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A P.& 2 .6 ,0616 n H'c n1 ir-!$ 2000 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats PREPARED FOR: 3M COVANCE STUDY NUMBER: 6329-224 000564 COVAfC> H E DEVELOPMENT SERVICES COMPANY Sponsor: 3M St. Paul, Minnesota FINAL REPORT Study Title: 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Author: Peter J. Thomford, PhD Study Completion Date. July 5, 2000 Performing Laboratory: Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Laboratory Study Identification: Covance 6329-224 Sponsor Project Identification: 3M T-6314.2 Page 1 o f 373 000565 Covance 6329-224 3M T-6314.2 QUALITY ASSURANCE STATEMENT This report, with the exception o f Appendix 7, has been reviewed by the Quality Assurance Unit o f Covance Laboratories Inc., in accordance with the Food and Drug Administration (FDA) Good Laboratory Practice Regulations, 21 CFR 58. The data in Appendix 7 was generated by and is the responsibility o f Pathology Associates International. The following inspections were conducted and findings reported to the study director and study director management. Inspection Dates________ From To Phase 06/04/98 06/04/98 Protocol Review 07/13/98 07/13/98 Postlife 09/16/98 09/25/98 Data Review 10/01/98 10/09/98 Data Review 10/19/98 10/22/98 Report Review 06/02/99 06/02/99 Protocol Amendment Review 05/02/00 05/03/00 Report Review Date Reported to Study Director and Study Director Management 06/04/98 07/13/98 09/25/98 10/09/98 10/22/98 06/02/99 05/03/00 Quality Assurance Unit OS' 3btu Jioo Date I 2 000566 Covance 6329-224 3M T-6314.2 STUDY IDENTIFICATION 4-W eek Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Test Material N-Methyl Perfluorooctanesulfonamido Ethanol (MeFOSE, T -6314) Sponsor 3M Toxicology Services Building 220-2E-02, 3M Center St. Paul, Minnesota 55144-1000 Study Monitor Andrew M. Seacat, PhD 3M Toxicology Services 651.575.3161 Alternate Study Monitor Marvin T. Case, DVM, PhD 3M Toxicology Services 651.733.5180 Study Location Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Study Director Peter J. Thomford, PhD Covance Laboratories Inc. P.O. Box 7545 Madison, Wisconsin 53707-7545 608.241.7207 Study Timetable Study Initiation Date In-Life Start Date In-Life End Date Study Completion Date June 8, 1998 June 12, 1998 July 13, 1998 July 5, 2000 3 000567 Covance 6329-224 3M T-6314.2 KEY PERSONNEL 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Study Director Study Toxicologist Study Coordinator Supervisor, Small Animal Toxicology Supervisor, Dose Formulation Supervisor, Chemistry/Tox Support Supervisor, Laboratory Animal Medicine Clinical Pathologist Supervisor, Clinical Pathology Anatomical Pathologist Supervisor, Anatomical Pathology Peter J. Thomford, PhD Thomas E. Ryan, BS Nii van Bruce-Konuah Nathan E. Snortum, BA, BT, ALAT Dixie Bushee, BS, LATG Brian Schoenike, BS Donna J. Clemons, DVM Diplomate, ACLAM Robert L. Hall, DVM, PhD Diplomate, ACVP (Clinical Pathology) Ronald Markevitch, BS, MT (ASCP) Richard Hamilton Bruner, DVM Diplomate, ACVP Pathology Associates International Deborah Pirkel, ALAT 4 000568 Covance 6329-224 3M T-6314.2 CONTENTS Page A B S T R A C T ..................................................................................................................................... 8 PURPOSE...................................................................................................................................... 10 REGULATORY COM PLIANCE.............................................................................................. 10 TEST MATERIAL AND V EH ICLE.........................................................................................10 Test M aterial............................................................................................................................. 10 V ehicle....................................................................................................................................... 10 Reserve (Archive) Sam ples..................................................................................................... 11 D isposition.................................................................................................................................11 TEST SY STEM ............................................................................................................................ 11 Test Animal............................................................................................................................... 11 Identification.............................................................................................................................. 11 Acclimation............................................................................................................................... 11 Housing and Maintenance....................................................................................................... 12 Justification............................................................................................................................... 12 PROCEDURES............................................................................................................................. 12 Group Designations and Dietary L evels............................................................................... 13 Dose Preparation...................................................................................................................... 13 Retention Sam ples.................................................................................................................... 14 Dose Analyses........................................................................................................................... 14 Method o f Administration....................................................................................................... 15 Clinical Observations............................................................................................................... 16 Body W eights............................................................................................................................ 16 Food Consumption...................................................................................................................16 Serum Perfluorooctane Sulfonic Acid Level (PFOS) Determination............................... 16 Clinical Pathology..................................................................................................................... 16 N ecropsy.................................................................................................................................... 17 Organ W eights...........................................................................................................................18 Cell Proliferation Tissue Collection and Immunohistochemical Evaluation.....................18 Palmitoyl-CoA Oxidase Tissue Collection and Analyses....................................................18 Liver PFOS Analyses............................................................................................................... 18 Tissue Preservation...................................................................................................................19 Statistical Analyses...................................................................................................................20 RECORD R ET EN TIO N .............................................................................................................20 5 000569 Covance 6329-224 3M T-6314.2 CONTENTS (Continued) Page RESU LTS...................................................................................................................................... 21 Dose Analyses...........................................................................................................................21 Clinical Observations and Survival........................................................................................ 21 Body Weights and Body Weight C hanges............................................................................22 Food Consum ption...................................................................................................................22 Test Material Consumption.....................................................................................................23 Serum Perfluorooctane Sulfonic Acid Level (PFOS) Determ ination............................... 23 Clinical Pathology.....................................................................................................................23 Cell Proliferation Tissue Collection and Immunohistochemical Evaluation.....................24 Liver PFOS Determination...................................................................................................... 24 Anatomical Pathology.......... .................................................................................................. 24 C O N C L U S IO N S ...........................................................................................................................25 SIGNATURES.............................................................................................................................. 26 R E F E R E N C E S .............................................................................................................................. 27 PATHOLOGY REPORT.............................................................................................................28 COMMENTS ON THE D A T A ................................................................................................. 33 CODES, ABBREVIATIONS, AND UNITS............................................................................35 General Codes and Abbreviations...........................................................................................36 Codes for Clinical Pathology.................................................................................................. 37 Abbreviations and Units for Clinical Hematology...............................................................40 Abbreviations and Units for Clinical Chem istry.................................................................. 42 Abbreviations and Units for Clinical Urinalysis................................................................... 44 Codes for Anatomical Pathology............................................................................................45 TABLES 1 Results o f Homogeneity Analyses (ppm ).......................................................................47 2 Results o f Stability Analyses (ppm )................................................................................ 49 3 Results o f Dose Preparation Analyses (ppm )................................................................ 51 4 Summary o f Clinical Observations.................................................................................. 53 5 Summary o f Body Weight Data (g )................................................................................ 54 6 Summary o f Body Weight Change Data ( g ) ................................................................. 58 7 Summary o f Food Consumption Data (g )......................................................................62 8 Summary o f Test Material Consumption Data (mg/kg/day)....................................... 66 9 Summary o f Clinical Hematology D ata.......................................................................... 68 10 Summary o f Clinical Chemistry D ata..............................................................................72 11 Summary o f Clinical Urinalysis D a ta ..............................................................................76 6 000570 Covance 6329-224 3M T-6314.2 CONTENTS (Continued) Page TABLES 12 Summary o f Absolute Organ Weight Data (g )..............................................................78 13 Summary o f Organ-to-Body Weight Percentages........................................................ 81 14 Summary o f Organ-to-Brain Weight Ratios...................................................................84 15 Incidence o f Macroscopic O bservations........................................................................ 87 16 Incidence o f Microscopic Observations......................................................................... 89 17 Incidence o f Severity o f Selected Microscopic Observations......................................97 APPENDIX 1................................................................................................................................ 98 Protocol Deviations................................................................................................................. 99 Protocol.................................................................................................................................... 100 Protocol Amendment No. 1 ..................................................................................................117 APPENDIX 2 .............................................................................................................................. 123 Individual Animal Fate D ata..................................................................................................124 Individual Clinical Observations...........................................................................................127 APPENDIX 3 .............................................................................................................................. 133 Individual Body Weight Data ( g ) .........................................................................................134 APPENDIX 4 .............................................................................................................................. 138 Individual Food Consumption Data (g ).............................................................................. 139 Individual Test Material Consumption D ata (mg/kg/day)................................................ 143 APPENDIX 5 .............................................................................................................................. 146 Individual Clinical Hematology D ata...................................................................................147 Individual Clinical Chemistry D a ta ...................................................................................... 159 Individual Clinical Urinalysis D ata....................................................................................... 167 APPENDIX 6 .............................................................................................................................. 179 Individual Absolute Organ Weight Data ( g ) ...................................................................... 180 Individual Organ-to-Body Weight Percentages..................................................................192 Individual Organ-to-Brain Weight R atios...........................................................................204 Individual Animal Pathology D ata....................................................................................... 216 APPENDIX 7 .............................................................................................................................. 359 Cell Proliferation R eport....................................................................................................... 360 7 000571 ABSTRACT Covance 6329-224 3M T-6314.2 The purpose o f this study was to assess the toxicity of the test material, N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) when administered in the diet to rats for at least 4 weeks. Six groups o f Crl:CD(SD) IGS BR rats were exposed to N-MeFOSE in the diet for at least 4 weeks. Each group contained six males and six females. The dose levels were 0 (control group), 1, 10, 30,100, and 500 ppm. Food was provided ad libitum, except when animals were fasted. Water was provided ad libitum. The animals were observed twice daily (a.m. and p.m.) for mortality and moribundity. At least once each week, each animal was removed from its cage and examined for abnormalities and signs of toxicity. Body weights and food consumption data were collected twice weekly for at least 4 weeks. Blood and urine samples were collected for hematology, clinical chemistry, and urinalysis tests from all surviving animals after 4 weeks o f treatment. After at least 4 weeks o f treatment, blood was also collected from all surviving animals for serum perfluorooctane sulfonic acid (PFOS) analyses. On Day 32, the animals were anesthetized, weighed, exsanguinated, and necropsied. At necropsy, macroscopic observations were recorded, selected organs were weighed, and selected tissues were collected and preserved. Samples o f liver were collected from all surviving animals for palmitoyl-CoA oxidase activity (by Covance) and proliferation cell nuclear antigen (PCNA) evaluation and liver PFOS analysis (by the Sponsor). The animal that died on test was also necropsied, but organ weights were not recorded. Microscopic examinations were done on tissues from each animal. One animal given 500 ppm N-MeFOSE died on Day 25. All other animals survived to the scheduled sacrifice. No clinical observations were noted that were considered to represent primary effects of the test material. Lower body weight, body weight gains, and food consumption in animals given 500 ppm were test material-related. Dietary administration of N-MeFOSE at a dose level o f 500 ppm for approximately 4 weeks was associated with several effects on clinical pathology test results including moderately lower red blood cell count, hemoglobin, and hematocrit; lower absolute eosinophil count; mildly higher urea nitrogen; moderately higher albumin and mildly to 8 000572 Covance 6329-224 3M T-6314.2 moderately lower globulin; markedly lower cholesterol; mildly to moderately higher total bilirubin, aspartate aminotransferase, and alanine aminotransferase; and moderately higher hepatic palmitoyl-CoA oxidase. O f uncertain relationship to administration o f N-MeFOSE were lower urine pH for males fed 500 ppm and small differences for animals fed 100 ppm including higher urea nitrogen, albumin, and alanine aminotransferase (males only) and lower cholesterol. O f the differences for animals fed 100 ppm, only the difference for alanine aminotransferase was statistically significant. Mean absolute and relative (to brain and body) liver weights for all males and females given 100 and 500 ppm N-MeFOSE were significantly increased over control values, and these variations were regarded as treatment-related. All additional mean organ weights, which varied significantly from control values, were considered to be within the range or normal biologic variation, or were manifestations o f slight weight loss associated with physiologic stress. Treatment-related microscopic findings were restricted to the liver and consisted o f minimal to severe centrilobular hepatocellular hypertrophy. Hypertrophic changes were slightly more severe in males; and at the high-dose level, liver cell swelling in several males was associated with acute necrosis. Necrosis was attributed to restricted blood supply (ischemia) from swollen liver cells rather than direct hepatocellular damage. Additional microscopic findings were consistent with common, spontaneous alterations in laboratory rats or changes associated with stress, nutritional deprivation, or tissue processing artifact. Based on the results o f this study, dietary administration o f N-MeFOSE to Crl:CD(SD) IGS BR rats for at least 4 weeks resulted in adverse effects at a dose level o f 500 ppm. The no-observable-adverse-effect level was determined to be 100 ppm. 9 000573 PURPOSE Covance 6329-224 3M T-6314.2 The purpose o f this study was to assess the toxicity of the test material, N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) when administered in the diet to rats for at least 4 weeks. REGULATORY COMPLIANCE The study was conducted in compliance with the Food and Drug Administration Good Laboratory Practice Regulations as set forth in Title 21 o f the US Code o f Federal Regulations, Part 58, issued December 22, 1978 (effective June 20, 1979), and with any applicable amendments. TEST MATERIAL AND VEHICLE Test Material The test material, N-Methyl Perfluorooctanesulfonamido Ethanol (MeFOSE, T-6314), Lot No. F-l 1364, is an off white powder. It was received at Covance on August 3, 1995. Information on synthesis methods, stability, purity, composition, or other characteristics that define the test material is on file with the Sponsor. The test material was stored at room temperature. Vehicle The vehicle was acetone (Spectrum Quality Products Inc., Gardena, California), Lot No. LH0253 (expiration date: June 2000). It was received at Covance on June 23, 1997. The vehicle was stored at room temperature. Information on synthesis methods, stability, purity, composition, or other characteristics that define the acetone is on file with the manufacturer. 10 000574 Covance 6329-224 3M T-6314.2 Reserve (Archive) Samples A reserve sample {approximately 5 g) of the test material was taken and stored at room temperature. These samples will be transferred to the Sponsor after authorization from the Sponsor. Disposition Remaining test material was retained for future use (see Protocol Deviations page for exception). TEST SYSTEM Test Animal Male and female Crl:CD(SD) IGS BR rats were obtained from the Raleigh, North Carolina, facility o f Charles River Laboratories, Inc., on June 2, 1998. The animals were 31 to 37 days old at initiation o f treatment. The males weighed from 144 to 194 g, and the females weighed from 114 to 158 g at initiation o f treatment. Identification Each animal was assigned a temporary number upon arrival. Before initiation o f treatment, a microchip identification device was implanted into each animal. After randomization for placement on test, each animal was assigned a permanent number, and the microchip was coded with the permanent number. All data for an animal are recorded under these numbers. Acclimation Forty-one males and 41 females were received on June 2, 1998, and acclimated in Animal Room 349 for 10 days before initiation o f treatment. In general, animals in this shipment appeared healthy. During acclimation, the animals were examined for abnormalities indicative o f health problems, and body weights were recorded for all animals at randomization. 11 000575 Covance 6329-224 3M T-6314.2 Housing and Maintenance Animal Room 349 was used for this study. Environmental controls for the animal room were set to maintain 18 to 26 C, a relative humidity o f 30 to 70%, and a 12-hour light/12-hour dark cycle. Variations from these conditions are documented in the data and are considered to have had no effect on the outcome o f the study. The animals were housed individually (except for the first 7 days o f acclimation when animals were group-housed) in stainless steel, screen-bottom cages. Certified rodent diet #5002 meal, (PMI Nutrition International) was provided ad libitum, except when animals were fasted. The diet is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. The results are on file with Covance-Madison. W ater was provided ad libitum. Samples o f the water are analyzed for specified microorganisms and environmental contaminants. The results are on file with Covance-Madison. There were no known contaminants in the diet or water at levels that would have interfered with this study. Animals not selected for the study (five males and five females) were removed from the study room and used for training procedures. Justification Rats historically have been used in safety evaluation studies and are recommended by appropriate regulatory agencies. PROCEDURES This study was conducted in accordance with the Protocol dated June 8, 1998, and Protocol Amendment No. 1. The protocol, protocol amendment, and protocol deviations are in Appendix 1. 