25628-14 25628-15 25628-16
M M M M M M M M F F F F F F 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
PAGE 49
-739-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25763-02 25763-03 25763-04 25763-05 25763-06 25763-07 25763-08 25763-09 25763-10 25763-11 25763-12 25763-13 25763-14 25763-15 25763-16 25763-17 25763-18
M M M M M M M M F F F F F F F F F 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
NA = NOT APPLICABLE
PAGE 50
-740-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25766-02 25766-03 25766-05 25766-06 25766-07 25766-08 25766-09 25766-10 25766-11
M M M F F F F F M 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
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 25689-02 25689-03 25689-04 25689-05 25689-06 25689-07
M M M M M M 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
PAGE 51
-741-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25689-09 25689-10 25689-11 25689-12 25689-13 25689-14 25689-15
F F F F F F F F
2.0 NA NA NA NA NA 2.9 NA NA NA NA NA 3.9 NA NA NA NA NA 2.9 NA NA NA NA NA 3.2 6.2 11.7 9.3 8.3 16.6 2.9 6.1 10.4 8.0 7.4 17.1 2.2 5.8 11.4 8.0 8.0 12.7 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
25708-01 25708-02 25708-03 25708-04 25708-05 25708-06 25708-07 25708-08 25708-09 25708-10 25708-11 25708-12 25708-13 25708-14
M M M M M M M M M F F F F 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
PAGE 52
-742-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25743-02 25743-03 25743-04 25743-05 25743-06 25743-08 25743-09 25743-10 25743-11 25743-12 25743-13 25743-14 25743-15 25743-16 25743-17
M M M M M M M M M F F F F F F 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
NA = NOT APPLICABLE
PAGE 53
-743-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25761-02 25761-03 25761-04 25761-05 25761-06 25761-07 25761-08 25761-09 25761-10 25761-11 25761-12 25761-13 25761-14 25761-15
M M M M M M M F F F F F F F 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
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
PAGE 54
-744-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25712-05 25712-06 25712-07 25712-08 25712-09 25712-10 25712-11 25712-12 25712-13 25712-14 25712-15 25712-16 25712-17
M M M F F F F F F F F F F F
3.3 NA NA NA NA NA 2.6 6.0 10.0 7.8 7.8 15.1 3.4 7.5 11.2 7.7 9.5 15.1 3.3 6.3 10.4 7.0 8.2 8.4 2.9 5.3 8.4 7.8 8.5 12.6 3.4 NA NA NA NA NA 3.3 NA NA NA NA NA 2.3 NA NA NA NA NA 2.6 NA NA NA NA NA 3.4 NA NA NA NA NA 2.9 NA NA NA NA NA 2.4 NA NA NA NA NA 3.0 6.5 10.2 7.2 9.0 14.0 2.5 7.1 9.3 7.7 8.3 13.7
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 25746-03 25746-04 25746-05 25746-06 25746-07 25746-08 25746-09
M M M M M M M 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
PAGE 55
-745-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25746-11 25746-12 25746-13 25746-14 25746-15 25746-16 25746-17 25746-18
M M F F F F F F F
3.3 NA NA NA NA NA 2.7 6.4 10.9 9.4 8.9 14.8 2.8 5.9 10.0 8.4 8.2 12.9 2.6 NA NA NA NA NA 2.2 5.5 8.8 9.1 9.4 66.9 2.6 6.2 10.1 9.1 8.3 29.0 2.6 NA NA NA NA NA 2.8 6.6 11.0 9.0 9.2 16.4 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
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
PAGE 56
-746-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25696-02 25696-03 25696-04 25696-05 25696-06 25696-07 25696-08 25696-09 25696-10 25696-11 25696-12 25696-13 25696-14 25696-15 25696-16
M M M M M M M M M M F F F F F F
2.9 NA NA NA NA NA 2.6 NA NA NA NA NA 2.3 NA NA NA NA NA 3.1 5.7 8.8 6.0 6.8 13.9 3.0 NA NA NA NA NA 2.2 5.0 6.8 7.4 6.4 12.6 3.0 4.9 8.9 7.1 6.6 14.3 2.9 NA NA NA NA NA 2.4 5.1 7.6 7.6 5.4 13.7 1.9 NA NA NA NA NA 2.9 6.4 8.2 6.5 6.9 11.7 1.9 NA NA NA NA NA 2.9 6.5 7.9 6.8 6.5 14.4 2.6 5.1 7.9 7.0 6.2 13.1 2.6 NA NA NA NA NA 2.6 5.9 8.8 8.0 6.5 14.1
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 25686-02 25686-03 25686-04 25686-05 25686-06
M M M M M 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
PAGE 57
-747-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25686-08 25686-09 25686-10 25686-11 25686-12 25686-13 25686-14 25686-15
M M F F F F F F F
2.6 NA NA NA NA NA 2.3 NA NA NA NA NA 2.7 5.7 8.4 7.1 5.2 12.0 2.2 4.9 8.0 6.3 5.1 9.6 2.4 6.5 8.4 7.1 5.3 11.8 2.1 NA NA NA NA NA 2.5 NA NA NA NA NA 2.4 NA NA NA NA NA 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
25639-01 25639-02 25639-03 25639-04 25639-05 25639-06 25639-07 25639-08 25639-09 25639-10 25639-11 25639-12 25639-13
M M M F M M M M M F F F 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
PAGE 58
-748-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25639-15 F 25639-16 F
2.9 5.9 9.9 8.8 6.1 11.4 1.7 NA NA NA NA NA 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 25658-04 25658-05 25658-06 25658-07 25658-08 25658-09 25658-10 25658-11 25658-12 25658-13 25658-14 25658-15
M M M M M M M F F F F F 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
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
PAGE 59
-749-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25676-05 25676-06 25676-07 25676-08 25676-09 25676-10 25676-11 25676-12 25676-13 25676-14 25676-15
M M M M F F F F F F F F
2.7 7.5 7.9 7.0 5.3 17.3 2.8 NA NA NA NA NA 2.9 7.7 8.6 7.9 6.5 16.2 2.7 NA NA NA NA NA 2.3 7.1 8.8 6.4 6.4 15.2 2.8 7.5 8.0 7.0 5.4 16.1 2.2 NA NA NA NA NA 1.9 NA NA NA NA NA 2.6 7.7 8.7 7.6 5.7 14.0 2.4 NA NA NA NA NA 2.5 NA NA NA NA NA 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
25600-01 25600-02 25600-03 25600-04 25600-05 25600-06 25600-07 25600-08 25600-09 25600-10
M M M M F F F F F 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
PAGE 60
-750-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25600-12 25600-13 25600-14 25600-15 25600-16 25600-17
F F F F F F F
3.8 7.3 10.5 7.9 7.8 17.6 3.7 6.6 10.4 7.9 8.6 14.1 3.6 NA NA NA NA NA 2.5 NA NA NA NA NA 3.9 7.7 9.4 7.8 8.8 14.0 2.4 NA NA NA NA NA 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
25603-01 25603-02 25603-03 25603-04 25603-05 25603-06 25603-07 25603-08 25603-09 25603-10 25603-11 25603-12 25603-13 25603-14
M M M M M F F F F F F F F 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
PAGE 61
-751-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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
2 56 3 0- 01 M 2 56 3 0- 02 M 2 56 3 0- 03 M 2 56 3 0- 04 M 2 56 3 0- 05 M 2 56 3 0- 06 M 2 56 3 0- 07 M 2 56 3 0--08 F 2 56 3 0--09 F 2 56 3 0- 10 F 2 56 3 0- 11 F 2 56 3 0- 12 F 2 56 3 0- 13 F 2 56 3 0- 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
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
PAGE 62
-752-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25703-05 25703-06 25703-07 25703-08 25703-09 25703-10 25703-11 25703-12 25703-13 25703-14 25703-15
M M F F F F F F F F F F
3.0 7.8 10.8 8.0 7.4 17.0 2.4 7.5 9.2 8.2 9.0 16.0 2.4 NA NA NA NA NA 2.2 NA NA NA NA NA 1.8 7.1 9.1 7.3 6.8 13.7 2.6 7.0 9.7 7.7 7.1 13.6 2.2 7.3 9.2 6.2 7.5 11.0 1.5 NA NA NA NA NA 2.3 NA NA NA NA NA 2.3 NA NA NA NA NA 2.8 8.1 9.4 8.2 6.6 14.0 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
25673-01 25673-02 25673-03 25673-04 25673-05 25673-06 25673-07 25673-08 25673-09 25673-10
M M M M M M M M M 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
PAGE 63
-753-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25673-12 25673-13 25673-14 25673-15
F F F F F
2.1 5.1 6.7 6.6 6.1 9.1 2.5 5.2 8.2 6.6 5.7 10.2 2.5 NA NA NA NA NA 2.2 4.4 6.4 6.1 5.8 9.0 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
25611-04 25611-05 25611-06 25611-07 25611-08 25611-09 25611-10 25611-11 25611-12 25611-13 25611-14 25611-15
M M M M M M M F F F F 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
PAGE 64
-754-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25619-03 25619-04 25619-05 25619-06 25619-07 25619-08 25619-09 25619-10 25619-11 25619-12 25619-13 25619-14
M M M M M F F F F F F F F
2.5 NA NA NA NA NA 3.0 6.0 8.9 8.3 4.4 12.2 2.1 3.8 6.5 5.7 4.3 6.9 2.9 5.4 10.1 7.4 4.7 13.3 2.4 NA NA NA NA NA 2.2 NA NA NA NA NA 2.3 5.2 9.5 7.0 5.5 12.2 2.2 NA NA NA NA NA 2.2 4.3 8.9 6.0 4.0 7.9 2.3 NA NA NA NA NA 2.6 5.3 9.3 4.0 4.8 8.3 2.0 NA NA NA NA NA 2.5 5.0 8.7 7.1 4.7 13.5
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 25705-02 25705-03 25705-04 25705-05 25705-06 25705-07 25705-08 25705-09
M M M M M M M F 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
PAGE 65
-755-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25705-11 25705-12 25705-13
F F F F
3.4 7.2 9.3 9.1 5.6 14.4 3.5 7.0 9.9 9.4 5.3 13.4 3.6 NA NA NA NA NA 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
25691-01 25691-02 25691-03 25691-04 25691-05 25691-06 25691-07 25691-08 25691-09 25691-10 25691-11 25691-12 25691-14 25691-15
F M M M M M M M M F F F F 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
PAGE 66
-756-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25717-04 25717-05 25717-06 25717-07 25717-08 25717-09 25717-10 25717-11 25717-12 25717-13 25717-14 25717-15
M M M M M M F F F F F F 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
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
PAGE 67
-757-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25616-06 25616-07 25616-08 25616-09 25616-10 25616-11 25616-12 25616-13 25616-14 25616-15
M M M F F F F M F F F
3.6 5.7 11.2 6.3 9.8 8.1 3.9 NA NA NA NA NA 4.3 NA NA NA NA NA 3.9 NA NA NA NA NA 3.1 NA NA NA NA NA 3.0 5.4 9.9 8.4 8.3 12.9 3.5 6.4 10.8 8.1 9.3 11.3 3.7 6.1 11.6 7.0 10.5 15.1 2.6 4.7 10.6 8.0 8.0 12.7 3.0 5.5 11.3 6.6 9.7 10.1 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
25715-03 25715-04 25715-05 25715-06 25715-07 25715-08 25715-09 25715-10 25715-11 25715-12 25715-13
M M M M M M M F F F 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
PAGE 68
-758-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25715-15 25715-16 25715-17
F F F F
2.3 NA NA NA NA NA 2.9 6.1 10.6 8.9 7.6 13.3 2.6 NA NA NA NA NA 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
25762-01 25762-02 25762-03 25762-04 25762-05 25762-06 25762-07 25762-08 25762-09 25762-10 25762-11 25762-12 25762-13 25762-14
M M M M M M F F F F F F F 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
PAGE 69
-759-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25599-02 25599-03 25599-04 25599-05 25599-06 25599-07 25599-09 25599-10 25599-11 25599-12 25599-13 25599-14 25599-15 25599-16 25599-17 25599-18
M M M M M M M M M F F F F F F F 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
NA = NOT APPLICABLE
PAGE 70
-760-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25647-03 25647-04 25647-05 25647-06 25647-07 25647-08 25647-09 25647-10 25647-11 25647-12 25647-13 25647-14
M M M M M M F F F F F M 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
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
PAGE 71
-761-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
POSTNATAL DAY ?UP 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 25747-06 25747-07 25747-08 25747-09 25747-10 25747-11 25747-12 25747-13 25747-14 25747-15 25747-16 25747-17
M M M F F F F F F F F F F
2.1 7.0 10.5 6.1 8.8 13.9 2.5 NA NA NA NA NA 2.8 NA NA NA NA NA 2.5 5.9 10.1 6.0 7.8 16.3 2.1 5.4 8.7 6.1 6.6 14.2 1.6 NA NA NA NA NA 2.1 NA NA NA NA NA 1.9 NA NA NA NA NA 2.1 6.7 11.1 5.2 7.3 15.8 2.3 NA NA NA NA NA 2.1 5.8 9.7 6.4 6.3 13.7 2.2 NA NA NA NA NA 2.6 NA NA NA NA NA
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 25744-02 25744-03 25744-04 25744-05 25744-06 25744-07 25744-08 25744-09
M M M M M M F F 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
PAGE 72
-762-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25744-11 25744-12 25744-13 25744-14 25744-15
F F F F F F
2.1 NA NA NA NA NA 3.2 6.5 10.8 8.0 7.7 14.7 2.8 NA NA NA NA NA 3.3 5.9 10.5 8.2 6.2 13.8 2.7 6.0 10.6 8.7 6.5 15.5 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
25707-01 25707-02 25707-03 25707-04 25707-05 25707-06 25707-07 25707-08 25707-09 25707-10 25707-12
M M M M M M M M F F 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
PAGE 73
-763-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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 25723-02 25723-03 25723-04 25723-05 25723-06 25723-07 25723-08 25723-09 25723-10 25723-11 25723-12 25723-13 25723-14 25723-15 25723-16 25723-17
M M M M M M M M M M M M F F F F 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
NA = NOT APPLICABLE
PAGE 74
-764-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 18 (F1 - PRE-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL OFFSPRING WEIGHT CHANGES [G]
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
PAGE 75
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
25654 25687 25637 25638 25692 25661
25702
PUP NO. SEX
13 F
12 F
1M
2M
1M
2M 3M
1M
2M 10 M
LACT DAY TISSUE
5
3
0 STOMACH
4
0 STOMACH
7 7
0 GENERAL COMMENT
0 STOMACH 1 GENERAL COMMENT
GROUP 1: FINDING
0 MG/KG/DAY
NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS
MILK NOT PRESENT
NO REMARKABLE OBSERVATIONS
MILK NOT PRESENT
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
TOO AUTOLYZED TO EXAMINE ABDOMINAL AND URINARY/REPRODUCTIVE
MILK NOT PRESENT TOO AUTOLYZED TO EXAMINE
ABDOMINAL AND URINARY/REPRODUCTIVE
GRADE CODE : 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 1
GRADE
P P
P P P
-766-
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
25668
PUP NO. SEX
1M
2F
LACT DAY TISSUE
1 GENERAL COMMENT
1 GENERAL COMMENT
25753
7M 13 F
1 STOMACH 4 VARIATION
25752
6M
2 GENERAL COMMENT
GROUP 2: 0.1 MG/KG/DAY FINDING
TOO AUTOLYZED TO EXAMINE ABDOMINAL AND URINARY/REPRODUCTIVE
TOO AUTOLYZED TO EXAMINE ABDOMINAL AND URINARY/REPRODUCTIVE
MILK NOT PRESENT RENAL PAPILLA(E) NOT DEVELOPED AND/OR DISTENDED URETER(S)
KIDNEY, LEFT (WOO AND HOAR GRADE 0)
CANNIBALIZED
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 2
GRADE P P P P P
-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
25698
PUP NO. SEX
15 F
LACT DAY TISSUE
3 GENERAL COMMENT
25677 25623 25722
1M 9F
1M 2M 12 F
16 M
4 4
0 STOMACH 0 STOMACH 7
0 GENERAL COMMENT
25642 10 F
6 GENERAL COMMENT
25628 25763
6M
3M 16 F
2
5 6 GENERAL COMMENT
25766
4M
3 GENERAL COMMENT
25743 25712 25746
7M 1F 2M
2 0 STOMACH 2
GROUP 3: 0.3 MG/KG/DAY FINDING
TOO AUTOLYZED TO EXAMINE ABDOMINAL AND URINARY/REPRODUCTIVE
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
MILK PRESENT MILK PRESENT NO REMARKABLE OBSERVATIONS
TOO AUTOLYZED TO EXAMINE THORACIC, ABDOMINAL AND URINARY/REPRODUCTIVE
TOO AUTOLYZED TO EXAMINE ABDOMINAL AND URINARY/REPRODUCTIVE
NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS TOO AUTOLYZED TO EXAMINE
ABDOMINAL AND URINARY/REPRODUCTIVE
TOO AUTOLYZED TO EXAMINE ABDOMINAL AND URINARY/REPRODUCTIVE
NO REMARKABLE OBSERVATIONS
MILK PRESENT
NO REMARKABLE OBSERVATIONS
GRADE CODE : 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 3
GRADE P
P P P P
P P
P
-768-
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
25658
PUP NO. SEX
1F
LACT DAY TISSUE
0 MALFORMATION MALFORMATION
25676 25611
25691 25717 25599 25647 25707
1M
1M 2F 3F
13 F
1M
8M
1M
13 F
STOMACH
0 STOMACH
0 STOMACH 0 STOMACH 0 STOMACH
1 STOMACH
0 STOMACH 2
0 STOMACH
3
GROUP 4: 1.0 MG/KG/DAY FINDING
MANDIBULAR MICROGNATHIA SITUS INVERSUS
TRACHEA, ESOPHAGUS, HEART, GREAT AND MAJOR VESSELS,. LUNGS, LIVER, STOMACH, PANCREAS, SPLEEN, KIDNEYS, ADRENAL GLANDS AND INTESTINE LATERALLY TRANSPOSED MILK NOT PRESENT
MILK NOT PRESENT
MILK NOT PRESENT MILK NOT PRESENT MILK NOT PRESENT
MILK PRESENT
MILK NOT PRESENT
NO REMARKABLE OBSERVATIONS
MILK PRESENT
NO REMARKABLE OBSERVATIONS
GRADE CODE:: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 4
GRADE P P
P P P P P P P
P
PPNRDv4.13 01/23/2007 R:01/23/2007
-769-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PUP
LACT
NO. SEX DAY TISSUE
25597
2M 5M 8F 12 F
21 21 21 21
25654
2M 7M 14 F
21 21 21
25632
4M 16 F
21 21
25610
1M 2M 3F 4F 5F
21 21 21 21 21
25618
2M 11 F
21 21
25621
2M 16 F
21 21
25687
3M 16 F
21 21
25633
9M 12 F 14 F
21 21 21
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
GROUP 1: 0 MG/KG/DAY FINDING
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE
1
GRADE
-0LL-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO..:06- 128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP NO. SEX
LACT DAY TISSUE
GROUP 1: FINDING
0 MG/KG/DAY
25681
5F 7M
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25615
1M 13 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25637
8M 14 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25638
4M 15 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25713
4M 5M 13 F 14 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25670
4M 15 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25657
2M 12 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25663
3M 6M 7F 8F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25690
3M 5M
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 2 GRADE
-ILL-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP
LACT
NO. SEX DAY TISSUE
GROUP 1: 0 MG/KG/DAY FINDING
25690
(CONTINUED) 7M 9F
17 F 18 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25666
2M 5M 7M 8F 13 F 14 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25692
2M 3M 5M 6F 12 F 14 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25701
2F 3M 6M 10 M 11 F 16 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25645
1M 2M 4M 7F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 3 GRADE
-772-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP
LACT
NO. SEX DAY TISSUE
GROUP 1: 0 MG/KG/DAY FINDING
25645 (CONTINUED) 11 F 12 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25661
4M 5M 10 F 11 F 12 F 14 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25767
1M 3M 5M 6M 7F 9F 12 F 16 F
21 21 21 21 21 21 21 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
25770
1M 2M 3M 4M 7F 9F 11 F 14 F
21 21 21 21 21 21 21 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
3M 4M
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 4 GRADE
-773-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP NO. SEX
LACT DAY TISSUE
GROUP 1: FINDING
0 MG/KG/DAY
(CONTINUED) 7M
12 M 13 F 15 F 16 F 18 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 5 GRADE
-774-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP
LACT
NO. SEX
DAY TISSUE
GROUP 2: 0.1 MG/KG/DAY FINDING
25648
3M 8M 11 F 16 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25694
3M 9F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25668
3M 4M 5M 6F 7F 10 F 12 F 16 F
21 21 21 21 21 21 21 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
2M 3M 10 F 13 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25660
7M 10 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25704
1M 6M 8F 11 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 6 GRADE
-775-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP
LACT
NO. SEX
DAY TISSUE
GROUP 2: 0.1 MG/KG/DAY FINDING
25665
3M 4M 6F 10 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25674
7M 16 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25652
2M 10 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25733
3M 11 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25748
2M 4M 6M 9F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25753
2M 16 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25672
2M 12 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25655
3M 11 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25727
2M 13 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE
7
GRADE
-776-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP
LACT
NO. SEX
DAY TISSUE
GROUP 2: 0.1 MG/KG/DAY FINDING
25626
6M 9F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25739
1M 6M 9M 11 F 13 F 14 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25749
2M 3M 7M 8F 9F 10 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25756
1M 3M 4M 11 F 15 F 16 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25741
1M 2M 3M 14 F 15 F 16 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 8 GRADE
-777-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP
LACT
NO. SEX
DAY TISSUE
GROUP 2: 0.1 MG/KG/DAY FINDING
25752
1M 3M 5M 11 F 14 F 15 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25758
1M 2M 5M 6M 8F 9F 10 F 12 F
21 21 21 21 21 21 21 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
3M 4M 7M 9M 13 F 14 F 15 F 17 F
21 21 21 21 21 21 21 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
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 9 GRADE
-778-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PUP
LACT
NO. SEX DAY TISSUE
25606
1M 2M 3M 4F 5F 8F 11 F 12 F
21 21 21 21 21 21 21 21
25614
7M 13 F
21 21
25671
2M 5M 8F 13 F
21 21 21 21
25698
6M 10 F
21 21
25609
2M 14 F
21 21
25677
2M 7M 10 F 12 F
21 21 21 21
25623
5M
21
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
GROUP 3: 0.3 MG/KG/DAY FINDING
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 10 GRADE
-779-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PUP
LACT
NO. SEX DAY TISSUE
25653
6F 7M 11 M 12 F
21 21 21 21
25604
2M 3M 8F 11 F
21 21 21 21
25678
6M 8F
21 21
25684
2M 3M 8F 11 F
21 21 21 21
25714
3M 5M 9F 10 F
21 21 21 21
25650
8M 13 M 14 F 19 F
21 21 21 21
25735
1M 7F
21 21
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
GROUP 3: 0.3 MG/KG/DAY FINDING
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 11 GRADE
-780-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP NO. SEX
LACT DAY TISSUE
GROUP 3: 0.3 MG/KG/DAY FINDING
25722
4M 13 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25642
2M 8M 13 F
21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25628
5M 15 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25763
2M 4M 7M 9F 10 F 15 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25766
2M 3M 7F 9F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25689
3M 4M 6M 7F 12 F 13 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25708
4M
21
NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 12 GRADE
-781-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PUP
LACT
NO. SEX DAY TISSUE
25708
(CONTINUED) 7M 9M
11 F 12 F 14 F
21 21 21 21 21
25743
2M 4M 9M 11 F 12 F 18 F
21 21 21 21 21 21
25761
4M 5M 6M 7M 8F 9F 13 F 15 F
21 21 21 21 21 21 21 21
25712
2M 3M 5M 6M 7F 8F 16 F 17 F
21 21 21 21 21 21 21 21
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
GROUP 3: 0.3 MG/KG/DAY FINDING
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 13 GRADE
-782-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP NO. SEX
LACT DAY TISSUE
GROUP 3: 0.3 MG/KG/DAY FINDING
3M 6M 7M 11 M 12 F 14 F 15 F 17 F
21 21 21 21 21 21 21 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
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 14 GRADE
-783-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP NO. SEX
LACT DAY TISSUE
GROUP 4: 1.0 MG/KG/DAY FINDING
25696
9M 13 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25686
3M 11 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25639
5M 14 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25658
3M 15 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25676
6M 9F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25600
1M 3M 5F 11 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25603
1M 2M 6F 12 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25630
5M 10 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25703
2M 5M
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 15 GRADE
-784-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP
LACT
NO. SEX
DAY TISSUE
GROUP 4: 1.0 MG/KG/DAY FINDING
25703 (CONTINUED) 9F
14 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25673
3M 12 F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25611
5M 10 M 12 F 13 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25619
1M 8F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25705
1M 9F
21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25691
2M 5M 12 F 15 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25717
6M 7M 11 F 14 F
21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25616
3M 10 F 11 F
21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 16 GRADE
-785-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP
LACT
NO. SEX
DAY TISSUE
GROUP 4: 1.0 MG/KG/DAY FINDING
25616 (CONTINUED)
12 M
21
NO REMARKABLE OBSERVATIONS
25715
4M 6M 8M 13 F 15 F 17 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25762
3M 5M 6M 7F 8F 14 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25599
3M 9M 10 M 12 F 17 F 19 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
25647
4M 6M 8F 12 F 13 M 14 F
21 21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 17 GRADE
-786-
PROJECT NO..:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO..:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP NO. SEX
LACT DAY TISSUE
GROUP 4: 1.0 MG/KG/DAY FINDING
25747
1M 3M 4M 5M 8F 9F 13 F 15 F
21 21 21 21 21 21 21 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
25744
1M 3M 4M 6M 8F 11 F 13 F 14 F
21 21 21 21 21 21 21 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
25707
3M 5M 7M 8M 9F 10 F 12 F 14 F
21 21 21 21 21 21 21 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
5M 6M 12 M
21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 - MARKED, P - PRESENT
PAGE 18 GRADE
-787-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 20 (F1 - PND 21 SCHEDULED NECROPSY) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PUP NECROPSY FINDINGS
PUP NO. SEX
LACT DAY TISSUE
GROUP 4: 1.0 MG/KG/DAY FINDING
25723
(CONTINUED) 13 F 15 F 16 F 17 M 18 F
21 21 21 21 21
NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS
GRADE CODE: 1 - SLIGHT, 2 - MODERATE, 3 -- MARKED, P - PRESENT
PAGE 19 GRADE
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
GROUP: 0 MG/KG/DAY
SEX: MALES
ANIMAL
DAY OF RESPONSE
WEIGHT GRAMS
PND===> 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
47 222.4 48 250.9 46 230.6 48 222.2 47 252.4 43 243.2 47 261.9 47 246.1 47 260.5 42 238.4 44 225.1 49 272.9 44 240.9 45 267.2 45 261.6 48 261.3 45 265.4 49 281.0 44 234.3 49 223.8
NNNNNY NNNNNNY NNNNY NNNNNNY NNNNNY NY NNNNNY NNNNNY NNNNNY Y NNY NNNNNNNY NNY NNNY NNNY NNNNNNY NNNY NNNNNNNY NNY NNNNNNNY
MEAN S.D.
N
46.2 2.09
20
248.1 18.08
20
N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY
PAGE
1
-789-
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
GROUP: 0.1 MG/KG/DAY SEX: MALES
ANIMAL
DAY OF RESPONSE
WEIGHT GRAMS
PND===> 42 43 44
5 46 47 48 49 50 51 52 53 54 55 56
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
46 246.6 50 246.2 56 377.6 45 279.0 45 242.2 45 238.0 49 256.5 45 273.6 48 237.2 45 275.2 42 245.4 46 239.2 48 245.8 46 246.7 44 245.4 45 259.2 49 292.3 47 306.7 55 356.7 43 255.4
NNNNY NNNNNNNNY NNNNNNNNNNNNNNY NNNY NNNY NNNY NNNNNNNY NNNY NNNNNNY NNNY Y NNNNY NNNNNNY NNNNY NNY NNNY NNNNNNNY NNNNNY NNNNNNNNNNNNNY NY
MEAN S.D.
N
47.0 3.56
20
268.2 38.92
20
N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY
PAGE
2
-790-
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
GROUP: 0.3 MG/KG/DAY SEX: MALES
ANIMAL
DAY OF RESPONSE
WEIGHT GRAMS
PND=== > 42 43 44 45 46 47 48
9 50 51 52 53 54 55 56
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
47 258.5 44 253.7 46 232.4 44 246.5 44 256.4 48 272.1 54 317.6 45 256.0 46 242.5 43 241.0 42 231.2 46 253.9 45 260.3 46 254.8 47 279.3 45 218.1 49 245.5 44 250.1 43 233.0 47 248.8
NNNNNY NNY NNNNY NNY NNY NNNNNNY NNNNNNNNNNNNY NNNY NNNNY NY Y NNNNY NNNY NNNNY NNNNNY NNNY NNNNNNNY NNY NY NNNNNY
MEAN S.D.
N
45.8 2.63
20
252.6 20.81
20
N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY
PAGE
3
-791-
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
GROUP: 1.0 MG/KG/DAY SEX: MALES
ANIMAL
DAY OF RESPONSE
WEIGHT GRAMS
PND===> 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
48 265.5 45 253.2 45 244.8 49 235.5 45 266.7 46 266.3 42 229.5 48 273.4 45 249.1 46 249.0 43 238.7 46 228.9 46 187.4 45 238.2 48 279.1 44 251.3 45 238.0 46 226.7 45 232.5 48 217.1
NNNNNNY NNN Y NNN Y NNNNNNN Y NNN Y NNNN Y Y NNNNNNY NNN Y NNNN Y NY NNNN Y NNNN Y NNN Y NNNNNNY NNY NNN Y NNNN Y NNN Y NNNNNNY
MEAN S.D.
N
45.8 1.77
20
243.5 21.43
20
N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY
PAGE
4
PJTBBv1.16 10/05/2006 R:10/10/2006
-792-
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
GROUP: 0 MG/KG/DAY
SEX: FEMALES
ANIMAL
DAY OF RESPONSE
WEIGHT GRAMS
PND=== > 28 29 30 31 32 33 34 35 36
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
33 92.9 33 97.2 30 96.2 32 79.0 32 112.1 31 113.6 32 109.8 32 106.6 31 104.8 31 114.0 33 96.2 32 107.3 33 129.0 29 103.9 31 105.1 32 118.2 32 111.1 32 117.7 31 109.0 31 92.0
NNNNNY NNNNNY NNY NNNNY NNNNY NNNY NNNNY NNNNY NNNY NNNY NNNNNY NNNNY NNNNNY NY NNNY NNNNY NNNNY NNNNY NNNY NNNY
MEAN S.D.
N
31.7 1.04
20
105.8 11.23
20
N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY
PAGE 1
-793-
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
GROUP: 0.1 MG/KG/DAY SEX: FEMALES
ANIMAL
DAY OF RESPONSE
WEIGHT GRAMS
PND===> 8 29 30 31 32 33 34 35 36
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
31 106.9 33 110.2 32 112.3 33 126.0 36 155.1 33 129.0 32 104.3 32 105.6 35 120.2 33 119.1 31 109.5 34 124.4 33 113.7 34 107.4 34 128.1 31 109.1 30 117.0 33 119.4 32 126.7 32 128.1
NNNY NNNNNY NNNNY NNNNNY NNNNNNNNY NNNNNY NNNNY NNNNY NNNNNNNY NNNNNY NNNY NNNNNNY NNNNNY NNNNNNY NNNNNNY NNNY NNY NNNNNY NNNNY NNNNY
MEAN S.D.
N
32.7 1.45
20
118.6 11.97
20
N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY
PAGE
2
-794-
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
GROUP: 0.3 MG/KG/DAY SEX: FEMALES
ANIMAL
DAY OF RESPONSE
WEIGHT GRAMS
PND=== > 28 29 30 31 32 33 34 35 36
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
35 122.3 31 99.9 32 100.8 30 107.2 33 117.8 34 124.9 33 117.3 32 111.0 33 121.2 32 115.4 28 94.2 31 114.6 30 101.2 32 105.8 32 94.7 34 115.1 31 115.5 32 111.3 33 110.0 31 111.9
NNNNNNNY NNNY NNNNY NNY NNNNNY NNNNNNY NNNNNY NNNNY NNNNNY NNNNY Y NNNY NNY NNNNY NNNNY N N N N NN Y NNNY NNNNY N N N N NY NNNY
MEAN S.D.
N
32.0 1.61
20
110.6 8.86 20
N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY
PAGE
3
-795-
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
GROUP: 1.0 MG/KG/DAY SEX: FEMALES
ANIMAL
DAY OF RESPONSE
WEIGHT GRAMS
PND===> 28 29 30 31 32 33 34 35 36
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
32 113.8 33 107.2 34 121.9 34 98.3 32 120.2 32 102.6 32 117.0 32 126.6 32 115.7 32 109.4 32 123.7 32 106.6 32 99.9 33 121.4 32 102.8 32 119.3 32 103.7 32 96.8 31 96.4 32 105.5
NNNNY NNNNNY NNNNNNY NNNNNNY NNNNY NNNNY NNNNY NNNNY NNNNY NNNNY NNNNY NNNNY NNNNY NNNNNY NNNNY NNNNY NNNNY NNNNY NNNY NNNNY
MEAN S.D.
N
32.3 0.72
20
110.4 9.74 20
N = NEGATIVE RESPONSE, Y = POSITIVE RESPONSE PND= POSTNATAL DAY
PAGE
4
PJTBBv1.16 10/05/2006 R:10/10/2006
-796-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25713-02
M M M M M M M M M M M M M
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25692-04
M M M M M M M
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 06-17-06 TO 08-08-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
08-03-06 08-03-06 08-04-06 08-04-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-06-06 08-06-06 08-06-06 07-14-06 07-21-06 07-28-06 07-28-06 08-04-06 08-04-06 08-04-06 08-06-06 08-06-06 07-14-06 08-06-06 08-06-06 08-06-06 08-06-06 08-06-06 08-07-06 07-08-06
6:55 6:56 7:06 7:07 7:14 7:10 7:10 7:14 7:10 7:45 7:45 7:50 7:45 8:41 10:11 10:12 6:32 6:32 6:32 7:07 7:07 10:17 7:45 7:45 7:45 7:46 7:46 7:22 6:40
P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 HAIR LOSS DORSAL NECK 1 HAIR LOSS VENTRAL NECK 1 HAIR LOSS VENTRAL NECK P SCABBING VENTRAL NECK P SCABBING VENTRAL NECK 1 HAIR LOSS VENTRAL NECK P SCABBING RIGHT LATERAL THORACIC AREA P SCABBING VENTRAL NECK 1 HAIR LOSS VENTRAL NECK P MOIST ALOPECIA DORSAL NECK P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE
1
-797-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 06-17-06 TO 08-08-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25692-04 M 0 MG/KG/DAY
25701-09 M 0 MG/KG/DAY 25645-06 M 0 MG/KG/DAY 25648-07 M 0.1 MG/KG/DAY 25674-02 M 0.1 MG/KG/DAY 25694-04 M 0.1 MG/KG/DAY 25631-04 M 0.1 MG/KG/DAY 25660-01 M 0.1 MG/KG/DAY 25704-03 M 0.1 MG/KG/DAY 25665-01 M 0.1 MG/KG/DAY 25652-04 M 0.1 MG/KG/DAY 25652-04 M 0.1 MG/KG/DAY
25733-07 M 0.1 MG/KG/DAY 25748-01 M 0.1 MG/KG/DAY 25753-06 M 0.1 MG/KG/DAY 25672-06 M 0.1 MG/KG/DAY 25655-01 M 0.1 MG/KG/DAY 25727-07 M 0.1 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION
07-08-06 07-15-06 07-15-06 07-22-06 07-22-06 07-29-06 07-29-06 08-05-06 08-05-06 08-07-06 08-07-06 08-07-06 08-08-06 08-03-06 08-04-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 07-06-06 07-06-06 08-05-06 08-06-06 08-06-06 08-06-06 08-06-06 08-06-06
6:40 6:13 6:13 8:44 8:44 6:16 6:16 6:36 6:36 7:08 7:08 7:22 7:17 6:57 7:06 7:10 7:15 7:10 7:10 7:10 7:11 7:04 7:04 7:15 7:46 7:46 7:46 7:46 7:46
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 2 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 HAIR LOSS DORSAL NECK P SCABBING DORSAL NECK P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
2
-798-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 25749-04 M 0.1 MG/KG/DAY 25739-07 M 0.1 MG/KG/DAY 25756-05 M 0.1 MG/KG/DAY 25741-07 M 0.1 MG/KG/DAY 25752-09 M 0.1 MG/KG/DAY 25671-04 M 0.3 MG/KG/DAY 25614-10 M 0.3 MG/KG/DAY 25698-05 M 0.3 MG/KG/DAY 25677-05 M 0.3 MG/KG/DAY 25604-04 M 0.3 MG/KG/DAY 25678-02 M 0.3 MG/KG/DAY 25678-02 M 0.3 MG/KG/DAY 25609-04 M 0.3 MG/KG/DAY 25623-08 M 0.3 MG/KG/DAY 25653-02 M 0.3 MG/KG/DAY 25653-02 M 0.3 MG/KG/DAY 25684-04 M 0.3 MG/KG/DAY 25684-04 M 0.3 MG/KG/DAY
25714-02 M 0.3 MG/KG/DAY 25650-11 M 0.3 MG/KG/DAY 25735-05 M 0.3 MG/KG/DAY 25722-01 M 0.3 MG/KG/DAY 25642-05 M 0.3 MG/KG/DAY 25628-07 M 0.3 MG/KG/DAY 25766-01 M 0.3 MG/KG/DAY
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION EYES/EARS/NOSE DISPOSITION DISPOSITION DISPOSITION EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION
08-06-06 08-06-06 08-07-06 08-07-06 08-08-06 08-08-06 08-03-06 08-04-06 08-04-06 08-04-06 08-04-06 08-04-06 06-28-06 08-05-06 08-05-06 08-05-06 06-22-06 08-05-06 06-22-06 06-22-06 06-29-06 06-29-06 08-06-06 08-06-06 08-06-06 08-06-06 08-06-06 08-06-06 08-06-06
7:46 7:46 7:23 7:23 7:17 7:17 6:55 7:06 7:08 7:08 7:06 7:08 7:04 7:15 7:11 7:11 6:35 7:11 6:36 6:36 6:33 6:33 7:47 7:51 7:47 7:47 7:47 7:47 7:47
P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
3
-799-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 25708-01 M 0.3 MG/KG/DAY 25708-01 M 0.3 MG/KG/DAY
25743-08 M 0.3 MG/KG/DAY 25743-08 M 0.3 MG/KG/DAY
25696-04 M 1.0 MG/KG/DAY 25686-04 M 1.0 MG/KG/DAY 25630-04 M 1.0 MG/KG/DAY 25673-09 M 1.0 MG/KG/DAY 25639-06 M 1.0 MG/KG/DAY 25658-08 M 1.0 MG/KG/DAY 25676-02 M 1.0 MG/KG/DAY 25600-02 M 1.0 MG/KG/DAY 25603-04 M 1.0 MG/KG/DAY 25603-04 M 1.0 MG/KG/DAY
25703-03 M 1.0 MG/KG/DAY 25705-07 M 1.0 MG/KG/DAY 25611-07 M 1.0 MG/KG/DAY
DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION
08-07-06 08-07-06 08-05-06 08-05-06 08-07-06 08-07-06 07-29-06 08-07-06 07-29-06 08-05-06 08-05-06 08-07-06 08-04-06 08-04-06 08-04-06 08-04-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 07-20-06 07-27-06 07-27-06 08-05-06 08-05-06 08-05-06 08-05-06 08-06-06
7:24 7:23 6:42 6:42 7:12 7:12 6:19 7:23 6:21 6:43 6:43 7:13 7:08 7:08 7:08 7:09 7:16 7:11 7:11 7:11 7:11 9:39 7:50 7:50 6:44 6:44 7:11 7:16 7:47
P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCABBING DORSAL THORACIC AREA 1 HAIR LOSS DORSAL THORACIC AREA P SCABBING DORSAL NECK 1 HAIR LOSS DORSAL NECK P SCABBING DORSAL THORACIC AREA P SCHEDULED EUTHANASIA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
4
-800-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 25619-04 M 1.0 MG/KG/DAY
DISPOSITION EYES/EARS/NOSE
08-06-06 06-17-06 06-17-06 06-23-06 06-23-06 06-30-06 06-30-06 06-30-06 06-30-06 07-07-06 07-07-06 07-07-06 07-07-06 07-14-06 07-14-06 07-14-06 07-21-06 07-21-06 07-21-06 07-21-06 07-28-06 07-28-06 07-28-06 08-04-06 08-04-06 08-04-06 08-06-06 08-06-06 08-06-06
7:51 11:31 11:31
6:54 6:54 6:22 6:22 6:24 6:24 6:49 6:49 6:50 6:50 7:52 7:53 7:53 8:50 8:50 8:51 8:51 10:22 10:22 10:22 6:46 6:46 6:47 7:13 7:13 7:13
P SCHEDULED EUTHANASIA P OPACITY RIGHT EYE P OPACITY LEFT EYE P OPACITY RIGHT EYE P OPACITY LEFT EYE P OPACITY LEFT EYE P OPACITY RIGHT EYE P EXOPHTHALMUS RIGHT EYE 1 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY LEFT EYE P OPACITY RIGHT EYE P EXOPHTHALMUS RIGHT EYE 1 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY RIGHT EYE P OPACITY LEFT EYE P EXOPHTHALMUS RIGHT EYE P OPACITY RIGHT EYE P OPACITY LEFT EYE P EXOPHTHALMUS RIGHT EYE 1 DRIED RED MATERIAL AROUND RIGHT EYE P OPACITY RIGHT EYE P OPACITY LEFT EYE P EXOPHTHALMUS RIGHT EYE P OPACITY RIGHT EYE P OPACITY LEFT EYE P EXOPHTHALMUS RIGHT EYE P OPACITY LEFT EYE P OPACITY RIGHT EYE P EXOPHTHALMUS RIGHT EYE
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
5
-801-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 25691-07 M 1.0 MG/KG/DAY 25717-04 M 1.0 MG/KG/DAY 25616-05 M 1.0 MG/KG/DAY 25715-07 M 1.0 MG/KG/DAY 25599-06 M 1.0 MG/KG/DAY 25599-06 M 1.0 MG/KG/DAY
25762-01 M 1.0 MG/KG/DAY 25647-07 M 1.0 MG/KG/DAY 25647-07 M 1.0 MG/KG/DAY
25597-17 F 25597-17 F
0 MG/KG/DAY 0 MG/KG/DAY
25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18
F F F F F F F F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
EYES/EARS/NOSE DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION EYES/EARS/NOSE
DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION
06-29-06 08-06-06 08-06-06 08-06-06 08-06-06 08-06-06 07-14-06 07-14-06 08-07-06 08-07-06 07-27-06 07-27-06 08-03-06 08-01-06 08-01-06 08-03-06 08-03-06 08-03-06 08-03-06 08-03-06 08-04-06 08-04-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-06-06 08-06-06
7:16 7:51 7:52 7:47 7:47 7:47 7:55 7:55 7:23 7:23 9:42 9:42 6:55 7:18 7:18 6:36 6:36 6:37 6:38 6:56 7:09 7:09 7:11 7:11 7:16 7:17 7:11 7:47 7:47
P APPARENT MECHANICAL INJURY RIGHT EYE P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 DRIED RED MATERIAL AROUND LEFT EYE 1 DRIED RED MATERIAL AROUND RIGHT EYE P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P MOIST ALOPECIA LEFT DORSAL HEAD P MOIST ALOPECIA RIGHT DORSAL HEAD P SCHEDULED EUTHANASIA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCABBING LEFT FORELIMB P SCABBING RIGHT FORELIMB P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
6
-802-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 06-17-06 TO 08-08-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25713-16 25670-18 25670-18
F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
25657-10 25663-09 25690-19 25666-09 25692-07 25692-07
F F F F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
25701-18 F 0 MG/KG/DAY 25645-08 F 0 MG/KG/DAY 25648-12 F 0.1 MG/KG/DAY 25674-11 F 0.1 MG/KG/DAY 25694-13 F 0.1 MG/KG/DAY 25631-05 F 0.1 MG/KG/DAY 25660-04 F 0.1 MG/KG/DAY 25704-09 F 0.1 MG/KG/DAY 25665-07 F 0.1 MG/KG/DAY 25652-13 F 0.1 MG/KG/DAY 25733-08 F 0.1 MG/KG/DAY 25748-08 F 0.1 MG/KG/DAY 25753-15 F 0.1 MG/KG/DAY 25672-15 F 0.1 MG/KG/DAY
DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION
08-06-06 08-06-06 07-21-06 07-21-06 07-28-06 07-28-06 07-28-06 07-28-06 08-06-06 08-06-06 08-06-06 08-06-06 08-07-06 08-07-06 08-07-06 08-07-06 08-08-06 08-03-06 08-04-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-06-06 08-06-06 08-06-06
7:52 7:48 8:57 8:57 10:26 10:26 10:26 10:27 7:48 7:52 7:48 7:48 7:24 7:15 7:15 7:24 7:17 6:57 7:07 7:11 7:11 7:17 7:12 7:12 7:12 7:18 7:48 7:48 7:48
P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 HAIR LOSS LEFT LATERAL THORACIC AREA P SCABBING LEFT LATERAL THORACIC AREA 1 HAIR LOSS LEFT LATERAL THORACIC AREA P SCABBING LEFT LATERAL THORACIC AREA 1 HAIR LOSS RIGHT LATERAL THORACIC AREA P SCABBING RIGHT LATERAL THORACIC AREA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
7
-803-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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 25727-16 F 0.1 MG/KG/DAY 25626-12 F 0.1 MG/KG/DAY 25749-11 F 0.1 MG/KG/DAY 25739-12 F 0.1 MG/KG/DAY 25756-13 F 0.1 MG/KG/DAY 25741-09 F 0.1 MG/KG/DAY 25752-13 F 0.1 MG/KG/DAY 25671-06 F 0.3 MG/KG/DAY 25614-17 F 0.3 MG/KG/DAY 25698-12 F 0.3 MG/KG/DAY 25677-08 F 0.3 MG/KG/DAY 25604-12 F 0.3 MG/KG/DAY 25678-11 F 0.3 MG/KG/DAY 25609-11 F 0.3 MG/KG/DAY 25623-15 F 0.3 MG/KG/DAY 25653-13 F 0.3 MG/KG/DAY 25684-06 F 0.3 MG/KG/DAY 25684-06 F 0.3 MG/KG/DAY
25714-13 F 0.3 MG/KG/DAY 25650-17 F 0.3 MG/KG/DAY 25735-08 F 0.3 MG/KG/DAY 25722-15 F 0.3 MG/KG/DAY 25722-15 F 0.3 MG/KG/DAY
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
08-06-06 08-06-06 08-06-06 08-06-06 08-07-06 08-07-06 08-08-06 08-08-06 08-03-06 08-04-06 08-04-06 08-04-06 08-04-06 08-04-06 08-05-06 08-05-06 08-05-06 08-05-06 06-22-06 06-22-06 06-29-06 06-29-06 08-06-06 08-06-06 08-06-06 08-06-06 07-14-06 07-14-06 07-21-06
7:49 7:53 7:48 7:48 7:24 7:24 7:18 7:18 6:56 7:07 7:09 7:07 7:10 7:10 7:12 7:12 7:12 7:18 6:37 6:37 6:40 6:40 7:48 7:49 7:53 7:49 8:01 8:01 9:01
P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
8
-804-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
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
25628-17 25766-06 25689-14 25708-15 25743-16 25642-12 25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14
F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION
07-21-06 07-21-06 07-21-06 08-04-06 08-04-06 08-06-06 08-06-06 08-06-06 08-06-06 08-07-06 08-07-06 08-07-06 08-06-06 08-04-06 08-04-06 08-04-06 08-04-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-05-06 08-06-06 08-06-06 08-06-06 08-06-06 08-06-06
9:02 9:02 9:02 6:58 6:58 7:21 7:21 7:49 7:49 7:24 7:24 7:25 7:49 7:10 7:07 7:10 7:11 7:18 7:19 7:12 7:12 7:19 7:12 7:12 7:49 7:49 7:49 7:49 7:49
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT HINDLIMB 1 HAIR LOSS LEFT HINDLIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
9
-805-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 23 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 06-17-06 TO 08-08-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25715-10 25599-11 25762-11 25647-11
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
DISPOSITION DISPOSITION DISPOSITION DISPOSITION
08-06-06 08-06-06 08-07-06 08-07-06
7:49 7:53 7:24 7:24
P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA P SCHEDULED EUTHANASIA
GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT
PAGE 10
PCRDv4.11 01/23/2007
-806-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PND 28
ANIMALS FROM GROUP 1:
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
75. 77. 79. 61. 87. 98. 94. 82. 90. 97. 86. 88. 96. 99. 101. 87. 97. 100. 88. 75.
MEAN S.D.
N
88. 10.5
20
APPENDIX 24 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS [G]
35 42
0 MG/KG/DAY
127. 135. 137. 108. 149. 167. 160. 145. 155. 174. 145. 154. 168. 177. 167. 151. 165. 163. 153. 123.
188. 205. 197. 172. 212. 236. 226. 208. 220. 239. 207. 218. 223. 246. 233. 214. 239. 231. 215. 175.
151. 17.9
20
215. 20.5
20
49
234. 257. 250. 231. 267. 288. 276. 261. 283. 307. 263. 274. 296. 313. 293. 270. 298. 280. 278. 224.
272. 24.6
20
MALES 56 63
274. 310. 299. 291. 319. 337. 324. 309. 338. 369. 312. 323. 353. 381. 348. 324. 357. 329. 327. 268.
325. 29.1
20
307. 347. 334. 325. 364. 374. 364. 346. 373. 419. 346. 350. 403. 419. 393. 351. 399. 376. 374. 311.
364. 32.3
20
70
334. 386. 372. 373. 393. 404. 403. 389. 404. 455. 386. 382. 441. 468. 439. 392. 454. 413. 408. 338.
402. 36.1
20
72
339. 386. 383. 383. 404. 413. 407. 401. 414. 477. 404. 392. 462. 484. 453. 405. 465. 423. 415. 346.
413. 39.2
20
PAGE 1
-807-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 24 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS [G]
MALES PND 28 35 42 49 56 63 70 72
ANIMALS FROM GROUP 2: 0.1 MG/KG/DAY
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
87. 76. 103. 101. 90. 91. 84. 96. 74. 99. 100. 89. 82. 86. 96. 91. 101. 103. 100. 102.
148. 132. 172. 181. 151. 151. 147. 174. 138. 174. 179. 153. 138. 151. 164. 164. 164. 180. 175. 175.
216. 191. 242. 255. 215. 213. 208. 248. 199. 250. 247. 207. 192. 215. 229. 233. 234. 260. 243. 245.
271. 234. 314. 326. 278. 268. 255. 315. 247. 313. 314. 265. 258. 277. 284. 289. 292. 329. 298. 308.
322. 286. 377. 389. 324. 321. 307. 385. 298. 363. 366. 317. 309. 339. 341. 350. 362. 384. 358. 352.
356. 318. 430. 447. 374. 357. 343. 444. 337. 412. 403. 358. 348. 393. 386. 388. 405. 449. 412. 402.
399. 351. 473. 500. 409. 401. 370. 503. 375. 450. 434. 380. 380. 437. 428. 428. 449. 499. 447. 440.
407. 362. 487. 514. 421. 409. 388. 520. 383. 467. 448. 396. 384. 453. 434. 435. 462. 516. 465. 455.
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
PAGE 2
-808-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 24 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS [G]
MALES PND 28 35 42 49 56 63 70 72
ANIMALS FROM GROUP 3: 0.3 MG/KG/DAY
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
83. 96. 79. 91. 95. 87. 92. 88. 93. 91. 100. 95. 97. 84. 99. 82. 74. 105. 95. 79.
146. 168. 135. 160. 168. 152. 156. 159. 156. 164. 168. 163. 165. 154. 169. 137. 136. 170. 162. 136.
219. 236. 199. 225. 241. 219. 226. 231. 217. 231. 230. 228. 232. 218. 237. 195. 195. 228. 226. 206.
280. 297. 255. 281. 304. 278. 284. 292. 267. 295. 279. 289. 297. 280. 295. 249. 246. 295. 279. 264.
348. 364. 317. 337. 364. 342. 330. 354. 323. 342. 332. 340. 352. 333. 346. 295. 294. 342. 323. 324.
390. 404. 366. 373. 410. 388. 376. 396. 356. 382. 366. 381. 398. 376. 385. 334. 320. 388. 365. 371.
432. 446. 409. 403. 464. 425. 413. 445. 398. 417. 412. 415. 435. 422. 425. 370. 357. 421. 401. 413.
456. 460. 419. 415. 474. 442. 431. 454. 411. 426. 419. 430. 448. 430. 433. 385. 366. 433. 407. 426.
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
PAGE 3
-809-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 24 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS [G]
MALES PND 28 35 42 49 56 63 70 72
ANIMALS FROM GROUP 4: 1.0 MG/KG/DAY
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
91. 157. 225. 277. 331. 366. 413. 434. 86. 153. 225. 287. 344. 379. 422. 433. 98. 156. 225. 275. 338. 382. 422. 434. 72. 124. 185. 238. 296. 327. 362. 377. 93. 161. 236. 301. 353. 402. 442. 455. 86. 150. 227. 294. 350. 392. 448. 459. 93. 162. 229. 279. 328. 363. 407. 417. 97. 165. 226. 287. 341. 379. 408. 418. 91. 158. 225. 281. 324. 368. 409. 420. 91. 149. 217. 273. 322. 353. 394. 403. 88. 155. 232. 301. 357. 408. 456. 463. 86. 150. 204. 245. 283. 310. 351. 358. 70. 125. 172. 221. 279. 308. 348. 360. 85. 150. 212. 275. 333. 375. 421. 425. 86. 148. 223. 292. 348. 387. 431. 449. 92. 157. 231. 305. 359. 404. 462. 475. 80. 144. 211. 272. 331. 374. 425. 433. 78. 133. 198. 238. 307. 346. 387. 399. 83. 144. 207. 261. 326. 366. 404. 419. 56. 104. 165. 223. 272. 305. 346. 361.
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
PAGE 4
-810-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PND 28
ANIMALS FROM GROUP 1:
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
65. 71. 83. 56. 81. 92. 81. 80. 82. 92. 69. 81. 88. 92. 87. 86. 81. 86. 86. 72.
MEAN S.D.
N
80. 9.6
20
APPENDIX 24 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS [G]
35 42
0 MG/KG/DAY
106. 113. 128.
99. 132. 153. 126. 121. 135. 146. 111. 125. 148. 140. 131. 141. 133. 135. 139. 115.
137. 157. 164. 144. 181. 180. 159. 150. 171. 186. 143. 159. 178. 171. 170. 181. 166. 176. 174. 137.
129. 14.4
20
164. 15.4
20
49
158. 176. 187. 174. 202. 215. 179. 169. 203. 214. 169. 183. 217. 184. 189. 217. 189. 197. 191. 154.
188. 19.0
20
FEMALES 56 63
173. 195. 209. 198. 222. 265. 202. 190. 237. 237. 187. 202. 243. 209. 212. 238. 207. 225. 216. 170.
212. 24.2
20
195. 216. 226. 223. 240. 267. 215. 193. 243. 267. 202. 224. 260. 233. 238. 258. 220. 229. 232. 187.
228. 23.5
20
70
202. 223. 246. 230. 262. 285. 229. 207. 266. 288. 218. 234. 279. 261. 255. 276. 232. 245. 244. 187.
243. 28.3
20
72
209. 227. 246. 243. 256. 283. 237. 208. 270. 277. 215. 228. 269. 273. 245. 281. 236. 248. 245. 197.
245. 25.7
20
PAGE 5
-811-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 24 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS [G]
FEMALES PND 28 35 42 49 56 63 70 72
ANIMALS FROM GROUP 2: 0.1 MG/KG/DAY
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
86. 76. 82. 84. 96. 90. 75. 73. 72. 84. 84. 78. 78. 68. 84. 85. 99. 86. 94. 101.
137. 126. 131. 140. 152. 138. 124. 125. 120. 133. 138. 132. 131. 116. 134. 136. 146. 130. 154. 153.
175. 163. 173. 174. 189. 179. 162. 164. 152. 169. 170. 175. 175. 157. 173. 175. 188. 166. 193. 192.
184. 183. 191. 200. 206. 203. 176. 182. 164. 193. 188. 191. 199. 183. 203. 206. 218. 185. 208. 236.
190. 212. 216. 225. 226. 236. 191. 213. 187. 215. 217. 200. 227. 214. 228. 236. 241. 196. 238. 253.
232. 232. 232. 244. 254. 247. 210. 235. 194. 227. 241. 225. 245. 230. 244. 252. 251. 213. 260. 268.
249. 245. 250. 257. 271. 254. 220. 252. 211. 249. 245. 237. 270. 260. 260. 266. 283. 227. 269. 303.
251. 246. 239. 267. 260. 269. 223. 250. 218. 244. 255. 236. 272. 263. 267. 258. 287. 221. 273. 303.
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
PAGE 6
-812-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 24 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS [G]
FEMALES PND 28 35 42 49 56 63 70 72
ANIMALS FROM GROUP 3: 0.3 MG/KG/DAY
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
77. 120. 165. 187. 207. 228. 240. 250. 78. 128. 167. 193. 208. 229. 242. 246. 73. 123. 157. 175. 206. 217. 234. 237. 91. 148. 189. 210. 231. 251. 256. 272. 82. 132. 168. 190. 219. 231. 240. 252. 82. 131. 172. 196. 219. 231. 248. 253. 78. 126. 163. 189. 204. 230. 251. 244. 78. 135. 170. 178. 219. 240. 258. 253. 85. 132. 155. 170. 193. 208. 217. 228. 86. 136. 177. 206. 212. 236. 252. 249. 94. 147. 179. 207. 222. 245. 252. 261. 93. 141. 193. 220. 246. 284. 264. 279. 85. 136. 182. 212. 245. 262. 274. 297. 78. 120. 163. 187. 201. 227. 237. 252. 71. 115. 149. 181. 204. 221. 246. 260. 70. 119. 156. 170. 181. 197. 216. 223. 94. 147. 177. 198. 211. 239. 252. 240. 84. 135. 154. 175. 189. 203. 222. 220. 73. 121. 139. 157. 171. 190. 209. 211. 86. 142. 186. 213. 244. 259. 277. 285.
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
PAGE 7
-813-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 24 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS [G]
FEMALES PND 28 35 42 49 56 63 70 72
ANIMALS FROM GROUP 4: 1.0 MG/KG/DAY
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
84. 137. 174. 191. 221. 236. 246. 246. 72. 125. 156. 173. 203. 223. 236. 236. 80. 124. 160. 179. 189. 208. 220. 220. 63. 105. 142. 161. 184. 198. 214. 219. 92. 143. 182. 219. 245. 266. 293. 296. 75. 125. 165. 192. 215. 237. 254. 268. 88. 139. 173. 193. 215. 230. 239. 240. 95. 148. 173. 186. 200. 220. 241. 239. 86. 132. 162. 181. 201. 213. 230. 229. 83. 131. 169. 189. 205. 229. 249. 241. 90. 147. 184. 205. 231. 251. 268. 260. 78. 125. 157. 172. 188. 205. 216. 219. 72. 124. 160. 203. 232. 256. 273. 278. 86. 137. 179. 206. 222. 241. 257. 272. 73. 124. 153. 186. 218. 232. 241. 261. 85. 145. 183. 215. 239. 262. 270. 268. 78. 128. 152. 179. 199. 217. 208. 231. 73. 117. 151. 177. 199. 221. 231. 246. 78. 124. 147. 163. 178. 188. 201. 198. 76. 125. 165. 196. 223. 239. 245. 260.
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
PAGE 8
PJTBWv4.22 10/10/2006
-814-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PND 28 - 35
ANIMALS FROM GROUP 1:
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
52. 59. 58. 48. 61. 69. 66. 63. 65. 77. 59. 66. 72. 77. 66. 64. 68. 63. 65. 47.
MEAN S.D.
N
63. 8.1
20
APPENDIX 25 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES [G]
35- 42 42- 49
0 MG/KG/DAY
60. 47. 69. 53. 60. 53. 64. 59. 63. 55. 69. 53. 66. 51. 63. 53. 66. 63. 65. 68. 62. 56. 64. 56. 55. 74. 69. 67. 66. 60. 63. 57. 74. 60. 67. 50. 62. 63. 53. 48.
64. 57. 4.8 7.0
20 20
49- 56
40. 53. 49. 60. 51. 48. 48. 48. 55. 63. 48. 49. 57. 68. 55. 54. 58. 49. 50. 45.
52. 6.5
20
MALES 56- 63 63- 70
33. 26. 36. 39. 35. 38. 34. 48. 46. 28. 37. 30. 40. 39. 37. 43. 35. 32. 49. 37. 34. 40. 27. 32. 50. 38. 39. 49. 45. 47. 27. 41. 42. 55. 47. 38. 46. 34. 43. 27.
39. 38. 6.8 7.8
20 20
70- 72
5. 0. 11. 10. 11. 9. 4. 13. 10. 22. 18. 10. 21. 16. 14. 12. 11. 9. 7. 8.
11. 5.3
20
28- 72
264. 309. 304. 322. 316. 315. 313. 319. 324. 380. 318. 304. 366. 385. 352. 318. 367. 323. 327. 271.
325. 31.7
20
PAGE 1
-815-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 25 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES [G]
PND 28 - 35
35 - 42
42- 49
49- 56
MALES 56- 63 63- 70
70- 72
28- 72
ANIMALS FROM GROUP 2: 0.1 MG/KG/DAY
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
60. 68. 55. 51. 34. 43.
8. 320.
56. 59. 43. 52. 32. 33. 11. 286.
69. 70. 72. 63. 53. 43. 14. 384.
80. 75. 71. 63. 58. 53. 14. 413.
60. 64. 63. 46. 51. 35. 11. 330.
61. 62. 55. 53. 36. 44.
8. 319.
63. 60. 48. 52. 36. 28. 17. 304.
78. 74. 66. 71. 58. 60. 16. 424.
64. 61. 49. 51. 39. 38.
8. 309.
75. 76. 64. 50. 49. 38. 17. 368.
79. 68. 67. 52. 38. 31. 14. 349.
64. 55. 58. 52. 41. 22. 16. 307.
56. 54. 65. 52. 38. 32.
5. 302.
65. 64. 62. 62. 54. 45. 15. 367.
68. 65. 55. 58. 44. 42.
7. 339.
72. 70. 56. 61. 37. 41.
6. 344.
64. 69. 59. 70. 44. 44. 13. 362.
78. 80. 68. 56. 65. 50. 18. 414.
75. 67. 55. 60. 54. 35. 18. 365.
73. 69. 63. 45. 49. 38. 15. 353.
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
PAGE 2
-816-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 25 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES [G]
PND 28 - 35
35 - 42
42- 49
49- 56
MALES 56- 63 63- 70
70- 72
28- 72
ANIMALS FROM GROUP 3: 0.3 MG/KG/DAY
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
64. 73. 61. 68. 42. 43. 24. 373.
72. 68. 61. 67. 40. 42. 14. 364.
57. 64. 56. 62. 48. 43. 11. 341.
69. 65. 56. 55. 36. 31. 11. 324.
73. 73. 63. 61. 45. 54. 10. 379.
65. 67. 59. 64. 46. 38. 17. 355.
64. 69. 58. 46. 47. 37. 18. 339.
71. 72. 61. 62. 42. 49.
8. 366.
63. 61. 50. 56. 33. 42. 12. 318.
73. 67. 64. 47. 40. 34. 10. 335.
69. 62. 49. 52. 35. 45.
8. 320.
68. 65. 61. 51. 41. 34. 15. 335.
68. 67. 66. 55. 46. 37. 13. 351.
70. 65. 62. 52. 43. 46.
9. 347.
70. 68. 58. 51. 39. 40.
8. 334.
55. 58. 54. 47. 39. 36. 16. 303.
62. 59. 51. 49. 26. 37.
9. 292.
65. 58. 67. 48. 46. 33. 12. 328.
67. 64. 54. 44. 42. 36.
6. 312.
56. 70. 58. 60. 47. 42. 13. 347.
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
PAGE 3
-817-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 25 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES [G]
PND 28 - 35
35 - 42
42- 49
49- 56
MALES 56- 63 63- 70
70- 72
28- 72
ANIMALS FROM GROUP 4: 1.0 MG/KG/DAY
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
66. 68. 52. 54. 35. 46. 21. 343.
68. 72. 62. 57. 35. 42. 12. 348.
57. 70. 50. 63. 44. 41. 12. 335.
53. 61. 53. 58. 31. 36. 15. 306.
67. 76. 64. 52. 49. 40. 14. 362.
64. 77. 67. 56. 41. 57. 11. 373.
70. 67. 50. 49. 36. 44. 10. 325.
68. 61. 60. 54. 38. 29. 10. 321.
67. 67. 57. 42. 44. 41. 11. 329.
58. 68. 56. 50. 31. 41.
9. 312.
67. 77. 70. 55. 52. 48.
7. 375.
64. 54. 41. 39. 27. 41.
7. 272.
56. 47. 48. 58. 29. 40. 12. 290.
65. 62. 62. 59. 42. 46.
4. 340.
63. 75. 68. 57. 38. 44. 19. 364.
65. 74. 74. 54. 45. 58. 13. 383.
64. 67. 61. 59. 43. 51.
9. 353.
54. 66. 40. 68. 39. 41. 12. 321.
61. 63. 54. 65. 40. 38. 15. 335.
48. 61. 57. 50. 33. 41. 15. 305.
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
PAGE 4
-818-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PND 28 - 35
ANIMALS FROM GROUP 1:
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
41. 42. 46. 43. 51. 61. 46. 41. 53. 54. 42. 45. 60. 47. 44. 55. 52. 49. 54. 44.
MEAN S.D.
N
48. 6.1
20
APPENDIX 25 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES [G]
35- 42 42 - 49
0 MG/KG/DAY
31. 21. 44. 19. 35. 23. 44. 31. 49. 22. 27. 35. 32. 21. 29. 19. 36. 32. 40. 28. 32. 27. 34. 24. 30. 39. 31. 13. 39. 19. 40. 36. 33. 23. 41. 21. 35. 17. 22. 17.
35. 24. 6.5 7.2
20 20
49- 56
15. 20. 22. 24. 20. 50. 23. 21. 34. 23. 17. 19. 26. 26. 23. 21. 18. 28. 25. 16.
24. 7.7
20
FEMALES 56- 63 63- 70
22. 7. 21. 6. 17. 20. 25. 7. 18. 22.
1. 18. 14. 14.
3. 14. 6. 23. 30. 21. 16. 16. 22. 10. 17. 20. 24. 27. 26. 17. 20. 18. 13. 12. 3. 16. 17. 12. 17. 0.
16. 15. 7.9 6.6
20 20
70- 72
7. 4. 0. 13. -5. -2. 8. 1. 4. -10. -3. -5. -10. 13. -10. 6. 4. 3. 0. 10.
1. 7.1
20
28- 72
144. 156. 163. 187. 176. 191. 157. 129. 189. 186. 146. 148. 182. 181. 157. 196. 154. 162. 159. 126.
164. 20.5
20
PAGE 5
-819-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 25 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES [G]
PND 28 - 35
35 - 42
42- 49
49- 56
FEMALES 56- 63 63- 70
70- 72
28- 72
ANIMALS FROM GROUP 2: 0.1 MG/KG/DAY
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
51. 39. 8. 7. 41. 17. 2. 165.
50. 38. 20. 28. 20. 13.
2. 171.
49. 42. 18. 25. 16. 18. -12. 157.
56. 35. 26. 25. 19. 13. 10. 183.
56. 37. 18. 20. 27. 17. -11. 164.
48. 40. 24. 33. 12.
7. 15. 178.
49. 38. 14. 16. 19. 9. 3. 148.
53. 39. 18. 31. 22. 18. -2. 178.
48. 32. 12. 22.
8. 17.
7. 146.
49. 36. 24. 22. 12. 22. -5. 160.
54. 32. 18. 30. 24. 4. 9. 170.
55. 43. 16.
9. 25. 13. -1. 159.
53. 44. 24. 28. 19. 25.
2. 194.
47. 42. 26. 31. 16. 30.
3. 195.
50. 39. 30. 26. 15. 17.
7. 184.
51. 39. 30. 30. 17. 13. -8. 173.
47. 42. 31. 23. 10. 32.
4. 188.
44. 36. 19. 11. 18. 14. -6. 136.
60. 39. 15. 31. 22. 9. 4. 179.
53. 39. 44. 17. 15. 35.
1. 203.
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
PAGE 6
-820-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 25 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES [G]
PND 28 - 35
35- 42
42- 49
49- 56
FEMALES 56- 63 63- 70
70- 72
28- 72
ANIMALS FROM GROUP 3: 0.3 MG/KG/DAY
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
43. 46. 21. 21. 21. 12. 10. 172.
51. 38. 26. 15. 21. 13.
4. 168.
49. 34. 19. 31. 12. 17.
3. 164.
57. 41. 21. 21. 21.
5. 16. 181.
50. 37. 22. 29. 12.
9. 12. 170.
50. 41. 23. 24. 12. 18.
5. 171.
48. 37. 26. 15. 26. 21. -7. 166.
57. 36.
8. 40. 21. 18. -5. 175.
47. 23. 15. 23. 14. 10. 11. 143.
50. 41. 29.
7. 23. 16. -3. 163.
53. 32. 29. 15. 23. 7. 9. 167.
48. 52. 27. 27. 38. -20. 14. 186.
51. 46. 29. 34. 17. 12. 23. 212.
42. 43. 24. 14. 27.
9. 15. 173.
44. 34. 32. 23. 17. 26. 14. 189.
49. 37. 15. 10. 16. 19.
7. 153.
53. 31. 21. 13. 28. 13. -12. 146.
51. 20. 21. 14. 15. 18. -2. 136.
48. 19. 18. 14. 19. 19.
3. 138.
57. 44. 26. 32. 15. 18.
8. 200.
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
PAGE 7
-821-
PROJECT NO.:WIL-180017J SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 25 (F1 - POST-WEANING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES [G]
PND 28 - 35
35- 42
42- 49
49- 56
FEMALES 56- 63 63- 70
70- 72
28- 72
ANIMALS FROM GROUP 4: 1.0 MG/KG/DAY
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
53. 37. 17. 30. 16. 10.
0. 163.
53. 31. 18. 29. 20. 13.
1. 165.
44. 36. 19. 10. 19. 12.
0. 140.
42. 38. 18. 23. 14. 16.
5. 156.
51. 39. 36. 27. 21. 27.
3. 204.
50. 39. 27. 24. 21. 18. 14. 193.
51. 34. 20. 21. 15. 9. 1. 151.
53. 25. 13. 14. 21. 20. -1. 144.
46. 30. 19. 20. 13. 17. -1. 143.
48. 38. 20. 16. 24. 20. -7. 159.
58. 37. 21. 27. 20. 17. -8. 170.
46. 33. 14. 16. 17. 11.
3. 141.
51. 37. 42. 29. 24. 17.
5. 206.
51. 42. 28. 16. 19. 16. 15. 187.
51. 29. 33. 32. 14.
9. 20. 188.
61. 38. 32. 23. 23.
8. -2. 184.
50. 24. 27. 20. 18. -9. 23. 154.
44. 34. 27. 21. 23. 10. 15. 173.
46. 23. 17. 15. 10. 13. -3. 121.
49. 40. 30. 28. 15.
6. 15. 184.