12 000578 Covance 6329-224 3M T-6314.2 The animals were examined by a laboratory animal veterinarian on June 10, 1998, and found to be suitable for study consideration. Selection of animals for the study was based on clinical observations, body weights, and other data as appropriate. Animals were assigned to treatment groups using a computerized blocking procedure designed to achieve body weight balance with respect to treatment group. At the time of randomization, the weight variation o f the animals for each sex used did not exceed 2 standard deviations o f the mean weight. Group mean body weights were analyzed using Levene's test for homogeneity of variance at the 5.0% probability level and found to be homogeneous. Animals were assigned to the study according to the following design: G roup Designations and D ietary Levels Number o f Animals Dietary Levels Group Male Female (ppm MeFOS)8 1 (Control)*1 6 6 0 2 (Low) 66 1 3 (Low-Mid) 6 6 10 4 (Mid) 66 30 5 (Mid-High) 6 6 100 6 (High) 66 500 a Dose levels were expressed as ppm o f MeFOS. b The control animals received the basal diet only. Dose Preparation Dietary concentrations were based on the test material as supplied. Diets were prepared pretest for homogeneity, and twice for use in the in-life phase. P rep aratio n o f Diet fo r G ro u p 1. The appropriate amount o f diet was weighed into a labeled container, and acetone was added at the same concentration as the high-dose concentration. The combination o f the diet and acetone was then mixed for 15 minutes. P rep aratio n of D iet fo r G ro u p 6. Each dose level was prepared independently. A specified amount o f diet was weighed into a labeled Hobart mixing bowl. The required amount of test material was weighed and transferred into a labeled container. Approximately 5 mL o f acetone was added to the container and mixed manually. 13 000577 Covance 6329-224 3M T-6314.2 Increments o f approximately 5 mL acetone were added as necessary until the test material had dissolved. To prepare a premix, the diet was transferred into a labeled Hobart mixing bowl. The test material and acetone were added to the mixing bowl, overlaid with a portion of diet from the mixing bowl, and thoroughly mixed. A portion o f diet from the mixing bowl was transferred to a second mixing bowl, mixed manually to recover residual test material, and returned to the first mixing bowl. The contents o f the mixing bowl were thoroughly mixed. P rep aratio n of Diets for G roups 2 through 5. Each dose level was prepared independently. A specified amount o f diet was weighed into a labeled Hobart mixing bowl and a specified amount of diet for Group 6 was weighed for each diet. A pocket was formed in the feed in the mixing bowl and the amount o f diet for Group 6 was transferred to the pocket. The contents o f the maxing bowl were thoroughly mixed for 10 minutes. Samples for dose analyses were taken directly from the mixing bowl. The prepared test diets were stored at room temperature in covered containers until dispensed into feeding jars. Retention Samples Samples (approximately 100 g) were taken from each dose preparation sampled for dose analyses and stored at room temperature. These samples were discarded on December 9, 1998 (see Protocol Deviations page for exception). Dose Analyses Analyses for the concentration o f test material in the dose preparations were done by Covance using an analytical method, MP-M324-MA, supplied by the Sponsor and validated by Covance. Homogeneity was determined for all test material dose preparations once pretest. One sample each (approximately 100 g) from the top, middle, and bottom o f the dose preparations mixed for homogeneity analyses was collected, divided into three subsamples for extraction and analyzed for test material content. All samples were stored at room 14 000578 Covance 6329-224 3M T-6314.2 temperature until analyzed. In addition, one sample each (approximately 100 g) from the top, middle, and bottom of the 1-ppm dose preparation mixed for the in-life portion o f the study was collected, divided into three subsamples for extraction and analysis, and analyzed for test material content. To evaluate the stability o f the test material in the diet, four sets o f samples (approximately 100 g each) were taken from the highest test material concentration used for the study. One set was analyzed on the day o f mixing; a second sample o f the high-dose preparation was stored at room temperature for at least 19 days, then analyzed. The third sample o f the high-dose preparation was stored at room temperature for 32 days, then analyzed. Another sample of the high-dose preparation was stored at room temperature for 62 days, then analyzed. The remaining sample o f the high-dose preparation was stored in a freezer set to maintain -10 to -30C for 8 weeks, then analyzed. In addition, three samples (approximately 100 g each) were taken from the low-dose level preparation mixed for the in-life portion o f the study and analyzed. Homogeneity samples collected from the middle o f the low-dose preparation were analyzed on the day o f mixing and used as the baseline value. Samples (approximately 100 g) from all dose preparations were analyzed. The homogeneity sample collected from the middle of the low-dose level preparation mixed for Weeks 1 through 4 was used for dose confirmation. All samples were stored at room temperature until analyzed. Method of Administration Dietary admixture was used because the potential route o f exposure in humans is oral. The dose preparations were administered ad libitum for at least 4 weeks, unless otherwise specified. 15 0 0 0 5 7 9 Covance 6329-224 3M T-6314.2 Clinical Observations The animals were observed twice daily (a.m. and p.m.) for mortality and moribundity. Signs o f poor health or abnormal behavior were recorded as they were observed. At least once each week, each animal was removed from its cage and examined. Any unusual or abnormal findings were recorded. Body Weights Individual body weight data were recorded on the first day of treatment and twice weekly thereafter. Food Consumption Individual food consumption data were recorded twice weekly during treatment. Serum Perfluorooctane Sulfonic Acid Level (PFOS) Determination After at least 4 weeks o f treatment, animals were fasted overnight, anesthetized with carbon dioxide, and blood (as much as possible) was collected via cardiac puncture from all surviving animals. All samples were collected without anticoagulant, allowed to clot, at room temperature and centrifuged. Serum was harvested and stored in a freezer set to maintain -60 to -80C until packed on dry ice and shipped to the Sponsor for analyses. The samples were analyzed for PFOS. Results o f analyses will be reported separately by the Sponsor. Clinical Pathology After at least 4 weeks of treatment, blood and urine samples were collected from each animal. Animals were fasted overnight, and urine was collected chilled (approximately 16 hours before blood sampling); water was provided ad libitum. The animals were anesthetized with carbon dioxide; blood was collected via cardiac puncture. Potassium EDTA was used as anticoagulant for hematology tests. Animals were bled in random order. The following were evaluated. 16 0005S0 Covance 6329-224 3M T-6314.2 Hematology red blood cell (erythrocyte) count hemoglobin hematocrit mean corpuscular volume mean corpuscular hemoglobin mean corpuscular hemoglobin concentration platelet count white blood cell (leukocyte) count differential blood cell count segmented neutrophil count lymphocyte count monocyte count eosinophil count basophil count Reticulocyte count smears were made and held for possible future examination. glucose urea nitrogen creatinine total protein albumin globulin cholesterol total bilirubin Clinical Chemistry alanine aminotransferase gamma glutamyltransferase aspartate aminotransferase calcium inorganic phosphorus sodium potassium chloride appearance volume specific gravity pH protein urobilinogen Urinalysis glucose ketones bilirubin blood microscopic examination of sediment The remaining urine (up to 10 mL) for each animal was stored in a freezer set to maintain -10 to -30C. Samples were packed on dry ice and shipped to the Sponsor. Urine samples will be stored by the Sponsor for possible future analysis. Necropsy A necropsy was done on the animal that was found dead. After at least 4 weeks of treatment, all surviving animals were fasted overnight, anesthetized with carbon dioxide, bled for clinical pathology tests and serum PFOS samples, weighed, exsanguinated, and necropsied. Animals were necropsied in random order. 17 0005S1 Covance 6329-224 3M T-6314.2 The necropsy included a macroscopic examination o f the external features of the carcass; all external body orifices; the abdominal, thoracic, and cranial cavities; organs; and tissues. Organ Weights At the scheduled sacrifice, the following organs (when present) were weighed; paired organs were weighed together (see Protocol Deviations for exception): adrenal(2) brain epididymis (2) kidney (2) liver ovary (2) spleen testis (2) thymus thyroid (2) with parathyroid Organ-to-body weight percentages and organ-to-brain weight ratios were calculated. Cell Proliferation Tissue Collection and Immunohistochemical Evaluation At the scheduled sacrifice, representative samples of left lateral lobe o f the liver were collected from each animal and preserved in zinc formalin. After fixation, samples were embedded in paraffin and shipped to Pathology Associates International for proliferation cell nuclear antigen (PCNA) evaluation. Results o f the evaluation are in Appendix 7. Palmitoyl-CoA Oxidase Tissue Collection and Analyses At the scheduled sacrifice, a sample (approximately 500 mg) o f the right lateral lobe of liver was collected from each animal, flash-frozen in liquid nitrogen, and stored in a freezer set to maintain -60 to -80C until analyzed for palmitoyl-CoA oxidase activity. Liver PFOS Analyses A portion of the liver was collected from each animal at the scheduled sacrifice and stored in a freezer set to maintain -60 to -80C until packed on dry ice and shipped to the Sponsor for PFOS and metabolites analyses. Results of these analyses will be reported separately by the Sponsor. 18 0 0 0 5 S 2 Covance 6329-224 3M T-6314.2 Tissue Preservation The following tissues (when present) from each animal were collected and preserved in 10% neutral-buffered formalin: a d r e n a l(2) aorta brain cecum cervix colon duodenum esophagus epididymis (2) eye (2) femur with bone marrow (articular surface o f the distal end) Harderian gland heart ileum with Peyer's patch (lymphoid aggregate) jejunum kidney (2) lesions liver lung with mainstem bronchi lymph nodes (mesenteric and mandibular) mammary glands (females only) ovary (2) pancreas pituitary prostate rectum salivary gland [mandibular (2)] sciatic nerve seminal vesicles skeletal muscle (thigh) skin spinal cord (cervical, mid-thoracic, and lumbar) spleen sternum with bone marrow stomach testis [(2) preserved in Bouin's fixative] thymus thyroid (2) with parathyroid trachea urinary bladder uterus vagina Zymbal's gland Tissues were shipped to Pathology Associates International for processing. The adrenals, brain, eyes, kidneys, liver, mesenteric lymph node, pancreas, spleen, testes, and ovaries from each animal were embedded in paraffin, sectioned, and stained with hematoxylin and eosin (see Protocol Deviations). The tissue slides were examined microscopically by Dr. Richard H. Bruner, DVM, DAVCP o f Pathology Associates International. Bone marrow smears from the femur o f each animal at the scheduled sacrifice were prepared, stained with Wright's stain, and retained for possible examination. 19 0G0583 Covance 6329-224 3M T-6314.2 Statistical Analyses Levene's test was done to test for variance homogeneity. In the case o f heterogeneity o f variance at p s 0.05, transformations were used to stabilize the variance. Comparison tests took variance heterogeneity into consideration. One-way analysis o f variance (ANOVA) was used (if applicable) to analyze body weights, body weight changes, food consumption, continuous clinical pathology values, and organ weight data. If the ANOVA was significant, Dunnett's t-test was used for control versus treated group comparisons. Group comparisons (Groups 2 through 6 versus Group 1) were evaluated at the 5.0%, two-tailed probability level. Only data collected on or after the first day o f treatment was analyzed statistically. RECORD RETENTION All raw data, documentation, records, protocol, and specimens generated as a result o f this study will be archived in the storage facilities o f Covance-Madison for a period o f 1 year. One year after the submission o f the final report, the Sponsor will determine the final disposition o f the materials. All raw data stored on magnetic media, the protocol and protocol amendments, study correspondence, and an original copy o f the final report will be retained by Covance-Madison. PCNA evaluation data, paraffin blocks, and tissue slides will be retained by Pathology Associates International. Liver, urine, and serum samples sent to the Sponsor and analysis data will be retained by the Sponsor. 20 0 0 0 5 8 4 RESULTS Covance 6329-224 3M T-6314.2 Dose Analyses Results o f the homogeneity, stability, and dose preparation analyses are in Tables 1 through 3. Mean values o f the homogeneity analyses ranged from 102-268%, 95.9-102%, 93.7-97.0%, 94.4-95.8%, and 94.0-101% of the theoretical concentrations for the diets containing 1,10, 30, 100, and 500 ppm N-MeFOSE, respectively. Because the results o f the analyses o f diets mixed on June 11, 1998, for the diet containing 1 ppm were high (118%, 268%, and 129%), they were reanalyzed. The results of the reanalyses were 116%, 114%, and 102%. These results indicate that the mixing procedure produced a homogeneous distribution o f the test material in the dose preparations. Results o f stability analyses o f samples stored for 19, 32, and 62 days at room temperature and 8 weeks under frozen conditions, indicated that the mean concentrations were 90.2%, 83.4%, 70.6% and 97.2%, respectively, of the theoretical concentrations of 500 ppm Results o f stability analyses of samples from the 1-ppm theoretical concentration, indicated that the mean concentrations were 132% and 72.6% for the diet preparations mixed pretest and the in-life portion o f the study, respectively. Therefore, the dose preparations were stable for 62 days at room temperature storage and 8 weeks under frozen conditions for mean concentration of 500 and 1 ppm respectively. The mean concentrations o f the dose preparation analyses for all levels ranged from 63.3% to 114% of the theoretical concentrations. These data indicate that the levels of N-methyl perfluorooctanesulfonamido ethanol (N-MeFOSE, T-6314) in the dose preparations were acceptable only for dose levels o f 10, 30 100, and 500 ppm Clinical Observations and Survival Clinical observations are summarized in Table 4; individual data are in Appendix 2. Individual animal fate data are also in Appendix 2. Covance 6329-224 3M T-6314.2 One animal given 500 ppm N-MeFOSE died on Day 25. This animal exhibited severe hepatocellular hypertrophy and moderately-severe liver necrosis at microscopic exam. All other animals survived to the scheduled sacrifice. No clinical observations were noted that were considered effects o f the test material. Body Weights and Body Weight Changes Body weight and body weight change data are summarized in Tables 5 and 6; individual data are in Appendix 3. Although not statistically significant, animals given 1,10, 30, or 100 ppm N-MeFOSE had lower mean body weights than those o f controls for most o f the study. Test material related lower body weight and body weight gains were noted for animals given 500 ppm. For males and females given 500 ppm, statistically lower body weights were apparent beginning on Days 8 and 11, respectively, and continuing through the end o f study. Mean body weight gains for animals given 500 ppm were lower than those of control animals throughout the study. Food Consumption Food consumption data are summarized in Table 7; individual data are in Appendix 4. Statistically test material related decreases in food consumption were noted in males given 500 ppm throughout the study and in females given 500 ppm beginning on Day 4 and continuing throughout the study. The overall mean food consumption for males fed the 100- or 500-ppm concentration was significantly reduced compared with that o f the controls, and the overall mean food consumption for females fed the 500-ppm concentration was significantly reduced compared with that o f the controls. There were no significant food consumption differences noted in animals given 1 ,1 0 or 30 ppm N-MeFOSE. 22 O Q 0 5 8 S Covance 6329-224 3M T-6314.2 Test Material Consumption Test material consumption data are summarized in Table 8. Individual data are in Appendix 4. Animals were fed diets containing 1,10, 30, 100, or 500 ppm N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314). The mean amounts of test material consumed by the animals in these groups were 0.087 to 0.140 mg/kg/day; 0.816 to 1.325 mg/kg/day; 2.432 to 4.030 mg/kg/day; 7.768 to 13.192 mg/kg/day; and 35.168 to 62.612 mg/kg/day for males, respectively. Values for females were 0.096 to 0.147 mg/kg/day; 0.848 to 1.399 mg/kg/day; 2.612 to 4.124 mg/kg/day; 8.485 to 13.802; and 38.527 to 62.217, respectively. The overall test material consumption ranged from 0.105 to 44.590 mg/kg/day for the males and 0.111 to 45.050 mg/kg/day for the females. Serum Perfluorooctane Sulfonic Acid Level (PFOS) Determination Results of serum PFOS level determination will be reported separately by the Sponsor. Clinical Pathology Hematology, coagulation, clinical chemistry and urinalysis data are summarized in Tables 9 through 11; individual data are in Appendix 5. The Pathology Report contains a discussion o f the data. Dietary administration of N-MeFOSE at a dose level o f 500 ppm for approximately 4 weeks was associated with several effects on clinical pathology test results including moderately lower red blood cell count, hemoglobin, and hematocrit; lower absolute eosinophil count; mildly higher urea nitrogen; moderately higher albumin and mildly to moderately lower globulin; markedly lower cholesterol; mildly to moderately higher total bilirubin, aspartate aminotransferase, and alanine aminotransferase; and moderately higher hepatic palmitoyl-CoA oxidase. O f uncertain relationship to administration of N-MeFOSE were lower urine pH for males fed 500 ppm and small differences for animals fed 100 ppm including higher urea nitrogen, albumin, and alanine aminotransferase (males only) and lower cholesterol. O f the differences for animals fed 100 ppm, only the difference for alanine aminotransferase was statistically significant. 23 0 0 0 5 S 7 Covance 6329-224 3M T-6314.2 Cell Proliferation Tissue Collection and Inununohistochemical Evaluation Results o f cell proliferation and immunohistochemical evaluation provided by Pathology Associates International are in Appendix 7. Results o f the cell proliferation evaluation will be provided by Pathology Associates International. Liver PFOS Determination Results of liver PFOS level determination will be reported separately by the Sponsor. Anatomical Pathology Terminal body weights, absolute organ weights, organ-to-body weight percentages, and organ-to-brain weight ratios are summarized in Tables 12 through 14; incidences o f macroscopic and microscopic observations are summarized in Tables 15 and 16; the incidence o f severity o f microscopic observations is summarized in Table 17. Individual data are in Appendix 6. The Pathology Report contains a discussion o f the data. Mean absolute and relative (to brain and body) liver weights for all males and females given 100 and 500 ppm N-MeFOSE were significantly increased over control values, and these variations were regarded as treatment-related. All additional mean organ weights, which varied significantly from control values, were considered to be within the range or normal biologic variation, or were manifestations of slight weight loss associated with physiologic stress. Treatment-related microscopic findings were restricted to the liver and consisted o f minimal to severe centrilobular hepatocellular hypertrophy. Hypertrophic changes were slightly more severe in males; and at the high-dose level, liver cell swelling in several males was associated with acute necrosis. Necrosis was attributed to restricted blood supply (ischemia) from swollen liver cells rather than direct hepatocellular damage. Additional microscopic findings were consistent with common, spontaneous alterations in laboratory rats or changes associated with stress, nutritional deprivation, or tissue processing artifact. 24 0005SS CONCLUSIONS Covance 6329-224 3M T-6314.2 Based on the results o f this study, dietary administration o f N-MeFOSE, T-6314 to Crl:CD(SD) IGS BR rats for at least 4 weeks resulted in adverse effects at a dose level o f 500 ppm. The no-observable-adverse-effect level was determined to be 100 ppm. 25 000589 SIGNATURES Covance 6329-224 3M T-6314.2 Nii van Bruce-Konuah Study Coordinator Covance Laboratories Inc. Covance Laboratories Inc. Date ^ ^ Dat 26 000590 Covance 6329-224 3M T-6314.2 REFERENCES Dunnett, C. W., "New Tables for Multiple Comparisons with a Control," Biometrics. 20:482-491 (1964). Levene, H., "Robust Tests for Equality of Variances," Contributions to Probability and Statistics, (eds.) I. Olkin et al., Ch. 25, pp. 278-292, Stanford University Press: Stanford, California (1960). Winer, B. J., "Design and Analysis o f Single-Factor Experiments," Statistical Principles in Experimental Design. Second Ed., Ch. 3, pp. 149-260, McGraw-Hill: New York, New York (1971a). Winer, B. J., "Analysis o f Covariance," Statistical Principles in Experimental Design. Second Ed., Ch. 10, pp. 752-812, McGraw-Hill: New York, New York (1971b). 27 000531 PATHOLOGY REPORT Covance 6329-224 3M T-6314.2 SUMMARY The purpose of this study was to assess the toxicity o f the test material, N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) when administered in the diet to rats for at least 4 weeks. The test material was administered at dose levels o f 1, 10, 30, 100, and 500 ppm. Dietary administration of N-MeFOSE at a dose level of 500 ppm for approximately 4 weeks was associated with several effects on clinical pathology test results including moderately lower red blood cell count, hemoglobin, and hematocrit; lower absolute eosinophil count; mildly higher urea nitrogen; moderately higher albumin and mildly to moderately lower globulin; markedly lower cholesterol; mildly to moderately higher total bilirubin, aspartate aminotransferase, and alanine aminotransferase; and moderately higher hepatic palmitoyl-CoA oxidase. O f uncertain relationship to administration o f N-MeFOSE were lower urine pH for males fed 500 ppm and small differences for animals fed 100 ppm including higher urea nitrogen, albumin, and alanine aminotransferase (males only) and lower cholesterol. O f the differences for animals fed 100 ppm, only the difference for alanine aminotransferase was statistically significant. Treatment-related microscopic findings were restricted to the liver and consisted o f minimal to severe centrilobular hepatocellular hypertrophy. Hypertrophic changes were slightly more severe in males; and at the high-dose level, liver cell swelling in several males was associated with acute necrosis. Necrosis was attributed to restricted blood supply (ischemia) from swollen liver cells rather than direct hepatocellular damage. Additional microscopic findings were consistent with common, spontaneous alterations in laboratory rats or changes associated with stress, nutritional deprivation, or tissue processing artifact. 