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
PAGE 8
PJTBWv4.22 10/10/2006
-822-
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 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:
1111111111
LACRIMATION
1111111111
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
1
-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 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:
1111111111
LACRIMATION
1111111111
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
2
-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 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:
1111111111
LACRIMATION
1111111111
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
3
-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 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:
1111111111
LACRIMATION
1111111111
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
4
-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 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:
1111111111
LACRIMATION
1111111111
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
5
-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 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:
1111111111
LACRIMATION
1111111111
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
6
-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 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:
1111111111
LACRIMATION
1111111111
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
7
-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 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:
1111111111
LACRIMATION
1111111111
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
8
-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 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:
1111111111
LACRIMATION
1111111111
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
9
-I8-
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:
1111111111
LACRIMATION
1111111111
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
-832-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-833-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-834-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-835-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-836-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-837-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-838-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-839-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-840-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-841-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-842-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-843-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-844-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-845-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-846-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-847-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-848-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-849-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-850-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-851-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-852-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-853-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
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
-854-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-855-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-856-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-857-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-858-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-859-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-860-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-861-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-862-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-863-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-864-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-865-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-866-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-867-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-868-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-869-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-870-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-871-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-872-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-873-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-874-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-875-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-876-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-877-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-878-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-879-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-880-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-881-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-882-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-883-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-884-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-885-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-886-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-887-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-888-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-889-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-890-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-891-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-892-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-893-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 2 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-894-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-895-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-896-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-897-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-898-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-899-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-900-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-901-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-902-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-903-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-904-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
11 12 112 11 1
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-905-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-906-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-907-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-908-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-909-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-910-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-911-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-912-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
11 1 1 1 12 11 1
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-913-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-914-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-915-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
11 1112 111 1
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-916-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
- 16-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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:
1111111111
LACRIMATION
1111111111
CHROMODACRYORRHEA
:1 1 1 1 1 1 1 1 1 1
SALIVATION
:1 1 1 1 1 1 1 1 1 1
PILOERECTION
1111111111
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
-918-
-W WITH VOCALIZATION -W/O WITHOUT VOCALIZATION
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
PARAMETER
SCORING CRITERIA
EASE OF REMOVAL FROM CAGE
1-VERY EASY 4-FREEZES
2-EASY 5-DIFFICULT
3-MODERATELY 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)
RESPIRATORY RATE
1-NORMAL (80-110)
2-DECREASED (<80)
3-INCREASED (>110)
RESPIRATORY CHARACTER
1-NORMAL
2-RALES
3-RETCHING
4-DYSPNEIC
5-GASPING
97
-919-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PARAMETER
APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS
SCORING CRITERIA
RED DEPOSITS - EYES RED DEPOSITS - NOSE RED DEPOSITS - MOUTH CRUSTY DEPOSITS - EYES CRUSTY DEPOSITS - NOSE CRUSTY DEPOSITS - MOUTH MUCOUS MEMBRANES - COLOR
EYE COLOR
PUPILLARY RESPONSE SKIN COLOR
: 1-PRESENT
2-ABSENT
: 1-PRESENT
2-ABSENT
: 1-PRESENT
2-ABSENT
: 1-PRESENT
2-ABSENT
: 1-PRESENT
2-ABSENT
: 1-PRESENT
2-ABSENT
: 1-PINK 4-DARKENED, BROWN
: 1-PINK 4-DARKENED, BROWN
: 1-ABSENT
2-PRESENT
: 1-PINK 4-DARKENED, BROWN
2-PALE 5-BRIGHT, DEEP RED FLUSH
2-PALE 5-BRIGHT, DEEP RED FLUSH
3-DARKENED 3-DARKENED
2-PALE 5-BRIGHT, DEEP RED FLUSH
3-DARKENED
PAGE 98
-920-
PROJECT NO.:WIL-180017H SPONSOR:3M CORPORATION SPONSOR NO.:06-128
PARAMETER
APPENDIX 26 (F1 - FUNCTIONAL OBSERVATIONAL BATTERY - HANDLING OBSERVATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL DETAILED CLINICAL OBSERVATIONS
SCORING CRITERIA
EYE PROMINENCE MUSCLE TONE
: 1-NORMAL
2-EXOPHTHALMUS
3-ENOPHTHALMUS
: 1-FIRM BUT NOT HARD
2-SOFT AND FLABBY
3-TENSE AND HARD
PAGE 99
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 PND 4
1
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 33333333333 11111111111
00000000000 00000000000
-----------
-----------
-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
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
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
:
GROOMING
:
URINATION
: 000000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE PND 4
2
-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 PND 4
3
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1111111111 11111111111 11111111111 33333333333 11111111111
00000000000 00000000000
-----------
-----------
-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
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
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
:
GROOMING
:
URINATION
: 000000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE PND 4
4
-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 PND 4
5
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 33333333333 11111111111
00000000000 00000000000
-----------
-----------
-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
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
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
:
GROOMING
:
URINATION
: 000000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE PND 4
6
-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 PND 4
7
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 33333333333 11111111111
00000000000 00000000000
-----------
-----------
-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
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
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
:
GROOMING
:
URINATION
: 000000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE PND 4
8
-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 PND 4
9
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 33333333333 11111111111
00000000000 00000000000
-----------
-----------
-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
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
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
:
GROOMING
:
URINATION
:000000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 10 PND 4
-I 6-
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 33333333333 11111111111
00000000000 00000000000
-----------
-----------
-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
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
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
:
GROOMING
:
URINATION
:000000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 12 PND 4
-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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 33333333333 11111111111
00000000000 00000000000
-----------
-----------
-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
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
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
:
GROOMING
:
URINATION
: 000000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 14 PND 4
-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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 33333333333 11111111111
00000000000 00000000000
-----------
-----------
-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
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
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
:
GROOMING
:
URINATION
:000000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 16 PND 4
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 11111111111 11111111111 33333333333 11111111111 00000000000
2 0000100110 00000000000
-----------
-----------
-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
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
111111111
GAIT
: 111111111
CONVULSIONS-CLONIC
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
: 000000000
GROOMING
:
URINATION
: 111000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 18 PND 11
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 11111111111 11111111111 33333333333 11111111111 00000000000
00000000001 00000000000
-----------
-----------
-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
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
111111111
GAIT
: 111111111
CONVULSIONS-CLONIC
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
: 000000000
GROOMING
:
URINATION
: 001132100
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 20 PND 11
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 11111111111 11111111111 33333333333 11111111111 00000000000
0 0 0 00 00 0 01 0 00000000000
-----------
-----------
-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
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
111111111
GAIT
: 111111111
CONVULSIONS-CLONIC
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
: 000000000
GROOMING
:
URINATION
: 101000010
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 22 PND 11
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 11111111111 11111111111 33333333333 11111111111 00000000000
2 31 0001 0002 00000000000
-----------
-----------
-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
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
111111111
GAIT
: 111111111
CONVULSIONS-CLONIC
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
: 000000000
GROOMING
:
URINATION
: 322 000000
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 24 PND 11
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 11111111111 11111111111 33333333333 11111111111 00000000000
2 000012 0000 00000000000
-----------
-----------
-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
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
111111111
GAIT
: 111111111
CONVULSIONS-CLONIC
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
: 000000000
GROOMING
:
URINATION
: 000100110
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 26 PND 11
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 11111111111 11111111111 33333333333 11111111111 00000000000
01 0 001 01 01 0 00000000000
-----------
-----------
-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
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
111111111
GAIT
: 111111111
CONVULSIONS-CLONIC
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
: 000000000
GROOMING
:
URINATION
: 010100301
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 28 PND 11
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 11111111111 11111111111 33333333333 11111111111 00000000000
122 1 0002 1 01 00000000000
-----------
-----------
-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
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
111111111
GAIT
: 111111111
CONVULSIONS-CLONIC
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
: 000000000
GROOMING
:
URINATION
: 1 02 01 0001
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 30 PND 11
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
11111111111 11111111111 11111111111 11111111111 11111111111 33333333333 11111111111 00000000000
3 0 0 01 01 0 01 0 00000000000
-----------
-----------
-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
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
111111111
GAIT
: 111111111
CONVULSIONS-CLONIC
111111111
CONVULSIONS-TONIC
111111111
TREMORS
: 111111111
AROUSAL
: 333333333
BIZARRE/STEREOTYPIC BEHAVIOR
111111111
BACKING
: 000000000
GROOMING
:
URINATION
: 011000001
DEFECATION
: 000000000
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) : _ _ _ _ _ _ _ _ _
PAGE 32 PND 11
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 3 0 0 2 1 3 120. 100. 90. 45. 120. 65. 110.0 70.0
1 1 1 1 1 3 1 0 10 0 0 2 1 3 125. 75. 85. 90. 105. 75. 105.0 80.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 115. 50. 120. 75. 135. 45. 123.3 56.7
1 1 1 1 1 3 1 0 1 0 0 2 1 3 95. 55. 95. 45. 55. 55. 81.7 51.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 150. 60. 105. 80. 125. 80. 126.7 73.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 55. 50. 95. 80. 120. 75. 90.0 68.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 145. 55. 100. 90. 120. 80. 121.7 75.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 125. 75. 120. 70. 115. 80. 120.0 75.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 225. 125. 180. 85. 180. 60. 195.0 90.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 140. 65. 190. 80. 120. 85. 150.0 76.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 155. 80. 160. 60. 95. 60. 136.7 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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 1 2 1 3 120. 90. 150. 60. 80. 40. 116.7 63.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 230. 170. 200. 135. 220. 95. 216.7 133.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 220. 85. 85. 75. 195. 85. 166.7 81.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 155. 80. 110. 95. 150. 65. 138.3 80.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 160. 100. 115. 90. 185. 105. 153.3 98.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 135. 85. 110. 90. 115. 75. 120.0 83.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 180. 70. 175. 105. 210. 80. 188.3 85.0
1 1 1 1 1 3 1 0 0 1 4 2 1 3 185. 90. 80. 85. 200. 100. 155.0 91.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 150. 110. 140. 65. 170. 110. 153.3 95.0
PAGE 34 PND 21
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 8 0 0 2 1 3 155. 50. 125. 95. 80. 75. 120.0 73.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 105. 65. 100. 45. 65. 90. 90.0 66.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 135. 75. 155. 75. 150. 105. 146.7 85.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 85. 100. 145. 65. 175. 75. 135.0 80.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 100. 80. 155. 95. 210. 115. 155.0 96.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 95. 175. 90. 160. 85. 151.7 90.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 130. 60. 145. 65. 140. 85. 138.3 70.0
1 1 1 1 1 3 1 0 0 0 2 2 1 3 135. 90. 150. 95. 125. 100. 136.7 95.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 115. 50. 140. 105. 120. 60. 125.0 71.7
1 1 1 1 1 3 1 0 1 0 0 2 1 3 95. 100. 100. 70. 200. 120. 131.7 96.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 145. 65. 160. 90. 140. 75. 148.3 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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 140. 80. 105. 75. 75. 45. 106.7 66.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 135. 65. 115. 75. 170. 45. 140.0 61.7
1 1 1 1 1 3 1 0 0 0 1 2 1 3 90. 115. 55. 65. 90. 75. 78.3 85.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 55. 155. 85. 175. 105. 150.0 81.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 160. 75. 115. 85. 165. 65. 146.7 75.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 215. 115. 120. 65. 135. 95. 156.7 91.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 160. 90. 145. 100. 155. 90. 153.3 93.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 140. 70. 220. 115. 180. 95. 180.0 93.3
1 1 1 1 1 3 1 0 1 0 0 2 1 3 215. 150. 160. 90. 100. 75. 158.3 105.0
PAGE 36 PND 21
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 5 1 0 2 1 3 180. 65. 140. 65. 85. 65. 135.0 65.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 140. 85. 185. 110. 140. 95. 155.0 96.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 100. 45. 85. 75. 90. 65. 91.7 61.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 75. 45. 75. 75. 120. 75. 90.0 65.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 170. 115. 165. 110. 130. 85. 155.0 103.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 115. 95. 100. 80. 120. 70. 111.7 81.7
1 1 1 1 1 3 1 0 0 0 2 2 1 3 105. 100. 75. 45. 120. 60. 100.0 68.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 245. 155. 120. 110. 190. 105. 185.0 123.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 120. 70. 75. 75. 125. 120. 106.7 88.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 145. 95. 125. 40. 115. 100. 128.3 78.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 110. 75. 135. 145. 150. 115. 131.7 111.7
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 210. 105. 100. 80. 170. 80. 160.0 88.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 145. 90. 165. 105. 100. 80. 136.7 91.7
1 1 1 1 1 3 1 0 1 0 0 2 1 3 125. 85. 190. 85. 190. 100. 168.3 90.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 170. 70. 170. 75. 170. 70. 170.0 71.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 165. 55. 145. 70. 115. 100. 141.7 75.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 160. 75. 85. 65. 150. 75. 131.7 71.7
1 1 1 1 1 3 1 0 0 0 4 2 1 3 110. 70. 70. 85. 165. 110. 115.0 88.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 140. 110. 120. 105. 90. 75. 116.7 96.7
1 1 1 1 1 3 1 0 0 0 1 2 1 3 120. 90. 105. 70. 120. 80. 115.0 80.0
PAGE 38 PND 21
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 170. 95. 120. 70. 100. 50. 130.0 71.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 165. 75. 105. 50. 130. 45. 133.3 56.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 130. 60. 120. 75. 220. 70. 156.7 68.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 75. 30. 150. 40. 170. 40. 131.7 36.7
1 1 1 1 1 3 1 0 0 0 1 2 1 3 90. 80. 135. 105. 175. 90. 133.3 91.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 135. 55. 155. 65. 85. 80. 125.0 66.7
1 1 1 1 1 3 1 0 0 1 1 2 1 3 110. 50. 120. 65. 160. 55. 130.0 56.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 115. 50. 80. 45. 120. 50. 105.0 48.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 75. 80. 170. 140. 125. 65. 123.3 95.0
1 1 1 1 1 3 1 0 0 0 2 2 1 3 130. 120. 200. 110. 120. 80. 150.0 103.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 50. 170. 75. 115. 70. 135.0 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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 115. 80. 180. 90. 120. 80. 138.3 83.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 65. 75. 75. 30. 100. 65. 80.0 56.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 90. 75. 105. 65. 190. 70. 128.3 70.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 70. 120. 65. 90. 60. 110.0 65.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 135. 65. 105. 75. 115. 55. 118.3 65.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 85. 45. 95. 45. 135. 80. 105.0 56.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 65. 55. 80. 40. 95. 70. 80.0 55.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 180. 75. 100. 85. 90. 75. 123.3 78.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 45. 50. 65. 40. 60. 40. 56.7 43.3
PAGE 40 PND 21
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 4 0 0 2 1 3 100. 55. 110. 80. 110. 45. 106.7 60.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 190. 95. 145. 80. 160. 60. 165.0 78.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 130. 85. 145. 65. 125. 40. 133.3 63.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 130. 45. 75. 45. 140. 50. 115.0 46.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 160. 80. 155. 60. 220. 90. 178.3 76.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 205. 155. 120. 75. 230. 125. 185.0 118.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 165. 70. 125. 65. 85. 60. 125.0 65.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 80. 50. 175. 70. 150. 75. 135.0 65.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 65. 190. 85. 180. 80. 163.3 76.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 85. 80. 85. 65. 115. 85. 95.0 76.7
1 1 1 1 1 3 1 0 1 0 0 2 1 3 145. 40. 150. 55. 170. 60. 155.0 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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 210. 95. 155. 75. 195. 115. 186.7 95.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 195. 70. 200. 75. 140. 95. 178.3 80.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 130. 70. 105. 50. 120. 95. 118.3 71.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 85. 65. 135. 95. 140. 75. 120.0 78.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 195. 95. 205. 75. 120. 100. 173.3 90.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 50. 45. 60. 70. 120. 55. 76.7 56.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 80. 120. 85. 120. 75. 120.0 80.0
1 1 1 1 1 3 1 0 0 1 2 2 1 3 170. 65. 170. 55. 170. 80. 170.0 66.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 145. 85. 165. 75. 155. 75. 155.0 78.3
PAGE 42 PND 21
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 6 0 0 2 1 3 75. 100. 120. 65. 125. 70. 106.7 78.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 75. 105. 70. 125. 70. 116.7 71.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 190. 75. 200. 80. 150. 70. 180.0 75.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 170. 75. 165. 50. 120. 75. 151.7 66.7
1 1 1 1 1 3 1 0 0 0 3 2 1 3 120. 75. 125. 105. 170. 85. 138.3 88.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 165. 60. 170. 80. 130. 105. 155.0 81.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 115. 125. 95. 75. 120. 75. 110.0 91.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 70. 45. 140. 50. 75. 60. 95.0 51.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 135. 50. 115. 55. 125. 70. 125.0 58.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 140. 120. 220. 80. 130. 65. 163.3 88.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 185. 75. 75. 85. 145. 75. 135.0 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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 145. 90. 170. 60. 155. 85. 156.7 78.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 125. 110. 165. 65. 130. 75. 140.0 83.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 95. 70. 55. 45. 100. 105. 83.3 73.3
1 1 1 1 1 3 1 0 0 0 1 2 1 3 185. 80. 110. 70. 165. 90. 153.3 80.0
1 1 1 1 1 3 1 0 0 2 1 2 1 3 110. 65. 145. 80. 130. 90. 128.3 78.3
1 1 1 1 1 3 1 0 0 1 1 2 1 3 145. 120. 135. 120. 170. 90. 150.0 110.0
1 1 1 1 1 3 1 0 0 0 3 2 1 3 120. 60. 175. 75. 190. 135. 161.7 90.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 180. 70. 115. 65. 120. 85. 138.3 73.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 240. 80. 220. 95. 205. 85. 221.7 86.7
PAGE 44 PND 21
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 2 0 0 2 1 3 145. 120. 170. 55. 170. 75. 161.7 83.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 80. 80. 110. 70. 90. 60. 93.3 70.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 60. 55. 110. 55. 170. 60. 113.3 56.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 60. 85. 210. 115. 95. 40. 121.7 80.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 115. 70. 110. 90. 115. 55. 113.3 71.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 160. 85. 80. 60. 170. 75. 136.7 73.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 170. 80. 140. 60. 160. 60. 156.7 66.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 100. 55. 100. 75. 130. 65. 110.0 65.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 230. 80. 105. 95. 130. 60. 155.0 78.3
1 1 1 1 1 3 1 0 0 1 1 2 1 3 200. 155. 145. 110. 220. 125. 188.3 130.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 90. 60. 125. 45. 70. 75. 95.0 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
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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 1 2 1 3 140. 95. 90. 90. 130. 110. 120.0 98.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 130. 80. 215. 85. 180. 90. 175.0 85.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 150. 95. 75. 80. 120. 95. 115.0 90.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 100. 60. 120. 75. 75. 45. 98.3 60.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 60. 30. 105. 95. 145. 50. 103.3 58.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 145. 120. 160. 95. 105. 95. 136.7 103.3
1 1 1 1 1 3 1 0 1 0 0 2 1 3 175. 65. 165. 80. 140. 80. 160.0 75.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 85. 70. 175. 75. 175. 70. 145.0 71.7
1 1 1 1 1 3 1 0 0 0 2 2 1 3 155. 50. 130. 65. 170. 105. 151.7 73.3
PAGE 46 PND 21
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 130. 50. 165. 75. 60. 65. 118.3 63.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 130. 95. 160. 75. 110. 90. 133.3 86.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 80. 65. 165. 65. 80. 100. 108.3 76.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 75. 30. 120. 75. 125. 45. 106.7 50.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 150. 75. 215. 105. 135. 105. 166.7 95.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 150. 100. 140. 60. 120. 70. 136.7 76.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 75. 90. 55. 120. 70. 110.0 66.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 60. 170. 75. 125. 80. 138.3 71.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 155. 55. 100. 120. 170. 95. 141.7 90.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 75. 125. 55. 135. 80. 126.7 70.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 75. 105. 85. 70. 170. 50. 110.0 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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 205. 75. 190. 100. 170. 75. 188.3 83.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 50. 75. 100. 80. 100. 45. 83.3 66.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 160. 85. 100. 75. 205. 95. 155.0 85.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 120. 60. 125. 80. 145. 65. 130.0 68.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 135. 65. 155. 65. 170. 60. 153.3 63.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 135. 80. 155. 75. 110. 75. 133.3 76.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 75. 75. 100. 45. 115. 55. 96.7 58.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 170. 75. 145. 75. 160. 120. 158.3 90.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 55. 40. 150. 95. 65. 40. 90.0 58.3
PAGE 48 PND 21
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 220. 305. 310. 205. 425. 255. 318.3 255.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 435. 315. 450. 215. 365. 395. 416.7 308.3
1 1 1 1 1 3 1 0 0 1 1 2 1 3 435. 410. 240. 295. 215. 380. 296.7 361.7
1 1 1 1 1 3 1 0 0 1 3 2 1 3 295. 265. 365. 265. 295. 260. 318.3 263.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 295. 245. 435. 480. 380. 325. 370.0 350.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 355. 420. 340. 230. 500. 265. 398.3 305.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 605. 390. 590. 325. 455. 305. 550.0 340.0
1 1 1 1 1 3 1 0 0 0 0 3 1 3 420. 440. 435. 235. 520. 255. 458.3 310.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 430. 365. 520. 265. 525. 345. 491.7 325.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 380. 365. 370. 245. 510. 380. 420.0 330.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 500. 225. 385. 240. 575. 245. 486.7 236.7
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 455. 340. 455. 340. 320. 440. 410.0 373.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 495. 480. 565. 310. 535. 475. 531.7 421.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 535. 570. 545. 565. 460. 310. 513.3 481.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 650. 315. 775. 480. 795. 300. 740.0 365.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 510. 270. 665. 430. 485. 280. 553.3 326.7
1 1 1 1 1 3 1 0 0 1 2 2 1 3 385. 395. 560. 355. 585. 325. 510.0 358.3
1 1 1 1 1 3 1 0 0 0 0 3 1 3 570. 220. 500. 225. 270. 185. 446.7 210.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 190. 190. 365. 175. 250. 245. 268.3 203.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 270. 140. 410. 235. 480. 255. 386.7 210.0
PAGE 50 PND 35
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 4 1 0 0 1 0 2 1 3 290. 455. 320. 410. 475. 305. 361.7 390.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 355. 475. 440. 495. 325. 350. 373.3 440.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 425. 210. 400. 470. 595. 300. 473.3 326.7
1 1 1 1 1 3 1 0 0 2 0 2 1 3 480. 280. 480. 290. 495. 510. 485.0 360.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 355. 250. 445. 525. 380. 400. 393.3 391.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 500. 240. 330. 200. 335. 270. 388.3 236.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 450. 280. 520. 315. 475. 465. 481.7 353.3
1 1 1 1 1 3 1 0 0 0 0 3 1 3 395. 310. 365. 615. 430. 305. 396.7 410.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 505. 245. 370. 315. 325. 410. 400.0 323.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 445. 450. 340. 545. 500. 575. 428.3 523.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 350. 465. 500. 330. 600. 295. 483.3 363.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 355. 525. 465. 430. 465. 320. 428.3 425.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 650. 455. 460. 600. 360. 270. 490.0 441.7
1 1 1 1 1 3 1 0 0 1 2 2 1 3 285. 195. 280. 170. 380. 270. 315.0 211.7
1 1 1 1 1 3 1 0 0 2 0 2 1 3 440. 515. 395. 345. 435. 335. 423.3 398.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 555. 620. 590. 505. 575. 545. 573.3 556.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 610. 300. 585. 180. 530. 225. 575.0 235.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 445. 305. 375. 205. 435. 220. 418.3 243.3
1 1 1 1 1 3 1 0 0 0 0 3 1 3 610. 250. 560. 365. 510. 210. 560.0 275.0
1 1 1 1 1 3 1 0 1 0 0 2 1 3 560. 185. 535. 270. 510. 110. 535.0 188.3
PAGE 52 PND 35
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 3 0 2 1 3 305. 410. 395. 280. 410. 350. 370.0 346.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 425. 345. 460. 520. 555. 590. 480.0 485.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 480. 460. 330. 515. 290. 435. 366.7 470.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 400. 255. 470. 500. 540. 320. 470.0 358.3
1 1 1 1 1 3 1 0 0 0 0 3 1 3 490. 395. 390. 475. 450. 350. 443.3 406.7
1 1 1 1 1 3 1 0 0 1 1 2 1 3 335. 450. 440. 330. 410. 425. 395.0 401.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 310. 205. 420. 360. 405. 520. 378.3 361.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 310. 250. 510. 550. 405. 365. 408.3 388.3
1 1 1 1 1 3 1 0 0 2 0 2 1 3 405. 370. 455. 235. 550. 410. 470.0 338.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 380. 135. 405. 220. 400. 350. 395.0 235.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 495. 300. 430. 330. 470. 460. 465.0 363.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 650. 250. 560. 320. 500. 385. 570.0 318.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 495. 380. 615. 475. 515. 455. 541.7 436.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 540. 455. 615. 530. 470. 350. 541.7 445.0
1 1 1 1 1 3 1 0 0 2 5 2 1 3 605. 375. 520. 390. 595. 330. 573.3 365.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 415. 355. 440. 300. 525. 600. 460.0 418.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 390. 215. 325. 330. 495. 335. 403.3 293.3
1 1 1 1 1 3 1 0 0 1 1 2 1 3 520. 230. 575. 255. 430. 215. 508.3 233.3
1 1 1 1 1 3 1 0 0 0 0 3 1 3 485. 330. 490. 285. 530. 305. 501.7 306.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 155. 410. 220. 445. 230. 455.0 201.7
PAGE 54 PND 35
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 565. 270. 395. 325. 355. 400. 438.3 331.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 410. 270. 285. 370. 490. 690. 395.0 443.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 455. 380. 325. 420. 435. 370. 405.0 390.0
1 1 1 1 1 3 1 0 3 1 0 3 1 3 265. 270. 495. 325. 350. 415. 370.0 336.7
1 1 1 1 1 3 1 0 0 0 1 2 1 3 495. 545. 375. 345. 465. 385. 445.0 425.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 405. 365. 435. 475. 405. 300. 415.0 380.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 505. 360. 505. 410. 385. 390. 465.0 386.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 605. 335. 555. 550. 515. 285. 558.3 390.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 285. 300. 545. 420. 505. 480. 445.0 400.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 575. 330. 410. 555. 305. 335. 430.0 406.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 325. 190. 370. 210. 410. 270. 368.3 223.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 500. 340. 550. 385. 495. 365. 515.0 363.3
1 1 1 1 1 3 1 0 0 1 3 2 1 3 390. 345. 460. 385. 290. 470. 380.0 400.0
1 1 1 1 1 3 1 0 0 0 2 2 1 3 260. 260. 235. 255. 375. 280. 290.0 265.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 275. 245. 485. 255. 355. 315. 371.7 271.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 330. 575. 495. 280. 300. 515. 375.0 456.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 310. 245. 360. 215. 320. 270. 330.0 243.3
1 1 1 1 1 3 1 0 0 1 1 2 1 3 335. 305. 320. 210. 265. 260. 306.7 258.3
1 1 1 1 1 3 1 0 0 0 2 2 1 3 560. 190. 525. 235. 520. 245. 535.0 223.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 280. 165. 325. 180. 215. 90. 273.3 145.0
PAGE 56 PND 35
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 430. 280. 475. 275. 500. 305. 468.3 286.7
1 1 1 1 1 3 1 0 1 0 0 2 1 3 375. 240. 380. 265. 360. 335. 371.7 280.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 425. 460. 245. 390. 355. 460. 341.7 436.7
1 1 1 1 1 3 1 0 0 1 2 2 1 3 265. 360. 275. 265. 295. 295. 278.3 306.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 385. 525. 555. 375. 450. 245. 463.3 381.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 475. 305. 475. 520. 600. 375. 516.7 400.0
1 1 1 1 1 3 1 0 0 2 1 2 1 3 515. 250. 500. 450. 320. 235. 445.0 311.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 505. 450. 355. 150. 465. 370. 441.7 323.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 555. 555. 535. 280. 525. 295. 538.3 376.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 355. 190. 405. 200. 400. 230. 386.7 206.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 340. 180. 385. 295. 435. 255. 386.7 243.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 4 1 0 0 0 0 2 1 3 455. 265. 505. 385. 525. 420. 495.0 356.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 395. 275. 585. 265. 500. 275. 493.3 271.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 405. 485. 445. 380. 420. 300. 423.3 388.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 290. 255. 440. 330. 405. 330. 378.3 305.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 455. 380. 510. 305. 615. 335. 526.7 340.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 385. 505. 595. 360. 595. 335. 525.0 400.0
1 1 1 1 1 3 1 0 1 0 0 2 1 3 535. 270. 485. 300. 485. 285. 501.7 285.0
1 1 1 1 1 3 1 0 0 0 3 2 1 3 465. 165. 380. 110. 370. 185. 405.0 153.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 345. 65. 255. 125. 280. 130. 293.3 106.7
PAGE 58 PND 35
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 415. 245. 355. 260. 270. 215. 346.7 240.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 385. 500. 260. 340. 425. 470. 356.7 436.7
1 1 1 1 1 3 1 0 0 1 0 3 1 3 420. 370. 485. 375. 355. 425. 420.0 390.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 405. 355. 460. 425. 455. 365. 440.0 381.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 460. 245. 360. 260. 340. 520. 386.7 341.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 550. 365. 405. 345. 320. 440. 425.0 383.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 430. 300. 575. 210. 360. 465. 455.0 325.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 250. 285. 335. 230. 250. 285. 278.3 266.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 460. 420. 565. 255. 440. 245. 488.3 306.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 370. 560. 430. 410. 435. 410. 411.7 460.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 375. 480. 485. 445. 555. 478.3 471.7
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 590. 455. 555. 385. 480. 600. 541.7 480.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 580. 405. 600. 675. 550. 525. 576.7 535.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 270. 200. 280. 435. 355. 235. 301.7 290.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 490. 365. 490. 370. 455. 510. 478.3 415.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 480. 285. 520. 450. 565. 420. 521.7 385.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 540. 305. 510. 195. 215. 110. 421.7 203.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 460. 175. 315. 215. 385. 200. 386.7 196.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 500. 260. 525. 315. 275. 220. 433.3 265.0
1 1 1 1 1 3 1 0 0 2 0 2 1 3 510. 255. 550. 230. 345. 250. 468.3 245.0
PAGE 60 PND 35
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 335. 195. 405. 370. 355. 300. 365.0 288.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 465. 290. 390. 435. 295. 235. 383.3 320.0
1 1 1 1 1 3 1 0 0 0 0 3 1 3 365. 265. 440. 540. 425. 275. 410.0 360.0
1 1 1 1 1 4 1 0 0 0 0 2 1 3 550. 380. 565. 310. 570. 340. 561.7 343.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 355. 230. 500. 245. 355. 245. 403.3 240.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 460. 330. 340. 300. 360. 215. 386.7 281.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 445. 300. 445. 300. 430. 270. 440.0 290.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 460. 330. 400. 245. 425. 285. 428.3 286.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 450. 350. 410. 360. 500. 420. 453.3 376.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 490. 275. 465. 490. 485. 320. 480.0 361.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 420. 535. 485. 400. 455. 475. 453.3 470.0
-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
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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 500. 675. 405. 480. 515. 245. 473.3 466.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 355. 350. 450. 340. 380. 310. 395.0 333.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 295. 235. 305. 265. 205. 165. 268.3 221.7
1 1 1 1 1 4 1 0 0 0 0 2 1 3 390. 380. 360. 220. 410. 515. 386.7 371.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 505. 315. 540. 405. 570. 400. 538.3 373.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 545. 225. 205. 120. 425. 220. 391.7 188.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 445. 270. 535. 270. 515. 185. 498.3 241.7
1 1 1 1 1 3 1 0 0 0 0 3 1 3 450. 205. 480. 350. 460. 240. 463.3 265.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 405. 315. 260. 365. 275. 485. 313.3 388.3
PAGE 62 PND 35
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 3 1 3 495. 265. 295. 330. 290. 510. 360.0 368.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 425. 350. 410. 260. 295. 540. 376.7 383.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 425. 210. 325. 290. 405. 500. 385.0 333.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 375. 230. 265. 450. 390. 325. 343.3 335.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 220. 280. 430. 360. 365. 375. 338.3 338.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 485. 395. 400. 350. 475. 520. 453.3 421.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 220. 485. 210. 215. 380. 265. 270.0 321.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 425. 250. 460. 245. 445. 265. 443.3 253.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 500. 360. 350. 370. 545. 290. 465.0 340.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 465. 405. 575. 400. 430. 300. 490.0 368.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 335. 560. 415. 325. 465. 330. 405.0 405.0
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 355. 220. 485. 550. 455. 360. 431.7 376.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 520. 215. 455. 410. 445. 505. 473.3 376.7
1 1 1 1 1 3 1 0 0 2 0 2 1 3 480. 370. 435. 595. 455. 485. 456.7 483.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 485. 215. 290. 220. 325. 200. 366.7 211.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 380. 245. 450. 570. 360. 440. 396.7 418.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 320. 245. 310. 325. 275. 440. 301.7 336.7
1 1 1 1 1 4 1 0 0 0 0 2 1 3 500. 275. 440. 455. 425. 245. 455.0 325.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 540. 165. 295. 255. 370. 195. 401.7 205.0
1 1 1 1 1 3 1 0 2 0 0 2 1 3 265. 165. 460. 215. 470. 150. 398.3 176.7
PAGE 64 PND 35
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 2 0 0 3 1 3 680. 285. 390. 270. 535. 270. 535.0 275.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 655. 245. 590. 370. 585. 355. 610.0 323.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 610. 525. 640. 405. 560. 475. 603.3 468.3
1 1 1 1 1 3 1 0 0 1 3 2 1 3 560. 710. 715. 385. 770. 530. 681.7 541.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 825. 450. 895. 575. 790. 575. 836.7 533.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 820. 890. 1015. 690. 890. 805. 908.3 795.0
1 1 1 1 1 3 1 0 0 3 0 2 1 3 965. 640. 725. 620. 875. 515. 855.0 591.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 895. 420. 860. 495. 620. 625. 791.7 513.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 915. 810. 885. 560. 720. 695. 840.0 688.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 255. 440. 250. 230. 515. 305. 340.0 325.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 695. 170. 630. 360. 435. 440. 586.7 323.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 2 2 1 3 530. 335. 245. 455. 285. 280. 353.3 356.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 495. 585. 930. 665. 900. 735. 775.0 661.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 770. 245. 755. 395. 480. 270. 668.3 303.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 435. 355. 785. 390. 630. 370. 616.7 371.7
1 1 1 1 1 3 1 0 0 0 1 2 1 3 665. 620. 870. 460. 680. 425. 738.3 501.7
1 1 1 1 1 3 1 0 0 0 3 2 1 3 865. 365. 520. 270. 790. 305. 725.0 313.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 395. 280. 275. 255. 405. 330. 358.3 288.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 410. 315. 245. 260. 375. 355. 343.3 310.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 560. 200. 255. 140. 270. 255. 361.7 198.3
PAGE 66 PND 45
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 735. 230. 560. 250. 625. 305. 640.0 261.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 845. 645. 600. 510. 520. 505. 655.0 553.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 980. 630. 660. 705. 725. 645. 788.3 660.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 1040. 510. 1085. 425. 1150. 645. 1091.7 526.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 905. 580. 695. 620. 565. 605. 721.7 601.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 845. 700. 1000. 680. 820. 560. 888.3 646.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 820. 490. 760. 735. 740. 690. 773.3 638.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 790. 655. 935. 510. 830. 610. 851.7 591.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 870. 710. 700. 465. 880. 670. 816.7 615.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 505. 300. 415. 325. 605. 305. 508.3 310.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 870. 685. 780. 575. 875. 800. 841.7 686.7
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 770. 510. 440. 310. 495. 390. 568.3 403.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 740. 445. 510. 160. 565. 230. 605.0 278.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 520. 335. 465. 380. 510. 265. 498.3 326.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 1025. 370. 415. 410. 855. 220. 765.0 333.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 470. 365. 270. 345. 495. 255. 411.7 321.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 525. 250. 360. 270. 440. 235. 441.7 251.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 395. 250. 220. 270. 460. 310. 358.3 276.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 395. 195. 500. 300. 320. 355. 405.0 283.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 525. 260. 335. 235. 515. 315. 458.3 270.0
PAGE 68 PND 45
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 545. 350. 620. 235. 705. 435. 623.3 340.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 850. 605. 885. 505. 695. 585. 810.0 565.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 690. 420. 705. 385. 520. 320. 638.3 375.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 790. 500. 735. 650. 655. 400. 726.7 516.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 780. 465. 775. 400. 810. 470. 788.3 445.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 780. 560. 860. 595. 805. 660. 815.0 605.0
1 1 1 1 1 2 1 0 0 0 0 2 1 3 595. 700. 595. 850. 510. 590. 566.7 713.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 895. 560. 495. 635. 805. 700. 731.7 631.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 875. 545. 895. 660. 805. 700. 858.3 635.0
1 1 1 1 1 2 1 0 0 0 0 2 1 3 840. 655. 610. 615. 775. 615. 741.7 628.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 530. 245. 390. 390. 735. 195. 551.7 276.7
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 665. 390. 705. 275. 490. 355. 620.0 340.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 805. 285. 740. 320. 355. 235. 633.3 280.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 505. 400. 315. 140. 415. 345. 411.7 295.0
1 1 1 1 1 3 1 0 0 0 1 2 1 3 720. 465. 880. 600. 480. 440. 693.3 501.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 535. 330. 285. 465. 705. 255. 508.3 350.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 610. 305. 560. 305. 455. 210. 541.7 273.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 355. 140. 365. 290. 315. 165. 345.0 198.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 300. 270. 315. 225. 230. 225. 281.7 240.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 555. 345. 445. 265. 410. 275. 470.0 295.0
PAGE 70 PND 45
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 2 0 2 1 3 875. 465. 740. 500. 890. 410. 835.0 458.3
1 1 1 1 1 3 1 0 0 3 8 2 1 3 710. 380. 635. 520. 605. 630. 650.0 510.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 880. 640. 925. 675. 975. 645. 926.7 653.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 795. 365. 540. 550. 595. 575. 643.3 496.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 780. 455. 930. 515. 910. 480. 873.3 483.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 745. 670. 840. 510. 775. 510. 786.7 563.3
1 1 1 1 1 3 1 0 0 2 0 2 1 3 875. 475. 660. 495. 815. 500. 783.3 490.0
1 1 1 1 1 3 1 0 0 2 0 2 1 3 845. 445. 895. 635. 930. 810. 890.0 630.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 815. 550. 1030. 520. 870. 610. 905.0 560.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 680. 635. 845. 485. 855. 620. 793.3 580.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 945. 410. 790. 765. 730. 490. 821.7 555.0
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 665. 300. 595. 250. 635. 415. 631.7 321.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 650. 435. 320. 250. 605. 320. 525.0 335.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 675. 490. 610. 365. 305. 315. 530.0 390.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 415. 345. 575. 385. 525. 260. 505.0 330.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 800. 355. 750. 500. 575. 165. 708.3 340.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 460. 355. 605. 350. 485. 490. 516.7 398.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 810. 270. 415. 295. 630. 315. 618.3 293.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 395. 190. 300. 170. 380. 335. 358.3 231.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 295. 210. 290. 265. 265. 270. 283.3 248.3
PAGE 72 PND 45
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 480. 145. 400. 295. 475. 220. 451.7 220.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 695. 285. 685. 525. 530. 205. 636.7 338.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 555. 680. 485. 510. 495. 660. 511.7 616.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 725. 540. 645. 440. 705. 510. 691.7 496.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 765. 550. 930. 645. 880. 580. 858.3 591.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 700. 560. 545. 585. 680. 555. 641.7 566.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 670. 600. 800. 645. 905. 620. 791.7 621.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 775. 420. 625. 835. 900. 445. 766.7 566.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 775. 485. 750. 695. 770. 635. 765.0 605.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 745. 255. 400. 180. 790. 315. 645.0 250.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 750. 210. 495. 230. 645. 220. 630.0 220.0
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 4 1 0 0 0 0 2 1 3 385. 155. 535. 470. 330. 215. 416.7 280.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 810. 310. 680. 280. 795. 340. 761.7 310.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 825. 430. 610. 535. 605. 480. 680.0 481.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 950. 750. 840. 125. 735. 415. 841.7 430.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 675. 570. 500. 620. 885. 430. 686.7 540.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 650. 705. 405. 390. 250. 315. 435.0 470.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 400. 315. 195. 220. 215. 225. 270.0 253.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 320. 340. 205. 125. 320. 215. 281.7 226.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 385. 290. 245. 240. 275. 210. 301.7 246.7
PAGE 74 PND 45
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 660. 165. 420. 190. 580. 270. 553.3 208.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 645. 525. 635. 620. 535. 530. 605.0 558.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 750. 645. 805. 390. 770. 385. 775.0 473.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 825. 690. 860. 705. 750. 610. 811.7 668.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 765. 605. 700. 650. 785. 630. 750.0 628.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 885. 675. 745. 315. 470. 500. 700.0 496.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 775. 500. 670. 505. 540. 490. 661.7 498.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 910. 605. 825. 665. 785. 610. 840.0 626.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 665. 415. 810. 750. 720. 640. 731.7 601.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 840. 300. 705. 425. 670. 500. 738.3 408.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 650. 330. 660. 415. 650. 365. 653.3 370.0
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 915. 500. 790. 390. 675. 530. 793.3 473.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 410. 365. 540. 430. 335. 270. 428.3 355.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 585. 300. 465. 345. 515. 370. 521.7 338.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 345. 420. 210. 155. 510. 320. 355.0 298.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 810. 445. 585. 465. 410. 490. 601.7 466.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 295. 140. 420. 220. 215. 240. 310.0 200.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 365. 270. 250. 265. 350. 305. 321.7 280.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 395. 355. 260. 270. 380. 405. 345.0 343.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 475. 230. 500. 205. 375. 305. 450.0 246.7
PAGE 76 PND 45
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 570. 400. 645. 330. 535. 365. 583.3 365.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 550. 395. 455. 465. 815. 520. 606.7 460.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 855. 550. 815. 580. 825. 685. 831.7 605.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 880. 690. 770. 580. 990. 650. 880.0 640.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 830. 420. 575. 455. 780. 525. 728.3 466.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 525. 510. 680. 360. 520. 490. 575.0 453.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 610. 585. 690. 665. 615. 505. 638.3 585.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 765. 390. 720. 520. 795. 635. 760.0 515.0
1 1 1 1 1 4 1 0 0 0 0 2 1 3 870. 690. 945. 470. 845. 545. 886.7 568.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 740. 505. 860. 555. 780. 670. 793.3 576.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 660. 480. 490. 365. 740. 410. 630.0 418.3
-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
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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 655. 345. 465. 340. 530. 255. 550.0 313.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 805. 520. 670. 460. 610. 295. 695.0 425.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 640. 310. 670. 355. 415. 385. 575.0 350.0
1 1 1 1 1 4 1 0 0 0 0 5 1 3 780. 305. 740. 270. 705. 465. 741.7 346.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 820. 425. 885. 505. 880. 430. 861.7 453.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 320. 235. 490. 250. 495. 195. 435.0 226.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 350. 275. 405. 220. 490. 240. 415.0 245.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 370. 165. 370. 295. 395. 275. 378.3 245.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 695. 350. 705. 330. 690. 290. 696.7 323.3
PAGE 78 PND 45
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 645. 620. 730. 560. 685. 490. 686.7 556.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 710. 380. 685. 620. 800. 465. 731.7 488.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 435. 540. 805. 525. 765. 520. 668.3 528.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 555. 380. 630. 365. 505. 525. 563.3 423.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 675. 690. 645. 580. 825. 580. 715.0 616.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 760. 515. 655. 590. 655. 565. 690.0 556.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 460. 470. 645. 580. 560. 560. 555.0 536.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 680. 485. 755. 415. 525. 610. 653.3 503.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 700. 520. 960. 430. 735. 515. 798.3 488.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 910. 575. 550. 670. 725. 585. 728.3 610.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 575. 460. 845. 500. 725. 640. 715.0 533.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 280. 585. 460. 360. 675. 435. 471.7 460.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 415. 265. 460. 165. 415. 405. 430.0 278.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 280. 430. 465. 320. 560. 385. 435.0 378.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 345. 245. 305. 225. 530. 285. 393.3 251.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 465. 450. 505. 365. 475. 310. 481.7 375.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 380. 250. 645. 220. 460. 325. 495.0 265.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 805. 285. 745. 515. 615. 275. 721.7 358.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 395. 270. 380. 150. 315. 105. 363.3 175.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 385. 200. 170. 115. 330. 165. 295.0 160.0
PAGE 80 PND 45
- toot-
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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 455. 455. 415. 460. 590. 515. 486.7 476.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 660. 680. 1060. 640. 1015. 445. 911.7 588.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 230. 235. 290. 320. 495. 240. 338.3 265.0
1 1 1 1 1 3 1 0 0 0 3 2 1 3 660. 430. 590. 360. 495. 445. 581.7 411.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 825. 370. 670. 500. 445. 485. 646.7 451.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 365. 205. 305. 220. 355. 420. 341.7 281.7
1 1 1 1 1 3 1 0 0 1 3 2 1 3 575. 305. 560. 550. 325. 265. 486.7 373.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 550. 365. 455. 395. 625. 440. 543.3 400.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 425. 160. 630. 220. 670. 210. 575.0 196.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 330. 270. 550. 385. 300. 195. 393.3 283.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 520. 270. 270. 155. 565. 365. 451.7 263.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 465. 240. 250. 190. 405. 175. 373.3 201.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 545. 555. 560. 415. 205. 220. 436.7 396.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 435. 245. 300. 200. 475. 325. 403.3 256.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 355. 325. 550. 215. 255. 305. 386.7 281.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 480. 185. 350. 545. 570. 610. 466.7 446.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 430. 365. 420. 270. 375. 355. 408.3 330.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 490. 280. 360. 365. 580. 240. 476.7 295.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 235. 295. 545. 270. 410. 205. 396.7 256.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 335. 260. 370. 305. 330. 225. 345.0 263.3
PAGE 82 PND 60
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 1 2 1 3 705. 705. 575. 565. 780. 290. 686.7 520.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 495. 220. 355. 275. 560. 230. 470.0 241.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 515. 330. 360. 410. 665. 495. 513.3 411.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 410. 400. 520. 240. 400. 205. 443.3 281.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 440. 390. 335. 240. 395. 295. 390.0 308.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 415. 425. 270. 625. 320. 520.0 335.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 610. 215. 530. 200. 585. 430. 575.0 281.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 415. 275. 595. 295. 355. 290. 455.0 286.7
1 1 1 1 1 3 1 0 0 1 1 2 1 3 565. 225. 325. 335. 505. 300. 465.0 286.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 490. 335. 570. 265. 405. 250. 488.3 283.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 995. 475. 370. 315. 475. 325. 613.3 371.7
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 1 1 0 2 1 3 440. 200. 285. 270. 470. 230. 398.3 233.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 560. 200. 455. 335. 340. 245. 451.7 260.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 380. 195. 630. 390. 390. 280. 466.7 288.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 490. 235. 455. 160. 415. 270. 453.3 221.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 610. 370. 515. 280. 650. 410. 591.7 353.3
1 1 1 1 1 3 1 0 0 1 1 2 1 3 385. 255. 575. 505. 430. 260. 463.3 340.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 560. 265. 250. 390. 595. 330. 468.3 328.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 470. 365. 275. 220. 230. 255. 325.0 280.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 275. 435. 270. 410. 330. 451.7 291.7
PAGE 84 PND 60
-SOOT-
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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 2 0 2 1 3 810. 510. 1040. 560. 905. 430. 918.3 500.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 500. 325. 505. 250. 435. 280. 480.0 285.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 525. 180. 525. 400. 315. 255. 455.0 278.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 560. 325. 305. 220. 470. 230. 445.0 258.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 540. 580. 540. 445. 315. 345. 465.0 456.7
1 1 1 1 1 3 1 0 1 1 1 2 1 3 335. 445. 355. 350. 470. 400. 386.7 398.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 610. 355. 445. 465. 220. 225. 425.0 348.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 375. 330. 630. 495. 545. 215. 516.7 346.7
1 1 1 1 1 3 1 0 1 1 0 2 1 3 530. 435. 460. 340. 505. 365. 498.3 380.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 625. 425. 510. 320. 230. 335. 455.0 360.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 610. 200. 510. 170. 280. 240. 466.7 203.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 230. 225. 455. 520. 400. 280. 361.7 341.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 395. 220. 400. 170. 415. 330. 403.3 240.0
1 1 1 1 1 3 1 0 0 2 3 2 1 3 250. 175. 635. 425. 270. 250. 385.0 283.3
1 1 1 1 1 3 1 0 0 1 3 2 1 3 440. 460. 375. 290. 330. 225. 381.7 325.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 325. 205. 475. 270. 295. 230. 365.0 235.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 430. 295. 400. 295. 405. 365. 411.7 318.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 475. 290. 265. 160. 465. 290. 401.7 246.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 405. 315. 325. 390. 475. 370. 401.7 358.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 530. 300. 510. 260. 510. 200. 516.7 253.3
PAGE 86 PND 60
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 430. 270. 480. 540. 510. 315. 473.3 375.0
1 1 1 1 1 3 1 0 0 1 1 2 1 3 495. 320. 305. 340. 395. 365. 398.3 341.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 505. 390. 320. 300. 660. 555. 495.0 415.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 310. 260. 285. 205. 315. 250. 303.3 238.3
1 1 1 1 1 3 1 0 0 1 1 2 1 3 340. 250. 330. 365. 245. 260. 305.0 291.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 705. 400. 420. 420. 565. 410. 563.3 410.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 545. 440. 725. 240. 640. 390. 636.7 356.7
1 1 1 1 1 3 1 0 0 1 0 2 1 3 290. 330. 385. 265. 325. 365. 333.3 320.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 755. 450. 690. 525. 765. 420. 736.7 465.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 385. 395. 375. 270. 330. 395. 363.3 353.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 275. 160. 620. 250. 260. 200. 385.0 203.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 1 0 2 1 3 315. 280. 420. 365. 620. 460. 451.7 368.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 375. 250. 320. 240. 565. 225. 420.0 238.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 655. 325. 445. 315. 535. 365. 545.0 335.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 660. 270. 295. 200. 560. 305. 505.0 258.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 285. 230. 360. 210. 235. 190. 293.3 210.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 335. 220. 355. 260. 330. 230. 340.0 236.7
1 1 1 1 1 3 1 0 0 1 1 2 1 3 590. 315. 525. 265. 510. 340. 541.7 306.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 595. 315. 245. 330. 855. 585. 565.0 410.0
1 1 1 1 1 3 1 0 0 1 0 2 1 3 415. 175. 285. 165. 255. 180. 318.3 173.3
PAGE 88 PND 60
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 660. 270. 575. 355. 540. 515. 591.7 380.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 390. 350. 515. 450. 420. 515. 441.7 438.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 325. 325. 500. 445. 600. 250. 475.0 340.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 315. 395. 345. 405. 445. 245. 368.3 348.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 335. 435. 765. 415. 370. 390. 490.0 413.3
1 1 1 1 1 3 1 0 1 0 0 2 1 3 590. 305. 590. 315. 275. 245. 485.0 288.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 365. 445. 285. 165. 580. 470. 410.0 360.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 390. 160. 460. 290. 240. 230. 363.3 226.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 315. 370. 225. 560. 310. 480.0 283.3
1 1 1 1 1 3 1 0 0 0 0 3 1 3 390. 350. 370. 245. 270. 180. 343.3 258.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 205. 255. 510. 200. 415. 230. 376.7 228.3
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 355. 155. 420. 190. 335. 220. 370.0 188.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 280. 470. 380. 285. 225. 421.7 295.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 285. 255. 365. 235. 720. 515. 456.7 335.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 445. 270. 505. 205. 295. 170. 415.0 215.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 315. 345. 625. 335. 215. 295. 385.0 325.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 435. 235. 380. 295. 185. 175. 333.3 235.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 365. 355. 375. 205. 390. 300. 376.7 286.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 505. 340. 205. 240. 455. 320. 388.3 300.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 275. 230. 210. 120. 135. 170. 206.7 173.3
PAGE 90 PND 60
-h o i-
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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 335. 490. 680. 570. 575. 575. 530.0 545.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 270. 255. 535. 235. 305. 305. 370.0 265.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 345. 285. 315. 320. 610. 340. 423.3 315.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 405. 350. 430. 395. 405. 365. 413.3 370.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 380. 280. 210. 200. 285. 160. 291.7 213.3
1 1 1 1 1 3 1 0 0 1 0 2 1 3 455. 205. 395. 350. 560. 225. 470.0 260.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 290. 390. 490. 400. 365. 370. 381.7 386.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 390. 195. 510. 355. 375. 355. 425.0 301.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 285. 160. 430. 290. 510. 255. 408.3 235.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 590. 410. 365. 300. 470. 415. 475.0 375.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 170. 170. 450. 200. 550. 185. 390.0 185.0
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 400. 190. 600. 390. 365. 225. 455.0 268.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 405. 235. 395. 240. 300. 315. 366.7 263.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 475. 220. 425. 230. 415. 240. 438.3 230.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 515. 205. 430. 175. 370. 365. 438.3 248.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 390. 315. 455. 300. 735. 675. 526.7 430.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 505. 250. 465. 205. 410. 340. 460.0 265.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 255. 225. 260. 225. 360. 240. 291.7 230.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 455. 445. 380. 465. 395. 275. 410.0 395.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 245. 170. 220. 160. 250. 165. 238.3 165.0
PAGE 92 PND 60
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 1060. 680. 920. 650. 840. 495. 940.0 608.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 370. 410. 400. 290. 345. 165. 371.7 288.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 540. 275. 450. 310. 205. 230. 398.3 271.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 640. 325. 250. 390. 560. 465. 483.3 393.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 490. 335. 285. 255. 660. 315. 478.3 301.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 320. 385. 630. 385. 490. 340. 480.0 370.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 415. 280. 260. 230. 505. 275. 393.3 261.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 505. 435. 480. 175. 645. 220. 543.3 276.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 565. 375. 365. 355. 405. 265. 445.0 331.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 570. 425. 305. 400. 465. 270. 446.7 365.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 255. 170. 455. 220. 470. 340. 393.3 243.3
-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
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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 445. 330. 465. 375. 545. 320. 485.0 341.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 230. 170. 490. 290. 280. 215. 333.3 225.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 405. 165. 330. 210. 375. 300. 370.0 225.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 225. 305. 405. 325. 450. 260. 360.0 296.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 470. 280. 535. 305. 430. 365. 478.3 316.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 590. 275. 450. 280. 220. 120. 420.0 225.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 240. 310. 230. 245. 170. 355.0 213.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 410. 220. 305. 315. 365. 270. 360.0 268.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 210. 240. 315. 255. 365. 250. 296.7 248.3
PAGE 94 PND 60
-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 GAIT CONVULSIONS-CLONIC CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 390. 365. 315. 250. 515. 455. 406.7 356.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 410. 415. 465. 375. 555. 370. 476.7 386.7
1 1 1 1 1 3 1 0 1 1 0 2 1 3 615. 275. 425. 315. 340. 255. 460.0 281.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 235. 155. 275. 130. 270. 215. 260.0 166.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 490. 350. 390. 365. 410. 275. 430.0 330.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 280. 290. 355. 280. 525. 300. 386.7 290.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 445. 205. 555. 480. 360. 415. 453.3 366.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 500. 240. 300. 210. 325. 400. 375.0 283.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 660. 325. 530. 365. 305. 255. 498.3 315.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 465. 380. 430. 320. 430. 355. 441.7 351.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 400. 370. 360. 295. 220. 391.7 326.7
-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
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 CONVULSIONS-TONIC TREMORS AROUSAL BIZARRE/STEREOTYPIC BEHAVIOR BACKING GROOMING URINATION DEFECATION 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)
1 1 1 1 1 3 1 0 0 0 0 2 1 3 500. 245. 390. 260. 465. 240. 451.7 248.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 350. 340. 600. 365. 390. 285. 446.7 330.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 355. 285. 480. 335. 355. 370. 396.7 330.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 305. 205. 140. 185. 250. 115. 231.7 168.3
1 1 1 1 1 3 1 0 0 0 0 2 1 3 250. 250. 270. 120. 420. 310. 313.3 226.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 510. 150. 390. 260. 305. 255. 401.7 221.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 465. 230. 390. 265. 255. 260. 370.0 251.7
1 1 1 1 1 3 1 0 0 0 0 2 1 3 450. 220. 305. 170. 570. 285. 441.7 225.0
1 1 1 1 1 3 1 0 0 0 0 2 1 3 325. 380. 315. 190. 405. 270. 348.3 280.0
PAGE 96 PND 60
-TOT-
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
PARAMETER
SCORING CRITERIA
MOBILITY
1-NORMAL 3-MODERATELY IMPAIRED
2-SLIGHTLY 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
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)
97
-1018-
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
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)
HINDLIMB GRIPSTRENGTH TRIAL 1 (GRAMS)
FORELIMB GRIPSTRENGTH TRIAL 2 (GRAMS)
HINDLIMB GRIPSTRENGTH TRIAL 2 (GRAMS)
PAGE 98
-1019-
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
PARAMETER
SCORING CRITERIA
FORELIMB GRIPSTRENGTH TRIAL 3 (GRAMS) HINDLIMB GRIPSTRENGTH TRIAL 3 (GRAMS)
PAGE 99
PFOBGv1.52 10/10/2006 R:01/26/2007
-1020-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
81 84 224 82 89 73 105 116 152 11 42 213 166 129 37
5 157 130 145 156
12 28 81
3 6 10 12 16 19 4 1 56 29 8 4 1 23 25 29 50
110. 60.6
20
21. 20.9
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
37 39 175 61 28 50
5 281 177
13 28 78 32 35
4 10 36 70
3 171
3 0 52 0 0 8 0 75 0 0 0 11 0 0 0 2 8 0 0 64
9 14 458
8 36 18 124 622 78
1 44 38 30 30
9 68 12 64 16 109
2 0 166 0 0 0 14 270 2 0 4 4 0 0 2 4 2 20 0 30
6 16
8 7 60 80 0 461 102 31 10 16 57 160 16 25 34 28 8 210
4 0 0 0 0 0 0 191 0 2 0 2 9 34 0 0 3 6 2 82
133 153 865 158 213 221 234 1480 509
56 124 345 285 354
66 108 239 292 172 646
21 28 299
3 6 18 26 552 21 6 5 73 38 42 6 7 36 51 31 226
67. 11. 75.0 23.2
89. 26. 160.0 68.2
67. 17. 107.9 45.3
333.
75.
336.3 135.7
PAGE
1
-1021-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
94 38 94 13 67 4 760 317 236 64 210 74 252 47 106 7 84 22 259 82 52 14 48 19 86 25 35 19 435 169 45 1 27 2 182 55 149 13 187 8
170. 172.2
20
50. 74.4
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
22 155 224 250
37 31 246 127 32 235 116 66 482
1 109
93 11 251 172 127
8 46 72 99
0 0 70 6 6 48 4 12 173 0 29 20 0 86 23 18
65 6
93 28 17 16 39 233 70 20 12
7 44
0 39 11 24 11 84 373
16 0 7 0 0 0 0
70 10
7 3 0 0 0 6 0 6 0 18 141
3 18 85
7 14 13 16 877 166
1 12 19 17 144 132 11 66 71 410 390
0 0 16 0 0 0 0 320 17 1 4 0 2 30 8 3 10 5 156 142
184 273 469 1045 304 270 553 1343 352 515 192 140 629 180 715 160 128 515 815 1077
62 59 99 416 64 74 117 403 55 138 25 31 200 49 212 24 18 146 210 309
139. 36. 117.8 44.8
60. 14. 90.3 33.7
124. 36. 213.7 80.5
493. 136. 351.8 121.6
PAGE
2
-zzoi-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
34 28 191 65 138 10 892 147 106
9 153 180 113
80 19 80
0 170
39 105
6 2 52 7 30 5 375 47 26 3 9 44 30 16 7 20 0 33 0 22
128. 190.0
20
37. 81.3
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
39 6
163 74 45 0
1115 74
354 112
15 21
9 96
0 0 0 5 81 8
11 0
33 17
0 0 455 12 76 25 0 0 0 1 0 0 0 0 18 1
5 13 110 92 28 62 77 14 31 19 25 32 481 60
5 29
0 31 27 94
0 0 29 6 4 12 20 0 0 3 4 2 221 8 0 0 0 0 0 22
22 12 288 387 24 21 47 39 146
5 2 7 790 15 9 26 0 102 3 0
0 0 35 119 0 4 3 2 30 0 0 4 348 0 0 0 0 0 0 0
100 59
752 618 235
93 2131
274 637 145 195 240 1393 251
33 135
0 308 150 207
17 2
149 149
34 21 853 61 132 31 13 50 599 25
7 20
0 33 18 45
111. 32. 250.6 101.1
62. 17. 103.8 48.9
97. 27. 192.7 80.3
398. 113. 522.2 218.5
PAGE
3
-1023-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
124 84
125 81 14 0
162 46
718 92 92 65
235 57 59
221 135
13 245
37
43 1
37 22
0 0 10 0 307 20 10 15 82 4 3 80 51 0 102 11
130. 155.8
20
40. 70.0
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
9 24 324 13 40 152 102 77 418 118 238 110 16 61 35 107
5 7 38 0
0 0 127 0 0 12 35 4 174 8 61 0 8 4 0 0 0 0 0 0
53 66 264
4 12 40 10
0 5 55 65 15 1 70 23 41 4 9 43 0
10 0
87 0 0 0 0 0 0 0
20 0 0 0 0 0 3 0 0 0
24 133 230
6 9 11 24 8 420 6 149 33 24 59 16 20 18 18 574 0
5 28 78
0 0 0 2 0 157 0 60 0 0 0 0 0 4 0 230 0
210 307 943 104
75 203 298 131 1561 271 544 223 276 247 133 389 162
47 900
37
58 29 329 22
0 12 47
4 638
28 151
15 90
8 3 80 58 0 332 11
95. 22. 113.1 47.2
39. 6. 58.4 19.7
89. 28. 153.5 61.6
353.
96.
377.0 160.8
PAGE
4
-1024-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1094 564 570 170 355 653 104 754 144 574 142 816 335 315 187 198 156
1181 579 521
426 194 211
41 98 244 25 251 36 169
6 295
74 107
72 61 42 508 195 214
471. 163. 317.8 135.8
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
532 334
71 6
372 191 320
61 44 60 43 236 42 16 11 276 87 685 295 487
174 99 4 0 66 64
119 8 0
14 0
55 0 0 0
100 0
242 60
165
344 62
153 40 40 47
324 444
34 111
17 680 150
7 3 258 19 661 77 207
139 0
37 0 0 0
113 158
0 0 0 215 0 0 0 70 0 237 20 51
32 12 13 65 15 11
0 679
33 31 19 523 11 25 51 30 13 522 41 29
6 0 0 5 0 0 0 260 0 2 0 174 0 0 0 0 4 165 12 0
2002 972 807 281 782 902 748
1938 255 776 221
2255 538 363 252 762 275
3049 992
1244
745 293 252
46 164 308 257 677
36 185
6 739
74 107
72 231
46 1152
287 430
208. 59. 199.2 71.4
184. 52. 208.8 77.7
108. 31. 203.9 74.6
971. 305. 772.8 302.8
PAGE
5
-1025-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
707 299 474 1388 785 829 410 169 529 373 760 335 305 666 665 273 468 840 1332 495
302 110 185 603 284 312 129
27 195 155 324
88 105 261 227
0 94 320 592 166
605. 224. 326.4 160.3
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
393 38
220 806 142
3 437 184 121
44 45 125
6 246 283 102 403
48 627 228
146 0
86 325
36 0
144 34 28 11 5 30 0 86 93 0
129 18
227 70
541 9
116 599 519
8 425 179
22 78 24
7 17 54 90 18 354 733 640 14
198 0
24 231 169
0 135
30 0
32 2 0 2
26 24
0 103 261 218
0
611 25
452 9
526 24
522 428
27 112
2 9 3 456 32 12 437 601 518 3
219 0
186 0
148 0
153 135
0 33
0 0 0 176 2 2 122 197 205 0
2252 371
1262 2802 1972
864 1794
960 699 607 831 476 331 1422 1070 405 1662 2222 3117 740
865 110 481 1159 637 312 561 226 223 231 331 118 107 549 346
2 448 796 1242 236
225. 73. 215.3 86.2
222. 73. 256.4 92.8
240. 79. 251.1 88.7
1293. 449. 832.6 345.2
PAGE
6
-1026-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
929 605 537 606 281 374 862 269 1361 410 472 692 696 534 671 1853 592 732 912 1248
413 195 223 221 117 107 324
64 587 128 174 230 222 188 192 851 226 260 331 500
732. 278. 387.9 187.5
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
873 426 557 720
0 84 482 239 303 543
2 349 501 262 487 805
46 455 292 764
390 145 209 288
0 12 182 41 74 131
0 104 158
86 177 337
6 133
91 307
802 416 446 533
15 1
563 0
294 560
1 54 383 296 542 186 37 572 590 751
372 89
194 200
2 0 188 0 85 145 0 0 105 87 180 56 0 220 221 275
674 373 493 460
2 69 471 21 132 100 11
2 477 461 340 126
67 370
19 793
289 97
185 197
0 7 145 0 26 0 6 0 174 144 94 35 2 124 0 340
3278 1820 2033 2319
298 528 2378 529 2090 1613 486 1097 2057 1553 2040 2970 742 2129 1813 3556
1464 526 811 906 119 126 839 105 772 404 180 334 659 505 643
1279 234 737 643
1422
410. 144. 262.2 115.5
352. 121. 265.9 108.1
273. 93. 246.4 104.1
1766. 635. 932.3 413.2
PAGE
7
-1027-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
67 15 51 15 435 153 173 53 383 133 119 21 356 113 114 24 705 259 73 24 342 102 373 125 915 389 112 10 76 2 733 267 982 391 321 77 973 386 358 52
383. 131. 315.0 134.6
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
140 8
663 457
77 163
15 123 510
3 855 185 487
22 25 812 697 371 862 921
14 0
255 102
4 10
0 4 152 0 344 0 206 0 0 349 283 116 330 330
279 1
682 1043
1 2 0 808 434 1 836 0 589 27 28 801 816 503 632 1054
80 0
270 409
0 0 0 317 126 0 330 0 269 0 0 322 285 181 219 446
43 12 524 841
0 35
9 817 414
4 454
10 697
8 86 784 706 511 583 541
0 0 215 334 0 0 0 294 106 2 170 0 313 0 2 316 264 202 235 203
529 72
2304 2514
461 319 380 1862 2063
81 2487
568 2688
169 215 3130 3201 1706 3050 2874
109 15
893 898 137
31 113 639 643
26 946 125 1177
10 4
1254 1223
576 1170 1031
370. 125. 333.9 141.5
427. 163. 393.8 158.8
354. 133. 326.4 133.1
1534. 551. 1200.5 488.1
PAGE
8
-1028-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
290 115 398 168 845 334 489 169 441 161 550 182 509 176 496 203 319 111 451 154 377 96 399 168 535 180 318 125 195 70 352 108 402 156 698 265 541 238 490 154
455. 144.9
20
167. 60.8
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
4 36 295 199 18 23
8 53 39 50 209
9 40
3 3 129 4 312 354 76
0 7 73 39 6 0 0 6 6 0 47 0 0 0 0 35 0 80 120 0
208 33 83 21 53 12 26
127 76 12 15 31
170 6 0
83 8
180 79 31
55 4 8 2 9 0 0
27 22
0 0 0 0 0 0 0 0 65 29 0
335 2 7 8
57 3 0 1
11 7
27 36 67
0 4 68 35 0 33 6
75 0 0 4
10 0 0 0 4 0 0 0 0 0 2 0 0 0 3 0
837 469 1230 717 569 588 543 677 445 520 628 475 812 327 202 632 449 1190 1007 603
245 179 415 214 186 182 176 236 143 154 143 168 180 125
72 143 156 410 390 154
93. 21. 115.3 34.4
63. 11. 63.0 19.2
35. 5. 74.1 16.7
646. 263.0
204. 94.8
PAGE
9
-1029-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
483 213 400 180 345 143 672 250 539 204 250 89 572 213 620 197 785 251 487 161 707 274 480 181 407 161 487 168 713 317 328 81 638 205 558 182 859 313 615 222
547. 158.2
20
200. 61.9
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
4 19 12 484
9 0 301 358 234 8 206 10 12 1 1 6 316 312 490 356
0 0 0 139 2 0 55 66 46 0 73 0 4 0 0 0 43 73 128 113
29 47 19 20 12
0 259 243 104
0 4 95 6 22 0 0 16 352 445 451
6 0 0 2 4 0 53 42 16 0 0 0 0 5 0 0 0 81 119 144
7 19 320 18
0 8 29 183 44 0 10 113 54 22 1 0 11 24 332 242
1 0 65 0 0 0 0 14 2 0 0 0 14 5 0 0 0 0 111 48
523 485 696 1194 560 258 1161 1404 1167 495 927 698 479 532 715 334 981 1246 2126 1664
220 180 208 391 210
89 321 319 315 161 347 181 179 178 317
81 248 336 671 527
157. 37. 181.0 47.6
106. 24. 154.0 43.1
72. 13. 108.1 28.9
882. 274. 483.6 142.2
PAGE 10
-1030-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
504 160 700 264 798 326 591 223 566 208 439 136 409 124 545 195 623 191 275 99 472 183 501 175 507 209 327 117 491 154 320 115 353 101 511 153 656 264 663 275
513. 136.5
20
184. 63.2
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
396 87
177 46
241 19
351 2
181 1 5 4
168 21
303 6
24 156 152 234
108 0
34 0
68 0
89 0 0 0 0 0
56 0
96 0 0
23 36 86
235 13 20 36 5 1 13 12 11 29 10 19
268 5
26 5
20 8
240 0
64 2 7 0 0 0 2 2 0 0 0 0
74 0 4 0 0 0
54 0
187 23 13 0 0 0 28 14 12 0 8 2
325 33
114 3 3 2
368 17
51 0 4 0 0 0 0 0 0 0 0 0
111 0 2 0 0 0
91 0
1322 823
1008 673 812 459 801 573 827 305 495 526
1268 386 934 334 400 677
1416 914
383 266 371 223 276 136 215 197 191
99 183 175 450 117 256 115 101 176 445 361
129. 30. 126.6 39.2
49. 10. 86.4 23.4
58. 13. 109.1 32.3
748. 237. 328.7 111.9
PAGE 11
-1031-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
633 259 758 811 632 643 447 505 522 547 801 455 352 445 465 569 332 488 729 1088
209 79
261 323 194 241 126 171 178 195 284 143 149 160 125 221 135 131 255 441
574. 195.1
20
201. 83.6
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
9 178
31 298 168
49 29 10 26 31 279
9 44 236 52
2 42 78 71 916
0 36
2 78 52
0 0 2 0 2 109 1 0 81 0 0 7 0 17 340
1 52
3 465
9 78
0 2 65 91 78 34 2 136 19 0 30 150 7 787
0 2 0 126 0 0 0 0 2 26 0 13 0 51 0 0 0 0 0 280
3 21
0 462
29 498
3 19
4 28 354 10 14 15
9 0 29 13 27 892
0 0 0 143 0 120 0 0 0 4 49 0 0 0 0 0 0 0 0 322
646 510 792 2036 838 1268 479 536 617 697 1512 508 412 832 545 571 433 729 834 3683
209 117 263 670 246 361 126 173 180 227 442 157 149 292 125 221 142 131 272 1383
128. 36. 207.5 78.8
100. 25. 192.6 67.0
122. 32. 239.7 79.7
924. 294. 763.6 288.3
PAGE 12
-1032-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1456 1416 1341 1060 1007 1149 1442 1269 1424 1488
589 1028 1415 1358 1158 1437 1734 1410 1424 1317
538 452 598 381 399 434 535 550 478 468 106 409 589 493 340 385 559 542 497 542
1296. 465. 243.7 112.3
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
1076 479 726 661 237 472 379 463 778 772 127 493 570 981 377 654
1135 803 722 619
380 172 288 242
52 104 134 157 253 229
13 153 236 366 102 210 331 257 225 192
620 350
1 0 23 391 33 21 713 403 71 353 463 240 160 331 579 545 432 774
194 115
0 0 0 52 7 4 207 122 2 124 190 74 35 92 156 174 104 243
626 1001
20 11
0 70
7 0 142 56 38 165 548 25 197 105 422 551 226 493
226 404
1 2 0 9 0 0 18 20 0 50 244 7 50 2 63 205 77 142
3778 3246 2088 1732 1267 2082 1861 1753 3057 2719
825 2039 2996 2604 1892 2527 3870 3309 2804 3203
1338 1143
887 625 451 599 676 711 956 839 121 736 1259 940 527 689 1109 1178 903 1119
626. 205. 261.6 97.3
325. 95. 248.5 80.4
235. 76. 278.3 111.5
2483. 840. 818.4 304.1
PAGE 13
-1033-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1248 1467 1283 1157 1092
988 1357 1150 1407 1567 1444 1424 1778 1287 1683 1779 1154 1430 1325 1488
422 524 373 447 480 391 561 413 614 567 618 555 720 539 801 657 402 621 482 608
1375. 540. 217.9 115.5
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
551 206 418 141 488 161 472 176 468 175 486 170 895 234 167 26 444 176 709 305 611 155 911 309 609 146 509 217 802 309 697 257 559 165 584 167 588 205 467 162
414 161 154 37 313 106 562 196 299 114 488 107 804 218
12 2 476 171 482 198 162 31 310 115 344 104 496 209 800 346 690 249 213 46 256 78 616 249 146 57
165 0
316 322
65 160 417
8 110 553 283
7 575 311 629 387 331 274 504 644
52 0
77 114
28 44 142
0 30 225 80
1 175 115 202 125
91 91 194 243
2378 2039 2400 2513 1924 2122 3473 1337 2437 3311 2500 2652 3306 2603 3914 3553 2257 2544 3033 2745
841 702 717 933 797 712 1155 441 991 1295 884 980 1145 1080 1658 1288 704 957 1130 1070
572. 193. 172.4 67.0
402. 140. 220.9 89.1
303. 101. 208.0 76.1
2652. 974. 624.4 271.6
PAGE 14
-1034-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
847 1746 1377 1418 1096 1240 1279 1375 1236 1081 1488 1654 1974 1650 1755
893 1729 1271 1402 1425
333 617 471 449 405 500 491 510 423 418 651 610 698 634 576 403 613 502 483 569
1397. 295.7
20
518. 98.8
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
320 475 231 883 219 318 537 543 406 550 652 757 689 747 1114 473 852 270 1188 411
96 186
69 295
20 101 213 178
95 177 290 294 241 258 413 179 218
86 498 116
215 541
40 239
1 12 335 130 299 261 581 604 756 486 875 271 526 539 587 171
76 194
4 58
0 1 123 27 86 62 216 220 230 166 252 101 156 207 184 61
249 357
1 0 1 0 289 0 39 0 599 277 432 699 742 362 86 470 438 483
74 156
0 0 0 0 79 0 2 0 124 92 113 260 253 160 10 182 112 159
1631 3119 1649 2540 1317 1570 2440 2048 1980 1892 3320 3292 3851 3582 4486 1999 3193 2550 3615 2490
579 1153
544 802 425 602 906 715 606 657 1281 1216 1282 1318 1494 843 997 977 1277 905
582. 201. 277.8 118.9
373. 121. 249.8 84.0
276. 89. 250.7 86.8
2628. 929. 884.5 312.9
PAGE 15
-1035-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1532 1103 1224 1481 1091 1177 1577 1504
874 1388 1601 1400 1314 1186 1200 1216 1341 1208 1448 1246
542 267 464 639 295 456 569 544 307 498 509 604 559 394 457 474 575 456 597 437
1306. 482. 186.8 104.5
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
933 305 502 548 547 360 592 708 447 312 1059 716 494 315 283 272 708 507 805 1397
326 75
156 143 181 102 245 258 159
97 435 300 187
86 95 75 285 144 292 501
207 667 521
0 498 189 175 348 336
1 281 383 1091 121 139 269 350 467 321 621
70 172 157
0 134
61 35 99 90
1 78 149 413 39 49 77 99 121 67 213
129 630 320
7 517 358 248 206 190
7 265 338 386 117
2 477 318 297 381 479
42 221
73 3
131 105
77 66 40
0 87 124 151 21
0 150 121 101 139 157
2801 2705 2567 2036 2653 2084 2592 2766 1847 1708 3206 2837 3285 1739 1624 2234 2717 2479 2955 3743
980 735 850 785 741 724 926 967 596 596 1109 1177 1310 540 601 776 1080 822 1095 1308
591. 207. 291.0 120.9
349. 106. 253.4 91.0
284. 90. 175.0 60.6
2529. 886. 567.1 235.9
PAGE 16
-1036-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
388 24
196 43 5
310 114
48 49 47 13 236 124 40 243 118 18 96 43 143
195 0
57 0 0
104 22 9 8 13 7 71 23 15 41 20 6 22 0 2
115. 107.9
20
31. 47.3
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
178 67 11 0 60
396 185
20 49
8 101
86 66 165 19 162 20 16 82 140
62 18
2 0 2 146 16 5 24 0 2 16 0 10 0 10 2 2 0 16
40 24 28
3 110 458
32 11
0 60 14
8 34 22 67
0 76 31 22 134
0 5 6 0 0 159 2 5 0 0 0 0 0 2 2 0 16 0 0 31
16 0
94 37 15
4 29 127
6 58 601 22 301 18 69 72 27 21 21 23
0 0 24 0 0 0 4 44 0 8 228 4 97 2 0 4 7 0 0 5
622 115 329
83 190 1168 360 206 104 173 729 352 525 245 398 352 141 164 168 440
257 23 89 0 2
409 44 63 32 21
237 91
120 29 43 34 31 24 0 54
92. 17. 94.3 33.7
59. 11. 100.6 35.5
78. 21. 140.3 53.8
343.
80.
263.0 104.6
PAGE 17
-eoi-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
87 304 204 1020
97 93 80 262 44 188 70 505 196 101 12 74 188 44 630 307
1 119
27 479
20 35
6 53
0 34 29 192 47 14
1 20 83
2 270
74
225. 75. 244.9 117.5
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
146 285
35 802 147 133
30 326
18 29 80 224 46 82 40 47 38 37 1085 490
14 114
4 324
0 50
2 137
0 4 0 116 0 1 6 6 2 0 496 152
88 367
2 583
29 274
19 66
4 50
7 649
79 70
6 21 19 63 766 628
2 163
0 228
0 104
0 0 0 5 0 307 1 5 0 0 0 0 328 272
27 307
31 91 11 816
6 145
19 65 27
5 477
12 18 10
7 106 902 392
2 136
3 0 0 356 0 28 0 15 0 0 195 0 0 0 2 22 394 151
348 1263
272 2496
284 1316
135 799
85 332 184 1383 798 265
76 152 252 250 3383 1817
19 532
34 1031
20 545
8 218
0 58 29 615 243 20
7 26 87 24 1488 649
206. 71. 284.3 129.8
190. 71. 258.1 118.1
174. 65. 271.4 120.9
795. 283. 904.3 409.2
PAGE 18
-80l-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
21 89 128 24 74 202 32 50 385 27 784 232 73 50 70
0 109 172
5 52
0 0 36 7 11 43 2 7 147 7 258 38 14 8 16 0 25 48 0 8
129. 180.2
20
34. 62.3
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
29 29 214 156 314
5 17
3 349
30 512
31 114
15 118
40 94 87
0 7
0 0 102 35 127 1 0 0 96 0 151 5 1 5 9 0 0 24 0 0
33 22 188 41 157 222 25 23 579
9 89 310 118 131 197 14
1 308
0 51
0 0 58 10 55 40 0 0 202 0 2 93 15 10 46 0 0 74 0 0
59 17 348
4 5 150 34 21 221 5 50 52 281 73 38 23 42 3 4 43
0 0 147 0 0 18 0 0 73 0 2 10 68 26 0 6 0 0 0 0
142 157 878 225 550 579 108
97 1534
71 1435
625 586 269 423
77 246 570
9 153
0 0 343 52 193 102 2 7 518 7 413 146 98 49 71 6 25 146 0 8
108. 28. 139.1 48.7
126. 30. 145.7 49.8
74. 18. 98.5 37.4
437. 109. 430.9 150.2
PAGE 19
-1039-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
62 1 29 9 71 1 282 61 30 5 80 15 26 8 26 6 105 9 220 76 156 25 35 1 211 54 122 27 33 3 131 19 76 22 70 5 148 25 133 48
102. 73.1
20
21. 22.1
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
330 75 8
216 0
19 14
0 47 134 28 15 502
8 0 3 55 24 36 99
114 4 0
47 0 0 0 0 0
44 0 0
227 1 0 3 0 3 0 0
608 0 6
69 14 29 11
1 368
13 295
8 10 343
1 13 57 21 30 18
233 0 0
24 2 0 0 0
123 0
94 0 0
108 0 1
12 3 0 0
79 400
12 6 0
15 25
9 581
9 21
8 163 771
1 5 138 9 3 8
14 250
0 0 0 0 0 0 234 0 3 0 44 360 0 2 26 0 0 0
1079 504 97 573 44 143 76 36
1101 376 500 66 886
1244 35
152 326 124 217 258
362 263
1 132
7 15
8 6 366 120 122 1 325 496 3 25 60 11 25 48
81. 22. 129.7 55.7
96. 30. 168.2 61.8
113. 47. 216.4 104.2
392. 120. 391.7 154.4
PAGE 20
-1040-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1378 737 293 13 33 380 143 580 212 956 571 924 382 183 741 668 939 465 689 587
654 279
53 0 2
129 33
222 68
420 163 328 105
45 278 243 391 161 269 186
544. 201. 351.6 164.5
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
678 330 441
8 11 16 155 477 124 277 595 302
9 7 365 560 27 133 438 457
243 110 136
0 0 2 0 167 17 127 176 115 4 0 113 192 5 37 150 144
38 57 67 43
7 25 415 473 11 31 246
3 1 4 428 483 187 0 37 387
8 14
0 0 0 6 126 177 0 8 73 0 0 0 177 163 66 0 14 130
27 4 5
53 1 2
522 425
19 138
36 0
18 4
230 38
438 1
34 483
4 0 0 6 0 0 155 153 0 55 0 0 4 0 73 0 157 0 0 148
2121 1128
806 117
52 423 1235 1955 366 1402 1448 1229 410 198 1764 1749 1591 599 1198 1914
909 403 189
6 2 137 314 719 85 610 412 443 113 45 641 598 619 198 433 608
271. 87. 224.2 79.9
147. 48. 183.4 67.3
124. 38. 185.2 62.4
1085. 374. 668.1 268.2
PAGE 21
-1041-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
832 973 225 628 748 458 662 602 624 562 492 550 357 384 1029 490 608 775 793 348
313 464
71 202 294 182 275 229 176 243 173 171 100 133 415 156 201 293 309 101
607. 225. 208.9 102.4
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
263 38 49 1
481 151 491 721 595
6 8 45 464 288 682 54 232 100 230 39
75 15
5 0 130 39 180 273 202 0 1 0 134 97 222 2 56 20 66 0
552 14
221 24
693 17
335 741 683
13 51 32 308 101 1019 26 27 31 185 12
160 0
57 0
262 2
102 252 247
0 0 0 86 20 414 0 0 12 28 4
728 13
266 71
812 33 66
650 715
10 190
33 131
61 778
78 8 0
22 47
249 4
89 0
317 2 0
233 252
0 61
6 35
0 294
0 0 0 0 10
2375 1038
761 724 2734 659 1554 2714 2617 591 741 660 1260 834 3508 648 875 906 1230 446
797 483 222 202 1003 225 557 987 877 243 235 177 355 250 1345 158 257 325 403 115
247. 76. 241.7 86.3
254. 82. 312.4 120.8
236. 78. 304.9 116.8
1344. 461. 914.4 350.7
PAGE 22
-1042-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
218 217 642 910 541 923 473 106 717 173 653 183 721 985 362 926 696 670 1120 364
59 82 270 380 195 360 150 23 294 34 220 45 281 370 45 353 250 259 475 86
580. 212. 306.9 138.8
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
18 208 1082 589
4 450 190
12 410
75 538
10 439 283 458 626 425 461 501 111
0 54 551 199
0 133
44 0
109 0
152 4
125 77
137 235 135 168 212
0
13 180
69 561
44 424 170
16 464
6 389
59 560 518 672 539 512 408 695
19
0 56
5 189
16 136
55 0
164 0
141 21
181 166 242 207 168 148 265
0
28 198 264 458
31 414 387
9 540
4 559
47 490 639 550 423
21 20 702 44
0 52 93 138 10 122 90
0 193
0 177
15 146 236 227 180
3 5 280 0
277 803 2057 2518 620 2211 1220 143 2131 258 2139 299 2210 2425 2042 2514 1654 1559 3018 538
59 244 919 906 221 751 339
23 760
34 690
85 733 849 651 975 556 580 1232
86
345. 117. 273.4 128.8
316. 108. 248.5 90.8
291. 98. 248.7 94.1
1532. 535. 924.5 370.3
PAGE 23
-1043-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
107 182 1143 655 304 299 260
88 171 665 749 268 856 983
79 621 831 664 1027 1235
0 38 508 205 86 72 83 17 49 307 332 88 310 428
4 244 303 260 410 507
559. 213. 376.0 171.0
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
553 518 427 709 280 317
61 2
98 101 294
26 690 453
3 508 332 387 708 952
198 195 203 261
56 106
0 0 0 25 134 0 233 163 0 183 105 130 201 317
493 165 187 69 625 258 600 224 197 56 309 127
61 0 29 0 303 73 26 0 258 59 12 0 599 189 741 281 16 0 442 141 122 13 519 207 622 207 900 298
471 16
310 726
27 36
6 14 325
3 517
11 85 523
5 106 427 460 944 1056
152 0
128 269
0 0 0 0 100 0 181 0 13 201 0 24 159 186 357 372
1624 903
2505 2690
808 961 388 133 897 795 1818 317 2230 2700 103 1677 1712 2030 3301 4143
515 302 1097 959 198 305
83 17 222 332 706 88 745 1073
4 592 580 783 1175 1494
371. 126. 271.8 99.4
353. 118. 273.2 104.1
303. 107. 330.2 124.0
1587. 564. 1109.6 432.4
PAGE 24
-1044-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
227 89 463 175 518 154 646 248 345 78 667 228 492 119 501 159 578 194 470 187 678 254 675 230 594 232 450 153 288 102 482 218 370 141 468 193 539 176 639 216
505. 128.5
20
177. 52.6
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
3 3 10 204 77 554 273 29 96 3 116 332 397 30 3 0 4 26 23 541
0 0 4 72 2 199 75 0 17 0 24 57 137 2 0 0 0 5 4 145
20 2
20 2
63 11 17
5 24
6 27 20 99
8 15
8 0 0 14 215
0 0 1 0 0 2 0 0 6 1 0 0 7 0 0 0 0 0 4 56
64 0 1
22 3
273 371
0 37 13
8 1 33 3 115 15 7 2 278 164
0 0 0 0 0 96 59 0 3 4 0 0 0 0 27 2 4 0 57 52
314 468 549 874 488 1505 1153 535 735 492 829 1028 1123 491 421 505 381 496 854 1559
89 175 159 320
80 525 253 159 220 192 278 287 376 155 129 220 145 198 241 469
136. 37. 184.1 59.3
29. 4. 49.7 12.5
71. 15. 111.9 27.9
740. 234. 367.2 117.1
PAGE 25
-1045-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
626 258 534 146 509 180 368 134 577 229 359 96 545 160 417 143 488 171 367 143 669 268 656 196 622 226 369 142 392 155 261 95 592 181 445 137 343 133 443 172
479. 119.5
20
168. 47.5
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
283 0 3
381 151
1 189 208
6 12 278 139 28 221
0 1 131 288 268 280
83 0 0
116 36 0 39 50 0 4 93 17 6 83 0 0 22 95 71 88
30 1
52 270 147
1 163
34 3
137 5
24 0
143 1 0
19 144
23 59
0 0 0 59 17 0 49 8 0 38 0 0 0 32 0 0 0 14 0 18
2 9 14 152 10 2 289 71 14 10 33 3 3 10 0 1 18 9 33 16
0 0 0 36 0 0 80 8 0 0 0 0 0 3 0 0 0 0 0 2
941 544 578 1171 885 363 1186 730 511 526 985 822 653 743 393 263 760 886 667 798
341 146 180 345 282
96 328 209 171 185 361 213 232 260 155
95 203 246 204 280
143. 40. 128.3 40.8
63. 12. 76.7 18.4
35. 6. 69.2 19.1
720. 250.9
227. 78.6
PAGE 26
-1046-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
624 210 660 254 669 260 700 253 589 223 426 157 438 160 982 395 539 182 407 124 590 206 366 106 284 78 813 262 314 92 631 222 666 240 463 178 561 164 544 206
563. 169.5
20
199. 72.8
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
148 131
33 77 63
0 230
0 13
1 347
14 2
370 70 43
117 214
66 135
45 24 16 19
0 0 54 0 2 0 83 0 0 111 4 0 20 53 12 49
24 258
28 35
4 11 312 22 35 28 429 132
4 308 222
0 35
4 57 159
0 74
0 6 0 0 65 0 12 0 124 26 0 73 22 0 0 0 0 51
1 405
36 10
1 18 74
5 20
2 127
45 12
0 78
0 142
0 16 279
0 108
0 2 0 0 7 0 12 0 19 0 0 0 0 0 16 0 0 91
797 1454
766 822 657 455 1054 1009 607 438 1493 557 302 1491 684 674 960 681 700 1117
255 460 276 280 223 157 286 395 208 124 432 132
78 446 118 222 276 231 176 397
104. 25. 111.1 31.6
105. 23. 130.3 35.6
64. 13. 106.0 30.4
836. 259. 345.2 115.8
PAGE 27
-1047-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
665 219 439 134 425 154 571 221 593 231 787 272 340 129 433 121 412 107 776 254 662 214 520 177 722 250 514 208 539 198 790 303 424 152 565 226 250 69 902 336
566. 170.8
20
199. 68.4
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
485 79
191 164 158 476 378
2 23 298 264 37 215 366 316 45 224 502
4 333
149 0
67 27 53 145 121
0 0 0 86 0 83 123 81 8 24 195 0 83
46 7 2
61 242 610
19 4
82 9
34 2
58 110
98 14 20 27
0 382
0 0 0 0 36 180 2 0 11 0 0 0 22 40 0 0 0 5 0 67
74 0
349 3
35 586
11 31 35 141 50
5 1 59 11 0 21 4 19 422
0 0 85 0 0 162 0 0 0 6 0 0 0 3 0 0 0 2 0 116
1270 525 967 799
1028 2459
748 470 552 1224 1010 564 996 1049 964 849 689 1098 273 2039
368 134 306 248 320 759 252 121 118 260 300 177 355 374 279 311 176 428
69 602
228. 62. 164.7 60.7
91. 18. 154.0 42.2
93. 19. 163.3 45.9
979. 298. 512.3 164.7
PAGE 28
-1048-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1262 1401 1102 1356
780 1222 1188 1208 1053 1253
967 1263 1486
830 974 1408 1151 1238 1176 1640
576 588 485 564 272 567 495 532 495 490 474 636 701 330 463 688 464 478 462 614
1198. 519. 211.4 105.1
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
892 377 556 228 647 270 666 245 244 61 264 96 618 246 484 208 762 345 388 115 404 164 431 169 608 234 326 124 557 214 819 364 516 174 709 279 147 62 652 205
418 581 328 717
46 193
62 126 414 284 425 221 493 224
1 732 165 283 521 349
170 216
98 260
2 67 15 36 160 83 189 90 212 79
1 299
58 72 213 107
483 850 343
78 3
85 153 419 455 560 389
97 341 124
43 224
1 398
47 4
176 389 119
34 0
10 35 162 217 158 168 16 91 24
4 57
0 139
16 0
3055 3388 2420 2817 1073 1764 2021 2237 2684 2485 2185 2012 2928 1504 1575 3183 1833 2628 1891 2645
1299 1421
972 1103
335 740 791 938 1217 846 995 911 1238 557 682 1408 696 968 753 926
535. 209. 198.9 91.8
329. 121. 209.9 87.8
255. 91. 230.8 100.7
2316. 940. 612.5 283.0
PAGE 29
-1049-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1261 1352 1098
975 1758 1125
997 1185 1032
946 945 988 1153 1262 1054 1356 1422 970 982 1360
612 537 488 387 828 434 475 516 498 450 449 439 588 482 467 616 592 427 395 625
1161. 515. 211.0 104.3
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
908 438 377 129 677 242 329 105 850 381 240 58 429 165 476 158 733 282 480 197 444 170 551 204 473 192 799 325 326 90 448 175 836 297 385 119 525 183 381 154
939 1
593 478 505 216 300 209 571 403 206 349 548 404
94 193 576 449 717 390
430 0
224 187 193
91 75 67 221 196 85 135 219 154 33 75 219 175 307 136
141 8
407 66
350 36
481 0
272 147 339 337 388 445
8 468 549
84 484 234
44 0
146 20
102 0
190 0
90 46 103 122 146 157
0 199 198
13 169
77
3249 1738 2775 1848 3463 1617 2207 1870 2608 1976 1934 2225 2562 2910 1482 2465 3383 1888 2708 2365
1524 666
1100 699
1504 583 905 741
1091 889 807 900
1145 1118
590 1065 1306
734 1054
992
533. 203. 197.4 98.0
407. 161. 223.1 99.8
262. 91. 186.3 72.3
2364. 971. 587.9 273.0
PAGE 30
-1050-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1112 1373
958 1279 1352 1330
766 1347 1018 1172 1062
890 1070 1375 1544 1505 1156 1363
616 975
489 621 454 628 618 629 350 644 400 522 451 377 473 612 713 571 445 535 205 370
1163. 505. 246.4 127.0
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
596 231 628 296 498 184 568 231 427 136 167 51 520 182 629 297 283 68 164 49 684 270 388 121 482 148 480 179 845 326 406 101 669 211 138 29 145 36 443 176
271 83 7
567 453
4 378 486
0 11 486 388 316 518 756
2 685 493
69 380
73 29
1 244 116
0 143 196
0 0 165 114 92 185 301 0 269 181 4 148
75 317
0 16 117 53 308 487 10 143 417 130 92 228 518 96 425 65
1 215
25 144
0 2 25 0 103 219 2 73 165 33 16 49 188 26 146 11 0 86
2054 2401 1463 2430 2349 1554 1972 2949 1311 1490 2649 1796 1960 2601 3663 2009 2935 2059
831 2013
818 1090
639 1105
895 680 778 1356 470 644 1051 645 729 1025 1528 698 1071 756 245 780
458. 166. 199.0 92.2
318. 113. 246.7 98.1
186. 66. 169.5 70.9
2124. 850. 653.7 297.9
PAGE 31
-isoi-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
MEAN S.D.
N
0 TO 15 MINS TOTAL AMB
1108 1398 1319 1264 1387 1159 1418 1396
957 928 938 1352 1280 1054 1370 1232 858 1194 1134 1601
478 661 663 511 624 490 682 666 354 458 343 594 609 518 520 622 346 571 485 608
1217. 540. 198.3 108.0
20
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
16 TO 30 MINS TOTAL AMB
31 TO 45 MINS TOTAL AMB
46 TO 60 MINS TOTAL AMB
COMBINED
TOTAL
AMB
558 224 511 204 827 341 425 157 522 201 596 223 718 291 735 320 417 157 514 241 150 39 702 293 750 316 569 255 467 140 617 242 594 213 750 328 555 210 729 275
177 472
70 0
514 493 488 523 476 157
23 553 357 254 485 178 231 657 446 671
73 178
15 0
203 191 187 247 157
38 5
218 157
90 156
45 79 282 159 265
4 469
23 0
402 113 456 254 244
66 0
156 536 349 477 229 129 435 199 427
0 196
0 0 156 10 206 75 83 22 0 49 221 138 146 78 42 191 58 163
1847 2850 2239 1689 2825 2361 3080 2908 2094 1665 1111 2763 2923 2226 2799 2256 1812 3036 2334 3428
775 1239 1019
668 1184
914 1366 1308
751 759 387 1154 1303 1001 962 987 680 1372 912 1311
585. 234. 156.0 74.4
361. 137. 207.6 88.3
248. 92. 183.3 78.1
2412. 1003. 592.1 275.9
PAGE 32
PMASUMv5.15 10/23/2006
-1052-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
MALE GROUP: 0 MG/KG/DAY
TEST PERIOD: PND 20
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
267.4 195.8 155.4 115.3 161.0 225.5 229.2 274.6
68.7 169.8 245.3 165.9
94.6 82.4 127.8 287.2 149.1 251.3 214.7 284.8
20.6 22.3 22.4 24.8 25.9 21.5 23.9 23.2 30.2 25.1 29.2 27.6 31.4 35.1 25.8 27.0 31.1 23.7 28.4 26.2
55.3 43.6 36.0 28.3 33.4 54.9 49.7 60.4 13.7 38.5 60.7 36.0 24.2 16.1 23.7 55.1 32.3 48.4 44.2 59.0
212.3 192.9 132.8
73.1 194.5 208.4 223.7 170.0
68.6 113.7 202.8 229.7
59.6 44.3 88.5 266.8 96.7 238.7 218.3 244.2
21.8 24.0 24.1 24.5 22.1 20.3 21.4 21.6 30.9 26.1 22.0 29.7 28.6 31.9 31.4 20.9 21.8 20.2 20.6 21.7
50.4 42.5 29.9 14.2 43.0 49.9 41.5 31.7 13.7 19.9 43.9 45.0 13.9
9.8 18.5 53.3 19.7 47.2 49.2 53.9
115.3 175.3 101.8
99.4 182.4 182.1 149.4 177.5
77.3 110.6 215.8 218.7
79.1 75.4 79.6 262.2 128.5 206.3 134.9 196.3
26.9 21.3 29.9 20.9 21.3 20.4 24.5 21.4 29.8 21.1 22.4 26.8 25.7 35.5 22.9 21.3 26.7 21.1 27.6 21.7
26.9 38.5 24.3 21.6 38.2 45.4 27.0 35.9 13.1 26.6 43.4 46.4 19.1 17.6 16.7 56.1 25.9 48.1 31.9 43.2
80.2 186.0 101.2 115.5
90.2 80.2 190.8 151.7 114.8 79.4 234.1 114.7 88.7 31.1 58.3 149.5 156.4 166.5 121.8 149.9
25.8 22.4 22.6 21.6 25.5 25.5 20.5 20.8 21.0 30.0 20.9 24.1 24.1 27.6 34.2 22.5 19.8 23.5 28.3 25.6
19.5 41.7 22.7 25.3 18.8 19.7 33.9 32.7 20.4 16.4 45.5 25.1 20.0
6.1 12.4 30.9 29.9 40.2 27.9 37.9
122.4 192.8 110.6 100.4 257.7
52.5 215.9 165.4 167.4 199.2 121.8
65.5 129.4
40.5 52.7 131.4 175.2 178.1 52.8 134.2
23.1 21.9 21.8 24.6 20.0 36.6 20.4 24.7 21.1 19.7 22.5 32.1 20.8 40.2 26.6 25.0 20.0 28.7 31.5 28.3
31.3 51.9 24.3 19.8 59.4 12.4 44.3 43.0 30.7 40.6 29.8 16.1 29.6 10.5 12.0 30.9 34.1 49.9 12.1 36.5
159.5 188.6 120.4 100.7 177.2 149.7 201.8 187.8
99.4 134.5 204.0 158.9
90.3 54.7 81.4 219.4 141.2 208.2 148.5 201.9
23.6 22.4 24.2 23.3 23.0 24.9 22.1 22.3 26.6 24.4 23.4 28.1 26.1 34.1 28.2 23.3 23.9 23.4 27.3 24.7
36.7 43.6 27.4 21.8 38.6 36.5 39.3 40.7 18.3 28.4 44.7 33.7 21.4 12.0 16.7 45.3 28.4 46.8 33.1 46.1
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)
1
-1053-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
MALE GROUP: 0.1 MG/KG/DAY
TEST PERIOD: PND 20
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
175.7 218.6 167.7 158.2 106.4 102.4 134.4
94.5 142.6 212.7 115.9
96.0 127.8 167.1 251.6
84.7 285.9 230.1 211.8 225.1
27.6 25.4 26.4 34.7 22.2 23.8 22.3 28.1 30.1 24.5 25.1 31.8 34.7 34.8 21.6 35.9 30.9 30.9 22.0 21.4
37.7 49.6 39.7 33.6 17.8 21.1 27.3 21.6 30.8 47.4 23.7 20.1 32.4 37.0 49.0 20.5 59.0 42.4 48.5 47.7
159.9 195.2 130.8 105.4 141.8
89.8 199.5
74.0 116.8 192.2 130.1
41.9 84.0 116.8 166.4 139.7 201.3 131.0 224.1 184.5
18.9 23.9 23.5 32.6 19.3 22.4 20.0 28.0 28.1 22.7 20.8 26.6 31.3 25.7 19.9 23.5 20.6 29.0 20.3 21.1
28.1 43.8 24.6 28.3 27.0 18.0 28.5 16.3 27.5 45.3 25.2
9.5 17.2 25.2 35.7 25.3 46.0 25.8 59.5 40.7
195.5 166.1 139.5
69.6 123.1
84.3 185.3 100.7 130.7 136.0 131.9
43.7 104.0
84.0 83.1 94.1 232.2 59.6 215.2 224.6
19.7 21.4 21.6 33.6 19.5 22.1 20.4 32.9 26.8 24.6 22.5 41.3 22.6 31.6 27.5 23.4 23.3 25.0 20.6 22.0
31.0 41.1 29.2 15.4 24.9 20.0 32.3 20.9 30.6 34.1 24.5
8.1 22.2 19.2 20.8 14.9 49.8 12.1 58.3 57.1
221.7 174.7 106.9 151.6 134.6 203.3 188.9 105.7 143.8 199.9 149.2
50.4 121.3
67.8 149.4 100.7 189.3
81.4 97.8 152.6
18.6 23.9 24.1 25.6 20.6 21.9 21.7 26.3 27.9 22.7 20.8 33.0 19.2 21.4 29.0 26.7 21.0 20.1 31.5 23.1
38.2 44.1 21.6 37.4 28.2 53.2 35.1 25.9 29.3 47.6 32.7
8.2 20.1 13.8 42.6 19.1 50.0 15.2 24.0 39.5
201.7 147.2
65.8 104.2 138.1 122.7 176.5
55.3 131.1 192.7 169.4 106.1 126.0 150.3 150.2
85.4 150.9
83.3 26.2 207.2
19.5 24.3 24.6 25.0 19.4 23.9 20.6 25.1 29.4 21.2 22.3 23.6 19.4 21.2 22.9 26.0 25.4 28.5 35.9 22.0
39.8 37.5 15.7 20.6 28.7 32.3 37.1 10.7 28.1 43.9 35.0 21.5 19.8 34.0 43.2 18.8 40.9 16.2
5.7 55.1
190.9 180.4 122.1 117.8 128.8 120.5 176.9
86.0 133.0 186.7 139.3
67.6 112.6 117.2 160.1 100.9 211.9 117.1 155.0 198.8
20.9 23.8 24.0 30.3 20.2 22.8 21.0 28.1 28.5 23.1 22.3 31.3 25.4 26.9 24.2 27.1 24.2 26.7 26.1 21.9
35.0 43.2 26.2 27.1 25.3 28.9 32.1 19.1 29.3 43.7 28.2 13.5 22.3 25.8 38.3 19.7 49.1 22.3 39.2 48.0
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
2
-1054-
Units= Vmax(millivolts), Tmax(milliseconds) , Vave(millivolts)
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
MALE GROUP: 0.3 MG/KG/DAY
TEST PERIOD: PND 20
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
170.6 142.3 234.5 216.2 214.4 104.3 219.5 108.4
56.3 73.0 165.3 153.9 210.8 243.5 190.4 95.9 104.0 196.7 170.3 156.5
21.6 27.6 21.4 21.1 24.0 24.3 20.7 28.0 22.5 28.4 29.0 32.4 23.0 25.3 23.4 31.8 31.4 28.6 30.8 28.6
32.3 25.2 57.8 42.9 58.1 18.0 47.4 24.7 10.2 16.1 38.1 27.9 38.3 54.2 45.0 21.7 20.0 34.4 35.1 33.2
177.0 122.2 169.1 102.3 211.4 106.9 207.5
76.9 73.8 52.1 198.1 134.3 201.7 232.6 176.9 87.1 60.5 128.4 166.8 169.8
21.1 23.3 22.4 23.6 21.2 20.0 21.6 25.2 21.4 33.7 20.4 25.2 28.3 21.8 19.1 31.0 27.5 23.6 23.3 20.2
33.5 27.5 38.5 22.4 59.2 16.1 42.8 13.8 13.2 11.4 37.7 25.6 38.3 40.8 41.9 21.1 12.4 27.4 31.4 33.3
159.9 116.9 186.7
21.1 189.8 124.8 206.4 127.2
97.8 64.2 224.8 170.8 244.1 243.5 160.4 123.3 56.3 61.4 101.8 131.6
23.0 23.7 19.8 33.1 21.3 20.7 22.0 20.4 21.7 25.5 19.2 22.8 32.3 20.1 21.1 19.7 31.0 28.7 24.2 24.5
30.0 24.5 43.4
2.8 56.7 20.9 44.9 26.3 21.0 13.0 46.4 28.8 50.0 48.7 37.6 26.3 11.9 12.2 20.2 30.1
155.9 72.9
169.7 54.8
167.5 142.7 197.7 137.6 115.3 121.5 282.3 188.9 130.7 265.7 121.7 149.1
58.7 88.1 126.4 115.3
21.9 25.0 20.2 26.1 21.5 20.2 24.1 20.4 21.0 23.4 18.9 20.0 26.2 21.5 23.1 21.1 29.5 23.6 23.3 28.1
31.3 15.2 44.2 10.8 50.5 27.8 42.1 36.9 26.0 25.2 57.5 36.5 33.0 52.3 25.4 31.8 13.4 15.0 25.6 24.5
118.8 111.9 156.1
70.4 147.3 116.5 168.1 159.7 110.9 113.2 230.6 246.9
60.8 193.3
94.5 150.5
95.8 119.8 122.7 159.5
24.9 22.5 21.3 25.7 34.8 22.0 20.8 21.5 27.9 25.0 20.7 20.0 34.2 23.3 22.2 20.8 33.6 30.5 27.8 19.5
25.7 21.0 36.7 15.9 43.5 23.9 38.4 38.1 24.3 25.3 50.6 52.7 14.9 43.5 19.0 33.0 20.0 29.6 27.0 33.4
156.4 113.2 183.2
93.0 186.1 119.0 199.8 122.0
90.8 84.8 220.2 179.0 169.6 235.7 148.8 121.2 75.1 118.9 137.6 146.5
22.5 24.4 21.0 25.9 24.6 21.4 21.8 23.1 22.9 27.2 21.6 24.1 28.8 22.4 21.8 24.9 30.6 27.0 25.9 24.2
30.6 22.7 44.1 19.0 53.6 21.3 43.1 28.0 18.9 18.2 46.1 34.3 34.9 47.9 33.8 26.8 15.5 23.7 27.9 30.9
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)
3
-1055-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
MALE GROUP: 1.0 MG/KG/DAY
TEST PERIOD: PND 20
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
127.9 76.8
236.0 196.5 136.1 161.5 240.6 266.9 188.2 192.7 176.5 145.3
21.2 274.9 140.1 114.4 249.0
99.3 127.5
82.8
23.1 29.0 27.2 27.1 21.5 27.9 20.6 20.4 23.2 24.7 26.0 30.1 36.8 19.7 31.2 35.4 20.9 33.6 21.7 29.9
27.3 17.8 62.5 46.3 28.1 36.4 52.2 63.4 29.9 44.3 48.4 36.3
4.1 59.0 38.4 30.4 57.4 21.4 29.0 20.8
111.5 38.1
179.4 146.5
62.6 173.5 250.6 175.1 217.3 135.0 133.9 119.6
15.4 216.7
95.5 90.9 273.5 59.8 102.9 86.3
24.4 27.3 24.8 23.1 30.5 24.4 20.3 20.9 19.9 27.9 20.0 27.2 35.9 24.3 26.1 27.7 19.6 30.8 22.2 25.2
22.0 9.5
44.8 32.6 16.5 34.1 48.1 37.0 33.6 27.2 34.3 28.7
3.1 45.6 22.4 22.5 61.9 12.6 23.3 19.4
157.5 53.7
111.1 35.0 81.6
194.0 152.4 154.9 225.8
75.2 112.9
99.7 13.3 166.2 77.6 70.3 294.4 70.3 126.7 62.9
20.7 28.0 30.2 34.4 25.9 23.0 22.7 22.6 20.0 38.2 21.1 29.0 32.5 23.9 27.2 26.0 19.9 29.4 23.3 29.2
30.6 10.2 25.6
8.3 15.6 43.5 32.1 35.0 39.3 15.8 29.1 19.8
2.0 40.3 19.0 16.0 72.4 15.3 30.8 14.8
77.7 56.3 46.1 72.0 104.1 150.0 186.8 204.4 237.8 143.4 117.6 126.2 17.8 141.0 84.9 63.4 240.9 78.0 87.1 76.6
24.5 23.6 28.2 22.2 23.8 20.6 20.5 20.2 22.1 22.4 19.6 20.5 21.0 20.3 31.5 20.8 21.0 22.6 28.5 23.1
15.8 11.5
9.7 15.2 20.0 34.4 31.2 43.0 37.6 30.5 31.0 24.2
2.7 27.1 20.5 11.4 61.6 14.7 21.1 18.3
63.4 57.4 80.3 85.0 119.2 131.2 200.3 218.1 206.7 126.5 91.8 162.7 12.0 216.3 78.6 134.0 201.6 123.6 25.7 84.7
23.0 35.8 30.4 24.8 19.7 25.2 27.4 20.4 22.8 21.6 22.4 20.3 30.4 19.1 24.0 21.4 24.6 21.2 26.7 21.8
11.4 11.3 23.7 20.1 25.3 30.3 42.2 51.8 38.8 30.7 20.6 36.4
1.9 41.4 19.0 31.0 47.6 26.1
6.1 20.4
107.6 56.5
130.6 107.0 100.7 162.0 206.1 203.9 215.2 134.6 126.5 130.7
15.9 203.0
95.3 94.6 251.9 86.2 94.0 78.7
23.1 28.7 28.2 26.3 24.3 24.2 22.3 20.9 21.6 27.0 21.8 25.4 31.3 21.5 28.0 26.3 21.2 27.5 24.5 25.8
21.4 12.1 33.3 24.5 21.1 35.7 41.2 46.0 35.8 29.7 32.7 29.1
2.8 42.7 23.9 22.3 60.2 18.0 22.1 18.7
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
4
-1056-
Units= Vmax(millivolts), Tmax(milliseconds) , Vave(millivolts)
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
FEMALE GROUP: 0 MG/KG/DAY
TEST PERIOD: PND 20
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
171.0 217.6 158.4 212.7 292.4 331.8 167.6 205.0 272.5 126.1
63.1 188.5 113.4 240.1
79.7 125.8 244.0 204.4 256.4 346.4
19.2 39.8 31.0 37.1 24.6 19.9 21.5 19.7 25.9 34.4 33.0 19.6 37.0 22.0 28.5 21.7 26.1 23.0 21.8 23.8
34.4 52.5 32.7 49.8 63.4 67.9 32.4 46.3 66.4 28.5 11.0 42.5 28.9 53.7 15.0 24.7 56.9 49.3 54.8 79.7
166.9 140.4 147.2 153.5 199.5 304.8 150.8 218.0 278.1 103.8
71.4 161.9 138.0
69.2 107.6 132.8 245.6 205.3 261.1 310.7
20.4 20.3 24.3 27.9 23.7 19.6 22.7 19.4 23.1 22.5 24.2 19.3 27.8 25.8 21.7 22.4 24.4 20.2 20.2 23.6
31.6 28.8 28.0 40.0 46.2 60.5 28.5 52.4 64.7 20.9 15.0 37.2 24.7 13.5 20.6 26.3 54.4 47.2 55.4 70.7
159.9 131.5 102.1 150.6 156.8 293.1 101.5 204.9 306.1 113.4
83.4 167.3 184.8
75.0 73.6 101.5 216.1 230.4 297.1 117.8
19.4 20.3 26.1 26.5 23.7 20.0 26.0 19.7 23.3 21.0 21.9 21.0 19.5 28.0 22.6 23.0 26.3 20.1 21.8 21.7
26.7 27.3 21.4 38.5 31.8 58.0 18.3 47.9 69.6 25.2 14.8 43.9 25.5 16.8 17.1 21.2 50.9 52.0 65.0 27.8
170.0 115.2 129.9 137.3 246.7 241.0
92.9 69.7 332.7 192.5 127.7 159.3 128.2 163.0 83.7 142.5 210.1 188.4 296.4 143.1
19.2 22.8 21.2 21.8 22.2 21.0 25.6 25.8 21.0 20.3 20.1 22.0 20.9 22.8 26.2 21.0 21.2 21.2 20.1 24.3
32.5 27.4 31.7 37.6 52.6 48.8 18.9 17.8 77.5 53.5 25.2 44.6 21.4 34.2 20.4 32.9 50.1 44.3 58.4 35.4
136.8 138.7 174.8 145.1 260.5 123.4
98.4 100.4 204.9
72.0 144.4
73.7 116.7 169.2 152.3
87.9 189.6 118.4 224.1 216.4
20.4 21.7 19.9 36.2 20.8 36.5 21.4 20.8 22.0 25.8 19.1 30.6 23.3 19.7 20.9 26.9 22.8 21.9 20.6 22.7
27.3 34.5 40.5 41.1 54.6 20.8 20.1 18.7 49.9 18.7 29.2 21.6 20.3 31.7 32.1 20.7 49.6 31.2 49.4 49.1
160.9 148.7 142.5 159.8 231.2 258.8 122.2 159.6 278.9 121.6
98.0 150.1 136.2 143.3
99.4 118.1 221.1 189.4 267.0 226.9
19.7 25.0 24.5 29.9 23.0 23.4 23.4 21.1 23.1 24.8 23.7 22.5 25.7 23.7 24.0 23.0 24.2 21.3 20.9 23.2
30.5 34.1 30.9 41.4 49.7 51.2 23.6 36.6 65.6 29.4 19.0 38.0 24.2 30.0 21.0 25.2 52.4 44.8 56.6 52.5
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)
5
-1057-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
FEMALE GROUP: 0.1 MG/KG/DAY
TEST PERIOD: PND 20
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
193.4 258.6 204.3 256.4 287.3 178.8 156.6 171.0
89.2 200.4 188.0
98.6 256.1 142.1 113.5 157.1 257.8 214.5 102.9 188.9
20.5 23.2 28.9 24.6 20.8 31.4 29.9 24.0 31.2 19.6 24.4 27.7 24.1 27.2 31.0 30.4 26.2 21.3 31.3 25.2
44.7 54.2 43.6 58.1 64.0 39.6 32.6 34.5 21.1 47.5 37.4 17.3 46.9 35.4 26.2 34.5 75.6 42.8 20.3 47.5
165.2 166.7 134.6 344.4 285.2 103.3 185.2 187.8 126.8 146.9 133.8 120.5
83.0 217.2 111.8 105.4 236.7 117.3
89.9 200.9
20.6 28.2 21.0 20.6 25.2 26.4 22.0 26.6 23.0 19.6 21.7 23.9 22.8 27.1 23.3 29.6 20.9 27.2 24.1 22.8
33.2 38.6 26.8 74.4 63.3 21.3 37.4 34.9 27.7 32.4 27.1 22.6 14.8 44.7 27.3 20.2 70.3 25.2 17.6 45.0
62.1 164.8 176.4 287.6 145.0 136.2 114.7 293.5 170.3 177.8
59.1 99.3 90.0 121.0 70.4 86.8 246.6 85.3 114.7 201.6
27.2 22.2 21.1 20.8 25.6 20.1 21.6 20.5 20.2 19.9 23.9 29.7 32.5 21.8 23.9 32.7 21.5 21.3 21.2 23.3
11.3 32.4 36.4 67.0 32.2 25.9 22.7 47.7 37.1 39.5 10.7 19.2 16.6 28.0 15.7 20.1 73.8 15.5 26.8 50.5
93.3 153.6
48.7 154.8 262.7 141.3 149.0 257.8 199.5 166.9
86.5 125.8
83.4 101.7 136.7
81.6 220.1
87.6 110.3 193.4
26.9 20.7 27.5 26.2 19.4 20.0 25.2 20.1 19.9 19.9 30.9 27.3 28.3 23.9 24.0 26.9 21.8 30.3 24.0 21.1
21.4 33.9 10.1 35.1 55.9 27.8 31.0 50.8 42.8 36.9 18.3 22.6 15.4 24.0 26.2 17.5 59.9 20.5 26.6 38.4
93.0 191.1
83.5 137.0 273.3 124.2 154.3 321.8 181.0 195.7
77.4 57.5 157.8 79.4 103.5 44.6 143.2 106.4 100.4 183.6
28.9 21.7 24.1 28.1 19.1 21.8 23.5 19.8 20.0 20.0 23.3 31.3 22.9 27.7 24.4 25.6 23.3 21.8 26.6 19.6
23.1 44.3 20.0 34.7 60.2 29.6 35.7 59.1 43.1 46.6 15.4 11.9 32.5 17.7 21.4 10.3 40.1 21.9 26.5 41.8
121.4 187.0 129.5 236.0 250.7 136.8 152.0 246.4 153.4 177.5 109.0 100.3 134.1 132.3 107.2
95.1 220.9 122.2 103.6 193.7
24.8 23.2 24.5 24.1 22.0 23.9 24.4 22.2 22.9 19.8 24.8 28.0 26.1 25.5 25.3 29.0 22.7 24.4 25.4 22.4
26.7 40.7 27.4 53.9 55.1 28.8 31.9 45.4 34.4 40.6 21.8 18.7 25.2 30.0 23.4 20.5 63.9 25.2 23.6 44.6
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)
6
-1058-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
FEMALE GROUP: 0.3 MG/KG/DAY
TEST PERIOD: PND 20
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
331.9 111.3 134.5 151.3 108.0 176.9 186.8 149.6
65.6 233.8 139.2 300.2 150.5
94.4 113.8 122.2 134.1 225.7 140.7 320.3
20.7 26.6 27.8 31.3 27.3 22.3 18.9 34.1 34.1 21.7 23.7 20.6 26.7 31.8 21.1 22.4 21.2 20.3 23.0 22.5
65.4 22.5 28.0 32.8 23.3 39.3 30.9 32.6 14.1 46.5 28.6 67.7 30.7 24.5 26.3 26.6 31.4 43.5 30.6 66.4
282.9 95.5
127.0 227.1
92.6 206.8 201.0 159.3
85.0 227.0 176.0 315.7 150.0
71.7 151.2
83.6 129.0 153.2 149.9 111.3
20.8 22.4 22.2 20.4 22.4 20.0 18.8 22.7 23.1 27.6 23.4 19.9 23.7 29.6 19.9 23.7 19.9 21.8 20.2 23.3
67.3 19.3 28.9 38.4 18.5 47.9 38.4 38.5 14.5 46.6 33.3 70.6 31.7 14.8 29.2 22.6 30.5 33.8 32.8 20.6
264.9 97.3 99.8
163.6 117.7 146.5 185.6 175.1
99.9 336.3 210.5 314.0 183.0
57.5 156.3 117.4 133.5 111.9 155.4 140.5
20.6 20.0 23.7 25.2 31.9 23.1 18.9 21.4 19.1 22.5 19.3 20.0 20.4 37.9 20.2 20.4 19.4 30.4 21.4 20.6
63.3 20.7 21.1 31.1 23.4 36.1 40.4 38.8 18.7 72.3 40.0 72.2 39.3 10.6 32.1 34.7 33.0 25.1 37.4 26.4
130.2 99.0
156.9 36.1
112.9 186.3 202.6 153.3 103.2 275.0 276.9 316.6 197.5
56.3 162.0
97.0 127.1
79.4 163.4 118.1
25.2 20.0 19.6 27.0 26.0 20.5 18.9 23.5 23.2 20.1 19.6 20.2 20.4 27.4 19.9 26.7 21.2 20.4 21.8 23.6
30.4 22.0 31.7
8.5 21.1 47.8 43.3 31.4 17.0 65.4 55.6 70.1 42.7 13.5 39.4 26.7 30.7 13.9 43.5 27.1
269.6 98.1
183.9 59.5
128.6 129.0 169.2 200.7
97.6 153.9 269.4 122.2
32.4 82.3 74.5 64.8 53.7 55.7 163.3 127.1
21.0 19.9 19.7 37.2 20.7 20.9 19.1 24.5 19.9 23.4 21.0 23.2 23.4 25.5 28.6 26.3 31.9 26.4 26.8 28.8
59.1 21.8 41.1 15.9 26.0 34.5 40.5 38.5 20.7 38.9 62.5 34.7
7.7 16.4 16.7 18.4 15.0
9.9 43.3 24.5
255.9 100.2 140.4 127.5 112.0 169.1 189.0 167.6
90.3 245.2 214.4 273.7 142.7
72.4 131.6
97.0 115.5 125.2 154.5 163.5
21.7 21.8 22.6 28.2 25.7 21.4 18.9 25.2 23.9 23.1 21.4 20.8 22.9 30.4 21.9 23.9 22.7 23.9 22.6 23.8
57.1 21.3 30.2 25.3 22.5 41.1 38.7 36.0 17.0 53.9 44.0 63.1 30.4 16.0 28.7 25.8 28.1 25.2 37.5 33.0
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)
7
-1059-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
FEMALE GROUP: 1.0 MG/KG/DAY
TEST PERIOD: PND 20
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
86.9 117.3 145.7 105.8 109.4 149.1 254.3 164.3 188.5
77.6 133.9 244.2 101.0 296.0 234.3 269.8 255.5 141.0 116.2 280.6
27.6 33.5 28.4 28.2 27.1 21.8 37.0 27.8 27.0 29.0 31.6 23.4 30.3 22.4 20.2 21.0 22.4 29.0 23.5 19.1
19.0 28.3 31.9 24.3 21.9 32.2 49.7 40.8 42.6 14.0 32.4 50.7 28.0 61.1 52.0 53.1 54.4 33.5 24.0 52.9
48.6 91.1 106.9 44.2 32.6 73.6 207.3 199.0 153.8 113.8 152.3 222.2 87.1 185.9 220.4 234.1 188.1 103.4 115.2 236.5
25.5 26.9 23.8 38.1 35.1 23.4 20.7 25.4 25.6 20.9 23.4 19.9 27.5 25.9 20.0 23.7 20.0 25.1 18.8 19.5
9.6 18.5 21.2
9.7 6.9 16.6 43.0 50.5 37.2 20.0 26.0 39.9 24.1 42.7 45.2 48.7 39.3 24.4 21.0 48.3
78.3 111.1 109.8 119.4
39.4 79.3 155.5 160.4 73.9 98.5 159.1 174.9 57.6 132.8 217.5 256.6 61.4 115.4 99.6 260.1
26.1 21.0 20.6 22.5 38.4 32.6 28.5 19.2 21.5 21.7 19.3 19.5 28.5 22.8 20.0 22.7 24.5 23.6 20.0 19.6
15.3 19.4 22.9 28.9
6.7 15.5 34.1 34.4 14.0 18.8 30.2 31.7 16.3 26.5 46.8 53.4 12.3 29.6 19.6 56.4
43.7 78.0 125.3 160.1 52.3 64.8 193.8 167.1 94.3 27.8 187.2 189.2 52.2 132.1 215.4 184.8 93.1 54.0 78.9 218.3
25.6 22.3 21.7 20.2 36.8 25.2 20.2 19.5 24.5 27.3 19.5 19.1 27.7 22.7 20.4 22.4 30.3 28.7 31.4 19.6
7.7 14.7 26.6 39.3
9.8 13.7 37.7 45.0 23.1
4.2 37.0 39.2 12.2 26.4 45.3 35.8 24.7 12.6 18.9 49.8
123.6 114.6 108.4 176.3
60.0 195.1
99.1 180.1
83.7 25.5 152.3 171.7 57.5 283.5 196.6 188.7 108.7 67.0 61.4 227.4
19.4 21.2 25.4 20.6 32.4 22.7 25.0 20.7 30.9 27.6 20.4 19.5 27.0 19.4 20.4 21.8 28.1 26.4 32.8 19.4
23.4 21.5 23.8 45.5 10.9 41.0 21.4 49.0 17.3
4.6 36.2 39.3 12.9 63.7 42.4 38.8 28.7 14.4 14.0 51.2
76.2 102.4 119.2 121.2
58.7 112.4 182.0 174.2 118.8
68.6 157.0 200.4
71.1 206.1 216.8 226.8 141.4
96.2 94.3 244.6
24.8 25.0 24.0 25.9 34.0 25.1 26.3 22.5 25.9 25.3 22.8 20.3 28.2 22.6 20.2 22.3 25.1 26.6 25.3 19.4
15.0 20.5 25.3 29.5 11.2 23.8 37.2 43.9 26.8 12.3 32.4 40.2 18.7 44.1 46.3 46.0 31.9 22.9 19.5 51.7
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)
8
-1060-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
MALE GROUP: 0 MG/KG/DAY
TEST PERIOD: PND 60
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
224.6 414.7 154.6 199.5 180.2 115.3 114.3
85.4 147.3 164.4 1011.6
38.5 60.1 47.2 109.4 255.7 83.0 202.6 194.2 1123.3
27.2 54.5 31.3 112.3 26.3 32.3 32.4 54.5 29.7 39.3 29.4 22.6 36.3 23.0 33.6 22.0 25.9 34.0 26.0 38.2 24.1 198.9 37.1 8.7 46.7 12.7 33.0 11.7 36.0 22.2 32.9 60.0 45.8 16.6 34.6 48.6 26.6 44.0 25.4 200.8
174.3 351.8 176.4 120.6 106.9 110.1
95.2 28.4 97.0 58.0 768.6 14.7 51.8 101.4 161.2 249.1 114.3 114.0 201.2 799.8
21.6 23.8 30.8 26.6 26.1 37.0 35.8 55.0 31.2 31.3 21.0 49.3 45.3 38.8 29.6 30.7 31.0 34.0 33.9 21.3
36.7 72.2 41.5 27.7 23.5 18.5 22.6
7.5 24.2 12.9 168.9
2.4 13.5 22.6 35.1 53.4 22.6 28.6 46.2 146.5
100.8 180.9
95.2 228.4
71.8 179.5
70.7 48.8 31.0 152.5 621.6 15.6 100.6 52.3 56.9 118.8 36.3 115.5 261.1 1011.4
29.0 23.1 36.5 25.7 31.9 29.0 41.4 36.3 29.5 31.6 24.3 37.3 29.1 26.1 43.4 32.0 25.8 41.8 29.5 25.9
18.2 37.0 18.9 54.4 17.1 34.1 13.7 10.9
6.4 34.7 128.3
2.9 20.1
9.9 12.2 24.2
7.7 28.5 57.3 191.6
136.1 225.9
98.1 243.7 101.5 101.7
53.3 49.5 27.9 32.0 631.6 25.0 62.4 72.9 52.4 94.7 29.7 83.0 274.2 458.5
29.3 31.7 35.7 27.0 24.8 33.1 35.3 48.4 36.6 40.5 27.1 49.7 27.1 32.6 44.0 25.5 40.6 35.7 30.3 22.9
32.2 48.4 17.2 54.0 23.5 17.9 10.6 14.1
4.9 8.3 131.2 5.2 10.8 13.9 12.4 19.8 6.0 20.8 61.9 84.9
104.4 221.8
91.4 123.5
99.1 40.4 52.4 36.8 57.5 25.3 261.9 14.5 52.2 58.7 32.2 61.0 65.1 87.2 181.1 498.2
27.2 32.2 29.3 35.5 32.3 45.0 27.4 41.8 55.1 42.2 28.1 56.7 25.8 29.7 37.7 52.9 26.9 37.5 31.3 23.8
26.6 52.4 20.0 23.8 21.9
9.7 12.0
9.7 14.3
5.1 52.9
2.7 8.9 10.5 7.1 15.3 13.1 21.4 34.7 94.0
148.0 279.0 123.1 183.1 111.9 109.4
77.2 49.8 72.1 86.4 659.1 21.7 65.4 66.5 82.4 155.9 65.7 120.5 222.4 778.2
26.9 28.4 31.7 29.4 29.0 34.7 35.2 43.0 35.7 34.3 24.9 46.0 34.8 32.0 38.1 34.8 34.0 36.7 30.3 23.9
33.6 64.5 26.0 42.9 25.1 20.6 16.4 12.8 16.8 19.8 136.0
4.4 13.2 13.7 17.8 34.5 13.2 29.6 48.8 143.6
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)
9
-1061-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
MALE GROUP: 0.1 MG/KG/DAY
TEST PERIOD: PND 60
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
581.2 161.3
75.5 57.8 380.6 39.8 52.3 134.8 73.9 76.8 84.1 94.6 207.1 116.3 144.9 42.5 78.3 122.0 89.2 124.0
22.7 31.3 38.6 33.9 24.5 35.8 58.3 24.3 41.0 31.5 27.9 40.7 24.6 30.0 32.5 41.2 42.5 37.5 34.1 30.3
123.9 32.7 16.7 11.3 78.2 8.6 13.9 35.0 21.0 19.3 14.5 23.4 45.2 24.4 35.1 10.0 20.8 32.8 24.2 26.0
379.9 161.8
77.0 55.1 286.6 28.2 42.1 155.6 67.6 67.8 104.2 226.6 133.9 69.5 37.9 35.2 118.7 61.6 72.3 64.8
26.6 34.6 40.1 38.0 27.9 51.6 37.1 25.5 45.7 35.0 33.7 29.0 22.8 39.3 56.5 30.7 30.0 41.0 28.2 34.8
76.3 33.8 17.8 11.9 60.3
5.6 9.3 36.8 15.6 16.2 20.0 55.0 28.1 16.6 9.4 6.7 25.5 12.1 16.5 15.5
179.2 303.0
83.0 21.9 261.4 10.4 29.1 95.9 63.0 90.1 48.5 73.9 224.0 51.3 42.2 56.2 91.9 52.4 104.4 71.0
31.5 28.7 22.6 41.5 28.8 44.1 46.3 27.5 40.1 27.6 46.1 33.6 24.9 41.5 29.2 34.0 29.7 49.8 48.9 30.2
35.5 55.1 18.8
4.1 56.1
1.2 7.6 22.2 12.8 17.3 8.7 18.7 51.8 10.4 9.6 13.2 27.1 12.1 22.1 17.7
272.0 68.0 55.5 30.5
282.3 9.8
32.5 72.0 58.2 71.3 54.3 262.6 275.2 42.9 59.4 50.1 56.6 72.1 37.4 56.6
25.5 38.1 61.2 40.4 28.4 31.6 44.8 41.7 36.6 31.9 33.6 27.5 23.5 25.0 44.5 35.8 42.8 47.8 43.0 28.5
49.7 12.8 14.1
7.8 59.7
0.9 7.2 20.1 14.8 13.8 10.5 56.7 59.7 7.6 13.1 10.5 15.5 22.4 9.0 9.1
494.9 26.2 48.7
108.3 178.0
9.2 70.1 67.7 51.0 38.9 176.3 49.4 252.5 25.6 83.8 63.8 88.3 79.5 40.4 68.8
20.1 32.9 48.4 46.4 29.1 37.9 32.9 37.4 31.2 31.5 29.4 35.7 22.7 44.5 33.9 33.0 39.2 34.4 51.4 36.9
84.3 4.5
13.8 33.2 36.5
1.2 15.1 12.5 11.5
7.8 31.2 12.2 52.4
4.5 17.3 11.6 21.1 18.6
9.1 14.4
381.4 144.1
67.9 54.7 277.8 19.5 45.2 105.2 62.7 69.0 93.5 141.4 218.5 61.1 73.6 49.6 86.8 77.5 68.7 77.0
25.3 33.1 42.2 40.0 27.7 40.2 43.9 31.3 38.9 31.5 34.1 33.3 23.7 36.1 39.3 34.9 36.8 42.1 41.1 32.1
73.9 27.8 16.2 13.7 58.2
3.5 10.6 25.3 15.1 14.9 17.0 33.2 47.4 12.7 16.9 10.4 22.0 19.6 16.2 16.5
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
10
-1062-
Units= Vmax(millivolts), Tmax(milliseconds)/ Vave(millivolts)
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
MALE GROUP: 0.3 MG/KG/DAY
TEST PERIOD: PND 60
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
147.7 58.3
156.6 76.4 32.2 61.3
185.6 32.3
249.9 66.0
206.9 156.6
83.4 476.1 314.1 113.6 114.2 324.8 178.0 217.7
24.4 37.4 34.9 37.2 54.1 33.7 21.5 32.2 23.6 41.6 25.2 29.7 38.0 30.6 28.7 31.3 40.3 22.8 35.5 35.7
30.2 12.3 29.5 17.3
6.8 14.5 36.7
7.0 59.5 17.6 43.6 33.7 22.5 105.5 70.1 24.7 30.2 66.6 38.4 41.4
209.6 86.5 65.7 25.6 55.8 53.0
103.9 27.7
247.4 106.0 191.1 312.6
59.0 383.0 415.6
57.3 64.1 215.3 221.6 134.1
25.7 33.4 38.9 29.2 36.4 34.6 28.2 51.8 26.9 30.2 24.9 29.6 46.7 28.9 23.8 37.1 39.7 26.5 27.0 42.0
43.5 15.3 15.0
5.9 13.8 10.0 20.8
6.1 50.5 20.7 37.8 64.0 16.6 90.2 77.9 13.2 14.6 44.2 45.4 25.5
88.9 40.7 70.6 49.7 15.9 78.5 150.4 45.3 205.1 120.3 146.2 195.4 34.8 228.0 379.6 29.4 67.1 191.7 186.8 139.0
34.0 24.1 34.1 37.9 40.7 32.1 21.6 39.1 28.6 28.0 23.8 30.7 53.9 31.3 23.9 46.0 27.7 29.6 26.9 38.5
19.6 6.5
13.3 11.1
2.2 15.9 30.6 13.3 34.7 24.9 30.2 42.5
9.3 49.5 70.1
4.7 14.9 46.8 39.9 26.2
172.5 68.7
223.6 24.3 27.8 58.2 95.9 24.7 93.3 38.8
119.0 35.4 90.8
161.4 212.2
12.6 23.5 172.2 102.6 149.7
37.0 28.0 25.3 46.6 49.3 31.3 23.1 40.6 30.4 21.4 26.1 36.5 27.2 25.4 23.3 20.0 32.3 34.2 28.0 35.9
32.9 11.6 48.8
5.3 7.0 11.8 19.6 6.4 15.3 7.5 24.1 9.0 17.9 33.0 39.6 1.9 4.9 39.8 20.1 27.4
169.4 46.0
207.6 23.4 34.5 27.5
101.2 33.9
131.0 129.1
81.7 55.6 55.1 200.1 362.0 60.5 43.1 135.8 271.3 92.2
31.5 43.8 24.0 39.8 37.1 47.3 25.7 57.1 30.2 24.8 42.2 38.8 36.2 31.7 21.8 47.5 30.2 34.0 27.5 36.1
24.6 8.6
49.5 4.5 5.1 4.6
19.8 10.3 21.2 23.2 18.6 12.4 13.0 48.8 71.7 13.2
9.2 29.1 49.0 16.3
157.6 60.0
144.8 39.9 33.2 55.7
127.4 32.8
185.3 92.0
149.0 151.1
64.6 289.7 336.7
54.7 62.4 208.0 192.1 146.5
30.5 33.3 31.4 38.1 43.5 35.8 24.0 44.2 27.9 29.2 28.4 33.1 40.4 29.6 24.3 36.4 34.0 29.4 29.0 37.6
30.2 10.9 31.2
8.8 7.0 11.4 25.5 8.6 36.2 18.8 30.9 32.3 15.9 65.4 65.9 11.5 14.8 45.3 38.6 27.4
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
11
-1063-
Units= Vmax(millivolts), Tmax(milliseconds)/ Vave(millivolts)
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
MALE GROUP: 1.0 MG/KG/DAY
TEST PERIOD: PND 60
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
203.6 150.1 112.1
27.6 383.8 131.5 149.0
83.0 103.3
55.3 176.0 267.4
19.3 194.3
81.1 187.4 237.9
51.0 104.7 273.6
29.9 30.6 39.2 18.0 27.2 37.1 29.4 32.7 31.2 36.0 30.3 30.0 42.8 27.0 34.3 27.9 28.1 44.6 37.3 26.0
45.5 39.4 26.3
4.1 65.5 32.0 35.3 18.7 23.7 14.1 31.0 63.8
4.4 32.8 19.2 35.3 46.3 11.6 21.4 48.8
97.3 67.9 55.0 17.9 317.1 32.3 219.5 62.7 68.0 48.3 57.1 355.6 15.3 188.4 115.2 112.9 162.6 38.0 46.0 93.1
21.6 40.3 45.7 13.9 20.0 34.3 26.0 47.9 40.8 46.5 33.0 28.7 57.3 25.1 32.4 35.2 27.9 31.8 39.4 31.8
18.6 15.0 14.1
2.6 50.4
7.5 50.5 14.9 14.4 10.9 12.6 79.8
2.4 38.0 23.2 22.3 31.0
7.3 7.9 19.7
90.5 57.5 38.0 17.7 291.3 118.1 61.5 46.2 39.3 60.5 123.6 179.2 14.1 128.4 40.8 99.6 42.5 21.5 24.6 99.8
30.4 32.6 42.6 16.3 24.7 32.5 27.1 37.8 43.1 27.2 38.2 28.3 52.1 39.4 41.7 37.2 50.9 47.5 53.5 34.4
19.1 14.2
6.2 1.7 50.9 22.9 12.8 8.1 9.0 15.0 30.4 42.1 2.2 22.8 6.8 20.4 11.1 4.6 4.2 21.9
45.5 77.7 96.9 16.2 245.6 38.9 147.6 24.9 37.4 21.1 83.9 136.3 10.9 143.0 35.5 39.8 110.3 50.0 30.2 327.5
34.8 33.7 31.9 14.9 36.3 35.9 28.5 39.8 46.1 38.2 37.1 29.0 60.6 24.0 40.0 36.2 41.7 48.4 41.6 28.8
9.5 20.3 27.1
1.6 40.4
7.5 34.2
4.5 9.8 4.2 18.8 30.0 1.6 26.1 6.7 7.5 22.0 13.8 5.1 65.3
56.7 15.5 32.7 12.4 269.9 16.7 175.2 29.6 95.5 56.6 126.8 33.3 30.8 167.8 55.1 11.4 25.7 18.6 50.3 135.9
31.4 34.9 25.8 14.7 34.6 33.3 30.5 29.8 31.0 42.6 28.4 36.9 59.2 28.1 36.2 25.1 48.5 42.4 38.9 30.9
12.0 2.3 7.4 0.9
46.3 2.9
33.8 5.1
20.4 10.6 23.7
5.9 7.7 29.2 12.5 1.8 6.7 3.8 11.1 27.6
98.7 73.7 66.9 18.4 301.5 67.5 150.6 49.3 68.7 48.4 113.5 194.4 18.1 164.4 65.5 90.2 115.8 35.8 51.2 186.0
29.6 34.4 37.0 15.6 28.6 34.6 28.3 37.6 38.4 38.1 33.4 30.6 54.4 28.7 36.9 32.3 39.4 42.9 42.1 30.4
20.9 18.2 16.2
2.2 50.7 14.6 33.3 10.3 15.5 11.0 23.3 44.3
3.7 29.8 13.7 17.5 23.4
8.2 9.9 36.7
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
12
-1064-
Units= Vmax(millivolts), Tmax(milliseconds)/ Vave(millivolts)
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
FEMALE GROUP: 0 MG/KG/DAY
TEST PERIOD: PND 60
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
159.3 146.7 105.6 103.2 221.1
56.4 96.6 179.7 101.6 78.4 93.0 35.4 130.3 42.6 32.8 79.0 115.1 121.5 154.0 286.7
28.9 30.5 41.8 28.3 27.8 35.5 37.5 35.1 29.6 24.5 33.9 41.8 29.1 31.3 32.6 26.5 29.8 34.5 30.5 22.9
35.5 32.0 19.4 19.8 52.5 11.9 18.8 34.1 18.4 13.0 16.6
7.9 32.3 10.2
4.6 20.7 23.5 25.9 32.7 55.1
143.4 158.5
47.9 82.2 230.1 23.4 36.2 40.2 44.2 58.2 32.0 64.1 75.5 32.4 16.3 73.4 56.8 44.3 55.4 147.8
27.9 39.7 29.3 28.9 26.3 35.2 30.7 34.2 35.2 25.9 31.5 46.5 46.9 40.2 39.3 46.3 37.1 34.8 32.7 26.9
28.9 32.6
8.8 17.2 44.8
4.2 8.9 7.3 8.5 11.1 8.8 14.6 17.3 6.0 1.9 20.2 13.5 7.5 12.2 24.5
87.5 87.5 66.4 62.9 105.2 19.6 51.5 28.6 33.3 105.7 31.8 31.9 56.8 29.9 12.1 71.2 36.8 71.4 87.1 111.8
37.5 28.3 30.3 37.4 35.5 33.9 40.7 32.0 38.4 33.5 40.5 41.9 43.3 45.5 40.4 45.2 37.8 31.3 37.5 31.0
14.8 16.8 14.7 12.4 17.7
3.1 12.5
4.8 5.4 17.0 4.8 8.8 13.1 7.1 1.6 18.6 7.0 14.1 19.3 16.6
82.8 57.9 43.0 137.5 22.2 21.3 59.5 56.7 26.3 43.2 58.1 25.7 23.1 24.4 41.3 48.4 44.6 49.4 71.9 87.5
35.4 31.1 32.2 25.6 40.7 41.1 38.2 25.7 40.4 25.5 30.6 29.5 48.8 50.8 26.9 35.5 45.3 42.8 37.9 27.8
16.0 10.5
8.0 26.4
3.3 3.3 14.2 10.4 4.3 9.2 9.6 5.4 4.7 4.8 5.5 12.2 10.8 9.8 18.2 16.0
118.8 41.1 68.2 84.2
101.9 61.5 39.9 38.0 36.1 46.7 17.0 18.0 32.8 21.2 30.3 35.7 46.2 72.3 53.2 86.7
31.6 36.2 34.3 28.5 32.0 36.7 31.7 31.7 39.0 37.5 44.7 38.9 37.9 49.3 29.4 42.2 27.5 41.8 43.3 26.1
24.2 5.9
14.5 15.6 17.7 12.0
9.1 6.0 8.2 9.9 3.3 3.6 6.8 5.5 4.0 6.7 9.5 15.4 11.9 14.1
118.4 98.3 66.2 94.0
136.1 36.4 56.7 68.6 48.3 66.4 46.4 35.0 63.7 30.1 26.6 61.5 59.9 71.8 84.3
144.1
32.3 33.2 33.6 29.7 32.5 36.5 35.8 31.7 36.5 29.4 36.2 39.7 41.2 43.4 33.7 39.1 35.5 37.0 36.4 26.9
23.9 19.6 13.1 18.3 27.2
6.9 12.7 12.5
9.0 12.0
8.6 8.1 14.8 6.7 3.5 15.7 12.9 14.5 18.9 25.3
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
13
-1065-
Units= Vmax(millivolts), Tmax(milliseconds)/ Vave(millivolts)
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
FEMALE GROUP: 0.1 MG/KG/DAY
TEST PERIOD: PND 60
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
70.0 126.9
87.8 65.0 88.9 17.8 51.1 102.3 95.9 73.9 84.9 53.4 75.8 150.3 76.2 89.9 61.8 105.0 74.1 122.4
32.3 27.5 34.6 26.7 39.9 49.3 51.0 24.6 32.5 39.7 37.0 30.9 38.7 34.5 43.1 30.4 29.0 30.5 23.3 28.6
13.5 29.3 19.1 10.3 16.9
3.2 11.7 20.8 18.7 16.0 18.5 11.2 16.9 29.1 12.4 17.6 13.3 20.3 15.7 25.4
98.8 51.6 92.9 45.2 60.3 24.8 56.9 74.0 67.9 64.5 29.3 24.1 33.9 53.1 41.0 45.0 59.8 97.4 57.7 134.6
27.8 29.5 30.4 30.0 26.8 35.4 37.1 32.7 34.1 46.8 40.0 43.7 43.4 34.6 45.3 39.1 37.9 34.4 34.5 31.9
18.2 11.1 22.9
8.4 10.7
4.1 10.8 13.2 14.7 12.8
5.9 3.9 7.3 11.2 8.7 9.6 12.4 19.7 11.7 21.7
68.8 49.9 63.8 32.4 78.6 38.5 49.7 103.3 31.2 78.4 29.5 13.3 78.1 29.9 18.3 30.5 20.2 102.1 22.6 187.4
25.2 32.5 43.2 39.7 27.1 42.7 34.0 42.8 30.4 25.2 30.9 41.2 33.6 31.5 42.5 32.1 30.0 27.2 27.9 24.3
12.2 9.6
15.2 5.9
13.8 7.4 8.0
19.6 5.6
12.8 5.9 1.8
16.3 5.2 2.3 5.6 4.0
17.3 5.5
31.9
46.9 56.7 50.2 32.9 52.1 16.0 27.5 38.3 18.5 33.0 65.6 26.2 71.4 11.6 44.3 30.1 32.0 69.9 45.0 169.0
34.5 24.2 38.8 46.2 39.0 42.0 38.8 47.7 32.7 30.3 46.5 38.7 29.5 37.0 39.8 33.4 45.7 26.8 49.0 25.1
8.6 12.9
9.0 7.7 9.1 3.0 5.9 8.2 3.1 5.3 12.1 4.8 10.6 1.4 8.0 4.9 6.3 15.8 9.1 30.5
51.5 96.0 71.7 50.5 32.5 24.4 23.3 94.9 14.7 94.9 27.8 36.3 20.9 47.5 14.3 52.9 51.5 109.7 28.6 136.6
43.7 29.5 28.7 35.0 45.5 35.4 32.2 44.0 38.8 33.3 32.7 41.9 58.9 29.2 42.0 38.9 35.2 30.4 33.6 28.9
8.9 18.4 15.7
9.4 5.0 5.3 3.7 17.7 2.0 20.1 4.4 7.6 4.5 8.7 2.3 12.5 9.9 19.0 6.7 26.6
67.2 76.2 73.3 45.2 62.5 24.3 41.7 82.6 45.6 68.9 47.4 30.7 56.0 58.5 38.8 49.7 45.1 96.8 45.6 150.0
32.7 28.6 35.1 35.5 35.7 41.0 38.6 38.4 33.7 35.1 37.4 39.3 40.8 33.4 42.5 34.8 35.6 29.9 33.7 27.8
12.3 16.3 16.4
8.3 11.1
4.6 8.0 15.9 8.8 13.4 9.4 5.9 11.1 11.1 6.7 10.0 9.2 18.4 9.7 27.2
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
14
-1066-
Units= Vmax(millivolts), Tmax(milliseconds)/ Vave(millivolts)
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
FEMALE GROUP: 0.3 MG/KG/DAY
TEST PERIOD: PND 60
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
105.3 23.0 66.2
130.1 22.0 90.9 52.1
135.8 29.2 76.9
234.4 131.3
67.0 63.2 88.9 42.4 98.6 170.0 119.8 111.8
32.9 60.8 40.6 31.7 38.3 31.3 24.2 32.9 34.7 34.6 35.5 38.8 33.9 25.1 33.7 38.6 39.7 26.4 28.1 35.9
23.7 4.4
18.6 28.4
3.1 24.1
7.5 30.7
6.8 11.4 49.7 29.0 14.2 10.9 16.0
7.6 24.1 27.8 23.5 22.4
88.6 10.2 66.2 75.7 21.9 51.0 61.1 141.7 53.0 91.8 76.7 51.2 42.0 86.2 42.7 34.4 96.6 69.6 165.2 67.9
40.9 45.1 37.5 36.6 37.9 45.8 40.0 37.9 45.0 29.0 27.7 40.0 44.3 26.7 43.4 37.0 24.0 24.5 27.2 35.0
19.1 1.3
18.1 18.3
5.9 13.0
8.5 23.0 12.0 17.3 15.2
9.6 9.5 16.1 9.4 6.6 19.6 12.1 27.5 16.1
103.2 12.8 43.6 58.6 17.2
130.2 8.2
46.8 53.1 91.3 61.9 95.3 38.6 34.4 47.3 25.1 84.1 52.1 36.5 81.5
25.4 39.6 34.1 36.7 47.2 23.9 37.5 27.4 39.8 36.0 30.0 32.8 32.3 39.7 41.1 43.0 23.7 35.6 25.1 40.0
22.1 1.9
10.1 11.5
2.9 32.8
1.5 9.0 10.0 14.9 10.4 19.8 9.5 6.7 11.8 5.6 16.2 9.9 5.4 17.4
56.6 11.2 60.4 80.9
8.2 57.0 25.9 54.4 43.5 105.8 100.6 76.6 35.5 15.5 44.8 17.0 121.7 72.5 78.9 94.3
37.0 61.2 31.6 36.7 44.5 28.4 41.5 36.5 38.6 26.6 28.2 31.5 43.8 34.8 43.5 38.3 23.8 29.8 29.8 35.2
11.8 1.3
12.3 19.5
1.0 11.2
6.1 13.7
8.8 19.2 18.4 14.9
6.8 3.6 9.2 2.8 30.1 13.2 14.5 23.7
49.3 8.3
71.9 157.4
6.2 46.2 16.1 98.5 17.5 186.6 110.7 33.6 51.6 76.9 25.4 27.0 100.6 58.0 105.8 51.8
45.9 43.1 32.4 32.0 49.8 31.1 43.5 29.3 61.1 23.2 29.2 41.1 49.2 30.8 50.7 32.5 26.6 35.7 23.9 37.6
10.7 1.3
19.0 29.4
0.9 10.0
2.7 22.1
3.7 32.2 20.5
8.0 9.4 16.7 5.2 5.0 20.9 10.8 20.0 9.4
80.6 13.1 61.7 100.5 15.1 75.1 32.7 95.4 39.3 110.5 116.9 77.6 46.9 55.2 49.8 29.2 100.3 84.4 101.2 81.5
36.4 50.0 35.2 34.7 43.5 32.1 37.3 32.8 43.8 29.9 30.1 36.8 40.7 31.4 42.5 37.9 27.6 30.4 26.8 36.7
17.5 2.0
15.6 21.4
2.8 18.2
5.3 19.7
8.3 19.0 22.8 16.3
9.9 10.8 10.3
5.5 22.2 14.8 18.2 17.8
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
15
-1067-
Units= Vmax(millivolts), Tmax(milliseconds)/ Vave(millivolts)
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL
TRIALS 1 - 10 Vmax Tmax Vave
APPENDIX 29 (F1) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL STARTLE RESPONSE DATA
TRIALS 11 - 20 Vmax Tmax Vave
FEMALE GROUP: 1.0 MG/KG/DAY
TEST PERIOD: PND 60
TRIALS 21 - 30
TRIALS 31 - 40
Vmax Tmax Vave Vmax Tmax Vave
TRIALS 41 - 50 Vmax Tmax Vave
PAGE
ALL TRIALS Vmax Tmax Vave
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
26.2 32.2 38.9 72.2 42.2 58.7 114.0 91.3 85.0 20.4 85.5 45.0 60.0 218.6 41.3 262.4 40.8 74.1 43.0 58.9
31.9 32.4 33.0 42.0 38.6 37.1 35.4 35.4 28.6 53.8 33.6 38.3 40.7 24.6 45.3 28.8 31.8 41.8 30.2 37.8
3.7 6.2 7.0 10.2 9.4 13.6 26.7 17.8 15.9 4.6 17.9 12.0 14.8 45.7 10.2 48.2 8.5 18.2 8.4 8.8
9.3 30.6 16.3 40.1 42.9 46.1 126.2 59.3 30.6 23.1 88.7 52.7 44.8 242.6 44.6 75.9 21.5 31.3 27.5
7.4
8.7 28.4 32.8 42.1 39.0 31.3 39.1 36.0 49.5 34.3 28.9 32.6 33.0 24.3 35.3 34.2 44.2 37.2 33.9 43.3
0.2 4.7 3.2 8.8 7.6 10.1 27.5 11.3 7.1 6.5 18.1 14.0 10.3 50.6 6.9 15.2 3.7 6.8 5.7 0.6
17.6 25.4 16.4 36.4 50.0 45.7 81.2 38.9 23.7 36.6 123.8 75.6 26.7 108.2 24.6 102.5 12.7 23.2 31.9 33.6
17.0 33.2 38.5 43.2 37.0 47.9 39.7 32.5 48.4 47.2 31.3 29.2 32.1 33.6 26.8 27.0 32.3 44.5 42.7 31.4
1.4 4.8 3.2 9.7 7.7 11.6 13.5 6.4 3.6 5.8 24.6 15.6 5.2 22.2 2.8 17.9 1.8 4.4 5.0 6.3
17.8 45.4 26.1 22.8 27.0 55.7 104.7 46.2 28.5 45.1 97.4 37.3 46.6 120.8
9.0 78.2 12.7 14.9 29.3 179.4
17.9 40.1 28.5 50.7 46.8 33.4 31.2 31.4 47.3 47.7 30.8 38.8 36.4 24.0 28.6 31.1 52.3 48.7 23.7 23.7
1.7 10.6
4.2 4.3 6.7 13.9 22.9 6.4 5.5 9.8 16.7 7.6 10.1 27.7 1.1 14.7 1.9 2.1 6.3 28.5
12.4 22.7 21.3 23.1 38.0 56.5 63.5 37.2 58.9 33.3 64.9 39.8 25.7 159.2 20.4 108.6 10.0 18.0 67.2 242.8
13.4 51.1 39.4 41.0 30.0 38.0 33.7 30.1 38.6 34.8 33.1 35.2 52.7 24.9 44.7 36.0 43.8 45.7 31.6 21.0
0.8 4.5 2.6 4.6 7.0 13.0 15.8 6.1 12.2 9.0 14.5 8.0 8.4 40.1 5.4 17.9 1.4 3.2 14.4 42.0
16.7 31.3 23.8 38.9 40.0 52.5 97.9 54.6 45.3 31.7 92.1 50.1 40.8 169.9 28.0 125.5 19.5 32.3 39.8 104.4
17.8 37.0 34.4 43.8 38.3 37.5 35.8 33.1 42.5 43.6 31.5 34.8 39.0 26.3 36.1 31.4 40.9 43.6 32.4 31.4
1.6 6.2 4.0 7.5 7.7 12.4 21.3 9.6 8.9 7.1 18.4 11.4 9.8 37.3 5.3 22.8 3.5 6.9 8.0 17.2
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
16
-1068-
Units= Vmax(millivolts), Tmax(milliseconds) , Vave(millivolts)
PSRSUMv5.12 10/12/2006
PROJECT NO..:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO..:06-128
GROUP 1: 0 MG/KG/DAY
PUP NO.
TRIAL NO. 1 TIME (SEC)
25597-04 25654-09 25632-07 25633-05 25618-08 25621-07 25687-07 25681-01 25615-03 25637-06 25638-07 25713-02 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
8.97 18.50 12.36 12.22
7.43 11.33 10.11
6.34 14.07 20.55 39.02
5.96 5.54 30.38 15.11 11.89 14.03 10.19 16.57 12.41
MEAN S.D.
N
14.15 8.201
20
APPENDIX 30 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS MALES
TRIAL NO. 2 TIME (SEC)
8.96 5.77 9.94 7.23 3.70 4.43 6.43 4.02 5.81 7.48 8.94 4.13 6.34 5.22 7.45 4.73 9.30 8.10 12.99 5.91
6.84 2.367
20
TRIAL NO. 3 TIME (SEC)
10.46 9.06 9.15
12.84 5.95 4.16 4.60 4.81 4.95 5.34 5.15 7.29 5.61 4.71 7.45 9.63 9.34
16.31 6.02 5.51
7.42 3.173
20
TRIAL NO. 4 TIME (SEC)
6.15 5.22 9.14 8.16 4.44 7.41 7.64 4.04 4.28 4.41 7.13 4.56 6.23 4.89 6.11 5.11 6.15 6.77 7.18 6.58
6.08 1.437
20
PAGE 1
OVERALL MEAN (SEC)
8.64 9.64 10.15 10.11 5.38 6.83 7.20 4.80 7.28 9.45 15.06 5.49 5.93 11.30 9.03 7.84 9.71 10.34 10.69 7.60
8.62 2.453
20
-1069-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP 2: 0.1 MG/KG/DAY
PUP NO.
TRIAL NO. 1 TIME (SEC)
25648-07 25674-02 25694-04 25631-04 25660-01 25704-03 25665-01 25652-04 25733-07 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25741-07 25752-09
9.19 24.02 26.73 17.54 24.01 17.63 14.94
9.57 15.13
9.39 12.71 11.00
6.37 16.15
7.92 39.02 15.81 21.28
8.45 8.07
MEAN S.D.
N
15.75 8.118
20
APPENDIX 30 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS MALES
TRIAL NO. 2 TIME (SEC)
5.74 4.59 9.06 5.89 8.46 6.38 10.41 5.74 6.27 6.47 5.72 22.63 6.09 5.43 4.45 11.57 4.58 14.20 9.97 5.10
7.94 4.344
20
TRIAL NO>. 3 TIME (SEC)
8.70 5.06 6.41 4.81 9.02 5.43 5.96 5.87 5.07 5.30 5.45 6.17 5.72 6.19 5.40 7.42 4.16 7.02 7.87 4.31
6.07 1.339
20
TRIAL NO. 4 TIME (SEC)
15.70 4.70 4.82 6.08 6.99 4.30
10.35 6.27 5.44 4.50 4.27 5.65 6.57 4.86 3.99 6.39 5.70
15.61 6.02 4.51
6.64 3.388
20
PAGE 2
OVERALL MEAN (SEC)
9.83 9.59 11.76 8.58 12.12 8.44 10.42 6.86 7.98 6.42 7.04 11.36 6.19 8.16 5.44 16.10 7.56 14.53 8.08 5.50
9.10 2.901
20
-1070-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP 3: 0.3 MG/KG/DAY
PUP NO.
TRIAL NO. 1 TIME (SEC)
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
11.81 11.59 16.88 12.05 29.66 14.22 13.47 15.04 12.14 15.55 15.64
7.05 9.44 9.58 11.16 10.24 33.55 14.57 16.69 19.56
MEAN S.D.
N
14.99 6.447
20
APPENDIX 30 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS MALES
TRIAL NO. 2 TIME (SEC)
9.70 5.14 6.17 5.87 6.71 4.82 13.02 5.93 4.45 5.11 7.09 5.90 6.84 6.45 5.64 6.61 9.48 3.98 5.01 7.61
6.58 2.110
20
TRIAL NO. 3 TIME (SEC)
6.95 9.74 5.64 4.97 4.08 5.66 9.59 5.37 4.52 5.13 5.09 5.03 5.79 12.50 5.35 6.46 5.28 8.20 4.21 13.19
6.64 2.645
20
TRIAL NO. 4 TIME (SEC)
12.61 3.88 8.30 3.24 5.55 7.49 5.02 4.07 5.33 3.99 7.48 6.20 5.00 6.02 9.28 4.69 5.73 4.84 5.17 8.70
6.13 2.265
20
PAGE 3
OVERALL MEAN (SEC)
10.27 7.59 9.25 6.53
11.50 8.05
10.28 7.60 6.61 7.45 8.83 6.05 6.77 8.64 7.86 7.00
13.51 7.90 7.77
12.27
8.58 2.027
20
-1071-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP 4: 1.0 MG/KG/DAY
PUP NO.
TRIAL NO. 1 TIME (SEC)
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
34.32 11.74 30.27 13.12 14.86 23.02 27.66
9.93 5.46 17.34 28.37 24.90 7.63 25.37 19.59 19.40 14.27 36.98 11.52 10.07
MEAN S.D.
N
19.29 9.172
20
APPENDIX 30 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS MALES
TRIAL NO. 2 TIME (SEC)
6.39 16.47
4.92 7.30 9.49 5.80 6.61 4.95 3.20 6.41 26.65 5.41 5.84 11.45 9.63 5.29 4.45 7.45 5.89 6.59
8.01 5.275
20
TRIAL NO. 3 TIME (SEC)
6.25 4.52 5.57 7.28 5.33 6.69 4.52 3.72 6.51 2.72 10.95 6.26 6.40 5.08 7.59 7.98 5.04 10.39 6.52 10.71
6.50 2.213
20
TRIAL NO. 4 TIME (SEC)
5.60 4.67 4.06 6.02 5.70 4.46 4.35 3.97 4.81 4.96 8.56 5.34 120.00 5.90 10.09 5.80 10.21 12.56 5.80 14.58
12.37 25.505
20
PAGE 4
OVERALL MEAN (SEC)
13.14 9.35
11.21 8.43 8.85 9.99
10.79 5.64 5.00 7.86
18.63 10.48 34.97 11.95 11.73
9.62 8.49 16.85 7.43 10.49
11.54 6.400
20
-1072-
PROJECT NO. :WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO. :06-128
GROUP 1: 0 MG/KG/DAY
PUP NO.
TRIAL NO. 1 TIME (SEC)
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
9.55 20.19 13.77 13.49
7.38 7.70 8.82 9.44 8.06 12.19 25.10 12.38 12.20 11.62 6.52 6.24 44.96 10.46 15.64 15.06
MEAN S.D.
N
13.54 8.735
20
APPENDIX 30 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS FEMALES
TRIAL NO. 2 TIME (SEC)
12.99 8.28 7.92 8.24 7.74 4.16
10.96 8.40
10.37 9.27 8.58 5.49 7.04
11.34 5.86 7.18 8.69 7.41 5.62 5.62
8.06 2.201
20
TRIAL NO. 3 TIME (SEC)
7.59 8.12 3.68 16.33 2.44 4.86 7.20 8.34 5.74 6.14 5.49 5.71 5.66 5.10 5.32 4.78 5.78 4.77 4.45 6.27
6.19 2.778
20
TRIAL NO. 4 TIME (SEC)
9.46 14.18
4.06 9.54 4.91 7.97 4.99 6.51 6.59 5.72 5.45 6.13 5.63 4.66 5.07 5.06 6.07 4.76 5.23 5.28
6.36 2.362
20
PAGE 5
OVERALL MEAN (SEC)
9.90 12.69
7.36 11.90
5.62 6.17 7.99 8.17 7.69 8.33 11.16 7.43 7.63 8.18 5.69 5.82 16.38 6.85 7.74 8.06
8.54 2.683
20
-1073-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP 2: 0.1 MG/KG/DAY
PUP NO.
TRIAL NO. 1 TIME (SEC)
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
9.84 28.73 21.24 20.24 16.49 20.62 15.87 20.92 24.91
5.42 15.22 21.31 13.75 30.56
7.24 19.78 13.36 12.85 29.64 20.98
MEAN S.D.
N
18.45 6.986
20
APPENDIX 30 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS FEMALES
TRIAL NO. 2 TIME (SEC)
4.45 7.74 4.63 5.04 8.85 5.52 9.24 10.08 5.91 9.12 7.07 7.20 9.58 7.06 5.31 5.50 6.34 17.49 7.96 4.05
7.41 2.999
20
TRIAL NO. 3 TIME (SEC)
5.41 8.31 8.09 10.59 6.76 5.27 8.31 7.77 6.92 5.36 5.27 6.29 6.21 4.81 8.59 4.79 3.94 6.72 5.59 5.41
6.52 1.655
20
TRIAL NO. 4 TIME (SEC)
4.97 5.79 6.17 7.79 6.73 5.14 6.97 8.02 6.81 4.30 5.36 5.43 8.96 5.16 6.85 6.34 4.38 4.54 5.48 4.31
5.98 1.320
20
PAGE 6
OVERALL MEAN (SEC)
6.17 12.64 10.03 10.92
9.71 9.14 10.10 11.70 11.14 6.05 8.23 10.06 9.63 11.90 7.00 9.10 7.01 10.40 12.17 8.69
9.59 1.946
20
-1074-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP 3: 0.3 MG/KG/DAY
PUP NO.
TRIAL NO. 1 TIME (SEC)
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
13.64 22.89 34.17 24.16
7.63 15.03 12.93
9.41 17.74 12.83 13.48
8.88 9.10 9.72 28.04 20.50 12.96 13.24 63.89 21.77
MEAN S.D.
N
18.60 12.782
20
APPENDIX 30 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS FEMALES
TRIAL NO. 2 TIME (SEC)
7.27 6.87 7.08 8.89 3.69 4.63 3.34 4.96 6.41 5.11 7.30 7.66 5.13 4.56 8.66 7.40 4.63 5.56 20.23 7.48
6.84 3.532
20
TRIAL NO. 3 TIME (SEC)
6.52 8.95 5.54 4.99 4.85 6.71 6.11 4.87 5.38 3.57 5.63 4.77 16.17 4.33 7.02 5.09 5.56 5.58 6.70 6.26
6.23 2.608
20
TRIAL NO. 4 TIME (SEC)
9.49 5.69 12.49 5.83 4.91 5.51 8.77 3.96 5.58 4.31 6.14 4.24 9.02 6.89 7.90 5.31 4.11 6.56 11.13 5.59
6.67 2.397
20
PAGE 7
OVERALL MEAN (SEC)
9.23 11.10 14.82 10.97
5.27 7.97 7.79 5.80 8.78 6.46 8.14 6.39 9.86 6.38 12.91 9.58 6.82 7.74 25.49 10.28
9.59 4.467
20
-1075-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP 4: 1.0 MG/KG/DAY
PUP NO.
TRIAL NO. 1 TIME (SEC)
25696-11 25686-10 25630-09 25673-10 25639-04 25658-14 25676-15 25600-15 25603-10 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25599-11 25762-11 25647-11
27.38 17.66 17.95 16.07 21.48
9.77 13.10
4.95 15.02
9.16 18.52 13.68
9.68 8.08 37.96 15.83 14.28 14.94 11.44 14.49
MEAN S.D.
N
15.57 7.267
20
APPENDIX 30 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE STRAIGHT CHANNEL SWIM TRIALS FEMALES
TRIAL NO. 2 TIME (SEC)
6.16 6.34 7.99 5.08 8.77 7.21 6.72 14.38 5.01 10.91 8.45 6.38 9.89 4.67 6.73 5.32 4.43 4.98 6.73 9.54
7.28 2.487
20
TRIAL NO. 3 TIME (SEC)
3.94 5.42 5.09 4.42 10.89 5.65 7.00 8.46 4.01 3.56 7.37 4.86 6.09 3.91 5.31 4.63 5.39 7.23 9.94 7.16
6.02 2.020
20
TRIAL NO. 4 TIME (SEC)
5.13 5.76 5.51 5.63 10.42 5.73 8.68 5.19 6.60 7.45 7.20 4.47 5.17 4.43 5.15 6.38 5.77 4.65 5.80 5.13
6.01 1.479
20
PAGE 8
OVERALL MEAN (SEC)
10.65 8.80 9.14 7.80
12.89 7.09 8.88 8.25 7.66 7.77
10.39 7.35 7.71 5.27
13.79 8.04 7.47 7.95 8.48 9.08
8.72 1.962
20
MANUALv1.0 10/05/2006 R:04/30/2007
-1076-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS MALES
PAGE
GROUP 1: 0 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 1
TIME
ERRORS
(SEC)
(NO.)
2 -A
TRIAL NUMBER 2
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 3
TIME
ERRORS
(SEC)
(NO.)
3 -A
TRIAL NUMBER 4
TIME
ERRORS
(SEC)
(NO.)
DAY 4 - B
TRIAL NUMBER 5
TRIAL NUMBER 6
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25597-04 180.00 E
26
41.06
4
25654-09
36.70
8 93.64
27
25632-07 136.52
29 18.42
0
25633-05
72.78
15 49.84
13
25618-08 165.31
29 21.74
3
25621-07
37.60
5 87.20
22
25687-07
24.34
4 76.13
18
25681-01 107.58
22 61.66
11
25615-03
63.82
13 117.37
36
25637-06
60.93
9 83.87
20
25638-07
77.00
18 25.03
4
25713-02 180.00 E
31
49.44
9
25670-09 159.91
36 48.34
10
25657-08
27.74
4 25.71
4
25663-04
18.55
1 33.72
7
25690-01
66.76
15 20.28
4
25666-01
20.43
3 20.57
3
25692-04
70.90
15 180.00 E 34
25701-09
25.68
4 65.02
14
25645-06
41.98
8 51.34
13
55.01
7 53.56
63.41
16 27.57
35.27
10 26.05
70.40
21 134.56
22.16
3 61.23
180.00 E 61 152.59
58.34
18 15.56
50.45
18 26.84
22.97
5 21.80
28.13
3 86.74
35.68
9 32.02
29.91
7 57.62
30.72
6 11.24
12.68
0 21.12
15.12
0 59.61
11.45
0 21.05
180.00 E 38 154.46
16.31
2 12.88
62.45
19 24.16
100.61
28 55.36
10 180.00 E 43 180.00 E 34
6 180.00 E 36 180.00 E 34
5 54.52
13 180.00 E
41
28 77.02
20 52.16
13
16 51.97
9 180.00 E
48
44 180.00 E 41 152.87
28
2 180.00 E 35 133.33
33
5 180.00 E 45 180.00 E 27
5 97.27
27 125.20
30
20 174.32
41 180.00 E
41
7 180.00 E 41 180.00 E 39
18 180.00 E 38 59.20
15
0 180.00 E 42 180.00 E 44
3 180.00 E 43 180.00 E 47
14 76.14
13 19.42
2
5 146.67
33 179.24
32
32 62.74
11 180.00 E
34
1 137.10
36 37.91
2
4 180.00 E 42 110.99
29
13 76.24
16 50.64
10
MEAN S.D.
N
78.73 56.080
20
15 10.8
20
58.52 40.115
20
13 10.5
20
54.05 48.823
20
14 15.1
20
52.80 45.443
20
12 11.6
20
137.70 52.358
20
31 12.6
20
136.05 58.799
20
29 13.9
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
1
-oi-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS MALES
PAGE 2
GROUP 1: 0 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 7
TIME
ERRORS
(SEC)
(NO.)
5 -B
TRIAL NUMBER 8
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 9
TIME
ERRORS
(SEC)
(NO.)
6 -B
TRIAL NUMBER 10
TIME
ERRORS
(SEC)
(NO.)
DAY 7 (PROBE) - A
TRIAL NUMBER 11
TRIAL NUMBER 12
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25597-04 180.00 E 29 180.00 E 26
25654-09 180.00 E 31 180.00 E 38
25632-07 109.23
31 30.49
6
25633-05
60.88
18 41.82
10
25618-08 180.00 E 52 180.00 E 42
25621-07 180.00 E
40
94.56
23
25687-07 180.00 E 46 180.00 E 47
25681-01 180.00 E 40 152.32
28
25615-03 131.62
44 29.02
7
25637-06
57.23
14 180.00 E 32
25638-07
49.52
8 54.30
13
25713-02 180.00 E 33 180.00 E 34
25670-09 180.00 E 31 180.00 E 25
25657-08 180.00 E
30
22.69
7
25663-04 131.28
29 106.99
28
25690-01 147.44
30 11.45
1
25666-01 180.00 E
34
65.26
12
25692-04
39.63
9 50.87
11
25701-09 180.00 E 46 180.00 E 40
25645-06 178.21
40 73.93
20
180.00 E 20 180.00 E 25
113.02
24 180.00 E 41
32.34
6 82.44
22
68.70
21 34.24
9
113.64
25 71.52
18
64.86
20 22.24
5
78.27
18 13.99
2
26.13
4 46.24
11
42.61
15 31.99
11
15.69
3 44.66
10
15.95
2 97.31
28
129.68
36 10.24
1
180.00 E 44 180.00 E 44
180.00 E
47
16.20
2
49.99
11 29.56
8
10.80
0 68.35
16
107.37
25 23.06
2
12.54
0 10.24
0
71.81
15 109.92
24
180.00 E
53
17.63
3
67.91 42.59 65.19 112.59 61.45 72.98 50.88 102.52 180.00 E 25.12 180.00 E 81.27 35.03 25.94 155.83 45.88 39.97 31.25 72.92 44.73
14 113.31 8 15.79
18 55.38 32 114.45 13 13.62 26 27.09
8 30.35 31 22.89 64 180.00 E
3 17.70 58 43.23 30 12.24
5 11.36 6 32.89 33 66.88 11 31.69 14 13.27 6 33.05 19 27.94 12 24.39
17 2
15 38
0 4 6 5 58 1 14 1 0 7 20 9 0 4 5 6
-1078-
MEAN S.D.
N
144.25 51.920
20
32 12.1
20
108.69 67.266
20
23 13.6
20
83.67 60.977
20
19 15.7
20
63.49 58.001
20
14 13.0
20
74.70 48.210
20
21 16.9
20
44.38 43.708
20
11 14.4
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
GROUP 2: 0.1 MG/KG/DAY
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS MALES
PAGE 3
PUP NO.
DAY
TRIAL NUMBER 1
TIME
ERRORS
(SEC)
(NO.)
2 -A
TRIAL NUMBER 2
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 3
TIME
ERRORS
(SEC)
(NO.)
3 -A
TRIAL NUMBER 4
TIME
ERRORS
(SEC)
(NO.)
DAY 4 - B
TRIAL NUMBER 5
TRIAL NUMBER 6
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25648-07
25.76
3 107.74
30
25674-02
75.09
13 109.59
29
25694-04 180.00 E
27
86.47
19
25631-04
52.45
8 29.18
8
25660-01 180.00 E
26
67.96
15
25704-03
38.74
9 140.13
35
25665-01
78.96
13 37.16
5
25652-04 158.25
28 68.42
13
25733-07 180.00 E 33 103.63
23
25748-01 118.52
23 56.06
11
25753-06
31.99
7 33.87
7
25672.06
42.91
8 27.56
3
25655-01 134.63
24 77.75
21
25727-07
20.19
3 44.47
10
25626-04
95.63
26 13.24
1
25749-04
13.97
0 68.86
12
25739-07
21.33
3 15.18
1
25756-05
45.09
8 180.00 E 40
25741-07
39.68
7 50.66
10
25752-09
52.17
11 16.59
1
22.33
6 29.36
24.93
6 20.89
19.41
2 10.91
21.19
4 12.26
13.18
0 149.73
35.47
7 24.88
58.56
17 12.86
180.00 E 45 110.12
51.56
10 16.62
58.74
16 39.20
96.20
29 21.16
27.55
3 38.94
30.45
8 18.37
94.44
28 12.34
13.24
1 36.82
40.54
8 18.21
85.05
15 24.77
160.48
31 35.51
25.27
3 23.42
28.09
3 110.42
5
180.00 E
36 180.00 E
36
5 164.49
41 180.00 E
58
0 59.80
15 180.00 E
31
0 180.00 E 34 33.99
7
33
180.00 E
27 180.00 E
26
3 80.10
15 166.54
28
0 180.00 E 38 27.51
2
23
180.00 E
30 180.00 E
46
1
180.00 E
35 180.00 E
27
8 76.13
18 82.22
18
5
180.00 E
28 177.03
40
7
180.00 E
38 137.35
24
4 89.81 24 155.78 32
0
180.00 E
44 155.16
37
10 121.04
37 108.58
32
2 75.95 15 71.56 18
4 140.60
28 78.41
14
5
180.00 E
38 180.00 E
29
2
180.00 E
40 180.00 E
28
28
180.00 E
34 180.00 E
39
MEAN S.D.
N
79.27 58.459
20
14 10.2
20
66.73 44.377
20
15 11.7
20
54.33 47.220
20
12 12.2
20
38.34 38.436
20
7 148.40 9.5 45.579
20 20
31 140.71 9.2 53.137
20 20
29 13.0
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
-1079-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS MALES
PAGE 4
GROUP 2: 0.1 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 7
TIME
ERRORS
(SEC)
(NO.)
5 -B
TRIAL NUMBER 8
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 9
TIME
ERRORS
(SEC)
(NO.)
6 -B
TRIAL NUMBER 10
TIME
ERRORS
(SEC)
(NO.)
DAY 7 (PROBE) - A
TRIAL NUMBER 11
TRIAL NUMBER 12
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25648-07 180.00 E 33 180.00 E 32
25674-02 164.78
43 50.62
16
25694-04
48.23
9 180.00 E 34
25631-04 177.06
35 157.38
41
25660-01 180.00 E 25 180.00 E 30
25704-03 180.00 E
42
45.33
10
25665-01
21.43
4 48.52
8
25652-04 114.30
21 180.00 E 41
25733-07
42.14
10 171.52
27
25748-01 180.00 E
46
99.55
20
25753-06 180.00 E
41
33.02
10
25672.06 180.00 E 39 180.00 E 48
25655-01 118.84
29 53.88
16
25727-07 126.13
30 19.67
6
25626-04
40.95
11 180.00 E 40
25749-04 100.79
18 11.49
0
25739-07 177.02
47 141.06
30
25756-05 180.00 E
39
63.39
17
25741-07 126.02
25 169.94
27
25752-09
71.82
10 37.14
5
180.00 E 40 180.00 E 41
10.25
0 180.00 E 50
47.20
9 22.59
4
180.00 E
40
30.16
4
144.62
43 180.00 E 41
78.08
14 12.09
1
60.87
13 69.91
14
180.00 E
42
66.08
14
180.00 E
53
73.05
19
13.14
0 10.92
0
180.00 E 43 104.20
27
180.00 E 39 116.78
27
25.80
8 27.16
7
25.13
6 16.26
2
22.36
3 22.90
6
42.70
6 27.66
4
133.17
34 54.68
12
117.26
25 66.45
10
180.00 E 28 104.09
17
69.74
14 43.44
5
69.70 56.51 69.50 23.92 60.56 152.28 180.00 E 60.66 41.84 46.64 72.28 27.46 30.68 73.08 71.43 131.48 180.00 E 30.39 21.95 99.20
20 180.00 E 18 40.80 21 52.70
6 67.37 22 17.50 50 69.20 57 165.56 16 31.91
6 33.73 13 73.31 24 28.45
1 91.86 6 86.79 18 34.74 25 24.91 29 104.86 46 180.00 E 4 48.93 2 13.90 31 45.58
38 11 15 20
2 16 41
3 5 18 9 14 37 8 6 27 43 11 0 9
-1080-
MEAN S.D.
N
129.48 57.075
20
28 13.8
20
109.13 67.274
20
23 14.0
20
102.52 68.748
20
23 17.4
20
70.42 56.758
20
15 14.7
20
74.98 49.299
20
21 15.9
20
69.61 51.904
20
17 13.5
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS MALES
PAGE
GROUP 3: 0.3 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 1
TIME
ERRORS
(SEC)
(NO.)
2 -A
TRIAL NUMBER 2
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 3
TIME
ERRORS
(SEC)
(NO.)
3 -A
TRIAL NUMBER 4
TIME
ERRORS
(SEC)
(NO.)
DAY 4 - B
TRIAL NUMBER 5
TRIAL NUMBER 6
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25671-04 25614-10 25698-05 25677-05 25604-04 25678-02 25609-04 25623-08 25653-02 25684-04 25714-02 25650-11 25735-05 25722-01 25642-05 25628-07 25766-01 25689-02 25708-01 25743-08
29.60 63.18 28.56 43.55 38.04 18.12 38.24 180.00 E 98.10 88.64 47.04 58.46 179.09 45.59 112.16 28.85 34.05 180.00 E 24.64 94.06
7 30.16 13 40.14
4 95.40 7 82.84 8 65.66 1 23.66 7 74.52 39 22.63 18 144.31 17 12.46 11 49.95 9 36.58 25 65.13 11 46.48 17 130.78 4 19.30 6 112.57 43 114.71 4 34.38 16 121.16
7 26.47 8 74.07 20 20.46 21 21.88 19 41.19 3 33.81 19 26.81 3 34.81 36 28.78 0 19.84 9 12.96 4 25.15 13 69.07 12 11.09 30 57.20 3 12.39 28 51.15 20 87.20 6 19.62 27 20.15
5 77.56 18 57.83
2 83.70 3 15.68 14 91.63 5 63.74 6 19.76 7 27.74 7 14.76 3 52.86 1 15.55 4 10.27 17 85.26 0 15.33 14 20.21 0 23.75 15 28.58 24 14.89 3 20.51 2 14.66
21 58.03
12 11.40
0
13 180.00 E 30 117.42
19
19 88.63
20 180.00 E
42
3 180.00 E 47 33.09
9
27 49.37
14 26.27
5
16 180.00 E 44 154.01
30
3 129.75
35 180.00 E
37
5 40.27
4 180.00 E
40
2 180.00 E 47 180.00 E 37
16 180.00 E 39 22.47
5
3 59.79
17 107.75
27
0 180.00 E 32 39.41
5
25 180.00 E 36 180.00 E 39
2 180.00 E 35 54.49
11
4 180.00 E 44 180.00 E 43
3 180.00 E 37 180.00 E 38
7 180.00 E 37 90.45
22
2 180.00 E 47 137.19
21
4 180.00 E 38 180.00 E 37
2 134.70
30 180.00 E
36
MEAN S.D.
N
71.50 53.639
20
13 11.2
20
66.14 41.239
20
14 10.5
20
34.71 21.907
20
8 6.9
20
37.71 28.372
20
9 8.7
20
145.03 53.498
20
32 12.6
20
120.70 66.215
20
25 14.7
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
5
-1081-
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS MALES
PAGE 6
GROUP 3: 0.3 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 7
TIME
ERRORS
(SEC)
(NO.)
5 -B
TRIAL NUMBER 8
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 9
TIME
ERRORS
(SEC)
(NO.)
6 -B
TRIAL NUMBER 10
TIME
ERRORS
(SEC)
(NO.)
DAY 7 (PROBE) - A
TRIAL NUMBER 11
TRIAL NUMBER 12
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25671-04
8.83
0 114.83
29
25614-10
53.62
10 31.24
7
25698-05 150.09
31 23.09
4
25677-05 123.74
32 20.24
4
25604-04 100.10
36 59.74
17
25678-02
35.56
8 15.41
2
25609-04 180.00 E 43 180.00 E 43
25623-08 180.00 E
38
71.53
15
25653-02 180.00 E
38
23.06
2
25684-04 180.00 E 37 180.00 E 49
25714-02
90.01
23 13.81
2
25650-11 180.00 E
24
50.99
6
25735-05 102.90
24 13.77
2
25722-01 180.00 E
30
90.92
25
25642-05 180.00 E 45 180.00 E 41
25628-07
97.07
22 91.81
19
25766-01 172.93
42 92.24
26
25689-02
86.74
30 32.00
8
25708-01 180.00 E
58
65.78
16
25743-08 180.00 E
41
79.56
21
54.13 13 6.78
0
31.08
4 29.09
5
170.63
36 163.70
33
18.46
3 17.09
2
12.62
2 148.38
48
26.00
5 29.84
7
180.00 E
48
38.44
9
97.20
22 21.09
1
76.45
22 180.00 E 44
124.13
33 24.46
3
8.46
0 9.45
0
36.74
6 21.58
2
11.59
0 110.98
23
20.16
2 10.84
0
180.00 E 50 102.43
33
22.91
5 30.83
6
47.66
12 180.00 E 46
14.94
1 10.57
0
45.05
7 130.45
38
158.15
31 180.00 E 39
142.89 122.91
28.14 76.72 131.03 85.38 22.36 79.52 35.13 38.78 171.31 64.10 57.85 80.84 122.12 153.09 64.85 47.37 41.81 99.51
38 62.66 34 29.82
5 16.20 27 44.59 44 96.56 32 107.48
7 53.65 24 31.80
8 143.78 8 47.98 44 16.10 16 42.03 17 10.97 28 39.57 31 66.54 45 63.32 21 38.06 16 11.86 9 32.57 19 73.11
15 7 2 9
34 32 16
8 55 15
2 11
0 13 22 15
8 0 7 14
-1082-
MEAN S.D.
N
132.08 56.344
20
31 13.8
20
71.50 55.902
20
17 14.7
20
66.82 61.737
20
15 16.3
20
72.30 67.910
20
17 18.5
20
83.29 44.296
20
24 13.1
20
51.43 34.062
20
14 13.3
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS MALES
PAGE 7
GROUP 4: 1.0 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 1
TIME
ERRORS
(SEC)
(NO.)
2 -A
TRIAL NUMBER 2
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 3
TIME
ERRORS
(SEC)
(NO.)
3 -A
TRIAL NUMBER 4
TIME
ERRORS
(SEC)
(NO.)
DAY 4 - B
TRIAL NUMBER 5
TRIAL NUMBER 6
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
179.05 19.76 82.18 49.06 72.17 85.97 37.91 32.43 32.22
180.00 E 101.10 180.00 E
27.26 157.94
14.63 37.72 180.00 E 41.74 60.27 24.59
38 64.88 3 26.33
18 17.20 11 134.21 17 124.30 16 16.56
7 169.22 7 25.97 6 64.64 36 58.82 18 27.31 42 43.24 4 46.49 23 75.36 1 100.31 8 93.67 39 180.00 E 7 62.81 14 29.02 3 26.72
15 4 2
34 41
1 34
4 13
7 4 10 10 11 22 19 44 13 4 5
17.84
3 19.91
3
24.39
5 180.00 E 35
12.06
0 18.63
2
73.55
22 125.59
37
22.62
4 25.68
6
39.48
11 23.27
4
16.55
1 24.69
4
14.92
3 19.79
2
31.95
6 23.25
5
108.41
34 10.79
1
17.36
2 14.77
2
83.05
27 40.37
5
24.84
3 20.93
4
180.00 E
40
31.47
7
17.73
1 36.47
6
12.40
0 23.13
4
96.23
30 32.26
6
48.86
11 21.52
2
13.42
2
C3
23.52
3 69.49
15
180.00 E
53
72.83
17
180.00 E
23
38.82
5
180.00 E
46
80.16
15
180.00 E 43 180.00 E 51
180.00 E 39 166.03
44
180.00 E 34 180.00 E 40
180.00 E
48
64.90
15
180.00 E 54 111.37
28
180.00 E
51
43.82
8
77.37
17 180.00 E 46
180.00 E
36
71.46
19
67.83
15 93.73
18
180.00 E 29 136.49
22
180.00 E 29 180.00 E 28
180.00 E 39 180.00 E 33
180.00 E 41 163.61
32
18.39
3 56.35
14
180.00 E 35 180.00 E 37
28.88
5 70.55
14
180.00 E
36
31.06
7
-1083-
MEAN S.D.
N
79.80 61.173
20
16 13.2
20
69.35 49.673
20
15 13.4
20
43.96 43.665
20
10 12.7
20
40.11 42.615
19
8 10.1
20
153.62 55.325
20
34 14.9
20
114.06 57.104
20
25 13.7
20
A = ANIMALS TESTED IN PATH A DIRECTION
(FORWARD ROUTE THROUGHMAZE)
B = ANIMALS TESTED IN PATH B DIRECTION
(REVERSE ROUTE THROUGHMAZE)
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS MALES
PAGE 8
GROUP 4: 1.0 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 7
TIME
ERRORS
(SEC)
(NO.)
5 -B
TRIAL NUMBER 8
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 9
TIME
ERRORS
(SEC)
(NO.)
6 -B
TRIAL NUMBER 10
TIME
ERRORS
(SEC)
(NO.)
DAY 7 (PROBE) - A
TRIAL NUMBER 11
TRIAL NUMBER 12
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25696-04 25686-04 25630-04 25673-09 25639-06 25658-08 25676-02 25600-02 25603-04 25703-03 25705-07 25611-07 25619-04 25691-07 25717-04 25616-05 25715-07 25599-06 25762-01 25647-07
153.50 180.00 E 130.87
68.37 180.00 E 180.00 E 173.09 180.00 E
38.77 171.70
39.29 29.93 180.00 E 180.00 E 156.87 126.34 29.17 49.24 180.00 E 84.38
40 14.99 32 90.84 29 16.09 20 133.85 41 86.39 51 51.47 40 115.63 47 46.23
9 47.60 38 180.00 E 12 59.66
5 117.38 30 180.00 E 21 40.06 35 15.53 35 13.99
9 78.29 8 180.00 E 34 179.38 18 26.17
1 19
1 38 17 11 24 10
9 43 15 36 34
6 1 1 23 36 43 4
33.94
7 25.34
94.25
19 49.04
14.29
1 12.62
132.69
30 143.10
180.00 E
51
56.51
155.43
38 180.00 E
33.45
3 44.62
15.99
1 50.97
72.04
20 30.81
180.00 E 37 126.80
54.93
14 64.13
19.66
3 30.02
180.00 E 36 180.00 E
180.00 E
32
15.34
10.58
0 25.61
10.81
0 22.37
65.98
18 39.36
180.00 E
38
75.14
98.80
23 66.70
27.45
4 38.88
3 87.07 13 102.52
0 172.09 43 71.69 15 55.57 48 80.65 10 31.21 12 180.00 E
7 111.82 34 56.26 11 41.78
6 59.99 39 18.63
0 180.00 E 4 50.46 4 66.05 10 23.74 15 77.19 5 77.71 4 174.11
21 26.34
5
29 149.72
35
58 34.51
8
22 43.56
8
15 104.34
28
30 56.38
14
6 49.98
12
65 180.00 E 61
36 22.61
5
14 41.55
10
16 48.36
16
16 31.58
6
3 54.38
16
40 52.83
8
15 180.00 E 53
19 37.36
9
5 19.71
3
17 73.30
20
24 14.98
2
44 41.82
7
-1084-
MEAN S.D.
N
125.58 61.184
20
28 14.0
20
83.68 60.728
20
19 15.1
20
87.01 67.916
20
19 16.1
20
63.87 51.948
20
14 14.6
20
85.93 52.157
20
25 16.7
20
63.17 50.376
20
16 16.2
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS FEMALES
PAGE 9
GROUP 1: 0 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 1
TIME
ERRORS
(SEC)
(NO.)
2 -A
TRIAL NUMBER 2
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 3
TIME
ERRORS
(SEC)
(NO.)
3 -A
TRIAL NUMBER 4
TIME
ERRORS
(SEC)
(NO.)
DAY 4 - B
TRIAL NUMBER 5
TRIAL NUMBER 6
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
180.00 E 98.31 66.99 58.97 31.21 62.77 61.52 24.93 44.49 52.59 44.62 67.18 35.05 36.94
180.00 E 16.20
108.09 39.21 44.17 25.84
41 31.81 25 60.45 14 59.95 13 180.00 E
4 180.00 E 15 28.05 15 76.32
4 180.00 E 10 115.58
7 109.05 9 14.09 10 49.21 8 65.00 5 13.59 38 36.08 1 79.21 19 76.05 8 22.34 10 13.83 4 40.34
3 15 15 41 44
6 18 45 29 24
0 10 17
1 5 14 11 3 1 10
88.68 62.03 13.88 178.21 65.04 100.70 10.70 127.50 24.38 73.61 50.71 17.59 15.59 65.18 85.98 26.49 75.87 61.53 44.62 40.98
17 87.99
15
20 14.38
2
0 12.26
0
38 43.20
11
14 11.38
0
37 180.00 E 58
0 35.88
9
34 14.36
1
2 14.41
1
13 82.93
15
11 11.58
0
2 26.99
4
1 29.43
10
12 21.38
3
20 39.63
9
6 15.91
2
19 54.98
10
19 22.75
4
11 46.43
11
8 30.15
4
180.00 E 33 113.66
18
116.13
23 180.00 E 39
180.00 E 51 180.00 E 39
180.00 E
41
47.49
14
180.00 E 44 180.00 E 39
180.00 E 43 150.16
29
95.91
28 116.74
32
180.00 E 42 180.00 E 33
180.00 E 33 180.00 E 29
180.00 E 33 180.00 E 31
180.00 E
41
99.20
21
90.87
23 180.00 E 30
61.44
12 109.20
31
180.00 E 34 180.00 E 35
180.00 E 51 180.00 E 44
180.00 E 33 180.00 E 38
32.37
8 180.00 E 37
180.00 E 41 180.00 E 39
180.00 E 28 116.45
14
180.00 E
27
91.46
15
-1085-
MEAN S.D.
N
63.95 45.821
20
13 10.7
20
71.55 55.083
20
16 14.2
20
61.46 42.016
20
14 11.7
20
39.80 39.740
20
8 12.7
20
154.84 47.173
20
33 11.5
20
150.22 41.379
20
30 9.3
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS FEMALES
PAGE
GROUP 1: 0 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 7
TIME
ERRORS
(SEC)
(NO.)
5 -B
TRIAL NUMBER 8
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 9
TIME
ERRORS
(SEC)
(NO.)
6 -B
TRIAL NUMBER 10
TIME
ERRORS
(SEC)
(NO.)
DAY 7 (PROBE) - A
TRIAL NUMBER 11
TRIAL NUMBER 12
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25687-15 25681-10 25615-10 25637-17 25638-18 25713-16 25670-18 25657-10 25663-09 25690-19 25666-09 25692-07 25701-18 25645-08
180.00 E 180.00 E 180.00 E
87.70 180.00 E
58.09 180.00 E
68.37 143.25 180.00 E
62.26 180.00 E
26.10 91.48 140.68 180.00 E 180.00 E 180.00 E 180.00 E 36.51
31 180.00 E 36 54.85 38 180.00 E 23 78.64 45 180.00 E 12 26.01 40 104.59 21 52.88 31 180.00 E 25 180.00 E 13 91.61 21 180.00 E
4 49.45 19 24.84 38 180.00 E 34 180.00 E 41 48.29 44 170.33 33 76.90
9 71.51
32 9
28 22 33
1 26 14 33 26 16 33 10
4 42 35 10 45 12 17
180.00 E 40 180.00 E
111.81
24 24.98
65.55
15 87.49
180.00 E 40 180.00 E
180.00 E 39 180.00 E
70.47
25 33.13
180.00 E
52
31.84
54.89
20 44.02
72.79
18 75.72
180.00 E 29 137.76
180.00 E
48
58.58
62.98
12 14.18
17.18
3 99.27
19.54
4 13.88
180.00 E 47 180.00 E
180.00 E 32 180.00 E
23.58
2 29.20
126.35
31 113.65
180.00 E 38 145.06
16.95
1 11.31
39 60.77 5 99.01
19 123.41 52 41.53 42 34.80
6 77.26 8 31.05 12 45.12 21 117.97 20 120.45 10 169.74 1 111.40 27 180.00 E 2 63.87 37 75.52 34 39.42 5 56.06 29 121.38 20 70.77 0 51.97
13 153.73 22 26.46 39 16.74 11 132.48
7 41.05 25 18.46
8 45.68 12 15.24 31 37.43 30 59.73 36 83.27 29 12.46 51 95.45 17 21.53 22 134.20 10 32.65 13 84.75 32 62.99 22 15.89 16 16.10
32 5 2
42 9 3
11 3 4
13 19
0 34
4 41
6 23 15
2 3
-1086-
MEAN S.D.
N
134.72 57.907
20
28 12.2
20
114.50 62.597
20
22 12.7
20
113.10 67.774
20
26 16.2
20
91.00 65.705
20
19 15.4
20
84.58 43.854
20
22 11.8
20
55.31 44.536
20
14 13.7
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS FEMALES
PAGE 11
GROUP 2: 0.1 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 1
TIME
ERRORS
(SEC)
(NO.)
2 -A
TRIAL NUMBER 2
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 3
TIME
ERRORS
(SEC)
(NO.)
3 -A
TRIAL NUMBER 4
TIME
ERRORS
(SEC)
(NO.)
DAY 4 - B
TRIAL NUMBER 5
TRIAL NUMBER 6
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
27.88 34.06 157.38 180.00 E 25.83 94.75 178.78 35.99 180.00 E 180.00 E 55.93 180.00 E 58.82 39.05 45.72 29.83 32.97 25.12 50.18 27.23
3 35.59 8 37.45 11 76.82 20 121.50 6 31.52 25 21.36 21 56.59 6 73.28 34 153.88 42 147.06 10 38.75 46 142.16 12 48.66 7 180.00 E 10 57.79 4 180.00 E 6 109.64 3 163.56 9 27.86 5 19.63
7 8 16 23 6 5 12 17 32 31 7 31 10 47 14 31 29 22 4 4
75.92
19 37.55
15
86.56
26 29.44
5
49.52
14 63.34
18
13.52
0 9.06
0
18.68
1 92.41
23
15.97
2 18.89
5
22.50
3 21.92
3
30.71
7 15.34
2
55.14
11 17.45
1
57.59
14 22.91
2
45.18
11 77.98
21
88.56
17 44.22
9
20.38
3 11.76
0
67.07
12 180.00 E 45
27.90
6 22.22
3
180.00 E
37
95.13
12
119.69
28 52.52
12
97.52
20 17.52
0
30.91
4 14.78
0
31.06
7 18.52
3
29.53
10 11.02
1
126.84
28 46.16
7
180.00 E 35 180.00 E 26
180.00 E
43
51.81
9
180.00 E 30 180.00 E 31
180.00 E 43 128.04
26
180.00 E 28 180.00 E 26
155.85
31 27.72
6
144.99
27 180.00 E 40
180.00 E
45
34.61
7
180.00 E 35 180.00 E 34
71.69
14 180.00 E 48
164.59
27 38.55
5
180.00 E 37 113.49
22
180.00 E 41 180.00 E 43
180.00 E 33 180.00 E 38
87.52
20 180.00 E 31
180.00 E 35 180.00 E 29
180.00 E 35 133.38
23
180.00 E
40
85.29
19
- 801-
MEAN S.D.
N
81.98 65.243
20
14 12.9
20
86.16 57.290
20
18 12.3
20
56.72 42.111
20
12 10.0
20
43.15 41.878
20
9 11.2
20
156.05 43.725
20
32 123.50
24
9.3 65.560 13.9
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS FEMALES
PAGE 12
GROUP 2: 0.1 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 7
TIME
ERRORS
(SEC)
(NO.)
5 -B
TRIAL NUMBER 8
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 9
TIME
ERRORS
(SEC)
(NO.)
6 -B
TRIAL NUMBER 10
TIME
ERRORS
(SEC)
(NO.)
DAY 7 (PROBE) - A
TRIAL NUMBER 11
TRIAL NUMBER 12
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25648-12 25674-11 25694-13 25631-05 25660-04 25704-09 25665-07 25652-13 25733-08 25748-08 25753-15 25672-15 25655-13 25727-16 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
180.00 E 20.47
180.00 E 74.49
180.00 E 17.68
180.00 E 180.00 E
37.02 121.17 180.00 E
84.31 50.84 19.99 180.00 E 180.00 E 180.00 E 180.00 E 26.38 131.58
38 45.18 4 13.56
36 180.00 E 20 145.46 29 180.00 E
1 22.24 38 115.14 40 42.07
3 79.53 26 51.18 25 180.00 E 24 60.98 12 60.65
3 22.59 40 180.00 E 30 180.00 E 39 180.00 E 39 71.68
5 19.88 35 125.67
9 1 42 33 25 2 32 7 9 8 26 14 18 4 45 25 37 10 1 38
128.61
29 45.77
19.11
5 8.16
180.00 E
42
48.88
18.07
3 180.00 E
180.00 E
44
86.24
14.53
0 20.18
26.56
7 180.00 E
103.13
27 89.78
30.99
5 11.91
63.66
18 45.16
34.52
5 40.20
22.18
3 61.74
180.00 E
51
33.80
23.17
4 68.24
83.70
21 109.74
120.03
21 180.00 E
180.00 E 30 180.00 E
32.06
3 26.74
111.62
27 12.88
60.77
14 14.77
15 61.77 0 122.87 7 128.30
40 37.66 11 80.50
1 76.99 42 180.00 E 18 26.03
0 76.91 10 35.91
7 74.83 12 33.20
6 25.88 14 105.37 28 159.95 38 58.63 32 51.94
4 88.21 0 24.27 1 132.91
22 14.66 24 26.78 35 52.18
7 43.34 22 44.25 25 61.20 51 180.00 E
3 38.06 22 107.12
7 40.25 18 145.41
5 14.28 6 22.43 23 51.95 50 44.31 14 60.70 14 31.31 22 24.82 4 23.88 53 27.83
2 8 13 12 10 16 61 4 29 8 33 0 4 9 10 10 6 5 2 8
-1088-
MEAN S.D.
N
119.20 68.931
20
24 14.5
20
97.79 64.979
20
19 14.7
20
80.64 62.479
20
18 15.6
20
72.21 61.696
20
14 14.1
20
79.11 46.200
20
21 15.5
20
52.74 43.343
20
13 14.1
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS FEMALES
PAGE 13
GROUP 3: 0.3 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 1
TIME
ERRORS
(SEC)
(NO.)
2 -A
TRIAL NUMBER 2
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 3
TIME
ERRORS
(SEC)
(NO.)
3 -A
TRIAL NUMBER 4
TIME
ERRORS
(SEC)
(NO.)
DAY 4 - B
TRIAL NUMBER 5
TRIAL NUMBER 6
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
36.34 36.27 62.82 27.90 62.56 47.34 48.96 38.36 85.56 132.66 48.60 34.84 28.09 40.23 33.16 27.64 14.36 53.30 21.06 126.16
6 56.20 6 15.26 12 80.96 4 27.11 17 29.03 10 116.53 9 65.62 10 74.93 21 44.55 32 41.25 8 35.06 5 36.20 4 29.01 8 12.84 7 34.41 3 77.17 1 180.00 E 10 31.95 1 121.52 20 14.56
13 1
18 6 8
37 17 13 10
7 4 6 6 1 7 20 30 5 22 1
79.18 131.13
12.01 27.30 43.09 18.20 11.53 70.02 19.20 25.45 35.99 29.91 28.86 18.12 51.49 38.58 16.75 20.63 49.84 93.16
15 29.23 29 22.18
0 23.25 4 19.99 12 49.52 2 20.69 0 8.04 22 13.37 2 15.61 4 25.33 11 96.77 7 30.59 4 32.59 2 11.16 13 55.01 8 74.56 1 32.97 3 15.20 12 41.13 25 16.56
3 180.00 E 41 180.00 E 35
3 37.67
6 180.00 E 36
3 180.00 E 37 180.00 E 44
2 64.86
13 21.44
4
17 180.00 E 34 171.90
50
4 82.06 22 20.77
3
0 180.00 E 39 180.00 E 28
2 180.00 E 46 180.00 E D
2
180.00 E
35
68.37
11
3 180.00 E 44 180.00 E 49
27
180.00 E
39
59.60
12
7 180.00 E 32 180.00 E 28
6
180.00 E
28
61.55
8
0 180.00 E 39 180.00 E 39
13 180.00 E 27 180.00 E 40
17 180.00 E 28 167.09
35
6 180.00 E 41 180.00 E 36
1 89.84 25 67.52 13
8 180.00 E 42 180.00 E 41
3 180.00 E 35 180.00 E 42
-1089-
MEAN S.D.
N
50.31 10 56.21 12 41.02
9 31.69
6 157.72
33 139.91
29
31.568
7.7 42.679
9.8
31.033
8.5 22.442
7.0
46.628
10.3
61.655
15.6
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS FEMALES
PAGE 14
GROUP 3: 0.3 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 7
TIME
ERRORS
(SEC)
(NO.)
5 -B
TRIAL NUMBER 8
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 9
TIME
ERRORS
(SEC)
(NO.)
6 -B
TRIAL NUMBER 10
TIME
ERRORS
(SEC)
(NO.)
DAY 7
TRIAL NUMBER 11
TIME
ERRORS
(SEC)
(NO.)
(PROBE) - A
TRIAL NUMBER 12
TIME
ERRORS
(SEC)
(NO.)