28 00053 METHODS Covance 6329-224 3M T-6314.2 Six groups o f Crl:CD(SD) IGS BR rats (six animals/sex/group) were fed diets containing the test material at a dose level o f 0 (control group; fed basal diet only), 1, 10, 30,100, or 500 ppm. Before the schedule sacrifice and necropsy during Week 5, blood and urine were collected for hematology, clinical chemistry, and urinalysis tests. At necropsy, macroscopic observations were recorded, organ weights were obtained, and tissues were placed in fixative as specified by the protocol. In addition, samples o f liver were collected for evaluation o f hepatocellular proliferation (by Pathology Associates International), determination of hepatic palmitoyl-CoA oxidase activity (by Covance), and analysis for PFOS and metabolites (by the Sponsor). The animal that died on test was also necropsied, but organ weights and liver samples for the special analyses were not obtained. Microscopic examinations were done on the following tissues from each animal: adrenals, brain, eyes, kidneys, liver, mesenteric lymph node, pancreas, spleen, testes, ovaries, and lesions. Statistically significant differences cited in the Results and Discussion section are based on comparisons between the control and treated groups. RESULTS AND DISCUSSION Mortality Animal No. C94523 given 500 ppm N-MeFOSE died on Day 25. The remaining animals survived to the scheduled sacrifice. Clinical Pathology Individual values for hematology, clinical chemistry, urinalysis, and hepatic palmitoyl-CoA oxidase are in Appendix 5. Mean values for each group and the results o f statistical comparisons are in Tables 9 through 11. 29 000593 Covance 6329-224 3M T-6314.2 W eek 5. There were several statistically significant or otherwise notable differences for clinical pathology results between control and treated animals; only one o f the statistically significant differences affected animals fed less than 500 ppm. Differences considered to be effects o f the test material were lower red blood cell count, hemoglobin, and hematocrit; lower absolute eosinophil count; higher urea nitrogen; higher albumin and lower globulin; lower cholesterol; higher total bilirubin, aspartate aminotransferase, and alanine aminotransferase; and higher hepatic palmitoyl-CoA oxidase. With the exception o f lower globulin and higher aspartate aminotransferase for the females, these differences were statistically significant. O f uncertain relationship to administration o f N-MeFOSE were lower urine pH for males fed 500 ppm and small differences for animals fed 100 ppm including higher urea nitrogen, albumin, and alanine aminotransferase (males only) and lower cholesterol. O f the differences for animals fed 100 ppm, only the minor difference for alanine aminotransferase was statistically significant. At dose levels below 100 ppm, clinical pathology results were unaffected by treatment. The effects on the erythrocyte parameters (moderately decreased), eosinophil count (decreased), and globulin (mildly to moderately decreased) were consistent with animals in relatively poor health, failing to gain weight appropriately. Mildly higher urea nitrogen and moderately higher albumin were most consistent with mild dehydration and indicated the effects on other parameters (e.g., the erythrocyte parameters) might have been greater if the animals were normovolemic. The mild to moderate effects on alanine aminotransferase, aspartate aminotransferase, and total bilirubin were indicative o f the hepatocellular degeneration. The effect on cholesterol was marked, but the mechanism for change was not apparent. Moderately higher hepatic palmitoyl-CoA oxidase was indicative of peroxisomal proliferation. Anatomical Pathology Individual anatomical pathology data are in Appendix 6. Individual absolute organ weights, organ-to-body weight percentages, and organ-to-brain weight ratios are also in Appendix 6. Mean values for absolute and relative organ weights for each group are in Tables 12 through 14. Incidence summaries o f the macroscopic and microscopic observations are in Tables 15 and 16; the incidence o f severity o f selected microscopic observations is summarized in Table 17. 30 0 0 0 5 3 4 Covance 6329-224 3M T-6314.2 Unscheduled Death. Animal No. C94523 given 500 ppm N-MeFOSE died on Day 25. Microscopically, this animal exhibited severe hepatocellular hypertrophy and moderately-severe liver necrosis. Terminal Sacrifice Organ Weights. Mean absolute and relative (to brain and body) liver weights for all males and females given 100 and 500 ppm N-MeFOSE were significantly increased over control values, and these variations were regarded as treatment-related. All additional mean organ weights, which varied significantly from control values, were considered to be within the range or normal biologic variation, or were manifestations o f slight weight loss associated with physiologic stress. Macroscopic Observations. Treatment-related, gross changes were restricted to the liver and stomach o f males given 500 ppm N-MeFOSE. Animal Nos. C94521 and C94522 displayed enlarged livers, and in Animal No. C94522, hepatic enlargement was associated with discoloration (diffusely brown with light areas). Microscopically, liver changes were attributed to hepatocellular hypertrophy and necrosis. In addition to liver changes, dark or red mucosal areas were present in the glandular stomach o f Animal Nos. C94521 and C94526 given 500 ppm N-MeFOSE and in the glandular stomach o f one control male (Animal No. C94493). Gastric areas were compatible with early "stress" erosions or ulcers. Microscopic Observations. Treatment-related microscopic changes were restricted to the liver o f both sexes and consisted o f hypertrophy (swelling) o f liver cells in centrilobular regions of the hepatic lobules. Occasionally, hypertrophic liver cells were associated with acute hepatic necrosis. Hepatocellular hypertrophy was not observed in controls or in animals given 1 or 10 ppm N-MeFOSE. At higher dose levels, hypertrophic changes were slightly more prevalent and severe in males, and at dose levels o f 30, 100, and 500 ppm N-MeFOSE, all males displayed minimal to slight, moderate to moderately-severe, and moderately-severe to severe liver cell hypertrophy, respectively. Liver cell hypertrophy was not observed in females given 30 ppm N-MeFOSE; however, at dose levels of 100 and 500 ppm N-MeFOSE, hepatocellular hypertrophy in females ranged from slight to moderate and from moderate to moderately-severe, respectively. Hepatocellular hypertrophy in both sexes was compatible with the proliferation of 31 000595 Covance 6329-224 3M T -6314.2 cytoplasmic smooth endoplasmic reticulum. Although at lower doses hypertrophy was restricted to centrilobular regions, at the high-dose level, hypertrophic hepatocytes often extended into panlobular regions. In addition to hypertrophic changes, moderate liver cell necrosis was observed in two males given 500 ppm. Necrosis was attributed to local ischemia associated with liver cell swelling and occlusion o f regional blood supplies. Minimal hepatic necrosis in one o f six males given 10 or 100 ppm and in one o f six females given 30 ppm w as consistent with com m on hepatic alterations in laboratory rats. All other microscopic findings were consistent with common spontaneous alterations in laboratory rats, including changes related to stress, nutritional status or tissue processing artifact. R obert L. Hall, DVM, PhD Diplomate, ACVP (Clinical Pathology) Diplomate, ACVP Pathology Associates International 32 000596 Covance 6329-224 3M T-6314.2 COMMENTS ON THE DATA Various models o f calculators, computers, and computer programs were used to analyze data in this study. Because different models round off or truncate numbers differently, values in some tables (e.g., means, standard deviations, or individual values) may differ slightly from those in other tables, from individually calculated data, or from statistical analysis data. Neither the integrity nor the interpretation of the data was affected by these differences. The number of animals listed in the heading o f the summary tables for clinical observations reflects the number o f animals assigned to each group at the start o f the study. The summary table for clinical observations indicate the number o f animals for which a condition was observed without regard to the specific nature, severity, reversibility, number of incidences/animal, or the length of time the condition persisted. Only observations other than normal are indicated on the summary clinical observations tables. Each animal with observations recorded as "Normal" throughout the study has the comment "Animal has no significant findings" indicated on the individual clinical observations tables. The specific details for comments in the individual clinical observations tables that are indicated with a "C" can be found at the end o f each group for each sex. The day o f initiation o f treatment is "Day 1, W eek 1." Body weight data are entered at the start o f a study week (e.g., a body weight recorded on Day 1 is considered a Week 1 body weight, a body weight recorded on Day 8 is considered a Week 2 body weight). Body weight change data are calculated from the first day of the study week to the first day of the following study week (e.g., Week 1 values are calculated from Day 1 through 7) and are indicated in the tables with the day being the first day o f the following week (e.g., Week 1 values are indicated as "Day 8"). Weekly food consumption and test material consumption are calculated from the first day o f the study week to the first day o f the following study week (e.g., Week 1 values are calculated from Day 1 through 7). The values for summary and individual test material consumption are reported with more significant figures than is appropriate for the data due to limitations o f the data collection and reporting software. 33 000597 Covance 6329-224 3M T-6314.2 COMM ENTS ON THE DATA (Continued) Diet test material concentrations provided by the data collection system (PTS) are calculated to the nearest 0.1 ppm. These values are used for calculation of test material consumption. For diet preparation purposes, the values are rounded to the appropriate accuracy for the balance used. Food consumption values are reported in whole numbers; however, PTS carries food consumption values to one place to the right of the decimal for test material consumption calculations. The differences in values generated do not influence the interpretation of the calculation. The comment "SPILLED" on individual food consumption data tables indicates that food consumption was not recorded due to spillage during the interval. The comment "NOT TAKEN" on individual food consumption data tables indicates the animal died before the end of the food consumption interval. Differences in the population size (N) on the summary tables for clinical and anatomical pathology are explained on the individual data tables or the codes sheets. The calculation for individual test material consumption is: Test material consumption = Diet ConcentrationxFood Consumption Food Consumption IntervalxfFirst Body Weight o f Interval+(Daily Body Weight GainxDay Factor)] where: Daily Body Weight Gain = Last Body W eight o f Interval- First Body Weight o f Interval Day o f Last Body W eight o f Interval- Day of First Body Weight of Interval and: Day Factor = (Food Consumption Start Day- Day of First Body Weight of Interval) + ^ 00c*Consumption Interval 2 and: Food Consumption Interval = Food Consumption End Day- Food Consumption Start Day On pages 4 and 7 of the protocol, the test material is indicated as MeFOS, T-6314 instead of MeFOSE, T-6314. 34 000598 CODES, ABBREVIATIONS, AND UNITS Covance 6329-224 3M T-6314.2 General Codes and Abbreviations Codes for Clinical Pathology Abbreviations and Units for Clinical Hematology Abbreviations and Units for Clinical Chemistry Abbreviations and Units for Clinical Urinalysis Codes for Anatomical Pathology Note: The following lists o f codes, abbreviations, and units are used by Covance. Some, but not necessarily all, o f this information may be needed for this report. 35 000599 Covance 6329-224 3M T-6314.2 General Codes and Abbreviations WK N Mean; MEAN SD; S.D.; STAND DEV; STANDARD DEV; sd -; NA P C UNSCHED DISPATCH TBW # CO Week. Number o f measurements in a group. Arithmetic mean. Standard deviation. Group mean is significantly different from the mean o f the control group (Group 1) at p ^ 0.05. No value; not applicable; not present. Present. Comment found at the end of each group for each sex. Unscheduled. Observations transferred from the in-life module of the data collection system to the necropsy module for reference during necropsy. Observations are duplicates of the last in-life observations. Terminal body weight. Number. Clinical observation. 36 000600 NS QS/QNS NR FS SC SH H SL L SI I NF U DT/DOT DB TJ TE RE EE SE PC PD PI PL PA CO HB PLASMO NO AGG FR UTD NO COAG Covance 6329-224 3M T-6314.2 Codes for Clinical Pathology GENERAL CODES No sample Quantity not sufficient No repeat (sample volume not sufficient for repeat analysis) Fibrin strands Sample clotted Slightly hemolyzed Hemolyzed Slightly lipemic Lipemic Slightly icteric Icteric Animal not fasted Unscheduled/moribund bleed Animal died on test Died during bleeding Technician judgment to repeat test Technical error (instrument or technician error that results in unacceptable data, e.g., unacceptable instrument output, sample spilled, entry o f invalid data) Recording error (recorded incorrect data, e.g., wrong number, spelling error, incorrect date) Entry error (incorrect keyboard entry) Sampling error Platelets clumped Platelets decreased Platelets increased Platelets large Platelets appear adequate Color interferes with test Heinz bodies observed Plasmodium No aggregation Fractious Unable to determine No coagulation 37 000(801 Covance 6329-224 3M T-6314.2 Codes for Clinical Pathology (Continued) RESULTS NOT INCLUDED IN STATISTICAL ANALYSES Hemolyzed clinical chemistry or coagulation samples Samples from animals at unscheduled intervals Prothrombin times (PT) greater than 50 seconds Activated partial thromboplastin times (PTT) greater than 110 seconds Bleed times (BLETIME) greater than 30 minutes CODES FOR BLOOD CELL MORPHOLOGY The following scale was used to measure the degree of anisocytosis (ANISO), poikilocytosis (POIK), polychromasia (POLY), hypochromasia (HYPO), or basophilic stippling (BASTIP) or the presence o f Howell-Jolly bodies (HJBODY), toxic neutrophils (TOXNEUT), or atypical lymphocytes (ATYPLYM): Scale - 1 2 3 4 Degree Normal for the species Slight Moderate Marked Not applicable Presence Not present Rare Few M oderate Many A Pale B Straw C Yellow D Dark yellow URINE APPEARANCE Color E Amber F Brown G Red H Green I Black P Blue/green Q Blue R Orange Clarity J Clear K Hazy L Cloudy Miscellaneous M Debris 0 Feces 38 000602 Covane* 6329-224 3M T-6314.2 Codes for Clinical Pathology (Continued) URINE CHEM ISTRY M ULTISTIX STRIP Urine Glucose + ++ +++ ++++ +++++ Negative 100 mg/dL 250 mg/dL 500 mg/dL 1,000 mg/dL *2,000 mg/dL Urine Ketone + ++ +++ ++++ +++++ Negative 5 mg/dL 15 mg/dL 40 mg/dL 80 mg/dL 160 mg/dL Urine Blood - Negative + Small ++ Moderate +++ Large Urine Urobilinogen + ++ +++ ++++ 0.2 mg/dL 1 mg/dL 2 mg/dL 4 mg/dL 8 mg/dL (1 mg = approximately 1 Ehrlich unit) Urine Bilirubin - Negative + Small ++ Moderate +++ Large URINE SEDIMENT Cells, Crystals, Casts, and Comments A Amorphous urates B Amorphous phosphates C Uric acid D Triple phosphates E Calcium oxalate F Calcium carbonate G Granular casts H Hyaline casts I Cellular casts J Waxy casts K Unknown crystal P Mucous threads Q Sperm R Fecal contamination S Pinworm ova found T Pinworm larvae found U Parasite ova found 0 Not present 1 1-5 per field 2 6-10 per field 3 11-20 per field 4 >20 per field Bacteria 0 Not present 1 Few 2 Moderate 3 Many 39 000603 Covance 6329-224 3M T-6314.2 Abbreviations and Units for Clinical Hematology Test Red blood cell count Hemoglobin Hematocrit Mean corpuscular volume Mean corpuscular hemoglobin Mean corpuscular hemoglobin concentration Platelet count Mean platelet volume Reticulocyte count Absolute reticulocyte count Heinz body count Erythrocyte sedimentation rate Prothrombin time Activated partial thromboplastin time Thrombin time Activated coagulation time Fibrinogen Fibrin/fibrinogen degradation products Platelet aggregation Collagen Adenosine diphosphate Alpha 2-antiplasmin Bleeding time Methemoglobin Plasma hemoglobin Myeloid/erythroid ratio Estimated myeloid/erythroid ratio White blood cell count Differential blood cell count Nucleated red blood cell count Corrected white blood cell count Segmented neutrophil count Band neutrophil count Lymphocyte count Monocyte count Eosinophil count Basophil count Anisocytosis Polychromasia Abbreviation (Units) RBC (E6/UL or X 106///L) HGB (G/DL) HCT (%) MCV (FL) MCH (PG) MCHC (%) PLT (E3/UL or X103//L) MPV (FL) RETIC (%) RETIC (E3/UL or XIOV^L) HEINZ (%) ESR (MM/HR) PT (SEC) PTT (SEC) TT (SEC) ACT (SEC) FBR (MG/DL) FDP (UG/ML) PAGG/COL (%) PAGG/ADP (%) ANTIPLAS (%) BLE TIME (SEC) METHGB (%) PLA HGB (MG/DL) M/E RATIO EST M/E RATIO WBC (E3/UL or X103/^L ) NRBC (/100 WBC) COR WBC (E3/UL or X103/^L ) N-SEG (E3/UL or X103///L) and % N-BAND (E3/UL or X10V//L) and % LYMPH (E3/UL or XlOV^uL) and % MONO (E3/UL or XloV^uL) and % EOSIN (E3/UL or X103/L) and % BASO (E3/UL or X IO V L ) and % ANISO (-,1,2,3) POLY (-,1,2,3) 40 0C0604 Covance 6329-224 3M T-6314.2 Abbreviations and Units for Clinical Hematology (Continued) Test Poikilocytosis Hypochromasia Howell-Jolly bodies Basophilic stippling Toxic neutrophils Atypical lymphocytes Aqueous white blood cell count (right eye) Aqueous white blood cell count (left eye) Abbreviation (Units) POIK (-,1,2,3) HYPO (-,1,2,3) HJBODY (-,1,2,3,4) BASTIP (-,1,2,3) TOXNEUT (-,1,2,3,4) ATYPLYM (-,1,2,3,4) R EYE (WBC/UL) L EYE (WBC/UL) 41 000605 Covance 6329-224 3M T-6314.2 Abbreviations and Units for Clinical Chemistry Test Glucose Urea nitrogen Urea Creatinine Total protein Albumin Globulin Albumin/globulin ratio Total bilirubin Direct bilirubin Indirect bilirubin Cholesterol Triglyceride Urea nitrogen/creatinine ratio Total lipids Phospholipids High-density lipoprotein cholesterol Low-density lipoprotein cholesterol Uric acid Aspartate aminotransferase Alanine aminotransferase Alkaline phosphatase Gamma glutamyl transferase Sorbitol dehydrogenase Lactate dehydrogenase Creatine kinase Amylase Lipase Palmitoyl CoA oxidase Calcium Ionized calcium Inorganic phosphorus Sodium Potassium Chloride Magnesium Zinc Strontium Iron Abbreviation (Units) GLU (MG/DL) UN (MG/DL) UREA (MG/DL) CREAT (MG/DL) T PRO (G/DL) ALB (G/DL) GLOB (G/DL) A/G RATIO T BILI (MG/DL) D BILI (MG/DL) I BILI (MG/DL) CHOL (MG/DL) TRIG (MG/DL) UN/CREAT (RATIO) T LIPIDS (MG/DL) P LIPIDS (MG/DL) HDL (MG/DL) LDL (MG/DL) UA (MG/DL) AST/SGOT (IU/L) ALT/SGPT (IU/L) ALKPHOS (IU/L) GGT (IU/L) SDH (IU/L) LDH (IU/L) CK (IU/L) AMYLASE (IU/L) LIPASE (IU/L) PCOAO (IU/G) CA (MG/DL) ION CA (MG/DL) IPHO S (MG/DL) NA (MMOL/L) K (MMOL/L) CL (MMOL/L) MG (MEQ/L or MG/DL) ZN (MG/L or PPM) SR (MG/L or PPM) FE (UG/DL) 42 Covance 6329-224 3M T-6314.2 Abbreviations and Units for Clinical Chemistry (Continued) Test Excess iron Total iron binding capacity Unbound iron binding capacity Percent iron saturation Plasma cholinesterase Red blood cell cholinesterase Brain cholinesterase Caudate putamen Hippocampus Frontal cortex Cerebellum Bicarbonate Serum hemoglobin Serum bile acids Fecal bile acids Average fecal weight Fecal bile acids (calculation) Osmolality Electrophoresis Albumin Apha-1 -globulin Alpha-2-globulin Beta globulin Gamma globulin High-density lipoprotein Low-density lipoprotein Very-low-density lipoprotein Insulin Adrenocorticotropic hormone Cortisol Glucagon Triiodothyronine Thyroxine Creatine kinase isoenzymes BB MB MM Abbreviation (Units) EX FE (UG/DL) TIBC (UG/DL) UIBC (UG/DL) FE %SAT (%) CHEP (MU/ML) CHER (MU/ML) CHEB (MU/ML) CAUD PUT (UMOL/G) HIPPOCAM (UMOL/G) F CORTEX (UMOL/G) CEREBELL (UMOL/G) BICARB (MMOL/L) SER HGB (MG/DL) SBA (UMOL/L or MG/DL) FBA (UG/ML) FCC WGT (G) FBA (MG/Day) OSMO (MOSM/KG) E ALB (G/DL) E A -l (G/DL) E A-2 (G/DL) E BETA (G/DL) E GAMMA (G/DL) E-HDL (%) E-LDL (%) E-VLDL (%) INSULIN (UU/ML) ACTH (PG/ML) CORTISOL (UG/ML) GLUCAGON (PG/ML) T3 (NG/DL) T4 (UG/DL) CK-BB (U/L) CK-MB (U/L) CK-MM (U/L) 43 0 0 0 6 0 7 Covance 6329-224 3M T-6314.2 Abbreviations and Units for Clinical Urinalysis Test Urine volume 8 hour urine volume Specific gravity Urine osmolality Quantitative urinary/cerebrospinal fluid protein Urine protein excretion Urine chemistry Multistix strip Urine pH Urine protein Urine glucose Urine ketones Urine bilirubin Urine blood Urine urobilinogen Urine reducing substances Microscopic examination of urine sediment Red blood cells per high-power field White blood cells per high-power field Epithelial cells per high-power field Bacteria per high-power field Casts per low-power field Crystals per low-power field Urine appearance Comments Abbreviation (Units) U VOL (ML) 8 HR VOL (ML) SPGR U OSMO (MOSM/KG) QUAN PRO (MG/DL) PRO EXC (MG) UPH U PRO (MG/DL) UGLU UKET U B IL I UBLOOD UROBILI U RE SUB RBC (PER HPF) WBC (PER HPF) EPITH (PER HPF) BACT (PER HPF) CASTS (PER LPF) CRYSTALS (PER LPF1 or PER LPF2) URINE APPI or URINE APP2 COMMENTS Miscellaneous Codes and Abbreviations for Clinical Pathology Fecal occult blood Fecal parasite detection Hemolytic potential Osmolality Not applicable Not applicable Not applicable OSMO (MOSM/KG) 44 000608 Code T D Codes for Anatomical Pathology Definition ANIMAL DEATH CODES Terminal sacrifice Found dead Covance 6329-224 3M T-6314.2 EX NOT TAKEN MISSING UNSUITABLE AUTOLYTIC EXCLUDE M ACROSCOPIC CODES Indicates that organ weight is excluded from calculations Organ weight not taken; explanation given in necropsy notes Organ missing or lost Organ technically unsuitable for weighing Organ autolyzed and could not be weighed Weight was taken, but was excluded from all calculations M ICROSCOPIC CODES Codes Prefacing Neoplastic Findings B- Primary, benign neoplasm M- Primary, malignant neoplasm N- Metastatic neoplasm I- Locally invasive neoplasm X- Other neoplasm Code Definition Distribution of Findings Focal Diffuse Multifocal 45 0 0 0 6 0 9 Covance 6329-224 3M T-6314.2 Codes for Anatomical Pathology (Continued) Grades for Severity or Amount 1 Minimal - the least amount of change that can be observed with the light microscope 2 Slight - less than average amount o f change, but readily discernible as abnormal 3 M oderate - the average amount of change that is expected for a lesion 4 Moderately severe (marked) - a marked amount of change with possible loss o f function of the affected cells or organs 5 Severe - a great amount of change with probable loss o f function o f the affected cell or organs and frequently involves large areas of the organ Other Microscopic Codes TL Total P Finding present Finding not present MN Mean TISSUE ABBREVIATIONS Abbreviation LN GL STOMACH, GL STOMACH, NONGL SALIV GL, MANDIB LN, ANT MES/PANC AUDITORY SEB GL LACRIMAL GLAND, EX HEMATO NEOPLASIA LACRIMAL GL, INT CAVITY, ABDOM SALIV GL,PAROTID LN, TRACHEOBRON CATHETER EXIT CATHETER ENTRANC CATHETER EXIT Definition Lymph node Gland Glandular stomach Nonglandular Mandibular salivary gland Anterior mesenteric/pancreatic lymph node Auditory sebaceous gland Exorbital lacrimal gland Hematopoietic neoplasia Internal lacrimal gland Abdominal cavity Parotid salivary gland Tracheobronchial lymph node Catheterization site: exit site from the body Catheterization site: entrance site into the vessel Catheterization site: tissues (vascular or extravascular) associated with the catheter near its tip 46 Covance 6329-224 3M T-6314.2 Table 1 Results o f Homogeneity Analyses (ppm) Mixed 5/19/98 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Sample Location Replicate 1 T-6314 (ppm) 10 30 100 500 Top 1 1.17 10.3 2 1.07 9.27 3 1.12 9.20 Mean 1.12 (112)a 9.59 (95.9) Middle 1 1.36 9.48 2 1.35 10.4 3 1.25 9.71 Mean 1.32(132) 9.86 (98.6) Bottom 1 1.89 10.6 2 1.21 10.9 3 1.19 9.13 Mean 1.43 (143) 10.2 (102) a Each value in parenthesis is the percent o f theoretical. 