25671-06 25614-17 25698-12 25677-08 25604-12 25678-11 25609-11 25623-15 25653-13 25684-06 25714-13 25650-17 25735-08 25722-15 25628-17 25766-06 25689-14 25708-15 25743-16 25642-12
180.00 E 180.00 E 113.04
10.91 23.45 71.80 158.91 100.77 32.38 180.00 E 180.00 E 180.00 E 103.62 33.84 50.71 25.53 180.00 E 180.00 E 180.00 E 180.00 E
33 180.00 E 42 180.00 E 29 41.18
0 11.31 5 20.76 22 24.16 36 48.94 25 81.66 5 49.04 48 97.08 42 177.61 37 21.65 26 67.12 10 180.00 E 13 40.52 6 16.06 42 180.00 E 43 180.00 E 40 180.00 E 30 180.00 E
27 38 20
0 3 5 11 21 9 15 37 3 15 53 7 2 44 42 39 34
125.99
28 21.60
180.00 E 36 180.00 E
24.44
4 103.51
11.81
0 60.90
28.45
4 19.13
26.93
6 35.63
60.89
18 25.52
16.96
3 76.28
180.00 E
43
43.26
65.90
19 41.96
15.63
3 25.68
9.56
0 10.07
89.04
18 50.31
48.38
12 26.20
34.75
6 36.33
9.20
0 10.18
109.13
21 180.00 E
180.00 E 23 132.31
108.76
22 89.70
180.00 E 29 112.88
4 44.31 39 67.32 25 180.00 E 13 51.22
2 79.38 12 70.08
5 9.65 23 48.59 11 46.72
7 72.61 6 41.91 0 29.56 13 16.28 6 180.00 E 5 81.64 0 80.36 42 19.96 32 53.13 18 62.05 20 86.00
8 27.89 14 85.18 67 180.00 E 17 14.19 25 80.80 26 82.99
0 9.00 22 180.00 E
9 75.41 24 47.44 12 89.12
5 18.34 2 125.63 56 85.68 28 51.56 25 58.13 3 44.43 10 23.29 16 18.33 15 86.41
5 18 53
2 23 27
0 69 16 14 33
2 37 27 13 14 10
3 2 20
-1090-
MEAN S.D.
N
117.25 67.598
20
27 15.3
20
97.85 71.613
20
21 16.7
20
75.29 64.213
20
15 12.9
20
64.07 52.824
20
14 12.5
20
66.04 44.900
20
19 16.9
20
69.19 49.461
20
19 18.0
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
PROJECT NO. :WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO. :06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS FEMALES
PAGE 15
GROUP 4: 1.0 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 1
TIME
ERRORS
(SEC)
(NO.)
2 -A
TRIAL NUMBER 2
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 3
TIME
ERRORS
(SEC)
(NO.)
3 -A
TRIAL NUMBER 4
TIME
ERRORS
(SEC)
(NO.)
DAY 4 - B
TRIAL NUMBER 5
TRIAL NUMBER 6
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25696-11
26.33
4 33.67
7
25686-10
180.00 E
24
100.68
25
25630-09
42.67
6 127.50
28
25673-10
180.00 E
41
132.49
29
25639-04
30.24
5 24.21
3
25658-14
74.06
12 72.31
12
25676-15
43.69
9 180.00 E 44
25600-15
174.24
37 16.95
1
25603-10
79.59
20 45.98
7
25703-10
50.38
11 103.16
27
25705-08
59.51
13 20.86
3
25611-11
102.35
26 21.96
2
25619-12
36.34
7 132.52
23
25691-11
34.63
6 52.43
9
25717-15
32.00
4 97.09
22
25616-14
24.57
3 90.34
21
25715-10
29.39
7 59.16
15
25599-11
180.00 E
30
98.53
21
25762-11
41.91
8 130.06
25
25647-11
69.10
17 73.17
16
40.20
9 33.23
7
45.17
10 20.78
3
31.18
6 37.04
7
38.17
10 34.25
11
38.47
5 33.02
5
180.00 E 41 180.00 E 36
172.55
60 30.39
6
34.20
6 18.87
2
17.97
1 14.38
1
37.37
10 33.00
7
18.50
3 23.62
6
33.18
7 28.29
4
180.00 E
39
60.09
14
46.59
12 173.34
35
88.79
21 16.83
0
36.42
8 33.85
7
16.81
4 32.56
8
180.00 E
40
42.99
8
78.13
19 55.99
12
44.72
12 42.37
12
44.82 155.30 142.49 180.00
62.70 128.95 109.84 180.00 180.00 180.00 180.00 180.00 180.00 180.00 180.00 180.00 180.00
28.23 82.56 180.00
E
E E E E E E E E E E
E
8 145.49 31 180.00 E 32 180.00 E 43 180.00 E
8 180.00 E 21 180.00 E 28 20.24 53 180.00 E 43 180.00 E 46 180.00 E 37 174.13 47 25.52 33 180.00 E 44 109.99 38 180.00 E 31 138.03 34 180.00 E
4 180.00 E 19 27.78 45 180.00 E
40 46 42 44 39 37
3 39 38 27 43
3 37 32 37 30 36 40
5 39
-1091-
MEAN S.D.
N
74.55 15 80.65 17 67.92 16 47.24 10 145.74 32 149.06 33
56.967
11.5
46.187
11.4
59.104
16.0
45.762
9.6
51.625
14.0
56.800
13.4
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
PROJECT NO.:WIL-180017S SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 31 (F1 - PND 22) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BIEL MAZE SWIM TRIALS FEMALES
PAGE 16
GROUP 4: 1.0 MG/KG/DAY
PUP NO.
DAY
TRIAL NUMBER 7
TIME
ERRORS
(SEC)
(NO.)
5 -B
TRIAL NUMBER 8
TIME
ERRORS
(SEC)
(NO.)
DAY
TRIAL NUMBER 9
TIME
ERRORS
(SEC)
(NO.)
6 -B
TRIAL NUMBER 10
TIME
ERRORS
(SEC)
(NO.)
DAY 7 (PROBE) - A
TRIAL NUMBER 11
TRIAL NUMBER 12
TIME
ERRORS
TIME
ERRORS
(SEC)
(NO.)
(SEC)
(NO.)
25696-11
27.06
6 35.82
5
25686-10
103.03
23 84.49
24
25630-09
49.76
11 19.54
2
25673-10
84.21
24 19.31
3
25639-04
180.00 E
42
52.42
9
25658-14
180.00 E
37
180.00 E
33
25676-15
20.16
3 81.49
20
25600-15
180.00 E
26
72.43
15
25603-10
180.00 E
36
180.00 E
38
25703-10
132.39
34 180.00 E 43
25705-08
41.51
8 43.08
9
25611-11
59.68
16 31.96
5
25619-12
29.94
9 180.00 E 42
25691-11
180.00 E
32
180.00 E
34
25717-15
180.00 E
39
154.52
30
25616-14
17.92
3 24.09
4
25715-10
153.23
41 88.86
30
25599-11
180.00 E
43
71.07
17
25762-11
180.00 E
44
49.00
9
25647-11
180.00 E
38
180.00 E
50
48.04
6 87.99
13.32
0 11.87
15.79
0 11.75
13.33
2 39.38
92.74
22 16.59
36.47
6 78.87
161.45
45 23.66
39.26
10 14.55
100.85
21 180.00 E
18.99
3 13.54
180.00 E
51
95.52
14.27
1 8.61
180.00 E 41 113.41
180.00 E 39 180.00 E
180.00 E 34 105.31
119.32
29 17.67
63.55
24 10.51
176.27
38 43.88
67.40
14 180.00 E
108.35
20 38.81
21 94.24 0 42.48 0 46.71
11 99.74 1 33.92
14 26.95 3 109.73 2 95.34
52 28.27 2 124.09
33 73.93 0 28.81
23 41.04 32 118.52 15 47.70
4 103.18 2 180.00 E 8 81.55 44 66.88 4 130.95
28 156.77 14 43.01 12 15.69 35 100.90
7C 6 66.48 41 18.13 34 49.89 5 30.91 41 81.56 27 51.86 4 13.09 12 17.18 37 24.92 7 85.25 27 49.47 64 52.99 13 126.03 19 42.98 38 49.68
41 13
2 27
1 19
4 14
8 26 18
0 3 4 19 18 21 34 9 14
-1092-
MEAN S.D.
N
116.94 67.633
20
26 14.8
20
95.40 64.422
20
21 15.4
20
90.47 65.982
20
20 16.7
20
63.60 60.844
20
14 15.7
20
78.70 42.154
20
24 16.2
20
56.67 38.853
19
15 11.4
20
A = ANIMALS TESTED IN PATH A DIRECTION
(FORWARD ROUTE THROUGHMAZE)
B = ANIMALS TESTED IN PATH B DIRECTION
(REVERSE ROUTE THROUGHMAZE)
C = TIME NOT RECORDED; NOTINCLUDED IN CALCULATION OF MEANS
E = ANIMAL DID NOT ESCAPE WITHIN 3 MINUTE LIMIT, PLACED ON HIDDEN PLATFORM FOR APPROXIMATELY 20 SECONDS
MANUALvl.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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: DILATED PELVIS RIGHT
GROSS:ADRENAL GLANDS EYES LYMPH NODE, MES PITUITARY SKIN TESTES URINARY BLADDER
BRAIN HEART LUNGS PROSTATE SPLEEN THYMUS
3
EPIDIDYMIDES INTESTINE MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
ESOPHAGUS LIVER PANCREAS SAL. GLAND MAND SEMINAL VESICLES TRACHEA
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-io n -
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-zoi t -
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: DILATED PELVIS RIGHT
GROSS:ADRENAL GLANDS EYES LYMPH NODE, MES PITUITARY SKIN TESTES URINARY BLADDER
BRAIN HEART LUNGS PROSTATE SPLEEN THYMUS
3
EPIDIDYMIDES INTESTINE MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
ESOPHAGUS LIVER PANCREAS SAL. GLAND MAND SEMINAL VESICLES TRACHEA
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-eon-
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-son-
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-on-
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-son-
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-oiii-
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: DILATED PELVIS BILATERAL
GROSS:ADRENAL GLANDS EYES LYMPH NODE, MES PITUITARY SKIN TESTES URINARY BLADDER
BRAIN HEART LUNGS PROSTATE SPLEEN THYMUS
3
EPIDIDYMIDES INTESTINE MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
ESOPHAGUS LIVER PANCREAS SAL. GLAND MAND SEMINAL VESICLES TRACHEA
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-m i-
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: EYE(S)- OPACITY BILATERAL; CEO OPACITY
GROSS:ADRENAL GLANDS HEART LYMPH NODE, MES PITUITARY SKIN TESTES URINARY BLADDER
BRAIN INTESTINE LUNGS PROSTATE SPLEEN THYMUS
P
EPIDIDYMIDES KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
ESOPHAGUS LIVER PANCREAS SAL. GLAND MAND SEMINAL VESICLES TRACHEA
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: DILATED PELVIS RIGHT
GROSS:ADRENAL GLANDS EYES LYMPH NODE, MES PITUITARY SKIN TESTES URINARY BLADDER
BRAIN HEART LUNGS PROSTATE SPLEEN THYMUS
2
EPIDIDYMIDES INTESTINE MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
ESOPHAGUS LIVER PANCREAS SAL. GLAND MAND SEMINAL VESICLES TRACHEA
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-eiii-
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
EYES
HEART
LIVER
LYMPH NODE, MES
PANCREAS
PITUITARY
SAL. GLAND MAND SKIN
SEMINAL VESICLES TESTES
TRACHEA
URINARY BLADDER
EPIDIDYMIDES INTESTINE LUNGS PROSTATE SPLEEN THYMUS
ESOPHAGUS KIDNEYS MAMMARY GLAND SPINAL CORD STOMACH THYROID GLANDS
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
THYMUS
NO SIGNIFICANT CHANGES OBSERVED
GROSS: GROSS:
DILATED PELVIS RIGHT
AREA(S), DARK RED MULTIPLE, IRREGULARLY
SHAPED
GROSS:ADRENAL GLANDS HEART LUNGS PANCREAS SKIN TRACHEA VAGINA
BRAIN INTESTINE MAMMARY GLAND PITUITARY SPLEEN URINARY BLADDER
ESOPHAGUS LIVER OVIDUCTS SPINAL CORD STOMACH UTERUS
2
P
EYES LYMPH NODE, MES OVARIES SAL. GLAND MAND THYROID GLANDS CERVIX
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-sill-
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: CONTENTS, CLEAR FLUID BOTH HORNS
GROSS:ADRENAL GLANDS HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS CERVIX
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS VAGINA
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA
P
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
-III-
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
- 8111-
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: DILATED PELVIS RIGHT
GROSS:ADRENAL GLANDS HEART LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
BRAIN INTESTINE MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
2
ESOPHAGUS LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
EYES LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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
NO SIGNIFICANT CHANGES OBSERVED
GROSS: CONTENTS, CLEAR FLUID BOTH HORNS
GROSS:ADRENAL GLANDS HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS CERVIX
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS VAGINA
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA
P
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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 HEART LYMPH NODE, MES OVARIES SAL. GLAND MAND THYMUS UTERUS
BRAIN INTESTINE LUNGS PANCREAS SKIN THYROID GLANDS CERVIX
ESOPHAGUS KIDNEYS MAMMARY GLAND PITUITARY SPLEEN TRACHEA VAGINA
EYES LIVER OVIDUCTS SPINAL CORD STOMACH URINARY BLADDER
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
ANIMAL NO.25597-07 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/13/06
DATE OF DEATH: 06/13/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5342 22.5 14.8 39.
REL. 3.934
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
1
GRADE
-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
ANIMAL NO.25654-05 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/13/06
DATE OF DEATH: 06/13/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5633 22.7 15.0 48.
REL. 3.257
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
2
GRADE
-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
ANIMAL NO.25632-06 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5922 22.4 15.1 57.
REL. 2.793
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
3
GRADE
- 11-
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
ANIMAL NO.25633-04 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.3776 20.7 14.5 35.
REL. 3.936
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
4
GRADE
-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
ANIMAL NO.25618-07 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6450 22.0 15.3 54.
REL. 3.046
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
5
GRADE
-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
ANIMAL NO.25621-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7036 22.7 15.4 56.
REL. 3.042
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
6
GRADE
-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
ANIMAL NO.25687-05 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6198 22.5 15.3 54.
REL. 3.000
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
7
GRADE
-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
ANIMAL NO.25681-06 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7520 22.9 15.4 57.
REL. 3.074
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
8
GRADE
-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
ANIMAL NO.25615-05 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6743 22.4 15.4 52.
REL. 3.220
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE
9
GRADE
-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
ANIMAL NO.25637-11 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6787 22.5 15.4 59.
REL. 2.845
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 10 GRADE
-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
ANIMAL NO.25638-05 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6259 22.4 15.2 56.
REL. 2.903
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 11 GRADE
-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
ANIMAL NO.25713-08 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6503 22.4 14.8 57.
REL. 2.895
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 12 GRADE
-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
ANIMAL NO.25670-03 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6338 22.2 14.9 57.
REL. 2.866
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 13 GRADE
-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
ANIMAL NO.25657-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4956 22.4 14.3 64.
REL. 2.337
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 14 GRADE
-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
ANIMAL NO.25663-02 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5796 22.4 15.0 63.
REL. 2.507
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 15 GRADE
-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
ANIMAL NO.25648-10 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/13/06
DATE OF DEATH: 06/13/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5226 22.1 14.7 46.
REL. 3.310
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 16 GRADE
-o s t i -
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
ANIMAL NO.25674-05 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5905 22.4 14.6 43.
REL. 3.699
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 17 GRADE
-isti-
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
ANIMAL NO.25694-11 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7530 22.9 15.4 62.
REL. 2.827
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 18 GRADE
-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
ANIMAL NO.25631-07 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6294 22.9 15.0 58.
REL. 2.809
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 19 GRADE
-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
ANIMAL NO.25660-02 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6608 22.7 15.2 58.
REL. 2.863
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 20 GRADE
-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
ANIMAL NO.25704-04 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5406 22.4 14.6 57.
REL. 2.703
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 21 GRADE
-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
ANIMAL NO.25665-02 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6061 22.6 14.7 45.
REL. 3.569
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 22 GRADE
-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
ANIMAL NO.25652-03 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5975 22.5 14.6 54.
REL. 2.958
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 23 GRADE
-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
ANIMAL NO.25733-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5312 22.1 14.8 42.
REL. 3.646
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 24 GRADE
-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
ANIMAL NO.25748-05 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6508 22.5 15.1 61.
REL. 2.706
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 25 GRADE
-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
ANIMAL NO.25753-03 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7192 22.7 15.2 56.
REL. 3.070
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 26 GRADE
-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
ANIMAL NO.25672-05 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5875 22.2 15.2 53.
REL. 2.995
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 27 GRADE
-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
ANIMAL NO.25655-07 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5492 22.2 14.7 51.
REL. 3.038
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 28 GRADE
-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
ANIMAL NO.25727-05 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5137 22.0 14.9 49.
REL. 3.089
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 29 GRADE
-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
ANIMAL NO.25626-07 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5539 22.3 15.1 61.
REL. 2.547
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 30 GRADE
-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
ANIMAL NO.25671-03 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/13/06
DATE OF DEATH: 06/13/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5957 22.9 15.1 56.
REL. 2.849
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 31 GRADE
-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
ANIMAL NO.25614-04 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4764 21.5 14.6 49.
REL. 3.013
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 32 GRADE
-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
ANIMAL NO.25698-02 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5305 21.8 15.1 45.
REL. 3.401
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 33 GRADE
-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
ANIMAL NO.25677-04 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5833 22.1 14.9 49.
REL. 3.231
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 34 GRADE
-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
ANIMAL NO.25604-06 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6137 22.3 14.9 55.
REL. 2.934
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 35 GRADE
-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
ANIMAL NO.25678-03 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4652 22.2 15.1 55.
REL. 2.664
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 36 GRADE
-0LU-
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
ANIMAL NO.25609-03 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5998 22.2 14.8 51.
REL. 3.137
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 37 GRADE
-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
ANIMAL NO.25623-04 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6663 22.4 15.2 50.
REL. 3.333
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 38 GRADE
-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
ANIMAL NO.25653-03 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5225 22.0 14.8 59.
REL. 2.581
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 39 GRADE
-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
ANIMAL NO.25684-05 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7210 22.0 15.3 59.
REL. 2.917
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 40 GRADE
-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
ANIMAL NO.25714-06 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6641 22.2 14.9 60.
REL. 2.774
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 41 GRADE
-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
ANIMAL NO.25735-04 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6405 22.5 14.9 61.
REL. 2.689
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 42 GRADE
-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
ANIMAL NO.25722-05 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5192 22.1 14.6 48.
REL. 3.165
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 43 GRADE
-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
ANIMAL NO.25628-09 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5399 22.2 15.2 53.
REL. 2.905
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 44 GRADE
-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
ANIMAL NO.25766-11 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5704 22.2 14.8 42.
REL. 3.739
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 45 GRADE
-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
ANIMAL NO.25696-07 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6459 22.5 15.1 52.
REL. 3.165
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 46 GRADE
- 0811-
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
ANIMAL NO.25686-02 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4767 21.9 14.6 47.
REL. 3.142
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 47 GRADE
-I8II-
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
ANIMAL NO.25630-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7562 22.7 15.4 54.
REL. 3.252
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 48 GRADE
-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
ANIMAL NO.25673-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4298 22.0 14.8 44.
REL. 3.250
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 49 GRADE
-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
ANIMAL NO.25639-09 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5940 22.0 15.0 56.
REL. 2.846
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 50 GRADE
-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
ANIMAL NO.25658-05 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5337 22.0 14.8 47.
REL. 3.263
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 51 GRADE
-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
ANIMAL NO.25676-03 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7188 22.9 14.9 60.
REL. 2.865
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 52 GRADE
-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
ANIMAL NO.25600-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7359 22.7 15.2 57.
REL. 3.045
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 53 GRADE
- 811-
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
ANIMAL NO.25603-05 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6978 22.3 15.0 56.
REL. 3.032
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 54 GRADE
-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
ANIMAL NO.25703-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7293 22.7 15.3 62.
REL. 2.789
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 55 GRADE
-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
ANIMAL NO.25705-05 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5358 21.8 15.0 56.
REL. 2.742
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 56 GRADE
-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
ANIMAL NO.25611-08 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6548 22.4 15.2 53.
REL. 3.122
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 57 GRADE
-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
ANIMAL NO.25619-05 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5516 22.2 14.9 51.
REL. 3.042
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 58 GRADE
-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
ANIMAL NO.25691-06 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6211 22.4 14.8 56.
REL. 2.895
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 59 GRADE
-eli-
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
ANIMAL NO.25717-03 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6253 22.2 14.9 46.
REL. 3.533
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 60 GRADE
-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
ANIMAL NO.25597-16 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/13/06
DATE OF DEATH: 06/13/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.3884 21.3 14.4 37.
REL. 3.752
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 61 GRADE
-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
ANIMAL NO.25654-11 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/13/06
DATE OF DEATH: 06/13/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5404 21.7 14.5 39.
REL. 3.950
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 62 GRADE
-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
ANIMAL NO.25632-10 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6386 22.6 15.4 58.
REL. 2.825
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 63 GRADE
-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
ANIMAL NO.25633-11 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4920 20.7 14.4 35.
REL. 4.263
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 64 GRADE
-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
ANIMAL NO.25618-15 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4737 21.7 14.6 50.
REL. 2.947
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 65 GRADE
-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
ANIMAL NO.25621-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6777 22.3 15.2 53.
REL. 3.165
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 66 GRADE
-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
ANIMAL NO.25687-14 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6004 22.2 15.0 49.
REL. 3.266
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 67 GRADE
-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
ANIMAL NO.25681-11 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6107 22.5 14.7 45.
REL. 3.579
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 68 GRADE
-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
ANIMAL NO.25615-08 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5897 21.4 14.7 56.
REL. 2.839
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 69 GRADE
-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
ANIMAL NO.25637-15 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7608 22.2 15.3 58.
REL. 3.036
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 70 GRADE
-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
ANIMAL NO.25638-16 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7253 22.7 15.4 55.
REL. 3.137
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 71 GRADE
-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
ANIMAL NO.25713-12 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6703 22.5 15.1 55.
REL. 3.037
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 72 GRADE
-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
ANIMAL NO.25670-16 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6038 21.9 14.6 48.
REL. 3.341
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 73 GRADE
-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
ANIMAL NO.25657-15 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5723 22.4 14.3 51.
REL. 3.083
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 74 GRADE
-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
ANIMAL NO.25663-10 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6434 22.3 15.3 60.
REL. 2.739
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 75 GRADE
-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
ANIMAL NO.25648-14 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/13/06
DATE OF DEATH: 06/13/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5386 21.8 14.6 46.
REL. 3.345
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 76 GRADE
-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
ANIMAL NO.25674-14 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4823 20.9 14.3 34.
REL. 4.360
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 77 GRADE
-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
ANIMAL NO.25694-15 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6310 22.0 14.8 58.
REL. 2.812
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 78 GRADE
-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
ANIMAL NO.25631-15 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5908 21.8 14.8 53.
REL. 3.002
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 79 GRADE
-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
ANIMAL NO.25660-13 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4944 21.9 14.9 57.
REL. 2.622
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 80 GRADE
-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
ANIMAL NO.25704-12 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5839 21.7 14.6 52.
REL. 3.046
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 81 GRADE
-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
ANIMAL NO.25665-05 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6624 22.2 15.0 51.
REL. 3.260
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 82 GRADE
-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
ANIMAL NO.25652-08 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6292 22.1 14.6 51.
REL. 3.195
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 83 GRADE
-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
ANIMAL NO.25733-15 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4735 21.5 14.4 45.
REL. 3.274
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 84 GRADE
-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
ANIMAL NO.25748-10 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5158 22.2 14.6 50.
REL. 3.032
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 85 GRADE
-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
ANIMAL NO.25753-17 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.7194 22.5 14.8 57.
REL. 3.016
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 86 GRADE
-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
ANIMAL NO.25672-16 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5217 21.5 14.7 40.
REL. 3.804
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 87 GRADE
-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
ANIMAL NO.25655-15 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5495 22.2 14.8 52.
REL. 2.980
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 88 GRADE
-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
ANIMAL NO.25727-10 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5787 22.0 15.1 47.
REL. 3.359
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 89 GRADE
-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
ANIMAL NO.25626-15 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5813 22.1 14.5 53.
REL. 2.984
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 90 GRADE
-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
ANIMAL NO.25671-09 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/13/06
DATE OF DEATH: 06/13/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5259 22.9 14.5 46.
REL. 3.317
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 91 GRADE
-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
ANIMAL NO.25614-18 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5253 21.8 14.7 47.
REL. 3.245
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 92 GRADE
-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
ANIMAL NO.25698-04 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5141 22.0 14.7 46.
REL. 3.292
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 93 GRADE
-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
ANIMAL NO.25677-13 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6806 22.1 15.3 52.
REL. 3.232
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 94 GRADE
-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
ANIMAL NO.25604-10 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4340 21.8 14.6 49.
REL. 2.927
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 95 GRADE
-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
ANIMAL NO.25678-13 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5368 22.3 14.9 49.
REL. 3.136
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 96 GRADE
-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
ANIMAL NO.25609-12 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6100 21.5 15.1 57.
REL. 2.825
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 97 GRADE
-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
ANIMAL NO.25623-14 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5838 22.2 15.2 49.
REL. 3.232
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 98 GRADE
-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
ANIMAL NO.25653-05 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5506 22.4 14.4 59.
REL. 2.628
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 99 GRADE
-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
ANIMAL NO.25684-12 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6199 22.5 15.1 54.
REL. 3.000
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 100 GRADE
-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
ANIMAL NO.25714-08 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6276 22.2 15.1 56.
REL. 2.906
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 101 GRADE
-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
ANIMAL NO.25735-10 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5448 22.4 15.0 58.
REL. 2.663
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 102 GRADE
-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
ANIMAL NO.25722-12 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5623 22.6 15.0 50.
REL. 3.125
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 103 GRADE
-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
ANIMAL NO.25628-14 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5093 22.5 14.5 53.
REL. 2.848
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 104 GRADE
-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
ANIMAL NO.25766-08 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5093 21.9 14.7 43.
REL. 3.510
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 105 GRADE
-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
ANIMAL NO.25696-16 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6080 22.4 15.0 53.
REL. 3.034
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 106 GRADE
-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
ANIMAL NO.25686-09 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5509 21.5 14.7 47.
REL. 3.300
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 107 GRADE
-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
ANIMAL NO.25630-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6530 22.0 15.2 54.
REL. 3.061
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 108 GRADE
-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
ANIMAL NO.25673-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4314 21.4 14.5 42.
REL. 3.408
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 109 GRADE
-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
ANIMAL NO.25639-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4790 21.7 14.6 53.
REL. 2.791
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 110 GRADE
-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
ANIMAL NO.25658-10 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5486 21.8 14.8 48.
REL. 3.226
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 111 GRADE
-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
ANIMAL NO.25676-12 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6938 22.9 15.1 55.
REL. 3.080
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 112 GRADE
-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
ANIMAL NO.25600-12 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6127 22.1 14.9 58.
REL. 2.781
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 113 GRADE
-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
ANIMAL NO.25603-07 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4966 21.6 14.3 50.
REL. 2.993
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 114 GRADE
-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
ANIMAL NO.25703-08 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6146 22.0 15.0 52.
REL. 3.105
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 115 GRADE
-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
ANIMAL NO.25705-10 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4230 21.8 14.4 55.
REL. 2.587
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 116 GRADE
-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
ANIMAL NO.25611-15 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.6533 22.2 15.3 54.
REL. 3.062
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 117 GRADE
-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
ANIMAL NO.25619-14 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4748 21.5 14.4 48.
REL. 3.073
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 118 GRADE
-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
ANIMAL NO.25691-14 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.5656 22.2 15.0 58.
REL. 2.699
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 119 GRADE
-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
ANIMAL NO.25717-13 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.4477 21.5 14.6 46.
REL. 3.147
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV
PAGE 120 GRADE
-1254-
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
PGRHv4.54 10/05/2006 R:01/26/2007
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
MALE GROUP: 0 MG/KG/DAY WIDTH(MM)
25597-07 25654-05 25632-06 25633-04 25618-07 25621-01 25687-05 25681-06 25615-05 25637-11 25638-05 25713-08 25670-03 25657-01 25663-02
39. 48. 57. 35. 54. 56. 54. 57. 52. 59. 56. 57. 57. 64. 63.
1.5342 1.5633 1.5922 1.3776 1.6450 1.7036 1.6198 1.7520 1.6743 1.6787 1.6259 1.6503 1.6338 1.4956 1.5796
22.5 22.7 22.4 20.7 22.0 22.7 22.5 22.9 22.4 22.5 22.4 22.4 22.2 22.4 22.4
14.8 15.0 15.1 14.5 15.3 15.4 15.3 15.4 15.4 15.4 15.2 14.8 14.9 14.3 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
PAGE 1
-1255-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
MALE GROUP: 0.1 MG/KG/DAY WIDTH(MM)
25648-10 25674-05 25694-11 25631-07 25660-02 25704-04 25665-02 25652-03 25733-01 25748-05 25753-03 25672-05 25655-07 25727-05 25626-07
46. 43. 62. 58. 58. 57. 45. 54. 42. 61. 56. 53. 51. 49. 61.
1.5226 1.5905 1.7530 1.6294 1.6608 1.5406 1.6061 1.5975 1.5312 1.6508 1.7192 1.5875 1.5492 1.5137 1.5539
22.1 22.4 22.9 22.9 22.7 22.4 22.6 22.5 22.1 22.5 22.7 22.2 22.2 22.0 22.3
14.7 14.6 15.4 15.0 15.2 14.6 14.7 14.6 14.8 15.1 15.2 15.2 14.7 14.9 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
PAGE
2
-1256-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
MALE GROUP: 0.3 MG/KG/DAY WIDTH(MM)
25671-03 25614-04 25698-02 25677-04 25604-06 25678-03 25609-03 25623-04 25653-03 25684-05 25714-06 25735-04 25722-05 25628-09 25766-11
56. 49. 45. 49. 55. 55. 51. 50. 59. 59. 60. 61. 48. 53. 42.
1.5957 1.4764 1.5305 1.5833 1.6137 1.4652 1.5998 1.6663 1.5225 1.7210 1.6641 1.6405 1.5192 1.5399 1.5704
22.9 21.5 21.8 22.1 22.3 22.2 22.2 22.4 22.0 22.0 22.2 22.5 22.1 22.2 22.2
15.1 14.6 15.1 14.9 14.9 15.1 14.8 15.2 14.8 15.3 14.9 14.9 14.6 15.2 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
PAGE
3
-1257-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
MALE GROUP: 1.0 MG/KG/DAY WIDTH(MM)
25696-07 25686-02 25630-01 25673-04 25639-09 25658-05 25676-03 25600-04 25603-05 25703-04 25705-05 25611-08 25619-05 25691-06 25717-03
52. 47. 54. 44. 56. 47. 60. 57. 56. 62. 56. 53. 51. 56. 46.
1.6459 1.4767 1.7562 1.4298 1.5940 1.5337 1.7188 1.7359 1.6978 1.7293 1.5358 1.6548 1.5516 1.6211 1.6253
22.5 21.9 22.7 22.0 22.0 22.0 22.9 22.7 22.3 22.7 21.8 22.4 22.2 22.4 22.2
15.1 14.6 15.4 14.8 15.0 14.8 14.9 15.2 15.0 15.3 15.0 15.2 14.9 14.8 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
PAGE
4
-1258-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
FEMALE GROUP: 0 MG/KG/DAY WIDTH(MM)
25597-16 25654-11 25632-10 25633-11 25618-15 25621-09 25687-14 25681-11 25615-08 25637-15 25638-16 25713-12 25670-16 25657-15 25663-10
37. 39. 58. 35. 50. 53. 49. 45. 56. 58. 55. 55. 48. 51. 60.
1.3884 1.5404 1.6386 1.4920 1.4737 1.6777 1.6004 1.6107 1.5897 1.7608 1.7253 1.6703 1.6038 1.5723 1.6434
21.3 21.7 22.6 20.7 21.7 22.3 22.2 22.5 21.4 22.2 22.7 22.5 21.9 22.4 22.3
14.4 14.5 15.4 14.4 14.6 15.2 15.0 14.7 14.7 15.3 15.4 15.1 14.6 14.3 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
PAGE 5
-1259-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
FEMALE GROUP: 0.1 MG/KG/DAY WIDTH(MM)
25648-14 25674-14 25694-15 25631-15 25660-13 25704-12 25665-05 25652-08 25733-15 25748-10 25753-17 25672-16 25655-15 25727-10 25626-15
46. 34. 58. 53. 57. 52. 51. 51. 45. 50. 57. 40. 52. 47. 53.
1.5386 1.4823 1.6310 1.5908 1.4944 1.5839 1.6624 1.6292 1.4735 1.5158 1.7194 1.5217 1.5495 1.5787 1.5813
21.8 20.9 22.0 21.8 21.9 21.7 22.2 22.1 21.5 22.2 22.5 21.5 22.2 22.0 22.1
14.6 14.3 14.8 14.8 14.9 14.6 15.0 14.6 14.4 14.6 14.8 14.7 14.8 15.1 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
PAGE
6
-1260-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
FEMALE GROUP: 0.3 MG/KG/DAY WIDTH(MM)
25671-09 25614-18 25698-04 25677-13 25604-10 25678-13 25609-12 25623-14 25653-05 25684-12 25714-08 25735-10 25722-12 25628-14 25766-08
46. 47. 46. 52. 49. 49. 57. 49. 59. 54. 56. 58. 50. 53. 43.
1.5259 1.5253 1.5141 1.6806 1.4340 1.5368 1.6100 1.5838 1.5506 1.6199 1.6276 1.5448 1.5623 1.5093 1.5093
22.9 21.8 22.0 22.1 21.8 22.3 21.5 22.2 22.4 22.5 22.2 22.4 22.6 22.5 21.9
14.5 14.7 14.7 15.3 14.6 14.9 15.1 15.2 14.4 15.1 15.1 15.0 15.0 14.5 14.7
MEAN S.D.
N
51. 4.9
15
1.5556 0.06085
15
22.2 0.37
15
14.9 0.29
15
PAGE
7
-1261-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 34 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
FEMALE GROUP: 1.0 MG/KG/DAY WIDTH(MM)
25696-16 25686-09 25630-11 25673-11 25639-11 25658-10 25676-12 25600-12 25603-07 25703-08 25705-10 25611-15 25619-14 25691-14 25717-13
53. 47. 54. 42. 53. 48. 55. 58. 50. 52. 55. 54. 48. 58. 46.
1.6080 1.5509 1.6530 1.4314 1.4790 1.5486 1.6938 1.6127 1.4966 1.6146 1.4230 1.6533 1.4748 1.5656 1.4477
22.4 21.5 22.0 21.4 21.7 21.8 22.9 22.1 21.6 22.0 21.8 22.2 21.5 22.2 21.5
15.0 14.7 15.2 14.5 14.6 14.8 15.1 14.9 14.3 15.0 14.4 15.3 14.4 15.0 14.6
MEAN S.D.
N
52. 4.6
15
1.5502 0.08778
15
21.9 0.41
15
14.8 0.31
15
PAGE
8
POFBWv4.14 10/05/2006 R:01/26/2007
-1262-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
MALE GROUP: 0 MG/KG/DAY
25597-07 25654-05 25632-06 25633-04 25618-07 25621-01 25687-05 25681-06 25615-05 25637-11 25638-05 25713-08 25670-03 25657-01 25663-02
39. 48. 57. 35. 54. 56. 54. 57. 52. 59. 56. 57. 57. 64. 63.
3.934 3.257 2.793 3.936 3.046 3.042 3.000 3.074 3.220 2.845 2.903 2.895 2.866 2.337 2.507
MEAN S.D.
N
54. 3.044 7.9 0.4336
15 15
PAGE 1
-1263-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
MALE GROUP: 0.1 MG/KG/DAY
25648-10 25674-05 25694-11 25631-07 25660-02 25704-04 25665-02 25652-03 25733-01 25748-05 25753-03 25672-05 25655-07 25727-05 25626-07
46. 43. 62. 58. 58. 57. 45. 54. 42. 61. 56. 53. 51. 49. 61.
3.310 3.699 2.827 2.809 2.863 2.703 3.569 2.958 3.646 2.706 3.070 2.995 3.038 3.089 2.547
MEAN S.D.
N
53. 3.055 6.8 0.3547
15 15
PAGE
2
-1264-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
MALE GROUP: 0.3 MG/KG/DAY
25671-03 25614-04 25698-02 25677-04 25604-06 25678-03 25609-03 25623-04 25653-03 25684-05 25714-06 25735-04 25722-05 25628-09 25766-11
56. 49. 45. 49. 55. 55. 51. 50. 59. 59. 60. 61. 48. 53. 42.
2.849 3.013 3.401 3.231 2.934 2.664 3.137 3.333 2.581 2.917 2.774 2.689 3.165 2.905 3.739
MEAN S.D.
N
53. 3.022 5.7 0.3150
15 15
PAGE
3
-1265-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
MALE GROUP: 1.0 MG/KG/DAY
25696-07 25686-02 25630-01 25673-04 25639-09 25658-05 25676-03 25600-04 25603-05 25703-04 25705-05 25611-08 25619-05 25691-06 25717-03
52. 47. 54. 44. 56. 47. 60. 57. 56. 62. 56. 53. 51. 56. 46.
3.165 3.142 3.252 3.250 2.846 3.263 2.865 3.045 3.032 2.789 2.743 3.122 3.042 2.895 3.533
MEAN S.D.
N
53. 3.066 5.3 0.2147
15 15
PAGE
4
-1266-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
FEMALE GROUP: 0 MG/KG/DAY
25597-16 25654-11 25632-10 25633-11 25618-15 25621-09 25687-14 25681-11 25615-08 25637-15 25638-16 25713-12 25670-16 25657-15 25663-10
37. 39. 58. 35. 50. 53. 49. 45. 56. 58. 55. 55. 48. 51. 60.
3.752 3.950 2.825 4.263 2.947 3.165 3.266 3.579 2.839 3.036 3.137 3.037 3.341 3.083 2.739
MEAN S.D.
N
50. 3.264 7.9 0.4411
15 15
PAGE 5
-1267-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
FEMALE GROUP: 0.1 MG/KG/DAY
25648-14 25674-14 25694-15 25631-15 25660-13 25704-12 25665-05 25652-08 25733-15 25748-10 25753-17 25672-16 25655-15 25727-10 25626-15
46. 34. 58. 53. 57. 52. 51. 51. 45. 50. 57. 40. 52. 47. 53.
3.345 4.360 2.812 3.002 2.622 3.046 3.260 3.195 3.274 3.032 3.016 3.804 2.980 3.359 2.984
MEAN S.D.
N
50. 3.206 6.5 0.4200
15 15
PAGE 6
-1268-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
FEMALE GROUP: 0.3 MG/KG/DAY
25671-09 25614-18 25698-04 25677-13 25604-10 25678-13 25609-12 25623-14 25653-05 25684-12 25714-08 25735-10 25722-12 25628-14 25766-08
46. 47. 46. 52. 49. 49. 57. 49. 59. 54. 56. 58. 50. 53. 43.
3.317 3.245 3.292 3.232 2.927 3.136 2.825 3.232 2.628 3.000 2.906 2.663 3.125 2.848 3.510
MEAN S.D.
N
51. 4.9
15
3.059 0.2557
15
PAGE 7
-1269-
PROJECT NO.:WIL-180017E SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 35 (F1 - PND 21 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
FEMALE GROUP: 1.0 MG/KG/DAY
25696-16 25686-09 25630-11 25673-11 25639-11 25658-10 25676-12 25600-12 25603-07 25703-08 25705-10 25611-15 25619-14 25691-14 25717-13
53. 47. 54. 42. 53. 48. 55. 58. 50. 52. 55. 54. 48. 58. 46.
3.034 3.300 3.061 3.408 2.791 3.226 3.080 2.781 2.993 3.105 2.587 3.062 3.073 2.699 3.147
MEAN S.D.
N
52. 4.6
15
3.023 0.2245
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
ANIMAL NO.25597-04 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/03/06
DATE OF DEATH: 08/03/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.19 21.3 15.7 339.
REL. 0.646
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 1 GRADE
-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
ANIMAL NO.25633-05 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 20.4 15.3 383.
REL. 0.546
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 2 GRADE
-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
ANIMAL NO.25621-07 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.19 21.2 15.8 413.
REL. 0.530
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 3 GRADE
-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
ANIMAL NO.25687-07 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.05 20.8 15.6 407.
REL. 0.504
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 4 GRADE
-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
ANIMAL NO.25615-03 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 20.3 15.7 414.
REL. 0.505
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 5 GRADE
-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
ANIMAL NO.25637-06 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.25 20.5 15.4 477.
REL. 0.472
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 6 GRADE
-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 BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.16 21.1 15.3 404.
REL. 0.535
BRAIN
NO SIGNIFICANT CHANGES OBSERVED
PERFUSED CYST(S)
ONE, 9 X 4 X 4 MM, EXTENDS INTO RIGHT CEREBRAL HEMISPHERE
GROSS:SPINAL C.-CERV. SPINAL C.-LUMB.
P
-LLZI -
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
ANIMAL NO.25670-09 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.28 20.9 15.6 462.
REL. 0.494
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 8 GRADE
-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
ANIMAL NO.25657-08 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.26 21.0 15.4 484.
REL. 0.467
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE
9
GRADE
-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
ANIMAL NO.25663-04 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.36 21.2 16.0 453.
REL. 0.521
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 10 GRADE
-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
ANIMAL NO.25690-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.17 20.3 15.5 405.
REL. 0.536
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 11 GRADE
-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
ANIMAL NO.25666-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.18 20.2 15.5 465.
REL. 0.469
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 12 GRADE
-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
ANIMAL NO.25692-04 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.28 20.8 15.4 423.
REL. 0.539
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 13 GRADE
-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
ANIMAL NO.25701-09 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.08 20.7 15.2 415.
REL. 0.501
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 14 GRADE
-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
ANIMAL NO.25645-06 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/08/06
DATE OF DEATH: 08/08/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.14 20.8 15.0 346.
REL. 0.618
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 15 GRADE
-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
ANIMAL NO.25694-04 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.29 21.0 15.5 487.
REL. 0.470
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 16 GRADE
-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
ANIMAL NO.25660-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.08 20.0 15.6 421.
REL. 0.494
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 17 GRADE
-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
ANIMAL NO.25704-03 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.14 20.4 15.4 409.
REL. 0.523
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 18 GRADE
-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
ANIMAL NO.25665-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.17 20.4 15.5 388.
REL. 0.559
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 19 GRADE
-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
ANIMAL NO.25652-04 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.37 20.8 15.8 520.
REL. 0.456
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 20 GRADE
-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
ANIMAL NO.25748-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.23 20.8 15.4 467.
REL. 0.478
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 21 GRADE
-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
ANIMAL NO.25753-06 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.34 21.9 15.6 448.
REL. 0.522
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 22 GRADE
-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
ANIMAL NO.25672-06 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.21 20.5 15.4 396.
REL. 0.558
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 23 GRADE
-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
ANIMAL NO.25655-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 20.1 15.4 384.
REL. 0.544
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 24 GRADE
-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
ANIMAL NO.25727-07 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.31 20.7 15.7 453.
REL. 0.510
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 25 GRADE
-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
ANIMAL NO.25626-04 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.33 20.9 15.7 434.
REL. 0.537
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 26 GRADE
-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
ANIMAL NO.25749-04 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.25 20.6 15.4 435.
REL. 0.517
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 27 GRADE
-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
ANIMAL NO.25739-07 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.38 21.5 16.0 462.
REL. 0.515
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 28 GRADE
-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
ANIMAL NO.25756-05 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.23 21.1 15.6 516.
REL. 0.432
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 29 GRADE
-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
ANIMAL NO.25752-09 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
08/08/06
DATE OF DEATH: 08/08/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.33 20.9 15.5 455.
REL. 0.512
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 30 GRADE
-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
ANIMAL NO.25671-04 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/03/06
DATE OF DEATH: 08/03/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.28 21.5 15.6 456.
REL. 0.500
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 31 GRADE
-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
ANIMAL NO.25698-05 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.19 21.2 15.4 419.
REL. 0.523
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 32 GRADE
-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
ANIMAL NO.25677-05 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.18 20.9 15.6 415.
REL. 0.525
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 33 GRADE
-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
ANIMAL NO.25678-02 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.12 20.4 15.2 442.
REL. 0.480
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 34 GRADE
-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
ANIMAL NO.25623-08 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.08 20.9 15.7 454.
REL. 0.458
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 35 GRADE
-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
ANIMAL NO.25653-02 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.05 20.4 15.1 411.
REL. 0.499
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 36 GRADE
-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
ANIMAL NO.25684-04 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.22 20.3 15.2 426.
REL. 0.521
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 37 GRADE
-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
ANIMAL NO.25714-02 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.33 20.8 15.7 419.
REL. 0.556
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 38 GRADE
-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
ANIMAL NO.25735-05 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.10 20.8 15.4 448.
REL. 0.469
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 39 GRADE
-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
ANIMAL NO.25722-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.17 20.3 15.2 430.
REL. 0.505
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 40 GRADE
-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
ANIMAL NO.25642-05 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.07 20.1 15.1 433.
REL. 0.478
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 41 GRADE
-nei-
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
ANIMAL NO.25628-07 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.22 20.2 15.5 385.
REL. 0.577
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 42 GRADE
-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
ANIMAL NO.25766-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 20.2 14.8 366.
REL. 0.571
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 43 GRADE
-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
ANIMAL NO.25708-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.18 20.6 15.7 407.
REL. 0.536
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 44 GRADE
-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
ANIMAL NO.25743-08 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.15 20.3 15.3 426.
REL. 0.505
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 45 GRADE
-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
ANIMAL NO.25696-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.25 21.2 15.6 434.
REL. 0.518
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 46 GRADE
-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
ANIMAL NO.25686-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 20.6 15.1 433.
REL. 0.483
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 47 GRADE
-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
ANIMAL NO.25630-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.38 20.8 16.0 434.
REL. 0.548
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 48 GRADE
-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
ANIMAL NO.25673-09 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 20.1 15.1 377.
REL. 0.554
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 49 GRADE
-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
ANIMAL NO.25658-08 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.28 20.4 15.6 459.
REL. 0.497
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 50 GRADE
-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
ANIMAL NO.25676-02 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.34 21.0 15.7 417.
REL. 0.561
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 51 GRADE
-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
ANIMAL NO.25600-02 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.22 20.7 15.6 418.
REL. 0.531
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 52 GRADE
-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
ANIMAL NO.25603-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.06 20.5 15.8 420.
REL. 0.490
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 53 GRADE
-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
ANIMAL NO.25703-03 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.16 20.2 15.7 403.
REL. 0.536
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 54 GRADE
-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
ANIMAL NO.25611-07 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.06 19.4 15.4 358.
REL. 0.575
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 55 GRADE
-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
ANIMAL NO.25616-05 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.29 20.8 15.5 475.
REL. 0.482
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 56 GRADE
-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
ANIMAL NO.25715-07 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 20.2 15.4 433.
REL. 0.483
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 57 GRADE
-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
ANIMAL NO.25599-06 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.21 20.8 15.4 399.
REL. 0.554
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 58 GRADE
-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
ANIMAL NO.25762-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.28 20.4 15.3 419.
REL. 0.544
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 59 GRADE
-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
ANIMAL NO.25647-07 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.21 20.3 15.6 361.
REL. 0.612
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 60 GRADE
-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
ANIMAL NO.25597-17 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/03/06
DATE OF DEATH: 08/03/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.79 19.9 14.4 209.
REL. 0.856
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 61 GRADE
-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
ANIMAL NO.25654-10 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/03/06
DATE OF DEATH: 08/03/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.07 20.5 15.1 227.
REL. 0.912
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 62 GRADE
-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
ANIMAL NO.25632-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.01 20.1 14.6 246.
REL. 0.817
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 63 GRADE
-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
ANIMAL NO.25633-13 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.83 19.2 14.5 243.
REL. 0.753
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 64 GRADE
-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
ANIMAL NO.25618-17 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.88 19.5 15.1 256.
REL. 0.734
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 65 GRADE
-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
ANIMAL NO.25621-10 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.11 20.4 15.3 283.
REL. 0.746
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 66 GRADE
-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
ANIMAL NO.25615-10 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.00 20.2 15.1 270.
REL. 0.741
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 67 GRADE
-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
ANIMAL NO.25637-17 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.14 19.6 15.4 277.
REL. 0.773
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 68 GRADE
-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
ANIMAL NO.25638-18 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.93 19.4 15.0 215.
REL. 0.898
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 69 GRADE
-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
ANIMAL NO.25670-18 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.07 19.9 15.1 269.
REL. 0.770
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 70 GRADE
-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
ANIMAL NO.25657-10 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.05 20.0 14.7 273.
REL. 0.751
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 71 GRADE
-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
ANIMAL NO.25690-19 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.10 20.4 15.2 281.
REL. 0.747
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 72 GRADE
-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
ANIMAL NO.25666-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.93 19.0 14.7 236.
REL. 0.818
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 73 GRADE
-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
ANIMAL NO.25701-18 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.00 19.5 14.8 245.
REL. 0.816
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 74 GRADE
-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
ANIMAL NO.25645-08 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/08/06
DATE OF DEATH: 08/08/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.96 19.5 14.6 197.
REL. 0.995
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 75 GRADE
-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
ANIMAL NO.25694-13 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.87 19.9 14.6 239.
REL. 0.782
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 76 GRADE
-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
ANIMAL NO.25631-05 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.06 20.4 14.8 267.
REL. 0.772
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 77 GRADE
-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
ANIMAL NO.25704-09 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.04 20.4 15.2 269.
REL. 0.758
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 78 GRADE
-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
ANIMAL NO.25665-07 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.10 19.9 15.2 223.
REL. 0.942
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 79 GRADE
-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
ANIMAL NO.25652-13 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.02 19.9 14.9 250.
REL. 0.808
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 80 GRADE
-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
ANIMAL NO.25748-08 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 19.9 14.9 244.
REL. 0.857
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 81 GRADE
-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
ANIMAL NO.25753-15 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.07 19.6 15.1 255.
REL. 0.812
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 82 GRADE
-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
ANIMAL NO.25672-15 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.99 19.5 15.1 236.
REL. 0.843
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 83 GRADE
-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
ANIMAL NO.25655-13 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.95 19.3 14.8 272.
REL. 0.717
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 84 GRADE
-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
ANIMAL NO.25626-12 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.03 19.6 14.9 267.
REL. 0.760
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 85 GRADE
-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
ANIMAL NO.25749-11 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.13 20.4 15.3 258.
REL. 0.826
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 86 GRADE
-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
ANIMAL NO.25739-12 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.00 20.4 14.8 287.
REL. 0.697
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 87 GRADE
-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
ANIMAL NO.25756-13 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.90 20.0 14.8 221.
REL. 0.860
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 88 GRADE
-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
ANIMAL NO.25741-09 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/08/06
DATE OF DEATH: 08/08/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.99 19.9 15.6 273.
REL. 0.729
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 89 GRADE
-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
ANIMAL NO.25752-13 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/08/06
DATE OF DEATH: 08/08/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 20.4 15.4 303.
REL. 0.690
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 90 GRADE
-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
ANIMAL NO.25671-06 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/03/06
DATE OF DEATH: 08/03/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.01 20.3 15.1 250.
REL. 0.804
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 91 GRADE
-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
ANIMAL NO.25698-12 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.98 20.3 14.9 237.
REL. 0.835
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 92 GRADE
-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
ANIMAL NO.25604-12 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.07 20.5 14.9 252.
REL. 0.821
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 93 GRADE
-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
ANIMAL NO.25678-11 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.02 20.2 15.4 253.
REL. 0.798
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 94 GRADE
-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
ANIMAL NO.25609-11 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.02 19.8 14.9 244.
REL. 0.828
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 95 GRADE
-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
ANIMAL NO.25623-15 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.03 19.6 14.9 253.
REL. 0.802
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 96 GRADE
-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
ANIMAL NO.25653-13 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.95 19.7 14.8 228.
REL. 0.855
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 97 GRADE
-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
ANIMAL NO.25714-13 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.07 19.6 15.4 261.
REL. 0.793
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 98 GRADE
-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
ANIMAL NO.25650-17 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.03 19.6 15.1 279.
REL. 0.728
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 99 GRADE
-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
ANIMAL NO.25722-15 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.96 19.7 14.9 252.
REL. 0.778
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 100 GRADE
-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
ANIMAL NO.25628-17 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.97 19.4 15.1 260.
REL. 0.758
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 101 GRADE
-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
ANIMAL NO.25766-06 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.97 19.4 15.0 223.
REL. 0.883
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 102 GRADE
-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
ANIMAL NO.25689-14 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.08 20.2 15.1 240.
REL. 0.867
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 103 GRADE
-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
ANIMAL NO.25708-15 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.10 19.8 15.0 220.
REL. 0.955
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 104 GRADE
-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
ANIMAL NO.25642-12 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.96 19.6 15.1 285.
REL. 0.688
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 105 GRADE
-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
ANIMAL NO.25696-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.07 20.5 15.5 246.
REL. 0.841
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 106 GRADE
-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
ANIMAL NO.25630-09 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.90 19.8 14.9 220.
REL. 0.864
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 107 GRADE
-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
ANIMAL NO.25673-10 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/04/06
DATE OF DEATH: 08/04/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.94 19.9 15.0 219.
REL. 0.886
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 108 GRADE
-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
ANIMAL NO.25676-15 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.11 20.1 15.3 240.
REL. 0.879
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 109 GRADE
-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
ANIMAL NO.25600-15 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.09 19.8 15.0 239.
REL. 0.874
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 110 GRADE
-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
ANIMAL NO.25703-10 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.05 20.3 15.3 241.
REL. 0.851
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 111 GRADE
-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
ANIMAL NO.25705-08 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/05/06
DATE OF DEATH: 08/05/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.01 20.1 14.9 260.
REL. 0.773
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 112 GRADE
-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
ANIMAL NO.25611-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.94 18.9 14.7 219.
REL. 0.886
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 113 GRADE
-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
ANIMAL NO.25619-12 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.92 19.3 14.8 278.
REL. 0.691
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 114 GRADE
-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
ANIMAL NO.25691-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.92 19.5 14.7 272.
REL. 0.706
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 115 GRADE
-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
ANIMAL NO.25717-15 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.99 19.4 14.8 261.
REL. 0.762
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 116 GRADE
-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
ANIMAL NO.25616-14 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.01 20.0 14.7 268.
REL. 0.750
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 117 GRADE
-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
ANIMAL NO.25715-10 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/06/06
DATE OF DEATH: 08/06/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 1.93 19.6 14.7 231.
REL. 0.835
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 118 GRADE
-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
ANIMAL NO.25762-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.04 20.3 14.9 198.
REL. 1.030
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 119 GRADE
-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
ANIMAL NO.25647-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
08/07/06
DATE OF DEATH: 08/07/06
ORGAN WEIGHT BRAIN BRAIN LENGTH(MM) BRAIN WIDTH(MM) FINAL BODY WT(G)
ABS.(G) 2.06 20.0 15.0 260.
REL. 0.792
PERFUSED NO SIGNIFICANT CHANGES OBSERVED GROSS:BRAIN
SPINAL C.-CERV. SPINAL C.-LUMB
PAGE 120 GRADE
-1390-
GROSS GRADE CODE: 1-SLIGHT, 2-MODERATE, 3-MARKED, P-PRESENT
PGRHv4.54 10/05/2006 R:01/24/2007
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
MALE GROUP: 0 MG/KG/DAY WIDTH(MM)
25597-04 25633-05 25621-07 25687-07 25615-03 25637-06 25638-07 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
339. 383. 413. 407. 414. 477. 404. 462. 484. 453. 405. 465. 423. 415. 346.
2.19 2.09 2.19 2.05 2.09 2.25 2.16 2.28 2.26 2.36 2.17 2.18 2.28 2.08 2.14
21.3 20.4 21.2 20.8 20.3 20.5 21.1 20.9 21.0 21.2 20.3 20.2 20.8 20.7 20.8
15.7 15.3 15.8 15.6 15.7 15.4 15.3 15.6 15.4 16.0 15.5 15.5 15.4 15.2 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
PAGE 1
-1391-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
MALE GROUP: 0.1 MG/KG/DAY WIDTH(MM)
25694-04 25660-01 25704-03 25665-01 25652-04 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25752-09
487. 421. 409. 388. 520. 467. 448. 396. 384. 453. 434. 435. 462. 516. 455.
2.29 2.08 2.14 2.17 2.37 2.23 2.34 2.21 2.09 2.31 2.33 2.25 2.38 2.23 2.33
21.0 20.0 20.4 20.4 20.8 20.8 21.9 20.5 20.1 20.7 20.9 20.6 21.5 21.1 20.9
15.5 15.6 15.4 15.5 15.8 15.4 15.6 15.4 15.4 15.7 15.7 15.4 16.0 15.6 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
PAGE
2
-1392-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
MALE GROUP: 0.3 MG/KG/DAY WIDTH(MM)
25671-04 25698-05 25677-05 25678-02 25623-08 25653-02 25684-04 25714-02 25735-05 25722-01 25642-05 25628-07 25766-01 25708-01 25743-08
456. 419. 415. 442. 454. 411. 426. 419. 448. 430. 433. 385. 366. 407. 426.
2.28 2.19 2.18 2.12 2.08 2.05 2.22 2.33 2.10 2.17 2.07 2.22 2.09 2.18 2.15
21.5 21.2 20.9 20.4 20.9 20.4 20.3 20.8 20.8 20.3 20.1 20.2 20.2 20.6 20.3
15.6 15.4 15.6 15.2 15.7 15.1 15.2 15.7 15.4 15.2 15.1 15.5 14.8 15.7 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
PAGE
3
-1393-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
MALE GROUP: 1.0 MG/KG/DAY WIDTH(MM)
25696-04 25686-04 25630-04 25673-09 25658-08 25676-02 25600-02 25603-04 25703-03 25611-07 25616-05 25715-07 25599-06 25762-01 25647-07
434. 433. 434. 377. 459. 417. 418. 420. 403. 358. 475. 433. 399. 419. 361.
2.25 2.09 2.38 2.09 2.28 2.34 2.22 2.06 2.16 2.06 2.29 2.09 2.21 2.28 2.21
21.2 20.6 20.8 20.1 20.4 21.0 20.7 20.5 20.2 19.4 20.8 20.2 20.8 20.4 20.3
15.6 15.1 16.0 15.1 15.6 15.7 15.6 15.8 15.7 15.4 15.5 15.4 15.4 15.3 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
PAGE
4
-1394-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
FEMALE GROUP: 0 MG/KG/DAY WIDTH(MM)
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25615-10 25637-17 25638-18 25670-18 25657-10 25690-19 25666-09 25701-18 25645-08
209. 227. 246. 243. 256. 283. 270. 277. 215. 269. 273. 281. 236. 245. 197.
1.79 2.07 2.01 1.83 1.88 2.11 2.00 2.14 1.93 2.07 2.05 2.10 1.93 2.00 1.96
19.9 20.5 20.1 19.2 19.5 20.4 20.2 19.6 19.4 19.9 20.0 20.4 19.0 19.5 19.5
14.4 15.1 14.6 14.5 15.1 15.3 15.1 15.4 15.0 15.1 14.7 15.2 14.7 14.8 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
PAGE
5
-1395-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
FEMALE GROUP: 0.1 MG/KG/DAY WIDTH(MM)
25694-13 25631-05 25704-09 25665-07 25652-13 25748-08 25753-15 25672-15 25655-13 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
239. 267. 269. 223. 250. 244. 255. 236. 272. 267. 258. 287. 221. 273. 303.
1.87 2.06 2.04 2.10 2.02 2.09 2.07 1.99 1.95 2.03 2.13 2.00 1.90 1.99 2.09
19.9 20.4 20.4 19.9 19.9 19.9 19.6 19.5 19.3 19.6 20.4 20.4 20.0 19.9 20.4
14.6 14.8 15.2 15.2 14.9 14.9 15.1 15.1 14.8 14.9 15.3 14.8 14.8 15.6 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
PAGE
6
-1396-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
FEMALE GROUP: 0.3 MG/KG/DAY WIDTH(MM)
25671-06 25698-12 25604-12 25678-11 25609-11 25623-15 25653-13 25714-13 25650-17 25722-15 25628-17 25766-06 25689-14 25708-15 25642-12
250. 237. 252. 253. 244. 253. 228. 261. 279. 252. 260. 223. 240. 220. 285.
2.01 1.98 2.07 2.02 2.02 2.03 1.95 2.07 2.03 1.96 1.97 1.97 2.08 2.10 1.96
20.3 20.3 20.5 20.2 19.8 19.6 19.7 19.6 19.6 19.7 19.4 19.4 20.2 19.8 19.6
15.1 14.9 14.9 15.4 14.9 14.9 14.8 15.4 15.1 14.9 15.1 15.0 15.1 15.0 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
PAGE
7
-1397-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G)
APPENDIX 37 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FINAL BODY AND BRAIN WEIGHTS AND BRAIN MEASUREMENTS
LENGTH(MM)
FEMALE GROUP: 1.0 MG/KG/DAY WIDTH(MM)
25696-11 25630-09 25673-10 25676-15 25600-15 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25762-11 25647-11
246. 220. 219. 240. 239. 241. 260. 219. 278. 272. 261. 268. 231. 198. 260.
2.07 1.90 1.94 2.11 2.09 2.05 2.01 1.94 1.92 1.92 1.99 2.01 1.93 2.04 2.06
20.5 19.8 19.9 20.1 19.8 20.3 20.1 18.9 19.3 19.5 19.4 20.0 19.6 20.3 20.0
15.5 14.9 15.0 15.3 15.0 15.3 14.9 14.7 14.8 14.7 14.8 14.7 14.7 14.9 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
PAGE 8
POFBWv4.14 10/05/2006 R:01/24/2007
-1398-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
MALE GROUP: 0 MG/KG/DAY
25597-04 25633-05 25621-07 25687-07 25615-03 25637-06 25638-07 25670-09 25657-08 25663-04 25690-01 25666-01 25692-04 25701-09 25645-06
339. 383. 413. 407. 414. 477. 404. 462. 484. 453. 405. 465. 423. 415. 346.
0.646 0.546 0.530 0.504 0.505 0.472 0.535 0.494 0.467 0.521 0.536 0.469 0.539 0.501 0.618
MEAN S.D.
N
419. 43.4
15
0.526 0.0506
15
PAGE 1
-1399-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
MALE GROUP: 0.1 MG/KG/DAY
25694-04 25660-01 25704-03 25665-01 25652-04 25748-01 25753-06 25672-06 25655-01 25727-07 25626-04 25749-04 25739-07 25756-05 25752-09
487. 421. 409. 388. 520. 467. 448. 396. 384. 453. 434. 435. 462. 516. 455.
0.470 0.494 0.523 0.559 0.456 0.478 0.522 0.558 0.544 0.510 0.537 0.517 0.515 0.432 0.512
MEAN S.D.
N
445. 42.1
15
0.508 0.0367
15
PAGE
2
-1400-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
MALE GROUP: 0.3 MG/KG/DAY
25671-04 25698-05 25677-05 25678-02 25623-08 25653-02 25684-04 25714-02 25735-05 25722-01 25642-05 25628-07 25766-01 25708-01 25743-08
456. 419. 415. 442. 454. 411. 426. 419. 448. 430. 433. 385. 366. 407. 426.
0.500 0.523 0.525 0.480 0.458 0.499 0.521 0.556 0.469 0.505 0.478 0.577 0.571 0.536 0.505
MEAN S.D.
N
422. 24.5
15
0.514 0.0358
15
PAGE
3
-1401-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
MALE GROUP: 1.0 MG/KG/DAY
25696-04 25686-04 25630-04 25673-09 25658-08 25676-02 25600-02 25603-04 25703-03 25611-07 25616-05 25715-07 25599-06 25762-01 25647-07
434. 433. 434. 377. 459. 417. 418. 420. 403. 358. 475. 433. 399. 419. 361.
0.518 0.483 0.548 0.554 0.497 0.561 0.531 0.490 0.536 0.575 0.482 0.483 0.554 0.544 0.612
MEAN S.D.
N
416. 32.7
15
0.531 0.0387
15
PAGE
4
-1402-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
FEMALE GROUP: 0 MG/KG/DAY
25597-17 25654-10 25632-09 25633-13 25618-17 25621-10 25615-10 25637-17 25638-18 25670-18 25657-10 25690-19 25666-09 25701-18 25645-08
209. 227. 246. 243. 256. 283. 270. 277. 215. 269. 273. 281. 236. 245. 197.
0.856 0.912 0.817 0.753 0.734 0.746 0.741 0.773 0.898 0.770 0.751 0.747 0.818 0.816 0.995
MEAN S.D.
N
248. 27.5
15
0.808 0.0770
15
PAGE 5
-1403-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
FEMALE GROUP: 0.1 MG/KG/DAY
25694-13 25631-05 25704-09 25665-07 25652-13 25748-08 25753-15 25672-15 25655-13 25626-12 25749-11 25739-12 25756-13 25741-09 25752-13
239. 267. 269. 223. 250. 244. 255. 236. 272. 267. 258. 287. 221. 273. 303.
0.782 0.772 0.758 0.942 0.808 0.857 0.812 0.843 0.717 0.760 0.826 0.697 0.860 0.729 0.690
MEAN S.D.
N
258. 22.8
15
0.790 0.0694
15
PAGE
6
-1404-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
FEMALE GROUP: 0.3 MG/KG/DAY
25671-06 25698-12 25604-12 25678-11 25609-11 25623-15 25653-13 25714-13 25650-17 25722-15 25628-17 25766-06 25689-14 25708-15 25642-12
250. 237. 252. 253. 244. 253. 228. 261. 279. 252. 260. 223. 240. 220. 285.
0.804 0.835 0.821 0.798 0.828 0.802 0.855 0.793 0.728 0.778 0.758 0.883 0.867 0.955 0.688
MEAN S.D.
N
249. 18.4
15
0.813 0.0646
15
PAGE
7
-1405-
PROJECT NO.:WIL-180017K SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL FBW(G) WEIGHT(G/100G)
APPENDIX 38 (F1 - PND 72 PUPS SELECTED FOR BRAIN WEIGHTS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BRAIN WEIGHTS RELATIVE TO FINAL BODY WEIGHTS
FEMALE GROUP: 1.0 MG/KG/DAY
25696-11 25630-09 25673-10 25676-15 25600-15 25703-10 25705-08 25611-11 25619-12 25691-11 25717-15 25616-14 25715-10 25762-11 25647-11
246. 220. 219. 240. 239. 241. 260. 219. 278. 272. 261. 268. 231. 198. 260.
0.841 0.864 0.886 0.879 0.874 0.851 0.773 0.886 0.691 0.706 0.762 0.750 0.835 1.030 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-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 39 (F0 DAMS - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
12.99 3.292
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 1 DAY 20
-1407-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 39 (F0 DAMS - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
11.96 3.048
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 2 DAY 20
-1408-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 39 (F0 DAMS - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
10.52 1.903
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 3 DAY 20
-1409-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 39 (F0 DAMS - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
10.93 2.538
10
ng/ml = NANOGRAMS/MILLILITER
PAGE
4
DAY 20
PCHEv4.03 10/05/2006 R:10/10/2006
-1410-
PROJECT NO.:WIL-180017C SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 40 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
12.08 4.389
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 1 DAY 20
-1411-
PROJECT NO.:WIL-180017C SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 40 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
10.52 2.667
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 2 DAY 20
-1412-
PROJECT NO.:WIL-180017C SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 40 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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 S.D.
N
9.35 2.175
8
ng/ml = NANOGRAMS/MILLILITER
PAGE
3
DAY 20
-1413-
PROJECT NO.:WIL-180017C SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 40 (F1 FETUSES - GESTATION DAY 20) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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 S.D.
N
9.70 2.125
8
ng/ml = NANOGRAMS/MILLILITER
PAGE
4
DAY 20
PCHEv4.03 10/05/2006 R:01/23/2007
-1414-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 41 (F0 DAMS - LACTATION DAY 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
10.21 3.908
10
ng/mL = NANOGRAMS/MILLILITER
PAGE 1 DAY 4
-1415-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 41 (F0 DAMS - LACTATION DAY 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
11.07 4.009
10
ng/mL = NANOGRAMS/MILLILITER
PAGE 2 DAY 4
-1416-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 41 (F0 DAMS - LACTATION DAY 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
8.53 1.073
10
ng/mL = NANOGRAMS/MILLILITER
PAGE DAY
3 4
-L i n -
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 41 (F0 DAMS - LACTATION DAY 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
10.16 2.681
10
ng/mL = NANOGRAMS/MILLILITER
PAGE DAY
4 4
PCHEv4.03 04/10/2007 R:04/10/2007
-1418-
PROJECT NO. :WIL-180017U SPONSOR:3M CORPORATION SPONSOR NO. :06-128
APPENDIX 42 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
5.58 2.001
10
ng/mL = NANOGRAMS/MILLILITER
PAGE DAY
1 4
-1419-
PROJECT NO.:WIL-180017U SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 42 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
5.50 0.738
10
ng/mL = NANOGRAMS/MILLILITER
PAGE DAY
2 4
-1420-
PROJECT NO.:WIL-180017U SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 42 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
4.79 2.203
10
ng/mL = NANOGRAMS/MILLILITER
PAGE DAY
3 4
-1421-
PROJECT NO.:WIL-180017U SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 42 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
5.43 1.973
10
ng/mL = NANOGRAMS/MILLILITER
PAGE DAY
4 4
PCHEv4.03 04/10/2007 R:04/10/2007
-1422-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 43 (F0 DAMS - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
17.04 6.708
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 1 DAY 21
-1423-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 43 (F0 DAMS - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
17.52 5.426
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 2 DAY 21
-1424-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 43 (F0 DAMS - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
14.76 4.086
10
ng/ml = NANOGRAMS/MILLILITER
PAGE
3
DAY 21
-1425-
PROJECT NO.:WIL-180017 SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 43 (F0 DAMS - LACTATION DAY 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
19.48 6.270
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 4 DAY 21
PCHEv4.03 10/05/2006 R:10/10/2006
-1426-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 44 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
7.63 1.963
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 1 DAY 21
-1427-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 44 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
9.94 2.886
10
ng/ml = NANOGRAMS/MILLILITER
PAGE
2
DAY 21
-1428-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 44 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
9.47 2.565
10
ng/ml = NANOGRAMS/MILLILITER
PAGE
3
DAY 21
-1429-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 44 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
8.79 1.380
10
ng/ml = NANOGRAMS/MILLILITER
PAGE
4
DAY 21
-1430-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 44 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
8.80 1.863
10
ng/ml = NANOGRAMS/MILLILITER
PAGE 5 DAY 21
-1431-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 44 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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 S.D.
N
8.87 2.462
9
ng/ml = NANOGRAMS/MILLILITER
PAGE
6
DAY 21
-1432-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 44 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
8.67 2.173
10
ng/ml = NANOGRAMS/MILLILITER
PAGE
7
DAY 21
-1433-
PROJECT NO.:WIL-180017V SPONSOR:3M CORPORATION SPONSOR NO.:06-128
APPENDIX 44 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL TSH VALUES
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
MEAN S.D.
N
8.41 2.072
10
ng/ml = NANOGRAMS/MILLILITER
PAGE
8
DAY 21
PCHEv4.03 10/05/2006 R:10/10/2006
-1434-
-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
ANIMAL NO.25679-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 1
GRADE 4 1
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
ANIMAL NO.25659-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 2
GRADE 3 1
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
ANIMAL NO.25634-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES LUMINAL DEBRIS, CELLULAR
PAGE 3
GRADE 3 2 1
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
ANIMAL NO.25620-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
MICRO: DECREASED COLLOID
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 4
GRADE 3
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
ANIMAL NO.25706-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 5
GRADE 4 1
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
ANIMAL NO.25612-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 6
GRADE 4 2
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
ANIMAL NO.25629-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 7
GRADE 4 1
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
ANIMAL NO.25718-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 8
GRADE 4 2
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
ANIMAL NO.25760-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 9
GRADE 3 1
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
ANIMAL NO.25683-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 10
GRADE 3 1
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
ANIMAL NO.25627-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 11 GRADE
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
ANIMAL NO.25669-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 12 GRADE
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
ANIMAL NO.25613-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 13 GRADE
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
ANIMAL NO.25607-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 14 GRADE
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
ANIMAL NO.25640-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 15 GRADE
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
ANIMAL NO.25711-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 16 GRADE
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
ANIMAL NO.25682-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 17 GRADE
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
ANIMAL NO.25651-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 18 GRADE
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
ANIMAL NO.25768-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 19 GRADE
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
ANIMAL NO.25643-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 20 GRADE
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
ANIMAL NO.25601-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 21 GRADE
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
ANIMAL NO.25644-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 22 GRADE
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
ANIMAL NO.25680-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 23 GRADE
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
ANIMAL NO.25675-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 24 GRADE
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
ANIMAL NO.25598-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 25 GRADE
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
ANIMAL NO.25667-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 26 GRADE
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
ANIMAL NO.25641-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 27 GRADE
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
ANIMAL NO.25662-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 28 GRADE
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
ANIMAL NO.25726-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 29 GRADE
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
ANIMAL NO.25596-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 30 GRADE
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
ANIMAL NO.25649-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 31
GRADE 3 1
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
ANIMAL NO.25608-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 32
GRADE 4 1
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
ANIMAL NO.25656-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED
NOT EXAMINED
MICRO:THYROID GLANDS
PAGE 33 GRADE
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
ANIMAL NO.25688-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 34
GRADE 3 1
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
ANIMAL NO.25625-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 35
GRADE 4 1
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
ANIMAL NO.25699-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 36 GRADE
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
ANIMAL NO.25750-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED
NOT EXAMINED
MICRO:THYROID GLANDS
PAGE 37 GRADE
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
ANIMAL NO.25734-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 38
GRADE 3 1
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
ANIMAL NO.25745-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 39 GRADE
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
ANIMAL NO.25693-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 40
GRADE 3 1
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
ANIMAL NO.25679-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 41
GRADE 3 1
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
ANIMAL NO.25659-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 42
GRADE 4 2
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
ANIMAL NO.25634-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 43
GRADE 4 2
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
ANIMAL NO.25620-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 44
GRADE 4 1
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
ANIMAL NO.25706-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 45
GRADE 4 2
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
ANIMAL NO.25612-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 46
GRADE 4 1
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
ANIMAL NO.25629-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED
NOT EXAMINED
MICRO:THYROID GLANDS
PAGE 47 GRADE
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
ANIMAL NO.25718-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES CONGESTION
PAGE 48
GRADE 3 1 3
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
ANIMAL NO.25760-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 49
GRADE 4 2
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
ANIMAL NO.25683-02 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 50
GRADE 4 2
MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT
-i486-
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
ANIMAL NO.25627-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 51 GRADE
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
ANIMAL NO.25669-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 52 GRADE
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
ANIMAL NO.25613-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 53 GRADE
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
ANIMAL NO.25607-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 54 GRADE
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
ANIMAL NO.25640-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 55 GRADE
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
ANIMAL NO.25711-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 56 GRADE
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
ANIMAL NO.25682-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 57 GRADE
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
ANIMAL NO.25651-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 58 GRADE
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
ANIMAL NO.25768-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 59 GRADE
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
ANIMAL NO.25643-02 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 60 GRADE
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
ANIMAL NO.25601-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 61 GRADE
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
ANIMAL NO.25644-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 62 GRADE
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
ANIMAL NO.25680-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 63 GRADE
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
ANIMAL NO.25675-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 64 GRADE
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
ANIMAL NO.25598-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 65 GRADE
MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT
-T O S I-
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
ANIMAL NO.25667-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 66 GRADE
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
ANIMAL NO.25641-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 67 GRADE
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
ANIMAL NO.25662-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 68 GRADE
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
ANIMAL NO.25726-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 69 GRADE
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
ANIMAL NO.25596-02 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 70 GRADE
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
ANIMAL NO.25649-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 71
GRADE 4 2
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
ANIMAL NO.25608-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/22/06
DATE OF DEATH: 05/22/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 72
GRADE 4 2
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
ANIMAL NO.25656-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 73
GRADE 3 1
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
ANIMAL NO.25688-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 74
GRADE 4 2
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
ANIMAL NO.25625-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: NOT EXAMINED NOT RECEIVED AT TRIMMING
NOT EXAMINED
MICRO:THYROID GLANDS
PAGE 75 GRADE
MICRO GRADE CODE: 1-MINIMAL, 2-MILD, 3-MODERATE, 4-SEVERE, P-PRESENT
-lisi-
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
ANIMAL NO.25699-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/23/06
DATE OF DEATH: 05/23/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 76 GRADE
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
ANIMAL NO.25750-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: NOT EXAMINED NOT RECEIVED AT TRIMMING
NOT EXAMINED
MICRO:THYROID GLANDS
PAGE 77 GRADE
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
ANIMAL NO.25734-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/24/06
DATE OF DEATH: 05/24/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 78
GRADE 3 2
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
ANIMAL NO.25745-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 79 GRADE
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
ANIMAL NO.25693-02 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/25/06
DATE OF DEATH: 05/25/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 80
GRADE 3 2
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25632-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
THYROID GLANDS
MICRO: DECREASED COLLOID
NO SIGNIFICANT
CHANGES OBSERVED
PAGE
1
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25618-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
MICRO: DECREASED COLLOID
NO SIGNIFICANT
CHANGES OBSERVED
PAGE
2
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25621-04 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE
3
GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25687-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE
4
GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25681-02 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
MICRO: LUMINAL DEBRIS, CELLULAR
NO SIGNIFICANT
CHANGES OBSERVED
PAGE
5
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25615-02 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE
6
GRADE 1
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
ANIMAL NO.25637-02 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 7
GRADE 1 1
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
ANIMAL NO.25638-03 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES LUMINAL DEBRIS, CELLULAR
PAGE 8
GRADE 1 1
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
ANIMAL NO.25670-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES LUMINAL DEBRIS, CELLULAR
PAGE 9
GRADE 1 1
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
ANIMAL NO.25657-03 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES DECREASED COLLOID
PAGE 10
GRADE 1 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25674-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 11 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25694-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 12 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25660-03 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 13 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25652-05 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 14 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25733-02 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 15 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25753-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 16 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25672-03 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 17 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25655-02 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 18 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25727-03 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 19 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25626-02 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 20 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25614-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 21 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25698-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 22 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25678-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 23 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25609-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 24 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25623-06 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 25 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25650-03 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 26 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25735-02 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 27 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25722-02 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 28 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25642-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 29 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25628-02 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 30 GRADE
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
ANIMAL NO.25696-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES DECREASED COLLOID
PAGE 31
GRADE 1 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25686-05 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 32 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25630-02 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
THYROID GLANDS
MICRO: DECREASED COLLOID
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 33
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25673-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 34 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25639-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 35 GRADE
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
ANIMAL NO.25658-06 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES ONE EXAMINED ONE THYROID LOBE IN PLANE OF SECTION, RECUT EXAMINED
PAGE 36
GRADE 1 P
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25676-05 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 37 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25705-02 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 38 GRADE
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
ANIMAL NO.25619-02 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 39
GRADE 1 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25616-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 40
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25632-11 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 41
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25618-12 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 42
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25621-11 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 43 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25687-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 44 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25681-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 45
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25615-07 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 46
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25637-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 47
GRADE 1 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25638-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 48
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25670-12 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: DECREASED COLLOID MITOTIC FIGURES
PAGE 49
GRADE 1 2
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25657-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 50
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25674-10 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 51 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25694-07 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 52 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25660-11 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 53 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25652-07 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 54 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25733-09 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 55 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25753-08 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 56 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25672-10 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 57 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25655-14 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 58 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25727-11 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 59 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25626-10 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 60 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25614-14 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 61 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25698-07 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 62 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25678-09 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 63 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25609-07 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 64 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25623-10 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 65 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25650-15 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 66 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25735-09 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 67 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25722-14 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 68 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25642-09 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 69 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25628-10 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 70 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25696-12 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 71 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25686-12 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
THYROID GLANDS
MICRO: DECREASED COLLOID
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 72
GRADE 1
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
ANIMAL NO.25630-08 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES ONE EXAMINED ONE THYROID LOBE IN PLANE OF SECTION, RECUT EXAMINED
PAGE 73
GRADE 1 P
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25673-13 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/28/06
DATE OF DEATH: 05/28/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED
NOT EXAMINED
MICRO:THYROID GLANDS
PAGE 74 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25639-10 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 75
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25658-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 76
GRADE 1
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25676-10 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: ONE EXAMINED ONE THYROID LOBE IN PLANE OF SECTION, RECUT EXAMINED
PAGE 77
GRADE P
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25705-12 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/29/06
DATE OF DEATH: 05/29/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 78 GRADE
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 4 6 (F1 PUPS - PND 4) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL MICROSCOPIC FINDINGS
ANIMAL NO.25619-07 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
MICRO: DECREASED COLLOID
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 79
GRADE 1
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
ANIMAL NO.25616-08 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
05/30/06
DATE OF DEATH: 05/30/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: NOT EXAMINED NOT IN PLANE OF SECTION, RECUT EXAMINED
NOT EXAMINED
MICRO:THYROID GLANDS
PAGE 80 GRADE
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
ANIMAL NO.25632-02 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE
1
GRADE
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
ANIMAL NO.25618-09 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES CYST, ULTIMOBRANCHIAL
PAGE 2
GRADE 1 P
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
ANIMAL NO.25621-03 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE
3
GRADE 1
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
ANIMAL NO.25687-04 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
MICRO: CYST, ULTIMOBRANCHIAL
NO SIGNIFICANT
CHANGES OBSERVED
PAGE
4
GRADE P
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
ANIMAL NO.25681-03 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE
5
GRADE
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
ANIMAL NO.25615-06 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES CYST, ULTIMOBRANCHIAL ECTOPIC THYMUS
PAGE 6
GRADE 1 P P
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
ANIMAL NO.25637-03 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE
7
GRADE
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
ANIMAL NO.25638-01 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE
8
GRADE 1
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
ANIMAL NO.25670-06 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE
9
GRADE 1
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
ANIMAL NO.25657-07 GROUP 1: 0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
THYROID GLANDS
MICRO: CYST, ULTIMOBRANCHIAL
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 10
GRADE P
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
ANIMAL NO.25674-04 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 11 GRADE
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
ANIMAL NO.25694-05 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 12 GRADE
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
ANIMAL NO.25660-06 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 13 GRADE
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
ANIMAL NO.25652-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 14 GRADE
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
ANIMAL NO.25733-06 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 15 GRADE
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
ANIMAL NO.25753-04 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 16 GRADE
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
ANIMAL NO.25672-09 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 17 GRADE
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
ANIMAL NO.25655-10 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 18 GRADE
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
ANIMAL NO.25727-06 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 19 GRADE
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
ANIMAL NO.25626-01 GROUP 2: 0.1 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 20 GRADE
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
ANIMAL NO.25614-05 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 21 GRADE
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
ANIMAL NO.25698-03 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 22 GRADE
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
ANIMAL NO.25678-07 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 23 GRADE
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
ANIMAL NO.25609-06 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 24 GRADE
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
ANIMAL NO.25623-03 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 25 GRADE
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
ANIMAL NO.25650-02 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 26 GRADE
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
ANIMAL NO.25735-06 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 27 GRADE
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
ANIMAL NO.25722-10 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 28 GRADE
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
ANIMAL NO.25642-04 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 29 GRADE
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
ANIMAL NO.25628-01 GROUP 3: 0.3 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 30 GRADE
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
ANIMAL NO.25696-06 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 31 GRADE
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
ANIMAL NO.25686-01 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 32
GRADE 1
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
ANIMAL NO.25630-06 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 33 GRADE
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
ANIMAL NO.25673-08 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 34 GRADE
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
ANIMAL NO.25639-03 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 35 GRADE
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
ANIMAL NO.25658-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES LUMINAL DEBRIS, CELLULAR
PAGE 36
GRADE 1 1
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
ANIMAL NO.25676-04 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 37 GRADE
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
ANIMAL NO.25705-06 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 38 GRADE
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
ANIMAL NO.25619-03 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 39
GRADE 1
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
ANIMAL NO.25616-02 GROUP 4: 1.0 MG/KG/DAY
MALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 40 GRADE
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
ANIMAL NO.25632-15 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 41
GRADE 1
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
ANIMAL NO.25618-18 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 42
GRADE 1
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
ANIMAL NO.25621-12 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 43 GRADE
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
ANIMAL NO.25687-10 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 44 GRADE
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
ANIMAL NO.25681-14 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 45
GRADE 1
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
ANIMAL NO.25615-09 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 46 GRADE
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
ANIMAL NO.25637-10 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 47 GRADE
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
ANIMAL NO.25638-11 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES LUMINAL DEBRIS, CELLULAR
PAGE 48
GRADE 1 1
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
ANIMAL NO.25670-17 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 49 GRADE
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
ANIMAL NO.25657-13 GROUP 1: 0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 50
GRADE 1
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
ANIMAL NO.25674-13 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 51 GRADE
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
ANIMAL NO.25694-08 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 52 GRADE
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
ANIMAL NO.25660-14 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 53 GRADE
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
ANIMAL NO.25652-11 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 54 GRADE
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
ANIMAL NO.25733-12 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 55 GRADE
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
ANIMAL NO.25753-09 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 56 GRADE
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
ANIMAL NO.25672-11 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 57 GRADE
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
ANIMAL NO.25655-12 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 58 GRADE
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
ANIMAL NO.25727-09 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 59 GRADE
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
ANIMAL NO.25626-08 GROUP 2: 0.1 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 60 GRADE
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
ANIMAL NO.25614-15 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 61 GRADE
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
ANIMAL NO.25698-14 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 62 GRADE
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
ANIMAL NO.25678-10 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 63 GRADE
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
ANIMAL NO.25609-15 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 64 GRADE
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
ANIMAL NO.25623-13 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 65 GRADE
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
ANIMAL NO.25650-01 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 66 GRADE
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
ANIMAL NO.25735-14 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 67 GRADE
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
ANIMAL NO.25722-11 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 68 GRADE
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
ANIMAL NO.25642-15 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 69 GRADE
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
ANIMAL NO.25628-16 GROUP 3: 0.3 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
NO SIGNIFICANT CHANGES OBSERVED
PAGE 70 GRADE
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
ANIMAL NO.25696-14 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 71
GRADE 1
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
ANIMAL NO.25686-15 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
THYROID GLANDS
MICRO: LUMINAL DEBRIS, CELLULAR
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 72
GRADE 1
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
ANIMAL NO.25630-13 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 73
GRADE 1
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
ANIMAL NO.25673-14 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/14/06
DATE OF DEATH: 06/14/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 74 GRADE
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
ANIMAL NO.25639-12 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 75
GRADE 1
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
ANIMAL NO.25658-13 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
NO SIGNIFICANT CHANGES OBSERVED
MICRO: MITOTIC FIGURES LUMINAL DEBRIS, CELLULAR
PAGE 76
GRADE 1 1
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
ANIMAL NO.25676-08 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
NO SIGNIFICANT CHANGES OBSERVED
MICRO:THYROID GLANDS
PAGE 77 GRADE
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
ANIMAL NO.25705-11 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/15/06
DATE OF DEATH: 06/15/06
THYROID GLANDS
MICRO: LUMINAL DEBRIS, CELLULAR
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 78
GRADE 1
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
ANIMAL NO.25619-10 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
THYROID GLANDS
MICRO: MITOTIC FIGURES
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 79
GRADE 1
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
ANIMAL NO.25616-13 GROUP 4: 1.0 MG/KG/DAY
FEMALE
SCHEDULED EUTH
06/16/06
DATE OF DEATH: 06/16/06
THYROID GLANDS
MICRO: LUMINAL DEBRIS, CELLULAR
NO SIGNIFICANT
CHANGES OBSERVED
PAGE 80
GRADE 1
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 Males
ANIMAL NUMBER: FOLLICLE1 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
THYROID COLLOID MEASUREMENTS AND AREAS
25615-02
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
119 38
93 34809
30 3622
96 31
66 19921
21 2073
91 29
67 19068
22 1984
80 26
43 10912
14 1135
88 28
56 15407
18 1603
65 21
48 9803 77
15 1020 25
63 15325
20 1595
61 52 9922
20 17 1032
62 20
47 9186
15 956
83 27
63 16281
20 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 Males
ANIMAL NUMBER:
FOLLICLE1 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 FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
FOLLICLE 10, SHORT AXIS
THYROID COLLOID MEASUREMENTS AND AREAS
25621-04
25632-01
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
131 42
69
120 49346
39 5135
66 14239
110 36
72
85 29523
27 3072
60 13487
84 27
101
62 16465
20 1713
73 23090
82 26
95
49 12500
16 1301
43 12979
79 25
70
56 13852
18 1441
57 12445
72 23
86
66 14954
21 1556
72 19420
93 30
76
77 22391
25 2330
64 15215
90 29
76
64 18307
21 1905
48 11589
96 31
72
88 26583
28 2766
49 10926
66 21
74
50 10385
16 1081
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 Males
ANIMAL NUMBER:
FOLLICLE1 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 FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
FOLLICLE 10, SHORT AXIS
THYROID COLLOID MEASUREMENTS AND AREAS
25637-02
25638-03
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
89 29
97
63 17610
20 1832
57 17353
95 31
106
74 22094
24 2299
103 34430
89 29
109
70 19642
23 2044
82 28230
118 38
93
79 29096
25 3028
61 17754
72 23
77
43 9698
14 1009
49 11828
77 25
70
45 10783
14 1122
52 11443
82 27
69
47 12261
15 1276
45 9892
73 23
62
42 9641
14 1003
44 8506
74 24
70
40 9379
13 976
65 14296
75 24
79
55 12960
18 1349
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 Males
ANIMAL NUMBER:
FOLLICLE1 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 FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
FOLLICLE 10, SHORT AXIS
THYROID COLLOID MEASUREMENTS AND AREAS
25657-03
25670-01
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
133 43
107
97 40478
31 4212
79 26576
109 35
114
77 26349
25 2742
78 27869
82 27
94
53 13672
17 1423
70 20674
84 27
86
62 16396
20 1706
71 19183
104 34
98
96 31438
31 3271
70 21495
130 42
104
104 42632
34 4436
77 25136
96 31
83
67 20210
22 2103
49 12847
85 28
71
62 16645
20 1732
48 10669
74 24
75
54 12729
18 1325
56 13095
75 24
87
58 13609
19 1416
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 Males
ANIMAL NUMBER:
FOLLICLE1 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 FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
FOLLICLE 10, SHORT AXIS
THYROID COLLOID MEASUREMENTS AND AREAS
25681-02
25687-01
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
105 34
100
76 25027
25 2604
82 25672
78 25
99
54 13281
17 1382
74 22907
131 42
97
68 28223
22 2937
74 22627
88 28
83
78 21639
25 2252
73 19103
72 23
106
52 11696
17 1217
83 27619
71 23
80
49 11015
16 1146
64 16042
68 22
78
47 10060
15 1047
55 13551
62 20
67
42 8171
13 850
51 10701
82 26
82
56 14344
18 1493
55 14192
73 24
84
58 13303
19 1384
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 Males
ANIMAL NUMBER:
FOLLICLE1 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
THYROID COLLOID MEASUREMENTS AND AREAS
25616-01
25619-02
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
134 43
82
92 38663
30 4023
66 16817
112 36
66
84 29501
27 3070
43 8793
115 37
114
60 21803
19 2269
67 24051
124 40
77
98 37949
31 3949
53 12800
92 30
84
55 15951
18 1660
56 14683
82 26
77
57 14789
19 1539
53 12844
70 23
62
56 12374
18 1288
43 8427
79 26
64
65 16329
21 1699
51 10316
74 24
57
47 11025
15 1147
41 7425
99 32
67
93 29062
30 3024
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 Males
ANIMAL NUMBER:
FOLLICLE1 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 FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
FOLLICLE 10, SHORT AXIS
THYROID COLLOID MEASUREMENTS AND AREAS
25630-02
25639-01
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
94 30
104
76 22570
25 2349
51 16552
94 30
77
80 23627
26 2459
40 9597
68 22
63
51 10813
16 1125
29 5735
78 25
91
60 14791
19 1539
53 15231
97 31
64
45 13588
14 1414
45 9153
79 26
88
45 11208
14 1166
45 12301
70 23
91
44 9763
14 1016
39 11061
73 23
80
40 9178
13 955
43 10689
64 21
85
39 7705
12 802
38 10226
66 21
69
36 7475
12 778
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 Males
ANIMAL NUMBER:
FOLLICLE1 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 FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
FOLLICLE 10, SHORT AXIS
THYROID COLLOID MEASUREMENTS AND AREAS
25658-06
25673-01
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
74 24
101
57 13301
18 1384
63 20065
131 42
84
94 38752
30 4032
67 17749
73 24
76
54 12291
17 1279
64 15391
81 26
75
53 13422
17 1397
54 12743
105 34
83
46 15076
15 1569
61 15924
88 28
102
56 15397
18 1602
81 25769
52 17
88
39 6404
13 666
85 23553
69 22
78
33 7055
11 734
52 12865
58 19
56
30 5434
10 565
37 6623
52 17
72
36 5846
12 608
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 Males
ANIMAL NUMBER:
FOLLICLE1 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 FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
FOLLICLE 10, SHORT AXIS
THYROID COLLOID MEASUREMENTS AND AREAS
25676-05
25686-05
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
98 31
123
66 20082
21 2090
58 22561
92 30
119
78 22726
25 2365
96 35715
105 34
86
75 24884
24 2589
51 13906
75 24
94
50 11870
16 1235
63 18614
60 19
81
53 10038
17 1045
64 16162
67 21
57
59 12289
19 1279
50 8964
84 27
88
65 17173
21 1787
81 22442
84 27
62
54 14366
17 1495
45 8739
69 22
67
38 8325
12 866
46 9612
64 21
71
50 9910
16 1031
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 Males
ANIMAL NUMBER:
FOLLICLE1 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 FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
FOLLICLE 10, SHORT AXIS
THYROID COLLOID MEASUREMENTS AND AREAS
25696-01
25705-02
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
77 25
67
47 11423
15 1189
65 13612
68 22
61
59 12574
19 1308
51 9921
101 33
52
68 21607
22 2248
41 6800
81 26
70
52 13213
17 1375
58 12623
82 27
67
52 13553
17 1410
52 10870
66 21
61
51 10528
16 1096
45 8637
76 24
67
69 16397
22 1706
58 12252
117 38
67
95 34969
31 3639
56 11799
95 31
64
46 13777
15 1434
50 9978
77 25
57
38 9302
12 968
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 Females
ANIMAL NUMBER:
FOLLICLE1 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
THYROID COLLOID MEASUREMENTS AND AREAS
25615-07
25618-12
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
84 27
131
80 21027
26 2188
77 31893
90 29
120
66 18646
21 1940
67 25253
71 23
86
47 10551
15 1098
70 19015
91 29
82
60 17207
19 1791
67 17361
90 29
93
51 14469
16 1506
59 17345
73 24
159
52 11995
17 1248
81 40336
55 18
130
49 8559
16 891
102 41592
78 25
94
62 15331
20 1595
50 14808
60 19
91
60 11313
19 1177
62 17626
72 23
96
42 9547
14 993
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 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25621-11
25632-11
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
122
39
110
FOLLICLE 1, SHORT AXIS
68 26173
22 2724
94 32294
FOLLICLE 2, LONG AXIS
113
36
75
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS
75 26529 96 77 23318
24 2761 31 25 2426
60 14152 97 89 27132
FOLLICLE 4, LONG AXIS 91 29
69
FOLLICLE 4, SHORT AXIS
59 17046
19 1774
57 12346
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS
90 74 20909 82
29 24 2176 27
82 61 15651 95
FOLLICLE 6, SHORT AXIS
54 13949
17 1452
72 21387
FOLLICLE 7, LONG AXIS 89 29
96
FOLLICLE 7, SHORT AXIS
66 18534
21 1929
82 24944
FOLLICLE FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
83 72 18827 75 39 9131 79
27 23 1959 24 13 950 26
80 51 12785 75 41 9739 77
FOLLICLE 10, SHORT AXIS
58 14477
19 1506
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 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25637-09
25638-09
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
122
39
107
FOLLICLE 1, SHORT AXIS
76 29079
24 3026
80 26959
FOLLICLE 2, LONG AXIS FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
97 47 14371 84
31 15 1495 27
141 66 29063
117
FOLLICLE 3, SHORT AXIS
63 16497
20 1717
53 19355
FOLLICLE 4, LONG AXIS 99 32
96
FOLLICLE 4, SHORT AXIS
65 20349
21 2118
58 17496
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS
105 80 26402 97
34 26 2747 31
91 60 17258 121
FOLLICLE 6, SHORT AXIS
63 19023
20 1980
96 36636
FOLLICLE 7, LONG AXIS 92 30
108
FOLLICLE 7, SHORT AXIS
69 20029
22 2084
52 17551
FOLLICLE FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
73 65 14842 231 115 83884 107
24 21 1544 75 37 8729 35
86 62 16721 100 70 22000 97
FOLLICLE 10, SHORT AXIS
125 42010
40 4371
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 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25657-09
25670-12
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS 97 31
139
FOLLICLE 1, SHORT AXIS
61 18419
20 1917
83 36250
FOLLICLE 2, LONG AXIS
128
41
157
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
84 33843 89
27 3522 29
98 48431 121
FOLLICLE 3, SHORT AXIS
64 18048
21 1878
59 22507
FOLLICLE 4, LONG AXIS
106
34
103
FOLLICLE 4, SHORT AXIS
65 21746
21 2263
57 18476
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS
85 53 14183 98
28 17 1476 32
96 46 13787 107
FOLLICLE 6, SHORT AXIS
58 18017
19 1875
66 22269
FOLLICLE 7, LONG AXIS 88 28
88
FOLLICLE 7, SHORT AXIS
58 15899
19 1654
75 20781
FOLLICLE FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
76 55 13270 74 52 12129 119
25 18 1381 24 17 1262 38
107 57 18932 95 58 17317 89
FOLLICLE 10, SHORT AXIS
115 42895
37 4464
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 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25681-09
25687-09
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
115
37
131
FOLLICLE 1, SHORT AXIS
62 22407
20 2332
82 33731
FOLLICLE 2, LONG AXIS
100
32
114
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS FOLLICLE 3, SHORT AXIS
66 20848 88 57 15691
21 2169 28 18 1633
66 23380 89 61 17028
FOLLICLE 4, LONG AXIS 86 28
123
FOLLICLE 4, SHORT AXIS
64 17254
21 1795
80 31018
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS
79 53 13186 93
25 17 1372 30
91 61 17395 99
FOLLICLE 6, SHORT AXIS
68 19791
22 2059
77 24024
FOLLICLE 7, LONG AXIS 76 24
139
FOLLICLE 7, SHORT AXIS
73 17469
24 1818
88 38387
FOLLICLE FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
73 64 14716 74 58 13432 78
24 21 1531 24 19 1398 25
88 52 14335 88 48 13399 97
FOLLICLE 10, SHORT AXIS
46 11313
15 1177
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 Females
ANIMAL NUMBER:
FOLLICLE1 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
THYROID COLLOID MEASUREMENTS AND AREAS
25619-07
25630-08
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
171 55
174
80 42918
26 4466
48 26493
97 31
118
65 19612
21 2041
68 25350
98 32
136
65 20074
21 2089
94 40392
62 20
78
48 9464
16 985
43 10392
81 26
82
60 15315
20 1594
57 14788
68 22
76
53 11298
17 1176
56 13407
73 24
81
47 10789
15 1123
56 14084
67 22
86
44 9265
14 964
56 15245
81 26
80
60 15295
19 1592
64 16121
74 24
82
45 10521
15 1095
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 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25639-10
25658-11
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
104
34
90
FOLLICLE 1, SHORT AXIS
70 22950
23 2388
50 14329
FOLLICLE 2, LONG AXIS 78 25
98
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
64 15657 98
21 1629 32
72 22126 97
FOLLICLE 3, SHORT AXIS
51 15862
17 1651
65 19858
FOLLICLE 4, LONG AXIS 82 26
76
FOLLICLE 4, SHORT AXIS
54 14028
18 1460
43 10352
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS
67 46 9696 82
22 15 1009 26
89 73 20478 78
FOLLICLE 6, SHORT AXIS
48 12188
15 1268
54 13120
FOLLICLE 7, LONG AXIS 68 22
92
FOLLICLE 7, SHORT AXIS
54 11616
17 1209
50 14523
FOLLICLE FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
74 61 14188 66 38 7882 56
24 20 1476 21 12 820 18
78 49 11873 86 58 15740 65
FOLLICLE 10, SHORT AXIS
38 6685
12 696
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 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25676-10
25686-12
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
156
50
126
FOLLICLE 1, SHORT AXIS
96 47110
31 4902
71 28177
FOLLICLE 2, LONG AXIS
121
39
106
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
82 31408 124
27 3268 40
62 20736 136
FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS
88 34441 167
28 3584 54
73 31352 116
FOLLICLE 4, SHORT AXIS
57 29873
18 3109
72 26351
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS
128 75 30189
107
41 24 3141 34
89 66 18436 108
FOLLICLE 6, SHORT AXIS
85 28413
27 2957
100 34104
FOLLICLE 7, LONG AXIS
139
45
84
FOLLICLE 7, SHORT AXIS
100 43624
32 4539
53 14151
FOLLICLE FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
93 61 17772 100 77 24297 98
30 20 1849 32 25 2528 32
75 57 13323 86 66 17909 75
FOLLICLE 10, SHORT AXIS
58 17871
19 1860
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 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25696-12
25705-12
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
106
34
121
FOLLICLE 1, SHORT AXIS
94 31556
30 3284
54 20760
FOLLICLE 2, LONG AXIS 88 29
109
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
54 14990 92
17 1560 30
71 24309 84
FOLLICLE 3, SHORT AXIS
78 22472
25 2338
55 14436
FOLLICLE 4, LONG AXIS 99 32
86
FOLLICLE 4, SHORT AXIS
79 24555
25 2555
58 15680
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS FOLLICLE 6, LONG AXIS
86 69 18739 74
28 22 1950 24
115 73 26493 99
FOLLICLE 6, SHORT AXIS
58 13570
19 1412
43 13235
FOLLICLE 7, LONG AXIS 83 27
98
FOLLICLE 7, SHORT AXIS
83 21507
27 2238
43 13219
FOLLICLE FOLLICLE FOLLICLE FOLLICLE FOLLICLE
8, LONG AXIS 8, SHORT AXIS 9, LONG AXIS 9, SHORT AXIS 10, LONG AXIS
78 65 16040 78 60 14664 67
25 21 1669 25 19 1526 22
85 52 13920 91 52 14882 79
FOLLICLE 10, SHORT AXIS
48 10101
16 1051
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 MEASUREMENTS
25615-02
25618-01
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
19.03
6.14
19.00
18.79
6.06
19.00
24.70
7.97
17.12
15.00
4.84
19.85
16.28
5.25
17.69
19.03
6.14
25.63
13.04
4.21
19.24
17.49
5.64
18.11
14.21
4.58
15.00
15.52
5.01
16.55
13.04
4.21
15.00
16.28
5.25
17.89
12.65
4.08
17.00
12.53
4.04
17.46
15.00
4.84
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 MEASUREMENTS
25621-04
25632-01
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
15.65
5.05
19.42
16.97
5.47
16.55
16.64
5.37
19.42
16.97
5.47
18.44
16.16
5.21
12.17
18.44
5.95
15.13
13.93
4.49
13.60
19.92
6.43
16.64
13.04
4.21
15.65
19.03
6.14
11.31
24.02
7.75
18.36
21.95
7.08
12.37
15.00
4.84
13.04
19.92
6.43
16.03
13.42
4.33
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 MEASUREMENTS
25637-02
25638-03
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
19.42
6.26
18.38
17.09
5.51
14.42
22.47
7.25
18.97
23.41
7.55
18.03
16.16
5.21
19.03
21.40
6.90
20.52
11.40
3.68
14.76
19.21
6.20
14.87
19.24
6.20
9.85
17.80
5.74
19.42
14.14
4.56
17.12
14.56
4.70
25.94
12.08
3.90
12.08
13.34
4.30
15.65
17.12
5.52
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 MEASUREMENTS
25657-03
25670-01
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
15.23
4.91
22.14
14.32
4.62
16.28
16.12
5.20
19.65
18.38
5.93
13.34
14.76
4.76
16.40
14.56
4.70
15.03
23.09
7.45
18.25
15.81
5.10
14.87
25.24
8.14
14.76
17.00
5.48
18.79
18.25
5.89
13.34
10.30
3.32
17.46
25.50
8.22
15.52
15.56
5.02
11.00
19.10
6.16
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 MEASUREMENTS
25681-02
25687-01
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
17.46
5.63
18.03
10.44
3.37
21.84
14.42
4.65
13.93
17.03
5.49
15.65
22.85
7.37
19.03
17.46
5.63
18.25
17.03
5.49
16.00
12.00
3.87
16.40
17.03
5.49
15.81
22.80
7.36
17.69
16.03
5.17
17.26
15.26
4.92
16.00
14.32
4.62
19.10
19.21
6.20
20.00
12.08
3.90
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 MEASUREMENTS
25616-01
25619-02
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
16.76
5.41
14.56
10.82
3.49
14.56
18.68
6.03
14.56
22.14
7.14
12.04
16.76 18.97
5.41 6.12
9.43 18.38
12.08
3.90
14.42
15.56
5.02
14.14
17.49
5.64
24.08
15.23
4.91
12.37
21.93
7.07
14.14
19.10
6.16
16.28
20.81
6.71
15.00
13.45
4.34
18.36
13.45
4.34
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
-\0L\-
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 MEASUREMENTS
25630-02
25639-01
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
14.32
4.62
11.00
12.53
4.04
13.04
20.25
6.53
11.18
17.46
5.63
14.87
12.37
3.99
13.00
16.12
5.20
17.89
14.32
4.62
18.38
17.46
5.63
11.70
21.40
6.90
12.37
20.22
6.52
12.37
23.02
7.43
15.81
22.20
7.16
21.40
17.80
5.74
15.00
14.87
4.80
13.89
16.12
5.20
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 MEASUREMENTS
25658-06
25673-01
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
14.42
4.65
19.24
18.03
5.82
23.54
25.00
8.06
20.00
14.56
4.70
16.28
17.03
5.49
16.00
21.10
6.80
13.89
21.26
6.86
18.03
20.62
6.65
13.00
13.93
4.49
19.00
15.00
4.84
18.25
19.24 17.89
6.20 5.77
16.64 16.76
17.26
5.57
15.52
13.00
4.19
11.05
11.18
3.61
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 MEASUREMENTS
25676-05
25686-05
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
15.00
4.84
20.10
16.28
5.25
17.46
13.15
4.24
21.59
16.55
5.34
16.55
17.00
5.48
17.00
18.44
5.95
16.03
15.03
4.85
11.05
12.53
4.04
10.20
13.42
4.33
12.53
14.87
4.80
17.00
12.21
3.94
18.38
17.12
5.52
17.49
14.32
4.62
17.03
18.03
5.82
15.23
17.03
5.49
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 MEASUREMENTS
25696-01
25705-02
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
17.69
5 .71
19.85
14.76
4 .76
14.76
17.46 17.26
5 .63 5 .57
17.09 25.00
17.72
5 .72
10.00
17.00
5 .48
23.43
15.26
4 .92
19.65
20.00
6 .45
22.36
21.10
6 .80
14.87
15.00
4 .84
20.88
14.87
4 .80
21.40
15.03
4 .85
19.24
27.20
8 .78
17.03
21.38
6 .90
15.81
18.60
6 .00
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 MEASUREMENTS
25615-07
25618-12
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
17.26
5.57
23.43
23.26
7.50
19.70
19.10
6.16
22.09
22.00
7.10
19.10
17.03
5.49
13.60
13.42
4.33
16.28
14.14
4.56
15.00
21.54
6.95
16.28
18.60
6.00
19.70
19.42
6.26
15.52
16.00
5.16
18.03
15.56 22.85
5.02 7.37
11.40 15.81
17.00
5.48
24.60
10.44
3.37
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 MEASUREMENTS
25621-11
25632-11
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
16.00
5.16
18.68
13.89
4.48
15.52
23.71
7.65
16.12
15.30
4.93
14.14
16.12
5.20
18.87
12.53
4.04
17.69
16.55
5.34
17.00
23.85
7.69
18.68
19.10
6.16
22.47
20.22
6.52
17.80
25.63
8.27
19.72
20.25
6.53
18.36
11.31
3.65
21.21
13.93
4.49
19.24
15.30
4.93
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
-L 0 L \-
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 MEASUREMENTS
25637-09
25638-09
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
21.02
6.78
19.85
19.65
6.34
16.12
19.42
6.26
16.03
15.03
4.85
11.70
19.03
6.14
14.32
15.65
5.05
13.04
18.03
5.82
17.03
19.03
6.14
12.04
23.09
7.45
17.12
14.21
4.58
25.18
21.10
6.80
20.88
19.92
6.43
11.40
18.03
5.82
12.37
21.02
6.78
14.32
23.32
7.52
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 MEASUREMENTS
25657-09
25670-12
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
18.03
5.82
21.10
18.00
5.81
19.42
11.66 12.17
3.76 3.92
27.46 17.89
17.46
5.63
26.83
24.21
7.81
12.37
17.12
5.52
16.49
24.04
7.76
17.72
23.54
7.59
15.23
23.00
7.42
15.81
13.60
4.39
21.38
17.26
5.57
21.02
13.89
4.48
15.81
14.76
4.76
21.21
15.26
4.92
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 MEASUREMENTS
25681-09
25687-09
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
19.24
6.20
13.04
24.19
7.80
13.45
20.00
6.45
14.32
16.16
5.21
17.69
18.03
5.82
18.60
21.26
6.86
17.12
17.12
5.52
16.28
15.62
5.04
13.60
14.14
4.56
19.03
15.65
5.05
17.46
18.79
6.06
18.03
14.14
4.56
17.12
12.81
4.13
16.12
17.00
5.48
12.53
13.04
4.21
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
-O U T-
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 MEASUREMENTS
25619-07
25630-08
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
15.81
5.10
21.19
17.26
5.57
14.21
14.87
4.80
17.12
13.89
4.48
21.63
17.49
5.64
20.00
14.42
4.65
16.49
13.60
4.39
16.00
18.03
5.82
17.80
15.52
5.01
23.43
22.02
7.10
17.26
14.21
4.58
20.81
15.23
4.91
24.08
16.64
5.37
18.60
23.00
7.42
20.00
15.30
4.93
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
-TUI-
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 MEASUREMENTS
25639-10
25658-11
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
12.81
4.13
13.15
15.52
5.01
19.24
13.60 17.69
4.39 5.71
14.76 17.00
18.03 24.02
5.82 7.75
17.46 17.69
20.62
6.65
17.09
20.00
6.45
14.14
18.38
5.93
15.65
16.00
5.16
20.25
16.12
5.20
17.09
16.00
5.16
23.71
17.49
5.64
14.04
17.49
5.64
17.09
18.25
5.89
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 MEASUREMENTS
25676-10
25686-12
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
18.68
6.03
16.76
15.26
4.92
14.87
18.03
5.82
17.03
14.76
4.76
19.70
20.10
6.48
21.26
22.20
7.16
20.88
13.42
4.33
17.49
22.36
7.21
14.04
18.68
6.03
20.22
15.03
4.85
15.65
21.47
6.93
22.02
27.02
8.72
20.40
19.31
6.23
15.26
18.03
5.82
23.02
16.49
5.32
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 MEASUREMENTS
25696-12
25705-12
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
19.21
6.20
16.40
19.00
6.13
19.42
25.18
8.12
17.03
18.38
5.93
19.10
20.62
6.65
16.00
16.76
5.41
24.21
19.65
6.34
23.09
15.81
5.10
19.03
24.02
7.75
21.00
13.15
4.24
15.00
15.26
4.92
16.03
15.26
4.92
22.14
16.28
5.25
21.02
19.10
6.16
18.44
22.47
7.25
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25615-06
25618-09
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
483 156
191
FOLLICLE 1, SHORT AXIS
167 253232
54 26351
131 78313
FOLLICLE 2, LONG AXIS
300 97
195
FOLLICLE 2, SHORT AXIS
160 151442
52 15759
109 66954
FOLLICLE 3, LONG AXIS
252 81
168
FOLLICLE 3, SHORT AXIS
160 126864
52 13201
136 72106
FOLLICLE 4, LONG AXIS
200 65
128
FOLLICLE 4, SHORT AXIS
144 90626
46 9430
98 39559
FOLLICLE 5, LONG AXIS
194 63
150
FOLLICLE 5, SHORT AXIS
118 71963
38 7488
112 53082
FOLLICLE 6, LONG AXIS
182 59
144
FOLLICLE 6, SHORT AXIS
78 44849
25 4667
113 51062
FOLLICLE 7, LONG AXIS
176 57
140
FOLLICLE 7, SHORT AXIS
161 89018
52 9263
125 54979
FOLLICLE 8, LONG AXIS
137 44
163
FOLLICLE 8, SHORT AXIS
102 43879
33 4566
79 40588
FOLLICLE 9, LONG AXIS
173 56
133
FOLLICLE 9, SHORT AXIS
143 77762
46 8092
128 53475
FOLLICLE 10, LONG AXIS
168 54
128
FOLLICLE 10, SHORT AXIS
136 71927
44 7485
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25621-03
25632-02
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
196
63
176
FOLLICLE 1, SHORT AXIS
138 85392
45 8886
103 56950
FOLLICLE 2, LONG AXIS
172
55
204
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
168 90739 157
54 9442 51
139 89295 184
FOLLICLE 3, SHORT AXIS
127 62770
41 6532
138 79790
FOLLICLE 4, LONG AXIS
181
58
278
FOLLICLE 4, SHORT AXIS
145 82373
47 8572
136 118841
FOLLICLE 5, LONG AXIS
156
50
178
FOLLICLE 5, SHORT AXIS
129 63100
42 6566
159 88621
FOLLICLE 6, LONG AXIS
129
42
176
FOLLICLE 6, SHORT AXIS
102 41190
33 4286
133 73594
FOLLICLE 7, LONG AXIS
157
51
146
FOLLICLE 7, SHORT AXIS
137 67500
44 7024
82 37615
FOLLICLE 8, LONG AXIS
162
52
203
FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS
90 45808 153
29 4767 49
172 109871 167
FOLLICLE 9, SHORT AXIS
109 52647
35 5478
157 82301
FOLLICLE 10, LONG AXIS
164
53
157
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25637-03
25638-01
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
194
62
285
FOLLICLE 1, SHORT AXIS
129 78419
42 8160
233 208815
FOLLICLE 2, LONG AXIS
283
91
239
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
180 159881 187
58 16637 60
156 117046 190
FOLLICLE 3, SHORT AXIS
126 73830
40 7683
100 59714
FOLLICLE 4, LONG AXIS
170
55
214
FOLLICLE 4, SHORT AXIS
111 59568
36 6199
151 101424
FOLLICLE 5, LONG AXIS
175
57
263
FOLLICLE 5, SHORT AXIS
139 76342
45 7944
134 110457
FOLLICLE 6, LONG AXIS
141
45
234
FOLLICLE 6, SHORT AXIS
101 44692
33 4651
176 129723
FOLLICLE 7, LONG AXIS
136
44
194
FOLLICLE 7, SHORT AXIS
130 55615
42 5787
112 68459
FOLLICLE 8, LONG AXIS
128
41
164
FOLLICLE 8, SHORT AXIS
94 37992
30 3953
152 78523
FOLLICLE 9, LONG AXIS
114
37
126
FOLLICLE 9, SHORT AXIS
82 29376
26 3057
98 38966
FOLLICLE 10, LONG AXIS
154
50
146
FOLLICLE 10, SHORT AXIS
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
-LILI-
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
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25657-07
25670-06
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
278
90
265
FOLLICLE 1, SHORT AXIS
168 146920
54 15288
158 131471
FOLLICLE 2, LONG AXIS
160
52
216
FOLLICLE 2, SHORT AXIS
128 64296
41 6691
124 84123
FOLLICLE 3, LONG AXIS
193
62
216
FOLLICLE 3, SHORT AXIS FOLLICLE 4, LONG AXIS
146 88343 177
47 9193 57
122 82787 174
FOLLICLE 4, SHORT AXIS
141 78264
45 8144
105 57139
FOLLICLE 5, LONG AXIS
154
50
205
FOLLICLE 5, SHORT AXIS
107 51825
35 5393
135 86802
FOLLICLE 6, LONG AXIS
151
49
200
FOLLICLE 6, SHORT AXIS
107 50467
34 5251
113 70777
FOLLICLE 7, LONG AXIS
147
47
186
FOLLICLE 7, SHORT AXIS
109 50333
35 5238
109 63480
FOLLICLE 8, LONG AXIS
137
44
170
FOLLICLE 8, SHORT AXIS
108 46454
35 4834
116 61952
FOLLICLE 9, LONG AXIS
161
52
176
FOLLICLE 9, SHORT AXIS
117 59098
38 6150
124 68309
FOLLICLE 10, LONG AXIS
170
55
160
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25681-03
25687-04
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
144
46
264
FOLLICLE 1, SHORT AXIS
80 36375
26 3785
224 185689
FOLLICLE 2, LONG AXIS
160
52
160
FOLLICLE 2, SHORT AXIS
151 76032
49 7912
139 69924
FOLLICLE 3, LONG AXIS
180
58
221
FOLLICLE 3, SHORT AXIS
99 56117
32 5839
162 112589
FOLLICLE 4, LONG AXIS
158
51
163
FOLLICLE 4, SHORT AXIS
107 53117
34 5527
105 53795
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS
129 113 46001
42 37 4787
199 157 98097
FOLLICLE 6, LONG AXIS
144
46
200
FOLLICLE 6, SHORT AXIS
95 42998
31 4474
125 78750
FOLLICLE 7, LONG AXIS
150
49
155
FOLLICLE 7, SHORT AXIS
129 60821
42 6329
92 45117
FOLLICLE 8, LONG AXIS
142
46
165
FOLLICLE 8, SHORT AXIS
126 55904
41 5817
119 61771
FOLLICLE 9, LONG AXIS
145
47
163
FOLLICLE 9, SHORT AXIS
111 50444
36 5249
131 67085
FOLLICLE 10, LONG AXIS
143
46
154
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25616-02
25619-03
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
239 77
201
FOLLICLE 1, SHORT AXIS
195 146626
63 15258
136 86188
FOLLICLE 2, LONG AXIS
213 69
164
FOLLICLE 2, SHORT AXIS
154 102632
50 10680
118 60847
FOLLICLE 3, LONG AXIS
195 63
231
FOLLICLE 3, SHORT AXIS
130 79612
42 8284
218 158867
FOLLICLE 4, LONG AXIS
205 66
170
FOLLICLE 4, SHORT AXIS
156 100566
50 10465
166 88814
FOLLICLE 5, LONG AXIS
196 63
149
FOLLICLE 5, SHORT AXIS
183 112455
59 11702
101 47438
FOLLICLE 6, LONG AXIS
173 56
156
FOLLICLE 6, SHORT AXIS
145 78642
47 8183
119 58665
FOLLICLE 7, LONG AXIS
155 50
152
FOLLICLE 7, SHORT AXIS
115 55867
37 5813
112 53607
FOLLICLE 8, LONG AXIS
129 42
143
FOLLICLE 8, SHORT AXIS
76 30793
25 3204
100 45062
FOLLICLE 9, LONG AXIS
163 53
136
FOLLICLE 9, SHORT AXIS
133 68231
43 7100
99 42650
FOLLICLE 10, LONG AXIS
201 65
151
FOLLICLE 10, SHORT AXIS
166 104560
54 10880
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25630-06
25639-03
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
223
72
214
FOLLICLE 1, SHORT AXIS
148 103597
48 10780
170 114662
FOLLICLE 2, LONG AXIS 322 104
150
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
196 197915 201
63 20595 65
110 51925 177
FOLLICLE 3, SHORT AXIS
89 56503
29 5880
145 80535
FOLLICLE 4, LONG AXIS
132
42
190
FOLLICLE 4, SHORT AXIS
95 39223
31 4082
138 82401
FOLLICLE 5, LONG AXIS
111
36
161
FOLLICLE 5, SHORT AXIS
93 32238
30 3355
105 53389
FOLLICLE 6, LONG AXIS
111
36
173
FOLLICLE 6, SHORT AXIS
70 24485
23 2548
120 65301
FOLLICLE 7, LONG AXIS
108
35
183
FOLLICLE 7, SHORT AXIS
98 33263
32 3461
134 76844
FOLLICLE 8, LONG AXIS
141
45
176
FOLLICLE 8, SHORT AXIS
100 44432
32 4623
112 61979
FOLLICLE 9, LONG AXIS
146
47
160
FOLLICLE 9, SHORT AXIS
112 51290
36 5337
114 57086
FOLLICLE 10, LONG AXIS
90
29
140
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25658-04
25673-08
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
190
61
183
FOLLICLE 1, SHORT AXIS
145 86386
47 8989
136 78024
FOLLICLE 2, LONG AXIS
223
72
202
FOLLICLE 2, SHORT AXIS
149 104230
48 10846
142 89873
FOLLICLE 3, LONG AXIS
206
67
203
FOLLICLE 3, SHORT AXIS
168 109091
54 11352
114 72810
FOLLICLE 4, LONG AXIS
233
75
199
FOLLICLE 4, SHORT AXIS
176 128757
57 13398
144 90264
FOLLICLE 5, LONG AXIS
193
62
147
FOLLICLE 5, SHORT AXIS
161 97286
52 10123
159 73661
FOLLICLE 6, LONG AXIS
259
83
159
FOLLICLE 6, SHORT AXIS
122 99390
39 10342
118 59094
FOLLICLE 7, LONG AXIS
182
59
185
FOLLICLE 7, SHORT AXIS
156 88968
50 9258
124 71886
FOLLICLE 8, LONG AXIS
153
49
143
FOLLICLE 8, SHORT AXIS
98 46900
31 4880
98 44021
FOLLICLE 9, LONG AXIS
143
46
100
FOLLICLE 9, SHORT AXIS
102 46018
33 4789
96 30242
FOLLICLE 10, LONG AXIS
151
49
200
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25676-04
25686-01
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
236
76
215
FOLLICLE 1, SHORT AXIS
201 149046
65 15509
136 91617
FOLLICLE 2, LONG AXIS
187
60
205
FOLLICLE 2, SHORT AXIS FOLLICLE 3, LONG AXIS
126 74009 206
41 7701 67
183 117456 177
FOLLICLE 3, SHORT AXIS
139 90246
45 9391
129 71478
FOLLICLE 4, LONG AXIS
185
60
253
FOLLICLE 4, SHORT AXIS
119 69306
38 7212
198 157283
FOLLICLE 5, LONG AXIS
217
70
156
FOLLICLE 5, SHORT AXIS
108 73745
35 7674
136 66802
FOLLICLE 6, LONG AXIS
153
49
156
FOLLICLE 6, SHORT AXIS
98 47087
32 4900
100 49148
FOLLICLE 7, LONG AXIS
172
56
143
FOLLICLE 7, SHORT AXIS
91 49053
29 5104
89 39818
FOLLICLE 8, LONG AXIS
181
58
143
FOLLICLE 8, SHORT AXIS FOLLICLE 9, LONG AXIS
142 80981 147
46 8427 47
107 47996 112
FOLLICLE 9, SHORT AXIS
121 55900
39 5817
88 31231
FOLLICLE 10, LONG AXIS
135
44
155
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Males
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25696-06
25705-06
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
179
58
208
FOLLICLE 1, SHORT AXIS
121 68272
39 7104
183 119716
FOLLICLE 2, LONG AXIS
207
67
203
FOLLICLE 2, SHORT AXIS
140 90803
45 9449
167 106194
FOLLICLE 3, LONG AXIS
158
51
196
FOLLICLE 3, SHORT AXIS
123 61124
40 6360
121 74810
FOLLICLE 4, LONG AXIS
165
53
134
FOLLICLE 4, SHORT AXIS
125 64523
40 6714
120 50642
FOLLICLE 5, LONG AXIS
146
47
162
FOLLICLE 5, SHORT AXIS
78 35677
25 3712
106 54105
FOLLICLE 6, LONG AXIS
167
54
140
FOLLICLE 6, SHORT AXIS
147 77407
48 8055
88 38880
FOLLICLE 7, LONG AXIS
132
42
174
FOLLICLE 7, SHORT AXIS
96 39571
31 4118
70 38343
FOLLICLE 8, LONG AXIS
122
39
122
FOLLICLE 8, SHORT AXIS
99 37968
32 3951
89 34040
FOLLICLE 9, LONG AXIS
136
44
126
FOLLICLE 9, SHORT AXIS
91 38976
29 4056
104 41348
FOLLICLE 10, LONG AXIS
115
37
113
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Females
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25615-09
25618-18
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
216 70
203
FOLLICLE 1, SHORT AXIS
156 105695
50 10998
151 96153
FOLLICLE 2, LONG AXIS
160 52
166
FOLLICLE 2, SHORT AXIS
88 44173
28 4597
110 57743
FOLLICLE 3, LONG AXIS
172 55
225
FOLLICLE 3, SHORT AXIS
135 72792
43 7575
195 137898
FOLLICLE 4, LONG AXIS
164 53
137
FOLLICLE 4, SHORT AXIS
119 61462
38 6396
78 33542
FOLLICLE 5, LONG AXIS
172 55
188
FOLLICLE 5, SHORT AXIS
101 54557
33 5677
122 72453
FOLLICLE 6, LONG AXIS
163 52
188
FOLLICLE 6, SHORT AXIS
113 57664
36 6000
115 67728
FOLLICLE 7, LONG AXIS
135 43
179
FOLLICLE 7, SHORT AXIS
105 44546
34 4635
157 88248
FOLLICLE 8, LONG AXIS
147 47
166
FOLLICLE 8, SHORT AXIS
113 52258
37 5438
143 74723
FOLLICLE 9, LONG AXIS
138 44
162
FOLLICLE 9, SHORT AXIS
88 37936
28 3948
95 48258
FOLLICLE 10, LONG AXIS
174 56
142
FOLLICLE 10, SHORT AXIS
106 57620
34 5996
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25621-12
25632-15
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
210
68
221
FOLLICLE 1, SHORT AXIS
157 104012
51 10823
159 110415
FOLLICLE 2, LONG AXIS
221
71
185
FOLLICLE 2, SHORT AXIS
149 103667
48 10787
120 69807
FOLLICLE 3, LONG AXIS
195
63
171
FOLLICLE 3, SHORT AXIS
123 75489
40 7855
98 52491
FOLLICLE 4, LONG AXIS
231
74
240
FOLLICLE 4, SHORT AXIS
157 113673
51 11829
171 128761
FOLLICLE 5, LONG AXIS
213
69
201
FOLLICLE 5, SHORT AXIS
161 107622
52 11199
164 103892
FOLLICLE 6, LONG AXIS
148
48
199
FOLLICLE 6, SHORT AXIS
90 41922
29 4362
147 92311
FOLLICLE 7, LONG AXIS
169
55
212
FOLLICLE 7, SHORT AXIS
101 53622
33 5580
151 100697
FOLLICLE 8, LONG AXIS
153
49
157
FOLLICLE 8, SHORT AXIS
103 49592
33 5160
110 54343
FOLLICLE 9, LONG AXIS
144
46
165
FOLLICLE 9, SHORT AXIS
124 56070
40 5835
144 74542
FOLLICLE 10, LONG AXIS
163
52
160
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25637-10
25638-11
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
180
58
183
FOLLICLE 1, SHORT AXIS
132 74411
43 7743
146 83740
FOLLICLE 2, LONG AXIS
185
60
163
FOLLICLE 2, SHORT AXIS
126 73501
41 7648
127 65073
FOLLICLE 3, LONG AXIS
196
63
172
FOLLICLE 3, SHORT AXIS
128 78867
41 8207
122 66034
FOLLICLE 4, LONG AXIS
230
74
195
FOLLICLE 4, SHORT AXIS
108 77705
35 8086
118 72105
FOLLICLE 5, LONG AXIS
239
77
169
FOLLICLE 5, SHORT AXIS
192 144539
62 15040
132 70143
FOLLICLE 6, LONG AXIS
185
60
147
FOLLICLE 6, SHORT AXIS
74 43332
24 4509
124 57154
FOLLICLE 7, LONG AXIS
132
42
137
FOLLICLE 7, SHORT AXIS
88 36335
28 3781
74 31999
FOLLICLE 8, LONG AXIS
222
72
154
FOLLICLE 8, SHORT AXIS
176 122999
57 12799
88 42751
FOLLICLE 9, LONG AXIS
141
45
134
FOLLICLE 9, SHORT AXIS
121 53539
39 5571
106 44643
FOLLICLE 10, LONG AXIS
211
68
140
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25657-13
25670-17
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
204
66
252
FOLLICLE 1, SHORT AXIS
130 83388
42 8677
183 144487
FOLLICLE 2, LONG AXIS
172
55
261
FOLLICLE 2, SHORT AXIS
107 57766
35 6011
216 176602
FOLLICLE 3, LONG AXIS
230
74
153
FOLLICLE 3, SHORT AXIS
104 75449
34 7851
96 45944
FOLLICLE 4, LONG AXIS
159
51
180
FOLLICLE 4, SHORT AXIS
112 55954
36 5822
116 65781
FOLLICLE 5, LONG AXIS
137
44
194
FOLLICLE 5, SHORT AXIS
116 50024
37 5205
145 88430
FOLLICLE 6, LONG AXIS
160
52
188
FOLLICLE 6, SHORT AXIS
82 41324
27 4300
153 90337
FOLLICLE 7, LONG AXIS
151
49
143
FOLLICLE 7, SHORT AXIS
88 41715
28 4341
122 55030
FOLLICLE 8, LONG AXIS
176
57
119
FOLLICLE 8, SHORT AXIS
80 44417
26 4622
85 32004
FOLLICLE 9, LONG AXIS
115
37
110
FOLLICLE 9, SHORT AXIS
68 24706
22 2571
87 30205
FOLLICLE 10, LONG AXIS
202
65
158
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 1 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25681-14
25687-10
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
179
58
184
FOLLICLE 1, SHORT AXIS
146 82496
47 8584
138 79660
FOLLICLE 2, LONG AXIS
176
57
200
FOLLICLE 2, SHORT AXIS
131 72588
42 7553
144 90619
FOLLICLE 3, LONG AXIS
159
51
192
FOLLICLE 3, SHORT AXIS
89 44511
29 4632
178 107447
FOLLICLE 4, LONG AXIS
159
51
168
FOLLICLE 4, SHORT AXIS
114 56787
37 5909
105 55393
FOLLICLE 5, LONG AXIS
165
53
234
FOLLICLE 5, SHORT AXIS
122 63041
39 6560
97 71371
FOLLICLE 6, LONG AXIS
137
44
228
FOLLICLE 6, SHORT AXIS
68 29433
22 3063
114 81870
FOLLICLE 7, LONG AXIS
134
43
146
FOLLICLE 7, SHORT AXIS
118 49745
38 5176
124 56961
FOLLICLE 8, LONG AXIS
123
40
137
FOLLICLE 8, SHORT AXIS
122 47115
39 4903
115 49332
FOLLICLE 9, LONG AXIS
111
36
152
FOLLICLE 9, SHORT AXIS
108 37544
35 3907
112 53531
FOLLICLE 10, LONG AXIS
121
39
178
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Females
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25616-13
25619-10
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
141 45
286
FOLLICLE 1, SHORT AXIS
106 47149
34 4906
162 145160
FOLLICLE 2, LONG AXIS
180 58
201
FOLLICLE 2, SHORT AXIS
166 94364
54 9819
106 66581
FOLLICLE 3, LONG AXIS
172 56
196
FOLLICLE 3, SHORT AXIS
131 70871
42 7375
150 92458
FOLLICLE 4, LONG AXIS
185 60
216
FOLLICLE 4, SHORT AXIS
152 88596
49 9219
169 114738
FOLLICLE 5, LONG AXIS
186 60
189
FOLLICLE 5, SHORT AXIS
119 69498
38 7232
142 84171
FOLLICLE 6, LONG AXIS
196 63
187
FOLLICLE 6, SHORT AXIS
71 43431
23 4519
98 57743
FOLLICLE 7, LONG AXIS
142 46
164
FOLLICLE 7, SHORT AXIS
115 51253
37 5333
82 42276
FOLLICLE 8, LONG AXIS
147 48
185
FOLLICLE 8, SHORT AXIS
110 50849
35 5291
134 78051
FOLLICLE 9, LONG AXIS
156 50
123
FOLLICLE 9, SHORT AXIS
103 50754
33 5281
65 25040
FOLLICLE 10, LONG AXIS
200 64
150
FOLLICLE 10, SHORT AXIS
129 80828
42 8411
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25630-13
25639-12
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
245
79
201
FOLLICLE 1, SHORT AXIS
174 133833
56 13926
109 68686
FOLLICLE 2, LONG AXIS
163
53
250
FOLLICLE 2, SHORT AXIS
131 67155
42 6988
120 94451
FOLLICLE 3, LONG AXIS
164
53
186
FOLLICLE 3, SHORT AXIS
122 62870
39 6542
156 91158
FOLLICLE 4, LONG AXIS
198
64
266
FOLLICLE 4, SHORT AXIS
111 69272
36 7208
154 128377
FOLLICLE 5, LONG AXIS
173
56
180
FOLLICLE 5, SHORT AXIS
154 83694
50 8709
102 58117
FOLLICLE 6, LONG AXIS
159
51
180
FOLLICLE 6, SHORT AXIS
89 44501
29 4631
104 58738
FOLLICLE 7, LONG AXIS
164
53
163
FOLLICLE 7, SHORT AXIS
157 80894
51 8418
107 54490
FOLLICLE 8, LONG AXIS
196
63
178
FOLLICLE 8, SHORT AXIS
123 75626
40 7869
116 64608
FOLLICLE 9, LONG AXIS
175
57
184
FOLLICLE 9, SHORT AXIS
136 75016
44 7806
148 85603
FOLLICLE 10, LONG AXIS
165
53
142
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25658-13
25673-14
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS 351 113
234
FOLLICLE 1, SHORT AXIS
183 201493
59 20967
185 135518
FOLLICLE 2, LONG AXIS
231
74
156
FOLLICLE 2, SHORT AXIS
96 69403
31 7222
124 60481
FOLLICLE 3, LONG AXIS
204
66
199
FOLLICLE 3, SHORT AXIS
171 109320
55 11376
121 75518
FOLLICLE 4, LONG AXIS
252
81
217
FOLLICLE 4, SHORT AXIS
149 117826
48 12261
120 82170
FOLLICLE 5, LONG AXIS
204
66
120
FOLLICLE 5, SHORT AXIS
112 71657
36 7456
93 34878
FOLLICLE 6, LONG AXIS
169
54
137
FOLLICLE 6, SHORT AXIS
144 76504
47 7961
118 50774
FOLLICLE 7, LONG AXIS
269
87
123
FOLLICLE 7, SHORT AXIS
226 191586
73 19936
88 34001
FOLLICLE 8, LONG AXIS
216
70
132
FOLLICLE 8, SHORT AXIS
128 86563
41 9008
104 43206
FOLLICLE 9, LONG AXIS
158
51
152
FOLLICLE 9, SHORT AXIS
122 60747
39 6321
90 42865
FOLLICLE 10, LONG AXIS
142
46
137
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25676-08
25686-15
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
224
72
261
FOLLICLE 1, SHORT AXIS
132 93050
43 9683
157 128423
FOLLICLE 2, LONG AXIS
222
72
217
FOLLICLE 2, SHORT AXIS
131 91114
42 9481
148 100758
FOLLICLE 3, LONG AXIS
191
61
184
FOLLICLE 3, SHORT AXIS
108 64362
35 6697
133 76676
FOLLICLE 4, LONG AXIS
161
52
187
FOLLICLE 4, SHORT AXIS
95 47987
31 4993
158 92711
FOLLICLE 5, LONG AXIS FOLLICLE 5, SHORT AXIS
201 115 72775
65 37 7573
178 148 82775
FOLLICLE 6, LONG AXIS
136
44
169
FOLLICLE 6, SHORT AXIS
98 42001
32 4371
108 57448
FOLLICLE 7, LONG AXIS
168
54
172
FOLLICLE 7, SHORT AXIS
143 75405
46 7846
135 73039
FOLLICLE 8, LONG AXIS
202
65
145
FOLLICLE 8, SHORT AXIS
170 107832
55 11221
98 44570
FOLLICLE 9, LONG AXIS
161
52
166
FOLLICLE 9, SHORT AXIS
133 67075
43 6980
106 55044
FOLLICLE 10, LONG AXIS
148
48
146
FOLLICLE 10, SHORT AXIS
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
APPENDIX 49 (F1 PUPS - PND 21) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL THYROID MORPHOMETRY
GROUP: 4 Female;
THYROID COLLOID MEASUREMENTS AND AREAS
ANIMAL NUMBER:
25696-14
25705-11
FOLLICLE1 NUMBER
LENGTH
AREA
LENGTH
AREA
LENGTH
AREA
AND DESCRIPTION
(PIXELS)(PIXELS 2)
(um)
(um2)
(PIXELS)(PIXELS 2)
FOLLICLE 1, LONG AXIS
174
56
229
FOLLICLE 1, SHORT AXIS
78 42963
25 4471
178 127982
FOLLICLE 2, LONG AXIS
150
48
224
FOLLICLE 2, SHORT AXIS
111 52098
36 5421
160 112860
FOLLICLE 3, LONG AXIS
115
37
201
FOLLICLE 3, SHORT AXIS
84 30280
27 3151
192 121085
FOLLICLE 4, LONG AXIS
134
43
218
FOLLICLE 4, SHORT AXIS
104 43684
34 4546
197 134671
FOLLICLE 5, LONG AXIS
174
56
201
FOLLICLE 5, SHORT AXIS
96 52338
31 5446
97 61068
FOLLICLE 6, LONG AXIS
144
46
215
FOLLICLE 6, SHORT AXIS
106 48204
34 5016
110 74211
FOLLICLE 7, LONG AXIS
116
38
188
FOLLICLE 7, SHORT AXIS
90 32909
29 3424
153 90244
FOLLICLE 8, LONG AXIS
104
34
156
FOLLICLE 8, SHORT AXIS
72 23715
23 2468
123 60311
FOLLICLE 9, LONG AXIS 96 31
156
FOLLICLE 9, SHORT AXIS
74 22199
24 2310
118 58157
FOLLICLE 10, LONG AXIS
113
36
185
FOLLICLE 10, SHORT AXIS
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 MEASUREMENTS
25615-06
25618-09
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
14.14
4.56
13.89
18.03
5.82
12.73
14.21
4.58
13.89
11.40
3.68
17.69
18.60
6.00
15.23
12.53
4.04
12.73
13.89
4.48
10.77
11.40
3.68
22.80
15.23
4.91
13.04
12.37
3.99
13.00
11.31
3.65
17.46
15.81
5.10
14.76
16.40
5.29
14.21
12.81
4.13
16.40
19.92
6.43
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 MEASUREMENTS
25621-03
25632-02
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
28.84
9.30
20.00
14.00
4.52
18.44
19.70
6.35
16.12
17.20
5.55
18.44
17.20
5.55
12.65
16.12
5.20
13.42
20.88
6.74
16.12
13.42
4.33
17.89
15.23
4.91
16.12
14.00
4.52
22.80
19.80
6.39
18.00
20.00
6.45
20.10
18.97
6.12
15.62
18.11
5.84
16.12
12.17
3.92
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 MEASUREMENTS
25637-03
25638-01
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
23.09
7.45
18.44
17.46
5.63
18.87
12.81
4.13
12.00
15.56
5.02
20.00
17.80
5.74
20.00
20.12
6.49
17.20
20.00
6.45
18.60
20.10
6.48
15.13
18.00
5.81
15.62
20.00
6.45
18.38
23.41
7.55
16.40
17.09
5.51
18.60
19.80
6.39
15.81
17.89
5.77
14.42
25.61
8.26
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 MEASUREMENTS
25657-07
25670-06
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
18.03
5.82
16.28
23.71
7.65
15.23
18.68
6.03
22.09
19.21
6.20
22.36
16.49
5.32
17.89
15.00
4.84
26.31
19.10
6.16
23.77
17.46
5.63
14.42
17.12
5.52
18.25
25.06
8.08
20.10
16.28
5.25
15.00
19.21
6.20
16.28
18.11
5.84
24.35
19.00
6.13
18.44
21.93
7.07
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 MEASUREMENTS
25681-03
25687-04
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
16.12
5.20
17.89
18.44
5.95
22.36
20.59
6.64
20.88
16.49
5.32
16.12
16.49 16.97
5.32 5.47
21.54 18.87
22.80
7.36
14.00
17.00
5.48
14.42
21.02
6.78
22.80
16.40
5.29
20.00
16.64
5.37
18.97
14.87
4.80
16.12
18.00
5.81
18.03
15.03
4.85
20.00
23.60
7.61
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 MEASUREMENTS
25616-02
25619-03
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
27.78
8.96
12.17
22.80
7.36
20.12
28.64
9.24
18.87
20.40
6.58
16.12
22.80
7.36
14.32
30.53
9.85
15.03
17.09
5.51
16.00
12.81
4.13
21.93
16.12
5.20
22.47
14.14
4.56
19.42
12.81
4.13
16.03
16.12
5.20
17.03
15.62
5.04
21.19
18.44
5.95
14.87
15.62
5.04
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 MEASUREMENTS
25630-06
25639-03
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
21.02
6.78
22.02
19.42
6.26
17.69
19.10
6.16
20.10
20.10
6.48
15.00
20.40
6.58
15.62
19.21
6.20
22.14
17.00
5.48
22.02
19.24
6.20
16.03
25.18
8.12
18.03
21.63
6.98
19.42
18.68
6.03
18.44
20.62
6.65
20.40
17.46
5.63
16.12
23.85
7.69
19.85
17.03
5.49
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 MEASUREMENTS
25658-04
25673-08
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
24.74
7.98
22.85
17.20
5.55
19.92
20.00 17.89
6.45 5.77
16.28 17.69
14.14
4.56
20.62
18.44
5.95
19.00
17.20
5.55
22.47
18.44 17.89
5.95 5.77
18.79 18.38
20.40
6.58
18.87
17.09
5.51
16.49
20.40
6.58
17.00
26.68
8.61
21.54
22.36
7.21
20.52
26.31
8.49
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 MEASUREMENTS
25676-04
25686-01
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
24.41
7.88
25.71
18.38
5.93
26.93
18.87
6.09
25.50
24.04
7.76
22.14
23.85 20.81
7.69 6.71
24.02 20.00
15.00
4.84
16.12
18.60
6.00
24.04
17.03
5.49
21.02
18.36
5.92
20.81
18.36
5.92
15.23
16.76
5.41
18.38
19.10
6.16
21.95
18.11
5.84
13.42
21.63
6.98
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 MEASUREMENTS
25696-06
25705-06
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
20.62
6.65
12.17
26.08
8.41
24.17
23.32
7.52
20.59
12.73
4.11
22.36
23.85 24.00
7.69 7.74
24.08 22.80
17.46
5.63
10.00
18.79
6.06
16.97
17.72
5.72
21.63
26.08
8.41
22.00
26.93
8.69
20.88
20.62
6.65
12.81
19.10
6.16
16.12
13.42
4.33
16.00
22.85
7.37
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 MEASUREMENTS
25615-09
25618-18
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
22.36
7.21
18.03
21.40
6.90
15.62
16.49 17.89
5.32 5.77
17.03 19.24
18.03
5.82
20.00
19.10
6.16
18.79
19.00
6.13
18.38
17.03
5.49
22.85
17.80
5.74
15.23
17.69
5.71
16.55
16.55
5.34
17.49
15.81
5.10
18.25
22.00
7.10
13.42
16.12
5.20
19.21
17.69
5.71
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 MEASUREMENTS
25621-12
25632-15
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
15.00
4.84
23.35
17.89
5.77
21.63
21.00
6.77
18.03
18.44
5.95
18.79
17.49
5.64
13.89
18.11
5.84
19.00
14.76
4.76
17.46
20.12
6.49
19.24
15.30
4.93
17.49
20.25
6.53
25.50
20.02
6.46
18.44
24.19
7.80
24.04
20.00
6.45
15.23
15.23
4.91
23.60
22.20
7.16
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 MEASUREMENTS
25637-10
25638-11
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
23.32
7.52
15.03
20.00
6.45
21.54
18.44
5.95
20.25
14.56
4.70
23.09
23.32
7.52
18.68
20.10
6.48
20.22
22.80
7.36
18.79
16.55
5.34
20.00
15.65
5.05
15.30
23.35
7.53
27.00
14.21 24.02
4.58 7.75
19.42 21.95
18.03
5.82
22.02
18.44
5.95
15.30
15.26
4.92
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 MEASUREMENTS
25657-13
25670-17
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
12.65
4.08
20.88
18.44
5.95
26.08
18.44
5.95
21.00
25.08
8.09
26.08
22.56
7.28
20.81
24.00
7.74
21.59
24.04
7.76
15.81
24.08
7.77
29.12
27.78
8.96
16.16
19.24
6.20
18.00
24.08
7.77
21.10
18.11
5.84
20.00
21.95
7.08
21.10
23.60
7.61
20.62
25.30
8.16
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 MEASUREMENTS
25681-14
25687-10
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
16.64
5.37
22.00
20.00
6.45
20.02
18.36
5.92
20.25
18.11
5.84
15.23
18.11
5.84
16.12
15.00
4.84
19.10
15.81
5.10
13.00
15.65
5.05
16.12
18.36
5.92
18.36
16.76
5.41
17.20
21.40
6.90
24.19
18.44
5.95
16.97
21.40
6.90
19.42
21.10
6.80
21.95
19.10
6.16
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 MEASUREMENTS
25616-13
25619-10
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
18.68
6.03
26.91
13.89
4.48
18.60
13.00
4.19
20.10
22.83
7.36
21.19
23.60
7.61
16.40
16.40
5.29
17.20
15.81
5.10
19.24
18.03
5.82
23.60
16.28 21.40
5.25 6.90
26.00 23.77
24.70 14.87
7.97 4.80
13.60 26.25
15.52
5.01
18.03
17.72
5.72
19.21
13.42
4.33
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 MEASUREMENTS
25630-13
25639-12
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
25.71
8.29
26.17
19.42
6.26
23.77
21.59
6.96
21.00
17.03
5.49
25.00
21.38 27.73
6.90 8.95
18.44 16.00
21.95
7.08
23.85
24.02
7.75
26.00
19.10
6.16
22.56
21.26
6.86
20.02
21.21
6.84
17.89
21.38
6.90
15.81
17.49
5.64
19.42
16.76
5.41
30.61
25.71
8.29
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 MEASUREMENTS
25658-13
25673-14
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
23.54
7.59
19.10
16.76
5.41
14.21
14.76
4.76
13.93
19.85
6.40
20.62
22.02
7.10
19.42
16.76
5.41
24.35
19.70
6.35
14.21
19.03
6.14
15.81
14.87
4.80
16.49
20.00
6.45
20.59
19.42
6.26
17.72
17.00
5.48
14.21
18.25
5.89
16.49
16.40
5.29
16.00
17.69
5.71
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 MEASUREMENTS
25676-08
25686-15
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
20.88
6.74
18.87
20.10
6.48
23.19
20.12
6.49
20.62
29.15
9.40
25.00
24.08
7.77
18.38
25.02
8.07
18.44
27.29
8.80
16.00
20.00
6.45
18.87
23.19
7.48
17.03
23.19
7.48
21.10
24.04
7.76
13.60
20.25
6.53
18.03
16.16
5.21
21.10
18.36
5.92
24.70
24.33
7.85
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 MEASUREMENTS
25696-14
25705-11
CELL HEIGHT
CELL HEIGHT
CELL HEIGHT
(PIXELS)
(um)
(PIXELS)
25.71
8.29
14.32
26.63
8.59
18.03
18.38
5.93
18.38
15.03
4.85
17.09
17.00
5.48
20.40
13.89
4.48
12.53
19.72
6.36
18.60
23.77
7.67
24.04
21.19 24.02
6.84 7.75
21.02 21.02
16.12
5.20
22.09
20.25
6.53
16.28
17.80
5.74
12.17
16.00
5.16
18.00
15.30
4.93
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
64 83 NEX 116 NEX NIP
MEAN SD N
42 35.5
7
MEAN SD N
18.6 5
NIP NOT IN PLANE OF SECTION; NEX TISSUE NOT RECEIVED
-1756-
CO CO CO CO
PAGE 2
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 o f thyroid morphometry and thyroid cell proliferation data to the protocol.
Approved By: 3M Corporation
John L. Butenhoff, PhD, CIH, DABT Sponsor Representative
Prepared By: WIL Research Laboratories, LLC
Date
Study Director
Date
Director, Development and Reproductive Toxicology
WIL R e s e a r c h La b o r a t o r i e s ,LLC i407 g e o r g e r o a d a s h l a n d ,o h 44805-9281 (4i9)289-8700 f a x <4i9)289-3650 Improving human health and protecting the environment through scientific research services,
-1761-
Study N um ber: W IL-180017
PROTOCOL AMENDMENT III 3M Study Number: 06-128
Sponsor: 3M C orporation
A. Title o f Study:
A n O ral (G avage) D evelopm ental N eurotoxicity and T hyroid F unction Study o f M T D ID 208 in R ats
B. Protocol M odification:
1) 9.6
Thyroid Histopathology and Morphometry:
B ased on the Study D irector N otification dated January 11, 2007, the first sentence is changed to read:
O ne pup/sex/litter from ten random ly selected litters/group on postnatal days 4 and 21 w ill h e prepared for thyroid m icroscopic exam ination and m orphom etry (thyroids for all groups w ill be processed; how ever, the control and high dose groups w ill be initially evaluated).
2) B a s e d o n th e S tu d y d ir e c to r N o tif ic a tio n d a te d J a n u a ry 11, 2 0 0 7 , S e c tio n
9.7 is replaced w ith the follow ing:
9.7 Thyroid Cell Proliferation Assay:
O ne fetus/sex/litter from 10 random ly selected litters/group on gestational day 20 w ill b e prepared for thyroid m icroscopic ex am ination (thyroids for all groups w ill be processed; how ever, the control and high dose groups w ill b e initially evaluated) and have a thyroid cell proliferation assay perform ed using K i67 im m unohistochem ical staining.
C. R eason for Protocol M odification:
1 ,2 ) B ased on the initial m icroscopic exam ination o f fetal and pup thyroids, the protocol w as am ended to require assessm ent o f thyroid cell proliferation for postnatal day 4 pups because o f an absence o f colloid. H ow ever, the boxes containing the gestation day 20 and postnatal day 4 thyroid slides w ere
W I L R e s e a r c h La b o r a t o r i e s ,llc 1407 g e o r g e r o a d As h l a n d ,o h 44805-9281 <419)289-8700 fax <419)289-3650 Improving human health and protecting the environment through scientific research services.
-1762-
WIL-180017
Protocol Amendment in
Page 2
m isidentified. T he thyroids w ithout colloid are actually from the gestation day 20 fetuses. T herefore, the cell proliferation assay w ill be perform ed on the gestation day 20 fetuses and thyroid m orphom etry w ill be perform ed on the postnatal day 4 pups.
A pproved By:
3M Corporation
John L. B utenhoff, PhD , CIH, D A B T Sponsor R epresentative
Prepared By:
WIL Research Laboratories, LLC
D ate
D onald G. Stum p, PhD , D A B T Study D irector
D ate
D irector, D evelopm ent and R eproductive T oxicology
usua
-1763-
W IL
Study N um ber: W IL-180017
PROTOCOL AMENDMENT II 3M Study Number: 06-128
Sponsor: 3M C orporation
A. T itle of Study:
A n O ral (G avage) D evelopm ental N eurotoxicity and T hyroid F unction Study of M T D ID 208 in R ats
B. Protocol M odification:
1) 9.6 Thyroid Histopathology and Morphometry:
T he first sentence is changes to read:
O ne fetus/sex/litter from each toxicokinetic phase fem ale euthanized on gestation day 20 and one pup/sex/litter from 10 random ly selected litters/group on postnatal day 21 w ill be p rep ared fo r thyroid m icroscopic exam ination and m orphom etry (thyroids for all groups w ill be processed; how ever, the control and high dose groups w ill be initially evaluated).
2) T he follow ing is added to the protocol:
9.7 Thyroid Cell Proliferation Assay:
O ne pup/sex/litter from 10 random ly selected litters/group on postnatal day 4 w ill be prepared for thyroid m icroscopic exam ination (thyroids fo r all gro u p s w ill be pro cessed ; ho w ev er, the co n tro l and h ig h dose groups w ill be initially evaluated) and have a thyroid cell proliferation assay perform ed using K i67 im m unohistochem ical staining.
C. R eason for P rotocol M odification:
1) T h e c lie n t in c o n s u lta tio n w ith th e S tu d y D ir e c to r h a s e le c te d to p e r fo r m
thyroid m orphom etry only on the toxicokinetic phase fem ales on gestation day 20 fetuses and postnatal day 21 pups.
W I L R e s e a r c h L a b o r a t o r i e s ,llc 1407 g e o r g e r o a d a s h l a n d ,o h 44805-9281 <4t9)289-8700 fax <4i9>289 3650 Improving human health and protecting the environment through scientific research services,
-1764-
WIL-180017 Protocol Amendment II Page 2
2) T he client has elected to perform a thyroid cell proliferation assay on the postnatal day 4 anim als.
A pproved By:
3M Corporation
< 7 ^ -- 3-- 5^
John L. B utenhoff, PhD , C M , D A B T Sponsor R epresentative
*7 AJr H
D ate
Prepared By:
WIL Research Laboratories, LLC
D onald G. Stum p, PhD , D A B T Study D irector
3 V'-'-j ocC
D ate
i Mark D .W m eefB sf DABT
D irector, D evelopm ent and R eproductive T oxicology
D ate
i.
wi
-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 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.
-1766-
W IL -180017 Protocol Amendment I Page 2
C. R eason for Protocol M odification:
1) T o p ro v id e a d isp o sitio n fo r the su rp lu s anim als.
2 and 3) T o include statistical analysis o f form er im plantation sites, unaccounted for sites, and tim e to escape the straight channel to the protocol.
A pproved By:
3M Corporation
John L. B utenhoff, PhD , CIH , D A B T Sponsor R epresentative
Prepared By:
WIL Research Laboratories, LLC
D ate
D onald G. Stum p, PhD , D A B T Study D irector
D ate
M ark D. Nem ec, B SfD A B T D irector, D evelopm ent and R eproductive T oxicology
g WI I
-1767Page 1of33
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 o f 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 o f 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 o f 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 o f 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 o f 33
W IL-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 o f 33
WIL-180017 April 20, 2006
6.3 Drinking Water:
Reverse osmosis-purified water will be available a d 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 a d 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 o f 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 o f 33
W IL-180017 April 20, 2006
(also possibly to a minor extent through feed). No direct administration to the F1animals 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 o f 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 o f 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.
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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 )* 20/sex/group (a )* 20/sex/group (a )*
PND 20 and 60 PND 13, 17, 21 and 61 PND 22
Auditory startle Locomotor activity 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
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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.
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Ease of removal from cage Ease of handling animal in
Lacrimation/
hand
chromodacryorrhea
Salivation
Piloerectiona,b
Fur appearancea,b
Palpebral closurea,b
Respiratory rate/character
Red/Crusty deposits Eye prominencea,b
Mucous membranes and skin color
Pupillary responsea,b
Eye colora,b
Mobilitya
Muscle tone
Gaita
Arousal
Convulsions/tremors
Urination/defecation
Groominga,b
Backinga
Bizarre/Stereotypic behavior Tail pinch response3,11
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
b
development. 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.
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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 (Vm a x ), average response amplitude (Va v e ) and latency to Vm a x (Tm a x ).
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
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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
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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
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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 qL 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 F ax:(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).
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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.
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9.3.5 Females Found Dead or Euthanized In E xtrem is:
Maternal animals found dead or euthanized in extrem is (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 extrem is 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 F1Deaths and F1Pups Euthanized in E xtrem is:
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 extrem is 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.
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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
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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):
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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
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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.
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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
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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.
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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
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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 QUALITYASSURANCE:
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.
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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.
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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.
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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 o f a protocol amendment. All alterations o f 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. N eurobehavioral Toxicology a n d Teratology 1985, 7, 579-586.
Biel, W.C. Early age differences in maze performance in the albino rat. Journal o f Genetic P sychology 1940, 56, 439-453.
Dunn, O.J. Multiple comparisons using rank sums. Technom etrics, 1964 6(3):241-252.
Dunnett, C.W. New tables for multiple comparisons with a control. Biom etrics 1964, 20, 482-491.
Gad, S.C. A neuromuscular screen for use in industrial toxicology. Journal o f Toxicology a n d E nvironm ental H ealth 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 o f American. College o f 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," Psychopharm acologia 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 o f Reproduction 1977, 17, 298-303.
Kruskal, W.H.; Wallis, W.A. Use of ranks in one-criterion variance analysis. Journal o f the A m erican 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 o f Amitraz. Toxicology a n d A p p lied P harm acology 1991, 108, 267-283.
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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 o f American College o f 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 - Schm iedebergs A rchiv f r Experim entelle Pathologie und Pharm akologie 1964, 247, 367.
Snedecor, G.W.; Cochran, W.G. One Way Classifications; Analysis of Variance. In Statistical M ethods, 7th ed.; The Iowa State University Press: Ames, IA, 1980; pp 215-237.
Steel, R.G.D.; Torrie, J.H. Principles and Procedures o f Statistics, A Biom etrical A pproach, 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 M utagenesis 1984, 4, 181-188.
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WIL-180017 Apnl 20, 2006
SA S P ro p rie ta ry S o ftw a re , V e rs io n 8 .2; S A S In s titu te , In c., C a ry , N C ., 1999-2001.
19 PROTOCOL APPROVAL:
A pproval for this protocol w as received via v " f
on H D ate
3M Corporation
lo h n L. B utenhoff, PhD , C IH , D A B T Sponsor R epresentative
WIL Research Laboratories, LLC
D onald G. Stum p, PhD , D A B T Study D irector
D ate
Ht*l/(?
D ate
' M ark D /N enlee7-B SiD A B T D irector, D evelopm ental and R eproductive T oxicology
D ate
WIL
WIL-180017 3M Corporation
-1800
MTDID 208 06-128
APPENDIX 53
Certificate Of Analysis (Sponsor-Provided Data)
-1801-
Centre Analytical Laboratories, Inc.
3048 Research Drive State College, PA 16801
www.centrelab.com
Phone: (814) 231-8032
Fax: (814) 231-1253 or (814) 231-1580
INTERIM CERTIFICATE OF ANALYSIS
Revision 3
Centre Analytical Laboratories COA Reference #: 023-018A 3M Product: PFOS,Lot217
Reference#: SD-018
Purity: 86.9%
Test Name
Specifications
Purity1
Result 86.9%
Appearance Identification
NMR
Metals (ICP/MS) 1. Calcium 2. Magnesium 3. Sodium 4. Potassium2 5. Nickel 6 . Iron 7. Manganese
Total % Impurity (NMR)
Total % Impurity (LC/MS) Total % Impurity (GC/MS)
Related Compounds POAA Residual Solvents (TGA) Purity by DSC
Inorganic Anions (IC) 1. Chloride 2. Fluoride 3. Bromide 4. Nitrate 5. Nitrite 6 . Phosphate 7. Sulfate4
Organic Acids 5 (IC) 1. TFA 2. PFPA 3. HFBA 4. NFPA
Elemental Analysis": 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine
White Crystalline Powder
aD) iKDEOVE IHl
y)T APR 1 Q wifi
1. Theoretical Value = 17.8% 2. Theoretical Value = 0% 3. Theoretical Value = 0% 4. Theoretical Value = 5.95% 5. Theoretical Value = 60%
Conforms
Positive
1. 0.005 wt./wt.% 2 . 0 . 0 0 1 wt./wt.% 3. 1.439 wt./wt.% 4. 6.849 wt./wt.% 5. <0.001 wt./wt.% 6 . 0.005 wt./wt.% 7. <0.001 wt.Avt.%
1.91 wt./wt.% 8.41 wt./wt.%
None Detected
0.33 wt./wt.% None Detected Not Applicable1
1. <0.015 wt./wt.% 2. 0.59 wt.Avt.% 3. <0.040 wt./wt.% 4. <0.009 wt.Avt.% 5. <0.006 wt.Avt.% 6 . <0.007 wt.Avt.% 7. 8.76 wt.Avt.%
1. <0.1 wt.Avt.% 2. <0.1 wt.Avt.% 3. 0.10 wt.Avt.% 4. 0.28 wt.Avt.%
1. 12.48 wt.Avt.% 2. 0.244 wt.Avt.% 3. 1.74 wt.Avt.% 4. 8.84 wt.Avt.% 5. 54.1 wt.Avt.%
COA023-018A
Page 1 o f 3
-1802-
Centre Analytical Laboratories, Inc.
3048 Research Drive State College, PA 16801
www.centrelab.com
Phone: (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 o f Last Analysis: 08/31/00
Expiration Date: 08/31/06
Storage Conditions: Frozen <-10C
Re-assessment Date: 08/31/06
'Purity = 100% - (sum o f metal impurities, 1.45% +LC/MS impurities, 8.41%+Inorganic Fluoride, 0.59%+NMR impurities, 1.905%+organic acid 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.
3Purity by DSC is generally not applicable to materials o f low purity. No endotherm was observed for this sample.
4Sulfiir 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 sulfur determination in the elemental analysis, lending confidence to this interpretation. Based on the results, the SO4 is not considered an impurity.
5TFA HFBA NFPA PFPA
Trifluoroacetic acid Heptafluorobutyric acid Nonafluoropentanoic acid Pentafluoropropanoic acid
th eo retica l value calculations based on the empirical formula, CgFnSCVK4 (MW=538)
This work was conducted under EPA Good Laboratory Practice Standards (40 CFR 160).
COA023-018A
Page 2 of 3
-1803-
Cntre Analytical Laboratories. Inc.
3048 Research Drive State College, PA 16801
www.centrelab.com
Phone: (814) 231 -8032
Fax: (814) 231 -1253 or (814) 231 -1580
INTERIM CERTIFICATE OF ANALYSIS
Revision 3 Centre Analytical Laboratories COA Reference #: 023-018A
LC/MS Purity Profile:
Impurity C4 C5 C6 C7
Total
wt./wt. % 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 from the C4 and C6 standard curves. Likewise, the C7 value was calculated using the average result from the C6 and C8 standard curves.
Prepared By: Scientist, Centre Analytical Laboratories
/O/ft / o f Date
: L in fLUd,qR eview ed By:
uTFahity
/
Date
Laboratory Manager, Centre Analytical Laboratories
COA023-018A
Page 3 of 3
WIL-180017 3M Corporation
-1804-
MTDID 208 06-128
APPENDIX 54
Analyses O f Dosing Formulations And Toxicokinetics Report (3M Corporation)
-1805-
3M Medical Department
Bioanalytical Laboratory
To: From: Study:
Donald Stump, Ph.D. David J. Ehresman, MT (ASCP) WIL Research Study No. 180017
Date:
December 28th, 2007
1. Introduction
Periluorooctanesulfonate (PFOS) was the test material used in WIL Research Study No. 180017 (Developmental Neurotoxicity Study in Rats). Dosing solutions and several batches of rat serum and liver samples were sent to the 3M Medical Department, Bioanalytical Laboratory for analyses of PFOS concentrations. All samples arrived frozen with sufficient remaining dry ice available.
2. Analytical Methods
2.1. Analytical Standards
PFOS internal standard used was 180 2-perfluorooctanesulfonate (180 2PFOS). This compound has two 180 oxygen's which increase the molecular weight by 4 amu. The labeled oxygen's are strategically located on the molecule and are carried through the primary ionization and are included in the product ions as well. PFOS interna! standard was synthesized by Research Triangle Institute (Research Triangle Park, NC, US). The primary PFOS standard was supplied by 3M {lot 217). PFOS stock solution was prepared as 10 mg PFOS per 100 mL in methanol. Appropriate dilutions in methanol were made to achieve working standards at concentrations of 0.5, 1.0 5.0 and 10.0 ng/pL.
2.2. HPLC Column Selections
The HPLC column used was a base-deactivated C-18 ACE column (2.1 mm i.d. x 100 mm, 5pm) purchased from MAC-MOD Analytical (Chadds Ford, PA, USA).
i
-1806-
2.3. Instrumentation
All analyses were accomplished using a Shimadzu HPLC system interfaced to an APi 4000 triple stage mass spectrometer (Applied Biosystems / MDS-Sciex Instrument Corporation, Foster City, CA, USA). The mass spectrometer was operated in the MS/MS mode using the Turbo Ion Spray source (pneumatically assisted electrospray ionization) in the negative-ion mode.
2.4. Sample Preparation
Sample Preparation: Serum
A constant, fixed amount of internal standard ( 0 2-labeled PFOS) was
added to new, clean, disposable, polypropylene tubes labeled for standards, blanks and control samples. The extraction was based on 100 pL of serum. 1.0 mL of 1.0 N formic acid was added to all tubes, followed by 100 pL saturated ammonium sulfate. Samples were vortexed between each addition.
Sample Preparation: Liver
Approximately 0.2 g of liver was weighed and homogenized with deionized water in a clean polypropylene tube. The ratio between liver and water was 1:4 (w/w). After the primary homogenization step, the whole homogenate was sonicated for 30 minutes, and 100 pL of homogenate was transferred to a clean polypropylene tube, followed by the addition of PFOS internal standard. One mL of 1.0 N formic acid was added to all tubes followed by 300 pL of water. Samples were vortexed between each addition. Samples were at a pH of approximately 2.5.
Sample Preparation: PFOS Standard Curve
To prepare a LC/MS-MS PFOS standard curve, a series of PFOS
solutions prepared in methanol were volumetrlcally delivered to clean
polypropylene tubes, and 100 pL of appropriate matrix (liver or serum
blank) was added to each tube to give final concentrations of PFOS of 0,
10, 25, 50, 75, 100, 250, 375, 500, 750 and 1000 pg/mL
18
0 2-labeled
PFOS Internal standard was added to all tubes followed by formic acid
and, for serum samples only, saturated ammonium sulfate.
Solid-Phase Extraction (SPE)
All extractions were based on 100 pL of sample matrix and utilized Waters Oasis hydrophilic-lipophilic balance (HLB) 3 mL columns with column conditioning, column loading, column wash, and column elution performed as described in Ehresman et al. Environmental Research, (2007). All
2
-1807-
elution collection tubes (standards and test samples) were then vortexed, and a 750 pL aliquot was transferred to polypropylene micro-vials, which were capped with special polypropylene snap caps. These micro-vials were then loaded onto the auto-sampler and run using the combined LCMS/MS system.
2.5. Analytical Methods The instrument used for analysis was an API 4000 mass spectrometer {Applied Biosystems / MDS-Sclex Instrument Corporation) configured with Turbo Ion Spray (pneumatically assisted electrospray ionization source) in negative ion mode. A Mac-Mod ACE C-18, 5 pm, 100 x 2,1 mm i.d. HPLC column with an isocratic flow rate of 0.35 mL/min was used for PFOS analysis. The mobile phase was 51% acetonitrile and 49% 2 mM ammonium acetate. All source parameters were optimized under these conditions according to manufacturer's guidelines. Transition ions for PFOS: 499 -> 80 atomic mass unit (amu) and the transition ions for internal standard 0 2-labeled PFOS: 503 -> 84 amu were monitored.
3. Results Results are displayed in Tables 1 - 6 below.
3
-1808-
Table 1: Dosing solution analyses summary
Homogeneity Samples
G roup #
P o sitio n
Dose C o n cen tratio n
(m g /m L )
Dose C o n cen tratio n (corrected for
K + cou nter ion w eig h t and purity of
86.9% ) (m g /m L)
D ilution F a c to r
PFOS C o n cen tratio n ,
corrected fo r d ilu tion (m g /m L )
Mean PFOS c o n c e n tra tio n (m g /m L )
% Target Dose
1 S a m p le 2 Mid Sam ple 2 Top
2 S a m p le 2 Mid
S a m p le 2 Bottom Sam p le 2 Top 3 S a m p le 2 Mid S a m p le 2 Bottom Sam ple 2 Top
4 S a m p le 2 Mid
S a m p le 2 Bottom
0 0 0 < LLOQ
100X
0 .0 1 5 9
0 .0 2 0
0.0161
100X
0 .0 1 5 9
100X
0 .0 1 5 8
2Q0X
0 .0 5 0 0
0 .0 6 0
0.0434
200X
0 .0 4 6 6
200 0.0452
1000X
0 .1 4 9
0 .2 0 0
0.161
1000X
0 .1 5 8
1000X
0 .1 5 0
Stability Samples
< LLOQ 0 .0 1 6
Not A p p lic a b le
9 8 .4 3
0 .0 4 7
9 7 .7 4
0 .1 5 2
9 4 .5 0
G roup # 2
3
4
P o sitio n Sam ple 2 Top S a m p le 2 Bottom Sam ple 2 Top S am p le 2 Bottom Sam ple 2 Top S a m p le 2 Bottom
Dose C o ncentration
(m g /m L ) 0 .0 2
006
0.2
Dose C o n cen tratio n (corrected for
K + cou nter ion w e ig h t and purity of
86.9% } (m g /m L )
0.0161
0 .0 4 8 4
0 .1 6 1 2
D ilution F a c to r 100X 100X 200X 200X 1000X 1000X
PFOS C o n cen tratio n ,
corrected for dilu tion (m g /m L )
0 .0 1 5 6
0.0161
0 .0 4 6 4
0 .0 4 6 3
0 .1 4 6 0
0 .1 6 0 0
Mean PFOS con centration (m g /m L )
0 .0 1 5 9
0 .0 4 7
0 .1 4 8
% Target Dose 9 8 .3 2
9 6 ,3 6
91.81
4
-1809-
Table 1 (continued):
Dosing Formulations
D a te 5/1/2 006 5/8/2 006 5 /1 5 /2 0 0 6 5 /2 2 /2 0 0 6 5 /2 9 /2 0 0 6 6/5/2 006 6 /1 2 /2 0 0 6
G roup #
1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4
Dose C o n cen tratio n
(m g /m L)
Dose C o ncentration (corrected for K+ c o u n te r ion w e ig h t
and purity o f 86.9% ) (m g /m L)
D ilution F a c to r
0 00
0 .0 2
0.0161
100x
0 .0 6
0 .0 4 8 4
200x
0.2
0 .1 6 1 2
1000x
0 00
0 .0 2
0 .0 1 6 1
100x
0 .0 6
0 .0 4 8 4
200x
0.2
0 .1 6 1 2
1000X
0 00
0 .0 2
0.0161
100x
0 .0 6
0 .0 4 8 4
200x
0.2
0 .1 6 1 2
1000x
0 00
0 .0 2
0.0161
100x
0 .0 6
0 .0 4 8 4
2Q0x
0.2
0 ,1 6 1 2
1000x
0 00
0 .0 2
0.0161
100x
0 .0 6
0 .0 4 8 4
200x
0 .2
0 .1 6 1 2
1 0 0 Ox
0 00
0 .0 2
0.0161
100x
0 .0 6
0 .0 4 8 4
200x
0.2
0 .1 6 1 2
100 0x
00
002
0.0161
100x
0 .0 6
0 .0 4 8 4
2Q0x
0.2
0 ,1 6 1 2
1 0 0 Ox
Dosing Formulations -
PFOS C o n cen tratio n
(m g /m L) < LLOQ
0 .0 1 5 0 .0 4 7 0 ,1 6 3 < LLOQ 0 .0 1 9 2 0 .0 4 6 1 0 .1 5 8 < LLOQ 0 .0 1 6 0 5 0 .0 4 7 6 0 .1 6 5 5 < LLOQ 0 .0 1 5 3 0 .0 4 8 0 5 0 .1 5 9 5 < LLOQ 0 .0 1 5 3 0 .0 4 7 0 5 0 1695 < LLOQ 0 .0 1 4 6 0 ,0 4 8 8 5 0 .1 6 5 < LLOQ 0 .0 1 5 4 0 .0 4 7 0 .1 5 5
Mean
% Target Dose Not Applicable
9 3 .0 5 9 7 .1 9 1 0 1 .1 2 Not Applicable 1 1 9 .1 1 95.33 98.01 N ot Applicable 9 9 .5 7 98.43 1 0 2 ,6 7 N o t Applicable 9 4 .9 1 9 9 .3 6 9 8 .9 4 N ot Applicable 94.91 9 7 .2 9 9 8 .9 4 N o t Applicable 9 0 .5 7 101.01 1 0 2 .3 6 Not Applicable 9 5 .5 3 9 7 .1 9 9 6 .1 5
G roup
#
Dose C o n cen tratio n
(m g /m L)
0
0.02 0.06 0.2
Dose C o ncentration (corrected for K+
c o u n te r ion w eigh t a n d p u rity o f B 6,9% )
(m g /m L )
0
0 .0 1 6 1
0.0484 0.1612
Mean PFOS C once ntrafion
M easured (m g /m L )
< LLOQ
0,0158 0.0474 0.1608
Mean PFOS C o n cen tratio n
M easured S ta n d a rd D e via tio n (m g /m L )
< LLOQ
0.0015 0.0009 0.0039
Mean % Target Dose
M easured (m g /m L )
Not Applicable
98.24 97.97 99.74
S ta n d a rd D e via tio n (m g /m L )
Not Applicable
9.60 1.83 2.40
5
-1810-
Table 2: Mean PFOS Concentrations ( standard deviation) in Serum and Liver
G D 20 L D 4 /P N D 4 L D 2 1 /P N D 2 1 PN D 72
Control
0.1 m g /k g -d 0.3 m g /k g -d
1 m g /k g -d
Control
0,1 m g /k g -d 0 .3 m g /k g -d
1 m g /k g -d
Control
0.1 m g /k g -d 0 .3 m g /k g -d
1 m g /k g -d
Control
0.1 m g /k g -d 0 .3 m g /k g -d
1 m g /k g -d
S e ru m [P F O S ], jtg /m L
Dam 0.006 (0.002) 1.722 (0.215) 6.245 (2.850) 26.630 (12.468) Dam 0.008 (0.001) 3.307 (0.254) 10.449 (0.739) 34.320 (3.648)
Dam
0.007 (0.001)
3.159 (0.257)
8.981 (0.868) 30.480 (+4.091)
Dam
NA
NA
NA
NA
Fetus 0.009 (0.002) 3.906 (0.302) 10.446 (0.822) 31,463 (2.920) Pup
< LOQ
2.236 (0.222)
6.960 (0.515) 22.440 (2.286)
Male Pup
<LOQ
1.729 (0.251)
5.048 (0.340) 18.611 (3.032)
Male Pup
< LOQ
0.042 (0.009)
0.120 (0.019)
0.560 (0.234)
Female Pup
<LOQ
1.771 (0.240)
5.246 (0.436) 18.010 (2.352) Female
Pup
< LOQ
0.207 (0.094)
0.556 (0.139)
1.993 (0.656)
L iv e r [P F O S ], p g /g
Dam < LOQ 8.349 (1.087) 21.725 (2.038) 48.875 (7.731) Dam
NA
NA
NA
NS
Dam
NA
NA
NA
NA
Dam
NA
NA
NA
NA
Fetus
< LOQ
3.205 (0.686)
5.814 (0.694) 20.025 (5.716)
Pup
< LOQ
9.463 {1.619) 20.130 (3.047) 50.180 (+3.553)
Male Pup
<LOG
5.980 (1.941) 14.780 (+2.631) 44.890 (8.338)
Male P u p
< LOQ
0.981 (0.203)
2.464 (0.163)
7.170 (0.854)
Female Pup
<LOG
5.278 (0.552) 13.550 (0.943) 41.230 (7.257)
Female Pup
< LOQ
0.801 (0.184)
2.252 (0.212)
7.204 (0.927)
6
-1811-
Table 3: Individual Data on GD 20
C ontrol 0.1 m g /k g -d 0.3 m g/kg-d 1 m g/kg-d
A n im al # 25612 25620 25629 25634 25650 25679 25683 25706 25718 25760 M ean SD N 25607 25613 25627 25640 25643 25651 25669 25682 25711 25768 M ean SD N 25596 25596 25601 25641 25644 25662 25667 25675 25680 25726 Mean SD N 25608 25625 25649 25656 25688 25693 25699 25734 25745 25750 Mean SD N
S erum [PFO S , ug/m L
Dam < LOQ
Fetus 0 ,0 0 9 5 4
< LOQ
0.0101
0 .0 0 5 0 6
0 .0 0 8 4 8
0 .0 0 5 1 7
0 .0 1 0 5
< LOQ
0 .0 0 6 1 7
< LOQ
0.00831
< LOQ
0.00741
< LOQ
0 .0 0 7 4 3
< LOQ
0 .0 1 0 3
0 .0 0 8 6 6
0 .0 1 1 2
< LOQ
0.009
< LOQ
0 .0 0 2
10 10
1.0 2 .0 4
4 .2 5 3.71
1.7 3.74
1 .3 6
3 .5 7
1 .6 3
4 .1 2
1.96 1.84 1.49
3.7 4 .1 7 4 .1 9
1.91
3 .4 4
1 .6 9
4 .1 7
1 ,7 2 2 0 .2 1 5
3 .9 0 6 0 .3 0 2
10 10
5.31
11.5
4 .3 6
9 .7 8
5.2 i n
5 .2 8
11.4
12.1
10
4.31
10.4
4 .5 5
NA
4 .5 2
9 ,1 9
5 .8 2 11
10.2 NA
6 .2 4 5
1 0 .4 4 6
2 .8 5 0
0 .8 2 2
10 8
2 1 .5
32.2
16,7
2 7 .6
1 6 ,8
35.1
1 9 .6 2 4 .4
31,1 27.1
2 9 .3
3 3 .6
5 4 .4
NA
22,1
3 0 .9
4 2 ,8
NA
18 7
34.1
2 6 .6 3 0 1 2 .4 6 8
3 1 .4 6 3 2 .9 2 0
10 8
L iver [P F O S ], ug/g
Dam
F e tu s
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
<100
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ
< LOQ < LOQ
< LOQ
< LOQ
10 10
7 ,9 4
2.51
7 .6 8
3 .1 7
8.6 3.01
9 ,7 7
3 .5 2
9 .0 5
4 .2 3
S 2.67
9 .5 2
3 .5 4
9 .2 6
2 .1 7
7 .3 5
4 .2 3
6 .3 2
3
8.349
3 .2 0 5
1.087
0 .5 8 6
10 10
2 4 .8 20
5 ,3 6 4 .8 7
23 5.88
2 0 .9
5 .3 7
NA NA
2 3 .3
6 .8 7
2 0 .8
5 .0 2
18.5
6 .2 2
2 2 .5
6 .4 2
NA NA
2 1 .7 2 5
5 .8 1 4
2,038
0 .6 9 4
88
5 6 .4
2 1 .5
5 3 .6
15
6 2 .5
2 9 ,2
4 3 .3
18.8
4 5 .7
12.5
46.1
27
NA NA
4 0 .7
19.3
NA NA
4 2 .7
16,9
4 8 .8 7 5
2 0 .0 2 5
7.731 8
5 .7 1 6 8
7
-1812-
Table 4: Individual Data on LD4 and PND4
C ontrol 0.1 m g /k g -d 0.3 m g/kg-d 1 m g/kg-d
A n im al # 25615 25618 25621 25632 25637 25638 25657 25670 25681 25687 M ean SD N 25626 25652 25655 25660 25672 26674 26694 25727 25733 25753 Mean SD N 25609 25614 25623 25628 25642 25650 25678 25698 25722 25735 Mean SD N 25616 25619 25630 25639 25658 25673 25676 25636 25696 25705 M ean SD N
S eru m [P F O S . ug/m L
Dam
Pup
0 .0 0 9 3 6
0 .0 0 6 5 9
0 .0 1 0 5
< LOQ
0.00841
< LOO
0 00727 0 .0 0 7 3 4
0 .0 0 5 0 3 < LOQ
0 .0 0 8 8 8
< LOQ
0 .0 0 7 6 3
< LOQ
0 .0 0 7 8 7
< LOQ
0 .0 0 9 2 7
< LOQ
0 .0 0 8 0 6
< LOQ
0 .0 0 8
< LOQ
0.001
< LOQ
10 10
3 .2 8
2 .3 5
3 .3 9
1.93
3.41
2 .3 5
3 .7 3 .1 2
2 .0 8 2 .1 4
3 .3 8
2 .5 7
3 .2 8
1.88
2 .8 8
2.31
3 .6 2
2 .3 2
3.01
2 .4 3
3 .3 0 7 0 .2 5 4
2 .2 3 6 0 .2 2 2
10 10
10.5
6 .7 7
10 7.04
11 7 .1 9
10.1
7 .7 9
9 .9 4
7.21
10.6
6 .3 6
9 .9 5
6.1
10.1
6 .8 3
12.3
7 .5 7
10 6.74
1 0 .4 4 9
6 .9 6 0
0 .7 3 9
0 .5 1 5
10 10
3 7 .7
2 2 .5
3 9 .9
2 0 .2
3 1 .9
2 1 .4
3 2 .5 3 6 .2
23 2 5 .3
29.1
2 2 .8
3 5 .5
2 4 .7
3 1 .3
2 4 .9
3 0 .9
2 1 .7
3 8 .2
17.9
3 4 .3 2 0
2 2 .4 4 0
3 .6 4 8
2 .2 8 6
10 10
L iv e r fP F O S . U 3'9
Dam
Pup
NS 0.0855
NS < LQQ
NS < LOQ
NS < LOQ
NS < LOQ
NS < LOQ
NS < LOQ
NS < LOQ
NS < LOQ
NS < LOQ
NA < LOQ
NA < LOQ
0 10
NS 8.63
N S 9.12
NS 6.62
NS 9.36
NS 7.82
NS 10.9
N S 11
NS 11.4
N S 8.58
NS 11.2
N A 9.463
N A 1.619
0 10
N S 17.1
NS 20.7
NS 24.7
NS 14.9
NS 20.9
NS 17.1
NS 24
NS 20.9
NS 20.8
NS 20.2
N A 20.130
N A 3.047
0 10
NS 48.7
NS 44.6
NS 49.7
NS 47.2
NS 54.1
NS 48.6
NS 52,2
NS 54.5
NS 47.3
NS 54,9
NA 50.180
NA 3.553
0|
10
g
-1813-
Table 5: Individual Data on LD21 and PND21
C ontrol 0.1 m g /k g -d 0.3 m glkg-d 1 m g/kg-d
A n im al # 25615 25618 25621 25632 25637 25638 25657 25670 25681 25687 M ean SD N 25626 25652 25655 25660 25672 25674 25694 25727 25733 25753 M ean SD N 25609 25614 25623 25628 25642 25650 25678 25698 25722 25735 M ean SD N 25616 25619 25630 25639 25658 25673 25676 25886 25696 25705 M ean SD N
S eru m fP FO S l, uq/m L
Dam NS
0 .0 0 7 7 8 0 ,0 0 6 4 6 0 .0 0 8 2 3 0 .0 0 5 4 8 0 .0 0 5 9 8 0 .0 0 5 5 0.00621 0 .0 0 6 6 5 0 .0 0 7 4 9
0 .0 0 7 0.001
9 3 .3 2 3 .3 5 2 .8 2 3 .1 7 3.71
3 2 .9 4 2 .9 8 3 .2 2 3 .0 8 3 .1 5 9 0 .2 5 7
10 10.3 8 .8 9 9 .9 8 8 ,6 7 8 .0 5 8 .2 3 7 .6 7 9 .1 2 9 ,8 6 9 .0 4 8.981 0 .8 6 8 10 3 0 .4 4 0 .6 3 2 .5 3 0 .8 2 8 .2 2 9 .6 3 0 ,9 29 2 5 ,3 2 7 ,5 3 0 .4 8 0 4.091 10
M ale < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ 10 1.45 1 .5 5 1.99 1 .5 5 2 .1 3 1.59 1.59 2.01 1.91 1 .5 2 1.729 0.251 10 4 .6 3 4 .8 6 5 ,0 9 4 .3 5 5 .0 5 5 .2 5 5 .1 9 5 .3 3 5 .3 7 5 .3 6 5 .0 4 8 0 .3 4 0 10 1 7 .2 16.1 19.1 1 7 .9 2 1 ,5 18.6 1 9 .6 13.5 24 18.611 3 .0 3 2 9
Pups Fem ale < LOQ < LOQ < LOQ 0 .0 1 4 4 < LOQ < LOQ < LOQ < LOQ < LOQ
< LOQ
< LOQ
< LOQ
10 1.72 1.78 1.98 1.52 1.86 1.47 1 .5 4 2 .1 6 2 .0 6 1 .6 2 1.771 0 .2 4 0 10 5 04 4 .6 6 5 .1 7 4 ,6 6 5 .1 6 4 .9 6 5 ,6 5 5 .8 7 5.55 5 .7 4 5 .2 4 6 0 .4 3 6 10 1 8 .6 16 1 8 .2 16.5 2 3 .7 20 16.1 1 6 .9 17 17.1 1 8 .0 1 0 2 .3 5 2 10
9
Dam NS NS NS NS NS NS NS NS NS NS NA NA 0 NS NS NS NS NS NS NS NS NS NS NA NA 0 NS NS NS NS NS NS NS NS NS NS NA NA 0 NS NS NS NS NS NS NS NS NS NS NA NA 0
L iv e r [P F O S 1 , u o a
M ale LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ 10 4 .7 5 4 .6 9 5 .1 5 5 .5 2 6 4 .4 3 5 .1 9 5.83 7 .2 4 11 5 .9 3 0 1.941 10 14.8 11.4 1 7 .7 16.1 11,2 1 1 .3 18.2 1 6 .5 1 5 .8 1 4 .8 1 4 .7 8 0 2.631 10 4 8 .6 4 0 .4 4 9 .4 4 6 .5 5 8 .3 5 2 .6 3 2 .3 34.1 3 7 .6 4 8 .6 4 4 .8 9 0 8 .3 3 8 10
Pu ps Fem ale < LOQ < LOQ < LOQ < LOQ
< LOQ
< LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ
10 5 .6 5 4 .3 8 6 .1 7 4 .6 6
5 4 .9 9 5 .3 6 5.91 5 .4 8 5 .1 8 5 .2 7 8 0 .5 5 2
10 12.6 12.1 14,4 14.4 13.3 12.9 15.2 13.2 13.4
14 1 3 .5 5 0 0 .9 4 3
10 4 5 .2 3 4 .6 4 1 .3 3 7 .2
54 4 5 .5 3 8 .3 3 1 .5 3 4 .9 4 9 .8 4 1 .2 3 0 7 .2 5 7
10
-1814-
Table 6: Individual Data on PND72
C ontrol 0,1 m g /k g -d 0.3 m g/kg -d 1 m g/kg-d
A n im al # 25654-09 25632-07 25618-08 25681-01 25713-02
M ean SD N
25648-07 25674-02 25631-04 25741-07 25733-07
Mean SD N
25614-10 25604-04 25689-02 25609-04 25650-11
Mean SD N
25639-06 25705-07 2 5 6 1 9 -0 4 25691-07 2 5 7 1 7 -0 4
Mean SD N
M ale Pups
S e ru m PFOS (ppm ) < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ
5 0 .0 3 5 6 0.0361 0 .0 3 4 3 0 .0 5 3 0 .0 4 8 6 0 .0 4 2 0 .0 0 9
5 0.11 0 ,1 0 6 0 ,1 3 2 0 .1 0 4 0 .1 4 8 0 .1 2 0 0 ,0 1 9
5 0 .5 2 2 0,51 0 ,5 4 2 0 .9 3 7 0.291 0 .5 6 0 0 .2 3 4
5
L iv e r PFOS (u g /g ) < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ
5 1 .2 6 0 795 0 ,8 5 7 0 .8 6 2 1 .1 3 0.981 0 .2 0 3
5 2 .2 7 2 .5 3 2 .3 2 2 .5 4 2 .6 6 2 .4 6 4 0 ,1 6 3
5 6 .4 4 8 .0 6 6 .1 2 7 .8 3 7,4 7 .1 7 0 0 .8 5 4
5
A n im al #
25687-15 25681-10 25713-16 25663-09 25692-07
M ean SD N
25648-12 25674-11 25660-04 25733-8 2 5 7 2 7 -1 6
M ean SD N
25677-08 25614-17 25743-16 2 5 6 8 4 -0 6 2 5 7 3 5 -0 8
M ean SD N
25658-14 25686-10 25639-04 25603-10 25599-11
M ean SD N
Fem ale Pups
S e ru m PFOS (ppm ) < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ
5 0 .3 0 .2 2 3 0 .2 8 2 0 .0 7 1 8 0 .1 5 7 0 .2 0 7 0 .0 9 4
5 0 .5 3 5 0 .6 4 2 0 .3 3 7 0 .5 6 3 0 .7 0 4 0 ,5 5 6 0 .1 3 9
5 0 .9 5 7 2 .2 9 1.96 2 .7 4 2 .0 2 1 .9 9 3 0 .6 5 6
5
L iv e r PFOS (u g /g ) < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ < LOQ
5 0 .8 0 6 0.561 0 .8 3 6 1.07 0 .7 3 3 0.801 0 .1 8 4
5 2 ,1 9 2 .0 2 2 .3 8 2 .5 5 2 .1 2 2 .2 5 2 0 .2 1 2
5 7 .2 9 7 .2 9 6 .1 7 8 .6 3 6 .6 4 7 .2 0 4 0 .9 2 7
5
10
-1815-
Discussion The analysis of potassium PFOS dosing solutions for PFOS anion demonstrated: (1 ) the solutions were homogeneous; and (2) actual concentrations were 91 to 99 % of the target concentrations. Serum and liver concentrations for dams and pups were in approximately linear proportion to dose at ail time points evaluated.
ii
Signatures
Principle Investigator:
jt r i 1
David J. Ehresman, MT (ASCP)
-1816-
Reviewers:
John L. Butenhoff, Ph.D., CIH, DABT
Sue Chang, M.S.