26.7 27.7 29.9 28.1 (93.7) 30.6 27.5 29.3 29.1 (97.0) 26.7 28.7 30.0 28.5 (95.0) 92.6 93.6 97.0 94.4 (94.4) 95.4 96.2 95.9 95.8 (95.8) 93.3 92.2 97.8 94.4 (94.4) 481 481 481 481 (96.2) 511 482 522 505 (101) 477 468 466 470 (94.0) 000611 47 Covance 6329-224 3M T-6314.2 Table 1 (Continued) Results of Homogeneity Analyses (ppm) Mixed 6/11/98 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Sample Location Replicate T-6314 (ppm) 1 Top 1 1.10 2 1.22 3 1.23 Mean 1.18 (118)a Top5 1 1.23 2 1.15 3 1.10 Mean 1.16(116) Middle 1 2.91 2 1.40 3 3.73 Mean 2.68 (268) Middle5 1 1.15 2 1.11 3 1.16 Mean 1.14(114) Bottom 1 1.20 2 1.45 3 1.21 Mean 1.29 (129) Bottom5 1 1.01 2 0.986 3 1.06 Mean 1.02(102) a Each value in parenthesis is the percent o f theoretical, b Reassay. 48 000612 Covance 6329-224 3M T-6314.2 Table 2 Results of Stability Analyses (ppm) Mixed 5/19/98 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Storage Conditions Replicate T-6314 (ppm) 1 500 Initial 1 2 3 Mean 1.36 1.35 1.25 1.32 (132)a 511 482 522 505 (101) At least 19 days, room temperature, 1 2 Mean - - - 457 444 451 (90.2) At least 32 days, room temperature 1 2 Mean - 420 414 417 (83.4) 8 weeks, frozen 1 2 Mean _ - 494 477 486 (97.2) 62 days, room temperature 1 2 Mean -- 304 402 353 (70.6) a Each value in parentheses is the percent of theoretical. 49 000613 Covance 6329-224 3M T-6314.2 Table 2 (Continued) Results of Stability Analyses (ppm) Mixed 6/30/98 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats T-6314 (ppm) Storage Conditions Replicate 1 Initial 1 2 Mean 0.777 0.674 0.726 (72.6)a a Each value in parenthesis is the percent of theoretical. 50 0 0 0 6 1 4 i Covance 6329-224 3M T-6314.2 Table 3 Results o f Dose Preparation Analyses (ppm) 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Week Replicate 0 1 T-6314 (ppm) 10 30 100 500 l-4 a 1 b 2.91 10.0 25.6 90.1 485 2 b 1.40 8.42 25.7 93.3 487 3 - 3.73 - - - - Mean - 2.68 (268)c 9.21 (92.1) 25.7 (85.7) 91.7(91.7) 486 (97.2) 1-4a'd 1 - 1.15 - - - - 2 - 1.11 - - - - 3 - 1.16 - - - - Mean - 1.14(114) - - - - 4 1 b 0.777 10.0 29.3 91.1 488 2 b 0.674 9.27 25.3 89.9 482 Mean - 0.726 (72.6) 9.64 (96.4) 27.3 (91.0) 90.5 (90.5) 485 (97.0) a Results for the 1 ppm levels were derived from the sample collected from the middle o f the dose preparations for homogeneity analysis, b Below the limit o f quantitation (<0.5 ppm), c Each value in parenthesis is the percent o f theoretical, d reassay. 000615 51 Table 3 (Continued) Results o f Dose Preparation Analyses (ppm) 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Week Replicate 0 T-6314 (ppm) 1 10 30 100 500 4d 1 2 Mean 0.615 0.651 0.633 (63.3)c 23.2 23.9 23.6 (78.7) - c Each value in parenthesis is the percent o f theoretical, d reassay. Covance 6329-224 3M T-6314.2 9T9000 52  i DAYS 1-32 CATEGORY KEYWORD QUALIFIER *** TOP OF LIST *** SKIN & PELAGE SORE/SCAB DORSAL-THORACIC-LEFT DORSAL-THORACIC-RIGHT *** END OF LIST *** Table 4 Summary of Clinical Observations 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS SEX GROUP DOSE NUMBER: NUMBER OF ANIMALS AFFECTED --------------- 23 1 10 4 30 56 100 500 666666 001000 0 01 00 0 Covance 6329-224 3M T-6314.2 PAGE: 1 000617 53 > DAY biA I GROUP : DOSE: UNITS: 1 0 PPM iN 6 MEAN 169 S.D. 11.2 4N 6 MEAN 193 S.D. 11.4 8N 6 MEAN 228 S.D. 13.3 11 N 6 MEAN 251 S.D. 14.8 15 N 6 MEAN 281 S.D. 15.7 18 N 6 MEAN 300 S.D. 18.2 22 N 6 MEAN 329 S.D. 20.8 Table 5 Summary of Body Weight Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS 2 1 PPM 6 167 13.1 6 192 14.1 6 225 15.8 6 248 17.0 6 279 17.6 6 297 18.1 6 324 22.3 3 10 PPM 6 170 13.4 6 192 14.5 6 227 17.5 6 252 18.1 6 280 19.6 6 299 21.0 6 327 23.9 4 30 PPM 6 166 14.7 6 188 15.5 6 221 20.7 6 245 19.5 6 271 21.4 6 286 24.3 6 313 28.3 5 100 PPM 6 168 14.6 6 189 15.5 6 221 16.3 6 242 14.4 6 271 14.7 6 286 16.5 6 312 14.5 6 500 PPM 6 164 11.4 6 177 10.5 6 195* 8.3 6 211* 9.9 6 224* 6.8 6 236* 10.7 6 243* 16.0 Covance 6329-224 3M T-6314.2 PAGE: 1 000618 54 SEX: - GROUP: 1 DOSE: 0 DAY UNITS: PPM 25 N 6 MEAN 347 S.D. 24.4 29 N 6 MEAN 367 S.D. 29.3 32 N 6 MEAN 352 S.D. 29.0 Table 5 Summary of Body Weight Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ------- ---- MALE234 1 10 30 PPM PPM PPM 6 342 23.4 6 359 24.6 6 347 24.9 6 343 23.1 6 362 25.9 6 348 26.4 6 328 30.5 6 350 32.8 6 334 32.0 5 100 PPM 6 327 13.8 6 344 15.7 6 329 14.6 6 500 PPM 5 251* 17.8 5 258* 15.7 5 238* 12.8 Covance 6329-224 3M T-6314.2 PAGE: 2 oc o 55 SEX: GROUP : DOSE: DAY UNITS: 1 0 PPM 1N 6 MEAN 137 S.D. 11.7 4N 6 MEAN 152 S.D. 12.5 8N 6 MEAN 172 S.D. 12.4 11 N 6 MEAN 183 S.D. 11.9 15 N MEAN S.D. 6 196 13.6 18 N 6 MEAN 201 S.D. 14.8 22 N 6 MEAN 216 S.D. 15.7 Table 5 Summary of Body Weight Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS 2 1 PPM 6 132 7.5 6 150 8.9 6 167 8.6 6 175 6.7 6 187 9.1 6 197 9.1 6 210 10.4 FEMALE3 10 PPM 4 30 PPM 6 135 16.0 6 151 20.5 6 168 19.5 6 178 22.3 6 193 27.1 6 199 26.1 6 209 28.8 6 135 11.2 6 147 13.3 6 166 13.5 6 177 14.3 6 190 16.2 6 195 16.8 6 208 20.3 5 100 PPM 6 132 12.0 6 147 13.7 6 162 15.1 6 173 15.7 6 183 16.7 6 189 16.8 6 201 15.6 6 500 PPM 6 135 12. 6 138 8. 6 148 8. 6 155* 9. 6 162* 12. 6 164* 12. 6 171* 13. Covance 6329-224 3M T-6314.2 PAGE: 3 DAY SEX: GROUP : DOSE: UNITS: 1 0 PPM 25 N 6 MEAN 225 S.D. 17.9 29 N MEAN S.D. 6 237 18.5 32 N 6 MEAN 223 S.D. 18.7 Table 5 Summary of Body Weight Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS --------- FEMALE234 1 10 30 PPM PPM PPM 6 218 11.2 6 230 12.7 6 215 11.3 6 218 32.3 6 226 34.4 6 214 31.7 6 217 20.8 6 227 22.2 6 213 20.8 5 100 PPM 6 206 16.7 6 215 16.1 6 202 13.7 6 500 PPM 6 174* 14.3 6 178* 16.0 6 164* 13.8 Covance 6329-224 3M T-6314.2 PAGE: 4 000G21 57 OOOG DAY SEX: GROUP: DOSE: UNITS: - 1 0 PPM 1-4 N MEAN S.D. 4-8 N MEAN S.D. 8-11 N MEAN S.D. 11-15 N MEAN S.D. 15-18 N MEAN S.D. 18-22 N MEAN S.D. 22-25 N MEAN S.D. 6 24 1.9 6 34 3.5 6 23 4.1 6 31 5.4 6 19 3.8 6 29 4.8 6 18 4.3 Table 6 Summary of Body Weight Change Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS 2 1 PPM 6 24 1.6 6 33 3.2 6 24 2.3 6 30 4.0 6 19 2.1 6 26 5.9 6 18 3.3 --------- MALE-3 10 PPM 4 30 PPM 6 22 1.7 6 35 4.5 6 25 2.1 6 28 5.1 6 19 2.1 6 29 3.7 6 16 2.9 6 22 2.2 6 33 5.9 6 24 2.0 6 26 3.0 6 15 3.7 6 27 4.9 6 15 4.0 5 100 PPM 6 21 2.1 6 32 2.5 6 22 3.3 6 29 2.4 6 15 2.7 6 26 3.0 6 15 1.4 6 500 PPM 6 13* 5. 6 19* 5. 6 16* 3. 6 13* 3. 6 12* 5. 6 8* 8. 5 7* 1. ro 58 Covance 6329-224 3M T-6314.2 PAGE: 1 DAY SEX: GROUP : DOSE: UNITS: 1 0 PPM 25-29 N MEAN S.D. 29-32 N MEAN S.D. 1-32 N MEAN S.D. 6 20 5.5 6 -15 2.2 6 183 26.2 T able 6 Summary of Body Weight Change Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS 2 1 PPM 6 18 4.5 6 -13 3.1 6 179 18.9 MALE3 10 PPM 4 30 PPM 6 19 4.5 6 -14 2.5 6 178 18.0 6 22 3.0 6 -15 2.7 6 168 21.5 5 100 PPM 6 16 2.6 6 -15 3.1 6 161 8.8 6 500 PPM 5 7* 4.1 5 -21* 3.8 5 75* 4.8 Covance 6329-224 3M T-6314.2 PAGE: 2 DAY SEX: GROUP : DOSE: UNITS: 1 0 PPM 1-4 N MEAN S.D. 4-8 N MEAN S.D. 8-11 N MEAN S.D. 11-15 N MEAN S.D. 15-18 N MEAN S.D. 18-22 N MEAN S.D. 22-25 N MEAN S.D. 6 15 1.8 6 20 1.4 6 11 2.7 6 13 3.5 6 5 2.7 6 15 4.7 6 10 5.2 Table 6 Summary of Body Weight Change Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS 2 1 PPM 6 18 4.4 6 17 1.6 6 8 3.7 6 12 3.2 6 10 1.3 6 14 2.7 6 8 3.1 -------- FEMALE3 10 PPM 4 30 PPM 6 16 5.6 6 17 2.4 6 10 7.7 6 15 8.8 6 6 7.3 6 10 3.7 6 10 4.3 6 13 5.4 6 19 1.0 6 11 2.8 6 13 2.4 6 6 1.4 6 13 4.0 6 9 3.2 5 100 PPM 6 15 4.7 6 15* 2.2 6 10 2.3 6 10 1.5 6 6 2.1 6 12 2.8 6 6 2.2 6 500 PPM 6 3* 5.6 6 10* 3.1 6 7 3.5 6 7* 3.5 6 2 4.5 6 7* 3.1 6 4 4.2 Covance 6329-224 3M T-6314.2 PAGE: 3 DAY SEX: GROUP: DOSE: UNITS : 1 0 PPM 25-29 N MEAN S.D. 29-32 N MEAN S.D. 1-32 N MEAN S.D. 6 12 3.3 6 -14 3.7 6 86 10.4 Table 6 Summary of Body Weight Change Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS 2 1 PPM 6 12 4.1 6 -15 2.0 6 83 6.9 -------- FEMA LE ---------34 10 30 PPM PPM 6 8 3.0 6 -12 6.8 6 79 19.5 6 10 2.0 6 -15 2.2 6 78 14.3 5 100 PPM 6 9 3.3 6 -13 2.9 6 70 5.8 6 500 PPM 6 4* 3. 6 -14 3. 6 29* 12. Covance 6329-224 3M T-6314.2 PAGE: 4 DAY SEX: GROUP: DOSE: UNITS: 1 0 PPM 1N MEAN S.D. 6 76 5.5 4N 6 MEAN 102 S.D. 6.3 8N MEAN S.D. 6 80 7.1 11 N MEAN S.D. 6 108 9.3 15 N MEAN S.D. 6 81 7.7 18 N 6 MEAN 108 S.D. 8.9 22 N MEAN S.D. 6 88 8.5 Table 7 Summary of Food Consumption Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS 2 1 PPM ---------- MALE- 3 10 PPM 4 30 PPM 6 76 7.3 6 102 8.4 6 80 7.2 6 109 9.0 6 82 7.1 6 108 10.9 6 89 7.0 6 72 4.3 6 100 6.5 6 80 4.4 6 105 8.0 6 80 5.2 6 105 6.7 6 87 6.3 6 71 4.2 6 96 7.9 6 77 4.2 6 101 6.8 6 73 6.5 6 100 8.4 6 80 5.0 5 100 PPM 6 71 5.8 6 94 7.6 6 73 4.7 6 100 7.7 6 74 5.6 6 98 6.1 6 78 4.4 6 500 PPM 6 64* 3.8 6 74* 6.9 6 60* 5.1 6 75* 4.9 6 59* 3.8 6 68* 7.1 5 54* 8.7 Covance 6329-224 3M T-6314.2 PAGE: 1 > Table 7 Summary of Food Consumption Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS SEX: -------------------------------------MALE GROUP : 1 2 3 DOSE: 0 1 10 DAY UNITS: PPM PPM PPM 4 30 PPM 25 1-25 N MEAN S.D. N MEAN S.D. 5 122 9.6 5 777 46.2 6 132 28.6 6 777 59.5 6 115 9.5 6 742 47.5 6 110 10.6 6 707 50.6 5 100 PPM 6 104 8.8 6 692* 47.9 6 500 PPM 5 72* 4.2 5 525* 23.0 Covance 6329-224 3M T-6314.2 PAGE: 2 000 vi 63 Table 7 Summary of Food Consumption Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY SEX: ------------------------------------FEMALE- GROUP : 1 2 3 DOSE: 0 1 10 UNITS: PPM PPM PPM 4 30 PPM 1N MEAN S.D. 4N MEAN S.D. 8N MEAN S.D. 11 N MEAN S.D. 15 N MEAN S.D. 18 N MEAN S.D. 22 N MEAN S.D. 6 61 7.1 6 77 8.4 6 58 5.2 6 80 4.7 6 58 3.1 6 77 6.4 6 62 7.5 6 62 5.2 6 78 2.8 6 58 2.8 6 79 5.9 6 60 4.4 6 79 5.9 6 63 5.1 6 60 10.2 6 74 10.9 6 56 10.4 6 77 15.8 6 55 9.6 6 69 12.0 6 58 9.0 6 58 6.9 6 76 6.9 6 58 5.5 6 76 7.6 6 55 5.6 6 75 10.7 6 60 9.5 5 100 PPM 6 58 3.8 6 72 3.4 6 56 2.7 6 72 4.0 6 53 3.1 6 73 6.5 6 55 3.3 6 500 PPM 6 51 6.2 6 53* 5.8 6 45* 2.9 5 55* 7.3 6 41* 8.1 6 52* 5.0 6 42* 5.2 Covance 6329-224 3M T-6314.2 PAGE: 3 9000 w QO 64 SEX: - GROUP : 1 DOSE: 0 DAY UNITS: PPM 25 1-25 N MEAN S.D. N MEAN S.D. 5 82 9.4 5 551 44.0 Table 7 Summary of Food Consumption Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS --------- FEMALE234 1 10 30 PPM PPM PPM 6 86 8.3 6 565 34.0 6 80 13.0 6 529 82.4 5 75 7.0 5 517 45.0 5 100 PPM 5 73 5.8 5 513 20.8 6 500 PPM 6 54* 7.6 5 388* 39.7 Covance 6329-224 3M T-6314.2 PAGE: 4 o o o N o 65 Table 8 Summary of Test Material Consumption Data (mg/kg/day) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 1 DAY SEX: -------------------- GROUP: 2 3 DOSE: 1 10 UNITS: PPM PPM 1N MEAN S.D. 4N MEAN S.D. 8N MEAN S.D. 11 N MEAN S.D. 15 N MEAN S.D. 18 N MEAN S.D. 22 N MEAN S.D. 6 0.140 0.005 6 0.123 0.006 6 0.113 0.005 6 0.103 0.005 6 0.095 0.005 6 0.087 0.007 6 0.089 0.004 6 1.325 0.044 6 1.191 0.048 6 1.117 0.047 6 0.984 0.054 6 0.921 0.030 6 0.837 0.027 6 0.863 0.041 - M A L E ------------------------------ 4 56 30 100 500 PPM PPM PPM ----------------------------- FEMALE------------ 23 45 1 10 30 100 PPM PPM PPM PPM 6 4.030 0.210 6 3.524 0.132 6 3.311 0.258 6 2.951 0.137 6 2.617 0.094 6 2.500 0.067 6 2.501 0.118 6 13.192 0.692 6 11.506 0.605 6 10.505 0.601 6 9.711 0.538 6 8.797 0.412 6 8.227 0.423 6 8.150 0.234 6 62.612 4.144 6 49.583 5.932 6 49.261 4.268 6 43.192 3.772 6 42.446 2.463 6 35.210 2.563 5 36.296 3.715 6 0.147 0.008 6 0.123 0.004 6 0.113 0.003 6 0.110 0.005 6 0.104 0.004 6 0.097 0.006 6 0.098 0.005 6 1.399 0.098 6 1.164 0.093 6 1.074 0.128 6 1.027 0.116 6 0.928 0.072 6 0.848 0.078 6 0.910 0.061 6 4.124 0.320 6 3.625 0.145 6 3.393 0.198 6 3.105 0.143 6 2.872 0.128 6 2.764 0.208 6 2.790 0.221 6 13.802 0.732 6 11.716 0.618 6 11.133 0.662 6 10.115 0.449 6 9.609 0.678 6 9.517 1.572 6 9.089 0.957 6 500 PPM 6 62.217 8.174 6 46.216 6.426 6 49.206 1.743 5 43.613 3.405 6 41.810 6.302 6 38.527 2.059 6 40.035 2.173 0C9G00 66 Table 8 Summary of Test Material Consumption Data (mg/kg/day) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 2 SEX: GROUP : 2 DOSE: 1 DAY UNITS: PPM 25 1-25 N MEAN S.D. MEAN 6 0.094 0.022 0.105 3 10 PPM ---M ALE ----4 30 PPM 5 100 PPM 6 0.816 0.020 1.007 6 2.432 0.146 2.983 6 7.768 0.406 9.732 6 500 PPM 5 35.168 1.938 44.590 2 1 PPM 6 0.096 0.005 0.111 3 10 PPM -- FEMALE---4 30 PPM 5 100 PPM 6 0.905 0.044 1.032 5 2.612 0.138 3.172 5 8.485 0.647 10.475 6 500 PPM 6 38.539 3.754 45.050 Table 9 Summary of Clinical Hematology Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DOSE SFOS RBC XIOVltL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT X 1 0 3/m L MEAN S.D. N MEAN S.D. N 10 MEAN S.D. N 30 MEAN S.D. N 100 MEAN S.D. N 500 MEAN S.D. N 7.29 .448 6 15.0 .58 6 44.6 1.89 6 61.2 1.82 6 7.34 .253 6 14.6 .58 6 44.1 2.12 6 60.0 2.26 6 7.27 .209 6 14.9 .43 6 44.0 1.27 6 60.6 1.76 6 7.40 .156 6 15.0 .44 6 44.5 1.07 6 60.2 1.16 6 7.00 .719 6 14.6 1.12 6 43.1 3.46 6 61.6 1.73 6 5.90 * .623 5 12.3 * 1.00 5 36.0 * 3.11 5 61.1 2.07 5 20.6 .72 6 20.0 .84 6 20.5 .70 6 20.2 .43 6 20.8 .75 6 20.9 1.10 5 33.6 .29 6 33.4 .68 6 33.8 .20 6 33.7 .47 6 33.8 .39 6 34.1 .67 5 988 133 6 1058 157 6 1044 110 6 1057 177 6 1114 148 6 967 183 5 Covance 6329-224 3M T-6314.2 000632 68 DOSE WBC =FOS XIOV/^L Table 9 Summary of Clinical Hematology Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS N-SEG LYMPH X103//^L X 1 0 3/^L MONO X 1 0 3/^L EOSIN X1 0 3/aL BASO x i o 3m l N-SEG% LYMPH% MONO% EOSIN% Covanee 6329-224 3M T-6314.2 BASO% MEAN 11.6 1.0 9.4 .9 .2 .0 S.D. 3.14 .43 2.46 .44 .17 .04 N 666666 9 82 8 1 0 2.5 4.6 3.6 1.0 .4 6 6 66 6 MEAN 11.7 1.4 9.5 .8 .1 .0 12 81 6 1 0 S.D. 3.43 .74 2.59 .40 .04 .04 3.6 4.4 1.6 .4 .0 N 66666666666 10 MEAN 13.6 1.4 11.2 .8 .2 .0 12 80 7 1 0 S.D. 4.76 .57 4.57 .22 .10 .04 5.1 9.9 4.5 .4 N 66666666666 30 MEAN 12.3 .8 10.6 .8 .1 .0 S.D. 1.13 .15 1.21 .33 .05 .00 N 666666 6 86 6 1 0 1.2 3.5 2.9 .0 .0 6 6 66 6 100 MEAN 13.0 1.1 11.1 .6 .1 .0 S.D. 3.24 .27 2.72 .48 .00 .04 N 666666 9 86 2.2 3.4 4 2.3 1 .0 0 .0 66 666 500 MEAN 10.4 1.3 8.4 .6 .0 * .0 12 82 5 0 0 S.D. 1.72 .82 1.40 .27 .04 .04 7.2 8.9 2.1 .4 .4 N 55555555555 C3790OO 69 Table 9 Summary of Clinical Hematology Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DOSE iFOS RBC X 1 0 6/^L HGB G/DL HCT % MCV FL MCH PG MCHC % PLT X 1 0 3/AiL MEAN S.D. N MEAN S.D. N 10 MEAN S.D. N 30 MEAN S.D. N 100 MEAN S.D. N 500 MEAN S.D. N 7.12 .613 6 14.8 .65 6 43.5 2.12 6 61.2 2.78 6 7.41 .316 6 15.3 .51 6 45.0 1.34 6 60.8 1.29 6 7.62 .466 6 15.6 .95 6 46.4 2.34 6 61.0 1.87 6 7.19 .272 6 14.8 .50 6 43.4 1.82 6 60.4 .67 6 7.40 .386 6 15.0 .58 6 44.1 1.61 6 59.6 1.46 6 6.34 * .381 6 12.6 * 1.08 6 36.8 * 3.47 6 58.1 3.37 6 20.8 1.05 6 20.7 .35 6 20.5 .46 6 20.6 .20 6 20.2 .45 6 20.0 1.00 6 34.0 .34 6 34.0 .35 6 33.6 .44 6 34.2 .43 6 33.9 .34 6 34.4 .58 6 1012 90 6 1005 133 6 976 131 6 1027 72 6 1069 123 6 1042 160 6 Covance 6329-224 3M T-6314.2 000634 70 > DOSE ppm N aFOS WBC X103/m L Table 9 Summary of Clinical Hematology Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS N-SEG X 1 0 3/m L LYMPH X1 0 3/a<L MONO xioV ml EOS IN BASO X103/AiL XloV/iL N-SEG% LYMPH% MONO% EOSIN% Covance 6329-224 3M T-6314.2 BASO% MEAN 7.1 .6 5.8 .7 .1 .0 10 82 8 1 0 S.D. 3.40 .33 2.77 .72 .04 .04 6.1 5.7 5.8 .0 .0 N 66666666666 MEAN 8.0 .6 7.0 .4 .1 .0 S.D. 3.87 .32 3.68 .13 .08 .00 N 666666 10 MEAN 8.0 .5 6.8 .6 .1 .0 S.D. 2.94 .33 2.34 .38 .04 .00 N 666666 30 MEAN l l .3 .9 9.8 .5 .1 .0 S.D. 3.55 .50 3.18 .25 .00 .00 N 666666 100 MEAN 11.6 .6 10.4 .5 .1 .0 S.D. 2.96 .08 2.99 .34 .05 .00 N 666666 500 MEAN 11.4 .6 10.5 .4 .0 * .0 S.D. 3.95 .28 3.85 .16 .00 .04 N 666666 8 86 4.6 5.6 5 2.0 1 .8 0 .0 6 6 66 6 7 85 7 1 0 2.2 3.4 3.0 .0 . 0 6 6 66 6 8 87 4.1 5.2 4 1.5 1 .0 0 .0 6 6 66 6 5 89 * 5 1 0 1.0 4.1 3.4 .4 .0 66666 5 91 * 3 0 0 2.9 3.3 1.3 .0 .0 66666 00063 C/1 71  O o a Cf) i DOSE ppm MeFOS Table 10 Summary of Clinical Chemistry Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL CHOL MG/DL 0 MEAN 155 14 .6 6.1 4.5 1.6 .2 47 S.D. 39.1 1.5 .15 .29 .26 .10 .10 9.7 N 66666666 1 MEAN 135 13 .6 6.3 4.6 1.7 S.D. 16.2 2.5 .21 .35 .26 .12 N 666666 .1 55 .10 13.2 66 10 MEAN 138 12 .6 6.1 4.5 1.6 S.D. 32.5 1.8 .20 .18 .10 .18 N 666666 .2 44 .16 12.6 66 30 MEAN 141 12 .6 6.2 4.5 1.6 S.D. 39.7 1.4 .14 .42 .22 .23 N 666666 .2 40 .16 11.0 66 100 MEAN 116 16 .6 6.2 4.8 1.5 S.D. 39.8 1.6 .10 .48 .29 .22 N 666666 .1 35 .08 18.7 66 500 MEAN 107 22 * .6 6.0 5.1 * .9 * .7 * S.D. 17.1 2.7 .26 .34 .36 .17 .28 N 5555555 1* 1.6 5 Covance 6329-224 3M T-6314.2 72 * * i t >> Table 10 Summary of Clinical Chemistry Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DOSE AST/SGOT ALT/SGPT ppm MeFOS IU/L IU/L GGT IU/L CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L PCOAO IU/G Covance 6329-224 3M T-6314.2 0 1 10 30 100 500 MEAN S.D. N MEAN S.D. N MEAN S.D. N MEAN S.D, N MEAN S.D. N MEAN S.D. N 96 5. 0 6 117 26.6 6 109 24.7 6 93 10.4 6 122 20.3 6 165 * 87.3 5 34 3.0 6 32 10.3 6 35 5.2 6 36 6.4 6 48 * 11.7 6 222 * 204.3 5 0 .0 6 10.9 .23 6 0 11.2 .5 .19 66 0 11.3 .0 .44 66 0 .5 6 11.2 .44 6 0 .0 6 10.8 .62 6 0 .0 5 10.4 .46 5 12.1 .84 6 12.1 1.54 6 11.8 1.92 6 11.0 .85 6 11.3 .84 6 10.8 1.22 5 148 2.6 6 148 1.6 6 148 2.9 6 149 .8 6 148 1.0 6 145 2.2 5 7.1 1.29 6 7.5 1.75 6 7.5 1.93 6 6.6 .56 6 7.2 .88 6 8.2 .42 5 102 1.2 6 101 1.4 6 102 .8 6 102 1.9 6 101 2 6 101 1 5 9 1.8 6 9 2.5 6 8 1.9 6 8 2.4 6 .8 32 * 4.3 5 000637 73 I* DOSE ppm MeFOS Table 10 Summary of Clinical Chemistry Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL CHOL MG/DL Covance 6329-224 3M T-6314.2 0 MEAN 103 14 .8 6.4 5.0 1.4 S.D. 11.3 1.0 .23 .75 .56 .25 N 666666 1 MEAN S.D. N 112 24.3 6 15 1.7 6 .6 6.5 5.1 1.4 .23 .36 .26 .27 6666 10 MEAN S.D. N 99 22.2 6 14 3.0 6 .6 6.4 .10 .37 66 5.1 .34 6 1.3 .10 6 30 MEAN 131 15 .7 6.4 5.1 1.3 S.D. 28.4 3.8 .24 .79 .67 .13 N 666666 100 MEAN S.D. N 112 33.9 6 17 5.8 6 .7 6.7 .15 .52 66 5.5 .34 6 1.2 .21 6 500 MEAN 100 26 * .6 7.0 5.9 * 1.1 S.D. 20.6 3.9 .18 .48 .29 .20 N 666666 .1 .10 6 .2 .10 6 .2 .08 6 .1 .15 6 .2 .08 6 .5 * .28 6 45 11.5 6 55 11.1 6 46 10.7 6 54 9.5 6 38 17.1 6 7* 5.9 6 000638 74 00063 i ( 5 t Table 10 Summary of Clinical Chemistry Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DOSE AST/SGOT ALT/SGPT aFOS IU/L IU/L GGT IU/L CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L PCOAO IU/G Covance 6329-224 3M T-6314.2 MEAN S.D. N MEAN S.D. N 10 MEAN S.D. N 30 MEAN S.D. N 100 MEAN S.D. N 500 MEAN S.D. N 104 14.0 6 107 15.1 6 125 36.5 6 100 22.0 6 90 9.1 6 118 21.4 6 27 2.7 6 30 1.2 6 27 6.1 6 28 7.4 6 29 4.8 6 60 * 16.4 6 0 .8 6 10.9 .66 6 0 .8 6 11.4 .47 6 0 11.1 .0 .59 66 1 11.1 1.5 .61 66 0 .0 6 11.4 .54 6 0 10.9 .0 .50 66 11.6 .95 6 12.4 1.63 6 11.9 1.20 6 10.5 .84 6 11.5 .99 6 10.6 .65 6 147 .9 6 147 2.5 6 146 1.4 6 146 2.7 6 147 1.3 6 148 1.8 6 7.9 1.34 6 8.2 1.76 6 8.9 .83 6 7.0 1.06 6 7.6 .49 6 6.8 .77 6 103 1.8 6 104 1.0 6 103 1.4 6 102 1.0 6 103 1.0 6 102 3.0 6 5 1.6 6 6 1.8 6 7 1.4 6 6 2.9 6 8 3.0 6 30 * 12.0 6 75  Table 11 Summary of Clinical Urinalysis Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DOSE bFOS U VOL ML SP GR U PH MEAN S.D. N MEAN S.D. N 10 MEAN S.D. N 30 MEAN S.D. N 100 MEAN S.D. N 500 MEAN S.D. N 18.5 9.86 6 27.7 22.39 6 28.4 13.81 6 26.0 14.80 6 15.9 17.26 6 20.4 15.52 5 1.017 .0096 6 1.015 .0112 6 1.010 .0027 6 1.013 .0069 6 1.023 .0107 6 1.019 .0126 5 7.4 .20 6 7.2 .27 6 7.2 .26 6 6.9 .20 6 6.9 .58 6 6.8 * .27 5 Covance 6329-224 3M T-6314.2 000640 76 t) Table 11 Summary of Clinical Urinalysis Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DOSE =FOS U VOL ML SP GR U PH MEAN S.D. N MEAN S.D. N 10 MEAN S.D. N 30 MEAN S.D. N 100 MEAN S.D. N 500 MEAN S.D. N 30.6 20.36 6 25.7 17.62 6 27.1 16.49 6 15.0 9.40 6 29.0 17.62 6 14.8 12.98 6 1.010 .0077 6 1.008 .0044 6 1.008 .0064 6 1.015 ,0097 6 1.008 .0056 6 1.011 .0046 6 7.1 .38 6 7.0 .32 6 6.9 .20 6 7.1 .38 6 7.0 .32 6 7.0 .32 6 Covance 6329-224 3M T-6314.2 00064 77 si TABLE 12 Summary of Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 1 TABLE INCLUDES: SEX=ALL ;GROUP=ALL ;WEEKS=ALL DEATH=T ;SUBSET=ALL SEX: GROUP : ---2 --- -------3------- MAI E ---------- 4-- ---5 --- ---6-- -- 1 --- -- 2 -- ------- FEM A LE---------3--- ---4--- -- 5-- -- 6-- NUMBER: 6 6 6 6 6 5 6 6 6 6 6 6 TERMINAL BODY WEIGHT (g) # IN GRP : MEAN: STAND DEV: 6 341.8 29.6 6 337.9 24.7 6 337.2 25.3 6 323.1 31.3 6 320.7 15.0 5 227.8* 11.4 6 213.3 17.8 6 205.9 12.0 6 203.7 32.0 6 204.3 21.1 6 193.6 13.9 6 156.6* 13.2 AD - ADRENAL # IN GRP : MEAN: STAND DEV: 6 0.0577 0.0106 6 0.0571 0.0063 6 0.0608 0.0088 6 0.0520 0.0086 6 0.0547 0.0094 5 0.0569 0.0112 6 0.0731 0.0148 6 0.0687 0.0071 6 0.0749 0.0229 6 0.0639 0.0087 6 0.0661 0.0068 6 0.0464* 0.0114 BR - BRAIN # IN GRP : MEAN: STAND DEV: 6 2.0588 0.1028 6 2.0352 0.0854 6 2.0175 0.1200 6 2.1275 0.1430 6 2.0927 0.0928 5 2.0009 0.1027 6 1.9550 0.0500 6 1.9833 0.1088 6 1.9873 0.0735 6 2.0235 0.1071 6 2.0041 0.0906 6 1.9920 0.1159 EP - EPIDIDYMIDES # IN GRP : 6 6 6 6 6 5 0 0 0 0 0 0 MEAN: 0.9214 0.8976 0.9760 0.8663 0.8447 0.7317* STAND DEV: 0.0821 0.0555 0.0886 0.0785 0.1274 0.0679 00 OG do 78 TABLE 12 Summary of Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 2 TABLE INCLUI)ES: SEX=ALL;C5R0UP=ALL;WEEKS =ALL D E A T H = T ; ;u b s e t =a l l SEX: GROUP : NUMBER: 6 ---2 --6 ---3 --6 ---4 --6 ---5--6 ---6- -- 5 ---1 --6 -- 2-- 6 -- 3-- 6 -- 4-- 6 ---5--6 --- 6 --6 KD - KIDNEY # IN GRP : MEAN: STAND DEV: 6 3.3984 0.3295 6 3.1034 0.3872 6 3.3466 0.2597 6 3.2329 0.3284 6 3.2922 0.2223 5 2.5925* 0.2256 6 2.0935 0.2961 6 1.9685 0.1666 6 2.2523 0.3837 6 2.0578 0.1457 6 2.1936 0.2491 6 1.7253 0.1934 LI - LIVER # IN GRP : MEAN: STAND DEV: 6 12.9118 1.7284 6 12.4546 1.0193 6 12.7132 0.8627 6 12.3245 1.7057 6 16.7113* 1.7399 5 19.6094* 1.0341 6 7.7513 0.7450 6 7.5539 0.6425 6 7.9991 1.2215 6 8.3214 1.2523 6 9.6111* 0.7628 6 12.3797* 1.7764 OV - OVARY # IN GRP : 0 0 0 0 0 0 6 6 6 6 6 6 MEAN: 0.1272 0.1311 0.1376 0.1185 0.1163 0.0763* STAND DEV: 0.0243 0.0128 0.0200 0.0273 0.0155 0.0181 SP - SPLEEN # IN GRP : MEAN: STAND DEV: 6 0.8049 0.0654 6 0.7518 0.0904 6 0.7777 0.0914 6 0.7072 0.1085 6 0.6731 0.1114 5 0.5820* 0.0775 6 0.5080 0.1069 6 0.5032 0.0719 6 0.4927 0.1181 6 0.4929 0.0710 6 0.4743 0.0810 6 0.4265 0.0686 o o o CO 7 9 TABLE 12 Summary of Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 3 TABLE INCLUD ES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E A TH=T;SUBSET=ALL SEX: GROUP: NUMBER: --- 1--6 -- 2-- 6 ---3 --6 ---4 --6 ---5 --6 ---6 --5 ---2 --- - -- 3-- 1""" -- _4-- -- 5-- -- 6-- 666 66 6 TE - TESTIS # IN GRP : 6 6 6 6 6 5 0 0 0 0 0 0 MEAN: 3.0558 2.9480 3.0071 2.9256 2.9717 2.9968 STAND DEV: 0.2644 0.1952 0.2583 0.2156 0.1282 0.2885 TH - THYMUS # IN GRP : MEAN: STAND DEV: 6 0.6039 0.1774 6 0.6833 0.1692 6 0.6890 0.1418 6 0.5854 0.0721 6 0.6600 0.1124 5 0.4490 0.1074 6 0.5455 0.0592 6 0.5229 0.1124 6 0.5321 0.0918 6 0.5484 0.0854 6 0.5062 0.1873 6 0.4587 0.1086 TT - THYROID/PARATHYR # IN GRP : MEAN: STAND DEV: 6 0.0206 0.0049 6 0.0234 0.0050 6 0.0226 0.0033 6 0.0206 0.0068 6 0.0219 0.0039 5 0.0197 0.0061 6 0.0159 0.0019 6 0.0181 0.0032 5 0.0193 0.0043 6 0.0184 0.0063 6 0.0181 0.0049 6 0.0137 0.0031 3000 TABLE 13 Summary of Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 1 TABLE INCLUDES: S E X=ALL;GROUP=ALL;WEEKS=ALL D E ATH=T;SUBSET=ALL SEX: GROUP: NUMBER: ------------------------------ MAL E ------------------------------ ----------------------------- FEMALE---------------------------- -- -1-- - -- 2-- -- 3 --- ---4 -- ---5 -- - --- 6 --- -- 1-- -- 2---- ---3 -- 4-- ---5 -- ---6 -- 666665666666 AD - ADRENAL # IN GRP : MEAN STAND DEV 6 0.0171 0.0044 6 0.0170 0.0027 6 0.0181 0.0031 6 0.0162 0.0030 6 0.0170 0.0023 566 0.0249* 0.0343 0.0042 0.0063 6 0.0333 0.0030 6 0.0363 0.0075 6 0.0312 0.0022 6 0.0342 0.0032 0.0295 0.0062 BR - BRAIN # IN GRP MEAN STAND DEV 6 0.6058 0.0562 6 0.6049 0.0496 6 0.6006 0.0511 6 0.6626 0.0650 6 0.6536 0.0404 5 0.8801* 0.0642 6 0.9213 0.0679 6 0.9648 0.0592 6 0.9925 0.1298 6 0.9962 0.0758 6 1.0372* 0.0438 6 1.2757 0.0644 EP - EPIDIDYMIDES # IN GRP 6 6 6 6 6 5 0 0 0 0 0 0 MEAN 0.2708 0.2672 0.2901 0.2688 0.2629 0.3208* STAND DEV 0.0282 0.0292 0.0251 0.0210 0.0316 0.0193 KD - KIDNEY # IN GRP MEAN STAND DEV 6 0.9957 0.0730 6 0.9210 0.1214 6 0.9927 0.0327 6 1.0030 0.0801 6 1.0264 0.0465 5 1.1372* 0.0646 6 0.9798 0.0858 6 0.9565 0.0640 6 1.1053* 0.0733 6 1.0105 0.0442 6 1.1315* 0.0744 6 1.1021 0.0843 000645 81 TABLE 13 Summary of Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 2 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL EATH=T; SUBSET=ALL SEX: GROUP: -- 2-- ------- m a l E -----------3--- ---4 --- ---5 --- -- -6 -- - -- 3.