/A/y
Date
03, J Arv O S?
Date
7 ^ >3, W 0$
Date
12
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
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:
B ROOM 47 RAT
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
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
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:
B ROOM 47 RAT
DATE
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
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 TIME DATE TIME
IN: IN: OUT: OUT:
CO
o o
04/18/06 11:00 08/08/06
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
ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS TEMPERATURE/HUMIDITY - END OF STUDY SUMMARY REPORT
9:23 26-Jan-07
STUDY 180017 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 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
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25679 25679 25659 25634 25634
F F F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
TABLE 1 (DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 05-25-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
DISPOSITION EYES/EARS/NOSE DISPOSITION DISPOSITION BODY/INTEGUMENT
05-22-06 05-11-06 05-22-06 05-23-06 05-04-06 05-04-06 05-05-06 05-05-06 05-06-06 05-06-06 05-07-06 05-07-06 05-08-06 05-08-06 05-09-06 05-09-06 05-10-06 05-10-06 05-11-06 05-11-06 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-15-06 05-15-06 05-16-06
6:45 6:15 6:45 6:36 7:20 7:20 7:22 7:22 8:23 8:23 6:51 6:51 6:15 6:15 7:37 7:37 6:09 6:09 6:16 6:16 6:13 6:13 8:47 8:47 9:50 9:50 6:14 6:14 8:02
P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE
1
-1827-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
ANIMAL SEX
GROUP
25634 F 0 MG/KG/DAY
25620 25706 25612 25629 25629
F F F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
GRADE CODE: 1 SLIGHT 2
TABLE 1 (DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 05-25-06
CATEGORY
DATE TIME GRADE OBSERVATIONS
BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
05-16-06 05-17-06 05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-23-06 05-23-06 05-24-06 05-24-06 05-07-06 05-08-06 05-09-06 05-10-06 05-11-06 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06
8:02 6:36 6:36 6:16 6:16 6:16 6:16 6:34 6:34 6:30 6:30 6:12 6:12 6:07 6:07 6:37 6:37 6:29 6:30 6:52 6:16 7:39 6:11 6:17 6:15 6:15 8:49 8:49 9:51
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 2 HAIR LOSS RIGHT FORELIMB
MODERATE 3 SEVERE P PRESENT
PAGE
2
-1828-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 1 (DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 05-25-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25629 F 0 MG/KG/DAY
25718 25718 25760 25760
F F F F
0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY 0 MG/KG/DAY
25683 F 0 MG/KG/DAY 25627 F 0.1 MG/KG/DAY 25669 F 0.1 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT DISPOSITION DISPOSITION DISPOSITION
05-14-06 05-15-06 05-15-06 05-16-06 05-16-06 05-17-06 05-17-06 05-18-06 05-18-06 05-19-06 05-19-06 05-20-06 05-20-06 05-21-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-24-06 05-24-06 05-24-06 05-08-06 05-25-06 05-21-06 05-22-06 05-25-06 05-22-06 05-22-06
9:51 6:17 6:17 8:03 8:03 6:37 6:37 6:18 6:18 6:18 6:18 6:35 6:35 6:32 6:32 6:14 6:14 6:10 6:10 6:15 6:15 6:31 6:17 6:26 6:33 6:16 6:26 6:46 6:47
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
3
-1829-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 1 (DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 05-25-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25613 F 0.1 MG/KG/DAY 25607 F 0.1 MG/KG/DAY 25640 F 0.1 MG/KG/DAY 25711 F 0.1 MG/KG/DAY 25682 F 0.1 MG/KG/DAY 25682 F 0.1 MG/KG/DAY 25651 F 0.1 MG/KG/DAY 25651 F 0.1 MG/KG/DAY
25768 F 0.1 MG/KG/DAY 25643 F 0.1 MG/KG/DAY 25601 F 0.3 MG/KG/DAY 25644 F 0.3 MG/KG/DAY 25680 F 0.3 MG/KG/DAY 25675 F 0.3 MG/KG/DAY 25598 F 0.3 MG/KG/DAY 25598 F 0.3 MG/KG/DAY
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION EYES/EARS/NOSE DISPOSITION EYES/EARS/NOSE
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION BODY/INTEGUMENT
05-23-06 05-23-06 05-23-06 05-24-06 05-24-06 05-06-06 05-24-06 05-06-06 05-07-06 05-08-06 05-25-06 05-25-06 05-22-06 05-22-06 05-23-06 05-23-06 05-23-06 05-06-06 05-07-06 05-08-06 05-09-06 05-10-06 05-11-06 05-12-06 05-14-06 05-15-06 05-16-06 05-17-06 05-18-06
6:38 6:39 6:39 6:31 6:32 8:29 6:33 8:29 6:55 6:22 6:27 6:27 6:47 6:48 6:40 6:40 6:41 8:31 6:57 6:25 7:45 6:19 6:24 6:23 10:00 6:24 8:10 6:44 6:25
P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
4
-1830-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 1 (DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 05-25-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25598 F 0.3 MG/KG/DAY
25667 F 0.3 MG/KG/DAY 25667 F 0.3 MG/KG/DAY 25641 F 0.3 MG/KG/DAY 25641 F 0.3 MG/KG/DAY
25662 25662 25662 25726 25596 25649 25608 25656 25688
F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 0.3 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION EYES/EARS/NOSE DISPOSITION BODY/INTEGUMENT
DISPOSITION BODY/INTEGUMENT EYES/EARS/NOSE DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION
05-18-06 05-19-06 05-20-06 05-20-06 05-21-06 05-22-06 05-22-06 05-23-06 05-23-06 05-07-06 05-24-06 05-14-06 05-14-06 05-15-06 05-15-06 05-21-06 05-23-06 05-23-06 05-24-06 05-24-06 05-24-06 05-17-06 05-16-06 05-25-06 05-25-06 05-22-06 05-22-06 05-23-06 05-23-06
6:25 6:24 6:41 6:41 6:39 6:23 6:23 6:16 6:42 6:58 6:33 10:00 10:00 6:25 6:25 6:40 6:16 6:16 6:19 6:19 6:34 6:45 8:11 6:27 6:27 6:49 6:49 6:42 6:43
1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; GESTATION DAY 20 1 HAIR LOSS RIGHT FORELIMB 1 DRIED RED MATERIAL AROUND NOSE P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20
GRADE CODE: 1 SLIGHT 2 MODERATE 3 SEVERE P PRESENT
PAGE
5
-I8I-
-1832-
1o 1 I-- 1
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 1 (DAILY EXAMINATIONS) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS [POSITIVE FINDINGS ONLY]
TABLE RANGE: 05-02-06 TO 05-25-06
ANIMAL SEX
GROUP
CATEGORY
DATE TIME GRADE OBSERVATIONS
25688 F
MG/KG/DAY
25625 25699 25750 25734 25745 25693
F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY F 1.0 MG/KG/DAY
BODY/INTEGUMENT
DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION DISPOSITION
05-08-06 05-09-06 05-09-06 05-10-06 05-10-06 05-10-06 05-11-06 05-11-06 05-12-06 05-12-06 05-13-06 05-13-06 05-14-06 05-14-06 05-22-06 05-22-06 05-23-06 05-23-06 05-23-06 05-23-06 05-24-06 05-24-06 05-25-06 05-25-06
6:29 7:49 7:49 6:22 6:22 6:22 6:28 6:28 6:27 6:27 9:00 9:00 10:04 10:04 6:28 6:28 6:18 6:18 6:44 6:44 6:35 6:36 6:27 6:27
1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCABBING LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB 1 HAIR LOSS LEFT FORELIMB 1 HAIR LOSS RIGHT FORELIMB P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20 P SCHEDULED EUTHANASIA; GESTATION DAY 20
GRADE CODE: 1 - SLIGHT 2 - MODERATE 3 - SEVERE P - PRESENT
PAGE
6
PCRDv4.11 10/05/2006
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 2 (1 HOUR POST-DOSING) ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL CLINICAL OBSERVATIONS
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
PAGE
1
PCRDv4.11 01/23/2007 R:01/23/2007
-1833-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 3 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]
PREGNANCY
STATUS
DAY 0
3
6
9 12 15 18 20
DAMS FROM GROUP 1:: 0 MG/KG/DAY
25679 25659 25634 25620 25706 25612 25629 25718 25760 25683
G G G G G G G G G G
239. 278. 275. 263. 256. 255. 256. 269. 274. 270.
263. 284. 292. 281. 271. 275. 283. 288. 291. 284.
280. 308. 311. 289. 279. 287. 302. 309. 304. 297.
291. 321. 327. 304. 297. 293. 307. 318. 311. 309.
306. 331. 343. 329. 310. 311. 327. 338. 328. 338.
338. 360. 371. 347. 331. 327. 353. 361. 339. 355.
366. 416. 401. 380. 376. 359. 393. 399. 362. 407.
398. 447. 429. 414. 407. 395. 428. 431. 372. 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
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 1
-1834-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 3 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]
PREGNANCY
STATUS
DAY 0
3
6
9 12 15 18 20
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
25627 25669 25613 25607 25640 25711 25682 25651 25768 25643
G G G G G G G G G G
259. 274. 268. 264. 258. 232. 256. 272. 278. 269.
267. 290. 284. 280. 278. 251. 270. 295. 291. 290.
283. 308. 300. 298. 296. 264. 283. 314. 306. 303.
293. 314. 312. 320. 315. 282. 286. 318. 313. 316.
304. 333. 337. 338. 335. 300. 304. 338. 337. 342.
331. 359. 354. 366. 357. 322. 328. 372. 360. 363.
379. 393. 391. 395. 396. 368. 372. 419. 411. 414.
412. 425. 417. 438. 429. 404. 406. 454. 443. 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
= GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 2
-1835-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 3 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]
PREGNANCY
STATUS
DAY 0
3
6
9 12 15 18 20
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
25601 25644 25680 25675 25598 25667 25641 25662 25726 25596
G NG G G G G G G NG G
244. 262. 273. 262. 259. 251. 268. 269. 283. 262.
277. 259. 286. 268. 267. 262. 286. 284. 290. 281.
286. 257. 291. 281. 284. 273. 291. 295. 289. 288.
295. 268. 303. 298. 299. 293. 298. 300. 293. 300.
306. 272. 330. 322. 319. 310. 313. 320. 305. 316.
334. 269. 351. 339. 337. 326. 340. 340. 308. 331.
372. 270. 396. 388. 385. 373. 372. 385. 313. 369.
410 275 435 419 420 403 403 428 319 399
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. '
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 3
-1836-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 3 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHTS DURING GESTATION [G]
PREGNANCY
STATUS
DAY 0
3
6
9 12 15 18 20
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
25649 25608 25656 25688 25625 25699 25750 25734 25745 25693
G G G G G NG G G NG G
251. 269. 267. 266. 262. 250. 260. 271. 289. 265.
269. 287. 283. 277. 277. 253. 273. 283. 289. 288.
283. 303. 295. 287. 296. 264. 279. 294. 299. 299.
291. 302. 314. 305. 316. 271. 285. 293. 295. 309.
300. 315. 336. 322. 336. 270. 306. 317. 310. 326.
330. 338. 360. 345. 359. 275. 331. 341. 308. 348.
373. 376. 405. 395. 412. 278. 367. 376. 323. 378.
410. 405. 449. 442. 449. 279. 395. 412. 327. 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
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 4
PGBWv4.05 10/05/2006
-1837-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 4 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]
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 25659 25634 25620 25706 25612 25629 25718 25760 25683
G G G G G G G G G G
24. 17. 11. 15. 32. 28. 32. 159.
6. 24. 13. 10. 29. 56. 31. 169.
17. 19. 16. 16. 28. 30. 28. 154.
18. 8. 15. 25. 18. 33. 34. 151.
15. 8. 18. 13. 21. 45. 31. 151.
20. 12.
6. 18. 16. 32. 36. 140.
27. 19.
5. 20. 26. 40. 35. 172.
19. 21.
9. 20. 23. 38. 32. 162.
17. 13.
7. 17. 11. 23. 10. 98.
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
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 1
-1838-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 4 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]
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 25669 25613 25607 25640 25711 25682 25651 25768 25643
G G G G G G G G G G
8. 16. 10. 11. 27. 48. 33. 153.
16. 18.
6. 19. 26. 34. 32. 151.
16. 16. 12. 25. 17. 37. 26. 149.
16. 18. 22. 18. 28. 29. 43. 174.
20. 18. 19. 20. 22. 39. 33. 171.
19. 13. 18. 18. 22. 46. 36. 172.
14. 13.
3. 18. 24. 44. 34. 150.
23. 19.
4. 20. 34. 47. 35. 182.
13. 15.
7. 24. 23. 51. 32. 165.
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
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 2
-1839-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 4 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]
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 25644 25680 25675 25598 25667 25641 25662 25726 25596
G NG G G G G G G NG G
33. 9. 9. 11. 28. 38. 38. 166.
-3. -2. 11. 4. -3. 1. 5. 13.
13. 5. 12. 27. 21. 45. 39. 162.
6. 13. 17. 24. 17. 49. 31. 157.
8. 17. 15. 20. 18. 48. 35. 161.
11. 11. 20. 17. 16. 47. 30. 152.
18. 5. 7. 15. 27. 32. 31. 135.
15. 11.
5. 20. 20. 45. 43. 159.
7. -1. 4. 12. 3. 5. 6. 36.
19. 7. 12. 16. 15. 38. 30. 137.
MEAN S.D.
N
15. 8.4
8
10. 4.1
8
12. 5.1
8
19. 5.1
8
20. 4.9
8
43. 6.0
8
35. 4.9
8
154. 11.6
8
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 3
-1840-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 4 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL BODY WEIGHT CHANGES DURING GESTATION [G]
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 25608 25656 25688 25625 25699 25750 25734 25745 25693
G G G G G NG G G NG G
18. 14. 8. 9. 30. 43. 37. 159.
18. 16. -1. 13. 23. 38. 29. 136.
16. 12. 19. 22. 24. 45. 44. 182.
11. 10. 18. 17. 23. 50. 47. 176.
15. 19. 20. 20. 23. 53. 37. 187.
3. 11. 7. -1. 5. 3. 1. 29.
13. 6. 6. 21. 25. 36. 28. 135.
12. 11. -1. 24. 24. 35. 36. 141.
0. 10. -4. 15. -2. 15.
4. 38.
23. 11. 10. 17. 22. 30. 35. 148.
MEAN S.D.
N
16. 3.9
8
12. 4.0
8
10. 8.5
8
18. 5.0
8
24. 2.5
8
41. 7.9
8
37. 6.5
8
158. 21.2
8
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN
PAGE 4
PGBWv4.05 10/05/2006
-1841-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 5 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
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 25659 25634 25620 25706 25612 25629 25718 25760 25683
G G G G G G G G G G
19. NA 21. NA NA NA NA NA
17. 23. 25. 26. NA
32. 27. 25.
22. 25. 23. 26. 28. 30. NA
NA
19. 20. 22. 23. 24. 28. 27. 23.
19. 21. 22. 22. 23. 27. 24. 23.
19. 21. 22. NA
22. 25. 27. 22.
22. 24. NA
27. 25. 29. 28. 25.
21. 25. 25. 26. 26. NA NA NA
20. 23. 26. 25. 27. 28. 27. 25.
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
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 1
-1842-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 5 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
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 25669 25613 25607 25640 25711 25682 25651 25768 25643
G G G G G G G G G G
19. 22. 21. 24. 23. 26. 28. 23.
23. 26. 24. 25. 28. 29. 28. 26.
19. 26. 23. 27. 25. 29. NA
NA
18. 22. 24. 25. 29. 30. NA
NA
21. 24. 23. 27. 25. 32. 28. 25.
16. 19. 23. 24. 26. 29. 28. 23.
20. 22. 22. NA
26. 32. 32. 25.
22. 23. 25. 26. 27. 29. 29. 26.
21. 23. 24. 25. 26. 30. 29. 25.
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
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 2
-1843-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 5 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
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 25644 25680 25675 25598 25667 25641 25662 25726 25596
G NG G G G G G G NG G
23. 23. 21. 25. 24. 27. 30. 25. 15. 17. 19. 17. NA NA NA NA 20. 20. 23. 25. 27. 31. 29. 25. 18. 22. 22. 26. 23. 31. 28. 24. 20. 23. 23. 24. 24. 29. 29. 24. 20. 24. 24. 25. 25. 30. 29. 25. 20. 19. 20. 22. 25. 30. 27. 23. 20. 22. 22. 23. 26. 29. 31. 24. 19. 19. 21. 20. 20. 21. 22. 20. 21. 20. 23. 23. 23. 25. 27. 23.
MEAN S.D.
N
20. 1.4
8
22. 1.8
8
22. 1.3
8
24. 1.4
8
25. 1.4
8
29. 2.1
8
29. 1.4
8
24. 0.8
8
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 3
-1844-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 5 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/ANIMAL/DAY]
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 25608 25656 25688 25625 25699 25750 25734 25745 25693
G G G G G NG G G NG G
20. 20. 21. 22. 22. 28. NA
NA
22. 24. 20. 25. 24. 28. NA
NA
21. 23. 23. 25. 26. 33. 31. 26.
19. 23. 24. 26. 29. 33. 35. 26.
21. 24. 24. 24. 26. 31. 32. 26.
18. 20. 19. 18. 16. 17. NA
NA
18. 20. 20. 22. 26. 27. 27. 22.
18. 24. 20. NA
26. NA
28. 23.
20. 26. 22. NA
20. 23. 24. 23.
21. 22. 23. 22. 26. 27. 30. 24.
MEAN S.D.
N
20. 1.5
8
23. 1.7
8
22. 1.8
8
24. 1.7
7
26. 2.0
8
30. 2.7
7
31. 2.9
6
25. 1.8
6
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 4
PGFWv4.08 01/23/2007
-1845-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 6 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
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 25659 25634 25620 25706 25612 25629 25718 25760 25683
G G G G G G G G G G
76. NA 73. NA NA NA NA NA
60. 78. 79. 80. NA
82. 63. 73.
77. 83. 72. 78. 78. 78. NA
NA
70. 70. 74. 73. 71. 77. 68. 71.
72. 76. 76. 72. 72. 76. 61. 73.
72. 75. 76. NA
69. 73. 72. 70.
81. 82. NA
85. 74. 78. 68. 76.
75. 84. 80. 79. 74. NA NA NA
71. 77. 84. 78. 81. 80. 74. 77.
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
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 1
-1846-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 6 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
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 25669 25613 25607 25640 25711 25682 25651 25768 25643
G G G G G G G G G G
72. 80. 73. 80. 72. 73. 71. 73.
82. 87. 77. 77. 81. 77. 68. 77.
69. 89. 75. 83. 72. 78. NA
NA
66. 76. 78. 76. 82. 79. NA
NA
78. 84. 75. 83. 72. 85. 68. 75.
66. 74. 84. 82. 84. 84. 73. 76.
76. 79. 77. NA
82. 91. 82. 80.
77. 75. 79. 79. 76. 73. 66. 75.
74. 77. 77. 77. 74. 78. 68. 73.
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
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 2
-1847-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 6 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
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 25644 25680 25675 25598 25667 25641 25662 25726 25596
G NG G G G G G G NG G
88. 82. 72. 83. 75. 76. 77. 79. 57. 66. 72. 63. NA NA NA NA 71. 69. 77. 79. 79. 83. 70. 75. 68. 80. 76. 84. 69. 85. 69. 75. 76. 83. 79. 78. 73. 80. 72. 75. 78. 90. 85. 83. 79. 86. 75. 80. 72. 66. 68. 72. 76. 84. 70. 72. 72. 76. 74. 74. 79. 80. 76. 73. 66. 66. 72. 67. 65. 68. 70. 67. 77. 70. 78. 75. 71. 71. 70. 72.
MEAN S.D.
N
75. 6.2
8
77. 8.2
8
76. 5.1
8
79. 4.6
8
75. 3.9
8
81. 5.1
8
72. 3.2
8
75. 3.0
8
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 3
-1848-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 6 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL FOOD CONSUMPTION DURING GESTATION [G/KG/DAY]
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 25608 25656 25688 25625 25699 25750 25734 25745 25693
G G G G G NG G G NG G
77. 72. 73. 74. 70. 80. NA
NA
79. 81. 66. 81. 73. 78. NA
NA
76. 80. 75. 77. 75. 86. 73. 77.
70. 82. 81. 83. 87. 89. 84. 79.
78. 84. 78. 74. 75. 80. 74. 77.
71. 77. 71. 66. 59. 61. NA
NA
67. 72. 71. 74. 82. 77. 71. 71.
65. 83. 68. NA
79. NA
71. 71.
69. 88. 74. NA
65. 73. 74. 75.
76. 75. 76. 69. 77. 74. 76. 73.
MEAN S.D.
N
74. 5.4
8
79. 4.9
8
74. 5.0
8
76. 4.8
7
77. 5.4
8
81. 5.2
7
75. 4.9
6
75. 3.4
6
G = GRAVID NG = NONGRAVID - WEIGHT(S) NOT INCLUDED IN CALCULATION OF MEAN NA = NOT APPLICABLE
PAGE 4
PGFWv4.08 01/23/2007
-1849-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 7 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PREGNANCY STATUS
DAMS FROM GROUP 1: 0 MG/KG/DAY
MATERNAL GROSS OBSERVATION
25679 25659 25634 25620 25706 25612 25629 25718 25760 25683
GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID
PAGE 1
-1850-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 7 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PREGNANCY STATUS
DAMS FROM GROUP 2: 0.1 MG/KG/DAY
MATERNAL GROSS OBSERVATION
25627 25669 25613 25607 25640 25711 25682 25651 25768 25643
GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID
PAGE 2
-1851-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 7 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PREGNANCY STATUS
DAMS FROM GROUP 3: 0.3 MG/KG/DAY
MATERNAL GROSS OBSERVATION
25601 25644 25680 25675 25598 25667 25641 25662 25726 25596
GRAVID NONGRAVID GRAVID GRAVID GRAVID GRAVID GRAVID GRAVID NONGRAVID GRAVID
PAGE 3
-1852-
PROJECT NO.:WIL-180017T SPONSOR:3M CORPORATION SPONSOR NO.:06-128
TABLE 7 ORAL DEV. NEURO/THYROID FUNCTION STUDY OF MTDID 208 IN RATS
INDIVIDUAL PREGNANCY STATUS
DAMS FROM GROUP 4: 1.0 MG/KG/DAY
MATERNAL GROSS OBSERVATION
25649 25608 25656 25688 25625 25699 25750 25734 25745 25693
GRAVID GRAVID GRAVID GRAVID GRAVID NONGRAVID GRAVID GRAVID NONGRAVID GRAVID
PAGE 4
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
P Ra t h o l o g y e p o r t
Pathology Department WIL Research Laboratories, LLC
-1-
WIL-180017 3M Corporation
-1857-
MTDID 208 06-128
Ta b l e Of Co n t e n t s
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 P h ase).............................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 D elivered......................................................................................7 3.1.4.2. Females That Failed To D eliv er....................................................................... 7 3.1.5. Terminal Procedures For Offspring Not Scheduled For Behavioral
Evaluations Or Brain W eight Determinations................................................ 8 3.1.5.1. F 1D eaths..............................................................................................................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 W eight M easurements................................. 9 3.1.7.1. Offspring Euthanized On PND 2 1 .................................................................... 9 3.1.7.1.1. Macroscopic Exam ination................................................................................ 9 3.1.7.1.2. Microscopic Exam ination................................................................................. 9 3.1.7.2. Animals Euthanized At Study Termination (PND 7 2 )................................ 10 3.1.7.2.1. Macroscopic Exam ination.............................................................................. 10 3.1.7.2.2. Microscopic Exam ination............................................................................... 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 M easurem ents........................... 15 4.4. Thyroid Histopathology And M orphometry..................................................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. In t r o d u c t i o n
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. S Dt u d y e s ig n
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 2 MTDID 208 3 MTDID 208 4 MTDID 208
a = The vehicle control was 0.5% Tween 20. b = Toxicokinetic/thyroid function satellite phase.
0 0.1 0.3 1.0
Number of Females
Main
TK b
25 10 25 10 25 10 25 10
F 1generation animals were potentially exposed to the test article in utero and via the milk during the lactation period. No direct administration to the F 1 animals occurred.
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3. Me t h o d s 3.1. T A , N A Po x i c o k i n e t i c n a l y s i s e c r o p s y n d a t h o l o g y 3.1.1. GD 20 (To x i c o k i n e t i c /Th y r o i d Fu n c t i o n Sa t e l l i t e Ph a s e )
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/Po s t n a t a l Da y (PND 4) (Ma i n St u d y )
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
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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(Ma in St u d y )
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.
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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.
T P F M F (D )e r m i n a l r o c e d u r e s o r a t e r n a l e m a l e s
ams
3.1.4.1. F T De m a l e s h a t e l i v e r e d
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. F T Fe m a l e s h a t a i l e d To De l i v e r
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.
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3.1.5. T P F O N S Fe r m i n a l r o c e d u r e s o r f f s p r in g o t c h e d u l e d o r
B E O B We h a v i o r a l v a l u a t i o n s r r a i n
e ig h t
De t e r m in a t io n s
3.1.5.1. Fi De a t h s
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. O S F Cf f s p r in g e l e c t e d o r u l l i n g 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. E O O N S F Bu t h a n a s i a f f f s p r in g o t e l e c t e d o r e h a v i o r a l O T F Er h y r o i d u n c t i o n v a l u a t i o n
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. O S F E A S Tf f s p r i n g c h e d u l e d o r u t h a n a s i a t t u d y e r m i n a t i o n
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.
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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.
O S F B W Mf f s p r i n g c h e d u l e d o r r a i n
e ig h t
ea surem ents
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. O Ef f s p r in g u t h a n i z e d On PND 21 3.1.7.1.1. M Ea c r o s c o p ic x a m i n a t i o n
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. M Eic r o s c o p ic x a m i n a t i o n
The brains from pups selected for macroscopic evaluation on PND 21 were prepared for possible future microscopic neuropathologic examination.
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3.1.7.2. An i m a l s E A Su t h a n i z e d t t u d y Te r m i n a t i o n (PND 72) 3.1.7.2.1. M Ea c r o s c o p ic x a m i n a t i o n
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. M Eic r o s c o p ic x a m i n a t i o n
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. T H , C P A Ah y r o i d i s t o p a t h o l o g y e l l r o l i f e r a t i o n s s a y n d Mo r p h o m e t r y
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
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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
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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 I.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)
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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.
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3.2. A A Db b r e v i a t i o n s n d e f i n i t i o n s
The following abbreviations and definitions may apply to this report:
Interval FD EE GD
PND LD SN
Significant
point in the study at which an animal died or was euthanized found dead euthanized in extremis gestation day postnatal day lactation day scheduled necropsy (end of dosing) As used in this study refers to statistical significance
3.3. D Ia t a n t e r p r e t a t i o n
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.
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4. Re s u l t s 4.1. T F Ah y r o i d u n c t i o n s s e s s m e n t
GD 20: TSH values of F0dams and Fi 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 F 1pups (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 F 1male 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 F 1female 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 F0dams or F 1pups on LD/PND 21.
4.2. G Or o s s b s e r v a t i o n s
Review of the gross necropsy observations revealed no test article-related alterations.
4.3. O W , B W B Mr g a n e i g h t s o d y e i g h t s a n d r a i n e a s u r e m e n t s
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. T H A Mh y r o i d i s t o p a t h o l o g y n d o r p h o m e t r y
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
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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
Females
Dosage (mg/kg/day)
0 0.1 0.3 1.0 0 0.1 0.3
Thyroid a
10 0 0 10 10 0 0
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
1.0 8 5.84 0.304
Text Table 1b
Thyroid Follicular Epithelial Cell Height, PND 21
Males
Females
Dosage (mg/kg/day)
0 0.1 0.3 1.0 0 0.1 0.3
Thyroid a
10 0 0
10 10 0 0
Mean epithelial cell height b 5.68 -
- 6.29** 6.28 -
-
Standard deviation
0.536 -
- 0.324 0.450 -
-
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
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Dosage (mg/kg/day) Thyroid a
Mean follicle area b Standard deviation
Text Table 2a
Thyroid Follicular Colloid Area , PND 4
Ma es
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 00 ---
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 00 --
--
1.0 10 7677 1857.8
Text Table 3
Ki-67-Positive Fo licular Epithelial Cells in Thyroid Gland, GD20
Males
Females
Dosage (mg/kg/day)
0 0.1 0.3 1.0 0 0.1 0.3
Thyroid a
6 0 0 6 70 0
Ki-67-positive cells b
40 -
- 32 42 -
-
Standard deviation
23.9 -
- 25.3 35.5 -
-
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)
1.0 5 88* 18.6
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5. Dis c u s s io n
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.
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6. Co n c l u s io n s
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 F 1fetuses/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.
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7. Report S ubmission
Report Submitted By:
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_.__H ' _t is
____________________
George A. Parker, DVM, PhD, DACVP, DABT
Study Pathologist
Report Reviewed Bv:
u
Catneri ne A. Picut, VMD, DACVP, DABT Reviewing Pathologist
Date
l-5 - g
Date
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8. Re f e r e n c e
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]. N au n yn - S c h m ie d e b e rg s A r c h iv f r E x p e rim e n te lle P a th o lo g ie u n d P h a r m a k o lo g ie 1964, 2 4 7 , 367.
Stuckhardt, J.L.; Poppe, S.M. Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. T era to g en esis, C a r c in o g e n e sis a n d M u ta g e n e s is 1984, 4, 181-188.
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APPENDIX 58
rtPCR Results
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U n iv e r s it y of M in n e so t a
Duluth Campus
Department o f Biochemistry and Molecular Biology
Medical School
December 14, 2007
John L. Butenhoff, Ph.D. Medical Department 3M Center Building 220 6W 08 St. Paul, MN 55144
252 Medical School 1035 University Drive Duluth, M N 55812-3031
Office: 218-726-7922 Fax: 218-726-8014 www. d.umn. edu/medweb/biochem/ Email: mdbc@d.umn.edu
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 house keeping 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 600^L 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). p Cr 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.
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The analyses employed the following primer sequences:
Gene 18s rR N A ACoA
PCNA M a lic Enzym e
Dio1
Por
ApoA1
Cyp1a1
Cyp3a1
Cyp4a1
Cyp7a1
Cyp2b2 U g t1 A commo n
Ugt1a1
U g t1 a 6
U g t2 b
U pper Prim er 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
Low er Prim er 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) R eferen ce
149 M 11188 338 NM 017340
198 NM 022381
140 A H 002199
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
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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 (V 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
-- --
-- --
-- --- --- --- --- --- --- --- -V --
-- --- --- --
PND 21 Dam NA NA
Male pup
V --
NA -NA -NA -NA -NA -NA -NA V NA V NA V
NA NA -NA -NA --
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
Male pup
NA 9.73E-05
NA 5.50E-05
NA 5.71E-05
NA 7.53E-05
NA 5.60E-05
NA 6.81E-05
NA 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
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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
Male pup
NA 8.09E-06
NA 5.74E-06
NA 9.23E-06
NA 8.43E-06
NA 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
Fetus 7.77E-07 4.80E-07 6.03E-07 7.58E-07 7.24E-07 6.68E-07 5.59E-08
4.46E-06 4.27E-06
4.23E-06 7.92E-06 5.22E-06 9.02E-07
0.303
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
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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
Male pup
NA 1.08E-05
NA 6.94E-06
NA 9.08E-06
NA 8.90E-06
NA 6.92E-06
NA 8.52E-06
NA 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
Male pup
NA 1.18E-05
NA 6.40E-06
NA 1.01E-05
NA 1.22E-05
NA 1.39E-05
NA 1.09E-05
NA 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
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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
Male pup
NA 5.51E-04
NA 2.58E-04
NA 6.47E-04
NA 5.38E-04
NA 5.83E-04
NA 5.15E-04
NA 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: Cyp1 a1, 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
Male pup
NA 7.10E-05
NA 3.66E-05
NA 5.49E-05
NA 5.01E-05
NA 4.36E-05
NA 5.12E-05
NA 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
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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
Male pup
NA 1.76E-04
NA 1.14E-04
NA 1.50E-04
NA 1.07E-04
NA 1.10E-04
NA 1.31E-04
NA 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
Male pup
NA 4.29E-06
NA 3.32E-06
NA 2.92E-06
NA 4.06E-06
NA 3.98E-06
NA 3.71E-06
NA 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
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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
Male pup
NA 2.48E-05
NA 2.18E-05
NA 3.99E-05
NA 3.54E-05
NA 1.76E-05
NA 2.79E-05
NA 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
Male pup
NA 3.54E-05
NA 2.18E-05
NA 2.36E-05
NA 1.70E-05
NA 1.33E-05
NA 2.22E-05
NA 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
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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
Male pup
NA 4.31E-06
NA 5.12E-06
NA 4.83E-06
NA 4.39E-06
NA 3.21E-06
NA 4.37E-06
NA 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
Male pup
NA 5.24E-01
NA 5.06E-01
NA 5.71E-01
NA 5.95E-01
NA 5.94E-01
NA 5.58E-01
NA 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
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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
Male pup
NA 1.05E-05
NA 1.20E-05
NA 1.10E-05
NA 2.13E-05
NA 1.73E-05
NA 1.44E-05
NA 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
Male pup
NA 7.28E-05
NA 3.19E-05
NA 5.24E-05
NA 3.73E-05
NA 3.88E-05
NA 4.67E-05
NA 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
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I hope you find these data useful. Sincerely,
Kendall B. Wallace, Ph.D. Professor
WIL-180017 3M Corporation
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MTDID 208 06-128
APPENDIX 59
Clinical Pathology Methods, Procedures And References
WIL 180017 3M Corporation
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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
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MTDID 208 06-128
APPENDIX 60
Statistical Analysis Report (BioSTAT Consultants, Inc.)
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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 Biel Maze Analysis Methodology 2 Results Table 2.1: Summary of Statistically Significant Dose Group Findings 3 Statistical Analysis Summaries Table 3.1: Analysis Summary Table for Motor Activity Table 3.2: Analysis Summary Table for Startle Response Table 3.3: Analysis Summary Table for Biel Maze
Report Approval:
3261 Lost Pine Way Portage, MI 49024 (269) 329-7976
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BioSTAT Consultants, Inc. Statement of Quality Control
2
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.
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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
3
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.
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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., 1999 2001) 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
TT T T TT
F Total
PND021 M Total F Total
T
PND061 M Total
F Total
T ( i ) D ose-related increase (decrease) through 1.0 m g/kg/day TT ( i i ) D ose-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.
3 Statistical Analysis Summaries Table 3.1: Analysis Summary Table for Motor Activity
Period PND013
Sex Variable M TOTAL
Minutes 0-15
16-30
31-45 46-60 Overall Cumulative
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference Control S.D. N
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
110 NA
60.6
67 NA 75.0
89 160.0
67 107.9
83 NA
333 NA
336.3 20
170 54.5 172.2
NT
139 107.5 117.8
NT
60 90.3
NT
124 213.7
NT
123 NA NT
493 48.0 351.8
20
128 16.4 190.0
NT
111 65.7 250.6
NT
62 103.8
NT
97 192.7
NT
99 NA NT
398 19.5 522.2
20
Statistical 1.0 Model
130 18.2 155.8
NT
95 41.8 113.1
NT
39 58.4
NT
89 153.5
NT
88 NA 0. 938
353 6.0 377.0 20
0.663 0.571 0.420
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
7
-1898-
Table 3.1: Analysis Summary Table for Motor Activity
Period PND013
Sex Variable F TOTAL
Minutes 0-15
16-30
31-45 46-60 Overall Cumulative
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference Control S.D. N
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
115 NA
107.9
92 NA 94.3
59 100.6
78 140.3
86 NA
343 NA
263.0 20
225 95.7 244.9
NT
206 123.9 284.3
NT
190 258.1
NT
174 271.4
NT
199 NA NT
795 131.8 904.3
20
129 12.2 180.2
NT
108 17.4 139.1
NT
126 145.7
NT
74 98.5
NT
109 NA NT
437 27.4 430.9
20
Statistical 1.0 Model
102 -11.3
73.1 NT
81 -12.0 129.7
NT
96 168.2
NT
113 216.4
NT
98 NA 0.702
392 14.3 391.7
20
0.047 0.913 0.730
ARI
-1899-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.1: Analysis Summary Table for Motor Activity
Period PND017
Sex Variable M TOTAL
Minutes 0-15
16-30
31-45 46-60 Overall Cumulative
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference Control S.D. N
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
471 NA
317.8
208 NA
199.2
184 208.8
108 203.9
243 NA
971 NA
772.8 20
605 28.5 326.4
NT
225 8.2 215.3 0.858
222 256.4
NT
240 251.1
NT
323 NA
0.299
1293 33.2 832.6
20
732 55.4 387.9
NT
410 97.1 2 62.2 0.031*
352 2 65.9 0.071
273 246.4 0.076
442 NA
0.012*
1766 81.9 932.3
20
Statistical 1.0 Model
383 -18.7 315.0 0. 643
370 77.9 333.9 0.023*
427 393.8 0.004*
354 326.4 0.009*
383 NA
0.030*
1534 58.0 1200.5
20
0.071 < 0 .001*
0 .0 0 2 *
AR1
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
9
-1900-
Table 3.1: Analysis Summary Table for Motor Activity
Period PND017
Sex Variable F TOTAL
Minutes 0-15
16-30
31-45 46-60 Overall Cumulative
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference Control S.D. N
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
544 NA
351.6
271 NA
224.2
147 183.4
124 185.2
271 NA
1085 NA
668.1 20
607 11. 6 208.9
NT
247 -8 .9 241.7
NT
254 312.4
NT
236 304.9
NT
336 NA NT
1344 23.9 914.4
20
580 6.6 306.9
NT
345 27.3 273.4
NT
316 248.5
NT
291 248.7
NT
383 NA NT
1532 41.2 924.5
20
Statistical 1.0 Model
559 2.8 376.0
NT
371 36. 9 271.8
NT
353 273.2
NT
303 330.2
NT
397 NA
0.074
1587 46.3 1109.6
20
0.324 0.295 0.147
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
10
-1901-
Table 3.1: Analysis Summary Table for Motor Activity
Period PND021
Sex Variable M TOTAL
Minutes 0-15
16-30
31-45 46-60 Overall Cumulative
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference Control S.D. N
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
455 NA
144.9
93 NA 115.3
63 63.0
35 74.1
162 NA
646 NA
263.0 20
547 20.2 158.2
NT
157 68.8 181.0
NT
106 154.0
NT
72 108.1
NT
221 NA NT
882 3 6.5 483.6
20
513 12.7 136.5
NT
129 38.7 126.6
NT
49 86.4
NT
58 109.1
NT
187 NA NT
748 15.8 328.7
20
Statistical 1.0 Model
574 26.2 195.1
NT
128 37.6 207.5
NT
100 192.6
NT
122 239.7
NT
231 NA
0.162
924 43.0 763.6
20
0.275 0.365 0.112
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
11
-1902-
Table 3.1: Analysis Summary Table for Motor Activity
Period PND021
Sex Variable F TOTAL
Minutes 0-15
16-30
31-45 46-60 Overall Cumulative
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference Control S.D. N
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
505 NA
128.5
136 NA
184.1
29 49.7
71 1 1 1 .9
185 NA
740 NA
367.2 20
479 -5.1 119.5
NT
143 5.1 128.3
NT
63 76.7
NT
35 69.2
NT
180 NA NT
720 -2.7 250.9
20
5 63 11.5 169.5
NT
104 -23.5 1 1 1 .1
NT
105 130.3
NT
64 106.0
NT
209 NA
0.413
836 13.0 345.2
20
Statistical 1.0 Model
566 12.1 170.8
NT
228 67 .6 164.7
NT
91 154.0
NT
93 163.3
NT
245 NA
0.027*
979 32.3 512.3
20
0.114 0.020 0.735
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
12
-1903-
Table 3.1: Analysis Summary Table for Motor Activity
Period PND061
Sex Variable M TOTAL
Minutes 0-15
16-30
31-45 46-60 Overall Cumulative
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference Control S.D. N
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
CO
o
co
CO
Dose Group (mg/kg/day) 0 0.1 0.3
1296 NA
243.7
626 NA
261.6
325 248.5
235 278.3
621 NA
2483 NA
818.4 20
CO CO
1375 6.1
217.9 NT
572
172.4 NT
402 220.9
NT
303 208.0
NT
663 NA NT
2652
624.4 20
1397 7 .8
2 95.7 NT
582 -7.0 277.8
NT
373 249.8
NT
276 250.7
NT
657 NA NT
2628 5.8
884.5 20
Statistical 1.0 Model
1306
186.8 NT
591 -5 .6 291.0
NT
349 253.4
NT
284 175.0
NT
632 NA
0.872
2529 1. 9
567.1 20
0.856 0.555 0.857
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
13
-1904-
Table 3.1: Analysis Summary Table for Motor Activity
Period PND061
Sex Variable F TOTAL
Minutes 0-15
16-30
31-45 46-60 Overall Cumulative
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean S.D. Linear Trend p-value#
Mean % Difference Control S.D. N
Trt F-test p-value++ Trt*Time p-value++ LinTrt*Time p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
1198 NA
211.4
535 NA
198.9
329 209.9
255 230.8
579 NA
2316 NA
612.5 20
1161 -3.1 211.0
NT
533 -0.4 197.4
NT
407 223.1
NT
262 186.3
NT
591 NA NT
2364 2.1
587 .9 20
1163 -2.9 246.4
NT
458 -14.4 199.0
NT
318 246.7
NT
186 169.5
NT
531 NA NT
2124 -8.3 653.7
20
Statistical 1.0 Model
1217 1. 6
198.3 NT
585 9.3 156.0
NT
361 207.6
NT
248 183.3
NT
603 NA
0. 937
2412 4.1
592.1 20
0.472 0.777 0.869
CS
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
14
-1905-
Table 3.2: Analysis Summary Table for Startle Response
Period PND020
Variable VMAX
Sex Blocks M 1-10
11-20
21-30
31-40
41-50
Overall
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
188.3 NA
69.33
164.0 NA
71.58
148.4 NA
55 .98
123.1 NA
49.89
133.3 NA
61.01
151.4 NA 20
165.5 -12.1 59.04
NT
141.3 -13.8 48.86
NT
130.2 -12.3 5 6.55
NT
139. 6 13.4
47.81 NT
129.5 -2.9
49.37 NT
141.2 NA 20 NT
161.3 -14.3 55.70
NT
142.8 -12.9 55.56
NT
140.6 -5.3
63.72 NT
143.1 16.2
59.29 NT
137.4 3.1
47.86 NT
145.0 NA 20 NT
Statistical 1.0 Model
162.7 -13.6 68.57
NT
134.2 -18.2 70.14
NT
116.8 -21.3 68.73
NT
115 .6 -6.1
62.87 NT
121.0 -9.2
63.22 NT
130.1 NA 20
0.226
0.578 0.374 0.627
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
15
-1906-
Table 3.2: Analysis Summary Table for Startle Response
Period PND020
Variable VMAX
Sex Blocks F 1-10
11-20
21-30
31-40
41-50
Overall
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
200.8 NA
77.89
178.3 NA
72.32
163.3 NA
74.00
168.5 NA
68.86
147.4 NA
52.11
171.7 NA 20
185.8 -7.5
58.51 NT
163.1 -8.5
67.72 NT
145.2 -11.1 70.10
NT
142.7 -15.3 59.87
NT
140.4 -4 .7
70.27 NT
155.4 NA 20 NT
169.5 -15.6 75.43
NT
159.8 -10.4 66. 95
NT
163.3 0.0
71. 98 NT
152.5 -9.5
73.89 NT
126.8 -14.0 67.83
NT
154.4 NA 20 NT
Statistical 1.0 Model
173.6 -13.5 72.22
NT
140.8 -21.0 67.49
NT
128.0 -21.6 62.63
NT
120.6 -28.4 63.85
NT
134.1 -9.0
67.19 NT
139.4 NA 20
0.073
0.314 0.511 0.530
AR1
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.2: Analysis Summary Table for Startle Response
Period PND020
Variable TMAX
Sex Blocks M 1-10
11-20
21-30
31-40
41-50
Overall
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
26.3 NA
3.77
24.3 NA
4.01
24.5 NA
4.06
24.3 NA
3.64
25.5 NA
5.82
25.0 NA 20
27.7 5.3
4.96 NT
23.9 -1. 6 4.13
NT
25.1 2.4
5.68 NT
24.0 -1.2 4.04
NT
24.0 -5 .9 3.96
NT
24.9 NA 20 NT
26.2 -0.4 3.90
NT
23.7 -2.5 3.84
NT
23.7 -3.3 4.29
NT
23.0 -5.3 2.86
NT
25.0 -2.0 4 .93
NT
24.3 NA 20 NT
Statistical 1.0 Model
26.5 0.8
5.21 NT
25.1 3.3
4.24 NT
26.4 7 .8
5.03 NT
22.9 -5.8 3.18
NT
24.2 -5.1 4.24
NT
25.0 NA 20
0.856
0.852 0.430 0.299
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
17
-1908-
Table 3.2: Analysis Summary Table for Startle Response
Period PND020
Variable TMAX
Sex Blocks F 1-10
11-20
21-30
31-40
41-50
Overall
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
26.5 NA
6. 62
22.7 NA
2.61
22.6 NA
2.69
22.0 NA
2.00
23.7 NA
5.11
23.5 NA 20
26.1 -1.5 3.95
NT
23.8 4 .8
2.87 NT
23.6 4 .4
3.99 NT
24.2 10.0 3.71
NT
23.7 0.0
3.45 NT
24.3 NA 20 NT
24.9 -6.0 4 .78
NT
22.3 -1.8 2.65
NT
22.8 0.9
5.00 NT
22.3 1.4
2.83 NT
24.4 3.0
4 .67 NT
23.3 NA 20 NT
Statistical 1.0 Model
26.5 0.0
4.71 NT
24.5 7 .9
4.96 NT
23.6 4 .4
5.02 NT
24.3 10.5 4.85
NT
24.1 1.7
4.53 NT
24.6 NA 20
0.391
0.392 0.741 0.776
AR1
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
18
-1909-
Table 3.2: Analysis Summary Table for Startle Response
Period PND060
Variable VMAX
Sex Blocks M 1-10
11-20
21-30
31-40
41-50
Overall
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
246.3 NA
294.08
194.7 NA
215.91
177.5 NA
236.83
142.7 NA
157.72
108.2 NA
112.74
173.9 NA 20
136. 9 -44 .4 129.08
NT
112.3 -42.3 91.82
NT
97 .6 -45.0 80.75
NT
96.0 -32.7 92.18
NT
101.1 -6.6
110.10 NT
108.8 NA 20 NT
162.6 -34.0 113.35
NT
151.7 -22.1 117.82
NT
123.2 -30.6 90.15
NT
95.4 -33.1 67.05
NT
113.1 4.5
90. 60 NT
129.2 NA 20 NT
Statistical 1.0 Model
149. 6 -39.3 93.03
NT
108.5 -44.3 95.35
NT
79.7 -55.1 66.70
NT
86.0 -39.7 82.05
NT
70.8 -34.6 69.90
NT
98 .9 NA 20
0.096
0.221 0.349 0.528
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
19
-1910-
Table 3.2: Analysis Summary Table for Startle Response
Period PND060
Variable VMAX
Sex Blocks F 1-10
11-20
21-30
31-40
41-50
Overall
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
Dose
117.0 NA
62.93
73.1 NA
54.88
59.5 NA
30.86
51.2 NA
28.27
52.5 NA
28.25
70.6 NA 20
# : Level of Significance tested = .05. * : Statistically Significant.
Group (mg/kg/day) 0.1 0.3
83.7 -28.5 29.45
NT
60. 6 -17.1 28.02
NT
56.3 -5.4 41.41
NT
46.9 -8 .4 33.49
NT
54.0 2.9
35.21 NT
60.3 NA 20 NT
92.9 -20.6 52.65
NT
69.7 -4 .7 36.89
NT
56.1 -5.7 32.53
NT
58.1 13.5 33.32
NT
65.0 23.8 49.19
NT
68.4 NA 20 NT
Statistical 1.0 Model
75.5 -35.5 61.68
NT
53.1 -27.4 52.79
NT
46.7 -21.5 33.15
NT
52.2 2.0
43.54 NT
56.2 7.0
56.70 NT
56.8 NA 20
0.323
0.524 0.509 0.116
AR1
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
20
Table 3.2: Analysis Summary Table for Startle Response
Period PND060
Variable TMAX
Sex Blocks M 1-10
11-20
21-30
31-40
41-50
Overall
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
32.0 NA
6.30
32.7 NA
9.10
31.5 NA
6.08
33.9 NA
7 .68
35.9 NA
10.06
33.2 NA 20
34.2 6. 9
8.36 NT
35.4 8.3
8.68 NT
35.3 12.1 8.58
NT
36. 6 8.0
9.41 NT
35.4 -1.4 7 .88
NT
35.4 NA 20 NT
32.9 2.8
7 .78 NT
33.1 1.2
7 .70 NT
32.6 3.5
8.15 NT
31.1 -8.3 8.04
NT
35.4 -1.4 9.12
NT
33.0 NA 20 NT
Statistical 1.0 Model
32.0 0.0
6.22 NT
34.0 4.0
10.57 NT
36. 9 17.1 9.84
NT
36.4 7 .4
9.54 NT
34.2 -4 .7 9.37
NT
34.7 NA 20
0.743
0.566 0.364 0.318
CS
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
21
-1912-
Table 3.2: Analysis Summary Table for Startle Response
Period PND060
Variable TMAX
Sex Blocks F 1-10
11-20
21-30
31-40
41-50
Overall
Statistic
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean % Difference Control S.D. Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
Dose Group (mg/kg/day) 0 0.1 0.3
31.6 NA
5.06
34.8 NA
6.70
37.1 NA
5.04
35.6 NA
7.86
36.0 NA
6.27
35.0 NA 20
34.2 8.2
7.60 NT
35.8 2.9
5.83 NT
33.2 -10.5
6.54 NT
37.3 4 .8
7.62 NT
36. 9 2.5
7.52 NT
35.5 NA 20 NT
34.9 10.4 7 .72
NT
36.3 4.3
7.28 NT
34.5 -7.0 6.82
NT
36.1 1.4
8 .41 NT
37.4 3.9
10.22 NT
35.8 NA 20 NT
Statistical 1.0 Model
36.1 14.2 6.67
NT
34.4 -1.1 8 .47
NT
35.8 -3.5 8.21
NT
35.7 0.3
10.35 NT
35.9 -0.3 9.60
NT
35.6 NA 20
0.702
0.968 0.460 0.314
CS
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
22
-1913-
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 M A LEARNING ESCTIME 1
2
3
4
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
23
-1914-
Dose Group (mg/kg/day) 0 0.1 0.3
78 .73 NA
56.080 20
58.52 NA
40.115 20
54.05 NA
48.823 20
52.80 NA
45.443 20
61.03 NA 20
79.27 0.7
58.459 20 NT
66.73 14.0
44.377 20 NT
54.33 0.5
47.220 20 NT
38.34 -27.4 38.436
20 NT
59.67 NA 20 NT
71.50 -9.2
53.639 20 NT
66.14 13.0
41.239 20 NT
34.71 -35.8 21.907
20 NT
37.71 -28.6 28.372
20 NT
52.51 NA 20 NT
Statistical 1.0 Model
79.80 1.4
61.173 20 NT
69.35 18.5
49.673 20 NT
43.96 -18.7 43.665
20 NT
40.11 -24.0 42.615
19 NT
58.23 NA 20
0.556
0.748 0.924 0.557
ARI
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 M A LEARNING ERRORS 1
2
3
4
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
24
Dose Group (mg/kg/day) 0 0.1 0.3
15 NA 10.8 20
13 NA 10.5 20
14 NA 15.1 20
12 NA 11.6 20
13 NA 20
14 -6.7 10.2
20 NT
15 15.4 11.7
20 NT
12 -14.3
12.2 20 NT
7 -41.7
9.5 20 NT
12 NA 20 NT
13 -13.3
11.2 20 NT
14 7 .7 10.5
20 NT
8 -42.9
6.9 20 NT
9 -25.0
8 .7 20 NT
11 NA 20 NT
Statistical 1.0 Model
16 6.7 13.2
20 NT
15 15.4 13.4
20 NT
10 -28.6
12.7 20 NT
8 -33.3
10.1 20 NT
12 NA 20 0.513
0.740 0.829 0.513
ARI
-1915-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 M B LEARNING ESCTIME 5
6
7
8
9
10
# : Level of Significance tested = .05. * : Statistically Significant.
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
25
-1916-
Dose Group (mg/kg/day) 0 0.1 0.3
137.70 NA
52.358 20
136.05 NA
58.799 20
144.25 NA
51.920 20
108.69 NA
67.266 20
83.67 NA
60.977 20
63.49 NA
58.001 20
148.40 7 .8
45.579 20 NT
140.71 3.4
53.137 20 NT
129.48 - 10.2
57.075 20 NT
109.13 0.4
67.274 20 NT
102.52 22.5
68.748 20 NT
70.42 10. 9
56.758 20 NT
145.03 5.3
53.498 20 NT
120.70 -11.3
66.215 20 NT
132.08 -8 .4
56.344 20 NT
71.50 -34.2 55.902
20 NT
66.82 -20.1 61.737
20 NT
72.30 13.9
67.910 20 NT
Statistical 1.0 Model
153.62 11. 6
55.325 20 NT
114.06 -16.2
57.104 20 NT
125.58 -12.9
61.184 20 NT
83.68 -23.0 60.728
20 NT
87.01 4.0
67.916 20 NT
63.87
0. 6
51.948 20 NT
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 M B LEARNING ESCTIME Overall
Statistic
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ TrtbTrial p-value++ LinTrtbTrial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
26
Dose Group (mg/kg/day)
0 Tl 0T3
31 116.77 101.40 NA NA NA 20 20 20
NT NT
Statistical 1MD Model
104.64 NA 20
0.299
0.535 0.610 0.267
CS
- I6 I-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 M B LEARNING ERRORS 5
6
7
8
9
10
# : Level of Significance tested = .05. * : Statistically Significant.
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
27
-1918-
oo oo
o o
Dose Group (mg/kg/day) 0 0.1 0.3
31 NA 12.6 20
29 NA 13.9 20
32 NA 12.1 20
23 NA 13.6 20
19 NA 15.7 20
14 NA 13.0 20
oo oo
31
9.2 20 NT
29
13.0 20 NT
28 -12.5
13.8 20 NT
23
14.0 20 NT
23 21.1 17.4
20 NT
15 7.1 14.7
20 NT
32 3.2 12.6
20 NT
25 -13.8
14.7 20 NT
31 -3.1 13.8
20 NT
17 -26.1
14.7 20 NT
15 -21.1
16.3 20 NT
17 21.4 18.5
20 NT
Statistical 1.0 Model
34 9.7 14 .9
20 NT
25 -13.8
13.7 20 NT
28 -12.5
14.0 20 NT
19 -17.4
15.1 20 NT
19
16.1 20 NT
14
14 .6 20 NT
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 M B LEARNING ERRORS Overall
Statistic
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ TrtbTrial p-value++ LinTrtbTrial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
28
Dose Group (mg/kg/day)
0 0.1 0.3
25 25 23 NA NA NA 20 20 20
NT NT
Statistical 1.0 Model
23 NA 20 0.384
0.802 0.868 0.641
CS
-1919-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type PND22 M A MEMORY
Variable Trial ESCTIME 11
12
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
29
Dose Group (mg/kg/day) 0 0.1 0.3
74 .70 NA
48.210 20
44.38 NA
43.708 20
59.54 NA 20
74.98 0.4
49.299 20 NT
69.61 56.8
51.904 20 NT
72.29 NA 20 NT
83.29 11.5
44.296 20 NT
51.43 15.9
34.062 20 NT
67.36 NA 20 NT
Statistical 1.0 Model
85.93 15.0
52.157 20 NT
63.17 42.3
50.376 20 NT
74.55 NA 20
0.307
0.629 0.372 0.943
CS
-1920-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type PND22 M A MEMORY
Variable Trial ERRORS 11
12
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
-1921-
o o
30
Dose Group (mg/kg/day) 0 0.1 0.3
21 NA 16.9 20
11 NA 14.4 20
16 NA 20
21
15 .9 20 NT
17 54.5 13.5
20 NT
19 NA 20 NT
24 14.3 13.1
20 NT
14 27.3 13.3
20 NT
19 NA 20 NT
Statistical 1.0 Model
25 19.0 16.7
20 NT
16 45.5 16.2
20 NT
21 NA 20 0.231
0.650 0.684 0.962
CS
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 F A LEARNING ESCTIME 1
2
3
4
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
31
Dose Group (mg/kg/day) 0 0.1 0.3
63.95 NA
45.821 20
71.55 NA
55.083 20
61.46 NA
42.016 20
39.80 NA
39.740 20
59.19 NA 20
81.98 28.2
65.243 20 NT
86.16 20.4
57.290 20 NT
56.72 -7 .7
42.Ill 20 NT
43.15 8 .4
41.878 20 NT
67.00 NA 20 NT
50.31 -21.3 31.568
20 NT
56.21 -21.4 42.679
20 NT
41.02 -33.3 31.033
20 NT
31.69 -20.4 22.442
20 NT
44 .81 NA 20 NT
Statistical 1.0 Model
74.55 16. 6
56.967 20 NT
80.65 12.7
46.187 20 NT
67.92 10.5
59.104 20 NT
47.24 18.7
45.762 20 NT
67.59 NA 20
0. 912
0.033 0.983 0.997
ARI
-1922-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 F A LEARNING ERRORS 1
2
3
4
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
32
Dose Group (mg/kg/day) 0 0.1 0.3
13 NA 10.7 20
16 NA 14.2 20
14 NA 11.7 20
8 NA 12.7 20
13 NA 20
14 7 .7 12.9
20 NT
18 12.5 12.3
20 NT
12 -14.3
10.0 20 NT
9 12.5 11.2
20 NT
13 NA 20 NT
10 -23.1
7 .7 20 NT
12 -25.0
9.8 20 NT
9 -35.7
8.5 20 NT
6 -25.0
7.0 20 NT
9 NA 20 NT
Statistical 1.0 Model
15 15.4 11.5
20 NT
17 6.3 11.4
20 NT
16 14.3 16.0
20 NT
10 25.0
9. 6 20 NT
14 NA 20 0. 967
0.065 0.990 0.992
ARI
-1923-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 F B LEARNING ESCTIME 5
6
7
8
9
10
# : Level of Significance tested = .05. * : Statistically Significant.
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
33
-1924-
Dose Group (mg/kg/day) 0 0.1 0.3
154.84 NA
47.173 20
150.22 NA
41.379 20
134.72 NA
57.907 20
114.50 NA
62.597 20
113.10 NA
67.774 20
91.00 NA
65.705 20
156.05 0.8
43.725 20 NT
123.50 -17.8
65.560 20 NT
119.20 -11.5
68.931 20 NT
97.79 -14 .6 64 .979
20 NT
80.64 -28.7 62.479
20 NT
72.21 -20 .6 61.696
20 NT
157.72 1.9
46.628 20 NT
139.91 -6.9
61.655 20 NT
117.25 -13.0
67.598 20 NT
97.85 -14.5 71.613
20 NT
75.29 -33.4 64.213
20 NT
64.07 -29.6 52.824
20 NT
Statistical 1.0 Model
145.74 -5 .9
51.625 20 NT
149.06 - 0.8
56.800 20 NT
116.94 -13.2
67.633 20 NT
95.40 -16.7 64.422
20 NT
90.47 - 20.0 65.982
20 NT
63.60 -30.1 60.844
20 NT
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 F B LEARNING ESCTIME Overall
Statistic
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ TrtbTrial p-value++ LinTrtbTrial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
34
Dose Group (mg/kg/day) 0 0.1 0.3
126.40 NA 20
108.23 NA 20 NT
108.68 NA 20 NT
Statistical 1.0 Model
110.20 NA 20
0.171
0.296 0.945 0.866
ARI
-1925-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 F B LEARNING ERRORS 5
6
7
8
9
10
# : Level of Significance tested = .05. * : Statistically Significant.
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
35
-1926-
Dose Group (mg/kg/day) 0 0.1 0.3
33 NA 11.5 20
30 NA 9.3 20
28 NA 12.2 20
22 NA 12.7 20
26 NA 16.2 20
19 NA 15.4 20
32 -3.0
9.3 20 NT
24 -20.0
13.9 20 NT
24 -14.3
14.5 20 NT
19 -13.6
14.7 20 NT
18 -30.8
15 .6 20 NT
14 -26.3
14.1 20 NT
33 0.0 10.3
20 NT
29 -3.3 15.6
19 NT
27 -3.6 15.3
20 NT
21 -4.5 16.7
20 NT
15 -42.3
12.9 20 NT
14 -26.3
12.5 20 NT
Statistical 1.0 Model
32 -3.0 14.0
20 NT
33 10.0 13.4
20 NT
26 -7.1 14.8
20 NT
21 -4.5 15.4
20 NT
20 -23.1
16.7 20 NT
14 -26.3
15.7 20 NT
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type
Variable Trial
PND22 F B LEARNING ERRORS Overall
Statistic
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ TrtbTrial p-value++ LinTrtbTrial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
36
Dose Group (mg/kg/day)
) 0.1
0.3
22 23 NA NA 20 20 NT NT
Statistical 1.0 Model
24 NA 20 0.442
0.217 0.850 0.589
AR1
-1927-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type PND22 F A MEMORY
Variable Trial ESCTIME 11
12
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-test p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested = .05. * : Statistically Significant.
37
Dose Group (mg/kg/day) 0 0.1 0.3
84.58 NA
43.854 20
55.31 NA
44.536 20
69. 94 NA 20
79.11 -6.5
46.200 20 NT
52.74 -4 .6
43.343 20 NT
65.92 NA 20 NT
66.04 -21.9 44.900
20 NT
69.19 25.1
49.461 20 NT
67 .61 NA 20 NT
Statistical 1.0 Model
78.70 -7.0
42.154 20 NT
56.67 2.5
38.853 19 NT
67.12 NA 20
0.865
0.988 0.198 0.358
ARI
-1928-
++ : Level of Significance tested = .01. NT : Not tested. NA : Not applicable.
Table 3.3: Analysis Summary Table for Biel Maze
Period Sex Path Type PND22 F A MEMORY
Variable Trial ERRORS 11
12
Overall
Statistic
Mean % Difference Control S.D. N Linear Trend p-value#
Mean % Difference Control S.D. N Linear Trend p-value#
Mean S.D. N Linear Trend p-value#
Trt F-t.est p-value++ Trt*Trial p-value++ LinTrt*Trial p-value# Covariance Structure
# : Level of Significance tested * : Statistically Significant.
.05 .
38
Dose Group (mg/kg/day) 0 0.1 0.3
22 NA 11.8 20
14 NA 13.7 20
18 NA 20
21 -4.5 15.5
20 NT
13 -7.1 14.1
20 NT
17 NA 20 NT
19 -13.6
16.9 20 NT
19 35.7 18.0
20 NT
19 NA 20 NT
Statistical 1.0 Model
24 9.1 16.2
20 NT
15 7.1 11.4
20 NT
19 NA 20 0. 622
0.918 0.246 0.601
ARI
-1929-
++ : Level of Significance tested = .01. 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: A ll
WIL Research Laboratories - Developmental and Reproductive Toxicology Historical Control Summary of Reproductive Performance
Species: Rat Strain: Crl:CD(SD)
Number of Studies/Data Sets: 62/ 96 Range of Study Dates: 08/00 - 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 1600
96.8 89.8 92.7
2248 97.8 91.3 92.9
1301 1151 145 11 3
S.D.
3.69 6.89 6.08
3.26 7.17 5.82
N
61 61 61
73 82 73
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: 62 / 96 Range of Study Dates: 08/00 - 09/05
Mean Estrous Cycle Length (days) Mean Pre-Coital Interval (days) Mean Gestation Length (days) Mean Number of Pups Born Mean Viable Litter Size (PND 0) Mean % Males/ Litter Mean % Females/ Litter Mean No. of Former Implantation Sites at Weaning Mean No. of Sites Unaccounted for at Weaning
Mean Viable Embryos/Dam (GD 15) Mean Viable Embryos (%/Litter)
Mean Viable Fetuses/Dam (GD 20) Mean Viable Fetuses (%/Litter)
Mean Post-Implantation Loss/Dam Mean Post-Implantation Loss (%/Litter)
Mean No. of Corpora Lutea/Dam Mean No. of Implantation Sites/Dam Mean Pre-Implantation Loss/Dam
Mean Pre-Implantation Loss (%/Litter) Mean Fetal Body Weight (GD 20) (g) Mean Primordial Follical Count of 10 Sections/Dam
Mean S.D.
4.5 0.41 3.0 0.52 21.9 0.20 14.3 0.91 14.1 0.94 50.08 2.78 49.92 2.78 15.2 0.87 0.9 0.24 14.9 0.79 95.0 1.84 14.3 0.79 94.6 1.34 0.8 0.24 5.1 1.65 16.7 0.88 15.3 0.81 1.4 0.41 8.2 2.42 3.6 0.16 115.2 31.74
N
63 74 46 46 46 58 58 44 44 25 25 16 16 41 41 41 41 41 41 16 11
Mean -/+ 2 S.D.
3.68 / 5.32 1.96 / 4.04 21.50 / 22.30 12.48 / 16.12 12.22 / 15.98 44.52 / 55.64 44.36 / 55.48 13.46 / 16.94 0.00 / 1.38 13.32 / 16.48 91.32 / 98.68 12.72 / 15.88 91.92 / 97.28 0.32 / 1.28 1.80 / 8.40 14.94 / 18.46 13.68 / 16.92 0.58 / 2.22 3.36 / 13.04 3.28 / 3.92 51.72 / 178.68
Mean -/+ 3 S.D.
3.27 / 5.73 1.44 / 4.56 21.30 ,/ 22.50 11.57 / 17.03 11.28 ,/ 16.92 41.74 / 58.42 41.58 / 58.26 12.59 / 17.81 0.18 / 1.62 12.53 / 17.27 89.48 / 100.00 11.93 / 16.67 90.58 / 98.62 0.08 / 1.52 0.15 / 10.05 14.06 / 19.34 12.87 / 17.73 0.17 / 2.63 0.94 / 15.46 3.12 / 4.08 19.98 / 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: A ll
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
M ean N um ber o f Pups Born
Mean S.D. 14.3 0.91
N 46
Mean -/+ 2 S.D. 12.48 / 16.12
Mean -/+ 3 S.D. 11.57 / 17.03
Observed Low/High Value 12.2 / 16.0
S urvival (% )
PND 0 (Relative to No. Born) PND 0 to PND 1 PND 1to 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
98.0 1.53 99.1 0.89 98.6 1.33 98.9 1.76 99.3 1.46 99.5 1.11 95.8 2.26 97.8 2.50
46 46 45 44 41 41 43 40
94.94 / 100.00 97.32 / 100.00 95.94 / 100.00 95.38 / 100.00 96.38 / 100.00 97.28 / 100.00 91.28 / 100.00 92.80 / 100.00
93.41 / 100.00 96.43 / 100.00 94.61 / 100.00 93.62 / 100.00 94.92 / 100.00 96.17 / 100.00 89.02 / 100.00 90.30 / 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: A ll
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
Males (g) PND
PND 1 PND 4 PND 7 PND 14 PND 21 PND 28 (weaned PND 28)
Mean
7.1 10.0 15.3 30.4 47.5 82.0
S.D.
0.25 0.58 1.22 3.70 5.18 6.86
N
46 45 44 36 41 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 / 7.85 8.26 / 11.74 11.64 / 18.96 19.30 / 41.50 31.96 / 63.04 61.42 / 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 PND 1 PND 4 PND 7 PND 14 PND 21
PND 28 (weaned PND 28)
Mean 6.7 9.5 14.5 29.2 45.6 75.8
S.D. 0.25 0.56 1.17 3.46 4.76 6.11
N 46 45 44 36 41 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: A ll
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: 62/ 96 Range of Study Dates: 08/00 - 09/05
Mean 1.4397 0.2058 0.1963
S.D. 0.04072 0.03054 0.02035
N 21 21 21
1.3931 0.2020 0.1987
0.03322 0.03048 0.02387
21 21 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-A ug-06
-1935-
WIL Research Laboratories - Developmental and Reproductive Toxicology
Sex: Male/Female Study Type: All
Historical Control Summary of Developmental Landmarks
Species: Rat
Number of Studies/Control Groups: 62/ 96
Strain: Crl:CD(SD)
Range of Study Dates: 08/00 - 09/05
Mean Male Anogenital Distance (PND1) (mm) Mean Female Anogenital Distance (PND1) (mm)
Mean S.D. 4.37 0.171 2.38 0.175
N 6 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 1.05 111.9 6.42
31 31
31.50 / 35.70 99.06 / 124.74
30.45 / 36.75 92.64 / 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 5.2 0.10 4.1 0.15 4.1 0.10 16.4 1.20 16.4 1.20 14.9 NA 14.9 NA 13.5 1.43 13.6 1.51 9.9 0.41 9.9 0.34
3 3 4 4 4 4 1 1 4 4 5 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: A ll
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: 62 / 96 Range of Study Dates: 08/00 - 09/05
Males Mean Age of Males at Necropsy (weeks) Mean Seminal Vesicle/Coagulating Gland Weight (g) Mean Prostate Weight (g) Mean Right Testis Weight (g) Mean Left Testis Weight (g) Mean Right Epidymis Weight (g) Mean Left Epidymis Weight (g) Mean Right Cauda Epidymis Weight (g) Mean Left Cauda Epidymis Weight (g)
Mean 22.2 2.21 1.07 1.79 1.80 0.72 0.72 0.3275 0.3309
S.D. 4.20 0.169 0.102 0.069 0.077 0.041 0.041 0.02230 0.02064
N 27 36 22 48 48 48 48 48 48
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
-LZ6 1 -
Females Mean Age of Females at Necropsy (weeks)
Mean Combined Ovary Weight (g)
23.2 5.03 0.1448 0.03004
19 19
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: A ll
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: 62/ 96 Range of Study Dates: 08/00 - 09/05
Mean Sperm Concentration (millions/ gram of tissue) Left Testis
Left Epididymis
Left Cauda Epididymis
Mean S.D.
80.9 7.33 454.5 49.37 666.2 57.99
N
43 37 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-
Me(amnilSlipoenrsm/ gPrraomduocftitoisnsuRea/teday) Mean Sperm Motility (%) Mean Progressive Sperm Motility (%)
13.4 1.21 85.4 3.01 72.5 3.70
Sperm Morphology Differential Count (%)
Normal
99.1 0.81
Normal Head Separated from Flagellum
0.4 0.40
Head Absent w/ Normal Flagellum
0.3 0.39
Head Absent w/ Abnormal Flagellum
0.0 0.00
Misshapen Head w/ Normal Flagellum
0.0 0.17
Misshapen Head w/ Abnormal Flagellum
0.0 0.06
Degenerative Flagellar Defects w/ Normal Head 0.0 0.00
Other Flagellar Defects w/ Normal Head
0.0 0.00
23 44 15
43 43 43 43 43 43 43 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
97.48 / 100.00 0.00 / 1.20 0.00 / 1.08 0.00 / 0.00 0.00 / 0.34 0.00 / 0.12 0.00 / 0.00 0.00 / 0.00
96.67 / 100.00 0.00 / 1.60 0.00 / 1.47 0.00 / 0.00 0.00 / 0.51 0.00 / 0.18 0.00 / 0.00 0.00 / 0.00
11.4 / 15.8 78.9 / 91.0 67.0 / 80.0
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. P itt, M ark D. N em ec, D o n ald G. Stum p, D eb o rah Shoup, G ordon G lenn and K im Rhodes
ABSTRACT
T he ob jectiv e o f th is study w as to ev alu ate v ario u s en d p o in ts w ith in th e U .S. E P A O P P T S G uideline 870.6300 (D evelopm ental N eurotoxicity). P ropylthiouracil (P T U ) w as adm inistered at dosage lev els o f 3.8, 19 and 38 m g /k g /d ay b y o ral g av ag e o n ce d aily fro m gestatio n day 6 th ro u g h lactatio n day 10 to S prag u e-D aw ley C rl:C D (SD )IG S B R rats. O ffsp rin g w ere evaluated by functional observational b attery, m o to r activity, acoustic startle response, and learn in g and m em ory in the B iel w ater m aze. L ive litter size w as red u ced in the 38 m g/kg/day group. P up viability from b irth to P N D 4 w as reduced in the 19 and 38 m g/kg/day groups. P up w eig h ts w ere red u ced b y 10% at b irth fo r all d o sag e lev els, and rem ain ed red u ced fo r th e d u ratio n o f th e study. T he o b serv atio n al b attery d em o n strated d elay s in p u p illary resp o n se, startle reactivity, m obility and n eu ro m u scu lar d evelopm ent on postnatal day (P N D ) 20. N eurom uscular m easures continued to b e im paired at the P N D 35 and 45 observations. M otor activity w as n o t affected. A co u stic startle resp o n se w as red u ce d at all do sag e lev els w h en ev alu ated o n P N D 22. L aten cy to escap e th e B iel m aze w as in creased fo r all do sag e lev els at th e P N D 22 evalu atio n ; h o w ev er, sw im m in g ability w as m ark ed ly red u ce d fo r all treatm en t groups. W h en assessed at P N D 62 sw im m in g ability w as co m p arab le b e tw ee n all groups. H o w ev er, tim e to escap e th e B iel m aze w a s in creased fo r m ales an d fem ales at all do sag e lev els by approxim ately 60% although there w as no dose response relationship. T he experim ental design u sed in th is study d em o n strated th at W IL R esearch L ab o rato ries, Inc. can d etect effects o f PT U , a know n developm ental neurotoxicant, and results can be considered to validate m ethodologies fo r O P P T S G u id elin e 87 0 .6 3 0 0 d ev elo p m en tal n eu ro to x icity studies.
Page 1 of 14
-1941-
INTRODUCTION
In 1998, th e U n ited States E nvironm ental P ro tectio n A gency (E P A ) released th e D evelopm ental N e u ro to x icity Study (O P P T S 870 .6 3 0 0 ) g u ideline (1). T he g u ideline re q u ire d th at v ario u s n eurobehavioral endpoints such as m o to r activity, auditory startle, and learning and m em ory along w ith appearance o f developm ental landm arks and o th er standard toxicologic indices be tested to support product registration u n d er F IF R A and T SC A . V alidation o f laboratory m eth o d o lo g ies is a req u irem en t o f th e guideline. W e chose to evaluate p o tential d ifferences in control and treated anim als using an agent w hich produces hypothyroidism , propylthiouracil (PTU ).
In rats, p re- and peri-natal h y p othyroidism produces b ehavioral deficits (2-4) and altered electro p h y sio lo g y (2,5,6) along w ith ch an g es in gross and m icro sco p ic m easu res o f b rain m orphology (7-12).
MATERIALS and METHODS Test Species and H usbandry
F em ale S prague-D aw ley C rl:C D (SD )IG S B R rats w ere o b tain ed fro m C h arles R iv er B reed in g L aboratories (R aleigh, N C , U S A ). T he anim als w ere individually h o u sed in clean suspended w ire-m esh cages in an environm entally controlled room d uring acclim ation. D uring c o h a b ita tio n , th e fe m a le s w e re p a ire d (1 m a le :1 fe m a le ) w ith re s id e n t m a le s in a s u s p e n d e d w ire m esh cage. M ating w as evidenced by vaginal p lug and/or the presence o f sperm in a vaginal sm ear. F ollow ing successful m ating, the fem ales w ere individually housed in plastic m aternity cag es w ith n e stin g m aterial (B e d -O 'Cobs ). O n p o stn a ta l day (P N D ) 4, p u p s w e re c u lle d to red u ce v ariab ility am o n g litter size (3:5, 4:4 o r 5:3 M :F ) an d d am s an d p u p s rem ain ed in th ese cages until the dam w as euthanized on P N D 21. E ach litter rem ain ed h o u sed to g eth er in plastic cages w ith nestin g m aterial th ro u g h P N D 28 w h ereu p o n they w ere h o u sed 2-3/cage by sex in w ire m esh cages. O n P N D 35 u n til sch ed u led e u th an asia all an im als w ere ind iv id u ally housed. E nvironm ental controls w ere set to m aintain tem perature at 72 4 F and relative hum idity betw een 30-70% . A ir han d lin g un its p rovided a m inim um o f 10 fresh air changes p e r hour. F lu o re sc e n t lig h tin g , c o n tro lle d b y tim e rs, p ro v id e d illu m in a tio n fo r a 1 2 -h o u r (6 :0 0 a.m . - 6 :0 0 p.m .) light/dark photoperiod. T em perature and relativ e hum idity w ere m o nitored continuously.
Page 2 of 14
-1942-
R e v e rs e o sm o sis-p u rifie d w a te r w a s a v a ila b le a d libitum. P M I N u tritio n In te rn a tio n a l, Inc. C e rtifie d R o d e n t L abD iet 5 0 0 2 w a s o ffe re d a d libitum d u rin g th e study.
Test M aterial and Preparation
6 -N -P ro p y l-2 -th io u ra c il (P T U ) w a s p u rc h a se d fro m S ig m a A ld ric h , St. L o u is, M O , (lo t #76H 2500). A n appropriate am ount o f P T U w as m ix ed w ith 0.5% m ethylcellulose (S igm a C h e m ic al C o., St. L o u is, M O , lo t # 9 7 H 0 9 8 0 ) to p ro d u c e d o sin g so lu tio n s o f 0 .3 0 4 , 1.52 an d 3 .0 4 m g/m l. D o sin g solutions w ere p rep ared w eekly and daily aliquots w ere dispensed fo r dosing.
Experim ental Design
F o u r g roups o f 25 b red rats receiv ed a d aily oral gavage o f 0, 3.8, 19 o r 38 m g /k g P T U daily
fro m g e statio n d ay (G D ) 6 th ro u g h P N D 10. T h e d o se v o lu m e w a s 12.5 m l/k g . D a m s w e re
ex am in ed daily fo r m ortality, m orbundity and fo r clinical signs o f toxicity. M aternal body
w eight and food consum ption w ere recorded tw ice w eekly from G D 0 through P N D 21. Pups
w ere ran d o m ized into treatm en t groups and th en assigned to testin g groups w ith in each treatm ent
group. T he follow ing table sum m arizes the testin g paradigm :
Number of Animals 10/s e x /g r o u p 10/s e x /g r o u p 10/s e x /g r o u p 10/s e x /g r o u p
3 -1 0 /se x /g ro u p
Age
PN D 20, 35, 45 and 60 PN D 22
P N D 13, 17, 21 and 60 P N D 21 and 62 PN D 4 and 28
Evaluation
F unctional O bservational B attery (FO B ) A uditory startle
L o co m o to r A ctivity L earning and M em ory
(B iel M aze) T 3, T 4 a n d T S H le v e ls
D ev elo p m en tal L andm arks: A n o g en ital d istan ce w a s m ea su re d o n P N D 1 fo r all live pups. B alan o p rep u tial sep aratio n w as o b serv ed fo r all m ale p u p s b eg in n in g o n p ostnatal day 35 and continued daily until balanopreputial separation w as present. T he body w eight o f each m ale w as reco rd ed o n the day o f acquisition o f balanopreputial separation. V aginal patency w as observed fo r all fem ale p ups b eg inning o n postnatal day 25 and continued daily un til vaginal perforation w as present. T he body w eig h t o f each fem ale w as recorded on the day o f acquisition o f vaginal patency.
Page 3 of 14
-1943-
B ehavioral T esting
T en p u p s/sex /g ro u p w ere assig n ed to o n e o f th e fo llo w in g tests: fu n ctio n al o b serv atio n al battery (F O B ), locom otor activity, auditory startle o r learning and m em ory. T he F O B u tilized w as based o n previously developed p rotocols (13-16). T esting w as perform ed by the sam e trained te c h n ic ia n s, w h e n e v e r p o ssib le , w h o d id n o t k n o w th e a n im a l's g ro u p a ssig n m en t. L o c o m o to r activity w as m onitored o n postnatal days 13, 17, 21 and 60 ( 2 days). T he sam e anim als w ere m o n ito red at each in terv al an d testin g o f treatm en t g ro u p s w as b alan ced acro ss test tim es. L o co m o to r activity w as m easured u sin g the D ig iscan M icro A nim al A ctivity S ystem (O m nitech E lectro n ics Inc., C olum bus, O hio) and th e test sessio n w as 41 m in u tes d u ratio n w ith 1 m in u te test intervals fo r each anim al. T he auditory startle resp o n se test w as p erfo rm ed o n P N D 22 u sin g an au to m ated A u d ito ry S tartle R esp o n se S ystem (C o u lb o u rn In stru m en ts, Inc., L eh ig h V alley, P ennsylvania). T he test session consisted o f a 5 m inute acclim ation p erio d w ith a b ackground noise level o f 70 db, follow ed by 50 presentations o f a 50-m s 120 db noise burst given at 8 seco n d intervals. M e a n am p litu d e o n each b lo ck (1-5) o f 10 tria ls w as re co rd e d fo r each anim al. L earn in g and m em ory w as tested on postnatal day 21 (4 days) and 62 (4 days) using a B iel m aze (22). D ifferent anim als w ere tested at each interval. T he B iel m aze is a w ater-filled m ultip le T -m aze w ith an escape ladder. T he tim e to escape and n u m b er o f errors (anim al d ev iates fro m th e correct ch an n el w ith all fo u r feet) w as reco rd ed and an im als w ere allow ed th ree m in u tes to escap e fro m th e m aze after w h ic h th ey w ere rem oved. T he m in im u m intertrial interval w ill b e one hour. A n im als w ill b e tested fo r seven consecutive days as follow s:
D a y 1: D ay s 2 and 3: D ays 4, 5 and 6: D ay 7:
E ach anim al is given 4 trials to escape fro m a straight channel. E ach anim al is given 2 trials p er day in P ath A. E ach anim al is given 2 trials p er day in P ath B (reverse o f P ath A). E ach anim al is given 2 trials in P ath A.
Statistical Analyses
A ll analyses w ere tw o-tailed fo r a significance level o f 1% and 5% b y a one-w ay analysis o f v a ria n ce (A N O V A ; 18). If sig n ifican t d ifferen ces w e re in d ic a te d b y th e A N O V A , D u n n ett's test (19) w as u sed to com pare the control and treated groups. F unctional observational battery p a ram ete rs w h ic h y ield sc a la r an d d escrip tiv e d a ta w e re an aly zed b y F ish e r's E x ac t T est (20). B o d y w eights, horm one concentrations, survival, developm ental landm arks, litter size, loco m o to r activity,
Page 4 of 14
-1944-
startle response and learning and m em ory w ere analyzed u sin g a one-w ay A N O V A . If significant trea tm e n t effe c ts w e re o b se rv ed at a g iv en tim e-p o in t, th e n D u n n ett's te st w a s co n d u cted to determ in e significant treatm en t differen ces fro m th e control group (p< 0.05).
RESULTS and DISCUSSION
T reatm ent w ith P T U significantly d ecreased m aternal body w eights in the 38 m g/kg/day group late in g estatio n (d ata n o t show n). P u p w e ig h ts o n P N D 1 w e re sig n ifican tly d e cre ased in all treated groups. A fter th e en d o f treatm en t o n P N D 10, b o d y w eig h ts in all P T U -treated groups re m a in e d s ig n ific a n tly d e c re a s e d in all g ro u p s a t e a c h d a y m e a s u re d (F ig u re 1). P u p w e ig h ts w ere red u ced b y app ro x im ately 10% at b irth fo r all do sag e lev els and rem ain ed red u ced th r o u g h o u t th e stu d y (F ig u re 1).
L ive litter size w as significantly red u ced in the 38 m g/kg/day group, and p up viability w as sig n ific a n tly re d u c e d fro m b irth to P N D 4 in th e 19 a n d 3 8 m g /k g /d a y g ro u p s (T a b le 1). T h e appearance o f balanopreputial separation w as significantly d elayed (3-4 days) in th e 19 and 38 m g /k g /d ay d ose groups. S im ilarly, vag in al p aten cy w a s also sig n ifican tly d elay ed b y 6-8 days (T a b le 1). T h e s e d e v e lo p m e n ta l la n d m a rk s a re b o d y w e ig h t d e p e n d e n t in th e ro d e n t a n d in th is case are p ro b ab ly in d icativ e o f a b o d y w eig h t and n o t an en d o crin e effect.
S erum T4 lev els w ere red u ced fo r each dose group on P N D 4 fo r b o th sexes co m b in ed and on P N D 28 fo r b o th sexes separately. S eru m T S H lev els w ere red u ce d at all do sag e lev els o n P N D 4 and serum T 3 levels w ere reduced fo r each m ale dose group on P N D 28, b u t n o t fo r fem ales (data n ot show n). T he adult rat is know n to be m ore sensitive to p erturbations o f th e pituitaryth y ro id axis th an h um ans (21); how ever, the sensitivity o f th e n eonatal rat com pared to the n eonatal h u m an is less w ell docum ented.
T he functional observational battery d em onstrated deficits in autonom ic (pupillary response, p alp eb ral clo su re), n e u ro m u scu lar (gait, m o b ility , fo o t splay, grip strength, rig h tin g reflex , rotorod), sensorim otor (startle), C N S activity (catalepsy, rearing, groom ing) and physiologic (b ody w eig h t, tem p eratu re) en d p o in ts o n P N D 20 in b o th sexes and in all d o se groups. M o st o f th ese findings w ere no lo n g er evident by P N D 35 although deficits in grip strength and body w eig h t w ere su stain ed th ro u g h P N D 6 0 (T able 2).
Page 5 of 14
-1945-
M o to r activity w as in creased in all m ale do se g roups o n P N D 21 an d in fem ales m o to r activity w a s in creased , alb eit n o t statistically n o r in a d ose resp o n se, o n P N D 17 an d 21 (F igure 2), and th erefo re the relationship to treatm ent is quesitonable. T he p eak auditory startle response w as significantly red u ced and th e latency to p eak response w as significantly increased fo r both sexes at all d o sag e lev els o n P N D 22 (F igure 3). S w im m in g ability w as strikingly red u ced fo r b o th sex es in all treatm en t g roups at P N D 21 alth o u g h on ly th e fem ale 19 m g /k g /d ay group reach ed sta tistic a l sig n ific a n c e (T a b le 1). B y P N D 61 th e re w a s n o d iffe re n c e in s w im m in g a b ility a c ro ss a ll tre a tm e n t g ro u p s (T a b le 1). A lso , w h ile o n P N D 6 2 sw im m in g a b ility w a s c o m p a ra b le b e tw ee n all groups, laten cy to escap e th e B iel m aze w as sig n ifican tly in creased fo r b o th sexes at all do sag e levels. H o w ev er, o n P N D 2 2 w h en sw im m in g ability w as sig n ifican tly reduced, laten cy to escap e th e B iel m aze w as also sig n ifican tly in creased at all do sag e levels. T he m ean n u m b er o f erro rs fo r all w a s n o t d iffere n t o n P N D 22, b u t w a s n u m erically in cre ased acro ss all groups on P N D 62.
In conclusion, S prague D aw ley C rl:C D (S D )IG S B R rats h av e b een show n to b e sensitive to the effects o f pre- and peri-natal P T U exposure as assessed by developm ental and behavioral assessm ents described by the U S E nvironm ental P rotection A gency D evelopm ental N eurotoxicity Study (O P P T S 870.6300) guidelines.
REFERENCES
1. E P A H e a lth E f f e c ts T e s t G u id e lin e s (1 9 9 8 ) O P P T S 8 7 0 .6 3 0 0 D e v e lo p m e n ta l N e u r o to x ic ity Study E P A 712-C -98-239.
2. E ay re , J.T . (1 9 6 6 ) T h ry o id an d c e n tra l n e rv o u se sy ste m d e v elo p m en t. In: Scientific basis o f medicine, annual reviews. T h e A th lo n e P re ss, L o n d o n .
3. E ssm an , W .B ., M en d o za, L .A . and H am b u rg h , M . (1968) C ritical p e rio d s o f m aze acquisition developm ent in euthyroid and hyp o th y ro id rodents. Psychol. R ep. 23:795-800.
4. C om er, C .P. and N o rto n , S. (1982) E ffects o f p erin atal m eth im azo le ex p o su re o n a d ev elo p m en tal test battery fo r n eu ro b eh av io ral to x icity in rats. T oxicol. A ppl. P harm acol. 6 3 :1 3 3 -1 4 1 .
5. A lb ee, R .R ., J.L . M attsso n , K .A . Jo h n so n , K irk , H .D . and B reslin , W .J. (19 8 9 ) N eu ro lo g ical co n seq u en ces o f co n g en ital h y p o th y ro id ism in F ish er 344 rats. N eu ro to x ico l. T eratol. 1 1 :1 7 1 -1 8 3 .
6. H erb ert, R ., L eL anglois, J.M . and D ussault, J.H . (1985) P erm an en t d efects in ra t p erip h eral
auditory fu n ctio n fo llo w in g p erin atal h y p o th y ro id ism : D eterm in atio n o f a critical period. D ev. B rain R es. 23:161-170.
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7. B eh n am -R asso li, M ., H erb ert, L .C ., H o w ard , V ., P h aro ah , P .O . and S tanisstreet, M . (1991) E ffect o f propylthiouracil treatm ent during prenatal and early postnatal developm ent o f the n eocortex o f rat pups. N euroendocrinol. 53:321-327.
8. M w an g i, D .K . (1998) E ffec t o f p ro p y lth io u racil in d u ced h y p o th y ro id ism in d ev elo p in g rat
cerebellum : com parison o f cerebellar param eters in five day old n orm al and treated rat pups. E a s t A fr. M ed . J. 7 5 :6 0 2 -6 0 8 . 9. W alk er, R .F ., G u erriero , F .L ., T o scan o , T .V . an d W eid em an , C .A . (19 8 9 ) R e la tiv e c ereb ellar w eight: a p o ten tial in d icato r o f d ev elo p m en tal n eu rotoxicity. N eu ro to x ico l T eratol. 1 1 :251 255. 10. C om er, C .P. and N o rto n , S. (19 8 5 ) E arly d e v elo p m en t in th e c au d ate an d th y ro id o f m eth im azo le-treated rats. N euro to x ico l. 6:25-36. 11. R u iz-M arc o s, A . a n d Ip in a, S.L. (1 9 8 6 ) H y p o th y ro id ism a ffects p re fe re n tia lly th e d en d ritic d en sities o n th e m o re su p erficial reg io n o f p y ram id al n eu ro n s o f th e ra t cerebral cortex. D ev. B rain R es. 28:259-262. 12. W a lte rs, S .N . a n d M o re ll, P. (1 9 8 1 ) E ffe c ts o f a lte re d th y ro id sta te s o n m y e lin o g e n e sis. J. N eurochem . 36:1792-1801. 13. Irw in, S. (1968) C o m p reh en siv e o b serv atio n al assessm ent: 1a. A sy stem atic qu an titativ e p rocedure fo r assessing th e behavioral physiological state o f the m ouse. P sychopharm acologia 13: 222-256. 14. M o ser, V .C ., M cC o rm ick , J.P. C reason, J.P. an d M acP h ail, R .C . (1 9 8 8 ) C o m p ariso n o f c h lo rd im efo rm an d carb ary l u sin g a fu n c tio n al o b se rv atio n al b attery. F u nd. A p p l. T oxicol. 11: 189-206. 15. H ag g erty , G .C . (1989) D ev elo p m en t o f T ier 1 N eu ro b eh av io ral T estin g C ap ab ilities fo r In c o rp o ra tio n in to P iv o tal R o d e n t S afety A sse ssm e n t S tudies. J. A m er. C oll. T oxicol. 8: 53-69. 16. O 'D onoghue, (1989) J.L. S creen in g fo r N eu ro to x icity U sin g a N eu ro lo g ically B ased E x a m in a tio n a n d N e u ro p ath o lo g y . J. A m er. C oll. T oxicol. 8: 97-116. 17. B ie l, W .C ., (1 9 4 0 ) E a rly A g e D iffe re n c e s in M a z e P e rfo rm a n c e in th e A lb in o R at. J. G en. Psych. 56: 439-453. 18. S n ed eco r, G .W . a n d C o ch ran , W .G . (1 9 8 0 ) O n e w a y classifica tio n s; a n aly sis o f v arian ce. In: S tatistical M eth o d s, S eventh E dition. Io w a State U n iv ersity P ress, A m es, IA , pp. 215-237. 19. D u n n e tt, C .W . (1 9 6 4 ) N e w tab le s fo r m u ltip le c o m p a riso n s w ith a control. Biometrics 2 0 :4 8 2 491. 20. Steel, R .G .D . and T orrie, J.H . (1980) P rin cip les and P ro ced u res o f Statistics, A B io m etrical A pproach, S econd E dition. M cG raw -H ill B o o k C om pany, N ew Y ork, N Y , pp. 504-506. 21. Siglin, J.C ., M attie, D .R ., D o d d , D .E ., H ild eb ran d t, P .K . and B ates, W .H . (2000) A 90-D ay D rin k in g W ater Study in R ats o f th e E n vironm ental C ontam inant A m m onium P erchlorate. 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)
-M ales -F em ales
Survival (Percent Per Litter)
-B irth-P N D 4 -PN D 4-w eaning
Developmental Landmarks
-B alanopreputial separation (PN D )
B ody w eight (gram s)
15.1 1 .5 14.2 3 .4 52.2 12.6
6.5 0.7 6.1 0 .7
88.1 2 4 .8 98.2 4.8
45.1 3 .0
212 1 6 .2
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 2.8 188 21.9**
-V aginal patency (PN D )
33.4 2.8
39.8 2.5**
B ody w eight (gram s)
101 9.0
113 15.4**
Anogenital Distance Relative to Cube-Root of Body Weight (PND 1)
-M ale
2.71 0 .6
2.58 0.5
-Fem ale
1.63 0 .5
1.54 0 .4
Swimming ability (Seconds) PND 21
-M ale
15.8 10.7
52.6 55.5
-Fem ale
14.3 9 .2
46.3 4 6 .8
Swimming ability (Seconds) PND 61
-M ale -Fem ale
7.0 2.3 8.3 3 .4
* = S ig n ifican tly d ifferen t fro m th e co n tro l group at P< 0.05.
**= S ig n ifican tly d ifferen t fro m th e co n tro l 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 1 6 .7
5.8 0.5** 5.5 0 .4 * *
77.4 28.8** 95.4 1 2 .6
49.5 4.0** 194 14.3** 41.5 3.0**
111 1 1 .6 *
2.59 0.7 1.58 0 .4
66.3 6 5 .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 2 4 .6
48.1 2 .4 * 190 14.7** 41.4 2.4**
1 1 0 1 5 .6
2.78 0.8 1.75 0 .6
56.1 6 8 .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
PND 20
PND 35
PND 45
PND 60
Autonomic Neuromuscular
Sensorimotor CNS Excitability CNS Activity Physiological
Lacrimation Salivation Pupil Response Palpebral Closure Defecation Urination Time to First Step Gait Score M obility Score Foot Splay Forelimb Grip Strength Hindlimb Grip Strength A ir Righting Rotorod Tail Pinch Startle Response Touch Response Approach Response Olfactory Response Ease o f Removal Handling Reactivity Clonic Movements Tonic Movements Arousal Vocalization Posture Catalepsy Rearing Grooming Backing Body Weight Body T emperature Appearance
Male
Female Male Female Male Female Male Female
NR: 2,3,4 NR: 2,3,4 D: 2,3,4 D: 2,3,4
D: 2,3,4 D: 2,3,4 D: 2,3,4 IM : 2,3,4 D: 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 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: 2,3,4 D: 2,3,4
D: 4 D: 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-
Grams
- -- 0 mg/kg/day
- 3.8 mg/kg/day
- - 19 mg/kg/day
Grams
BC AC
Postnatal Day
- 38 mg/kg/day 450 400 350 300
250 I 200 150 100 50 0
450 400 350 300 250
C3
200 150 100 50 0
FIGURE 1. M e a n S D b o d y w e i g h t o f C o n tr o l a n d P T U - t r e a t e d r a t p u p s . S ig n if ic a n c e
b e tw ee n th e co n tro l an d treated groups is in d icated b y * (p < 0 .0 5 ) and ** (p< 0.01).
T he ro w o f */** in d icates w h ich g roups is d ifferen t fro m co n tro l w ith to p , m id d le
and b o tto m s ro w s co rresp o n d in g to 3.8, 19 and 38 m g /k g /d ay , respectively.
B C = B efore culling
A C = A fter culling
Page 10 of 14
-1950-
0 mg/kg/day
3.8 mg/kg/day
300
- 250
2
| 200
u
150
e
o
2
100
Pm 50
0 PND 13 PND 17 PND 21 PND 60
19 mg/kg/day
38 mg/kg/day
FEMALE
.LI.
11 1 1 1 1111
PND 13 PND 17 PND 21 PND 60
FIGURE 2. L o c o m o t o r a c tiv ity e x p r e s s e d a s a p e r c e n ta g e o f c o n tr o l i n m a l e ( le f t) a n d f e m a le
(right) pups. S ig n ifican ce is in d icated b y an * (p< 0.05).
Page 11 of 14
-1951-
125 " 100 .
Peak Response
Male Female
75 "
O
50
25
0
Control
3.8 mg/kg 19 mg/kg 38 mg/kg
Latency to Peak Response
F IG U R E 3. M ean SD auditory startle response on P N D 22. S ignificance betw een the control and treated g roups is in d icated b y * (p< 0.05) and ** (p< 0.01).
Page 12 of 14
-1952-
(A ) L aten cy to E scap e 200
Male Female
180
160
140
120
100
80
60
40
20
0
0 mg/kg 3.8 mg/kg 19 mg/kg 38 mg/kg
Group
0 mg/kg
3.8 m g/kg 19 mg/kg Group
38 mg/kg
FIGURE 4. M e a n S D B i e l m a z e r e s p o n s e o n P N D 2 2 . S i g n i f ic a n c e b e tw e e n t h e c o n tr o l a n d
trea te d g roups is in d icated b y * (p< 0.05) and ** (p< 0.01). N o statistical an alysis w as perform ed on th e m ean total n u m b er o f errors.
Page 13 of 14
-1953-
(A) Latency to Escape 140
Male
Female
** -i**
0 mg/kg
3.8 mg/kg 19 mg/kg Group
38 mg/kg
(B) Number of Errors 30
25
VI
20
W
15
i. &
.Q | 10
z
5
0 0 m g/kg 3.8 m g/kg 19 m g/kg 38 mg/kg
Group
FIGURE 5. M e a n S D B i e l m a z e r e s p o n s e o n P N D 6 2 . S i g n i f ic a n c e b e tw e e n t h e c o n tr o l a n d
trea te d g roups is in d icated b y * (p< 0.05) and ** (p< 0.01). N o statistical an alysis w as perform ed on th e m ean total n u m b er o f errors.
Page 14 of 14
-1954-
WIL-99140
D ate R ange: A pril 12-13, 1999
D eterm in atio n o f T est S ession D u ratio n and T est Interval fo r the S an D iego P h o to b eam A ctiv atio n S ystem U sin g U ntreated R ats
Study O bjective:
R egulatory guidelines require th at th e length o f the lo co m o to r activity m o n ito rin g session b e long enough to allow un treated rats to approach norm al activity levels by th e last 20% o f th e sessio n fo llo w in g th eir p lacem en t into a n o v el en v iro n m en t habituation). T he prim ary objective o f th is study w as to determ ine the appropriate test session d uration fo r the locom otor activity m easu rin g apparatus (S an D iego Instrum ents - P ho to b eam A ctivity S ystem [SD I-PA S ]). A secondary objective w as to collect data th at could b e used to d eterm ine an appropriate interval length (epoch) w ith in th e test sessio n fo r th e cap tu rin g and re p o rtin g o f lo co m o to r activity data.
T est System :
Ju v en ile (ap p ro x im ately six -w eek o ld) S prag u e-D aw ley C rl:C D (SD )IG S B R rats w eighing approxim ately 225 + 75 gram s (m ales) and 135 + 25 gram s (fem ales) w ere u sed o n th e study. T he rats w ere arbitrarily selected fro m av ailab le stock.
E n v iro n m en tal C onditions:
T he rats w ere acclim ated to laboratory conditions fo r five days prio r to m onitoring lo co m o to r activity. A n im als w ere h o u sed and m ain tain ed u n d e r co n d itio n s co n sisten t w ith m aintaining good health and as p er W IL Standard O perating Procedures. T em perature and hum idity w ere m aintained at 72 + 4 F and 50 + 20% , respectively, in a ro o m w ith a 12 h ours light/12 hours dark (0600-1800 hrs) photoperiod. T he facilities at W IL R esearch L aboratories, Inc. are fully accredited by the A sso ciatio n fo r A ssessm en t and A ccred itatio n o f L aboratory A nim al C are International.
L ocom otor A ctivity M onitoring M ethods:
L o co m o to r activity o f 24 u ntreated rats (12 p er sex) w as m o nitored to d eterm ine the accep tab le test sessio n d u ratio n and test in terv al to b e u sed o n su b seq u en t studies. (T he test interval is the frequency at w h ich activity counts are captured.) F o r this testing, th e d uration o f th e test session w as 120 m inutes. T he test interval w as one m inute. T hat is, total activity (p h o to b eam in terru p tio n s) w as reco rd ed at o n e-m in u te intervals fo r 120 m inutes. M onito rin g com m enced one m inute after placem en t o f the rats in to th e m o n ito rin g units.
-1955-
WIL-99140
L o co m o to r activity m o n ito rin g w as p erfo rm ed u sin g the SD I P h o to b eam A ctivity S ystem (S an D ieg o Instru m en ts, Inc., S an D ieg o , C A ), w h ich in clu d es P h o to b eam A ctivity S ystem (P A S ) softw are, analyzer and 24 activity m onitors. A local personal c o m p u te r lin k e d to th e lab o ra to ry 's m ain fram e c o m p u te r co n tro ls th e S D I P A S .
E ach locom otor activity m onitoring unit consists o f seven p hotobeam em itting/detecting units attached to a m o u n tin g fram e. A clear acrylic shoe b o x -style cage (18.5"L x 9.5"W x 8"H ) fits in to th e m o u n tin g fram e to co n tain a single anim al d u ring th e test session. A ctiv ity is m easu red as in terru p tio n s o f th e p h otobeam s.
P hotobeam diagnostic checks w ere p erform ed prio r to and fo llo w in g com pletion o f the test session. C o n firm atio n th at th e so ftw are-d riv en p ro ced u re w as o p eratin g correctly w as obtained by m anually b lo ck in g th e p hotobeam s w ith pre-cut p ieces o f cardboard.
M onitoring w as p erform ed in a sound-attenuated room equipped w ith a w hite-noise generator set to operate at approxim ately 70 db.
R esults:
M ean total locom otor activity d ata are presen ted graphically as b o th one-m inute and fiv e-m in u te test in terv als (ep o ch s) fo r th e en tire 120-m inute test sessio n in F ig u res 1 and 2 , respectively. C orresponding num erical data are presented in T ables 1 and 2.
M ean to tal activity co u n ts p e r m in u te w ere c alcu lated u sin g all 2 4 an im als at each tim e po in t. F ive-m inute epochal data rep resen t grand m ean activity counts fo r each five-m inute interval.
D iscussion:
F ollow ing th eir placem en t into th e m o n ito rin g units, u ntreated rats retu rn ed to norm al locom otor activity levels after 36 m inutes. T herefore, although a 45-m inute test session w o u ld b e adequate to allow rats to fu lly habituate to a novel environm ent, a 60-m inute test session w as selected fo r future studies. A test session o f 6 0 m inutes duration w ould com fortably m eet the criterion fo r approaching norm al locom otor activity levels by the last 2 0 % o f the test session, w hile prov id in g a slightly extended sessio n th at m ay allo w fo r d etectio n o f d elay ed effects.
N o differences in loco m otor activity levels w ere apparent w h en th e data w ere exam ined in one-m inute versus five-m inute test intervals (epochs). T herefore, collection and repo rtin g o f locom otor activity w ith the S D I-P A S u sin g a five-m inute test in terv al w as ju d g ed to b e ad eq u ate to d etect alteratio n s in lo co m o to r activity.
-1956-
W IL-99140 A lternative locom otor activity m on ito rin g parad ig m s can b e em ployed as appropriate, necessary o r requested, b u t the above conditions (60-m inute test session w ith fivem inute epochs) are considered to b e acceptable standards fo r this laboratory and equipm ent.
WIL-99140
Figure 1
Habituation Locomotor Activity in One-Minute Epochs
-1957-
In te rv al (M in u te s )
Page 1
WIL-99140
Figure 2
Habituation Locomotor Activity in Five-Minute Epochs
-1958-
In te rv al (M in u te s )
Page 1
WIL-99140
Interval MAC
1 71.95833 2 48.625 3 45.45833 4 42.0833 5 40.95833 6 29.70833 7 37.70833 8 21.58333 9 27.16667 10 20.83333 11 14.95833 12 13.16667 13 10.91667 14 11.45833 15 10.45833 16 11.125 17 12.70833 18 10.70833 19 8.625 20 9.458333 21 11.45833 22 9.541667 23 9.458333 24 9.833333
Interval
Table 1 Locomotor Activity Data in 1-Minute Epochs
MAC
Interval
MAC
Interval
MAC
25 10.41667 26 11.04167 27 8.041667 28 12.25 29 8.083333 30 3.541667 31 7.25 32 5.291667 33 3.083333 34 2.125 35 3.791667 36 3.416667 37 1.208333 38 0.416667 39 0.375 40 0.458333 41 0.5 42 1.916667 43 0.791667 44 0.958333 45 0 46 0.708333 47 0.625 48 1.083333
49 3.083333 50 3.375 51 4.125 52 0.5 53 0.583333 54 0.625 55 0.75 56 2.416667 57 1.083333 58 1.708333 59 2.666667 60 1 61 2.125 62 3.625 63 4.875 64 4.291667 65 3.458333 66 1.583333 67 2.333333 68 1.333333 69 1.666667 70 1.75 71 2.5 72 1.666667
73 2.5 74 0.541667 75 1 76 1.375 77 2.541667 78 1.875 79 2.833333 80 1.041667 81 0.5 82 1.333333 83 3.625 84 0.708333 85 0.791667 86 1.416667 87 0.791667 88 0.5 89 0.375 90 0.25 91 1.291667 92 0.083333 93 0.75 94 1.625 95 1.75 96 0.375
Interval
MAC
97 1.208333 98 0.458333 99 0.333333 100 0.25 101 1.583333 102 3.708333 103 1.416667 104 2.625 105 6.333333 106 2.416667 107 0.333333 108 0.875 109 0.625 110 1.125 111 2.208333 112 0.708333 113 0.208333 114 0.791667 115 0.125 116 0 117 0.333333 118 0 119 0.166667 120 0.541667
-1959-
MAC = Mean A ctivity C ount
Page 1
WIL-99140
Interval MAC
5 49.81667 10 27.4 15 12.19167 20 10.525 25 10.14167 30 8.591667 35 4.308333 40 1.175
Table 2 Mean Total Activity Counts in 5-Minute Epochs
Interval MAC
45 0.833334 50 1.775 55 1.316667 60 1.775 65 3.675 70 1.733333 75 1.641667 80 1.933333
Interval MAC
85 1.391667 90 0.666667 95 1.1 100 0.525 105 3.133333 110 1.075 115 0.808333 120 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:
R egulatory guidelines require th at th e testing laboratory dem onstrate th e ability to detect chem ical-induced alterations in startle response. T herefore, the objective o f th is study w as to dem onstrate th at th e acoustic startle response m easuring apparatus (S an D iego Instrum ents SR L A B S tartle R esponse System ) is able to detect chem ical-induced alterations in startle response w ith e a c h o f th e fo llo w in g te s tin g p a ra d ig m s (F ig u re 1):
A. Habituation of the Acoustic Startle Response
T he acoustic startle response is a centrally m ed iated reflex. T his reflex is evaluated in an apparatus in w h ich the test subject is placed in an acrylic cylinder th at is m o u n ted on a platform that is enclosed in a sound-attenuating cham ber. T here is a piezoelectric force-transducer m ounted on the underside o f the platform to w hich the acrylic cylinder is affixed. W h en th e anim al reacts to th e startle stim ulus, the a n im a l's m o v e m e n t p ro d u c e s a d e fle c tio n o f th e p latfo rm , w h ic h in d u c e s a v o lta g e change in th e piezoelectric force-transducer. T his signal is am plified and converted to a digital signal fo r analysis. Startle response m easures obtained are m axim um r e s p o n s e a m p litu d e (V max), a v e r a g e r e s p o n s e a m p l i tu d e ( V ave) a n d la t e n c y t o V max (Tmax).
B. Prepulse inhibition of the Acoustic Startle Response
P repulse inhibition is w h en a w eak er stim ulus is p resented p rio r to th e startle stim ulus. In this case, th e prepulse inhibits th e strength o f the startle response. B y vary in g th e am plitude o f the prepulse stim ulus, one can obtain an inhibition curve w h ere th e degree o f suppression o f th e startle response increases as the m agnitude o f th e prepulse signal is increased.
Test and Control Articles:
O n e te s t a rtic le w a s e m p lo y e d to e lic it c h a n g e s in th e a u d ito ry s ta rtle re s p o n s e , 3 '- 3 ' Im inodipropionitrile (ID P N ; A ldrich, M ilw aukee, W I, lot no. 90906A T ). Physiological salin e (B ax ter H ealth care C o rporation, D eerfield , IL ) w as u sed as th e v eh icle control.
Page 1 of 24
-1962-
W IL -99144
Test System:
Ju v en ile (ap p ro x im ately 4-5 w eek s old) S prag u e-D aw ley C rl:C D (SD )IG S B R rats w eig h in g ap p ro x im ately 154 g (m ales) an d 129 g (fem ales) at ran d o m izatio n w ere u sed in th is study. T he rats w ere assigned to three treatm ent groups using a com puter-based random ization p rocedure w h ich ensures hom ogeneity o f group m ean s and variances fo r body w eight. E ight m ale and eight fem ale rats w ill b e ran d o m ized into each study group. F ollo w in g the group random ization procedure, th e 8 rats/sex/group w ere ran d o m ized into study replicates as d escribed in W IL S tandard O perating P rocedure N o. T 1-126 (as revised). E ach dose group and sex w ere equally rep resen ted in each study replicate to avoid th e introduction o f bias into the reco rd ed observations related to these variables.
Environmental Conditions:
W eanling anim als w ere housed three p e r cage, b y sex in suspended w ire-m esh cages in an environm entally controlled room , fo r approxim ately three days fo llo w in g receipt. T hereafter, all anim als w ere ho u sed individually. T he anim als w ere ho u sed and m aintained un d er conditions consistent w ith m aintaining good h ealth and as p er W IL standard operating procedures. T em perature and relative hum idity at approxim ately w ere m aintain at 72 4F and 3 0 -7 0 % , resp ectiv ely in a ro o m w ith a 12 h o u r lig h t/d ark p h o to p erio d (6 a.m . to 6 p.m .). T em perature and relative hum idity w ill b e recorded once p er day. The facilities at W IL R esearch L aboratories, Inc. are fully accred ited b y th e A sso ciatio n fo r A ssessm en t and A ccreditation o f L aboratory A nim al C are International (A A A L A C International).
Treatment Regimen:
A n im als w ere assigned to treatm ent groups as follow s:
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
8 8 8
Females
8 8 8
T he test and control articles w ere adm inistered by intraperitoneal injection (ip) fo r three co n se cu tiv e days. In d iv id u al d o se s w e re calcu lated b a se d u p o n th e an im al's b o d y w e ig h t tak e n ju st before adm inistration o f th e test article.
Startle Response Assessment:
A ll startle resp o n se m easu rem en ts w ere m ad e u sin g th e S R -L ab S tartle R esp o n se S ystem (S an D iego Instrum ents, San D iego, C A ). T he apparatus consisted o f a slotted acrylic c y lin d er (6" lo n g b y 2 .25" in d iam eter) m o u n ted in a h o rizo n tal o rien tatio n o n a p latfo rm and
Page 2 of 24
-1963-
WIL-99144
enclosed in a sound-attenuating cham ber. A piezoelectric force tran sd u cer is m o unted on the u n d er side o f th e platform .
W h en an anim al placed inside th e cylinder reacts to the startle stim ulus, the m ovem ent produces a deflection o f the platform , w hich induces a voltage change in the piezoelectric force transducer. T his voltage signal is am plified and converted to a digital signal fo r a n a ly s is . S t a r tl e r e s p o n s e m e a s u r e s o b t a i n e d a r e m a x i m u m r e s p o n s e a m p l i tu d e ( V max), l a t e n c y o r t i m e t o V max ( T max) a n d a v e r a g e r e s p o n s e a m p l i tu d e ( V ave).
S tartle response evaluations w ere p erform ed in a sound-attenuated room equipped w ith a w hite-noise generator set to operate at approxim ately 70 db. T he transducers w ere calibrated to provide the correct average output and sound checks w ere p erform ed on the cham ber and ro o m w hite no ise generators p rio r to d ata collection. T esting w as controlled and d ata are cap tured/converted v ia a local PC (486D X 2 o r better). D ata w ere tran sferred to the m ainfram e com puter system fo r subsequent p resentation and evaluation.
A. Habituation of the Acoustic Startle Response:
H a b i tu a t io n o f t h e a c o u s tic s ta r tle r e s p o n s e w a s e v a l u a t e d f o r a ll a n im a ls f o u r a n d 11 days fo llo w in g dose adm inistration u sin g an autom ated startle response-m easuring device (S R -L A B S tartle R esponse System , San D iego Instrum ents, San D iego, CA). T he test session consisted o f a five-m inute acclim ation period w ith a 65-db b ro ad b an d back g ro u n d w hite noise. T he startle stim ulus fo r each trial w as a 115-db, m ix ed frequency n oise b u rst stim ulus (20 m s in duration). R esponses w ere recorded d u rin g th e first 100 m s fo llo w in g startle signal o n set fo r each trial. T he test session consisted o f 50 trials w ith an eight-second inter-trial-interval. S tartle response data w a s a n a l y z e d i n f i v e b l o c k s o f 10 t r ia l s e a c h p l u s a ll 5 0 t r ia ls c o m b i n e d .1,2
B. Prepulse Inhibition of the Acoustic Startle Response:
P rep u lse inhibition o f th e acoustic startle resp o n se w as ev aluated fo r all anim als 12 days fo llo w in g dose adm inistration. P repulse trials w ere identical to habituation trials except th at th e prepulse trial startle signal w as preced ed by a less intense, but otherw ise identical signal o f 20-m s in duration (m easured fro m prepulse signal onset to startle signal onset). F iv e prepulse intensities w ere u sed (70-, 75-, 80-, 85- and 90-db). T hese five, plus no-prepulse trials, constituted th e six trial types. E ach trial type w as p resen ted eight tim es fo r a total o f 48 trials. T rial o rd er fo r prep u lse trials w as b alanced u sing a L atin-square design w ith th e p rovision th at the first trial w as a n o - p r e p u l s e t r ia l .1,2 P r e p u l s e in h ib i t io n r e s p o n s e w a s a n a l y z e d i n s ix t r ia l b l o c k s b y p repulse intensity (0-, 70-, 75-, 80-, 85- and 90-db).
Page 3 of 24
-1964-
W IL -99144
Statistical Methods:
Startle R esponse activity data w as analyzed u sin g a tw o-w ay rep eated m easure analysis o f variance w ith trial as th e w ithin-subject factor. Significant (p< 0.05) treatm ent o r treatm ent-tim e interactions w ere subjected to a one-w ay A N O V A at each tim e-point. S ignificant treatm ent effects at a g iv en tim e -p o in t w e re th e n su b jected to D u n n ett's te st to d eterm in e sig n ifican t treatm ent differences fro m the control group.
Quality Assurance:
T he raw d ata and d raft rep o rt w ill b e audited by th e W IL Q uality A ssurance U n it p rio r to assure th at th e final rep o rt accurately describes th e co n d u ct and the findings o f the study.
Results:
G r o u p m e a n v a lu e s o f V max, T max a n d V ave f o r A c o u s t i c S ta r tle I n h ib itio n , f o u r d a y s a f te r term in atio n o f dosing, are p re sen te d b y sex an d in terv al in F ig u res 1-6. G ro u p m e a n v a lu e s o f V max, T max a n d V ave f o r A c o u s t i c S ta r tle I n h ib itio n , 11 d a y s a f te r t e r m i n a t io n o f d o s in g , a re p r e s e n t e d b y s e x a n d i n te r v a l i n F i g u r e s 7 -1 2 . G r o u p m e a n v a lu e s o f V max, T max a n d V ave f o r P re-pulse Inhibition o f the A coustic S tartle Inhibition, 12 days after term ination o f dosing, are p resen ted by sex an d interval in F ig u res 13-18.
A. Habituation of the Acoustic Startle Response:
H ab itu atio n o f th e acoustic startle resp o n se w a s d em o n strated fo r all 400 m g /k g tre a te d a n im a ls f o u r a n d 11 d a y s fo llo w in g te rm in a tio n o f d o s e a d m in istra tio n . A t th e f o u r d a y p o s t-d o s e in te rv a l, Vmax in th e m a le 4 0 0 m g /k g d o s e g ro u p w a s d e c r e a s e d b y 7 1 1 - 9 9 4 % a c r o s s a ll t r ia l b l o c k s a n d V ave w a s d e c r e a s e d b y 6 4 7 1 0 5 4 % a c r o s s a ll tr ia l b lo c k s . T max w a s i n c r e a s e d i n t h e 4 0 0 m g /k g d o s e g r o u p b y 57-68% across all trial blocks. S im ilar effects w ere o b served in th e m ale 400 m g/kg d o s e g ro u p 11 d a y s a fte r te rm in a tio n o f d o sin g . T h e re w e re n o a p p a re n t d iffe re n c e s b e tw e e n th e 2 0 0 m g /k g d o s e g ro u p a n d th e c o n tro l in a n y e n d p o in t f o u r o r 11 d a y s after term ination o f dosing.
I n f e m a le s , Vmax i n th e 4 0 0 m g /k g d o s e g r o u p w a s d e c r e a s e d b y 7 2 - 2 4 7 % a c r o s s a ll t r ia l b l o c k s a n d Vave w a s d e c r e a s e d b y 7 4 - 2 8 2 % a c r o s s a ll tr ia l b lo c k s . Tmax w a s increased in th e 400 m g/kg dose group by 75-100% across all trial blocks. Sim ilar e ffe c ts w e re o b s e rv e d in th e m a le 4 0 0 m g /k g d o se g ro u p 11 d a y s a fte r te rm in a tio n o f dosing. T here w ere no apparent differences b etw een th e 200 m g/kg dose group and th e c o n tro l in an y e n d p o in t f o u r o r 11 d a y s a fte r te rm in a tio n o f d o sin g .
Page 4 of 24
-1965-
WIL-99144 B. Prepulse Inhibition of the Acoustic Startle Response:
P rep u lse in h ib itio n o f th e aco u stic startle resp o n se w as d em o n strated fo r all anim als 12 d a y s f o l lo w in g d o s e a d m in is tr a tio n . I n t h e c o n tr o l a n d 2 0 0 m g /k g g r o u p s , V max a n d V ave i n b o t h m a l e a n d f e m a le s d e c r e a s e d w i t h in c r e a s in g p r e p u ls e s tim u lu s ( F ig u r e s 1 3 -1 4 , 1 7 -1 8 ). T h e r e w a s n o a p p a r e n t c h a n g e i n t h e V max o r V ave r e s p o n s e in the 400 m g/kg dose group in response to increasing prepulse stim ulus (Figures 1 5 -1 6 ). V max o r V ave w a s i n c r e a s e d in m a l e s o f t h e 4 0 0 m g /k g d o s e g r o u p o v e r 0 -, 7 0 - a n d 7 5 - d b c o m p a r e d t o t h e c o n tr o l g r o u p , w h i l e T max w a s s i m il a r i n a ll f e m a le groups across th e ran g e o f prep u lse stim uli.
Discussion:
T he d ata in d icate th at th e S R -L A B S tartle R esp o n se System is capable o f detecting test articlein d u c e d c h a n g e s in c h a n g e s i n t h e V max, V ave a n d T max o f th e a c o u s tic s ta r tle r e s p o n s e . T h e ability to d etect prepulse inhibition o f th e acoustic startle response w as dem onstrated in the control and 2 0 0 m g /k g dose group. T he inability o f th e 4 0 0 m g /k g dose group to resp o n d to the prepulse inhibition o f th e acoustic startle response indicates th at th e S R -L A B S tartle R esponse System is capable o f detecting test article-induced changes in prepulse inhibition.
References:
1. C Y P 2 D 1 p o l y m o r p h i s m i n m e th a m p h e ta m in e - t r e a te d ra ts : G e n e tic d if f e r e n c e s in n e o n a ta l m ortality an d effects o n spatial learn in g and acoustic startle. (1998) V orhees, C .V ., R eed, T .M ., S chilling, M .A ., F isher, J.E ., M oran, M .S ., C appon, G .D ., N eb ert, D .W . N eu ro to x . T eratol. 20:265-273.
2. M ethods fo r d etecting long-term C N S d ysfunction after pren atal exposure to n eu ro to x in s. (1997) D ru g and C hem . T oxicol. 20:387-399.
Page 5 of 24
WIL-99144
Figure 1. Graphic Depiction of the Acoustic Startle and Prepulse Inhibition Responses. Startle Habituation
T rial 1,T rial 2,T rial 3, e tc...
-1966-
P repulse Stim ulus
, e t c ..
cStartle stimulus-----
Prepulse Inhibition
---------------
--------
------^ ---------------------- C
>
> <>
>
Startle Response
Page 6 of 24
WIL-99144 Figure 2. Male Startle Habituation (Vmax) Four Days Following Termination of Dosing
-1967-
275 250 225 200 175 150
xro
> 125
100 75 50 25 0
Trial 1-50
Trial 1-10
Trial 11-20
Trial 21-30
Page 7 of 24
Trial 31-40
Trial 41-50
WIL-99144 Figure 3. Female Startle Habituation (Vmax) Four Days Following Termination of Dosing
-1968-
Trial 1-50
Trial 1-10
Trial 11-20
Trial 21-30
Page 8 of 24
Trial 31-40
Trial 41-50
WIL-99144
Tmax (mSec)
-1969-
Figure 4. Male Startle Habituation (Tmax) Four Days Following Termination of Dosing
0 mg/kg/day
IH200 mg/kg/day
IH400 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
Trial 41-50
Trial 1-50
Page 9 of 24
WIL-99144 Figure 5. Female Startle Habituation (Tmax) Four Days Following Termination of Dosing
Tmax (mSec)
-1970-
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
IH200 mg/kg/day
IH400 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
-1973-
300
275
250
225
200
I 75
E. 150
ra E > 125
100
75
50
25
0
Trial 1-50
Trial 1-10
Trial 11-20
Trial 21-30
Page 13 of 24
Trial 31-40
Trial 41-50
WIL-99144
Figure 9. Female Startle Habituation (Vmax) 11 Days Following Termination of Dosing
Control
IH200 mg/kg
IH400 mg/kg
-1974-
Trial 1-50
Trial 1-10
Trial 11-20 P age 14 o f 24
Trial 21-30
Trial 31-40
Trial 41-50
WIL-99144
Figure 10. Male Startle Habituation (Tmax) 11 Days Following Termination of Dosing
0 mg/kg/day
ITi2QQ mg/kg/day
IH400 mg/kg/day
Tmax (mSec)
-1975-
Page 15 of 24
WIL-99144
Tmax (mSec)
-1976-
Figure 11. Female Startle Habituation (Tmax) 11 Days Following Termination of Dosing 0 mg/kg/day IH200 mg/kg/day IH400 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
Vaverage (mV)
-1977-
WIL-99144 Figure 12. Male Startle Habituation (Vave) 11 Days Following Termination of Dosing 0 mg/kg/day IH200 mg/kg/day IH400 mg/kg/day
Page 17 of 24
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 40.0 30.0 20.0 10.0
Vaverage (mV)
-1978-
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
Figure 15. Female Prepulse Inhibition (Vmax) of the Acoustic Startle Response 12 Days Following Termination of Dosing
0 mg/kg/day IH200 mg/kg/day IH400 mg/kg/day
180.0
160.0
140.0
120.0
100.0
80.0
60.0
40.0
20.0
0.0
0 db
70 db
75 db
80 db
Page 20 of 24
85 db
90db
WIL-99144
Figure 16. Male Pre-pulse Inhibition (Tmax) of the Acoustic Startle Response 12 Days Following Termination of Dosing
0 mg/kg/day IH200 mg/kg/day IH400 mg/kg/day 60.0
Tmax (mSec)
-1981-
50.0 40.0 30.0 20.0 10.0
0 .0
0 db
70 db
75 db
80 db
o p u s e s * iomu24s (db)
85 db
90db
WIL-99144
Figure 17. Female Pre-pulse Inhibition (Tmax) of the Acoustic Startle Response 12 Days Following Termination of Dosing
Tmax (mSec)
-1982-
0 db
70 db
75 db
80 db
85 db
90db
Pre-pulse stimulus (db)
Page 22 of 24
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 IH200 mg/kg/day IH400 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 IH200 mg/kg/day IH400 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
D ate R ange: M ay 17-21, 1999
D em onstration o f th e S ensitivity o f th e S D I-P A S to D etect A lterations in L ocom otor A ctivity in R ats
Study O bjective:
R egulatory guidelines require that the testing laboratory dem onstrate that the devices and system s u sed fo r m easu rin g locom otor activity be able to detect chem icallyin d u ced in creases and d ecreases in lo co m o to r activity. T he o b jectiv e o f th is study w as to dem onstrate th at th e locom otor activity m easu rin g apparatus (S an D iego Instrum ents - P h o to b eam A ctivity S ystem [S D I-P A S ]) and the testin g p arad ig m used by W IL R esearch L ab o rato ries, In c., m et th is criterion.
T est A nd C ontrol A rticles:
T w o test articles w ere em ployed, one to elicit increases in m o to r activity (d -am p h etam in e sulfate, R esearch B io ch em icals In tern atio n al, N atick , M A , L ot. N o. B S -1 11-100) and one to elicit decreases in m o to r activity (chlorprom azine h y d ro c h lo rid e , S ig m a C h e m ic al C o m p an y , St. L o u is, M O , L o t N o. 4 8 H 1403). P hysiological saline w as u sed as th e vehicle and fo r treatm ent o f th e concurrent n egative control group.
T est System :
Ju v en ile (ap p ro x im ately six -w eek o ld) S p rag u e-D aw ley C rl:C D (SD )IG S B R rats w eighing 175 + 27 gram s (m ales) and 146 + 20 gram s (fem ales) at the tim e o f random ization w ere u sed on the study. T he rats w ere random ly assigned to treatm ent groups by b ody w eig h t stratification in a b lock design, and subsequently allocated to group- and sex-uniform replicates fo r the locom otor activity evaluations. D o sin g and lo co m o to r activity ev alu atio n s o ccu rred o n th e day after ran d o m izatio n (D ay 0).
E n v iro n m en tal C onditions:
T h e ra ts w e re a cc lim ate d to la b o ra to ry co n d itio n s fo r 13 d a y s p rio r to do sin g . A nim als w ere housed and m aintained u n d er conditions consistent w ith m aintaining good health and as p er W IL S tandard O perating Procedures. T em perature and hum idity w ere m aintained at 72 + 4 F and 50 + 20% , respectively, in a room w ith a 12 h o u rs light/12 h o u rs d ark (0 6 0 0 -1 8 0 0 h rs) photo p erio d . T he facilities at W IL R esearch L aboratories, Inc. are fu lly accredited by th e A sso ciatio n fo r A ssessm en t and A ccred itatio n o f L aboratory A nim al C are International.
-1986-
W IL-99149 T reatm ent R egim en:
A nim als w ere assigned to treatm en t groups as follow s:
G roup N um ber
T est A rticle
D osage Level
(m g/kg)
D osage C oncentration
(m g/m l)
D osage V olum e (m g/kg)
Num ber of
A nim als
M ale
Fem ale
1 PS
0
2 AMP 2
3 AMP 4
4 CPZ 5
5 C PZ 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
T he test and control articles w ere adm inistered as a single intraperitoneal injection (D ay 0). Individual d oses w ere calcu lated b ased on th e anim als' b o d y w eig h ts recorded on the day o f dose adm inistration.
L ocom otor A ctivity M onitoring M ethods:
L o co m o to r activity w as m o nitored once 4-5 days p rio r to dose adm inistration (pretest) and o n th e day o f dose adm inistration. T he d uration o f each test session w as 60 m inutes. T he test interval w as five m inutes. M o n ito rin g fo llo w in g dosing co m m en ced 15 m in u tes after test o r co n tro l article adm inistration. T he d u ratio n o f the test session and len gth o f the test interval w ere selected b ased o n results o f a previous study (W IL -99140).
L o co m o to r activity m o n ito rin g w as p erfo rm ed u sin g the S D I P h otobeam A ctivity S ystem (S an D iego In stru m en ts, Inc., S an D ieg o , C A ), w h ich includes P hotobeam A ctivity S ystem (P A S ) softw are, analyzer and 24 activity m onitors. A local personal c o m p u te r lin k e d to th e lab o ra to ry 's m ain fram e c o m p u te r co n tro ls th e S D I-P A S .
E ach locom otor activity m o n ito rin g u n it consists o f seven pho to b eam em itting/detecting units attached to a m o u n tin g fram e. A clear acrylic shoe b o x -style cage (18.5"L x 9.5"W x 8"H ) fits into th e m o u n tin g fram e to co n tain a single anim al d u ring th e test session. A ctiv ity is m easu red as in terru p tio n s o f th e p h otobeam s.
P hotobeam diagnostic checks w ere perfo rm ed p rio r to and follow ing com pletion o f the test session. C o n firm atio n th at th e so ftw are-d riv en p ro ced u re w as o p eratin g correctly w as o btained by m anually b lo ck in g the ph o to b eam s w ith p re-cu t p ieces o f cardboard o r o th er appropriate devices. A fter com pletion o f the test session, m otor
-1987-
WIL-99149
activity and p hotobeam files are tran sferred electronically to the m ain fram e com puter fo r su b seq u en t m an ip u latio n an d p resen tatio n o f th e co llected in fo rm atio n , i.e., g eneration o f tables, in cluding statistical analysis.
A ctivity counts are presented as T otal A ctivity C ounts (am bulatory plus stereotypic counts) and A m bulatory A ctivity C ounts. S equential interruption o f 2 o r m ore p hotobeam s, i.e., g ro ss m o to r m o v em en t, is reco rd ed as one am b u lato ry activity count. R ep eated b e am b reak s o f th e sam e p h o to b eam , i.e., fin e m o to r m o v em en t, is reco rd ed as one stereo ty p ic count.
M onitoring w as p erform ed in a sound-attenuated room equipped w ith a w hite-noise generator set to operate at approxim ately 70 db.
S tatisical A nalysis:
L ocom otor activity data w ere analyzed by analysis o f variance. A one-w ay A N O V A fo llo w ed b y D u n n e tt's te st w a s co n d u cted to d eterm in e sig n ifican t trea tm e n t d ifferen ces fro m th e co n tro l group at sig n ifican ce lev els o f p < 0.05 and p < 0.01.
Q uality A ssurance:
T he raw d ata and d raft rep o rt w ere audited by th e W IL Q uality A ssurance U n it to assure th at th e fin al rep o rt accu rately d escrib es th e co n d u ct and fin d in g s o f th e study.
R esults:
G ro u p m e a n lo c o m o to r a c tiv ity c o u n ts a re p r e s e n te d in T a b le 1. T h e d a ta a re p re se n te d g ra p h ic ally b y sex, in te rv al an d a c tiv ity ty p e in F ig u re s 1-8.
D iscussion:
T here w ere no differences in eith er total o r am bulatory activity counts fo r eith er sex during the pretest evaluations.
D o se-dependent increases in b o th total and am bulatory activity counts w ere observed fo r b o th m ales and fem ales fo llo w in g adm inistration o f d -am phetam ine sulfate (A M P). F o r m ales, over the entire 60-m inute test session, total (am bulatory) counts w ere increased 103 (135)% at 2 m g /k g A M P and 166 (193)% at 4 m g/kg A M P. F or fem ales, o v er th e entire 60-m inute test session, total (am bulatory) activity counts w ere increased 37 (46)% at 2 m g /k g A M P and 146 (184)% at 4 m g /k g A M P. W ith th e ex cep tio n o f th e 2 m g /k g A M P fem ales, all d ifferen ces fro m th e v eh icle co n tro l group w ere statistically sig n ifican t (p < 0.01).
-1988-
W IL-99149
D o se-dependent decreases in b o th total and am bulatory activity counts w ere observed fo r bo th m ales and fem ales follow ing adm inistration o f chlorprom azine hydrochloride (C PZ). F o r m ales, o v er the entire 60-m inute test session, total (am bulatory) counts w ere decreased 77 (85)% at 5 m g/kg C PZ and 96 (98)% at 10 m g/kg CPZ. F or fem ales, o v er th e entire 60-m inute test session, total (am bulatory) activity counts w ere decreased 88 (92)% at 5 m g/kg C PZ and 97 (99)% at 10 m g /k g CPZ. A ll d ifferen ces fro m th e v eh ic le co n tro l group w ere statistically sig n ifican t (p < 0.01).
B ased on th e resu lts obtained, the S D I-P A S is sufficiently sensitive to detect doserelated increases and decreases in locom otor activity u n d er th e testing p arad ig m that w as 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
GROUP:
0 MG/KG
.... M A L E
2 MG/KG AMP
4 MG/KG AMP
5 MG/KG CPZ
10 MG/KG CPZ
PRETEST TOTAL MEAN S.D. N AMBULATORY MEAN S.D. N
DAY 0 TOTAL MEAN S.D. N AMBULATORY MEAN S.D. N
1019. 398.2
12
309. 139.5
12
794. 293.6
12
234. 114.9
12
934. 447.5
12
281. 177.0
12
1609.** 655.8
12
549.** 254.8
12
1246. 735.0
12
391. 280.9
12
2110.** 638.9
12
686.** 330.0
12
1163. 377.1
12
376. 154.3
12
184.** 195.6
12
34.** 71.3
12
1221. 444.6
12
366. 194.8
12
33.** 25.6
12
5.** 6.0
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
GROUP:
0 MG/KG
.... F E M A L E
2 MG/KG AMP
4 MG/KG AMP
5 MG/KG CPZ
10 MG/KG CPZ
PRETEST TOTAL MEAN S.D. N AMBULATORY MEAN S.D. N
DAY 0 TOTAL MEAN S.D. N AMBULATORY MEAN S.D. N
1033. 463.6
12
357. 193.8
12
1223. 676.1
12
442. 251.0
12
1190. 543.2
12
399. 204.5
12
1672. 759.8
12
646. 348.5
12
974. 343.2
12
312. 128.3
12
3005.** 773.4
12
1255.** 451.5
12
853. 231.6
12
277. 105.3
12
142.** 116.9
12
36.** 39.5
12
1347. 695.0
12
480. 309.4
12
31.** 45.4
12
4.** 5.2
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-
M ean A c iv ity C o u n t
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-
WIL-99149
450 400 350 300 >1 250 > o < 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-
M ean A c tiv ity C o unt
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-
WIL-99149
600
500
400
>i
I 300
o <
C (5 <D
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
Figure 5
Male Day 0 Total Activity
Mean Activity Count
-1995-
Treatment = Significantly different from control group 1 at 0.01 using Dunnett's test
Page 1
WIL-99149
Figure 6
Male Day 0 Ambulatory Activity
Mean Activity Count
-1996-
Treatment = Significantly different from control group 1 at 0.01 using Dunnett's test
Page 1
WIL-99149
Figure 7
Female Day 0 Total Activity
Mean Activity Count
-1997-
Treatment = Significantly different from control group 1 at 0.01 using Dunnett's test
Page 1
WIL-99149
Figure 8
Female Day 0 Ambulatory Activity
Mean Activity Count
-1998-
Treatment = Significantly different from control group 1 at 0.01 using Dunnett's test
Page 1
-1999-
WIL-99168
A STUDY WITH UNTREATED STOCK RATS TO EXPAND THE WIL DEVELOPMENTAL NEUROTOXICITY HISTORICAL CONTROL DATABASE
Study Objective:
T he objective o f th is study w as to generate historical control data fo r developm ental n e u ro to x ic ity stu d ie s fo c u s in g o n p o s tn a ta l d a y 11 ra t b ra in m o rp h o m e trie s , lo c o m o to r activity and acoustic startle response. T his d raft rep o rt includes th e acoustic startle response d ata collected fro m th e SR L ab Startle R esponse S ystem (S an D iego Instrum ents, San D iego, C A ) and brain m orphom etry.
Test and Control Articles:
N o test o r control article w as em ployed to elicit changes in the auditory startle response as th is study is d e sig n ed to p ro d u c e h isto rical co n tro l data.
Test System:
T en m ale and ten fem ale neonatal (20 day old) rats w eighing 47 + 9 gram s (m ales) and 40 +
10 g r a m s ( f e m a le s ) a t t h e t i m e o f t h e s t a r tl e r e s p o n s e e v a l u a t i o n s w e r e u s e d o n t h e s tu d y .
T he neonates w ere b orn o f dam s bred at W IL R esearch L aboratories, In c. usin g standard p ro ced u res. T he p aren tal an im als w ere S prag u e-D aw ley C rl:C D (S D )IG S B R strain rats. T w o neonates p e r sex w ere selected from the litters o f five different dam s based on health and apparent norm al developm ent.
Environmental Conditions:
T he anim als w ere ho u sed and m aintained u n d er conditions consistent w ith m aintaining good h ealth and as p er W IL standard operating procedures. T em perature and relative hum idity at approxim ately w ere m aintain at 72 4F and 30-70% , respectively in a ro o m w ith a 12 h our lig h t/d ark p h o to p erio d (6 a.m . to 6 p.m .). T em p eratu re an d relativ e h u m id ity w ill b e reco rd ed once p er day. T he facilities at W IL R esearch L aboratories, Inc. are fully accredited by the A ssociation fo r A ssessm ent and A ccreditation of L aboratory A n im al C are International (A A A L A C International).
Viability Observations:
T he rats w ere o b serv ed fo r m o rtality/m oribundity and general condition tw ice daily, in the m o rn in g and in th e afternoon.
Page 1 of 19
-2000-
W IL -99168
Body Weights:
B ody w eights w ere reco rd ed on P N D 17, P N D 20 (the day o f evaluation) and P N D 21.
Startle Response Assessment:
A ll startle resp o n se m easu rem en ts w ere m ad e u sin g th e S R -L ab S tartle R esp o n se S ystem (S an D iego Instrum ents, San D iego, C A ). T he apparatus consisted o f a slotted acrylic c y lin d er (6" lo n g b y 2.25" in diam eter) m o u n te d in a h o rizo n tal o rien tatio n o n a p latfo rm and enclosed in a sound-attenuating cham ber. A piezoelectric force tran sd u cer is m o unted on the u n d er side o f th e platform .
W h en an anim al placed inside th e cylinder reacts to the startle stim ulus, the m ovem ent produces a deflection o f the platform , w hich induces a voltage change in the piezoelectric force transducer. T his voltage signal is am plified and converted to a digital signal fo r a n a ly s is . S t a r tl e r e s p o n s e m e a s u r e s o b t a i n e d a r e m a x i m u m r e s p o n s e a m p l i tu d e ( V max), l a t e n c y o r t i m e t o V max ( T max) a n d a v e r a g e r e s p o n s e a m p l i tu d e ( V ave).
S tartle response evaluations w ere p erform ed in a sound-attenuated room equipped w ith a w hite-noise generator set to operate at approxim ately 70 db. T he transducers w ere calibrated to provide the correct average output and sound checks w ere p erform ed on the cham ber and ro o m w hite no ise generators p rio r to d ata collection. T esting w as controlled and d ata are cap tured/converted v ia a local PC (486D X 2 o r better). D ata w ere tran sferred to the m ainfram e com puter system fo r subsequent p resen tatio n and evaluation.
A. Habituation of the Acoustic Startle Response:
H abituation o f the acoustic startle response w as evaluated fo r tw o rats/sex from five different litters (N =10). T he test session consisted o f a 5-m inute acclim ation period w ith a 65-db broadband b ackground w hite noise. T he startle stim ulus fo r each trial w as a 1 15-db, m ix ed frequency n oise b u rst stim ulus (20 m s in duration). R esponses w e re reco rd ed d u rin g th e first 100 m s fo llo w in g startle signal o n set fo r each trial. T he test session consisted o f 50 trials w ith an eight-second inter-trial-interval. S tartle re sp o n se d a ta w a s an aly zed in fiv e b lo ck s o f 10 tria ls e ach p lu s all 50 trial c o m b i n e d .1,2
B. Prepulse Inhibition of the Acoustic Startle Response:
P rep u lse inhibition o f th e acoustic startle resp o n se w as ev alu ated fo r all anim als 12 days follow ing dose adm inistration. Prepulse trials w ere identical to habituation trials except th at th e prepulse trial startle signal w as preced ed by a less intense, bu t otherw ise identical signal o f 20-m s in duration (m easured fro m prepulse signal onset to startle signal onset). F iv e prepulse intensities w ere used (70-, 75-, 80-, 85- and 90-db). T hese five, plus no-prepulse trials, constituted th e six trial types. E ach trial
Page 2 of 19
-2001-
WIL-99168
type w as p resen ted eight tim es fo r a total o f 48 trials. T rial o rd er fo r prep u lse trials w as b alanced u sing a L atin-square design w ith th e p rovision th at the first trial w as a n o - p r e p u l s e t r ia l .1'2 P r e p u l s e i n h ib i t io n r e s p o n s e w a s a n a l y z e d i n s ix t r ia l b l o c k s b y p repulse intensity (0-, 70-, 75-, 80-, 85- and 90-db).
Morphometry:
O n postnatal day 11, one pup/sex from six litters w as euthanized b y carbon dioxide inhalation a n d p e rfu s e d in situ. T h e b ra in s w e re p ro c e ss e d fo r m o rp h o m e tric e v a lu a tio n as p e r W IL standard o perating p rocedures (T 4-035, as revised). T en linear m easurem ents (based on th o se o f R o d ier and G ram ann, 1979) w ere m ad e on fo u r coronal sections o f cerebrum and m id b rain and one sagittal section o f cerebellum and brainstem from each pup. Im ages w ere c a p t u r e d u s i n g t h e P a x - I t TM C o m p u t e r S y s te m a s p e r W I L s t a n d a r d o p e r a t i n g p r o c e d u r e s (T 8-005, as revised). T he follo w in g b rain areas w ere m easured:
R1
R2
R3 R4 R5 R6 R7
R8 R9 R10 R34
W idth o f hem isphere, perpendicular to height and adj acent to top o f dorsal w hite m atter tract. H eig h t o f hem isphere, im m ediately adjacent to m edial m arg in o f lateral v e n tric le . V ertical th ick n ess o f the frontoparietal cortex, parallel to h eig h t m easurem ent. W idth o f caudoputtam en o f hem isphere. O n e-h alf the w id th o f th e base o f the forrix. V ertical H eight fro m th e base o f th e b rain to th e anterior com m issure. V ertical th ick n ess o f the frontoparietal cortex m easured at th e highest poin t o f the corpus callosum . R ad ial th ic k n e ss o f th e p arietal c o rtex (ap p ro x im ately 10 o 'clo ck position). T hickness o f the piriform cortex (m easured at surface indentation). T hickness o f th e corpus callosum at th e m idline. H eight o f the cerebellum (highest dim ension), parallel to thickness o f pons,
Quality Assurance:
T he raw d ata and d raft rep o rt w ill b e audited by th e W IL Q uality A ssurance U n it p rio r to assure th at the final rep o rt accurately describes th e co n d u ct and the findings o f the study.
Results:
A. Viability:
N o d eath s o r o v ert signs o f clin ical illn ess o ccu rred o n th e study.
Page 3 of 19
-2002-
WIL-99168 B. Body Weights:
T here w ere no rem arkable differences in body w eight or changes in body w eight g ain (T ab le 1).
C. Habituation:
S t a r t l e r e s p o n s e , a s m e a s u r e d b y V max a n d V ave, d e c r e a s e d o v e r t i m e f o r b o t h m ale s an d fe m a le s (F ig u res 1-6). C o m p a re d to th e in itia l tria ls (tria l b lo c k 1 -10), V max d e c re a s e d 1 4 .9 % , 2 2 .3 % , 2 6 .0% and 2 6 .1% (m ales) and 2 2 .8 % , 32.3% , 34.7% and 50.3% (fem ales) fo r trial blo ck s 11-20, 21-30, 31-40 and 41-50, respectively. C o m p a r e d t o t h e i n i t i a l t r i a l s ( tr ia l b l o c k 1 -1 0 ), V ave w a s d e c r e a s e d 1 2 .1 % , 2 0 .6 % , 2 3 .1% and 2 2 .2% (m ales) and 17.7% , 26.5% , 30.4% and 4 4 .0% (fem ales) fo r trial blo ck s 11-20, 21-30, 31-40 and 41-50, respectively. N o e ffe c t o n Tmax w a s a p p a re n t f o r e ith e r sex.
D. Prepulse Inhibition:
S ta r tle re s p o n s e , a s m e a s u r e d b y V max a n d V ave, d e c r e a s e d w ith in c r e a s in g prepulse signal intensity fo r b o th m ales and fem ales (F igures 7-12). C o m p a re d to th e n o -p re p u ls e tria ls, V max w a s d e c re a s e d 7 .8 % , 1 5 .0 % , 3 2 .5 % , 38.5% and 54.4% (m ales) and 3.1% , 8.0% , 18.5% , 38.3% and 55.1% (fem ales) fo r th e 70-, 75-, 80-, 85- and 90-decibel prepulse signal intensities, respectively. C o m p a r e d t o t h e n o - p r e p u l s e t r ia l s , V ave w a s d e c r e a s e d 1 2 .3 % , 1 6 .6 % , 3 2 .8 % , 39.0% and 50.4% (m ales) and 5.7% , 10.1% , 2 2 .7 % , 4 0 .3 % and 56.4% (fem ales) fo r th e 70-, 75-, 80-, 85- and 90-decibel prepulse signal intensities, respectively. N o e ffe c t o n Tmax w a s a p p a re n t f o r e ith e r sex.
E. Morphometry:
A ll m easu rem en ts p ro v id ed ro b u st m easu rem en ts (T able 2). M easu rem en ts w ere repeatable across hem ispheres (data n o t show n).
Page 4 of 19
-2003-
WIL-99168 Discussion:
T he expected hab itu atio n over tim e to rep eated auditory stim uli o f the sam e intensity w as observed, as w as the expected d ecrease in auditory startle response associated w ith in creasin g prep u lse signal intensity. B o th Vmax a n d Vave d a ta sh o w e d c le a r tim e - (h a b itu a tio n ) o r s ig n a l- (p re p u ls e in h ib itio n ) related decreases in startle response. T he results o f this investigation dem onstrate that the equipm ent and testin g paradigm s used are cap ab le o f d e te ctin g ch an g e s in startle re sp o n se in y o u n g (P N D 20) rats.
References:
1. C Y P 2 D 1 p o l y m o r p h i s m i n m e th a m p h e ta m in e - t r e a te d ra ts : G e n e tic d if f e r e n c e s i n n e o n a ta l m ortality an d effects on spatial learn in g and acoustic startle. (1998) V orhees, C .V ., R eed, T .M ., S chilling, M .A ., F isher, J.E ., M oran, M .S ., C appon, G .D ., N ebert, D .W . N eu ro to x . T eratol. 20:265-273.
2. M ethods fo r d etecting long-term C N S d ysfunction after prenatal exposure to neurotoxins. (1997) D ru g and C hem . T oxicol. 20:387-399.
Page 5 of 19
-2004-
WIL-99168
Table 1. Individual Body Weights.
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
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
-2006-
WIL-99168 Figure 1: Habituation to Acoustic Startle Response (Vmax) in Untreated PND 20 Male Rats
Trials 1-10 Trials 11-20 Trials 21-30 Trials 31-40 Trials 41-50 Trials 1-50
Trial Blocks
Page 8 of 19
-2007-
WIL-99168 Figure 2: Habituation to Acoustic Startle Response (Vmax) in Untreated PND 20 Female Rats
Trials 1-10 Trials 11-20 DTrials 21-30 DTrials 31-40 DTrials 41-50 DTrials 1-50
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
Trials 11-20
Trials 21-30
Trials 31-40
Trials 41-50
Trials 1-50
-2008-
Trial Blocks
Page 10 of 19
Tmax (mSec)
-2009-
WIL-99168 Figure 4: Habituation to Acoustic Startle Response (Tmax) in PND 20 Female Rats
Trials 1-10 Trials 11-20 Trials 21-30 Trials 31-40 Trials 41-50 Trials 1-50
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
Trials 11-20
Trials 21-30
Trials 31-40 DTriais 41-50
Trials 1-50
-2010-
Trial Blocks
Page 12 of 19
-2011-
WIL-99168 Figure 6: Habituation to Acoustic Startle Response (Vave) in Untreated PND 20 Female Rats
Trials 1-10 Trials 11-20 DTrials 21-30 DTrials 31-40 DTrials 41-50 DTrials 1-50
Trial Blocks
Page 13 of 19
WIL-99168
Figure 7: Prepulse Inhibition of Acoustic Startle Response (Vmax) in Untreated PND 20 Male Rats
0 dB
70 dB
D75 dB
0 8 0 dB
0 8 5 dB
D90 dB
Vmax (mV]
-zioz-
Prepulse Intensity
Page 14 of 19
WIL-99168
Figure 8: Prepulse Inhibition of Acoustic Startle Response (Vmax) in Untreated PND 20 Female Rats
0 dB
D70 dB
D75 dB
0 8 0 dB
0 8 5 dB
D90 dB
Vmax (mV]
-2013-
Prepulse Intensity
Page 15 of 19
WIL-99168
Figure 9: Prepulse Inhibition of Acoustic Startle Response (Tmax) in Untreated PND 20 Male Rats
0 dB
D70 dB
D75 dB
0 8 0 dB
0 8 5 dB
D90 dB
Tmax (mSec)
-2014-
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
D7Q dB
D75 dB
0 8 0 dB
D85 dB
D90 dB
Tmax (mSec]
-2015-
Prepulse Intensity
Page 17 of 19
WIL-99168
Figure 11: Prepulse Inhibition of Acoustic Startle Response (Vave) in Untreated PND 20 Male Rats
0 dB
70 dB
D75 dB
D80 dB
0 8 5 dB
D90 dB
Vave (mV]
-2016-
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
D75 dB
0 8 0 dB
0 8 5 dB
D90 dB
Vave (mV]
-2017-
Prepulse Intensity
Page 19 of 19
-2018-
Validation Of Developmental Neurotoxicity Endpoints In Rats Administered Methimazole In Drinking Water
G .J. S ch aefer, M .D . N em ec, M .T . H erb erth , J.A . P itt, A .E . R ad o v sk y an d J.F. K n ap p . W IL R esearch L aboratories, Inc., A shland , O H .
T he p u rp o se o f th is study w as to v alid ate p ro ced u res o u tlin ed in th e U .S. E P A O P P T S 870.6300 guideline fo r developm ental neurotoxicity (D N T ) studies. P reg n an t S prague-D aw ley rats (N = 25/group) w ere adm inistered either 0, 10, 30 or 100 pp m m ethim azole (used to treat hum an hyperthyroidism ) in drinking w ater from gestation day 6 through postnatal day (PN D ) 21. E ndpoints evaluated in the dam s included a m odified functional observational battery (m FO B ), body w eights, and fo o d and w ater consum ption. In th e pups, b rain w eights, qualitative neuropathology and quantitative b rain m orphom etry w ere evaluated at P N D 11, 22 and 72. A uditory startle, locom otor activity, learn in g and m em ory (B iel M aze) and m F O B w ere assessed in th e o ffsp rin g rep eated ly th ro u g h o u t th eir dev elo p m en t. D u rin g lactation, th e d am s in all three ex p o su re g roups w eig h ed sig n ifican tly less, an d co n su m ed less fo o d and w a ter th an controls. L o co m o to r a ctiv ity w a s re d u c e d o n P N D 13 an d in c re a se d o n P N D 21 fo r 30 an d 100 p p m o f f s p r in g r e la tiv e to c o n tro ls . A u d ito r y s ta rtle r e s p o n s e e n d p o in ts (Vmax, Tmax a n d Vave) w e r e affected in the 30 and 100 ppm offspring at P N D 20 and 60. P up body w eights w ere reduced fro m P N D 1-70 fo r b o th sexes in all ex p o su re groups relativ e to controls. D e lay e d sexual m atu ratio n (b alan o p rep u tial sep aratio n and v ag in al p aten cy ) w a s read ily ap p aren t in all th ree e x p o s u re g ro u p s , e x c e p t f o r v a g in a l p a te n c y a t 10 p p m . In a d d itio n , o n P N D 11 a n d 2 2 b o th m a le and fem ale offsp rin g m ean brain w eig h ts (100 ppm ) w ere red u ced relative to controls. B rain w eights w ere red u ced on P N D 72 fo r 100 p p m m ale offsp rin g only. N o dam o r offspring exposure-related deficits w ere n o ted in th e m F O B at any tim e point. Q ualitative neuropathology a n d q u a n tita tiv e m o rp h o m e try a t P N D 11 (c o m p a rin g im m e rs io n a n d p e rfu s io n fix a tio n at P N D 11), 2 2 and 72, a lo n g w ith learn in g and m em o ry data, w ill b e p resented. T he d ata an aly zed th u s far are b e in g u sed to assess th e appropriateness o f m ethim azole as a positive control agent fo r D N T studies.
In t r o d u c t io n
In hum ans, hypothyroidism causes irreversible m ental retardation and various neurom otor disabilities. M ethim azole adm inistration to p regnant rats is a com m only u sed experim ental m odel o f hum an congenital hypothyroidism . T he objective o f this study w as to evaluate the sensitivity o f th e ex p erim en tal d esig n d escrib ed b y U .S. E P A O P P t S G u id elin e 8 7 0 .6300 (D evelopm ental N eurotoxicity) to predict the adverse effects in rats o f a know n hum an developm ental neurotoxicant.
Ma t e r ia ls a n d Metho ds
M eth im azo le w as ad m in istered to g roups o f 25 b re d fe m ale C rl:C D (SD ) IG S B R S pragueD aw ley (C harles R iver) at dosage levels o f 0, 10, 30 or 100 ppm in drinking w ater from gestation day 6 through postnatal day (PN D ) 21. O ffspring w ere evaluated by use o f a m odified
-2019-
functional observational battery (P N D 4, 11, 21, 35, 45 and 60) and evaluated fo r m o to r activity (P N D 13, 17, 21 and 61), auditory startle response (P N D 20 and 60) and learn in g and m em ory in the B iel w ater m aze (P N D 22 and 62). Q ualitative n europathology and quantitative m o rp h o m e try e v a lu a tio n s w e re c o n d u c te d at P N D 11 (c o m p a rin g im m e rsio n a n d p e rfu s io n fix atio n at P N D 11), 22 and 72. F o r quantitative m orp h o m etry , 10 m easu rem en ts w ere m ad e on 3 levels. A ll d ata are p resen ted in tab les and fig u res as m ean stan d ard deviation.
Re s u lt s
M a tern a l b o d y w eig h ts, fo o d c o n su m p tio n an d w a te r c o n su m p tio n w e re re d u ce d in all m eth im azo le-treated groups th ro u g h o u t th e en tire lactatio n period.
L ive litter size w as u naffected in any o f the treated groups; how ever, pup viability w as red u ced fro m b irth (P N D 0) to P N D 4 in th e 10 and 100 ppm groups (data n o t show n). P up w eig h ts w ere red u ced at b irth fo r all ex p o su re lev els and rem ain ed red u ced th ro u g h o u t th e study.
M ark ers o f sex u al m atu ratio n w ere d elay ed in all m eth im azo le-treated g roups w ith th e excep tio n o f vaginal patency in the 10 ppm group.
T he m odified functional observational battery detected no differences in dam or offspring fin d in g s w hen com paring the treated groups to th e concurrent control group.
M o to r activity w a s red u ced o n P N D 13 and in creased o n P N D 21 fo r p u p s in th e 30 an d 100 p p m groups. A uditory startle response w as affected fo r both sexes at the 30 and 100 ppm d o sag e lev els o n P N D 20 and 60. S w im m in g ability w as m ark ed ly red u ced fo r b o th sexes at 30 and 100 ppm , and latency to escape the B iel m aze w as increased at the 30 and 100 ppm d o sag e lev els o n P N D 22. O n P N D 62, sw im m in g ab ility w a s co m p arab le b e tw ee n all groups, b u t laten cy to escap e th e B iel m aze w as still in creased fo r b o th sex es at th e 30 and 100 p p m dosage levels. T he m ean n u m b er o f errors com m itted d uring th e sw im m ing trials, h o w ev er, w as co m p arab le am o n g all g roups o n b o th P N D 2 2 and 62.
O n P N D 11 a n d 2 2 b o th m a le a n d fe m a le p u p b ra in w e ig h ts in th e 100 p p m g ro u p w e re red u ced relative to th e control group. O n P N D 72 b rain w eights w ere red u ced fo r 100 ppm m ale pups only, bu t gross b rain lengths w ere red u ced in b oth sexes. C oronal sections o f the cerebrum and a m id-sagittal section o f the cerebellum and brainstem o f the 100 ppm pups h ad sig n ifican tly red u ced m easu rem en ts at all tim e points.
T h ere w e re q u alitativ e h isto p ath o lo g ic ab n o rm alities in th e b ra in s o f 100 p p m p u p s at all tim e p o in ts . O n P N D 11 th e r e w e r e a n in c r e a s e d n u m b e r o f u n d if f e r e n tia te d c e lls u n d e r th e ep endym a o f th e ro o f o f th e lateral ventricle, and a disproportionately short ventral lim b o f the dentate hilus in the hippocam pus in 100 pp m pups o f bo th sexes in both the perfused and im m ersion-fixed groups. O n P N D 22, 100 ppm pups h ad p ersistence o f th e external granule cell layer o f th e cerebellum w h ich h ad disap p eared in control groups at this tim epoint. O n PN D 72, there w ere increased m alalignm ents o f the pyram idal neurons o f the hippocam pus in 100 pp m pups o f b oth sexes and m ales had instances o f abnorm al foliation in cerebellar lo b u le s 8 an d /o r 9.
-2020-
Co n c l u s io n s B a s e d o n th e e n d p o in ts a ffe c te d (e.g., p u p b o d y w e ig h t, lo c o m o to r a c tiv ity , a u d ito ry sta rtle
response, learning and m em ory, b rain w eig h t and length, qualitative and quantitative neuropathology), m ethim azole altered m ultiple functional dom ains in the Fi generation d em onstrating th at th is co m pound is acceptable fo r use as a po sitiv e control agent in D N T studies. B o th im m ersion and perfu sio n fix atio n o f th e P N D i i pup b rains p rovided adequate tissue sam ples fo r quantitative m o rp h o m etrics and qualitative histopathology.
Ac kno w ledg em ents
T he authors w ish to acknow ledge the fo llo w in g W IL R esearch L aboratories, Inc. personnel fo r th eir assistance in th e conduct o f th is project and prep aratio n o f m aterials fo r this poster.
K im C ollings, L orelei W atson, R oxanne P hillips and R o n W ilson
-2021-
M W C C D Ga t e r n a l a t e r a n d o m p o u n d o n s u m p t i o n u r i n g e s t a t i o n a n d La c t a t i o n
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
F1 BODY W EIGHTS Male
% o> \*
* = Significantly different from the control group at p<0.05 **= Significantly different from the control group at p<0.01
450
400
350 Xfl
300
250 200 *
150 aoa
s
s
100 <
50
0
-2022-
60
50
40
JaSt
30
s
poa 20
a
as 10
0
F1 BODY WEIGHTS Female
V <5 0 <\ % 0) ^
4^ 4^ ^ ^^
* = Significantly different from the control group at p<0.05 ** = Significantly different from the control group at p<0.01
450
400
350
300
250
<D
200
"o
150
100
50
0
-2023-
Total Activity Counts for PND 13 Male Rats Exposed to Methimazole
0 ppm -- 10 ppm - a - 30 ppm --x- 100 ppm 250
200
-2024-
150
c
3 O
100
50
0 0-15
15-30
31-45
Interval (min)
46-60
Total Activity Counts for PND 17 Male Rats Exposed to Methimazole
-2025-
450
400
350
300
<0
250
3
O 200
O
150
100
50
0
--0 ppm -- 10 ppm - 30 ppm --x- -100 ppm
0-15
15-30
31-45
46-60
Interval (min)
Total Activity Counts for PND 21 Male Rats Exposed to Methimazole
-2026-
600
500
400
Vi
c
3 300
oO
200
100
0
0 ppm MMZ 0-15
10 ppm MMZ - -A- -30 ppm MMZ --X- -100 ppm MMZ
16-30
31-45
Interval (min)
46-60
Total Activity Counts in PND 61 Male Rats Exposed to Methimazole
1200 i
--0 ppm -- 10 ppm - 30 ppm --x- 100 ppm
1000
-2027-
800
<0
io 600
O
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 --x- -100 ppm 250
200
-2028-
Vi 150
c
3 O
O 100
50
0 0-15
16-30
31-45
Interval (min)
46-60
Total Activity Counts in PND 17 Female Rats Exposed to Methimazole
-2029-
450
400
350
300
Vi
c 250
3
oO 200
150
100
50
0
--0 ppm -- 10 ppm - 30 ppm --x- -100 ppm
0-15
16-30
31-45
46-60
Interval (min)
Total Activity Counts in PND 21 Female Rats Exposed to Methimazole
--0 ppm -- 10 ppm - 30 ppm --x- -100 ppm 600
500
Vi
c
400
3
oO 300
(0
o 200
-2030-
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 --x- 100 ppm
1000
-2031-
800
<0
io 600
O
400
200
0 0-15
16-30
31-45
Interval (min)
46-60
Preweaning Total Activity Counts in Male Rats Exposed to Methimazole
0 ppm MMZ 10 ppm MMZ 30 ppm MMZ 100 ppm MMZ
-2032-
PND 13
PND 17
Age at Testing
PND 21
Preweaning Total Activity Counts in Female Rats Exposed to Methimazole
0 ppm 10 ppm 30 ppm 100 ppm
-2033-
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 - A- -30 ppm MMZ --* -100 ppm MMZ 250
200
-2034-
| 150
x
(0
E 100
>
50
0
T 1r
-
+
+
............................. ,
k-++-
,,.
,, ----------- -i
[ k
+
+
] .............................i l +
+
i ............................. .......
++
> $ + + --. 1
1 . ::
i< + + ------------------------- < + + -------------------------- > $ - + + -- - -- - -- X
1-10
11-20
21-30
31-40
41-50
Trial Block
Peak Response in PND 60 Male Rats Exposed to Methimazole
600 n
0 ppm MMZ
10 ppm MMZ - A- -30 ppm MMZ --* -100 ppm MMZ
500
^ 400
E
^ 300
(0
E
> 200
A++ X .++'
++"
Xr* +
++
% ++
-2035-
100
0 1-10
11-20
21-30
Trial Block
31-40
41-50
40
35
30
o
<D 25
V)
E 20
x
(0
E 15
10
5
0
Latency to Peak Response in PND 20 Male Rats Exposed to Methimazole
--0 ppm -- 10 ppm - 30 ppm --x- 100 ppm
1-10
11-20
21-30
31-40
41-50
Trial Block
-2036-
50
45
40
o 35
<D V)
30
E x
25
| 20
1" 15
10
5
0
Latency to Peak Response in PND 60 Male Rats Exposed to Methimazole
--0 ppm -- 10 ppm - 30 ppm --x- 100 ppm
+ ++
1-10
11-20
21-30
31-40
41-50
Trial Block
-2037-
Peak Response in PND 20 Female Rats Exposed to Methimazole
--0 ppm -- 10 ppm - 30 ppm --x- -100 ppm 250
200
-2038-
| 150
x
(0
E 100
>
50
0
a + + - - ..
U + + `
>*++ -- . _
-- x ++
-it+ + -X ++
1-10
11-20
21-30
Trial Block
a ++ X-++
31-40
++ ++
41-50
Peak Response in PND 60 Female Rats Exposed to Methimazole
600 n
0 ppm -- 10 ppm - 30 ppm --x- -100 ppm
500
-2039-
^ 400
E
^ 300
(0
E
> 200
100
0 1-10
11-20
21-30
Trial Block
31-40
41-50
40
35
30
o
<D V)
25
E 20
x
(0
E 15
10
5
0
Latency to Peak Response in PND 20 Female Rats Exposed to Methimazole
--0 ppm -- 10 ppm - 30 ppm --x- 100 ppm
1-10
11-20
21-30
31-40
41-50
Trial Block
-2040-
50
45
40
o 35
<D V)
30
E x 25
20
" 15
10
5
0
Latency to Peak Response in PND 60 Female Rats Exposed to Methimazole
----0 ppm -- 10 ppm - 30 ppm --x- -100 ppm
++ ++
1-10
11-20
21-30
31-40
41-50
Trial Block
-2041-
180 160 140
o' 120 tn 100
<D
E
80
60
40
20
0
Time to Escape in PND 22 Male Rats Exposed to Methimazole
0 ppm
10 ppm - A - -30 ppm --X -100 ppm
^++
X
x
\
S 12 3 4
5 6 7 8 9 10
Trial
) ^ + + .. - \ T ++ +^c++
11 12
-2042-
Number of Errors in PND 22 Male Rats Exposed to Methimazole
0 ppm -- 10 ppm - A- 30 ppm --X- -100 ppm
Errors
-2043-
12
34
5 6 7 8 9 10
Trial
11 12
Time to Escape in PND 22 Female Rats Exposed to Methimazole
-2044-
180 160 140 120
o 100
80 60 40 20
0
**
i
i
S
0 ppm -- 10 ppm - 30 ppm --x- -100 ppm
a ++
/++
k
12 3 4
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 --x- 100 ppm
-2045-
Time to Escape in PND 62 Male Rats Exposed to Methimazole
0 ppm 10 ppm - A- -30 ppm --X- -100 ppm
-2046-
Number of Errors in PND 62 Male Rats Exposed to Methimazole
0 ppm 10 ppm - A- -30 ppm --X- -100 ppm
-2047-
Time to Escape in PND 62 Female Rats Exposed to Methimazole
--0 ppm -- 10 ppm - 30 ppm --x- -100 ppm
-2048-
Number of Errors in PND 62 Female Rats Exposed to Methimazole
--0 ppm -- 10 ppm - 30 ppm --x- 100 ppm
-2049-
Le v e l 1 - Co r o n a l Se c t i o n
(Midway between olfactory bulbs and optic chiasm)
Line B - Vertical thickness of cortex
Line A B
PND 11
Males Females
PIPI NS * ** ** NS * ** **
-2050-
Line A - Height of hemisphere
Line A B
PND 22 MF NS * NS NS
PND 72
MF 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
Le v e l 3 - Co r o n a l Se c t i o n
(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
Line
C D E F
PND 11 Males Females PIPI
NS NS NS NS
NS * NS NS * ** ** **
N S N S ** N S
PND 22 PND 72
Line M F M F
C NS NS NS NS
D NS NS NS NS
E ** * N S N S F N S N S N S **
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
L 5 - M -e v e l
id sa g it t a l se c t io n
(cerebellum and brain stem)
Line H - Distance across base of lobule #9
Line G H
PND 11
Males Females
PIPI NS * NS NS
* * NS **
-2052-
Line G - Vertical thickness of the pons (perpendicular to the caudal spinal cord)
Line G H
PND 22 MF NS NS NS NS
PND 72 MF 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 Br a in W e ig h t s a n d Le n g t h s
Brains either immersion fixed or perfusion fixed for PND 11 pups. Brains perfusion fixed on PND 22 and 72. Brain lengths measured after fixation.
MALE
PND 11
PND 11
PND 22
PND 72
Immersion
Perfusion
Perfusion
Perfusion
0 PPM 100 PPM
Weight
1.(2g9) 0.075 1.08 0.188**
Length (mm)
16.6 0.51 15.2 1.23**
Weight
1.(2g3) 0.121 1.06 0.173*
Length (mm)
16.0 0.67 15.1 1.05*
Weight
1.(7g1) 0.072 1.56 0.117**
Length (mm)
18.5 0.50 17.5 0.49**
Weight
1.(9g7) 0.154 1.79 0.134**
Length (mm)
20.5 0.91 19.4 1.05*
PND 11 Immersion
fem ale
PND 11 Perfusion
PND 22 Perfusion
PND 72 Perfusion
0 PPM 100 PPM
Weight
(g)
1.26 (0.077) 1.07 0.153**
Length (mm)
16.3 0.63 15.5 1.04*
Weight
(g)
1.23 0.082 0.99 0.127**
Length (mm)
16.4 0.48 14.8 0.90**
Weight
(g)
1.65 0.828 1.49 0.128**
Length (mm)
18.3 0.36 17.5 0.51**
Weight
(g)
1.75 0.130 1.69 0.104
Length (mm)
20.6
1.52 19.3
0.86*
* = Significantly different from the control group at p<0.05 ** = Significantly different from the control group at p<0.01
IO M H 1
TlDji;-
-2054-
m < ;ii ] posi-: h b)
Ih rtftCLLU U H
silln I VKNt u i e LIMB
m o i d o se 2 2 s%
-- *V
A 'S & T r
1 1\(WL-j
jffip s 1
iE 11 SI0
' 1 ^4/ IB
JJEH ISftTl7V T O T . H N 1 h m
IIK.II LKJSH ' 1 II;'
I f if lk ' >' M
/
MaljlHwl
-2055-
WIL-99263
AN INTER-OBSERVER RELIABILITY STUDY OF TECHNICIANS ASSIGNED TO PERFORM FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENTS IN RATS
Study Date Range: D e c e m b e r 14, 2 0 0 1 - O c to b e r 9, 2 0 0 2
S O :t u d y b j e c t iv e
T he objective o f this study w as to train personnel to conduct the F unctional O bservational B attery (FO B ) and to assess inter-observer reliability o f the sam e technicians. FO B . inter-observer reliability studies serve as training fo r new em ployees, as w ell as on-going training fo r current em ployees.
C A :o n t r o l r t ic l e s
D eio n ized w ater w as u sed as th e n eg ativ e co n tro l article. T w o p o sitiv e co n tro l articles, 3 ,3 '-Im in o d ip ro p io n itrile (ID P N ) an d P a ra th io n , w e re u se d to e lic it b e h av io ral ch an g e s in th e anim als. ID P N w as ad m in istered orally at 2000 m g /k g , and P arath io n w as ad m in istered orally at 4 m g/kg. A ll co n tro l articles w ere ad m in istered as a single dose.
Te s t Sy s t e m :
A ll an im als u se d o n th e study w e re fe m a le S p rag u e-D aw ley C rl:C D (S D )IG S B R rats o b tain ed fro m th e W IL R esearch L ab o rato ries, Inc. stock colony. A n im als w ere random ly assigned to treatm ent groups usin g a com puter program . T he study w as conducted according the protocol and W IL standard operating procedures.
E C :n v i r o n m e n t a l o n d i t i o n s
T he anim als w ere h o used and m ain tain ed u n d er conditions co nsistent w ith m aintaining good health. T em perature and relative hum idity w ere set to m aintain at 71 5 C and 3 0 -7 0 % , re sp ec tiv e ly , in a ro o m w ith a 12 h o u r lig h t (6 a.m . to 6 p .m .)/d a rk p h o to p erio d . T em p eratu re and relativ e h u m id ity w ere reco rd ed o n ce daily. T h e facilities at W IL R esearch L aboratories, Inc. are fully accredited by th e A ssociation fo r A ssessm en t and A ccred itatio n o f L aboratory A nim al C are International (A A A L A C International).
V O :i a b i l i t y b s e r v a t io n s
T he rats w ere observed fo r m ortality/m oribundity and general condition tw ice daily, in th e m o rn in g and in the afternoon.
Bo d y We ig h t s :
B o d y w eig h ts w ere reco rd ed o n d ays o f d o sin g fo r calcu latio n o f d o ses only.
-2056-
WIL-99263
F O B A :u n c t i o n a l b s e r v a t io n a l a t t e r y s s e s s m e n t s
T he F unctional O bservational B attery u sed at W IL R esearch L ab o rato ries, Inc. is b ased o n p re v io u sly d e v elo p ed p ro to c o ls (M o ser et al., 1999; Irw in, 1968; G ad, 1982; M o ser et a l., 1 9 8 8 ; H a g g e r ty , 1 9 8 9 ; O 'D o n o g h u e , 1 9 8 9 ). T e s t i n g f o r P h a s e I I I ( d e s c r i b e d b e lo w ) w as p erfo rm ed b y train ed tech n ician s w h o d id n o t k n o w th e a n im a l's group assignm ent. T he tim e o f testin g w as determ ined by th e Study D irecto r based on th e appearance o f the expected b ehavioral signs fo llo w in g dosing. A nim als w ere observed fo r th e follow ing param eters as described below (see W IL standard operating procedure N o. T 1-112, as rev ised , fo r a d escrip tio n o f sco rin g criteria):
H C O :o m e a g e b s e r v a t io n s
P osture C onvulsions/T rem ors Feces consistency
B iting P alpebral (eyelid) closure
H O :a n d l i n g b s e r v a t io n s
E ase o f rem oval from cage L acrim ation/chrom odacryorrhea P iloerection P alpebral closure R ed/crusty deposits E ye prom inence
E ase o f han d lin g anim al in hand S alivation F ur appearance R espiratory rate/character M ucous m em branes/eye/skin color M uscle tone
O F O :p e n i e l d b s e r v a t io n s ( e v a l u a t e d o v e r a 2 - m in u t e o b s e r v a t i o n p e r io d )
M obility R earing C onvulsions/trem ors G room ing B izarre/stereotypic behavior T im e to first step (seconds)
G ait A rousal U rination/defecation G ait score B acking
S O :e n s o r y b s e r v a t io n s
A pproach response S tartle response Pupil response F orelim b extension A ir righting reflex
T ouch response T ail pinch E yeblink response H indlim b extension O lfactory orientation
T he study design co nsisted o f th ree d istinct phases to ensure the m o st adequate training and reliability am ong th e technicians. P hases w ere designed as a pro g ressio n to allow fo r
-2057-
WIL-99263
training and discussion prio r to the final phase, w hich evaluated the inter-observer reliability. T h e p h ases o f testin g are d escrib ed as follow s:
Ph a s e I:
P h ase I testin g co n sisted o f F O B assessm en ts o n n aiv e stock anim als. E ach tech n ician observed up to 60 rats th ro u g h the entire F O B assessm ent. T he pu rp o se o f P h ase I testin g w as to en su re co n sisten t and accurate u se o f all eq u ip m en t an d to gain a strong k n o w led g e o f th e stereo ty p ic b eh av io r o f n aiv e anim als. A ll rats u sed in P hase I testing w ere returned to stock follow ing FO B assessm ents.
Ph a s e II:
P h a s e II te s tin g c o n s is te d o f a n o p e n d is c u s s io n o f e a c h a n im a l's o b se rv a tio n s co n d u cted in a group setting. T w o an im als p e r group w ere d o sed w ith P arath io n , ID P N o r deionized w ater and evaluated by the observers once the effects w ere apparent. P h ase II allow ed fo r o p en d iscu ssio n o f o b serv atio n s and in terp retatio n o f the findings. A ll anim als u sed in P h ase II testin g w ere euthanized by carbon dioxide in h alatio n and carcasses d iscard ed fo llo w in g testing.
Ph a s e III:
P hase III testing consisted o f three anim als p e r group dosed w ith a single dose o f P arathion, ID P N o r deio n ized w ater and observed at a tim e determ ined by th e Study D irecto r. E ach tech n ician individually reco rd ed observations fo r each anim al to evaluate the in ter-o b serv er reliab ility . A ll anim als u sed in P h ase III testin g w ere euthanized by carbon dioxide inhalation and carcasses discarded follow ing testing.
C E T :r i t e r i a f o r v a l u a t i o n o f e c h n i c i a n s
T he fo llo w in g criteria w ere u sed to ev alu ate th e ability o f tech n ician s to reliab ly distinguish signs o f neurotoxicity.
1. N o o m i s s i o n o f f i n d i n g s w i t h i n t h e c a t e g o r i e s o f H o m e C a g e O b s e r v a ti o n s , H andling O bservations, O pen F ield O bservations and Sensory O bservations.
2. A d ifference o f no m o re th an tw o grad es (severity) fo r a given fin d in g in each c a te g o ry .
Re s u l t s : V :i a b i l i t y
A ll anim als survived u n til scheduled euthanasia.
-2058-
WIL-99263
F O B A :u n c t i o n a l b s e r v a t io n a l a t t e r y s s e s s m e n t s
T echnicians w ere consistent in the findings reported w hen deionized w ater, ID P N or P a ra th io n w a s a d m in is te re d (T a b le 1). T h e re w e re n o o b v io u s o r g ro ss inconsistencies am ong the calls.
It w as determ ined that the p reviously established criteria fo r evaluation w ere fulfilled to a degree deem ed acceptable b y the S tu d y D irector. It should be n o ted th at there w ere a few apparent om issions o f findings (T able 2) w hich upon further review w ere fo u n d to be o f no p ractical significance.
C :o n c l u s io n s
It w as determ ined th at the technicians fulfilled the criteria fo r reliably observing FO B param eters to assess behavioral changes in rats in a m anner consistent w ith good science and W IL R esearch L aboratories, Inc. standard operating procedures.
R :e f e r e n c e s
G ad, S.C . A n eu ro m u scu lar screen fo r u se in in dustrial toxicology. Journal o f T oxicology a n d E n viro n m en ta l H ea lth 1982, 9(5-6), 6 9 1 -7 0 4 .
H aggerty, G .C . D ev elo p m en t o f tie r I neu ro b eh av io ral testing capabilities fo r in c o rp o ra tio n in to p iv o ta l ro d e n t safety a sse ssm e n t stu d ies. Journal o f the American
College o f Toxicology 1989, 8(1), 5 3 -6 9 .
Irw in , S. C o m p reh en siv e o b serv atio n al assessm en t: Ia. a sy stem atic, q u an titativ e procedure fo r assessing th e behavioral and physiologic state o f the m ouse.
P sychopharm acologia 1968, 13, 2 2 2 -2 5 7 .
M oser, V .C .; M cC orm ick, J.P .; C reason, J.P.; M acP hail, R .C . C om parison o f c h lo rd im efo rm an d carb ary l u sin g a fu n c tio n al o b serv atio n al b attery. Fundamentals
o f A p p lie d Toxicology 1988, 11(2), 1 8 9 -2 0 6 .
M oser, V .C .; M cD aniel, K .L .; P hillips, P.M . R at strain and stock co m parisons u sin g a functional observational battery: baseline values and effects o f am itraz.