-- --- 2-- ------ FEMALE--------- ---3--- -- 4-- -- 5-- ---6 --- NUMBER : 6 6 6 6 6 5 6 6 6 6 6 6 LI - LIVER # IN GRP : MEAN: STAND DEV: 6 3.7673 0.2855 6 3.6892 0.2180 6 3.7731 0.1192 6 3.8050 0.2642 6 5.2193* 0.5890 5 8.6147* 0.4240 6 3.6336 0.1378 6 3.6701 0.2643 6 3.9342 0.2503 6 4.0598* 0.2523 6 4.9671* 0.2573 6 7.8932 0.7492 OV - OVARY # IN GRP : 0 0 0 0 0 0 6 6 6 6 6 6 MEAN: 0.0595 0.0638 0.0681 0.0580 0.0603 0.0485 STAND DEV: 0.0086 0.0070 0.0093 0.0122 0.0092 0.0097 SP - SPLEEN # IN GRP : MEAN: STAND DEV: 6 0.2374 0.0317 6 0.2226 0.0242 6 0.2311 0.0261 6 0.2193 0.0297 6 0.2110 0.0412 5 0.2566 0.0414 6 0.2377 0.0411 6 0.2446 0.0344 6 0.2398 0.0285 6 0.2407 0.0167 6 0.2447 0.0353 6 0.2727 0.0400 TE - TESTIS # IN GRP : 6 6 6 6 6 5 0 0 0 0 0 0 MEAN: 0.8974 0.8749 0.8978 0.9084 0.9280 1.3135* STAND DEV: 0.0834 0.0693 0.1212 0.0596 0.0567 0.0803 o o o ff) 82 TABLE 13 Summary of Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 3 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T; SUBSET=ALL SEX GROUP NUMBER -------- MAL E -------- ---2 --- ---3--- -- 4-- ---5--- ---6--- 6666656 -- 2 --6 ------- FEMALE - 4 --- 66 ---5--6 --- 6 --6 TH - THYMUS # IN GRP MEAN STAND DEV 6 0.1768 0.0498 6 0.2015 0.0425 6 0.2027 0.0277 6 0.1820 0.0234 6 0.2068 0.0401 5 0.1970 0.0465 6 0.2566 0.0280 6 0.2553 0.0627 6 0.2628 0.0391 6 0.2695 0.0417 6 0.2598 0.0915 6 0.2915 0.0530 TT - THYROID/PARATHYR # IN GRP MEAN STAND DEV 6 0.0060 0.0011 6 0.0070 0.0016 6 0.0067 0.0009 6 0.0063 0.0017 6 0.0068 0.0011 5 0.0087 0.0027 6 0.0075 0.0013 6 0.0088 0.0015 5 0.0098 0.0024 6 0.0090 0.0028 6 0.0093 0.0021 6 0.0088 0.0020 )f r t r TABLE 14 Summary of Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 1 TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L DEATH=T ;SUBSET=ALL GROUP NUMBER -- 2-- 66 # IN GRP MEAN STAND DEV 6 0.0282 0.0056 6 0.0281 0.0035 # IN GRP MEAN STAND DEV 6 1.0000 0.0000 6 1.0000 0.0000 # IN GRP MEAN STAND DEV 6 0.4479 0.0374 6 0.4419 0.0357 # IN GRP MEAN STAND DEV 6 1.6539 0.1800 6 1.5214 0.1402 6 6 0.0303 0.0052 6 1.0000 0.0000 6 0.4852 0.0526 6 1.6641 0.1680 --4--6 ---5--6 -- 6-- 5 ---2--- -- 3-- 1" " 666 AD - ADRENAL 6 0.0243 0.0028 6 0.0263 0.0055 5 0.0285 0.0060 6 0.0375 0.0081 6 0.0348 0.0049 6 0.0375 0.0109 BR - BRAIN 6 1.0000 0.0000 6 1.0000 0.0000 5 1.0000 0.0000 6 1.0000 0.0000 6 1.0000 0.0000 6 1.0000 0.0000 EP - EPIDIDYMIDES 66 500 0 0.4082 0.4057 0.3658* 0.0411 0.0763 0.0305 KD - KIDNEY 6 1.5184 0.0923 6 1.5770 0.1476 5 1.2978* 0.1248 6 1.0710 0.1534 6 0.9951 0.0990 6 1.1299 0.1651 4-- -- 5-- -- -6-- 666 6 0.0316 0.0037 6 0.0330 0.0029 6 0.0232* 0.0055 6 1.0000 0.0000 6 1.0000 0.0000 6 1.0000 0.0000 000 6 1.0175 0.0597 6 1.0924 0.0845 6 0.8659* 0.0839 00064 84 GO Ii TABLE 14 Summary of Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covanee 6329-224 3M T-6314.2 PAGE: 2 TABLE INCLUD ES: SEX=ALL;G ROUP=ALL;WEEKS=ALL D E A TH=T;SUBSET=ALL SEX: GROUP: NUMBER: -- 2-- ---3--- ---4 --- ---5--- ---6--- 666 6 6 5 ---2 --66 LI - LIVER # IN GRP : MEAN: STAND DEV: 6 6.2701 0.7779 6 6.1241 0.4911 6 6.3108 0.4252 6 5.8070 0.8457 6 8.0008* 0.9384 5 9.8193* 0.6974 6 3.9653 0.3785 6 3.8077 0.2222 OV - OVARY # IN GRP : 0 0 0 0 0 0 6 6 MEAN: 0.0650 0.0663 STAND DEV: 0.0114 0.0075 SP - SPLEEN # IN GRP : MEAN: STAND DEV: 6 0.3911 0.0264 6 0.3698 0.0453 6 0.3881 0.0648 6 0.3329 0.0479 6 0.3229 0.0593 5 0.2909* 0.0359 6 0.2598 0.0548 6 0.2551 0.0471 TE - TESTIS # IN GRP : MEAN: STAND DEV: 6 1.4847 0.1098 6 1.4512 0.1214 6 1.4952 0.1644 6 1.3776 0.1037 6 1.4226 0.0946 5 1.5006 0.1628 0 0 ---4-- -- 5--- -- 6-- - 6666 6 4.0137 0.5071 6 4.1069 0.5175 6 4.7927* 0.2526 6 6.2027* 0.7044 6 0.0691 0.0086 6 0.0586 0.0130 6 0.0581 0.0077 6 0.0382* 0.0082 6 0.2466 0.0519 6 0.2435 0.0310 6 0.2359 0.0329 6 0.2140 0.0314 0000 000649 85 TABLE 14 Summary of Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 3 TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L DEATH=T ;SUBSET=ALL SEX GROUP NUMBER -- -2-- 66 -------- MAL E ----------3--- ---4--- -- 5-- 6 66 -- 6-- 5 ------- FEMALE --2-- -4--- -- -5-- --- 6 --- 666666 TH - THYMUS # IN GRP MEAN STAND DEV 6 0.2911 0.0722 6 0.3343 0.0739 6 0.3413 0.0659 6 0.2745 0.0201 6 0.3156 0.0545 5 0.2256 0.0603 6 0.2795 0.0342 6 0.2664 0.0704 6 0.2676 0.0440 6 0.2705 0.0352 6 0.2506 0.0856 6 0.2295 0.0474 TT - THYROID/PARATHYR # IN GRP MEAN STAND DEV 6 0.0100 0.0021 6 0.0116 0.0029 6 0.0112 0.0012 6 0.0097 0.0030 6 0.0104 0.0016 5 0.0098 0.0025 6 0.0081 0.0011 6 0.0091 0.0012 5 0.0098 0.0023 6 0.0091 0.0030 6 0.0090 0.0023 6 0.0069 0.0017 oo o a o 86 i >t TABLE 15 Incidence of Macroscopic Observations Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS C o v a n c e 6329-224 3M T-6314.2 PAGE: 1 TABLE INCLUDES: SEX=ALL ;GR0UP=ALL ;WEEKS=ALL D E A TH=T;SUBSET=ALL -- N U M B E R - O F - A N I M A L S - A F F E C T E D ---SEX: ------------- MAL E ------------- ------------ FEMALE GROUP: -1- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- -6- ORGAN AND KEYWORD (S) OR PHRASE NUMBER: 6 6 6 6 6 5 6 6 6 6 6 6 ** TOP OF LIST ** GENERAL COMMENT (GC) ......... 6 666 6 5 666 6 66 MALOCCLUSION NO MACROSCOPIC LESIONS BONE MARROW SMEAR TAKEN ANIMAL THIN DISCHARGE-OCULAR 000001000000 565560555635 666665666666 00 00 0 10 00 0 01 000001000000 KIDNEY (KD) ................... 666665666666 NOT REMARKABLE: 6 6 6 6 6 5 6 5 6 6 6 6 LARGE PELVIS(ES) 000000010000 LIVER (LI) .................... .......................... NUMBER EXAMINED: 6 6 6 6 6 5 6 6 6 6 6 6 NOT REMARKABLE: 6 6 6 6 6 3 6 6 6 6 6 6 LARGE LIGHT FOCUS(I)/AREA(S) DIFFUSELY DARK 000002000000 000001000000 000001000000 ADRENAL, CORTEX (AC) ......... 6666 656 66666 NOT REMARKABLE: 6 6 6 5 6 4 6 6 6 6 6 6 SMALL DIFFUSELY RED 00 01 000 00000 000001000000 87 3000 I TABLE INCLUDES: SEX=ALL ;GR0UP=ALL ;WEEKS=ALL D E ATH=T;SUBSET=ALL ORGAN AND KEYWORD(S) OR PHRASE STOMACH, GL (ST) RED FOCUS(I)/AREA(S) DARK FOCUS(I)/AREA(S) LN, MANDIBULAR (MN) .... MOTTLED SKIN (SK) ................ CRUSTED A R E A (S ) ALOPECIA-FOCAL UTERUS (UT) ............. LUMEN FILLED WITH FLUID SEMINAL VESICLES (SV) ... SMALL ** END OF LIST ** TABLE 15 incidence of Macroscopic Observations Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 2 -- N U M B E R - 0 F - ANI M A LS- A F F E C T E D -- SEX: GROUP: -l- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- -6- NUMBER: 6 =-------------------- ----------- - - 6 -= - 6 -=- 6 -=- 6 -= -- 5 - =- 6 "=' 6 --= -- 6 ---- -- 6 --= -- NUMBER EXAMINED: 6 6 6 6 6 5 6 6 6 6 NOT REMARKABLE: 5 6 6 6 6 3 6 6 6 6 66 _=_ 66 66 000001000000 100001000000 NUMBER EXAMINED: 6 6 6 6 6 5 6 6 6 6 6 6 NOT REMARKABLE: 6 6 6 6 6 4 6 6 6 6 6 6 000001000000 NUMBER EXAMINED: 6 6 6 6 6 5 6 6 6 6 6 6 NOT REMARKABLE: 6 6 5 6 6 5 6 6 6 6 6 5 001000000000 0 0 0 0 000 0 0 0 01 NUMBER EXAMINED: 0 0 0 0 0 0 6 6 6 6 6 6 NOT REMARKABLE: 0 0 0 0 0 0 5 6 5 6 3 6 000000101030 NUMBER EXAMINED: 6 6 6 6 6 5 0 0 0 0 0 0 NOT REMARKABLE: 6 6 6 6 6 4 0 0 0 0 0 0 000001000000 88 000652 i TABLE 16 Incidence of Microscopic Observations Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 1 TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D EATH=ALL;F I N D=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION ** TOP OF LIST ** EYE (EY) ........................................... --VASCULARIZATION, CORNEAL -- INFILTRATE, LYMPHOCYTIC --ONE EXAMINED BRAIN (BR) ......................................... --VACUOLATION KIDNEY (KD) ........................................ --DEGENERATION, TUBULAR --HYALINE DROPLETS, TUBULAR EPITHELIUM --INFLAMMATION, CHRONIC --PYELITIS --CYST --DILATATION, PELVIC LIVER (LI) ......................................... --INFLAMMATION, SUBACUTE --HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR -- VACUOLATION, HEPATOCELLULAR ** CONTINUED ON NEXT PAGE ** -- N U M B E R - O F - A N I M A L S - A F F E C T E D ---- SEX: -- MALE -- FEMALE-- G R O U P : -1- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- -6- NUMBER: 6 6 6 6 6 6 6 6 6 6 6 6 6 66 66 6 6 66 6 66 NOT REMARKABLE: 6 5 4 6 6 6 6 6 6 6 6 5 010000000000 000000000001 002000000000 666666666666 NOT REMARKABLE: 0 0 1 0 0 0 1 0 0 1 1 0 66 5 66 6 5 66 5 56 666666666666 NOT REMARKABLE: 5 2 6 4 5 6 5 3 4 2 5 5 100010010000 12 0000000000 02 01 0 000 01 00 010000012211 0001 0 0 100 0 00 000000010100 6666 6 6 66 66 66 NOT REMARKABLE: 2 2 3 0 0 0 1 1 4 3 0 0 44 34 5 12 0 01 30 000666000066 0000204 52120 89 000653 TABLE 16 incidence of Microscopic Observations Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 2 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=ALL;FIND=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION ** FROM PREVIOUS PAGE ** LIVER (LI) ........... --NECROSIS SPLEEN (SP) .......... PANCREAS (PA) ........ --INFLAMMATION, CHRONIC -- HEMORRHAGE LN, MESENTERIC (MS) ...... --HEMORRHAGE ADRENAL, CORTEX (AC) .... -- 'VACUOLATION ADRENAL, MEDULLA (MA) N U M B E R - 0 F - A N I M A L S - A F F E C TED "" SEX: GROUP: -1NUMBER: 6 -26 -36 -46 -56 -66 -i6 -26 -36 -46 -56 - 6- 6 0NUMBER EXAMINED: 6 6 6 6 6 6 6 6 6 6 6 6 NOT REMARKABLE: 2 2 3 0 0 0 1 1 4 3 0 001013000100 NUMBER EXAMINED: 6 6 6 6 6 6 6 6 6 6 6 6 NOT REMARKABLE: 6 6 6 6 6 6 6 6 6 6 6 6 NUMBER EXAMINED: NOT REMARKABLE: 6 6 6 6 6 6 6 6 6 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 000010000000 000010000000 NUMBER EXAMINED: 6 6 6 6 6 6 6 5 6 6 6 5 NOT REMARKABLE: 6 6 6 6 6 5 6 5 6 6 6 5 000001 000000 NUMBER EXAMINED: 6 6 6 6 6 6 6 6 6 6 6 NOT REMARKABLE: 4 5 4 5 6 6 6 6 6 6 6 2 12 1 000 000 00 NUMBER EXAMINED: 6 6 6 6 6 6 6 6 6 6 6 6 6NOT REMARKABLE: 6 6 6 6 6 6 6 6 6 6 6 <010 TABLE 16 Incidence of Microscopic Observations Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 3 TABLE INCLUDES: SEX=ALL ;GR0UP=ALL ;WEEKS=ALL D E A T H = A L L ;F I N D = A L L ;S U B S E T = A L L ORGAN AND FINDING DESCRIPTION OVARY (OV) ..................... TESTIS (TE) .................... BONE, FEMUR (FE) .............. MARROW, FEMUR (FM) ............ MARROW, STERNUM (SE) BONE, STERNUM (SB) . LUNG (LU) .......... ___ N U M B E R - 0 F - A N I M A L S - A F F E C T E SEX: GROUP: -1- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- NUMBER: 6 6 6 6 6 6 6 -= -- -=- - =- - =- -=" - = - -= - NUMBER EXAMINED: 0 0 0 0 0 0 6 NOT REMARKABLE: 0 0 0 0 0 0 6 6666 -- = -- - =- ------ 6666 6666 NUMBER EXAMINED: 6 6 6 6 6 6 0 0 0 0 0 NOT REMARKABLE: 6 6 6 6 6 6 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 6 66 0 0 0 0 oo NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 9000 tn CA 91 > TABLE 16 Incidence of Microscopic Observations Covanee 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 4 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=ALL;FIND=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION TRACHEA (TR) ESOPHAGUS (ES) HEART (HT) ......... MUSCLE, SKELETAL (SM) NERVE, SCIATIC (SN) . STOMACH, GL (ST) --EROSION STOMACH, NONGL (SU) . -- N U M BER - 0 F - ANI M A LS- A F F E C T E D -- SEX: GROUP: -1- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- -6NUMBER: 6 6 6 6 6 6 6 6 6 6 6 6 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 1 0 0 0 0 2 0 0 0 0 0 0 NOT REMARKABLE: 1 0 0 0 0 1 0 0 0 0 0 0 00 00 0 10 0 00 0 0 NUMBER EXAMINED: 1 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 1 0 0 0 0 0 0 0 0 0 0 0 92 000656 >! TABLE 16 Incidence of Microscopic Observations Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 5 TABLE INCLUDES: SEX=ALL ;GROUP=ALL ;WEEKS=ALL DEATH=ALL;FIND=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION DUODENUM (DU) ................. JEJUNUM (JE) .................. ILEUM (IL) .................... LN, POPLITEAL (PP) ........... CECUM (CE) COLON (CO) RECTUM (RE) --- N U M B E R - 0 F - A N I M A L S - A F F E C T E D -- SEX: GROUP: -1- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- -6- NUMBER: 6 6 6 6 6 6 6 -- -= - -= - --= -- --= " -= -- -= " -=- NUMBER EXAMINED: 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 66666 --=" ------ "--~ -=- 00000 00000 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 93 000657 I TABLE 16 incidence of Microscopic Observations Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 6 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=ALL;FIND=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION THYROID (TY) PARATHYROID (PT) AORTA (AO) PITUITARY (PI) THYMUS (TH) ....... SPINAL CORD (SC) HARDERIAN GLAND (HG) ___ N U M B E R - 0 F - A N I M A L S - A F F E C T E D -- SEX: GROUP: -1- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- -6NUMBER: 6 6 6 6 6 6 6 6 6 6 6 6 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 o o in 00 94 TABLE 16 Incidence of Microscopie Observations Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 7 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=ALL;FIND=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION AUDITORY SEB GL (AS) ......... SALIV GL, MANDIB (SG) ........ LN, MANDIBULAR (MN) .......... SKIN (SK) ....................... --INVOLUTION, FOLLICULAR -- INFLAMMATION, CHRONIC-ACTIVE MAMMARY, FEMALE (MF) ........... URINARY BLADDER (UB) ........... N M B ER -0 F -AN IM A LS -A F F E C TE D -- SEX: G R O U P : -1- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- -6- NUMBER: 6 6 6 6 -- -=" ~=" -=- -=- NUMBER EXAMINED: 0 0 0 0 NOT REMARKABLE: 0 0 0 0 666666 -= - -=- --= -- --= -- --= " 000000 000000 66 "=_ 00 00 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 1 0 0 0 0 0 0 0 0 1 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 000000000001 0 01 00 0 0 00 0 00 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 i TABLE 16 Incidence of Microscopic Observations Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 8 TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D EATH=ALL;FIND=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION CERVIX (CV) .................... UTERUS (UT) .................... --DILATATION VAGINA (VA) .................... PROSTATE (PR) .................. SEMINAL VESICLES (SV) ......... -- SECRETION, DECREASED EPIDIDYMIDES (EP) ............. ** END OF LIST ** o o o a CTj o N UM BE R -O F -A N IMA L S -A F F EC T E D -- SEX: G R O U P : -1- -2- -3- -4- -5- -6- -1- -2- -3- -4- -5- -6- ----------N-U-M-B-E-R-: 6 -= " 6 "=- 6 -~- 6 --= - 6 66666 -=- --= -- -= ~ --= " 66 "=_ NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 1 0 1 0 3 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 0000001 01030 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 1 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 0000010 000 00 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 0 0 0 0 TABLE 17 Incidence of Severity of Selected Microscopic Observations Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 1 TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E A T H = A L L ;F I N D = A L L ;S U B S E T = T ORGAN/TISSUE EXAMINED ** TOP OF LIST ** LIVER (LI) ................. --INFLAMMATION, SUBACUTE --HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR --VACUOLATION, HEPATOCELLULAR --NECROSIS ** END OF LIST ** -- N U M B ER -O F -AN IM A L S -A FFE C T ED -- SEX: GROUP: -i- -3- -4- NUMBER: 6 6 6 6 6 6 6 6 6 6 6 6 -- -= " -=-- -= " -= - --=- -= -- -= - --= " -=- "= " "=" NUMBER EXAMINED: 6 -> 2 1> 4 2> 0 TL> 6 MN> 0.7 6 2 4 0 6 0.7 6 3 3 0 6 0.5 6 2 3 1 6 0.8 6 1 4 1 6 1.0 6 5 1 0 6 0.2 6 4 2 0 6 0.3 6 6 0 0 6 0.0 6 6 0 0 6 0.0 6 5 1 0 6 0.2 6 3 3 0 6 0.5 6 6 0 0 6 0.0 -> 6 1> 0 2> 0 3> 0 4> 0 5> 0 TL> 6 MN> 0.0 6 0 0 0 0 0 6 0.0 6 0 0 0 0 0 6 0.0 0 5 1 0 0 0 6 1.2 0 0 0 4 2 0 6 3.3 0 0 0 0 3 3 6 4.5 6 0 0 0 0 0 6 0.0 6 0 0 0 0 0 6 0.0 6 0 0 0 0 0 6 0.0 6 0 0 0 0 0 6 0.0 0 0 4 2 0 0 6 2.3 0 0 0 1 5 0 6 3.8 -> 6 1> 0 TL> 6 MN> 0.0 6 0 6 0.0 6 0 6 0.0 6 0 6 0.0 4 2 6 0.3 6 0 6 0.0 2 4 6 0.7 1 5 6 0.8 4 2 6 0.3 5 1 6 0.2 4 2 6 0.3 6 0 6 0.0 -> 6 1> 0 3> 0 4> 0 TL> 6 MN> 0.0 6 0 0 0 6 0.0 5 1 0 0 6 0.2 6 0 0 0 6 0.0 5 1 0 0 6 0.2 3 0 2 1 6 1.7 6 0 0 0 6 0.0 6 0 0 0 6 0.0 6 0 0 0 6 0.0 5 1 0 0 6 0.2 6 0 0 0 6 0.0 6 0 0 0 6 0.0 0006G1 97 APPENDIX 1 Protocol Deviations Protocol Protocol Amendment No. 1 Covance 6329-224 3M T-6314.2 98 000662 Protocol Deviations Covance 6329-224 3M T-6314.2 Protocol. Test material. Disposition o f Test Material. After authorization from the Sponsor, any remaining test material will be returned to the Sponsor. Actual Procedure. Remaining test material was retained for future use. Protocol. Dosing Procedures. Retention Samples. "Samples (approximately 100 g) will be taken from each dose preparation sampled for dose analyses and stored at room temperature. Unless used for analyses, these samples will be discarded approximately 1 month after completion o f the in-life phase." Actual Procedure. Retention samples were not discarded approximately 1 month after completion o f the in-life phase. Protocol. Termination. Organ Weights. At the scheduled sacrifice, thyroid (2) with parathyroid was to be weighed. Actual Procedure. One thyroid with parathyroid was not weighed for Animal No. C94539. Protocol. Experimental Design. Postmortem Procedures. "The following tissues (when present) will be collected from each animal and preserved in 10% phosphate-buffered formalin." Gross lesions were not to be processed and examined microscopically. Actual Procedure. Some tissues, required by the protocol, were not available for histopathologic examination. Missing tissues are listed with appropriate comments in the pathology data sheets for individual animals. Summary tables do not include them as having been examined. Gross lesions were processed and examined microscopically. These deviations are not expected to have affected the results of the study. 99 0006G3 Protocol COV/HYCE^ THE DEVELOPMENT SERVICES COMPANY Sponsor: 3M St. Paul, Minnesota PROTOCOL Study Title: 4-W eek Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Date: June 8,1998 Performing Laboratory: Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Laboratory Study Identification: Proposal No. 90545C Covance 6329-224 100 000664 Covance 6329-224 ________ ____________ Page 2 Study 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Purpose To assess the toxicity o f the test material when administered in the diet to rats for at least 4 weeks Sponsor 3M Toxicology Services Building 220-2E-02, 3M Center St. Paul, Minnesota 55144-1000 Study Monitor Andrew M. Seacat, PhD 3M Toxicology Services Telephone No.: 612.575.3161 Facsimile No.: 612.733.1773 Alternate Study Monitor Marvin T. Case, DVM, PhD 3M Toxicology Services Telephone No.: 612.733.5180 Facsimile No.: 612.733.1773 Study Location Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Mailing Address: PO Box 7545 Madison, Wisconsin 53707-7545 101 OGQGS Covance 6329-224 ___________________________________________ _ _ _ _ _ _ _ _ _ _ _ __________ ______________ Page 3 Study Director Peter J. Thomford, PhD Covance Laboratories Inc. Telephone No.: 608.241.7207 Facsimile No.: 608.242.2736 Toxicologist Thomas E. Ryan, BS Covance Laboratories Inc. Proposed Study Timetable In-Life Start Date: June 12, 1998 In-Life End Date: July 13. 1998 Audited Draft Report Date: October 18, 1998 Regulatory Compliance This study will be conducted in compliance with the Food and Drug Administration Good Laboratory Practice Regulations as set forth in Title 21 of the US Code of Federal Regulations, Part 58, issued December 22, 1978 (effective June 20, 1979), and with any applicable amendments. Animal Care and Use Statement All procedures in this protocol are in compliance with the Animal Welfare Act Regulations, 9 CFR 1-4. In the opinion of the Sponsor and study director, the study does not unnecessarily duplicate any previous work. Quality Assurance The protocol, study conduct, and final report will be audited by the Covance Quality Assurance Unit (QAU). The proliferation cell nuclear antigen evaluation, data, and report will be audited by the QAU of Pathology Associates International. Liver and serum analyses, data, and report will be audited by the QAU of 3M Environmental Technology and Safety Services. 102 Test Material Covance 6329-224 __________Page 4 Identification N-Methyl Perfluorooctanesulfonamido Ethanol (MeFOS, T-6314) Lot Number The lot numbers will be maintained in the raw data. Purity Responsibility of the Sponsor Stability Responsibility of the Sponsor Storage Conditions At room temperature Characteristics Information on synthesis methods, composition, or other characteristics that define the test material is on file with the Sponsor. Reserve (Archive) Samples A reserve sample (approximately 5 g) of each lot will be taken and stored at room temperature. These samples will be transferred to the Sponsor after completion of the in-life phase. Disposition of Test Material After authorization from the Sponsor, any remaining test material will be returned to: Andrew M. Seacat, PhD 3M Toxicology Services Building 220-2E-02, 3M Center St. Paul, Minnesota 55144-1000 Telephone No.: 612.575.3161 Facsimile No.: 612.733.1773 103 0006S Animals Species Rat Covance 6329-224 __________Page 5 Strain Crl:CD*(SD) IGS BR Source Charles River Laboratories, Inc., Raleigh, North Carolina Age at Initiation of Treatment Preferably less than 6 weeks o f age, but not more than 8 weeks o f age Weight at Initiation of Treatment 100 to 300 g Number and Sex 36 males and 36 females Identification Implantable microchip identification device Husbandry Housing Individual (may be group-housed during acclimation). Animals will be housed in suspended, stainless steel cages. Diet Certified Rodent Diet #5002, meal (PMI Nutrition International) ad libitum, unless otherwise specified. The diet is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Specified nutrient and contaminant analyses are on file at Covance-Madison. 104 0 0 0 6 6 8 Covance 6329-224 ____________________________________ _____________________ ___________ Page 6 W ater Ad libitum. Samples of the water are routinely analyzed for specified microorganisms and environmental contaminants. The results are on file at Covance-Madison. Contaminants There are no known contaminants in the diet or water at levels that might interfere with this study. Environment Environmental controls for the animal room will be set to maintain 18 to 26C, a relative humidity of 30 to 70%, and a 12-hour light/12-hour dark cycle. Acclimation At least 1 week Randomization Selection of animals for the study will be based on body weights, clinical observations, and other data as appropriate. Animals will be assigned to treatment groups using a computerized blocking procedure designed to achieve body weight balance with respect to treatment groups. At the time o f randomization, the weight variation o f the animals of each sex used will not exceed 2 standard deviations of the mean weight, and the mean body weight for each group of each sex will not be statistically different at the 5.0% probability level. Justification Rats historically have been used in safety evaluation studies and are recommended by appropriate regulatory agencies. 