T oxicology a n d A p p lie d P h a rm acology 1991, 108(2), 2 6 7 -2 8 3 .
O 'D o n o g h u e , J .L . ( 1 9 8 9 ) S c r e e n in g f o r n e u r o to x ic ity u s i n g a n e u r o lo g i c a l ly b a s e d e x a m in a tio n a n d n e u ro p a th o lo g y . J. A m er. Coll. Toxicol. 8 :9 7 -1 1 6 .
WIL-99263
TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS
PAGE 1
TREATMENT:
CONTROL
IDPN
Parathion
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
POSTURE 1 - S IT T IN G O R S T A N D IN G N O R M A L L Y
1 2 12
3 2 32
2 - A S L E E P , LY IN G O N S ID E O R C U R L E D U P 3 - A LE R T , O R IE N T E D T O W A R D O B S E R V E R
2 1 2 13 3 33
11
4 - S IT T IN G , H E A D H E L D L O W 5 - F L A T T E N E D , L IM B S M A Y BE E X T E N D E D
6 - L Y IN G O N S ID E , L IM B S IN A IR 7 - IM M O B ILE
8 - R E A R IN G
9 - S P L A Y E D H IN D L E G S 10 - P R O S T R A T IO N
C O N V U L S IO N S - C LO N IC 1 - ABSENT
3
3 33 3
3
33
2
3 33
2 - T W IT C H E S (B A C K M U S C LE S ) 3 - IR R E G U L A R J E R K IN G M O V E M E N T S O F T H E L IM B S
4 - C L O N IC W H O L E -B O D Y C O N V U L S IO N S
5 - H E A D A N D /O R B O D Y T W IT C H E S (M Y O C L O N U S )
6 - M U S C LE F A S IC U LA T IO N S
7 - R E P E T IT IV E M O V E M E N T O F M O U T H A N D JA W S (C H E W IN G )
C O N V U L S IO N S - T O N IC
1 - ABSENT
3
3 33 3
3
33
3
3 33
2 - T O N IC : C O N T R A C T IO N O F E X T E N S O R S S U C H T H A T L IM B S A R E R IG ID A N D E X T E N D E D 3 - O P IS T H O T O N U S : H E A D , B O D Y A N D L IM B S R IG ID L Y A R C H E D B A C K W A R D S
4 - E M P R O S T H O T O N U S : H E A D , B O D Y A N D L IM B S E X T E N D E D F O R W A R D
5 - 'P O P C O R N S E IZ U R E ': A N IM A L R E P E A T E D L Y J U M P S O R B O U N C E S IN A IR
6 - A S P H Y X IA L : B O U T S O F S E V E R E C L O N IC -T O N IC C O N V U L S IO N S
TR EM O R S
1 - NONE
3
3 33 3
3
33
3
3 33
2 - S L IG H T (1 .5m m ) 3 - M O D E R A T E L Y C O A R S E (3 m m )
4 - M A R K E D L Y C O A R S E (4 .5m m ) 5 - E X T R E M E L Y C O A R S E (6 m m )
-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
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
B IT IN G 1 - NONE 2 - B IT IN G O F C A G E 3 - B IT IN G O F S E L F PALPEBRAL CLOSURE 1 - E Y E L ID S W ID E O P E N 2 - E Y E L ID S S L IG H T L Y D R O O P IN G 3 - D R O O P IN G E Y E L ID S (H A L F -C L O S E D ) 4 - E Y E L ID S C O M P L E T E L Y S H U T FE C E S C O N S IS T E N C Y 1 - PELLETS 2 - P E L L E T S , P A R T IA L L Y F O R M E D 3 - U N F O R M E D , D IA R R H E A 4 - PELLETS ABSENT EASE OF REMOVAL 1 - V E R Y E A S Y : A N IM A L S IT S Q U IE T LY , A L L O W S IN V E S T IG A T O R T O P IC K IT U P 2 - E A S Y : W IT H /W IT H O U T V O C A L IZ A T IO N , W IT H O U T R E S IS T A N C E O R S L IG H T R E S IS T A N C E 3 - M O D E R A T E L Y D IF F IC U L T : A N IM A L R E A R S , O F T E N F O L L O W IN G T H E IN V E S T IG A T O R 'S H A N D 4 - F R E E Z E S : W IT H /W IT H O U T V O C A L IZ A T IO N 5 - D IF F IC U L T : R U N S A R O U N D C A G E , IS H A R D T O G R A B , W IT H /W IT H O U T V O C A L IZ A T IO N 6 - V E R Y D IF F IC U L T : T A IL A N D T H R O A T R A T T L E S W IT H /W IT H O U T V O C A L IZ A T IO N ; M A Y A T T A C K E A S E O F H A N D L IN G IN H A N D 1 - L O W : N O R E S IS T A N C E , A N IM A L IS E A S Y T O H A N D L E 2 - M O D E R A T E L Y LO W : S L IG H T R E S IS T A N C E T O B E IN G H A N D L E D , W IT H /W IT H O U T V O C A L IZ A T IO N 3 - M O D E R A T E L Y H IG H : M A Y F R E E Z E , BE T E N S E O R R IG ID , W IT H /W IT H O U T V O C A L IZ A T IO N 4 - H IG H : S Q U IR M S , T W IS T S , A T T E M P T S T O B IT E , W IT H /W IT H O U T V O C A L IZ A T IO N L A C R IM A T IO N 1 - NONE 2 - S LIG H T 3 - SEVERE CHR OM O DACRYORRHEA 1 - ABSENT 2 - PRESENT
3
3 33 3
3
33
3
2 33
1 2 12
2 3 33 1
2 1 2 13 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
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
S A L IV A T IO N 1 - NONE 2 - S LIG H T 3 - SEVERE P IL O E R E C T IO N 1 - NONE 2 - S LIG H T 3 - SEVERE FUR APPEARANCE 1 - NORMAL: CLEAN AND GROOM ED 2 - S L IG H T L Y S O IL E D 3 - V E R Y S O IL E D , C R U S T Y PALPEBRAL CLOSURE 1 - E Y E L ID S W ID E O P E N 2 - E Y E L ID S S L IG H T L Y D R O O P IN G 3 - D R O O P IN G E Y E L ID S (H A L F -C L O S E D ) 4 - E Y E L ID S C O M P L E T E L Y S H U T R E S P IR A T O R Y R A TE 1 - N O R M A L : BY O B S E R V A T IO N (8 0 -1 1 0 /M IN .) 2 - D E C R E A S E D : B E L O W 8 0/M IN . 3 - IN C R E A S E D : A B O V E 110/M IN . R E S P IR A T O R Y C H A R A C T E R 1 - NORMAL 2 - R A LE S : A B N O R M A L S O U N D A C C O M P A N Y IN G B R E A T H IN G 3 - R E T C H IN G 4 - D Y S P N E IC : S H O R T O F B R E A T H 5 - G A S P IN G
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
R E D D E P O S IT S - eyes 1 - PRESENT 2 - ABSENT R E D D E P O S IT S - 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
R E D D E P O S IT S - m outh 1 - PRESENT 2 - ABSENT C R U S T Y D E P O S IT S - eyes 1 - PRESENT 2 - ABSENT C R U S T Y D E P O S IT S - nose 1 - PRESENT 2 - ABSENT C R U S T Y D E P O S IT S - m o u th 1 - PRESENT 2 - ABSENT M U C O U S M E M B R A N E S - c o lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - B R IG H T , D E E P R E D F L U S H E Y E S - c o lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - B R IG H T , D E E P R E D F L U S H S K IN - c o lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - B R IG H T , D E E P R E D F L U S H
TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS
PAGE 4
TREATMENT:
CONTROL
IDPN
Parathion
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
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
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
EYE P R O M IN E N C E 1 - NORMAL 2 - EXOPHTHALMUS 3 - ENOPHTHALM US MUSCLE TONE 1 - M U S C L E IS F IR M B U T N O T H A R D (N O R M A L ) 2 - M U S C L E IS S O F T A N D F L A B B Y 3 - M U S C L E IS T E N S E A N D H A R D T IM E T O F IR S T S T E P (se co nd s) R E Q U IR E S N U M E R IC A L IN P U T
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
M O B ILIT Y 1 - NORMAL 2 - S L IG H T L Y IM P A IR E D 3 - M O D E R A T E L Y IM P A IR E D 4 - T O T A L L Y IM P A IR E D , L O C O M O T IO N IM P O S S IB L E G A IT 1 - NORMAL 2 - W A L K S O N TIP T O E S 3 - BODY DRAGS, ABDOM EN CONTACTS SURFACE, BODY SW AYS 4 - H IN D L IM B S S P L A Y E D O R D R A G G IN G , U N A B L E T O S U P P O R T W E IG H T 5 - HUNCHED BODY 6 - A T A X IA , E X C E S S IV E S W A Y , R O C K S O R L U R C H E S A S P R O C E E D S F O R W A R D 7 - W ALKS ON METATARSUS C O N V U L S IO N S - C LO N IC 1 - ABSENT 2- T W IT C H E S (B A C K M U S C LE S ) 3 - R E P E T IT IV E M O V E M E N T O F M O U T H A N D JA W S 4 - C L O N IC T R E M O R S O F T H E L IM B S 5 - W HOLE BODY TREMORS 6 - C L O N IC C O N V U L S IO N S 7 - W ET 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
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
C O N V U L S IO N S - T O N IC 1 - ABSENT 2 - T O N IC : C O N T R A C T IO N O F E X T E N S O R S S U C H T H A T L IM B S A R E R IG ID A N D E X T E N D E D 3 - O P IS T H O T O N U S : H E A D , B O D Y A N D L IM B S R IG ID L Y A R C H E D B A C K W A R D S 4 - E M P R O S T H O T O N U S : H E A D , B O D Y A N D L IM B S E X T E N D E D F O R W A R D 5 - 'P O P C O R N S E IZ U R E ': A N IM A L R E P E A T E D L Y J U M P S O R B O U N C E S IN A IR 6 - A S P H Y X IA L : B O U T S O F S E V E R E C L O N IC -T O N IC C O N V U L S IO N S TR EM O R S 1 - NONE 2 - S L IG H T (1 .5m m ) 3 - M O D E R A T E L Y C O A R S E (3 m m ), S L IG H T IM P A IR M E N T O F L O C O M O T IO N 4 - M A R K E D L Y C O A R S E (4.5m m ), M O D E R A T E /M A R K E D IM P A IR M E N T O F L O C O M O T IO N 5 - E X T R E M E L Y C O A R S E (6 m m ), L O C O M O T IO N IM P O S S IB L E G A IT S C O R E 1 - NORMAL 2 - S L IG H T IM P A IR M E N T , B U T D E F IN IT E 3 - C O N S ID E R A B L E IM P A IR M E N T , W IT H O U T F A LLIN G 4 - M A R K E D IM P A IR M E N T , F A LL S E V E R Y 4 T O 6 S T E P S 5 - S E V E R E IM P A IR M E N T , C A N N O T W A L K W IT H O U T F A LLIN G AROUSAL 1 - V E R Y LO W : S T U P O R , C O M A , L IT T L E O R N O R E S P O N S IV E N E S S 2 - LOW : SO M EW HAT STUPO R O U S 3 - NORM AL: ALERT, EXPLO R ATO RY M O VEM ENTS 4 - S O M E W H A T H IG H : S L IG H T E X C IT E M E N T , T E N S E , S U D D E N D A R T IN G O R F R E E Z IN G 5 - V E R Y H IG H : H Y P E R A L E R T , E X C IT E D , S U D D E N B O U T S O F R U N N IN G O R B O D Y M O V E M E N T S
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
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
B IZ A R R E /S T E R E O T Y P IC B E H A V IO R
1 - NONE
3 3 33
2 - H E A D F LIC K : H E A D S H A K IN G O R B A C K W A R D F LIP O F H E A D
3
3 - H E A D S E A R C H : S T E R E O T Y P E D , R E P E T IT IV E T U R N IN G O F H E A D F R O M S ID E T O S ID E
3
4 - H A L L U C IN A T O R Y : A P P E A R S T O B E R E S P O N D IN G T O O B J E C T S N O T P R E S E N T
5 - C O M P U L S IV E L IC K IN G O R B IT IN G
6 - P R A N C IN G : R E S T L E S S S H IF T IN G F R O M O N E F O R E LIM B T O T H E O T H E R
7 - U P R IG H T W A LK IN G : O N H IN D L IM B S O N LY
8 - A IM L E S S W A N D E R IN G : P R O G R E S S IV E , S LO W , P LO D D IN G M O V E M E N T S , N O A P P A R E N T P U R P O S E
9 - C IR C L IN G : T E N D E N C Y T O M O V E IN C IR C L E S A R O U N D O B J E C T S , O R IN A N O P E N E N V IR O N M E N T
2
10 - W A L T Z IN G : R A P ID T U R N IN G IN C IR C L E S
11 - R E T R O P U L S I O N : A N I M A L W A L K S B A C K W A R D S
1
12 - S P A T IA L D IS O R IE N T A T IO N : W A L K IN G O R S T U M B L IN G IN T O O B J E C T S
13 - S ID E T O S ID E R O C K IN G
14 - S T R A U B T A IL: IN C R E A S E D T A IL E L E V A T IO N
15 - V E R T IC A L JU M P IN G
16 - P A C IN G W IT H O U T P U R P O S E
17 - H E A D B O B B IN G
18 - W R IT H IN G : LY IN G D O W N , W A V E L IK E M O V E M E N T S O F A B D O M E N , A L T E R N A T IN G LIM B M O V E M E N T S
R E A R IN G
R E Q U IR E S N U M E R IC A L IN P U T
17 17 17 17 1
B A C K IN G
R E Q U IR E S N U M E R IC A L IN P U T
0 0 00 4
G R O O M IN G
R E Q U IR E S N U M E R IC A L IN P U T
3 3 33 1
U R IN A T IO N
R E Q U IR E S N U M E R IC A L IN P U T
0 0 00 1
D E F E C A T IO N
R E Q U IR E S N U M E R IC A L IN P U T
1 1 110
2 3 23 3 33
2 22
2 22 2 22 1
1 11
1 1 1 13 13 13 13
4
44
2
2 22
1 11 2
2 22
1
11
1
1 11
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
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
APPROACH RESPONSE 1 - N O R E A C T IO N 2 - S L O W A P P R O A C H , S N IF F IN G O R TU R N IN G A W A Y 3 - M O R E E N E R G E T IC R E S P O N S E T H A N (2), W IT H /W IT H O U T V O C A L IZ A T IO N 4 - F R E E Z E S , A C T U A L M U S C L E C O N T R A C T IO N 5 - B IZ A R R E R E A C T IO N : JU M P S , B IT E S O R A T T A C K S TOUCH RESPONSE 1 - N O R E A C T IO N 2 - A N IM A L M A Y S LO W L Y TU R N , W A L K A W A Y 3 - M O R E E N E R G E T IC R E S P O N S E T H A N (2), W IT H /W IT H O U T V O C A L IZ A T IO N 4 - F R E E Z E S , A C T U A L M U S C L E C O N T R A C T IO N 5 - B IZ A R R E R E A C T IO N : JU M P S , B IT E S O R A T T A C K S STARTLE RESPONSE 1 - N O R E A C T IO N 2 - S L IG H T R E A C T IO N , E A R F L IC K O R S O M E E V ID E N C E T H A T S N A P W A S H E A R D 3 - M O R E E N E R G E T IC R E S P O N S E T H A N (2), W IT H /W IT H O U T V O C A L IZ A T IO N 4 - F R E E Z E S , A C T U A L M U S C L E C O N T R A C T IO N 5 - B IZ A R R E R E A C T IO N : JU M P S , B IT E S O R A T T A C K S
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
T A IL P IN C H R E S P O N S E 1 - N O R E A C T IO N 2 - A N IM A L M A Y S LO W L Y TU R N , W A L K A W A Y 3 - M O R E E N E R G E T IC R E S P O N S E T H A N (2), W IT H /W IT H O U T V O C A L IZ A T IO N 4 - F R E E Z E S , A C T U A L M U S C L E C O N T R A C T IO N 5 - B IZ A R R E R E A C T IO N : JU M P S , B IT E S O R A T T A C K S O L F A C T O R Y O R IE N T A T IO N 1 - N O R E A C T IO N P R E S E N T 2 - R E A C T IO N P R E S E N T : A N IM A L A P P R O A C H E S S W A B M A K IN G S N IF F IN G M O V E M E N T S W IT H N O S E P U P IL R E S P O N S E 1 - N O P U P IL R E S P O N S E 2 - P U P IL R E S P O N S E P R E S E N T E Y E B LIN K R E S P O N S E 1 - N O E Y E B LIN K R E S P O N S E 2 - E Y E B LIN K R E S P O N S E P R E S E N T
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
F O R E L IM B E X T E N S IO N 1 - N O F O R E L IM B E X T E N S IO N 2 - F O R E L IM B E X T E N S IO N P R E S E N T H IN D L IM B E X T E N S IO N 1 - N O H IN D L IM B E X T E N S IO N 2 - H IN D LIM B E X T E N S IO N P R E S E N T A IR R IG H T IN G R E F L E X 1 - NORMAL 2 - S L IG H T L Y U N C O O R D IN A T E D 3 - L A N D S O N S ID E 4 - LANDS ON BACK
TABLE 1 FOB OBSERVATIONS - NO. OF OCCURRENCES OF FINDINGS
PAGE 9
TREATMENT:
CONTROL
IDPN
Parathion
T E C H N IC IA N G R G M JM TAP A Z G R G M JM TAP A Z G R G M JM TA P A Z
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-
W IL-99263
TABLE 2 FO B O B SE R V A T IO N S - FIN D IN G S O M ITT E D
PAGE 1
TECHNICIAN
TAP AZ GRG M JM
TREATMENT
ID PN ID PN PA R A T H IO N PA R A T H IO N
CATEGORY OMITTED
R E SPIR A T O R Y C H A R A C T E R EASE OF REM OVAL
C O N V U L SIO N S - C LO N IC B IT IN G
-2069-
WIL-99310
AN INTER-OBSERVER RELIABILITY STUDY OF INDIVIDUALS ASSIGNED TO PERFORM FUNCTIONAL OBSERVATIONAL BATTERY OBSERVATIONS FOR NEUROTOXICITY STUDIES
Study Date Range: A p ril 1 3 -2 9 , 2 0 0 4
St u d y Ob j e c t iv e :
T he objective o f th is study w as to train personnel to conduct th e F unctional O bservational B attery (F O B ) and to assess in ter-o b serv er reliability o f th e sam e individuals. T he in ter-o b serv er reliab ility also in clu d ed o n e in d iv id u al th at h ad b een previously trained to further dem onstrate inter-observer reliability o f the new ly trained individuals w ith those currently approved to conduct n eurotoxicity studies. F O B inter-observer reliability studies serve as training fo r new em ployees, as w ell as on-going training fo r current em ployees.
Co n t r o l Ar t ic l e s :
M azola co rn o il w as u se d as th e n eg ativ e co n tro l article. T h ree p o sitiv e co n tro l articles, 3 ,3 '-Im in o d ip ro p io n itrile (ID P N ), P a ra th io n an d d -A m p h etam in e, w e re u se d to elicit b eh av io ral ch an g es in th e anim als. ID P N w as ad m in istered orally (gavage) at 2000 m g/kg, P arath io n w as adm inistered orally (gavage) at 4 m g/kg, and d-A m phetam ine w as ad m in istered b y in trap erito n eal in jectio n at 2 m g/kg. A ll p o sitiv e and n eg ativ e control articles w ere adm inistered as a single dose.
Te st Sy s t e m :
A ll an im als u se d o n th e study w e re fe m a le S p rag u e-D aw ley C rl:C D (S D )IG S B R ra ts o b tain ed fro m th e W IL R esearch L ab o rato ries, Inc. stock colony. A n im als w ere random ly assigned to treatm ent groups u sin g a co m p u ter pro g ram . T he study w as conducted according the protocol and W IL standard operating procedures.
En v ir o n m e n t a l Co n d it io n s :
T he anim als w ere h o u sed and m ain tain ed u n d er conditions consistent w ith m aintaining good health. T em perature and relative hum idity w ere set to m aintain at 71 5 C and 30 -7 0 % , resp ectiv ely , in a ro o m w ith a 12 h o u r lig h t (6 a.m . to 6 p .m .)/d a rk p h o to p erio d . T em p eratu re and relativ e h u m id ity w ere reco rd ed o n ce daily. T he v en tilatio n rate w a s set at a m in im u m o f 10 ro o m air c h an g e s p e r h o u r u sin g 100% fre sh air. T h e fa cilitie s at W IL R esearch L aboratories, Inc. are fully accredited by the A sso ciatio n fo r A ssessm ent and A ccreditation o f L aboratory A nim al C are International (A A A L A C International).
-2070-
WIL-99310
V O :i a b i l i t y b s e r v a t io n s
T he rats w ere observed fo r m ortality/m oribundity and general condition tw ice daily, in th e m o rn in g and in the afternoon.
Bo d y We ig h t s :
B o d y w eig h ts w ere reco rd ed o n d ays o f dose ad m in istratio n fo r calcu latio n o f d o ses only.
F O B A :u n c t i o n a l b s e r v a t io n a l a t t e r y s s e s s m e n t s
T he F unctional O bservational B attery u sed at W IL R esearch L ab o rato ries, Inc. is b ased o n p re v io u sly d e v elo p ed p ro to c o ls (M o ser et al., 1999; Irw in, 1968; G ad, 1982; M o ser et a l., 1 9 8 8 ; H a g g e r ty , 1 9 8 9 ; O 'D o n o g h u e , 1 9 8 9 ). T e s ti n g f o r t h e I n t e r - o b s e r v e r R e l i a b i l i t y testing (described below ) w as p erform ed by train ed technicians w ho did not k now the a n im a l's group assignm ent. T he tim e o f testin g w a s d eterm in ed b y th e Study D ire cto r b ased on the appearance o f th e expected b ehavioral signs fo llo w in g dosing. A nim als w ere observed fo r the follow ing param eters as described below (see W IL standard o p eratin g p ro ced u re N o. T 1-112, as rev ised , fo r a d escrip tio n o f sco rin g criteria):
H C O :o m e a g e b s e r v a t io n s
P osture C onvulsions/T rem ors Feces consistency
B iting P alpebral (eyelid) closure
H O :a n d l i n g b s e r v a t io n s
E ase o f rem oval from cage L acrim ation/chrom odacryorrhea P ilo e re c tio n P alpebral closure R ed/crusty deposits E ye prom inence
E ase o f han d lin g anim al in hand S alivation F ur appearance R espiratory rate/character M ucous m em branes/eye/skin color M uscle tone
O F O :PEN i e l d b s e r v a t io n s ( e v a l u a t e d o v e r a 2 - m in u t e o b s e r v a t i o n p e r io d )
M obility R earing C onvulsions/trem ors G room ing B izarre/stereotypic behavior T im e to first step (seconds)
G ait A rousal U rination/defecation G ait score B acking
-2071-
WIL-99310
S O :e n s o r y b s e r v a t io n s
A pproach response Startle response Pupil response F orelim b extension A ir righting reflex
T ouch response T ail p in ch E yeblink response H indlim b extension O lfactory orientation
T he study design consisted o f three distinct phases to ensure the m o st adequate training and reliability am ong th e technicians. P hases w ere designed as a pro g ressio n to allow for training and discussion prio r to the final phase, w hich evaluated the inter-observer reliability. T h e p h ases o f testin g are d escrib ed as follow s:
Ph a s e I:
P h ase I testin g co n sisted o f F O B assessm en ts o n n aiv e stock anim als. E ach tech n ician observed up to 60 rats th ro u g h the entire F O B assessm ent. T he purpose o f P h ase I testin g w as to en su re c o n sisten t and accurate u se o f all eq u ip m en t an d to gain a strong k n o w led g e o f th e stereo ty p ic b eh av io r o f n aiv e anim als. A ll rats u sed in P hase I testing w ere returned to stock follow ing FO B assessm ents.
Ph a s e II:
P h a s e II te s tin g c o n s is te d o f a n o p e n d is c u s s io n o f e a c h a n im a l's o b se rv a tio n s co n d u cted in a group setting. T w o an im als p e r group w ere d o sed w ith ID P N , P arathion, d-A m phetam ine o r corn oil and evaluated by th e observers once the effects w ere apparent. P hase II allow ed fo r open discussion o f observations and interpretation o f the findings. A ll anim als u sed in P hase II testin g w ere euthanized by carb o n d io x id e in h alatio n and carcasses d iscard ed fo llo w in g testing.
Ph a s e III:
Inter-observer R eliability testin g consisted o f three anim als p er group dosed w ith a single dose o f P arathion, ID P N , d-A m phetam ine o r corn oil and observed at a tim e determ ined b y the Study D irecto r o r designee. E ach ob serv er individually recorded observations fo r each anim al to evaluate th e in ter-o b serv er reliability. A ll anim als u sed in Inter-observer R eliability testin g w ere euthanized by carb o n dioxide in h alatio n and carcasses d iscard ed fo llo w in g testing.
C E T :r i t e r i a f o r v a l u a t i o n o f e c h n i c i a n s
T h e fo llo w in g criteria w ere u sed to ev alu ate th e ability o f tech n ician s to reliab ly distinguish signs o f neurotoxicity.
1. N o o m i s s i o n o f f i n d i n g s w i t h i n t h e c a t e g o r i e s o f H o m e C a g e O b s e r v a ti o n s , H andling O bservations, O pen F ield O bservations and Sensory O bservations.
-2072-
WIL-99310
2. A d ifference o f no m o re th an tw o grad es (sev erity ) fo r a g iv en fin d in g in each c a te g o ry .
Re s u l t s : V :i a b i l i t y
A ll anim als survived u ntil scheduled euthanasia.
F O B A :u n c t i o n a l b s e r v a t io n a l a t t e r y s s e s s m e n t s
O b serv ers B , C , D an d E w e re c o n sisten t in th e fin d in g s re p o rte d w h e n co rn oil, ID P N , P a ra th io n o r d -A m p h e ta m in e w a s a d m in is te re d (T a b le 1). T h e re w e re n o obvious o r gross inconsistencies am ong the calls w ith the exception o f o b serv er E w ho differed consistently w hen evaluating pupillary response. T herefore, these four observers w ere considered to have m et acceptable fo r perfo rm in g the functional observational b attery on n eu ro to x icity studies. H ow ever, p rio r to w o rk in g independently o n studies, ob serv er E w ill undergo additional train in g and dem onstrate p ro ficien cy in the ev aluation o f p u p illary response.
O bserver A differed significantly from the com m on response o f the o th er observers in several categories. T herefore, ob serv er A w as n o t considered to h ave m et acceptable criteria fo r perform ing functional observational b attery testing on neurotoxicity stu d ie s .
It should be n o ted there w ere six apparent om issions o f observations (T able 2) w hich u pon fu rth er rev iew w ere fo u n d to b e o f n o consequence.
R ;e f e r e n c e s
G ad, S.C . A n eu ro m u scu lar screen fo r use in in dustrial toxicology. Journal o f T oxicology a n d E n viro n m en ta l H ea lth 1982, 9(5-6), 6 9 1 -7 0 4 .
H aggerty, G .C . D ev elo p m en t o f tie r I neu ro b eh av io ral testin g capabilities fo r in c o rp o ra tio n in to p iv o ta l ro d e n t safety a sse ssm e n t stu d ies. Journal o f the American
College o f Toxicology 1989, 8(1), 5 3 -6 9 .
Irw in , S. C o m p reh en siv e o b serv atio n al assessm en t: Ia. a sy stem atic, q u an titativ e procedure fo r assessing th e behavioral and physiologic state o f the m ouse.
P sychopharm acologia 1968, 13, 2 2 2 -2 5 7 .
M oser, V .C .; M cC orm ick, J.P .; C reason, J.P.; M acP hail, R .C . C om parison o f c h lo rd im efo rm an d carb ary l u sin g a fu n c tio n al o b serv atio n al b attery. Fundamentals
o f A p p lie d Toxicology 1988, 11(2), 1 8 9 -2 0 6 .
-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 a n d A p p lie d P harm acology 1991, 108(2), 267-283. O'Donoghue, J.L. (1989) Screening for neurotoxicity using a neurologically based examination and neuropathology. J. A m er. Coll. Toxicol. 8:97-116.
WIL-99310
TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS
O b s e rv e r: POSTURE 1 - S IT T IN G O R S T A N D IN G N O R M A L L Y 2 - A S L E E P , L Y IN G O N S ID E O R C U R L E D U P 3 - A LE R T , O R IE N T E D T O W A R D O B S E R V E R 4 - S IT T IN G , H E A D H E LD LO W 5 - F LA T T E N E D , L IM B S M A Y B E E X T E N D E D 6 - L Y IN G O N S ID E , L IM B S IN A IR 7 - IM M O B IL E 8 - R E A R IN G 9 - S P L A Y E D H IN D L E G S 10 - P R O S T R A T IO N C O N V U L S IO N S - C L O N IC 1 - ABSENT 2 - T W IT C H E S (B A C K M U S C LE S ) 3 - IR R E G U L A R J E R K IN G M O V E M E N T S O F T H E LIM B S 4 - C L O N IC W H O L E -B O D Y C O N V U L S IO N S 5 - H E A D A N D /O R B O D Y T W IT C H E S (M Y O C L O N U S ) 6 - M U S C L E F A S IC U L A T IO N S (C H E W IN G ) C O N V U L S IO N S - T O N IC 1 - ABSENT 2 - T O N IC : C O N T R A C T IO N O F E X T E N S O R S S U C H T H A T L IM B S A R E R IG ID A N D E X T E N D E D ARCHED BACKW ARDS EXTENDED FORW ARD 5 - 'P O P C O R N S E IZ U R E ': A N IM A L R E P E A T E D L Y J U M P S O R B O U N C E S IN A IR 6 - A S P H Y X IA L : B O U T S O F S E V E R E C L O N IC -T O N IC C O N V U L S IO N S
A nim al #52298 A EDCB
X XX X
XX
XXXXX
XXXXX
A nim al #52277 A EDC B
XX
XX
X
XXXXX XXXXX
A nim al #52222 A EDC B
X
XX
X
X XXXXX
XXXXX
A nim al #52210 A EDC B XXXXX
XXXX X
XXXXX
A nim al #52321 A EDC B X
XXXX
XXXXX
XXXXX
A nim al #52315 A EDC B XXXXX
X XXXXX
XXXXX
-2074-
WIL-99310
TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS
POSTURE TREM O RS
1 - ABSENT 2 - S L IG H T (1 .5 m m ) 3 - M O D E R A T E L Y C O A R S E (3 m m ) 4 - M A R K E D L Y C O A R S E (4 .5 m m ) 5 - E X T R E M E L Y C O A R S E (6 m m ) B IT IN G 1 - NONE 2 - B IT IN G O F C A G E 3 - B IT IN G O F S E L F PALPEBRAL CLOSURE 1 - E Y E L ID S W ID E O P E N 2 - E Y E L ID S S L IG H T L Y D R O O P IN G 3 - D R O O P IN G E Y E L ID S (H A L F -C L O S E D ) 4 - E Y E L ID S C O M P L E T E L Y S H U T F E C E S C O N S IS T E N C Y 1 - PELLETS 2 - P E LLE T S , P A R T IA L L Y F O R M E D 3 - U N F O R M E D , D IA R R H E A 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
XX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XX
XXXXXXXXXXXXXXXXXXXXXXXXX
X XX
XXXXXXXXXXXXXXXXXXXXXXXXX
XXXX
E A S E O F H A N D L IN G IN H A N D 1 - L O W : N O R E S IS T A N C E , A N IM A L IS E A S Y T O H A N D LE 2 - M O D E R A T E L Y LO W : S L IG H T R E S IS T A N C E T O B E IN G H A N D L E D , W IT H /W IT H O U T V O C A L IZ A T IO N 3 - M O D E R A T E L Y H IG H : M A Y F R E E Z E , B E T E N S E O R R IG ID , W IT H /W IT H O U T V O C A L IZ A T IO N
XXXXXXX
XXXXXX
XXXXXXXXXXXXXXX
XX
4 - H IG H : S Q U IR M S , T W IS T S , A T T E M P T S T O B IT E , W IT H /W IT H O U T V O C A L IZ A T IO N L A C R IM A T IO N
1 - NONE 2 - S L IG H T 3 - SEVERE CHRO M O DACRYO RRHEA 1 - ABSENT 2 - PRESENT
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
-2075-
WIL-99310
TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS
O b se rve r: 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
S A L IV A T IO N
1 - NONE
XXXXXXXXXXXXXXX
XXXXXXXXXXXXXX
2 - S L IG H T
X
3 - SEVERE
P IL O E R E C T IO N
1 - NONE
XXXXXXXXXX
XXX
XXXXXXXXXX
XX
2 - S L IG H T
XX
X XX
3 - SEVERE
FUR APPEARANCE
1 - NORM AL: CLEAN AND G RO O M ED
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
2 - S L IG H T L Y S O IL E D
3 - V E R Y S O IL E D , C R U S T Y
PALPEBRAL CLOSURE
1 - E Y E L ID S W ID E O P E N 2 - E Y E L ID S S L IG H T L Y D R O O P IN G
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
3 - D R O O P IN G E Y E L ID S (H A L F -C L O S E D )
4 - E Y E L ID S C O M P L E T E L Y S H U T
R E S P IR A T O R Y R A T E
1 - N O R M A L: B Y O B S E R V A T IO N (8 0 -1 1 0 /M IN .) 2 - D E C R E A S E D : B E L O W 8 0 /M IN . 3 - IN C R E A S E D : A B O V E 110/M IN .
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
R E S P IR A T O R Y C H A R A C T E R 1 - NORMAL 2 - R A LE S : A B N O R M A L S O U N D A C C O M P A N Y IN G B R E A T H IN G 3 - R E T C H IN G 4 - D Y S P N E IC : S H O R T O F B R E A T H 5 - G A S P IN G R E D D E P O S IT S - eyes 1 - PRESENT 2 - ABSENT R E D D E P O S IT S - nose 1 - PRESENT 2 - ABSENT
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
X
XXXXXXXXXXXXXXXXXXXXXXXXXX
XXX
-2076-
WIL-99310
POSTURE R E D D E P O S IT S - m outh 1 - PRESENT 2 - ABSENT C R U S T Y D E P O S IT S - eyes 1 - PRESENT 2 - ABSENT C R U S T Y D E P O S IT S - nose 1 - PRESENT 2 - ABSENT C R U S T Y D E P O S IT S - m outh 1 - PRESENT 2 - ABSENT M U C O U S M E M B R A N E S - c o lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROW N 5 - B R IG H T , D E E P R E D F LU S H E Y E S - co lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROW N 5 - B K IG H I, D E tP R E D F LU S H S K IN - c o lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROW N 5 - B R IG H T , D E E P R E D F LU S H E Y E P R O M IN E N C E 1 - NORMAL 2 - EXOPHTHALM US 3 - ENOPHTHALM US
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
XX
-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
M USCLE TONE
1 - M U S C L E IS F IR M B U T N O T H A R D (N O R M A L )
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
2 - M U S C L E IS S O F T A N D F L A B B Y
3 - M U S C L E IS T E N S E A N D H A R D
M O B IL IT Y
1 - NORMAL
XXXXXXXXXXX
XXXXXXXXXXXX
2 - S L IG H T L Y IM P A IR E D
XXXXX
3 - M O D E R A T E L Y IM P A IR E D
4 - T O T A L L Y IM P A IR E D , L O C O M O T IO N IM P O S S IB L E
G A IT
1 - NORMAL
XXXX
XXXXXXXXXXXXXX
XX
2 - W A L K S O N T IP T O E S
XX
3 - BODY DRAGS, ABDOM EN CONTACTS SURFACE,
BODY SW AYS
4 - H IN D L IM B S S P L A Y E D O R D R A G G IN G , U N A B L E T O S U P P O R T W E IG H T 5 - HUNCHED BODY 6 - A T A X IA , E X C E S S IV E S W A Y , R O C K S O R LU R C H E S AS PROCEEDS FORW ARD 7 - W ALKS ON M ETATARSUS C O N V U L S IO N S - C L O N IC
1 - ABSENT 2- T W IT C H E S (B A C K M U S C LE S ) 3 - R E P E T IT IV E M O V E M E N T O F M O U T H A N D JA W S 4 - C L O N IC T R E M O R S O F T H E LIM B S 5 - W HO LE BODY TREM ORS 6 - C L O N IC C O N V U L S IO N S
7- W EI dog^H A K E S
XX XX
X
XXXX
X
XXXX
XXXXXXXXXXX
X
XX
XX
XXXXXXXXXXXXX
C O N V U L S IO N S - T O N IC 1 - ABSENT
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
-2078-
2 - T O N IC : C O N T R A C T IO N O F E X T E N S O R S S U C H T H A T L IM B S A R E R IG ID A N D E X T E N D E D 3 - O P IS T H O T O N U S : H E A D , B O D Y A N D L IM B S R IG ID L Y ARCHED BACKW ARDS 4 - E M P R O S T H O T O N U S : H E A D , B O D Y A N D LIM B S EXTENDED FORW ARD
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 - 'P O P C O R N S E IZ U R E ': A N IM A L R E P E A T E D L Y J U M P S O R B O U N C E S IN A IR
6 - A S P H Y X IA L : B O U T S O F S E V E R E C L O N IC -T O N IC C O N V U L S IO N S
TREM O RS
1 - NONE 2 - S L IG H T (1 .5 m m )
XXXXXXXXXXXXXXXXXXXXXXXXX
XXXX
X
3 - M O D E R A T E L Y C O A R S E (3 m m ), S L IG H T IM P A IR M E N T O F L O C O M O T IO N
4 - M A R K E D L Y C O A R S E (4 .5 m m ), M O D E R A T E /M A R K E D IM P A IR M E N T O F L O C O M O T IO N
5 - E X T R E M E L Y C O A R S E (6 m m ), LO C O M O T IO N IM P O S S IB L E
G A IT S C O R E
1 - NORMAL 2 - S L IG H T IM P A IR M E N T , B U T D E F IN IT E 3 - C O N S ID E R A B L E IM P A IR M E N T , W IT H O U T F A LLIN G
XXXXXXXXXXXXXXXXXXXXXXXXX XXXX
X
-2079-
4 - M A R K E D IM P A IR M E N T , F A L L S E V E R Y 4 T O 6 S T E P S
5 - S E V E R E IM P A IR M E N T , C A N N O T W A L K W IT H O U T F A LLIN G AROUSAL
1 - V E R Y LO W : S T U P O R , C O M A , L IT T L E O R N O R E S P O N S IV E N E S S
2 - LOW : SO M EW H AT STUPO RO US 3 - NORM AL: ALERT, EXPLO RATO RY M O VEM ENTS
X
XXXXXXXXXXXXXXXXXXXXXXXX
XXXXX
4 - S O M E W H A T H IG H : S L IG H T E X C IT E M E N T , T E N S E , S U D D E N D A R T IN G O R F R E E Z IN G
5 - V E R Y H IG H : H Y P E R A L E R T , E X C IT E D , S U D D E N B O U T S O F R U N N IN G O R B O D Y M O V E M E N T S
WIL-99310
TABLE 1 FOB2 - INTEROBSERVER COMPARISIONS
-2080-
O b se rve r: 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
B IZ A R R E /S T E R E O T Y P IC B E H A V IO R
1 - NONE
XXXXXXXXXXXXXXXXXX
XXXXXX
2 - H E A D F LIC K : H E A D S H A K IN G O R B A C K W A R D F LIP OF HEAD
XXXXX
X
3 - H E A D S E A R C H : S T E R E O T Y P E D , R E P E T IT IV E T U R N IN G O F H E A D FR O M S ID E T O S ID E
4 - H A L L U C IN A T O R Y : A P P E A R S T O B E R E S P O N D IN G TO OBJECTS NOT PRESENT 5 - C O M P U L S IV E L IC K IN G O R B IT IN G 6 - P R A N C IN G : R E S T L E S S S H IF T IN G F R O M O N E F O R E L IM B T O T H E O T H E R 7 - U P R IG H T W A L K IN G : O N H IN D L IM B S O N L Y 8 - A IM L E S S W A N D E R IN G : P R O G R E S S IV E , S LO W , P L O D D IN G M O V E M E N T S , N O A P P A R E N T P U R P O S E
B IZ A R R E /S T E R E O T Y P IC B E H A V IO R (C o n tin u e d )
X XX
9 - C IR C L IN G : T E N D E N C Y T O M O V E IN C IR C L E S A R O U N D O B J E C T S , O R IN A N O P E N E N V IR O N M E N T 10 - W A L T Z IN G : R A P ID T U R N IN G IN C IR C L E S 11 - R E T R O P U L S IO N : A N IM A L W A L K S B A C K W A R D S
X
XX X
12 - S P A T IA L D IS O R IE N T A T IO N : W A L K IN G O R S T U M B L IN G IN T O O B J E C T S 13 - S ID E T O S ID E R O C K IN G 14 - S T R A U B T A IL : IN C R E A S E D T A IL E LE V A T IO N
X
15 - V E R T IC A L JU M P IN G
16 - P A C IN G W IT H O U T P U R P O S E
17 - H E A D B O B B IN G
XX
18 - W R IT H IN G : LY IN G D O W N , W A V E L IK E M O V E M E N T S O F A B D O M E N , A L T E R N A T IN G LIM B M O V E M E N T S
P U P IL R E S P O N S E 1 - N O P U P IL R E S P O N S E 2 - P U P IL R E S P O N S E P R E S E N T A IR R IG H T IN G R E F L E X
XXXXX
XX
XXXXXXXXXXX
XXXXXXXXX
XXX
1 - NORMAL 2 - S L IG H T L Y U N C O O R D IN A T E D 3 - L A N D S O N S ID E 4 - LANDS ON BACK
XXXXXXXXXXXXXXXXXXXXXXXXX
XX
XX
X
WIL-99310
TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS
-2081-
O bserver: POSTURE 1 - S IT T IN G O R S T A N D IN G N O R M A LLY 2 - A S LE E P , LY IN G O N S ID E O R C U R L E D U P 3 - A LE R T , O R IE N T E D T O W A R D O B S E R V E R 4 - S IT T IN G , H E A D H E LD LO W 5 - FLA T T E N E D , LIM B S M A Y BE E X T E N D E D 6 - L Y IN G O N S ID E , L IM B S IN A IR 7 - IM M O B ILE 8 - R EA R IN G 9 - S P LA Y E D H IN D LE G S 10 - P R O S T R A T IO N C O N V U LS IO N S - C LO N IC 1 - ABSENT 2 - T W IT C H E S (B A C K M U SC LES) 3 - IR R E G U LA R JE R K IN G M O V E M E N T S O F T H E LIM BS 4 - C LO N IC W H O L E -B O D Y C O N V U LS IO N S 5 - H E A D A N D /O R B O D Y T W IT C H E S (M Y O C LO N U S ) 6 - M U S C LE F A S IC U LA T IO N S 7 - R E P E T IT IV E M O V E M E N T O F M O U TH A N D JA W S (C H E W IN G ) C O N V U LS IO N S - T O N IC 1 - ABSENT 2 - TO N IC : C O N T R A C T IO N O F E X T E N S O R S S U C H T H A T LIM B S A R E R IG ID A N D E X T E N D E D 3 - O P IS T H O T O N U S : H EAD , B O D Y A N D LIM B S R IG ID LY ARCHED BACKWARDS 4 - E M P R O S T H O T O N U S : H E A D , B O D Y A N D LIM B S EXTENDED FORW ARD 5 - 'P O P C O R N S E IZ U R E ': A N IM A L R E P E A T E D L Y JU M P S O R B O U N C E S IN A IR 6 - A S P H Y X IA L: B O U T S O F S E V E R E C L O N IC -T O N IC C O N V U LS IO N S TREMORS 1 - ABSENT 2 - S LIG H T (1.5m m ) 3 - M O D E R A T E L Y C O A R S E (3 m m )
A n im a l #52247 A E DC B
XX
XX
X
XX XXX XX XXX
XX XXX
A n im a l #52225 A E DC B XXXXX
XXXXX
XXXXX
XXXXX
A n im a l #52216 A EDCB XXXX X
XXXX X
XXXX X
XXX X X
A n im a l #51868 A E DC B XXXXX
XXX XX XXXXX
XXXXX
A n im a l #52254 A E DC B XXXXX
XXXXX
XXXXX
XXXXX
A n im a l #52338 A E DC B
XXXXX
XXXXX XXXXX
XXX
X
X
WIL-99310
TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS
-2082-
4 - M A R K E D LY C O A R S E (4.5m m ) 5 - E X T R E M E LY C O A R S E (6 m m ) B ITIN G 1 - NONE 2 - B IT IN G O F C A G E 3 - B IT IN G O F S E LF PALPEBRAL CLOSURE 1 - E Y E LID S W ID E O PEN 2 - E Y E LID S S LIG H T LY D R O O P IN G 3 - D R O O P IN G E Y E LID S (H A LF -C LO S E D ) 4 - E Y E LID S C O M P LE T E LY S H U T FE C E S C O N S IS T E N C Y 1 - PELLETS 2 - P E LLE T S , P A R T IA LLY F O R M E D 3 - U N F O R M E D , D IA R R H E A 4 - PELLETS ABSENT
A n im a l #52247 O bserver: A E D C B
XXX XX
XXX XX
X XX XX
X
E A S E O F H A N D L IN G IN H A N D 1 - LO W : N O R E S IS T A N C E , A N IM A L IS E A S Y TO HANDLE 2 - M O D E R A T E LY LO W : S LIG H T R E S IS T A N C E TO B E IN G H A N D LE D , W IT H /W IT H O U T V O C A LIZ A T IO N 3 - M O D E R A T E LY H IG H : M A Y F R E E Z E , BE T E N S E OR R IG ID , W IT H /W IT H O U T V O C A LIZ A T IO N 4 - H IG H : S Q U IR M S , T W IS T S , A T T E M P T S TO BITE, W IT H /W IT H O U T V O C A LIZ A T IO N LA C R IM A T IO N 1 - NONE 2 - S LIG H T 3 - SEVERE CHRO M O DACRYO RRHEA 1 - ABSENT 2 - PRESENT S A LIV A T IO N 1 - NONE 2 - S LIG H T 3 - SEVERE
XXX XX
XXX XX XXX XX XXX XX
A n im a l #52225 A E DC B XXXXX XXXXX XXXXX
XXXXX
XXXXX XXXXX XXXXX
A n im a l #52216 A EDCB
XXXX X
XXXX X
XXXX X
XXXX X
X X XXX XXXX X XXXX X
A n im a l #51868 A E DC B
XXXXX
XX X XX
XXXX X
XXXXX
XXXX X XXXXX XXXXX
A n im a l #52254 A E DC B
XXXXX
X
XX XX
XX
X X X
XXXXX
X XX XX
XXXXX
XXXXX
A n im a l #52338 A E DC B
XXXXX
XXXXX
XXX X
XX
XXXXX
XXXX X
XXXXX XXXXX
WIL-99310
TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS
-2083-
O bserver: P ILO E R E C T IO N 1 - NONE 2 - S LIG H T 3 - SEVERE FUR APPEARANCE 1 - NORMAL: CLEAN AND G ROOM ED 2 - S LIG H T LY S O ILE D 3 - V E R Y S O ILE D , C R U S T Y PALPEBRAL CLOSURE 1 - E Y E LID S W ID E O PEN 2 - E Y E L ID S S LIG H T LY D R O O P IN G 3 - D R O O P IN G E Y E LID S (H A LF -C LO S E D ) 4 - E Y E LID S C O M P LE T E LY S H U T R E S P IR A T O R Y R ATE 1 - N O R M A L: BY O B S E R V A T IO N (80-110/M IN .) 2 - D E C R E A S E D : B E LO W 80/M IN . 3 - IN C R E A S E D : A B O V E 110/M IN .
A n im a l #52247 A E DC B XXXX
X
XXX XX XXX XX
XXX XX
R E S P IR A T O R Y C H A R A C T E R 1 - NORMAL 2 - R ALES: A B N O R M A L SO U N D A C C O M P A N Y IN G B R E A T H IN G 3 - R E T C H IN G 4 - D Y S P N E IC : S H O R T O F BR EATH 5 - G A S P IN G R ED D E P O S IT S - eyes 1 - PRESENT 2 - ABSENT R ED D E P O S IT S - nose 1 - PRESENT 2 - ABSENT R E D D E P O S IT S - m outh 1 - PRESENT 2 - ABSENT C R U S T Y D E P O S IT S - eyes 1 - PRESENT 2 - ABSENT
XXX XX
XXX XX X
X XXX XXX XX XXX XX
A n im a l #52225 A E DC B XXXXX XXXXX XXXXX
XXXXX XXXXX
XXXXX XXXXX XXXXX XXXXX
A n im a l #52216 A EDCB XXXX X
XXXX X
XXXX X
XXXX X
XXXX X
X XXX X
XXXX X XXXX X XXXX X
A n im a l #51868 A E DC B XXXXX
XXXX X
XXXX X
XXXXX
XXXXX
X X XXX XX
XXX X X XXX
XXXXX
A n im a l #52254 A E DC B
XXXXX
XXX XX
X
XX
X
X
XXXXX
XXXXX
X X XXX
X X XXX
XXXXX
XXXXX
A n im a l #52338 A E DC B XXXXX XXXXX XXXXX
XXXXX XXXXX
XXXXX XXXXX XXXXX XXXXX
WIL-99310
TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS
C R U S T Y D E P O S IT S - nose 1 - PRESENT 2 - ABSENT C R U S T Y D E P O S IT S - m outh 1 - PRESENT 2 - ABSENT M U C O U S M E M B R A N E S - co lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BR IG H T, D E E P R E D FLU SH E Y E S - co lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BR IG H T, D E E P R E D FLU SH
A n im a l #52247 O bserver: A E D C B
XXX XX XXX XX XXX XX
XXX XX
S K IN - co lo r 1 - P IN K 2 - PALE 3 - DARKENED 4 - DARKENED, BROWN 5 - BR IG H T, D E E P R E D FLU SH EY E P R O M IN E N C E 1 - NORMAL 2 - EXOPHTHALMUS 3 - ENOPHTHALMUS MUSCLE TONE 1 - M U S C L E IS F IR M B U T N O T H A R D (N O R M A L ) 2 - M U S C L E IS S O F T A N D F L A B B Y 3 - M U S C L E IS T E N S E A N D H A R D
XXX XX
XXX XX XXXX
X
A n im a l #52225 A E DC B XXXXX XXXXX XXXXX
XXXXX
XXXXX
XXXXX XXXXX
A n im a l #52216 A EDCB XXXX X XXXX X XXXX X
XXXX X
XXXX X
XXXX X XXXX X
A n im a l #51868 A E DC B XXXXX XXXXX XXXXX
XXXXX
XXXX X
XXXXX
XX
XX
X
A n im a l #52254 A E DC B XXXXX XXXXX XXXXX
XXXXX
XXXXX
XXXXX
XX
XX
X
A n im a l #52338 A E DC B XXXXX XXXXX XXXXX
XXXXX
XXXXX
XXXXX XXXXX
-2084-
WIL-99310
TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS
-2085-
O bserver: M O B ILITY 1 - NORMAL 2 - S L IG H T L Y IM P A IR E D 3 - M O D E R A T E L Y IM P A IR E D 4 - T O T A L L Y IM P A IR E D , L O C O M O T IO N IM P O S S IB LE G A IT 1 - NORMAL 2 - W A LK S O N T IP TO E S 3 - BODY DRAGS, ABDOMEN CONTACTS SURFACE, BODY SWAYS 4 - H IN D LIM B S S P LA Y E D O R D R A G G IN G , U N A B LE TO S U P P O R T W E IG H T 5 - HUNCHED BODY 6 - A T A X IA , E X C E S S IV E S W A Y , R O C K S O R LU R C H E S AS PROCEEDS FORW ARD 7 - W ALKS ON METATARSUS C O N V U LS IO N S - C LO N IC 1 - ABSENT 2- T W IT C H E S (B A C K M U SC LES) 3 - R E P E T IT IV E M O V E M E N T O F M O U TH A N D JA W S 4 - C L O N IC T R E M O R S O F T H E LIM B S 5 - W HOLE BODY TREMORS 6 - C LO N IC C O N V U LS IO N S 7 - W ET DOG SHAKES
A n im a l #52247 A E DC B XXX XX
XXX X XX
XXX XX
C O N V U LS IO N S - T O N IC
1 - ABSENT 2 - TO N IC : C O N T R A C T IO N O F E X T E N S O R S S U C H T H A T LIM B S A R E R IG ID A N D E X T E N D E D
XXX XX
3 - O P IS T H O T O N U S : H EAD , B O D Y A N D LIM B S R IG ID LY ARCHED BACKWARDS
4 - E M P R O S T H O T O N U S : H E A D , B O D Y A N D LIM B S EXTENDED FORW ARD
5 - 'P O P C O R N S E IZ U R E ': A N IM A L R E P E A T E D L Y JU M P S O R B O U N C E S IN A IR
6 - A S P H Y X IA L: B O U T S O F S E V E R E C LO N IC -T O N IC C O N V U LS IO N S
A n im a l #52225 A E DC B XXXXX XXXXX
XXXXX
XXXXX
A n im a l #52216 A EDCB XXXX X XXXX
X XXXX X
XXXX X
A n im a l #51868 A E DC B
XXX XX
XX XX
XX X
XXX
XXXX
X
XXXXX
A n im a l #52254 A E DC B
XXXXX
X X XX XXXXX XXXX XXX
X
X XXXXX
A n im a l #52338 A E DC B XXXXX XXX
XX XXXXX
XXXXX
WIL-99310
TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS
-2086-
O bserver: TREMORS 1 - NONE 2 - S LIG H T (1.5m m ) 3 - M O D E R A T E L Y C O A R S E (3 m m ), S L IG H T IM P A IR M E N T O F LO C O M O TIO N 4 - M A R K E D LY C O A R S E (4.5m m ), M O D E R A T E /M A R K E D IM P A IR M E N T O F LO C O M O TIO N 5 - E X T R E M E L Y C O A R S E (6 m m ), LO C O M O T IO N IM P O S S IB LE G A IT S C O R E 1 - NORMAL 2 - S LIG H T IM P A IR M E N T, B U T D E F IN IT E 3 - C O N S ID E R A B L E IM P A IR M E N T , W IT H O U T FA LLIN G 4 - M A R K E D IM P A IR M E N T , F A L L S E V E R Y 4 TO 6 STEPS 5 - S E V E R E IM P A IR M E N T , C A N N O T W A L K W IT H O U T FA LLIN G AROUSAL 1 - V E R Y LO W : S T U P O R , C O M A , LIT T LE O R NO R E S P O N S IV E N E S S 2 - LOW : SO M EW HAT STUPO RO US 3 - NORMAL: ALERT, EXPLORATORY MOVEMENTS 4 - S O M E W H A T H IG H : S L IG H T E X C IT E M E N T , T E N S E , S U D D E N D A R T IN G O R FR E E ZIN G 5 - V E R Y H IG H : H Y P E R A LE R T , E X C IT E D , S U D D E N B O U T S O F R U N N IN G O R B O D Y M O V E M E N T S B IZ A R R E /S T E R E O T Y P IC BEH A V IO R 1 - NONE 2 - H E A D FLIC K : H E A D S H A K IN G O R B A C K W A R D F LIP OF HEAD 3 - H E A D S E A R C H : S T E R E O T Y P E D , R E P E T IT IV E T U R N IN G O F H E A D FR O M S ID E TO SID E 4 - H A LLU C IN A T O R Y : A P P E A R S TO BE R E S P O N D IN G TO OBJECTS NOT PRESENT 5 - C O M P U L S IV E L IC K IN G O R B IT IN G 6 - P R A N C IN G : R E S T LE S S S H IF T IN G F R O M O N E F O R E LIM B TO TH E O TH E R 7 - U P R IG H T W A LK IN G : O N H IN D LIM B S O N LY 8 - A IM L E S S W A N D E R IN G : P R O G R E S S IV E , SLO W , P L O D D IN G M O V E M E N T S , NO A P P A R E N T P U R P O S E
A n im a l #52247 A E DC B XXX XX
XXX XX
XXX XX XXX XX
A n im a l #52225 A E DC B XXXXX
XXXXX
XXXXX XXXXX
A n im a l #52216 A EDCB
XX
X
XX
XXXX X
XXXX X XXXX X
A n im a l #51868 A E DC B XXXXX
XXX XX
XXXXX
X XX XXXX
A n im a l #52254 A E DC B
XXXXX
XX
XX
X
X XX XX
XXXXX XXXX
X
A n im a l #52338 A E DC B
XXX
X
X
XXXXX
XX XXX
X XXX
WIL-99310
TABLE 1 FOB2 - INTER-OBSERVER COMPARISONS
O bserver: B IZ A R R E /S T E R E O T Y P IC B E H A V IO R (C o n tin u e d ) 9 - C IR C L IN G : T E N D E N C Y T O M O V E IN C IR C L E S A R O U N D O B J E C T S , O R IN A N O P E N E N V IR O N M E N T 10 - W A L T Z IN G : R A P ID T U R N IN G IN C IR C L E S 11 - R E T R O P U L S IO N : A N IM A L W A L K S B A C K W A R D S 12 - S P A T IA L D IS O R IE N T A T IO N : W A L K IN G O R S T U M B L IN G IN T O O B JE C T S 13 - S ID E TO S ID E R O C K IN G 14 - S T R A U B T A IL: IN C R E A S E D T A IL E LE V A T IO N 15 - V E R T IC A L JU M P IN G 16 - P A C IN G W IT H O U T P U R P O S E 17 - H E A D B O B B IN G
A n im a l #52247 A E DC B
A n im a l #52225 A E DC B
A n im a l #52216 A EDCB
A n im a l #51868 A E DC B
XX
X
XXXXX
XX
A n im a l #52254 A E DC B
XX
XX
XX
XX
A n im a l #52338 A E DC B
-2087-
18 - W R IT H IN G : LYIN G D O W N , W A V E L IK E M O V E M E N T S O F A B D O M E N , A L T E R N A T IN G LIM B M O V E M E N T S
P U P IL R E S P O N S E
1 - NO P U P IL R E S P O N S E
X
X
XX
XXXX XXXXX
X
2 - PU P IL R E S P O N S E P R E S E N T
X XXXX XXXX X XX
X XXX
A IR R IG H T IN G R E F LE X
1 - NORMAL
XXX XXXXX XXXXXX X
XXXX
2 - S LIG H T LY U N C O O R D IN A T E D
X
3 - LA N D S O N SID E 4 - LANDS ON BACK
XXX
X
X
X XX
XX
-2088-
W IL -99310
TABLE 2 FO B O B SE R V A T IO N S - FIN D IN G S O M ITT E D
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
887
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
102
100
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 88 118 118
00 22 113 115 31 00
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
887
119
118
98
22
1 20
119 118
109 108
30 116 118
33 116 115
98
98
0 98
0 98
20
20
0 20
0 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
w i l 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
887
119
118
98
EASE OF HANDLING 1 VERY EASY 2 2W EASY WITH VOCALIZATION 2W/O EASY WITHOUT VOCALIZATION 3W/O MODERATELY DIFFICULT WITHOUT VOCALIZATION 4W FREEZES WITH VOCALIZATION
116 116 00 12 20 20 00
98 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 30 71 20 00 00
98 0 0 0 0 0
EYE COLOR* 1 PINK
0 0 98
EYE PROMINENCE* 1 NORMAL
0 0 98
FORELIMB GRIPSTRENGTH* MEAN S.D. MAX MIN N
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 60 788 98 118 118
97 114 112 022 001 022 022 001
78 101 97 16 17 14 2 03 022 101 100
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
887
119
118
98
FUR APPEARANCE** 1 NORMAL CLEANED AND GROOMED 2 SLIGHTLY SOILED
GAIT 1 NORMAL 3 WALKS ON TIPTOES 4 HINDLIMBS SPLAYED, DRAGGING CANNOT SUPPORT WEIGHT 5 HUNCHED BODY, ARCHED BACK
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 98 010
10 98 98 080 010 010
12 20 80 00
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 60 788 98 118 118
98 118 117 001
98 118 118 000 000 000
0 9 16 010 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
DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04
Male
5 of 17
Timepoint (PND) Number of Studies Total Number of Animals Tested Test
4 11 21 22 35 45 60
8871788
119
118
98
20
98 118 118
HINDLIMB GRIPSTRENGTH TRIAL* MEAN S.D. MAX MIN N
0 0 70 54 128 317 483 0 0 26 14 54 149 218 0 0 130 100 270 800 1375 0 0 20 30 30 50 100 237 234 174 60 174 234 234
LACRIMATION 1 NONE
109 108
98
20
98 118 118
MOBILITY SCORE BASED ON FIRST 30 SECONDS IN OPEN FIELD ARENA 1 NORMAL 2 SLIGHTLY IMPARED
20 110 98 20 98 118 118 0800000
MUCOUS MEMBRANES COLOR 1 PINK
119 118
98
20
98 118 118
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
98 118 117
12 0 0 0 0 0 0
0000001
PALPEBRAL CLOSURE* 1 EYELIDS WIDE OPEN
0 0 98 20 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
Timepoint (PND) Number of Studies Total Number of Animals Tested Test
PILOERECTION** 1 NONE 2 SLIGHT
PUPIL RESPONSE* 1 NO PUPIL RESPONSE 2 PUPIL RESPONSE PRESENT
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
REPIRATORY RATE 1 NORMAL
DNT Functional Observational Battery Range of Study Dates 7/13/99 - 6/10/04
Male
4 11 21
887
119
118
98
0 108 00
00 00
20 107 108
10 118 118
10 118 118
119 118
119 117
98 0
2 66
0 98
0 98
1 97
98
98
22 1 20
20 0
0 20
0 20
0 20
0 20
20
20
6 of 17
35 45 60 788 98 118 118
98 118 116 002
101 67 88 87
013 98 117 115
011 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
887
119
118
98
22 1 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
8871788
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 12 03 96
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
0100000
10 10 10 0 10 10 10 IGS DNT FOB v 1 .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
88
119
118
21 7 98
108 108
119 117 01
119 117 01
00 108 108
119 118
32 116 116
98
98 0
98 0
0 98
98
0 98
22 1 19
19
19 0
19 0
0 19
19
0 19
9 of 17
35 45 60
788
98
117
117
98 117 117
98 117 117 000
98 117 117 000
02 0 98 115 117
98 117 117
12 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
88
119
118
21 7 98
22 1 19
10 of 17
35 45 60
788
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 v 1 .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 50
EYE COLOR* 1 PINK
EYE PROMINENCE* 1 NORMAL
4 11 21 22 35 45 60
8871788
119
118
98
19
98
117
117
115 116
97
19
80
93 102
2 0 1 0 15 19 9
2 10 01 13
0 10 02 13
0000010
0000010
000010
0 0 98 19 98 117
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 v 1 .
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
4
11 21 22 35
45
60
8871788
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
FUR APPEARANCE** 1 NORMAL CLEANED AND GROOMED
0 108 98 19 98 117 117
GAIT 1 NORMAL 3 WALKS ON TIPTOES 4 HINDLIMBS SPLAYED, DRAGGING CANNOT SUPPORT WEIGHT
10 101 98 19 98 117 117 05 0 00 0 0 02 0 00 0 0
GENERAL BODY POSTURE 1 SITTING OR STANDING NORMALLY 2 ASLEEP, LYING ON SIDE OR CURLED UP 3 ALERT, OREIENTED TOWARD OBSERVER
13 20 70 00
0 19 00 00
0 5 13
000
0 14
6
-2101-
PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11
IGS DNT FOB v 1 .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
88
119
118
21 7 98
22 1 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 00
98 0
19 0
35 7 98
0.04 0.25
2 0 98
117 53 290 30 174
98 0
13 of 17
45 60
88
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 01
-2102-
PND = Postnatal day * = Animals were not tested until PND 21 ** = Animals were not tested until PND 11
1GS DNT FOB v 1 .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 NOTHARD (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
88
119
118
21 7 98
20 111 07
119 118
109 118 10 0
00
0 108
00 00
98 0
98
98 0
98
98
3 65
22 1 19
19 0
19
19 0
19
19
0 19
14 of 17
35 45 60
788
98
117
117
98 117 117 000
98 117 117
98 117 117 000
98 117 117
98 117 117
000 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
88
119
118
21 7 98
00 108 108
10 118 118
50 114 118
119 118 00
119 118
119 118
1 97
0 98
0 98
98 0
98
98
22 1 19
0 19
0 19
0 19
19 0
19
19
15 of 17
35 45 60
788
98
117
117
0 14 98 116 113
000 98 117 117
05 0 98 112 117
98 117 116 001
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
88
119
118
21 7 98
22 1 19
119 118
98
19
119 117 01
98 0
19 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
88
117
117
117 117
117 117 00
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
1GS DNT FOB v 1 .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% g u m a r a b i c a n d 0. 0 1 % T w e e n 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 Acti ity 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 14 6 154 167 130 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 Acti ity 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 14 0 121 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- 4 5 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 S.D.
S.E.M. Count
Minimum Maximum
404 5.1 3.6
2 401 408
Males - PND 23
16- 30 M I N NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA
31- 4 5 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
222
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
-LUZ-
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 14 6 143 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 14 0 141
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
-LZIZ-
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 rCrl: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 31-40 41-50
161.2 137.8 144.8 151.1
63.6
77.6
69.6
70.7
232.3 180.6 203.8 206.6
136.7 81.3 106.7 113.9
130.6 130.0 136.9 123.7
75.6
93.5
86.6
59.3
188.2 177.8 191.7 200.2
87.1
88.1
86.6
89.9
149.2 134.1 125.8 135.8
70.1
72.2
78.2
55.6
160.8 159.1 140.4 117.6
87.1 102.3 99.6
98.6
144.1 167.9 160.7 143.7
75.0
68.2
63.5
45.4
NA NA NA NA
NA NA NA NA
149.8 134.4 137.2 123.7
71.2
74.2
75.7
85.9
169.9 145.9 132.7 105.2
89.3
66.1
69.4
65.6
172.1 139.3 151.2 155.2
80.3
63.0
44.4
63.9
232.7 206.9 189.2 161.2
124.5 92.7 110.0 134.6
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
Tmax 1-10 11-20 21-30 31-40 41-50 28.8 25.6 26.3 26.3 25.5
4.3 4.7 6.8 4.4 6.9 26.6 24.8 25.4 23.8 23.8 4.4 3.1 6.1 5.1 4.5 30.0 27.1 26.8 24.9 25.7 9.2 8.0 7.6 4.5 7.1 25.6 23.6 22.4 22.8 21.2 4.1 4.4 3.1 2.5 1.6 26.5 22.7 22.7 24.9 22.4 5.4 2.1 3.2 6.6 4.2 26.7 24.6 25.2 23.3 25.4 5.3 3.9 5.9 2.8 4.4 25.8 24.8 22.8 23.0 23.5 2.5 4.1 2.7 3.4 3.3
NA NA NA NA NA NA NA NA NA NA 27.1 26.4 23.8 25.2 25.2 3.7 5.4 2.9 5.7 4.5 24.8 24.3 24.1 24.9 25.1 3.8 4.8 3.4 4.2 3.6 24.8 26.3 25.6 25.4 23.9 4.1 3.4 4.0 5.5 3.2 24.5 22.8 23.7 24.3 25.7 3.1 3.8 5.3 4.7 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
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
Tmax
1-10 11-20 21-30 31-40 41-50
24.7 23.3 23.2 23.5 23.2
2.9 1.3 3.3 4.7 3.5
28.8 27.6 27.0 27.6 29.0
10.7 10.2
7.0
8.5
7.6
26.0 24.0 24.2 24.6 24.3
6.3 4.5 4.3 7.0 5.4
25.8 23.4 25.3 24.6 23.9
3.8 3.6 6.1 4.7 4.1
NA NA NA NA NA
NA NA NA NA NA
NA NA NA NA NA
NA 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 Respnse v 2 .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.
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
All Trials
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
All Trials
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
Grand Mean S.D.
S.E.M. Count
Minimum 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 NA NA NA NA NA
NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 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 Respnse v 2 .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
Tmax
All
Number
1-10 11-20 21-30 31-40 41-50 Trials 1-10 11-20 21-30 31-40 41-50 Trials Vave
1
Mean 290.2 238.6 157.6 135.6 155.4
195.5
28.5 27.6 29.3 32.5 33.8
30.4
42.7
S.D. 167.9 135.5 77.9 65.1 123.1
90.9
3.1 3.1 6.3 6.2 7.3
4.4 18.8
2
Mean 329.7 237.5 175.9 176.0 130.4
209.9
31.8 34.6 31.9 29.8 29.6
31.5
46.5
S.D. 206.8 179.9 122.6 111.2 88.1
129.0
7.4 8.0 7.0 3.0 5.0
4.8 28.0
3
Mean 207.7 152.1 124.2 110.6 95.2
138.0
29.5 28.7 32.2 33.5 37.0
32.2
29.3
S.D. 124.4 102.6 68.4 63.5 67.7
64.3
4.3 1.5 5.3 4.2 7.5
2.7 12.8
4
Mean 341.0 272.6 253.2 195.5 173.2
247.1
30.8 32.7 34.3 35.6 34.5
33.6
53.0
S.D. 161.3 198.7 257.3 146.5 143.2
162.7
5.6 7.5 8.0 7.1 9.4
5.9 33.5
5
Mean 295.0 258.0 193.0 214.7 188.3
229.8
30.7 32.3 35.4 32.2 34.7
33.1
46.6
S.D. 292.0 326.5 297.3 361.5 243.5
299.3
8.8 10.8
9.3
6.5
8.6
7.0 57.0
6
Mean 126.7 109.5 93.0 79.0 72.0
96.0
33.2 32.4 38.7 37.8 37.7
36.0
21.2
S.D.
90.7
111.0 74.1
63.9
56.8
58.2
5.2 5.8 8.6 7.1 10.0
5.1
12.2
7
Mean 127.2 107.7 73.5 70.2 57.3
87.2
34.8 36.4 40.4 39.0 44.2
39.0
21.2
S.D. 71.4
98.8 39.8 47.9 37.2
48.0
5.6 7.2
6.5 10.2 13.5
5.5
12.7
8
Mean 198.4 141.2 128.9 93.0 90.4
130.4
30.3 30.7 32.4 34.7 32.7
32.2
28.7
S.D. 106.8
91.4 102.0 69.6
66.4
68.1
7.1 5.5 6.7 5.9 6.6
3.9 14.0
9
Mean 141.8 96.4 58.6 75.5 72.0
88.8
32.7 32.4 33.7 37.0 36.5
34.5
20.0
S.D. 134.9
81.2
50.0
57.6
70.4
73.8
8.9 5.4
7.8 10.2 10.5
5.8
16.3
10
Mean 316.6 241.8 198.8 154.9 168.8
216.2
30.3 31.4 32.0 28.3 26.6
29.7
42.7
S.D. 315.1 219.9 176.5 149.5 155.4
183.8
8.5 8.1
7.5 10.8 6.7
5.7 38.1
11
Mean 184.9 189.0 133.6 98.7 149.6
151.1
31.2 32.6 36.8 32.2 36.8
33.9
33.1
S.D. 113.5 161.3 122.7 75.5 162.0
112.0
5.2 9.4 12.1 8.6
9.2
7.1 21.5
12
Mean 308.1 206.6 141.2 147.6 154.2
191.5
31.5 32.1 31.0 31.5 36.0
32.4
39.7
S.D. 235.1 173.4 88.0 144.1 189.9
128.6
8.6 7.1 4.9 5.4 11.5
5.1
23.0
13
Mean 177.0 136.7 131.2 154.6 118.1
143.5
32.4 31.4 29.8 28.5 27.2
29.9
28.5
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 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 Respnse 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
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 Respnse 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 Respnse v 2 .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 Respnse v 2 .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
Tmax
All
Number
1-10 11-20 21-30 31-40 41-50 Trials 1-10 11-20 21-30 31-40 41-50 Trials Vave
1
Mean 144.7 98.1 100.5 111.5 79.4
106.8
32.8 32.6 35.5 34.9 32.1
33.6
21.5
S.D. 92.6 77.5 68.5 88.9 58.2
56.0
5.3 7.9 6.5 8.6 4.2
4.5 11.0
2
Mean 116.8 81.3 72.3 61.8 58.8
78.2
33.5 32.0 36.7 33.9 35.2
34.3
16.8
S.D. 53.1 47.2 40.7 45.9 33.2
36.1
5.4 5.3 6.3 7.1 4.5
4.4
7.6
3
Mean 163.1 83.4 71.2 76.6 62.1
91.3
29.6 33.7 33.8 35.0 33.3
33.1
18.6
S.D. 105.8 56.5 55.0 41.8 40.6
53.7
4.9 6.4 7.4 6.7 6.3
4.7 11.7
4
Mean 167.6 139.7 93.3 90.8 110.4
120.3
29.3 31.4 31.1 30.0 31.9
30.8
23.5
S.D. 91.1 98.5 52.3 66.3 111.7
73.6
4.4 6.6 4.6 5.0 6.2
3.4 15.9
5
Mean 177.5 176.7 146.6 122.1 114.7
147.5
29.1 30.8 34.3 34.9 33.5
32.5
29.1
S.D. 131.5 184.5 168.2 125.6 120.0
140.0
6.3 6.7 9.3 9.1 6.0
6.8 25.6
6
Mean 87.8 59.9 68.5 51.9 44.2
62.5
33.4 35.8 38.7 39.9 38.5
37.2
12.4
S.D. 45.0 43.3 43.8 20.8 20.6
24.7
8.5 11.4 11.8
6.6
6.8
5.7 4.7
7
Mean 102.1 91.6 89.9 64.1 65.6
82.6
37.4 36.2 34.7 39.7 37.6
37.1
18.1
S.D. 61.0 66.9 55.8 41.2 55.2
41.3
6.3 11.8
6.8
7.5
9.8
5.8
9.0
8
Mean 111.9 80.7 68.4 74.0 69.9
81.0
30.4 31.6 33.7 32.6 34.8
32.6
16.0
S.D. 87.3 64.2 64.5 71.5 79.6
70.6
5.5 6.1 8.1 8.5 7.9
5.1 13.3
9
Mean 72.4 51.2 42.6 39.5 37.1
48.6
35.3 36.2 38.5 37.3 36.1
36.7
11.0
S.D. 44.3 31.5 24.2 27.6 20.9
24.4
8.3 6.6 6.1 8.5 6.9
5.1
5.9
10
Mean 147.9 109.2 101.9 94.4 70.0
104.3
31.2 29.5 30.9 30.7 30.4
30.6
16.5
S.D. 71.6 58.1 61.1 62.9 41.6
48.4
6.9 4.9 7.9 8.1 6.9
5.0
8.3
11
Mean 163.7 121.4 88.3 109.3 67.1
109.9
31.0 35.3 35.3 31.1 39.3
34.4
22.9
S.D. 117.4 110.1 66.3 58.7 43.9
61.6
9.2 11.2
9.2
7.3
9.8
6.3 12.1
12
Mean 146.0 101.2 81.7 137.6 116.0
116.5
29.9 35.5 30.5 30.9 32.2
31.8
24.6
S.D. 100.3 41.0 46.0 171.5 152.1
75.0
3.9 8.3 5.1 8.5 5.9
4.2 14.4
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.
34.8 37.8 36.1
36.0
10.0
IGS Rat DNT Auditory Startle Response v2
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 Respnse v2.1
WIL-180017 3M Corporation
-2141-
MTDID 208 06-128
APPENDIX 66
W IL B iel M aze H istorical Control D ata V ersion 1.2 [C rl:C D (SD ) Rats]
w i l Historical Control Data cri: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)
1 of 27
Path A Trials (Learning) 1234
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) 56789
Path A Trials (Memory)
10 11 12
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
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
w i l 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)
2 of 27
Path A Trials (Learning) i234
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) 56789
Path A Trials (Memory)
10 11 12
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
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 SEC = Seconds PND = Postnatal day NA = Not applicable
(20 males and 20 females tested)
IGS Rat Biel Maze HC v1.2
w i l 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)
3 of 27
Path A Trials (Learning) i234
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) 56789
Path A Trials (Memory)
10 11 12
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
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 SEC = Seconds PND = Postnatal day NA = Not applicable
(19 males and 20 females tested)
IGS Rat Biel Maze HC v1.2
w i l 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)
4 of 27
Path A Trials (Learning) 1234
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) 56789
Path A Trials (Memory)
10 11 12
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
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 SEC = Seconds PND = Postnatal day NA = Not applicable
(10 males and 10 females tested)
IGS Rat Biel Maze HC v1.2
w i l Historical Control Data cri: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)
5 of 27
Path A Trials (Learning) 12 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) 56789
Path A Trials (Memory)
10 11 12
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
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
w i l Historical Control Data Crl:CD(SD) Rat*
Male PND 63 Mean Time (SEC) S.D. S.E. Min. Max.
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)
6 of 27
Path A Trials (Learning) 1234
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) 56 7 8 9
Path A Trials (Memory)
10 11 12
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
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
w i l Historical Control Data cri: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)
7 of 27
Path A Trials (Learning) 1234
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) 56789
Path A Trials (Memory)
10 11 12
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
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
w i l Historical Control Data cri: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)
8 of 27
Path A Trials (Learning) 123 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) 56789
Path A Trials (Memory)
10 11 12
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
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 SEC = Seconds PND = Postnatal day NA = Not applicable
(18 males and 20 females tested)
IGS Rat Biel Maze HC v1.2
w i l Historical Control Data cri:CD(SD) Rat*
M a l e 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) 1234
Path B Trials (Learning) 56789
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
42.7 6.5
130.3 28.9
87.3 16.2
97.8 23.0
103.1 22.5
83.0 17.8
50.0 12.2
155.1 28.8
110.6 17.4
116.2 18.6
86.0 15.3
64.7 10.3
67.6 11.4
122.6 25.2
150.2 31.0
90.0 15.9
114.3 28.2
78.7 13.8
63.1 11.5
113.3 20.8
97.0 16.3
90.6 15.5
86.5 15.8
70.8 12.9
62.1 10.0
136.4 25.5
103.6 19.0
108.3 19.0
59.9 8.6
69.3 12.4
40.6 6.7
158.5 32.1
115.3 22.6
104.9 22.9
84.3 15.6
69.2 13.2
71.3 12.2
144.5 31.5
109.7 20.7
87.3 18.8
79.3 14.9
69.2 13.6
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
w i l Historical Control Data cri:CD(SD) Rat*
M a l e 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) 1234
Path B Trials (Learning) 56789
1 0 of 27
Path A Trials (Memory)
10 11 12
58.6 9.9
53.1 9.3
68.3 12.4
45.3 7.2
93.5 13.3
73.4 12.7
104.9 17.3
72.5 13.4
78.9 16.6
100.4 20.6
56.2 13.2
54.0 11.9
88.7 19.2
62.8 13.1
43.2 8.3
32.0 6.7
78.4 13.8
52.6 10.9
66.3 13.8
46.0 9.5
79.4 12.9
54.4 9.3
68.1 14.4
52.7 9.9
98.9 20.2
55.3 10.8
54.3 11.9
49.5 11.0
152.2 32.0
92.4 18.5
116.7 24.6
62.5 13.9
63.2 14.7
44.4 9.4
134.4 19.8
128.3 17.7
124.2 13.5
117.1 15.0
90.3 10.6
96.1 12.4
151.3 33.3
86.7 15.3
148.5 34.0
115.7 24.0
88.2 15.6
75.5 14.1
133.8 26.0
136.7 29.7
121.1 25.4
117.5 26.0
82.1 15.7
67.4 15.5
147.2 27.8
138.3 29.1
111.5 23.5
77.8 16.1
87.0 16.5
44.8 8.6
141.9 27.1
107.5 21.1
95.6 19.7
71.7 13.5
65.8 14.3
74.0 15.4
136.6 29.3
128.1 26.9
108.8 25.5
78.7 14.8
37.5 9.1
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
w i l Historical Control Data cri:CD(SD) Rat*
M a l e 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) i234
Path B Trials (Learning) 56789
1 1 of 27
Path A Trials (Memory)
10 ii 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, SEC = Seconds PND = Postnatal day NA = Not applicable
2005,
this
strain of rat was designated the Crl:CD(SD)IGS BR rat.
IGS Rat Biel Maze HC v1.2
w i l Historical Control Data Crl:CD(SD) Rat*
F e m a l e 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 23 4
Path B Trials (Learning) 567 89
1 2 of 2 7
Path A Trials (Memory)
10 11 12
94.0 14.6
48.2 8.2
63.6 12.5
39.6 5.8
66.5 11.3
73.6 16.5
74.3 15.9
58.6 12.0
66.8 11.9
52.3 6.7
43.4 6.7
48.1 8.5
64.2 9.5
84.4 15.0
74.5 13.5
46.1 7.8
99.2 17.6
114.6 17.1
58.1 11.3
65.0 14.2
55.5 11.3
69.4 14.2
72.3 15.0
38.7 6.2
76.5 13.6
78.0 12.5
64.5 13.1
50.3 8.8
69.3 14.6
72.2 15.8
63.6 11.8
29.3 7.2
166.5 30.1
102.1 19.4
87.5 14.6
46.6 8.4
51.9 8.5
33.6 5.2
164.3 31.1
112.4 19.8
100.3 22.3
73.0 13.3
71.0 14.8
43.5 11.7
115.7 13.7
109.8 19.6
63.6 6.0
77.8 9.6
55.5 16.9
72.5 13.3
168.6 29.5
116.3 20.9
120.9 21.1
106.5 21.4
125.0 24.2
52.3 8.7
116.4 21.8
119.7 22.1
111.0 19.3
99.0 17.6
72.3 14.9
54.7 9.2
147.7 23.0
147.5 22.2
101.3 16.2
61.1 8.9
99.9 16.5
61.8 12.2
123.2 24.8
128.9 24.9
102.3 21.3
80.6 14.4
86.8 15.7
47.6 6.5
147.1 25.3
106.4 17.2
109.0 23.1
60.7 10.7
63.2 13.1
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
w i l Historical Control Data cri:CD(SD) Rat*
F e m a l e 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) i234
Path B Trials (Learning) 56789
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
w i l Historical Control Data cri:CD(SD) Rat*
F e m a l e 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) i234
Path B Trials (Learning) 56789
14 of 27
Path A Trials (Memory)
10 ii 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, SEC = Seconds PND = Postnatal day NA = Not applicable
2005,
this
strain of rat was designated the Crl:CD(SD)IGS BR rat.
IGS Rat Biel Maze HC v1.2
WIL Historical Control Data Crl:CD(SD) Rat*
M a l e PND 24 Study 18 Mean Time (SEC) Mean No. Errors
F e m a l e 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 C o n d u c t e d B e t w e e n 6/14/99 an d 6/28/04)
Path A Trials (Learning) i234
Path B Trials (Learning) 56789
15 of 27
Path A Trials (Memory)
10 ii 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, SEC = Seconds PND = Postnatal day NA = Not applicable
2005,
this
strain of rat was designated the Crl:CD(SD)IGS BR rat.
IGS Rat Biel Maze HC v1.2
WIL Historical Control Data Crl:CD(SD) Rat*
M a l e PND 26 Study 12 Mean Time (SEC) Mean No. Errors
F e m a l e 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 C o n d u c t e d B e t w e e n 6/14/99 an d 6/28/04)
Path A Trials (Learning) i234
Path B Trials (Learning) 56789
16 of 27
Path A Trials (Memory)
10 ii 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, SEC = Seconds PND = Postnatal day NA = Not applicable
2005,
this
strain of rat was designated the Crl:CD(SD)IGS BR rat.
IGS Rat Biel Maze HC v1.2
WIL Historical Control Data Crl:CD(SD) Rat*
M a l e PND 60 Study 17 Mean Time (SEC) Mean No. Errors
F e m a l e 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 C o n d u c t e d B e t w e e n 6/14/99 an d 6/28/04)
Path A Trials (Learning) i234
Path B Trials (Learning) 56789
17 of 27
Path A Trials (Memory)
10 ii 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, SEC = Seconds PND = Postnatal day NA = Not applicable
2005,
this
strain of rat was designated the Crl:CD(SD)IGS BR rat.
IGS Rat Biel Maze HC v1.2
w i l Historical Control Data cri:CD(SD) Rat*
M a l e 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) i234
Path B Trials (Learning) 56789
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
91.3 15.5
48.1 9.2
65.6 10.8
49.4 8.9
131.4 21.3
122.4 22.9
71.1 9.6
37.5 7.3
93.2 17.1
51.8 8.6
142.4 22.0
86.2 12.2
85.4 13.3
55.8 9.3
25.3 2.6
23.2 3.0
101.2 20.1
119.8 24.6
80.1 18.8
35.6 8.3
23.3 4.2
24.6 4.2
137.0 24.7
105.7 18.3
81.3 17.5
33.3 5.7
39.1 7.3
43.9 8.9
140.7 25.8
107.9 20.8
71.9 12.6
30.0 4.8
34.8 6.7
20.4 3.2
157.4 19.4
79.9 12.6
34.6 5.5
34.2 6.2
27.1 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
w i l Historical Control Data Crl:CD(SD) Rat*
M a l e 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) 1 234
Path B Trials (Learning) 56789
19 of 27
Path A Trials (Memory)
10 ii 12
76.1 14.8
35.1 8.0
66.0 14.3
22.0 3.7
77.6 15.1
44.7 9.0
26.9 4.8
28.3 5.3
95.3 17.7
94.2 18.5
54.5 13.7
27.5 6.5
59.1 12.2
52.2 11.1
62.6 16.8
39.0 8.0
61.0 10.8
54.6 11.9
44.4 8.7
48.7 10.5
63.2 14.6
45.8 10.5
57.6 15.1
33.6 7.3
54.9 10.7
55.7 11.9
40.6 8.5
29.7 6.6
78.9 15.3
51.2 10.5
57.5 10.0
25.3 4.9
164.4 32.0
109.0 17.7
47.8 8.2
39.0 5.7
47.7 5.7
34.9 4.2
108.4 20.6
89.1 15.4
74.9 10.6
45.4 6.0
42.1 6.7
24.9 4.1
145.5 30.9
95.2 19.3
67.3 11.9
27.2 4.1
31.9 5.9
26.3 6.9
82.9 16.5
78.0 17.3
30.2 7.0
26.0 4.2
26.5 4.5
13.7 1.2
147.4 27.5
98.1 18.6
75.0 15.9
41.9 8.9
18.0 1.8
16.5 2.0
127.9 24.5
76.3 15.0
49.4 9.8
32.2 6.9
59.3 11.4
37.7 7.5
128.4 29.0
99.2 21.5
85.2 16.7
59.8 10.4
39.7 6.4
28.9 4.7
133.5 22.7
91.5 17.8
81.7 13.5
55.3 9.6
60.6 9.8
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
w i l Historical Control Data cri:CD(SD) Rat*
M a l e 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 23 4
Path B Trials (Learning) 567 89
2 0 of 2 7
Path A Trials (Memory)
10 11 12
61.8 11.9
56.7 13.3
36.4 7.5
32.3 8.9
45.5 9.8
41.6 9.5
25.8 5.5
15.4 2.8
76.6 14.2
58.1 11.2
45.0 11.0
42.3 9.6
60.4 14.2
47.8 9.8
40.0 8.5
28.1 5.8
129.1 20.5
74.5 12.0
70.2 13.2
57.5 8.9
109.8 20.7
54.2 12.3
47.3 9.3
20.4 5.7
59.6 12.6
36.4 9.5
25.7 5.6
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
w i l Historical Control Data cri:CD(SD) Rat*
F e m a l e 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 23 4
Path B Trials (Learning) 567 89
2 1 of 2 7
Path A Trials (Memory)
10 11 12
82.3 16.8
51.7 10.7
60.6 13.0
43.4 9.5
97.5 17.5
53.6 10.8
36.4 6.3
39.4 7.3
81.0 15.5
66.6 12.6
42.7 7.7
30.3 5.6
71.4 13.1
44.9 9.2
38.6 8.1
28.9 6.3
40.2 5.6
46.7 7.8
40.4 7.0
30.9 4.5
81.0 15.0
59.8 13.3
37.2 8.5
36.2 8.5
72.0 11.8
72.0 16.3
34.0 6.0
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
w i l Historical Control Data cri:CD(SD) Rat*
F e m a l e 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 23 4
Path B Trials (Learning) 567 89
2 2 of 2 7
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
64.4 8.9
68.0 11.8
54.0 8.7
36.2 4.9
121.2 24.7
72.2 13.9
80.7 13.8
39.5 6.1
43.2 7.7
23.4 3.5
116.2 27.3
112.0 21.0
98.8 20.7
73.5 10.8
57.2 10.8
49.2 7.8
110.3 23.3
61.2 13.6
56.6 13.3
28.2 5.1
22.9 4.1
27.7 5.4
116.3 23.6
99.0 17.8
62.2 11.1
47.5 7.9
21.5 1.8
30.4 5.2
126.4 21.8
98.2 17.5
71.8 11.8
51.0 7.4
41.3 6.0
46.7 7.4
137.8 31.6
104.4 23.8
50.2 9.5
39.1 6.1
42.8 7.1
28.7 4.4
141.7 25.1
100.4 20.8
89.0 15.9
47.7 8.0
39.3 7.1
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
w i l Historical Control Data cri:CD(SD) Rat*
F e m a l e 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) i234
Path B Trials (Learning) 56789
23 of 27
Path A Trials (Memory)
10 11 12
71.6 15.8
43.6 9.7
39.2 8.4
32.1 7.2
92.9 19.8
41.2 8.3
50.4 11.5
22.5 3.7
87.1 17.3
67.1 15.1
45.1 10.4
27.5 5.3
51.6 9.3
67.4 15.6
34.7 7.7
36.6 8.2
86.6 12.6
80.4 15.3
47.5 8.3
44.7 8.4
77.9 15.0
65.3 13.1
45.8 8.0
31.4 6.3
98.4 20.1
37.1 8.3
32.7 7.1
32.7 7.8
125.0 29.8
103.6 24.0
90.7 18.2
43.9 9.4
31.1 5.2
26.6 3.6
165.3 36.1
80.5 15.2
59.5 13.7
30.5 5.8
43.4 9.1
33.8 7.5
126.8 27.9
92.0 19.7
96.0 20.4
58.2 11.7
55.2 10.6
44.0 8.2
127.5 28.7
109.1 23.8
64.1 14.9
30.7 6.4
29.9 5.3
25.3 4.7
131.3 23.8
136.8 23.0
110.1 19.7
74.5 9.6
48.8 8.0
48.3 7.2
139.5 24.4
92.4 16.3
60.6 8.6
26.7 3.1
27.4 3.4
32.4 5.6
139.6 27.9
82.8 19.6
53.1 13.3
33.4 6.6
37.6 6.8
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
w i l Historical Control Data cri: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) i234
Path B Trials (Learning) 56 78 9
24 of 27
Path A Trials (Memory)
10 ii 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, SEC = Seconds PND = Postnatal day NA = Not applicable
2005,
this
strain of rat was designated the Crl:CD(SD)IGS BR rat.
IGS Rat Biel Maze HC v1.2
w i l Historical Control Data cri:CD(SD) Rat*
M a l e PND 70 Study 24 Mean Time (SEC) Mean No. Errors Study 25 Mean Time (SEC) Mean No. Errors
F e m a l e 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) i234
Path B Trials (Learning) 56789
25 of 27
Path A Trials (Memory)
10 ii 12
81.6 16.7
51.6 12.5
42.1 9.7
29.5 6.9
73.0 15.4
43.1 9.4
34.4 7.0
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, SEC = Seconds PND = Postnatal day NA = Not applicable
2005,
this
strain of rat was designated the Crl:CD(SD)IGS BR rat.
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 C o n d u c t e d B e t w e e n 6/14/99 an d 6/28/04)
Path A Trials (Learning) i234
Path B Trials (Learning) 56789
26 of 27
Path A Trials (Memory)
10 ii 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, SEC = Seconds PND = Postnatal day NA = Not applicable
2005,
this
strain of rat was designated the Crl:CD(SD)IGS BR rat.
IGS Rat Biel Maze HC v1.2
WIL Historical Control Data Crl:CD(SD) Rat*
Biel Maze - Grand Mean Data ( 2 7 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
Maze HC v1.2