105 0G06G9 Group Designations and Dietary Levels Covance 6329-224 __________ Page 7 Number of Animals Dietary Levels Group Male Female (ppm MeFOS)1 1 (Control)1' 2 (Low) 3 (Low-Mid) 6 6 6 6 6 6 0 1 10 4 (Mid) 5 (Mid-High) 6 6 6 6 30 100 6 (High) 66 500 a Dose levels are expressed as ppm of MeFOS. b The control animals will receive the basal diet only. Dosing Procedures Method of Administration Dietary, 7 days/week for at least 4 weeks. Treatment will continue through the day before necropsy. Reason for Dosing Route The potential route of exposure in humans is oral. Dose Preparation All dose preparations will be mixed according to the study-specific mixing procedure developed by Covance. Dose concentrations will be based on the MeFOS content as supplied. All dose preparations will be stored at room temperature. Retention Samples Samples (approximately 100 g) will be taken from each dose preparation sampled for dose analyses and stored at room temperature. Unless used for analyses, these samples will be discarded approximately 1 month after completion of the in-life phase. 106 0 0 0 6 7 0 Covance 6329-224 ___________________________________________ ______________________________________ Page 8 Dose Analyses By Covance, using a method supplied by the Sponsor and validated by Covance Homogeneity Homogeneity will be determined for all treated dose level preparations once pretest. One sample each (approximately 100 g) from the top, middle, and bottom o f the dose preparations mixed for homogeneity analyses will be collected, divided into three subsamples for extraction and analysis, and analyzed for test material content. All samples will be stored at room temperature until analyzed. In addition, one sample each (approximately 100 g) from the top, middle, and bottom of the 1-ppm dose preparation mixed for the in-life portion o f the study will be collected, divided into three subsamples for extraction and analysis, and analyzed for test material content. Homogeneity analysis will be repeated if batch size changes by more than 30%. Stability Four sets o f samples (approximately 100 g each) will be taken from the low- and high-dose level concentrations of diet preparations mixed pretest. Homogeneity samples collected from the middle of the pretest dose preparations will be analyzed on the day of mixing and used as the baseline value. The remaining samples from lowdose level preparation mixed pretest will be discarded. One sample of the high-dose preparation will be stored at room temperature for at least 19 days, then analyzed. The third sample of the high-dose preparation will be stored at room temperature after at least 32 days, then analyzed. The remaining sample of the high-dose preparation will be stored in a freezer set to maintain -10 to -30C for 8 weeks, then analyzed. In addition, three samples (approximately 100 g each) will be taken from the low-dose level preparation mixed for the in-life portion of the study and analyzed according to the schedule used for the samples of pre-test high-dose preparation. Homogeneity samples collected from the middle of the low-dose level preparation will be analyzed on the day of mixing and used as the baseline value. Dose Confirmation Samples (approximately 100 g) from all dose preparations will be analyzed. The homogeneity sample collected from the middle of the low-dose level preparation mixed for the in-life portion of the study will be used for dose confirmation. All samples will be stored at room temperature until analyzed. 107 000671 Covance 6329-224 __________ Page 9 Observation of Animals Clinical Observations Each animal will be observed twice daily (a.m. and p.m.) for mortality and moribundity, recording findings as they are observed. At least once weekly, each animal will be observed (cage will be opened, and the animal will be removed); abnormal findings or an indication of normal will be recorded. Additional findings will be recorded as they are observed. Body Weights Each animal will be weighed at least once prior to treatment, on the first day o f treatment, and twice weekly thereafter. Food Consumption Food consumption will be recorded for each animal twice weekly during treatment. Clinical Pathology Frequency After at least 4 weeks of treatment Number of Animals All Method of Collection Animals will be fasted overnight; blood will be collected from a jugular vein. The anticoagulant will be potassium EDTA for hematology tests. Urine will be collected chilled overnight (approximately 16 hours). 108 000672 Tests Hematology Covance 6329-224_________Page 10 red blood cell (erythrocyte) count hemoglobin hematocrit mean corpuscular volume mean corpuscular hemoglobin mean corpuscular hemoglobin concentration platelet count white blood cell (leukocyte) count differential blood cell count blood cell morphology reticulocyte smear (made, but not examined) glucose urea nitrogen creatinine total protein albumin globulin cholesterol total bilirubin Clinical Chemistry alanine aminotransferase gamma glutamyltransferase aspartate aminotransferase calcium inorganic phosphorus sodium potassium chloride appearance volume specific gravity pH protein urobilinogen Urinalysis glucose ketones bilirubin blood microscopic examination of sediment The remaining urine (up to 10 mL) for each animal will stored in a freezer set to maintain -10 to -30C. Samples will be packed on dry ice and shipped to: Kris J. Hansen, PhD 3M Environmental Technology and Safety Services 935 Bush Avenue Building 2-3E-09 St. Paul, Minnesota 55133-3331 Telephone No.: 612.778.6018 Facsimile No.: 612.778.6176 109 000673 Covance 6329-224 _________ P a g a li Urine samples will be stored by the Sponsor for possible future analysis. Serum Perfluorooctane Sulfonic Add (PFOS) Analyses Frequency and Number o f Animals All animals after at least 4 weeks of treatment Method of Collection Animals will be fasted overnight; blood (approximately 2 mL) will be collected from a jugular vein. Samples will be collected without anticoagulant. C Sample Handling Blood samples will be allowed to clot at room temperature and centrifuged. Serum samples will be harvested and stored in a freezer set to m aintain -60 to -80C . Samples will be packed on dry ice and shipped to; Kris J. Hansen, PhD 3M Environmental Technology and Safety Services 935 Bush Avenue Building 2-3E-09 St. Paul, Minnesota 55133-3331 Telephone No.: 612.778.6018 Facsimile No.: 612.778.6176 Serum samples will be analyzed for PFOS and metabolites by the Sponsor. Results will be reported separately by the Sponsor. Termination Unscheduled Sacrifices and Deaths Necropsies will be done. Animals to be sacrificed will be anesthetized with carbon dioxide, weighed, and exsanguinated. Scheduled Sacrifice After at least 4 weeks of treatment, all surviving animals will be fasted overnight, bled for clinical pathology tests and PFOS samples, then anesthetized with carbon dioxide, weighed, exsanguinated, and necropsied. 110 000674 Postmortem Procedures Covance 6329-224 _________ Page 12 Necropsy The necropsy will include an examination of the external features of the carcass; all external body orifices; the abdominal, thoracic, and cranial cavities; organs; and tissues. O rgan Weights At the scheduled sacrifice, the following organs (when present) will be weighed; paired organs will be weighed together: adrenal (2) brain epididymis (2) kidney (2) liver ovary (2) spleen testis (2) thymus thyroid (2) with parathyroid Organ-to-body weight percentages and organ-to-brain weight ratios will be calculated. Bone Marrow Smear From the femur of each animal at the scheduled sacrifice only; made but not examined Cell Proliferation Tissue Collection and Immunohistochemical Evaluation At the scheduled sacrifice, representative samples of left lateral lobe o f the liver from each animal will be collected and preserved in zinc formalin. After fixation, each sample of liver will be embedded in paraffin, and the paraffin blocks will be shipped to: Sandra R. Eldridge, PhD Pathology Associates International 5 Worman's Mill Court, Suite I Frederick, Maryland 21701 Telephone No.: 301.663.1644, ext. 2201 Facsimile No: 301.663.8994 111 000675 Covance 6329-224 _________ Page 13 Proliferation cell nuclear antigen (PCNA) evaluation will be done on the samples. Results will be provided for inclusion in the final report. Palmitoyl-CoA Oxidase Tissue Collection and Analyses At the scheduled sacrifice, a sample (approximately 500 mg) of the right lateral lobe of the liver will also be collected from each animal and flash-frozen in liquid nitrogen. The liver tissue will be stored in a freezer set to maintain -60 to -80 C until analyzed by Covance for palmitoyl-CoA oxidase activity. Liver PFOS Analysis At scheduled sacrifice, a portion of the liver from each animal will be stored in a freezer set to maintain -60 to -80C. Samples will be packed on dry ice and shipped to Kris J. Hansen, PhD, 3M Environmental Technology and Safety Services. Liver samples wifi be analyzed for PFOS and metabolites by the Sponsor. Results will be reported separately by the Sponsor. Tissue Preservation The following tissues (when present) from each animal will be preserved in 10% neutral-buffered formalin: a d r e n a l (2) aorta brain cecum cervix colon duodenum esophagus epididymis (2)) eye (2) femur with bone marrow (articular surface of the distal end) Harderian gland heart ileum with Peyer's patch (lymphoid aggregate) jejunum kidney (2) lesions liver lung with mainstem bronchi lymph nodes (mesenteric and mandibular) mammary glands (females only) ovary (2) pancreas pituitary prostate rectum salivary gland [mandibular (2)] sciatic nerve seminal vesicles 112 000678 Covance 6329-224 _________ Page L4 skeletal muscle (thigh) skin spinal cord (cervical, mid-thoracic, and lumbar) spleen sternum with bone marrow stomach testis [(2) preserved in Bouin's fixative] thymus thyroid (2) with parathyroid trachea urinary bladder uterus vagina Zymbal's gland Histopathology The adrenals, brain, eyes, kidneys, liver, mesenteric lymph node, pancreas, spleen, testes, and ovaries from each animal will be embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Tissue slides will be shipped to: Richard H. Bruner, D.V.M. DAVGP Pathology Associates International Ohio Operations 6217 Centre Park Drive West Chester, Ohio 45069 Telephone No.: 513.779.9600 Facsimile No.: 513.779.9603 Tissue slides will be examined microscopically by Dr. Bruner and the results from his evaluation will be included in the final report. After completion of the examination, slides will be returned to Covance-Madison. Reports One copy of the draft report will be sent to the Sponsor. The report will include the following information: Experimental Design and Methods Results dose analyses mortality clinical observations body weights 113 000677 Covance 6329-224_________ Page IS body weight changes food consumption test material consumption clinical pathology results organ weights organ-to-body weight percentages organ-to-brain weight ratios palmitoyl CoA oxidase activities macroscopic observations microscopic observations cell proliferation assessments (provided by the Sponsor's designee) Statistical Evaluation Levene's test will be done to test for variance homogeneity. In the case of heterogeneity of variance at p s 0.05, transformations will be used to stabilize the variance. Comparison tests will take variance heterogeneity into consideration. One-way analysis of variance (ANOVA) will be used (if applicable) to analyze body weights, body weight changes, food consumption, continuous clinical pathology values, and organ weight data. If the ANOVA is significant, Dunnett's t-test will be used for control versus treated group comparisons. If the ANOVA shows significance for body weights at Week 1, one-way analysis of covariance (ANCOVA) will be used to analyze body weights, with initial body weights as the covariate. If the ANCOVA is significant, covariate-adjusted means will be used for control versus treated group comparisons. Group comparisons (Groups 2 through 6 versus Group 1) will be evaluated at the 5.0%, two-tailed probability level. Only data collected on or after the first day of treatment will be analyzed statistically. At the end of 1 year after issuance of the audited draft report, if no requested revisions or instructions to finalize have been communicated by the Sponsor, then the audited draft report will be considered 'final' and issued as the final report, signed by the study director, and submitted to the Sponsor. Any modifications or changes to the audited draft report requested 1 year after issuance will be performed at additional cost to the Sponsor. 114 0 G 0 6 7 8 Covance 6329-224 _________ Page 16 Two copies o f the signed final report (one unbound and one bound) will be sent to the client. Record Retention All raw data, documentation, records, protocol, specimens, and final report generated as a result of this study will be archived in the storage facilities of Covance-Madison for a period of 1 year following submission of the final report to the Sponsor. All raw data stored on magnetic media, the protocol and protocol amendments, study correspondence, and the original report will be retained by Covance. One year after submission o f the final report, all of the aforementioned materials will be sent to the Sponsor, and a return fee will be charged. The Sponsor may elect to have the materials retained in the Covance archives for an additional period of time, and Covance will charge a storage fee. If the Sponsor chooses to have Covance dispose of the materials, a disposal fee will be charged. PCNA evaluation data, paraffin blocks, and tissue slides will be retained by Pathology Associates International. Liver, urine, and serum samples sent to the Sponsor and analysis data will be retained by the Sponsor. 115 PROTOCOL APPROVAL Covance 6329-224 _________ Page 17 Andrew M. Seacat, PhD Study Monitor 3M Date 116 000680 Protocol Amendment No. 1 TH E DEVELOPMENT SERVICES COMPANY PROTOCOL AMENDMENT NO. 1 Covance 6329-224 4-Week Range-Finding Dietary Toxicity Study with N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE, T-6314) in Rats Sponsor: Study Monitor: Testing Facility: Study Director: 3M, St. Paul, Minnesota Andrew M. Seacat, PhD Covance Laboratories Inc., Madison, Wisconsin Peter J. Thomford, PhD This amendment modifies the following portions of the protocol: Effective June 8,1998 1. Page 4. To include the vehicle used to dissolve the test material before mixing with the diet, add the following section, Vehicle I d e n tific a tio n Acetone Lot Numbers The lot numbers will be maintained in the raw data. Purity On file with the manufacturer Stability On file with the manufacturer Storage Conditions At room temperature 117 Covance 6329-224 Protocol Amendment No. 1 ________________________________________ __________________________________________ Page 2 Characteristics Information on synthesis methods, composition, or other characteristics that define the vehicle is on file with the manufacturer. Effective June 19,1998 2. Page 9, Clinical Pathology, Method of Collection To indicate that a different method of collection is required to provide additional blood, delete the text in this section and replace with the following: Animals will be fasted overnight and anesthetized with carbon dioxide; blood will be collected via cardiac puncture. The anticoagulant will be potassium EDTA for hematology tests. Urine will be collected chilled overnight (approximately 16 hours). 3. Page 11, Serum Perfluorooctane Sulfonic Acid (PFOS) Analyses, Method of Collection. To indicate that a different method of collection is required to provide additional blood for PFOS analyses, delete the text in this section and replace with the following: Animals will be fasted overnight and anesthetized with carbon dioxide; blood (as much as possible) will be collected via cardiac puncture. Samples will be collected without anticoagulant. 4. Page 11, Termination, Scheduled Sacrifice. To indicate a change in necropsy procedures required for collection of additional blood for PFOS analysis, delete the text in this section and replace with the following: After at least 4 weeks of treatment, all surviving animals will be fasted overnight, then anesthetized with carbon dioxide, bled for clinical pathology tests and PFOS samples, weighed, exsanguinated, and necropsied. 118 00068 o Covance 6329-224 Protocol Amendment No. 1 _________________ Page 3 Effective July 13,1998 5. Page 3, Quality Assurance. To indicate that quality assurance for tissue processing will be done by Pathology Associates International, delete the text in this section and replace with the following: The protocol, study conduct, and final report will be audited by the Covance Quality Assurance Unit (QAU). Tissue processing will be audited by the QAU of Pathology Associates International, Ohio Operations. The proliferation cell nuclear antigen evaluation, data, and report will be audited by the QAU of Pathology Associates International, Frederick, Maryland. Liver and serum analyses, data, and report will be audited by the QAU of 3M Environmental Technology and Safety Services. 6. Page 12, Postmortem Procedures, Histopathology. To reflect the decision to ship tissues to Pathology Associates International for processing, delete the text in this section and replace with the following: Tissue will be shipped for processing to: Ms. Sheree Lovelace Pathology Associates International Ohio Operations 6217 Centre Park Drive West Chester, Ohio 45069 The adrenals, brain, eyes, kidneys, liver, mesenteric lymph node, pancreas, spleen, testes, and ovaries from each animal will be embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Tissue slides will be examined microscopically by Richard H. Bruner, D.V.M. DAVCP of Pathology Associates International and the results from his evaluation will be included in the final report. After completion of the examination, slides and tissues will be returned to Covance-Madison. 119 000683 Effective July 20,1998 Covance 6329-224 Protocol Amendment No. 1 __________________ Page 4 7. Page 2, Study Monitor and Alternate Study Monitor. To indicate the change in the area code, delete the text in these section and replace with the following: Study Monitor Andrew M, Seacat, PhD 3M Telephone No.: 651.575.3161 Facsimile No.: 651.733.1773 Alternate Study Monitor Marvin T. Case, DVM, PhD 3M Toxicology Services Telephone No.: 651.733.5180 Facsimile No.: 651.733.1773 8 Page 4, Disposition of Test Material. To indicate the change in the area code, delete the text in these section and replace with the following: After authorization from the Sponsor, any remaining test material will be returned to: Andrew M. Seacat, PhD 3M Toxicology Services Building 220-2E-02, 3M Center St. Paul, Minnesota 55144-1000 Telephone No.: 651.575.3161 Facsimile No.: 651.733.1733 9. Page 10, Clinical Pathology, Tests, Urinalysis, Paragraph 2. To indicate the change in the area code, delete the text in this paragraph and replace with the following: The remaining urine (up to 10 mL) for each animal will stored in a freezer set to maintain -10 to -30C. Samples will be packed on dry ice and shipped to: 120 0006S4 Covanee 6329-224 Protocol Amendment No. 1 _________________ Page 5 Kris J. Hansen, PhD 3M Environmental Technology and Safety Services 935 Bush Avenue Building 2-3E-09 St. Paul, Minnesota 55133-3331 Telephone No.: 651.778.6018 Facsimile No.: 651.2.778.6176 10. Page 11, Serum Perfluorooctane Sulfonic Acid (PFOS) Analyses, Sample Handling, Paragraph 1. To indicate the change in the area code, delete the text in this paragraph and replace with the following: Blood samples will be allowed to clot at room temperature and centrifuged. Serum samples will be harvested and stored in a freezer set to maintain -60 to -80 C. Samples will be packed on dry ice and shipped to: Kris J. Hansen, PhD 3M Environmental Technology and Safety Services 935 Bush Avenue Building 2-3E-09 St. Paul, Minnesota 55133-3331 Telephone No.: 651.778.6018 Facsimile No.: 651.778.6176 Effective December 15,1998 11. Page 13, Postmortem Procedures, Ceii Proliferation Tissue Collection and Immunobistochemieal Evaluation, Paragraph 3. To include examination of liver sections will be stained with hematoxylin and eosin as part of the cell proliferation evaluation, delete this paragraph and replace with the following: Proliferation cell nuclear antigen (PCNA) evaluation will be done on the samples. In addition, liver sections will be stained with hematoxylin and eosin and examined microscopically. Results will be provided for inclusion in the final report. 121 OOOGS Covance 6329-224 Protocol Amendment N o. 1 Page 6 AMENDMENT APPROVAL Andrew M. Seacat, PhD Study Monitor 3M Date 0/ Date> iff 122 000686 APPENDIX 2 Individual Animai Fate Data Individual Clinical Observations Covance 6329-224 3M T-6314.2 123 000687 ii APPENDIX 2 Individual Animal Fate Data 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL DOSE NUMBER GROUP C94491 C94492 C94493 C94494 C94495 C94496 C94497 C94498 C94499 C94500 C94501 C94502 C94503 C94504 C94505 C94506 C94507 C94508 C94509 C94510 C94511 C94512 C94513 C94514 C94515 C94516 C94517 C94518 C94519 C94520 C94521 C94522 C94523 C94524 i i i i i i 2 2 2 2 2 2 3 3 3 3 3 3 4 4 4 4 4 4 5 5 5 5 5 5 6 6 6 6 SEX MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE MALE DEATH CODE TYPE OF DEATH DESCRIPTION OF DEATH T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE D UNSCHEDULED UNSCHEDULED DEATH T SCHEDULED TERMINAL SACRIFICE DATE OF DEATH DAY OF STUDY 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/06/98 07/13/98 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 25 32 WEEK OF STUDY 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 4 5 Covance 6329-224 3M T-6314.2 PAGE: 1 124 0006S8 t APPENDIX 2 Individual Animal Fate Data 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL DOSE NUMBER GROUP SEX C94525 C94526 C94527 C94528 C94529 C94530 C94531 C94532 C94533 C94534 C94535 C94536 C94537 C94538 C94539 C94540 C94541 C94542 C94543 C94544 C94545 C94546 C94547 C94548 C94549 C94550 C94551 C94552 C94553 C94554 C94555 C94556 C94557 C94558 6 MALE 6 MALE 1 FEMALE 1 FEMALE 1 FEMALE 1 FEMALE 1 FEMALE 1 FEMALE 2 FEMALE 2 FEMALE 2 FEMALE 2 FEMALE 2 FEMALE 2 FEMALE 3 FEMALE 3 FEMALE 3 FEMALE 3 FEMALE 3 FEMALE 3 FEMALE 4 FEMALE 4 FEMALE 4 FEMALE 4 FEMALE 4 FEMALE 4 FEMALE 5 FEMALE 5 FEMALE 5 FEMALE 5 FEMALE 5 FEMALE 5 FEMALE 6 FEMALE 6 FEMALE DEATH CODE T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T T TYPE OF DEATH SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED DESCRIPTION OF DEATH TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE DATE OF DEATH DAY OF STUDY 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 07/13/98 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 32 WEEK OF STUDY 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Covance 6329-224 3M T-6314.2 PAGE: 2 125 0006S9 ?s APPENDIX 2 Individual Animal Fate Data 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL DOSE NUMBER GROUP SEX C94559 C94560 C94561 C94562 6 FEMALE 6 FEMALE 6 FEMALE 6 FEMALE DEATH CODE T T T T TYPE OF DEATH SCHEDULED SCHEDULED SCHEDULED SCHEDULED DESCRIPTION OF DEATH TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE DATE OF DEATH DAY OF STUDY 07/13/98 07/13/98 07/13/98 07/13/98 32 32 32 32 WEEK OF STUDY 5 5 5 5 Covance 6329-224 3M T-6314.2 PAGE: 3 069000 126 t Appendix 2 Individual Clinical Observations 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 1 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 PPM DAYS 1-32 OBSERVED DURING THE DAYS LISTED BELOW; ' C - COMMENTS LISTED AT END OF OBSERVATIONS C94491 C94492 C94493 C94494 C94495 C94496 T T T T T T 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS T69000 127 11 l t 1 1 1 f Appendix 2 Individual Clinical Observations 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 2 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M2 DOSE: 1 PPM DAYS 1-32 - OBSERVED DURING THE DAYS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS C94497 C94498 C94499 C94500 C94501 C94502 T T T T T T 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS o c 112988 Appendix 2 Individual Clinical Observations 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 3 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 10 PPM DAYS 1-32 - OBSERVED DURING THE DAYS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS C94503 T C94504 C94505 C94506 C94507 C94508 T T T T T 5 SKIN & PELAGE SORE/SCAB DORSAL-THORACIC-LEFT DORSAL-THORACIC-RIGHT 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS Appendix 2 Individual Clinical Observations 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 4 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 30 PPM DAYS 1-32 OBSERVED DURING THE DAYS LISTED BELOW; C1 - COMMENTS LISTED AT END OF OBSERVATIONS C94509 C94510 C94511 C94512 C94513 C94514 T T T T T T 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS  i i i i Appendix 2 Individual Clinical Observations 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 5 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M5 DOSE: 100 PPM C94515 C94516 C94517 C94518 C94519 C94520 T T T T T T 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS OBSERVED DURING THE DAYS LISTED BELOW; C* - COMMENTS LISTED AT END OF OBSERVATIONS 690G0 C/I 131 s Appendix 2 Individual Clinical Observations 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 6 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M6 DOSE: 500 PPM C94521 C94522 C94523 C94524 C94525 C94526 T T D T T T 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 4 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS 5 ANIMAL HAS NO SIGNIFICANT FINDINGS OBSERVED DURING THE DAYS LISTED BELOW; C' - COMMENTS LISTED A T END OF OBSERVATIONS 000696 132 APPENDIX 3 Individual Body Weight Data (g) Covance 6329-224 3M T-6314.2 133 00069 ANIMAL NUMBER DAY 1 DAY 4 GROUP: MALE 1 - 0 PPM C94491 C94492 C94493 C94494 C94495 C94496 167 181 181 173 153 161 193 204 207 195 178 183 GROUP: MALE 2 - 1 PPM C94497 C94498 C94499 C94500 C94501 C94502 166 170 184 145 175 164 190 192 210 168 201 188 GROUP: MALE 3 - 10 PPM C94503 C94504 C94505 C94506 C94507 C94508 173 188 153 168 157 180 196 210 173 189 179 205 GROUP : MALE 4 - 30 PPM C94509 C94510 C94511 C94512 173 144 156 183 191 165 178 207 Appendix 3 Individual Body Weight Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY DAY DAY DAY DAY DAY 8 11 15 18 22 25 226 248 280 296 325 338 237 263 294 315 346 369 244 267 290 308 330 347 234 257 296 319 354 374 212 240 272 295 327 347 212 228 255 269 294 306 228 252 281 299 329 341 223 243 273 289 310 328 246 273 309 330 365 387 198 221 255 276 304 324 232 255 280 298 323 341 222 246 274 291 310 328 235 258 288 305 334 347 251 278 307 328 358 373 208 234 269 289 319 340 219 246 267 286 314 330 209 231 254 270 292 307 239 263 293 314 347 360 224 245 267 279 300 311 187 214 238 249 269 284 213 238 261 274 302 312 247 270 298 318 348 365 Covance 6329-224 3M T-6314.2 PAGE: 1 DAY 29 DAY 32 359 347 389 371 366 349 402 388 369 355 317 302 363 355 342 328 407 393 346 331 352 343 345 330 366 351 393 380 366 348 345 334 321 306 382 370 328 312 305 293 333 318 390 376 t ANIMAL NUMBER DAY 1 DAY 4 GROUP : MALE 4 - 30 PPM C94513 C94514 163 178 185 202 GROUP: MALE 5 - 100 PPM C94515 C94516 C94517 C94518 C94519 C94520 169 154 194 162 156 171 190 172 217 185 179 191 GROUP : MALE 6 - 500 PPM C94521 C94522 C94523 C94524 C94525 C94526 155 176 171 146 164 171 170 194 182 164 173 177 GROUP: FEMALE 1 - 0 PPM C94527 C94528 C94529 C94530 C94531 C94532 139 128 149 145 143 118 154 141 167 161 157 134 Appendix 3 Individual Body Weight Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY 8 DAY 11 DAY 15 DAY 18 DAY 22 DAY 25 219 243 271 290 321 341 236 261 290 305 335 353 222 248 276 292 319 334 201 223 250 261 289 306 249 265 292 310 330 346 213 235 261 279 305 320 213 236 267 281 308 324 225 247 279 293 321 334 188 201 217 226 243 250 203 222 229 251 261 270 203 218 228 236 238 183 197 214 221 215 223 195 215 230 240 248 252 200 213 226 239 254 262 171 178 193 199 205 222 160 175 191 193 211 219 187 197 215 221 235 246 181 191 202 211 230 243 177 189 200 202 219 223 155 165 174 178 193 197 Covance 6329-224 3M T-6314.2 PAGE: 2 DAY 29 DAY 32 364 344 378 363 351 340 317 304 363 346 337 325 342 326 351 332 256 236 279 255 236 219 256 239 265 240 239 224 233 217 257 241 253 245 233 215 205 194 000693 135 > i Appendix 3 Individual Body Weight Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 3 ANIMAL NUMBER DAY 1 DAY 4 GROUP: FEMALE 2 - 1 PPM C94533 C94534 C94535 C94536 C94537 C94538 130 135 136 125 143 123 146 149 162 146 160 139 GROUP: FEMALE 3 - 1 0 PPM C94539 C94540 C94541 C94542 C94543 C94544 141 132 158 144 115 120 163 143 182 157 127 133 GROUP: FEMALE 4 - 30 PPM C94545 C94546 C94547 C94548 C94549 C94550 135 130 153 121 141 128 141 150 171 134 150 138 GROUP: FEMALE 5 - 100 PPM C94551 C94552 C94553 C94554 114 146 141 130 129 158 165 142 DAY 8 165 164 178 161 177 157 180 162 195 176 145 148 160 170 189 152 169 155 142 173 184 157 DAY 11 172 176 179 171 184 165 188 170 201 202 151 156 169 180 201 160 183 170 149 184 194 167 DAY 15 184 185 195 180 200 176 203 178 210 233 160 174 178 194 216 172 198 181 158 193 207 177 DAY 18 194 197 205 188 209 186 212 181 226 227 166 181 184 200 223 178 203 184 164 197 213 180 DAY 22 206 209 219 205 225 196 225 186 241 236 174 189 192 217 240 186 216 196 176 208 220 192 DAY 25 212 214 224 216 237 205 238 193 257 244 178 198 201 230 250 198 222 201 180 215 227 195 DAY 29 227 221 242 225 248 215 243 198 267 256 183 206 209 242 263 208 230 211 189 222 231 204 DAY 32 211 207 225 213 231 201 227 185 245 252 178 196 196 228 245 196 216 195 180 211 215 193 c 136 ANIMAL DAY DAY NUMBER 1 4 GROUP: FEMALE 5 - 100 PPM C94555 C94556 124 139 136 152 GROUP : FEMALE 6 - 500 PPM C94557 C94558 C94559 C94560 C94561 C94562 141 140 114 126 145 144 138 141 121 137 142 146 Appendix 3 Individual Body Weight Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY DAY DAY DAY DAY DAY 8 11 15 18 22 25 152 166 176 183 197 206 165 175 186 195 210 215 147 155 164 159 162 172 153 157 162 166 169 171 131 136 138 140 149 149 150 158 166 174 184 191 155 159 171 170 179 182 151 164 169 173 180 179 Covance 6329-224 3M T-6314.2 PAGE: 4 DAY DAY 29 32 215 201 229 213 170 160 176 161 152 140 198 180 188 171 184 171 000701 137 APPENDIX 4 Covance 6329-224 3M T-6314.2 Individual Food Consumption Data (g) Individual Test Material Consumption Data (mg/kg/day) 138 000702 ANIMAL NUMBER DAY 1 DAY 4 GROUP: MALE 1 - 0 PPM C94491 73 99 C94492 74 97 C94493 85 111 C94494 79 108 C94495 70 99 C94496 72 96 GROUP : MALE 2 - 1 PPM C94497 77 107 C94498 73 95 C94499 87 116 C94500 65 94 C94501 78 104 C94502 73 98 GROUP : MALE 3 - 10 PPM C94503 75 105 C94504 75 107 C94505 67 97 C94506 69 93 C94507 68 92 C94508 77 104 GROUP : MALE 4 - 3 0 PPM C94509 71 98 C94510 65 82 C94511 73 98 C94512 77 106 Appendix 4 Individual Food Consumption Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY DAY DAY DAY DAY DAY 8 11 15 18 22 25 76 105 77 104 89 109 85 123 81 111 69 95 85 112 73 102 91 125 73 105 82 106 77 101 81 112 87 113 80 107 77 94 74 96 81 105 73 98 75 94 79 100 84 114 80 105 84 115 80 110 87 117 81 106 87 123 94 122 102 138 82 112 89 116 70 95 76 SPILLED 85 113 86 126 73 97 82 105 94 125 102 135 81 113 89 126 80 104 85 113 78 97 87 186 82 106 86 113 82 108 75 100 72 94 82 107 94 116 92 127 89 120 81 107 78 101 86 120 68 97 66 87 71 99 84 113 75 101 74 98 80 113 88 128 Covance 6329-224 3M T-6314.2 PAGE: 1 000703 139 ANIMAL DAY DAY NUMBER 1 4 GROUP: MALE 4 - 30 PPM C94513 C94514 68 73 94 98 GROUP: MALE 5 - 100 PPM C94515 68 92 C94516 61 81 C94517 78 102 C94518 71 93 C94519 71 96 C94520 74 101 GROUP : MALE 6 - 500 PPM C94521 C94522 C94523 C94524 C94525 C94526 61 68 68 65 59 62 73 60 78 75 78 77 GROUP: FEMALE 1 - 0 PPM C94527 C94528 C94529 C94530 C94531 C94532 53 67 69 59 63 52 63 79 85 78 85 72 Appendix 4 Individual Food Consumption Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY DAY DAY DAY DAY DAY 8 11 15 18 22 25 73 102 77 100 74 98 64 87 74 103 72 97 76 103 77 110 51 72 60 67 58 75 62 80 64 77 65 79 50 77 64 83 61 83 61 78 59 84 54 72 72 100 76 102 81 108 81 110 73 98 63 88 77 98 74 97 75 104 79 105 78 103 72 90 83 115 74 100 81 111 81 107 54 69 52 72 63 70 62 75 54 63 NOT TAKEN 59 57 43 69 59 68 50 66 62 78 64 76 52 66 57 84 57 80 61 92 60 81 64 89 60 84 75 SPILLED 59 79 64 79 59 74 53 68 o o o "vi o > 140 Covance 6329-224 3M T-6314.2 PAGE: 2 ANIMAL NUMBER DAY 1 DAY 4 GROUP: FEMALE 2 - 1 PPM C94533 C94534 C94535 C94536 C94537 C94538 57 60 71 62 65 58 77 79 81 74 81 76 GROUP: FEMALE 3 - 10 PPM C94539 C94540 C94541 C94542 C94543 C94544 67 54 76 62 54 48 84 74 85 78 68 56 GROUP: FEMALE 4 - 30 PPM C94545 C94546 C94547 C94548 C94549 C94550 51 65 67 54 60 52 68 79 87 73 77 70 GROUP : FEMALE 5 - 100 PPM C94551 C94552 C94553 C94554 55 61 62 53 69 75 77 69 Appendix 4 Individual Food Consumption Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY DAY DAY DAY DAY DAY 8 11 15 18 22 25 56 76 56 74 59 80 61 80 63 84 60 84 59 87 61 77 66 95 57 72 55 81 68 82 61 85 66 85 69 98 54 75 57 70 57 78 59 76 59 77 62 83 53 70 47 62 53 67 58 78 67 83 71 95 73 106 63 78 64 96 50 69 48 63 52 69 42 60 44 52 47 72 50 66 48 60 49 66 58 77 58 79 63 81 66 87 64 90 75 SPILLED 55 72 53 71 57 74 62 82 57 80 62 83 58 72 52 67 51 71 52 65 52 85 58 SPILLED 58 73 53 70 54 73 59 77 57 69 56 69 54 70 49 67 49 67 Covance 6329-224 3M T-6314.2 PAGE: 3 000705 141 ANIMAL NUMBER DAY 1 DAY 4 GROUP: FEMALE 5 - 100 PPM C94555 C94556 55 60 70 73 GROUP : FEMALE 6 - 500 PPM C94557 C94558 C94559 C94560 C94561 C94562 43 60 48 53 46 54 49 55 54 62 46 49 Appendix 4 Individual Food Consumption Data (g) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY 8 DAY 11 DAY 15 DAY 18 DAY 22 DAY 25 57 73 52 73 57 75 54 72 57 76 57 82 44 54 31 46 40 45 45 53 42 52 41 61 40 44 32 46 33 45 46 63 46 58 49 59 44 60 43 56 44 61 49 SPILLED 52 51 42 55 Covance 6329-224 3M T-6314.2 PAGE: 4 000706 142 ANIMAL NUMBER DAY 1 DAY 4 GROUP: MALE 2 - 1 PPM C94497 C94498 C94499 C94500 C94501 C94502 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 GROUP : MALE 3 - 10 PPM C94503 C94504 C94505 C94506 C94507 C94508 1.4 1.2 1.3 1.2 1.4 1.3 1.3 1.1 1.3 1.2 1.3 1.2 GROUP : MALE 4 - 30 PPM C94509 C94510 C94511 C94512 C94513 C94514 3.9 3.5 4.2 3.5 4.4 3.8 3.9 3.5 3.9 3.5 3.8 3.4 GROUP : MALE 5 - 100 PPM C94515 C94516 C94517 C94518 12.6 12.5 12.7 13.6 11.2 10.9 10.9 11.7 Appendix 4 Individual Test Material Consumption Data (mg/kg/day) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS DAY 8 DAY 11 DAY 15 DAY 18 DAY 22 DAY 25 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 1.1 1.0 0.9 0.8 0.9 0.8 1.1 1.0 0.9 0.8 0.8 0.8 1.2 1.1 1.0 0.9 0.9 0.8 1.1 0.9 0.9 0.8 0.8 0.8 1.1 1.0 0.9 0.8 0.9 0.8 1.1 0.9 0.9 0.8 0.8 0.8 3.1 2.9 2.5 2.5 2.5 2.4 3.7 3.1 2.7 2.5 2.7 2.5 3.5 3.0 2.7 2.6 2.6 2.6 3.2 3.0 2.7 2.5 2.5 2.5 3.2 3.0 2.6 2.5 2.4 2.3 3.1 2.7 2.6 2.4 2.4 2.3 10.5 9.4 8.6 8.0 8.0 7.5 10.1 9.2 8.2 8.0 8.1 7.2 9.6 9.2 8.5 7.7 8.2 8.1 10.7 9.8 9.1 8.3 7.9 7.6 Covance 6329-224 3M T-6314.2 PAGE: 1 000707 143 Appendix 4 Individual Test Material Consumption Data (mg/kg/day) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER DAY 1 DAY 4 GROUP: MALE 5 - 100 PPM C94519 C94520 14.1 13.6 12.2 12.1 GROUP : MALE 6 - 500 PPM C94521 C94522 C94523 C94524 C94525 C94526 62.6 61.3 64.2 69.9 58.4 59.4 51.0 37.8 50.6 54.0 53.0 51.1 GROUP : FEMALE 2 - 1 PPM C94533 C94534 C94535 C94536 C94537 C94538 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.1 GROUP : FEMALE 3 - 1C1 PPM C94539 C94540 C94541 C94542 C94543 C94544 1.5 1.2 1.3 1.2 1.5 1.1 1.4 1.2 1.5 1.3 1.3 1.0 DAY 8 11.3 10.9 43.7 47.1 45.9 54.4 52.0 52.5 0.1 0.1 0.1 0.1 0.1 0.1 1.1 1.1 1.0 1.3 1.1 0.9 DAY 11 10.2 10.5 43.1 37.1 42.0 48.7 43.3 45.0 0.1 0.1 0.1 0.1 0.1 0.1 1.0 1.0 0.9 1.2 1.1 0.9 DAY 15 9.1 9.2 40.6 43.8 38.8 45.2 41.8 44.4 0.1 0.1 0.1 0.1 0.1 0.1 0.9 0.9 1.0 0.9 1.0 0.8 DAY 18 DAY 22 DAY 25 8.8 8.5 8.3 8.6 8.2 7.8 36.8 34.2 33.2 32.7 34.8 39.6 35.2 38.9 NOT TAKEN 32.7 33.3 41.3 35.6 34.2 NOT TAKEN 37.6 32.5 36.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.9 0.9 0.9 0.8 0.9 0.9 0.9 1.0 0.9 0.8 0.9 1.0 0.9 1.0 1.0 0.7 0.8 0.9 Covance 6329-224 3M T-6314.2 PAGE: 2 000708 144 Appendix 4 Individual Test Material Consumption Data (mg/kg/day) 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER DAY 1 DAY 4 GROUP: FEMALE 4 - 30 PPM C94545 C94546 C94547 C94548 C94549 C94550 3.7 3.4 4.6 3.7 4.1 3.6 4.2 3.8 4.1 3.6 3.9 3.6 GROUP : FEMALE 5 - 100 PPM C94551 C94552 C94553 C94554 C94555 C94556 15.1 13.4 13.5 13.0 14.1 13.7 12.7 11.3 11.0 11.5 12.2 11.5 GROUP : FEMALE 6 - 500 PPM C94557 C94558 C94559 C94560 C94561 C94562 51.4 71.2 68.1 67.2 53.4 62.1 43.0 46.8 53.6 54.0 38.7 41.2 DAY 8 DAY 11 3.0 2.9 3.3 3.1 3.4 3.1 3.5 3.3 3.5 3.2 3.6 3.1 11.9 10.8 10.4 11.1 11.9 10.6 10.6 9.7 9.6 10.2 10.7 10.0 48.6 48.4 49.9 49.8 46.7 51.9 42.3 41.5 40.1 48.6 45.5 SPILLED DAY 15 2.7 2.9 2.9 3.0 2.8 2.8 10.8 9.1 9.0 9.2 9.7 10.0 32.0 42.7 38.4 45.1 42.0 50.7 DAY 18 2.4 2.8 2.9 2.9 2.9 2.6 12.5 8.6 8.0 9.0 9.6 9.4 35.8 38.8 39.8 40.5 40.1 36.1 DAY 22 DAY 25 2.5 2.8 3.1 3.0 2.8 2.6 2.4 2.6 SPILLED 2.7 2.8 2.6 10.9 8.5 8.4 8.4 9.4 8.9 SPILLED 8.4 7.5 8.4 8.9 9.2 39.9 40.2 36.9 43.6 40.6 39.0 32.9 43.9 37.4 37.9 41.2 37.9 Covance 6329-224 3M T-6314.2 PAGE: 3 000709 145 APPENDIX 5 Individual Clinical Hematology Data Individual Clinical Chemistry Data Individual Clinical Urinalysis Data Covance 6329-224 3M T-6314.2 146 0 0 0 7 1 0 > tI ) i ANIMAL NUMBER Appendix 5 Individual Clinical Hematology Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS RBC XloVjlL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT XlOVjlL Covance 6329-224 3M T-6314.2 Group: 1 C94491 C94492 C94493 C94494 C94495 C94496 MEAN S.D. Dose Level: 0 7.82 7.56 7.47 6.91 6.61 7.39 15.3 15.5 14.9 14.9 13.9 15.3 7.29 .448 15.0 .58 Dosage Unit: ppm MeFOS 45.6 46.4 44.8 43.7 41.2 45.7 58.2 61.4 60.0 63.3 62.3 61.9 19.6 20.5 20.0 21.6 21.0 20.8 44.6 1.89 61.2 1.82 20.6 .72 33.6 33.4 33.3 34.1 33.8 33.5 33.6 .29 1220 985 940 989 986 808 988 133.1 Group: 2 Dose Level: 1 Dosage Unit: ppm MeFOS C94497 C94498 C94499 C94500 C94501 C94502 7.43 7.06 7.09 7.23 7.68 7.55 15.0 15.0 14.5 13.6 15.2 14.6 45.3 44.4 42.6 40.5 46.2 45.3 61.0 62.9 60.0 56.0 60.2 60.0 20.2 21.3 20.4 18.9 19.8 19.4 33.2 33.9 34.1 33.7 32.9 32.3 969 1170 949 1301 877 1079 MEAN S.D. N 7.34 .253 6 14.6 .58 6 44.1 2.12 6 60.0 2.26 6 20.0 .84 6 33.4 .68 6 1058 157 6 Group: 3 Dose L e v e l : 10 Dosage Unit: ppm MeFOS C94503 C94504 C94505 C94506 C94507 C94508 6.96 7.06 7.41 7.44 7.44 7.31 14.2 15.1 15.2 14.9 14.5 15.3 42.0 44.3 45.3 44.0 43.1 45.2 60.3 62.8 61.1 59.2 58.0 61.9 20.5 21.4 20.6 20.0 19.4 20.9 33.9 34.1 33.7 33.8 33.5 33.8 1139 1036 1204 1012 899 977 MEAN 7.27 14.9 44.0 60.6 20.5 33.8 1044 S.D. .209 .43 1.27 1.76 .70 .20 110 N 6666666 o 147 I# I }t I Appendix 5 ANIMAL NUMBER Individual Clinical Hematology Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS RBC x i o 6/h l HGB G/DL HCT % MCV FL MCH PG MCHC % PLT X1 0 3/HL Covance 6329-224 3M T-6314.2 Group: 4 Dose L e v e l : 30 Dosage Uni t : ppm MeFOS C94509 C94510 C94511 C94512 C94513 C94514 7.53 7.38 7.63 7.39 7.25 7.23 15.1 15.0 15.3 15.6 14.5 14.5 44.0 45.2 45.7 45.5 43.2 43.6 58.4 61.2 59.9 61.6 59.5 60.3 20.0 20.3 20.0 21.1 20.0 20.1 34.2 33.2 33.4 34.3 33.7 33.3 1009 770 1016 1121 1116 1310 MEAN S.D. N 7.40 .156 6 15.0 .44 6 44.5 1.07 6 60.2 1.16 6 20.2 .43 6 33.7 .47 6 1057 177. 6 Group: 5 Dose L e v e l : 100 Dosage Unit: ppm MeFOS C94515 C94516 C94517 C94518 C94519 C94520 6.08 6.40 7.99 6.86 7.61 7.08 12.9 14.1 16.2 14.5 15.3 14.3 38.3 40.9 47.9 43.0 46.0 42.4 62.9 63.8 60.0 62.8 60.5 59.8 21.2 22.0 20.3 21.1 20.1 20.2 33.8 34.4 33.8 33.6 33.2 33.8 1052 1069 1114 1251 894 1306 MEAN S.D. N 7.00 .719 6 14.6 1.12 6 43.1 3.46 6 61.6 1.73 6 20.8 .75 6 33.8 .39 6 1114 148. 6 Group: 6 Dose Level: 500 Dosage Unit: ppm MeFOS C94521 C94522 C94524 C94525 C94526 5.18 6.57 5.63 5.58 6.54 11.8 13.5 11.6 11.3 13.2 33.6 39.3 34.1 33.5 39.5 64.8 59.9 60.5 60.0 60.4 22.8 20.5 20.6 20.3 20.1 35.1 34.3 34.0 33.8 33.3 1059 899 677 1069 1132 MEAN S.D. N 5.90 .623 5 12.3 1.00 5 36.0 3.11 5 61.1 2.07 5 20.9 1.10 5 34.1 .67 5 967 183. 5 148 ANIMAL NUMBER Group: 1 C94491 C94492 C94493 C94494 C94495 C94496 MEAN S.D. N Group: 2 C94497 C94498 C94499 C94500 C94501 C945D2 MEAN S.D. N Group: 3 C94503 C94504 C94505 C94506 C94507 C94508 MEAN S.D. N WBC X 1 0 3/JlL Appendix 5 Individual Clinical Hematology Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS N-SEG LYMPH X103/J1L X l 0 3/}iL MONO XloVjlL EOS IN X 1 0 3/|1L BASO N-SEG% XloVjlL LYMPH% MONO% Covance 6329-224 3M T-6314.2 EOSIN% BASO% Dose Level : 0 Dosage Unit: ppm MeFOS 14.7 .8 12.5 1.2 .1 .1 6 85 8 11.2 1.2 9.3 .6 .1 .0 10 83 6 13.6 1.3 10.9 .9 .5 .0 9 80 7 13.3 1.7 10.3 1.1 .2 .0 13 78 8 6.0 .5 5.4 .2 .0 .0 8 89 3 10.5 .8 8.1 1.4 .2 .0 7 77 14 11 10 30 10 00 20 11.6 1.0 9.4 .9 .2 .0 3.14 .43 2.46 .44 .17 .04 666666 9 2.,5 6 82 4. 6 6 8 3.,6 6 1 1. 0 6 0 4 6 Dose Level : 1 Dosage Uni t : ppm MeFOS 7.4 1.0 6.0 .4 .1 .0 13 80 6 1 0 9.1 1.0 7.7 .4 .1 .0 11 84 4 1 0 11.9 1.4 9.5 .8 .1 .0 12 80 7 1 0 16.7 2.8 12.3 1.5 .0 .1 17 74 9 00 14.5 .8 12.6 .9 .1 .0 6 87 6 1 0 10.8 1.1 8.7 .8 .1 .0 10 81 7 1 0 11.7 1.4 9.5 .8 .1 .0 12 81 6 1 0 3.43 .74 2.59 .40 .04 .04 3..6 4..4 1..6 .4 .0 6 6 6 6 6 6 6 6 6 66 Dose Level : 10 Dosage Unit: ppm MeFOS 15.8 2.2 12.3 1.2 .2 .0 14 78 7 18.4 1.0 16.4 .7 .2 .1 6 89 4 11.2 1.3 9.1 .7 .1 .0 12 81 6 16.2 2.1 12.9 .9 .3 .0 13 80 6 5.2 1.0 3.2 .9 .0 .0 20 62 16 15.1 1.0 13.4 .6 .1 .0 7 89 4 10 10 10 20 11 10 13.6 1.4 11.2 .8 .2 .0 12 80 7 10 4.76 .57 4.57 .22 .10 .04 5..1 9.,9 4.,5 .4 .4 6 6 6 6 6 6 6 6 6 66 000713 149 ANIMAL NUMBER WBC x i o 3/h l Appendix 5 individual Clinical Hematology Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS N-SEG XloVjlL LYMPH X 1 0 3/HL MONO X 1 0 3/HL EOSIN XlOVjlL BASO N-SEG% X 1 0 3/(1L LYMPH % MONO% Covance 6329-224 3M T-6314.2 EOSIN% BASO% Group: 4 Dose Level : 30 Dosage Unit: ppm MeFOS C94509 C94510 C94511 C94512 C94513 C94514 13.3 .7 11.6 .7 .2 .0 13.1 .7 11.6 .6 .2 .0 10.6 .7 8.5 1.3 .1 .0 13.1 1.1 10.9 1.0 .1 .0 11.2 .8 9.8 .6 .1 .0 12.4 .8 11.0 .4 .1 .0 5 88 5 5 89 5 6 80 12 8 84 7 7 87 5 6 89 4 10 10 10 10 10 10 MEAN S.D. N 12.3 .8 10.6 .8 .1 .0 1.13 .15 1.21 .33 .05 .00 66 66 66 6 86 1. 2 3. 5 66 6 2. 9 6 1 0 6 0 6 Group: 5 Dose Level : 100 Dosage Unit: ppm MeFOS C94515 13.4 1.4 11.3 .6 .1 .0 10 85 4 10 C94516 10.9 1.0 9.6 .2 .1 .0 9 88 2 1 0 C94517 18.6 1.4 15.5 1.5 .1 .1 8 83 8 10 C94518 13.4 1.0 12.1 .2 .1 .0 7 90 2 10 C94519 12.5 .7 11.0 .7 .1 .0 6 88 5 10 C94520 9.0 1.1 7.3 .5 .1 .0 12 81 5 1 0 MEAN S.D. N 13.0 1.1 11.1 .6 .1 .0 3.24 .27 2.72 .48 .00 .04 66666 6 9 2.,2 6 86 3.,4 6 4 2.,3 6 1 .0 6 0 6 Group: 6 Dose Level : 500 Dosage Unit: ppm MeFOS C94521 9.8 .7 8.7 .4 .0 .0 7 89 4 0 0 C94522 12.5 2.3 9.1 1.0 .0 .1 18 73 8 01 C94524 8.1 .7 7.1 .3 .1 .0 8 88 3 1 0 C94525 11.6 .6 10.3 .6 .0 .0 5 89 5 0 0 C94526 9.8 2.0 7.0 .7 .0 .0 21 72 7 0 0 MEAN S.D. N 10.4 1.3 8.4 .6 .0 .0 12 82 5 0 0 1.72 .82 1.40 .27 .04 .04 7..2 8..9 2..1 .4 5 5 5 5 5 5 5 5 5 55 o si 150 Appendix 5 Individual Clinical Hematology Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 C94491 C94492 C94493 C94494 C94495 C94496 Group : 2 C94497 C94498 C94499 C94500 C94501 C94502 Group: 3 C94503 C94504 C94505 C94506 C94507 C94508 Group: 4 C94509 C94510 C94511 C94512 C94513 C94514 Dose Level: 0 --- ----- Dose Level: 1 _----- -- Dose Level: 10 ------ -- Dose Level: 30 -- -- -- -" -- -- Dosage Unit: ppm MeFOS Dosage Unit: ppm MeFOS Dosage Unit: ppm MeFOS Dosage Unit: ppm MeFOS Covance 6329-224 3M T-6314.2 Appendix 5 Individual Clinical Hematology Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 5 C94515 C94516 C94517 C94518 C94519 C94520 Group : 6 C94521 C94522 C94524 C94525 C94526 Dose Level: 100 Dose Level: 500 Dosage Unit: ppm MeFOS Dosage unit: ppm MeFOS Covance 6329-224 3M T-6314.2 000716 152 t i Appendix 5 ANIMAL NUMBER Individual Clinical Hematology Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS RBC X 1 0 6/HL HGB G/DL HCT % MCV FL MCH MCHC PLT PG % X I O V U L Group: 1 C94527 C94528 C94529 C94530 C94531 C94532 MEAN S.D. N Group: 2 C94533 C94534 C94535 C94536 C94537 C94538 MEAN S.D. N Group: 3 C94539 C94540 C94541 C94542 C94543 C94544 MEAN S.D. N Dose Level: 0 6.11 6.96 7.65 6.86 7.77 7.37 13.8 14.6 15.6 14.3 15.1 15.1 7.12 .613 6 14.8 .65 6 Dose Level: 1 7.65 7.82 7.11 7.28 7.56 7.03 16.0 15.7 14.9 15.2 15.4 14.6 7.41 .316 6 15.3 .51 6 Dose L e v e l : 10 8.09 6.98 7.43 8.11 7.83 7.25 17.0 14.7 15.3 16.4 15.6 14.6 7.62 .466 6 15.6 .95 6 Dosage Unit: ppm MeFOS 40.5 43.4 46.1 41.6 45.1 44.2 66.2 62.3 60.2 60.7 58.1 59.9 22.6 21.0 20.4 20.8 19.4 20.5 43.5 2.12 6 61.2 2.78 6 20.8 1.05 6 Dosage Unit: ppm MeFOS 46.5 45.7 44.4 44.7 46.0 42.8 60.7 58.5 62.4 61.5 60.9 60.9 20.9 20.1 21.0 20.9 20.4 20.8 45.0 1.34 6 60.8 1.29 6 20.7 .35 6 Dosage Unit: ppm MeFOS 49.8 44.8 45.9 48.5 46.1 43.5 61.6 64.1 61.8 59.8 58.9 60.0 21.0 21.1 20.6 20.2 20.0 20.2 46.4 2.34 6 61.0 1.87 6 20.5 .46 6 34.2 33.8 33.9 34.3 33.4 34.2 34.0 .34 6 34.4 34.3 33.7 34.0 33.5 34.2 34.0 .35 6 34.1 32.9 33.4 33.7 34.0 33.6 33.6 .44 6 939 1072 979 1031 903 1148 1012 90. 3 6 1226 974 1109 921 898 904 1005 133. 7 6 1041 830 919 1156 1065 845 976 131. 4 6 Covance 6329-224 3M T-6314.2 153 000717 it Appendix 5 ANIMAL NUMBER individual Clinical Hematology Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS RBC XlOVjlL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT X1 0 3/JIL Group: 4 C94545 C94546 C94547 C94548 C94549 C94550 MEAN S.D. N Group: 5 C94551 C94552 C94553 C94554 C94555 C94556 MEAN S.D. N Group: 6 C94557 C94558 C94559 C94560 C94561 C94562 MEAN S.D. N Dose L e v e l : 30 7.11 7.09 7.17 7.07 6.97 7.73 14.7 14.5 14.9 14.5 14.6 15.8 7.19 .272 6 14.8 .50 6 Dose Level: 100 7.45 7.22 7.33 6.87 8.05 7.46 14.8 14.8 14.8 14.4 16.1 14.9 7.40 .386 6 15.0 .58 6 Dose Level: 500 5.96 6.34 6.12 6.09 6.53 7.00 12.4 12.3 11.1 12.6 13.1 14.4 6.34 .381 6 12.6 1.08 6 Dosage Uni t : ppm MeFOS 42.8 42.2 42.9 43.0 42.6 47.1 60.1 59.5 59.7 60.8 61.1 60.9 20.6 20.5 20.7 20.5 21.0 20.5 43.4 1.82 6 60.4 .67 6 20.6 .20 6 Dosage Unit: ppm MeFOS 43.4 43.0 44.0 42.8 47.2 44.2 58.2 59.5 60.1 62.3 58.6 59.2 19.9 20.5 20.2 21.0 19.9 19.9 44.1 1.61 6 59.6 1.46 6 20.2 .45 6 Dosage Unit: ppm MeFOS 35.6 36.6 31.6 37.1 37.9 42.3 59.7 57.8 51.7 60.9 58.0 60.4 20.8 19.5 18.2 20.7 20.1 20.6 36.8 3.47 6 58.1 3.37 6 20.0 1.00 6 34.3 34.4 34.7 33.7 34.3 33.6 34.2 .43 6 34.1 34.5 33.7 33.7 34.1 33.6 33.9 .34 6 34.9 33.7 35.2 34.0 34.6 34.1 34.4 .58 6 934 1058 1021 950 1106 1092 1027 72. 6 1016 1061 1228 1075 1165 871 1069 123. 6 759 1027 1057 1091 1255 1065 1042 160. 6 Covance 6329-224 3M T-6314.2 154 000718 ANIMAL NUMBER WBC XlOVjlL Appendix 5 Individual Clinical Hematology Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS N-SEG XlOVjO- LYMPH X 1 0 3/^L MONO x i o V m-l EOSIN x i o 3/h l BASO N--SEG% x i o 3/u l LYMPH% MONO% Covance 6329-224 3M T-6314.2 EOSIN% BASO% Group: 1 C94527 C94528 C94529 C94530 C94531 C94532 MEAN S.D. N Group: 2 C94533 C94534 C94535 C94536 C94537 C94538 MEAN S.D. N Group: 3 C94539 C94540 C94541 C94542 C94543 C94544 MEAN S.D. N Dose Level : 0 5.6 2.8 12.0 7.4 5.0 10.0 1.2 .2 .5 .6 .6 .5 7.1 3.40 6 .6 .33 6 Dose Level : 1 12.1 4.4 8.5 4.3 5.7 13.1 .8 .2 .9 .3 .9 .4 8.0 3.87 6 .6 .32 6 Dose Level : 10 12.3 5.4 9.9 5.3 9.2 5.6 8.0 2.94 6 1.2 .4 .5 .4 .4 .3 .5 .33 6 Dosage Unit: ppm MeFOS 4.1 .2 2.5 .1 9.4 2.0 5.8 .9 4.2 .2 8.8 .6 .1 .0 .1 .1 .1 .1 5.8 .7 .1 2.77 .72 .04 666 Dosage Unit: ppm MeFOS 10.8 .4 .1 3.8 .4 .0 7.1 .3 .2 3.7 .2 .0 4.3 .4 .0 12.0 .6 .1 7.0 .4 .1 3.68 .13 .08 666 Dosage Unit: ppm MeFOS 9.8 4.5 8.4 4.7 8.3 4.8 6.8 2.34 6 1.2 .5 .8 .1 .4 .5 .6 .38 6 .1 .1 .1 .1 .1 .0 .1 .04 6 .0 21 74 4 .0 9 88 2 .1 4 78 17 .0 8 79 12 .0 11 84 4 .0 5 88 6 10 10 10 10 10 10 .0 10 82 8 1 0 .04 6. 1 5. 7 5. 8 .0 6 6 6 6 66 .0 7 90 3 1 0 .0 5 86 8 0 0 .0 11 84 3 2 0 .0 8 86 5 1 0 .0 16 76 7 1 0 .0 3 92 5 0 0 .0 8 86 5 1 0 .00 4. 6 5..6 2. 0 .8 6 6 6 6 66 .0 10 80 10 10 .0 7 84 8 1 0 .0 5 85 8 1 0 .0 8 88 2 1 0 .0 4 90 4 1 0 .0 6 85 8 1 0 .0 7 85 7 1 0 .00 2..2 3. 4 3.,0 .0 6 6 6 6 66 o o o vf 155 u> ) #i iI ANIMAL NUMBER WBC X 1 0 3/HL Appendix 5 Individual Clinical Hematology Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS N-SEG XloVjlL LYMPH x i o 3/h l MONO EOSIN X 1 0 3/(1L X103/|1L BASO N-SEG% x i o 3/h l LYMPH% MONO% Covance 6329-224 3M T-6314.2 EOSIN% BASO% Group: 4 Dose Level : 30 Dosage Unit: ppm MeFOS C94545 11.3 1.7 8.8 .7 .1 .0 15 78 6 1 0 C94546 15.1 .6 13.6 .8 .1 .0 4 90 5 1 0 C94547 12.5 1.0 10.8 .6 .1 .0 8 86 5 10 C94548 5.2 .2 4.8 .1 .1 .0 4 93 2 1 0 C94549 9.7 .9 8.4 .4 .1 .0 9 86 4 1 0 C94550 14.0 .9 12.5 .5 .1 .0 6 90 3 1 0 MEAN S.D. N 11.3 .9 9.8 .5 .1 .0 3.55 .50 3.18 .25 .00 .00 666 666 8 4. 1 6 87 5. 2 6 4 1. 5 6 1 .0 6 0 6 Group: 5 C94551 C94552 C94553 C94554 C94555 C94556 Dose Level : 100 12.1 13.6 12.1 7.0 15.3 9.5 .6 .7 .6 .5 .6 .5 Dosage Unit: ppm MeFOS 10.5 12.8 11.1 6.2 14.2 7.9 .8 .1 .4 .3 .3 1.0 .1 .0 .1 .0 .1 .1 .0 .0 .0 .0 .0 .0 5 87 7 5 94 1 5 91 3 7 88 5 4 93 2 6 83 10 10 00 10 10 10 10 MEAN S.D. N 11.6 .6 10.4 .5 .1 .0 2.96 .08 2.99 .34 .05 .00 6 66 6 6 6 5 1..0 6 89 4.,1 6 5 3.,4 6 1 .4 6 0 6 Group: 6 Dose Level : 500 Dosage Unit: ppm MeFOS C94557 9.0 .4 8.3 .3 .0 .0 4 92 3 0 0 C94558 9.5 1.1 8.1 .3 .0 .0 11 85 3 0 0 C94559 13.5 .6 12.3 .5 .0 .0 5 91 4 0 0 C94560 17.2 .6 16.4 .2 .0 .0 3 95 1 0 0 C94561 13.3 .5 12.1 .6 .0 .1 4 91 5 0 0 C94562 6.2 .3 5.7 .2 .0 .0 5 91 3 0 0 MEAN S.D. N 11.4 .6 10.5 .4 .0 .0 3.95 .28 3.85 .16 .00 .04 6 66 6 6 6 5 2..9 6 91 3..3 6 3 1.,3 6 0 .0 6 0 6 t*0 o 156 0007 Appendix 5 Individual Clinical Hematology Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group : 1 C94527 C94528 C94529 C94530 C94531 C94532 Group: 2 C94533 C94534 C94535 C94536 C94537 C94538 Group : 3 C94539 C94540 C94541 C94542 C94543 C94544 Group: 4 C94545 C94546 C94547 C94548 C94549 C94550 Dose Level: 0 __ ----- -- Dose Level: 1 ----- - Dose Level: 10 -_ ----- -- Dose Level: 30 -_ -- -- -- -- -- Dosage Unit: ppm MeFOS Dosage Unit: ppm MeFOS Dosage Unit: ppm MeFOS Dosage Unit: ppm MeFOS Covance 6329-224 3M T-6314.2  o o q vl CO N s t f i Appendix 5 Individual Clinical Hematology Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 5 C94551 C94552 C94553 C94554 C94555 C94556 Group: 6 C94557 C94558 C94559 C94560 C94561 C94562 Dose Level: 100 ___ --- --- Dose Level: 500 1 Dosage Unit: ppm MeFOS __ -- -Dosage Unit: ppm MeFOS Covance 6329-224 3M T-6314.2 158 ftjr* *# ANIMAL NUMBER Appendix 5 Individual Clinical Chemistry Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL CHOL MG/DL Covance 6329-224 3M T-6314.2 Group: i Dose Level : 0 Dosage Uni t : ppm MeFOS C94491 C94492 C94493 C94494 C94495 C94496 140 15 .5 6.3 4.6 1.7 .3 56 194 14 .8 6.4 4.8 1.6 .2 50 211 13 .5 5.6 4.1 1.5 .0 49 149 16 .8 6.3 4.6 1.7 .2 56 111 13 .5 6.2 4.7 1.5 .1 33 127 12 .7 6.0 4.3 1.7 .1 37 MEAN S.D. N 155 14 .6 6.1 4.5 1.6 .2 47 39.1 1. 5 .15 .29 .26 .10 .10 9. 7 6 666 6 66 6 Group: 2 Dose Level : 1 Dosage Unit: ppm MeFOS C94497 C94498 C94499 C94500 C94501 C94502 133 15 1.0 6.3 4.5 1.8 .1 43 124 10 .6 6.9 5.0 1.9 .0 80 165 16 .7 6.3 4.5 1.8 .0 56 139 11 .4 5.8 4.2 1.6 .2 48 123 12 .5 6.3 4.7 1.6 .2 48 124 15 .7 6.3 4.6 1.7 .2 56 MEAN S.D. N 135 13 .6 6.3 4.6 1.7 .1 55 16.2 2..5 .21 .35 .26 .12 .10 13..2 66666666 Group: 3 Dose Level : 10 Dosage Uni t : ppm MeFOS C94503 C94504 C94505 C94506 C94507 C94508 129 12 .5 6.2 4.4 1.8 .2 43 197 11 .6 6.4 4.6 1.8 .0 28 137 15 .9 6.2 4.4 1.8 .4 40 128 10 .3 5.9 4.4 1.5 .0 65 98 13 .7 6.0 4.6 1.4 .3 37 136 13 .5 6.0 4.4 1.6 .2 50 MEAN S.D. 138 12 .6 6.1 4.5 1.6 .2 44 32.5 1.,8 .20 .18 .10 .18 .16 12..6 N 66666666 o o o *\1 N5 co 159 ANIMAL NUMBER Appendix 5 Individual Clinical Chemistry Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL CHOL MG/DL Covance 6329-224 3M T-6314.2 Group: 4 Dose Level : 30 Dosage Unit: ppm MeFOS C94509 C94510 C94511 C94512 C94513 C94514 119 13 .4 5.7 4.4 1.3 .0 30 97 14 .6 6.0 4.4 1.6 .2 30 122 11 .6 6.0 4.4 1.6 .4 39 184 12 .7 6.7 4.9 1.8 .2 59 196 11 .5 6.0 4.4 1.6 .0 35 126 14 .8 6.7 4.7 2.0 .3 44 MEAN S.D. N 141 12 .6 6.2 4.5 1.6 .2 40 39.7 1. 4 .14 .42 .22 .23 .16 11. 0 6 66 6 6 6 6 6 Group: 5 Dose Level : 100 Dosage Uni t : ppm MeFOS C94515 C94516 C94517 C94518 C94519 C94520 167 16 80 15 80 13 90 18 119 16 161 15 .6 5.8 4.5 1.3 .7 6.0 4.7 1.3 .6 6.1 4.8 1.3 .8 6.9 5.1 1.8 .5 5.9 4.4 1.5 .7 6.8 5.1 1.7 .0 55 .0 43 .1 7 .2 53 .1 23 .0 30 MEAN S.D. N 116 16 .6 6.2 4.8 1.5 .1 35 39.8 1..6 .10 .48 .29 .22 .08 18..7 66666666 Group: 6 Dose Level : 500 Dosage Unit: ppm MeFOS C94521 C94522 C94524 C94525 C94526 97 22 .6 6.0 5.2 .8 1.0 120 23 .9 6.1 5.1 1.0 .4 82 17 .7 6.2 5.0 1.2 .5 121 22 .2 5.5 4.6 .9 .8 116 24 .7 6.4 5.6 .8 1.0 4 1 0 0 1 MEAN 107 22 .6 6.0 5.1 .9 .7 1 S.D. 17.1 2.,7 .26 .34 .36 .17 .28 1..6 N 55555555 o o c 160 *> ANIMAL NUMBER Appendix 5 Individual Clinical Chemistry Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS AST/SGOT ALT/SGPT IU/L IU/L GGT IU/L CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Covance 6329-224 3M T-6314.2 PCOAO IU/G Group: i C94491 C94492 C94493 C94494 C94495 C94496 MEAN S.D. N Group: 2 C94497 C94498 C94499 C94500 C94501 C94502 MEAN S.D. N Group: 3 C94503 C94504 C94505 C94506 C94507 C94508 MEAN S.D. N Dose L e v e l :: 0 97 29 91 37 97 37 90 34 102 34 101 36 96 5.0 6 34 3. 0 6 Dose L e v e l :: 1 98 34 168 36 114 41 115 40 112 31 94 13 117 26.6 6 32 10.,3 6 Dose L e v e l :: 10 89 27 95 30 98 39 96 39 121 38 154 37 109 24.7 6 35 5. 2 6 Dosage Unit: ppm MeFOS 0 11.1 0 11.2 0 10.9 0 10.7 0 10.6 0 11.0 12.1 13.5 12.5 11.5 11.1 12.0 0 .0 6 10.9 .23 6 12.1 .84 6 Dosage Unit: ppm MeFOS 1 11.2 14.9 0 11.5 12.5 1 11.1 10.8 0 11.1 11.6 0 11.0 10.7 0 11.0 12.3 0 .5 6 11.2 .19 6 12.1 1.54 6 Dosage Unit: ppm MeFOS 0 11.6 12.4 0 11.5 10.9 0 12.0 15.5 0 10.9 11.2 0 11.0 10.7 0 11.0 10.4 0 .0 6 11.3 .44 6 11.8 1.92 6 149 146 147 146 153 148 148 2..6 6 7.2 9.4 6.4 6.1 5.9 7.4 7.1 1.29 6 147 149 148 147 151 147 148 1..6 6 9.7 6.8 6.2 6.6 6.0 9.8 7.5 1.75 6 145 148 145 148 153 147 148 2..9 6 7.8 7.0 11.2 6.5 6.1 6.2 7.5 1.93 6 102 103 100 101 102 103 102 1. 2 6 100 101 101 100 103 103 101 1..4 6 101 101 101 102 103 101 102 8 6 10 6 9 11 8 10 9 1. 8 6 8 10 13 6 10 7 9 2.,5 6 5 6 7 9 8 10 8 1.,9 6 N 01 161 0007 I >t t i i ! ANIMAL NUMBER Appendix 5 individual Clinical Chemistry Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS AST/SGOT ALT/SGPT IU/L IU/L GGT IU/L CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Covance 6329-224 3M T-6314.2 PCOAO IU/G Group: 4 C94509 C94510 C94511 C94512 C94513 C94514 MEAN S.D. N Dose Level : 30 89 28 104 40 85 34 109 42 86 29 87 42 93 10.4 6 36 6.4 6 Dosage Unit: ppm MeFOS 0 10.7 11.6 0 10.7 11.7 1 11.3 11.6 0 11.8 9.9 1 11.5 11.0 0 11.2 9.9 0 11.2 .5 .44 66 11.0 .85 6 148 150 149 148 148 149 149 8 6 7.1 6.9 7.2 5.7 6.5 6.4 6.6 .56 6 104 104 104 101 100 101 102 1.9 6 5 9 7 5 9 11 8 2.4 6 Group: 5 Dose Level: 100 Dosage Unit: ppm MeFOS C94515 C94516 C94517 C94518 C94519 C94520 126 48 106 51 147 45 143 70 99 40 108 37 0 10.2 10.3 147 6.4 101 0 10.3 11.0 149 7.4 104 0 11.2 12.8 147 8.5 102 0 11.0 11.5 147 7.7 100 0 10.5 10.9 147 7.4 101 0 11.8 11.3 149 6.1 97 7 5 7 6 7 7 MEAN S.D. N 122 20.3 6 48 11..7 6 0 .0 6 10.8 .62 6 11.3 .84 6 148 1.0 6 7.2 .88 6 101 2.3 6 6 6 Group: 6 C94521 C94522 C94524 C94525 C94526 MEAN S.D. N Dose Level : 500 100 92 316 569 164 240 125 138 122 73 165 87.3 5 222 204. 3 5 Dosage Unit: ppm MeFOS 0 10.5 11.6 0 11.0 10.1 0 10.2 12.3 0 9.8 10.9 0 10.7 9.2 0 .0 5 10.4 .46 5 10.8 1.22 5 148 145 145 142 144 145 2.2 5 8.0 8.3 8.1 8.9 7.8 8.2 .42 5 104 100 101 100 102 101 1.7 5 36 33 27 27 35 32 4 5 o o o J 'lJ 162 Appendix 5 ANIMAL NUMBER individual Clinical Chemistry Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL CHOL MG/DL Group : 1 C94527 C94528 C94529 C94530 C94531 C94532 MEAN S.D. N Group : 2 C94533 C94534 C94535 C94536 C94537 C94538 MEAN S.D. N Group: 3 C94539 C94540 C94541 C94542 C94543 C94544 MEAN S.D. N Dose Level : 0 82 15 112 15 110 13 104 13 101 13 111 13 103 11.3 6 14 1. 0 6 Dose Level : 1 128 14 88 14 104 18 81 14 131 16 139 14 112 24.3 6 15 1..7 6 Dose Level : 10 144 12 90 12 90 16 86 15 93 10 91 18 99 22.2 6 14 3..0 6 Dosage Unit: ppm MeFOS .5 5.9 4.5 .8 7.1 5.5 .5 5.8 4.7 .8 5.9 4.6 1.1 6.2 5.1 .8 7.6 5.9 .8 6.4 5.0 .23 .75 .56 666 Dosage Unit: ppm MeFOS .9 6.8 5.1 .7 6.4 4.9 .9 6.3 5.2 .4 5.9 4.9 .5 6.5 5.0 .4 6.9 5.6 .6 6.5 5.1 .23 .36 .26 666 Dosage Unit: ppm MeFOS .6 6.9 5.5 .5 5.8 4.6 .7 6.2 4.9 .8 6.3 4.9 .6 6.3 5.1 .6 6.6 5.4 .6 6.4 5.1 .10 .37 .34 666 1.4 1.6 1.1 1.3 1.1 1.7 1.4 .25 6 1.7 1.5 1.1 1.0 1.5 1.3 1.4 .27 6 1.4 1.2 1.3 1.4 1.2 1.2 1.3 .10 6 .0 38 .0 57 .0 53 .1 41 .2 27 .2 53 .1 45 .10 11. 5 66 .1 55 .4 73 .2 46 .2 43 .2 52 .3 63 .2 55 .10 11..1 66 .1 47 .2 42 .2 46 .2 31 .1 48 .3 64 .2 46 .08 10.,7 66 Covance 6329-224 3M T-6314.2 0007 vi 163 >t Appendix 5 ANIMAL NUMBER Individual Clinical Chemistry Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL CHOL MG/DL Group : 4 C94545 C94546 C94547 C94548 C94549 C94550 MEAN S.D. N Group: 5 C94551 C94552 C94553 C94554 C94555 C94556 MEAN S.D. N Group: 6 C94557 C94558 C94559 C94560 C94561 C94562 MEAN S.D. N Dose Level : 30 137 11 122 13 158 19 83 12 125 16 160 20 131 28.4 6 15 3. 8 6 Dose Level : 100 101 16 158 29 147 14 107 14 76 15 81 15 112 33.9 6 17 5. 8 6 Dose Level : 500 100 21 86 23 105 28 85 32 138 25 85 25 100 20.6 6 26 3..9 6 Dosage Unit: ppm MeFOS .5 5.8 4.5 .5 5.8 4.6 .9 6.5 5.2 .7 6.6 5.3 .4 5.8 4.7 1.0 7.8 6.3 .7 6.4 5.1 .24 .79 .67 666 Dosage Unit: ppm MeFOS .5 5.9 5.0 .8 7.0 5.6 .5 6.9 5.8 .7 7.2 5.8 .8 7.1 5.7 .8 6.3 5.2 .7 6.7 5.5 .15 .52 .34 666 Dosage Unit: ppm MeFOS .4 6.8 5.8 .6 7.3 6.1 .8 6.1 5.4 .7 7.1 5.9 .4 7.3 6.2 .8 7.3 6.1 .6 7.0 5.9 .18 .48 .29 666 1.3 1.2 1.3 1.3 1.1 1.5 1.3 .13 6 .9 1.4 1.1 1.4 1.4 1.1 1.2 .21 6 1.0 1.2 .7 1.2 1.1 1.2 1.1 .20 6 .0 .4 .1 .2 .1 .0 .1 .15 6 .3 .2 .2 .3 .2 .1 .2 .08 6 .5 .2 .5 1.0 .6 .3 .5 .28 6 55 69 54 39 52 54 54 9. 5 6 19 39 46 64 40 19 38 17..1 6 1 2 6 8 10 17 7 5..9 6 Covance 6329-224 3M T-6314.2 -I N 00 164 000 I s >> ANIMAL NUMBER Appendix 5 Individual Clinical Chemistry Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS AST/SGOT ALT/SGPT IU/L IU/L GGT IU/L CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Covance 6329-224 3M T-6314.2 PCOAO IU/G Group: i Dose L e v e l :: 0 Dosage Unit: ppm MeFOS C94527 C94528 C94529 C94530 C94531 C94532 95 29 130 26 110 25 98 32 102 27 92 25 0 10.3 12.0 147 9.2 106 2 11.0 12.6 148 8.2 101 0 11.5 12.5 146 9.2 104 0 10.3 11.1 146 7.6 103 0 10.4 10.1 148 5.6 102 1 11.8 11.3 147 7.5 102 7 5 5 3 7 4 MEAN S.D. N 104 14.0 6 27 2. 7 6 0 .8 6 10.9 .66 6 11.6 .95 6 147 9 6 7.9 1.34 6 103 1. 8 6 5 1. 6 6 Group: 2 Dose L e v e l :! 1 Dosage Unit: ppm MeFOS C94533 C94534 C94535 C94536 C94537 C94538 113 32 128 30 107 29 102 31 111 31 82 29 0 11.3 14.6 1 11.3 11.7 2 11.3 12.9 0 10.7 10.7 0 12.1 13.9 0 11.7 10.8 145 10.6 151 7.2 146 9.1 148 6.2 144 9.6 148 6.8 102 105 104 104 103 103 5 6 5 9 7 4 MEAN S.D. N 107 15.1 6 30 1.,2 6 0 .8 6 11.4 .47 6 12.4 1.63 6 147 2..5 6 8.2 1.76 6 104 1..0 6 6 1..8 6 Group: 3 Dose Level:: 10 Dosage Unit: ppm MeFOS C94539 C94540 C94541 C94542 C94543 C94544 113 26 128 19 102 28 109 33 102 21 197 34 0 11.6 11.2 0 10.1 10.2 0 11.7 13.4 0 11.0 13.1 0 10.8 11.7 0 11.3 11.7 146 8.2 144 9.9 146 8.7 145 10.0 148 8.1 147 8.7 101 103 104 102 105 103 7 5 6 9 7 6 MEAN S.D. N 125 36.5 6 27 6..1 6 0 .0 6 11.1 .59 6 11.9 1.20 6 146 1..4 6 8.9 .83 6 103 1..4 6 7 1,,4 6 o c >1 N C4) 165 I ANIMAL NUMBER Appendix 5 Individual Clinical Chemistry Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS AST/SGOT ALT/SGPT IU/L IU/L GGT IU/L CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Covance 6329-224 3M T-6314.2 PCOAO IU/G Group: 4 Dose L e v e l : 30 Dosage Uni t : ppm MeFOS C94545 C94546 C94547 C94548 C94549 C94550 105 29 94 30 81 25 142 41 91 23 88 20 1 10.9 10.2 147 6.8 104 0 11.2 11.3 145 7.9 101 4 11.1 10.0 145 6.0 102 0 10.5 9.9 151 5.8 103 1 10.6 11.8 143 8.5 102 0 12.2 9.8 147 7.3 102 7 3 11 7 4 5 MEAN S.D. N 100 22.0 6 28 7. 4 6 1 11.1 1.5 .61 66 10.5 .84 6 146 2. 7 6 7.0 1.06 6 102 1. 0 6 6 2. 9 6 Group: 5 Dose L e v e l : 100 Dosage Unit: ppm MeFOS C94551 C94552 C94553 C94554 C94555 C94556 101 33 91 28 76 20 82 31 94 32 94 31 0 11.0 12.8 146 8.4 102 0 11.5 11.1 146 7.8 103 0 12.4 10.4 146 7.1 102 0 11.1 10.6 146 7.7 104 0 11.6 12.5 149 7.7 102 0 11.0 11.6 148 7.1 104 11 3 9 7 9 11 MEAN S.D. N 90 9.1 6 29 4. 8 6 0 .0 6 11.4 .54 6 11.5 .99 6 147 1. 3 6 7.6 .49 6 103 1.,0 6 8 3.,0 6 Group: 6 Dose Level: 500 Dosage Unit: ppm MeFOS C94557 C94558 C94559 C94560 C94561 C94562 95 57 128 49 145 67 117 54 130 89 90 43 0 11.2 10.9 147 6.5 102 0 10.5 10.3 149 6.4 99 0 10.4 10.4 148 7.6 107 0 11.1 11.6 147 7.4 99 0 11.7 10.9 146 7.5 101 0 10.6 9.7 151 5.7 103 46 22 20 26 45 22 MEAN S.D. N 118 21.4 6 60 16.,4 6 0 .0 6 10.9 .50 6 10.6 .65 6 148 1. 8 6 6.8 .77 6 102 3..0 6 30 12.,0 6 o o c ) o 166 Appendix 5 Individual Clinical Urinalysis Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER U VOL ML SP GR U PH Group: i C94491 C94492 C94493 C94494 C94495 C94496 MEAN S.D. N Group: 2 C94497 C94498 C94499 C94500 C94501 C94502 MEAN S.D. N Group: 3 C94503 C94504 C94505 C94506 C94507 C94508 MEAN S.D. N Dose Level: 0 5.7 31.5 26.9 19.0 9.4 18.5 1.032 1.010 1.010 1.015 1.026 1.010 18.5 9.86 6 1.017 .0096 6 Dose Level: 1 10.2 48.9 a 4.4 7.4 47.0 a 48.3 a 1.020 1.005 1.029 1.026 1.004 1.007 27.7 22.39 6 1.015 .0112 6 Dose Level: 10 35.0 14.3 44.9 14.7 41.7 19.8 1.010 1.013 1.008 1.012 1.006 1.012 28.4 13.81 6 1.010 .0027 6 Dosage Unit: ppm MeFOS 7.0 7.5 7.5 7.5 7.5 7.5 7.4 .20 6 Dosage Unit: ppm MeFOS 7.0 7.0 7.5 7.0 7.5 7.5 7.2 .27 6 Dosage Uni t : ppm MeFOS 7.0 7.0 7.0 7.5 7.0 7.5 7.2 .26 6 a Sample was overflowing at the time of collection. Covance 6329-224 3M T-6314.2 Appendix 5 Individual Clinical Urinalysis Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER U VOL ML SP GR U PH Covance 6329-224 3M T-6314.2 Group: 4 Dose L e v e l :: 30 Dossaaggie Unit: pp m MeFOS C94509 C94510 C94511 C94512 C94513 C94514 37.0 22.8 9.5 26.0 48.5 a 12.4 1.005 1.012 1.023 1.012 1.008 1.020 6.5 7.0 7.0 7.0 7.0 7.0 MEAN S.D. N 26.0 14.80 6 1.013 .0069 6 6.9 .20 6 Group: 5 Dose L e v e l :: 100 Dossaaggie Unit: pp m MeFOS C94515 C94516 C94517 C94518 C94519 C94520 7.5 7.3 3.0 10.6 17.3 49.8 a 1.034 1.028 1.030 1.025 1.016 1.005 6.5 6.5 8.0 7.0 6.5 7.0 MEAN S.D. N 15.9 17.26 6 1.023 .0107 6 6.9 .58 6 Group: 6 Dose L e v e l ;: 500 Dossaaggie Unit: pp m MeFOS C94521 C94522 C94524 C94525 C94526 17.5 43.9 a 26.4 4.6 9.6 1.014 1.007 1.010 1.038 1.024 7.0 7.0 7.0 6.5 6.5 MEAN S.D. N 20.4 15.52 5 1.019 .0126 5 6.8 .27 5 c a Sample was overflowing at the time of collection. 0007.33 Appendix 5 Individual Clinical Urinalysis Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLQOROOCTANESULFONAMIDO ETHANOL {N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER U PRO MG/DL U GLU u KET U BILI U BLOOD UROBILI Group: 1 C94491 C94492 C94493 C94494 C94495 C94496 Group: 2 C94497 C94498 C94499 C94500 C94501 C94502 Group: 3 C94503 C94504 C94505 C94506 C94507 C94508 Group: 4 C94509 C94510 C94511 C94512 C94513 C94514 Dose Level: 0 30 _ 30 10 10 30 30 Dose Level: 1 30 10 100 30 0 10 _ - - - - Dose Level: 10 10 30 10 30 10 - 10 * Dose Level: 30 0_ 10 30 10 10 30 - Dosage Unit: ppm MeFOS ++ _ --++ ++ + Dosage Unit: ppm MeFOS +_ -- +++ -- -- Dosage Unit: ppm MeFOS _ -+ ------ Dosage Unit: ppm MeFOS __ +++ --_ -- _ - - - - _ - - - _ - 169 Covance 6329-224 3M T-6314.2 Appendix 5 Individual Clinical Urinalysis Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER U PRO MG/DL U GLU u KET U BILI U BLOOD UROBILI Group : 5 C94515 C94516 C94517 C94518 C94519 C94520 Group: 6 C94521 C94522 C94524 C94525 C94526 Dose Level : 100 30 30 100 10 10 0 - - Dose Level: 500 10 _ 010 30 10 - Dosage Unit : ppm MeFOS ++ ++ +++ ++ +++ + - - - + - ++ - - Dosage Unit: ppm MeFOS + + +++ + ++ + _ - _ - Covance 6329-224 3M T-6314.2 000734 170 It Appendix 5 ANIMAL NUMBER Individual Clinical Urinalysis Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS RBC PER HPF WBC PER HPF EPITH PER HPF BACT PER HPF CASTS PER LPF CRYSTALS PER LPF1 URINE APPI COMMENTS Group : 1 C94491 C94492 C94493 C94494 C94495 C94496 Group : 2 C94497 C94498 C94499 C94500 C94501 C94502 Group : 3 C94503 C94504 C94505 C94506 C94507 C94508 Group: 4 C94509 C94510 C94511 C94512 C94513 C94514 Dose Level : 0 10 00 00 00 00 00 Dose Level: 1 00 00 00 04 00 00 Dose Level : 10 00 00 00 00 00 10 Dose Level : 30 00 00 00 00 00 00 Dosage Unit: ppm MeFOS 020 12 0 110 110 120 110 Dosage Unit: ppm MeFOS 12 0 130 110 12 0 110 120 Dosage Unit: ppm MeFOS 110 110 12 0 120 120 110 Dosage Unit : ppm MeFOS 010 110 110 110 130 010 4D 4D 4D 4D 4D 4D 4D 3B1D 4D 4D 4D 4D 3D 0 0 4D 0 3D 0 4D 4D ID 3D 4D CJ BJ BJ BJ BJ AJ BJ AJ CJ BK AJ BJ AJ BJ BJ BJ AJ BJ AJ BJ BJ BJ BJ BJ P Q P PQ PQ Q PQ Q PQ Q Q Q Q Q Q Q PQ Q Q PQ Q Q Q - Covance 6329-224 3M T-6314.2 o o 0 >1 5 01 171 Appendix 5 ANIMAL NUMBER Individual Clinical Urinalysis Data Males Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS RBC PER HPF WBC PER. HPF EPITH PER HPF BACT PER HPF CASTS PER LPF CRYSTALS PER LPF1 URINE APP1 COMMENTS Group: 5 C94515 C94516 C94517 C94518 C94519 C94520 Group: 6 C94521 C94522 C94524 C94525 C94526 Dose Level: 100 30 00 00 00 00 00 Dose Level: 500 00 00 00 00 01 Dosage Unit: ppm MeFOS i10 i20 030 120 110 110 Dosage Unit: ppm MeFOS 010 010 010 120 110 4D 3D 2B4D 4D 3D 0 2D 0 4D ID 4D CJ BJ FL BJ BJ AJ BJ AJ BJ CJ BJ PQ PQ Q PQ PQ Q Q - Q PQ Covance 6329-224 3M T-6314.2 o o o >3 172 Appendix 5 Individual Clinical Urinalysis Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER U VOL ML SP GR U PH Group : 1 Dose Level:: 0 Dosagg:e Unit: p p m MeFOS C94527 C94528 C94529 C94530 C94531 C94532 14.5 7.1 49.0 a 48.0 15.0 50.0 a 1.015 1.022 1.004 1.005 1.010 1.002 7.5 6.5 7.0 7.0 7.5 7.0 MEAN S.D. N 30.6 20.36 6 1.010 .0077 6 7.1 .38 6 Group: 2 Dose Level :: 1 Dossaaggie Unit: pp m MeFOS C94533 C94534 C94535 C94536 C94537 C94538 11.6 17.1 15.0 14.0 46.6 a 50.0 a 1.013 1.005 1.010 1.013 1.004 1.004 7.5 6.5 7.0 7.0 7.0 7.0 MEAN S.D. N 25.7 17.62 6 1.008 .0044 6 7.0 .32 6 Group: 3 Dose Level :: 10 Dossaaggie Unit: pp m MeFOS C94539 C94540 C94541 C94542 C94543 C94544 46.8 a 47.0 a 28.2 9.9 16.8 14.0 1.002 1.003 1.010 1.018 1.002 1.010 6.5 7.0 7.0 7.0 7.0 7.0 MEAN S.D. N 27.1 16.49 6 1.008 .0064 6 6.9 .20 6 a Sample was overflowing at the time of collection. Covance 6329-224 3M T-6314.2 If Appendix 5 Individual Clinical urinalysis Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER U VOL ML SP GR U PH Covance 6329-224 3M T-6314.2 Group: 4 Dose Level :: 30 Dos aggie Unit: p p m MeFOS C94545 C94546 C94547 C94548 C94549 C94550 16.5 5.4 3.4 28.0 14.8 21.6 1.010 1.028 1.026 1.008 1.010 1.006 7.5 6.5 7.0 7.0 7.5 7.0 MEAN S.D. N 15.0 9.40 6 1.015 .0097 6 7.1 .38 6 Group: 5 Dose Level :: 100 Dossaaggie Unit: ppm MeFOS C94551 C94552 C94553 C94554 C94555 C94556 24.0 10.7 30.0 49.0 a 50.0 a 10.3 1.007 1.010 1.008 1.003 1.003 1.018 7.5 7.0 7.0 7.0 7.0 6.5 MEAN S.D. N 29.0 17.62 6 1.008 .0056 6 7.0 .32 6 Group : 6 Dose Level:: 500 Dossaaggie Unit: p p m MeFOS C94557 C94558 C94559 C94560 C94561 C94562 15.0 9.6 11.6 4.0 40.2 8.2 1.010 1.016 1.013 1.006 1.005 1.015 7.0 7.0 6.5 7.5 7.0 7.0 MEAN S.D. N 14.8 12.98 6 1.011 .0046 6 7.0 .32 6 o a Sample was overflowing at the time of o C*J 00 174 0007 * 4 <A> * 'i t Appendix 5 Individual Clinical Urinalysis Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 C94527 C94528 C94529 C94530 C94531 C94532 Group: 2 C94533 C94534 C94535 C94536 C94537 C94538 Group: 3 C94539 C94540 C94541 C94542 C94543 C94544 Group: 4 C94545 C94546 C94547 C94548 C94549 C94550 Dose Level: 0 10 10 0010 0- Dose Level: 1 0_ 010 000- Dose Level: 10 00010 00 Dose Level: 30 10 _ 10 10 010 0- Dosage Unit: ppm MeFOS _------------ Dosage Unit: ppm MeFOS _-_ --- --- --- -- - - - Dosage Unit: ppm MeFOS - -_ ---------- Dosage Unit: ppm MeFOS _-_ ---------- - - _ - - - _ - _ - - 175 Covance 6329-224 3M T-6314.2 Appendix 5 Individual Clinical Urinalysis Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 5 Dose Level: 100 C94551 C94552 C94553 C94554 C94555 C94556 0 0 0 0 0 0 Group: 6 Dose Level: 500 C94557 C94558 C94559 C94560 C94561 C94562 0 10 0 0 0 0 Dosage Unit: ppm MeFOS Dosage Unit: ppm MeFOS ++ +++ Covance 6329-224 3M T-6314.2 fc- N-3 176 I iit ANIMAL NUMBER Appendix 5 Individual Clinical Urinalysis Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS RBC PER HPF WBC PER HPF EPITH PER HPF BACT PER HPF CASTS PER LPF CRYSTALS PER LPF1 URINE APP1 COMMENTS Group: 1 C94527 C94528 C94529 C94530 C94531 C94532 Group: 2 C94533 C94534 C94535 C94536 C94537 C94538 Group: 3 C94539 C94540 C94541 C94542 C94543 C94544 Group: 4 C94545 C94546 C94547 C94548 C94549 C94550 Dose Level: 0 00 00 00 00 01 00 Dose Level: 1 00 00 00 00 04 00 Dose L e v e l : 10 00 00 00 00 00 00 Dose L e v e l : 30 14 00 00 00 00 01 Dosage Unit: ppm MeFOS 120 110 110 110 110 120 Dosage Unit: ppm MeFOS 010 020 120 110 110 010 Dosage Unit: ppm MeFOS 020 110 010 110 010 010 Dosage Unit: ppm MeFOS 120 110 110 110 110 010 4D ID 0 4D 3D 4B 4D 0 0 4D 0 3D 2B 0 0 40 ID 0 2B4D 0 4D 4D 4D 0 BJ BJ AJ AJ BJ AJ BJ AJ BJ BJ AJ AJ AJ AJ AJ BJ BJ BJ BJ CJ BJ BJ CJ AJ - - - - P - P - _ - - - _ - - Covance 6329-224 3M T-6314.2 o o o 177 i Appendix 5 ANIMAL NUMBER Individual Clinical Urinalysis Data Females Week 5 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS RBC PER HPF WBC PER HPF EPITH PER HPF BACT PER HPF CASTS PER LPF CRYSTALS PER LPF1 URINE APP1 COMMENTS Group: 5 Dose Level: 100 Dosage Unit: ppm MeFOS C94551 0 0 i 1 0 0 AJ - C94552 0 0 i 1 0 0 AJ - C94553 0 0 i 1 0 0 AJ - C94554 0 0 0 1 0 0 AJ - C94555 0 0 1 1 0 0 AJ - C94556 0 1 1 1 0 0 BJ P Group : 6 Dose L e v e l : 500 Dosage Unit: ppm MeFOS C94557 0 0 1 2 0 0 BJ _ C94558 0 0 1 2 0 0 BJ - C94559 0 0 1 1 0 0 BJ - C94560 0 0 1 1 0 0 AJ - C94561 0 0 0 1 0 ID AJ - C94562 0 0 0 1 0 3D BJ - Covance 6329-224 3M T-6314.2 '.000 178 APPENDIX 6 Individual Absolute Organ Weight Data (g) Individual Organ-to-Body Weight Percentages Individual Organ-to-Brain Weight Ratios Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 179 0 0 0 APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 1 TABLE INCLUDES: SEX=ALL;G ROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, OV - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV M 1 C94491 M 1 C94492 M 1 C94493 M 1 C94494 M 1 C94495 M 1 C94496 335.4 361.6 339.1 379.4 343.5 291.7 0.0612 0.0515 0.0563 0.0634 0.0416 0.0725 2.1109 1.9843 1.9218 2.1238 2.1985 2.0137 1.0347 0.8785 0.8731 1.0167 0.8446 0.8805 3.6123 3.2546 3.6572 3.7571 3.2033 2.9056 14.0407 13.6908 12.4081 14.3488 13.3219 9.6607 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 341.8 29.6 6 0.0577 0.0106 6 2.0588 0.1028 6 0.9214 0.0821 6 3.3984 0.3295 6 12.9118 1.7284 M 2 C94497 M 2 C94498 M 2 C94499 M 2 C94500 M 2 C94501 M 2 C94502 345.7 321.0 384.3 320.2 332.4 323.8 0.0579 0.0630 0.0454 0.0575 0.0621 0.0565 1.8832 2.0462 2.0893 2.1243 2.0688 1.9994 0.8967 0.9478 0.8275 0.8480 0.9718 0.8940 2.5682 2.8116 3.4950 3.5756 3.0639 3.1062 11.7523 11.9965 14.2738 11.9975 11.6636 13.0440 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 337.9 24.7 6 0.0571 0.0063 6 2.0352 0.0854 6 0.8976 0.0555 6 3.1034 0.3872 6 12.4546 1.0193 M 3 C94503 M 3 C94504 M 3 C94505 338.4 369.1 337.9 0.0719 0.0644 0.0562 1.8517 2.0698 2.1689 1.0084 0.8887 1.0062 3.4730 3.7053 3.3038 12.6442 13.2875 13.4179 ** CONTINUED ON NEXT PAGE * SP 0.9276 0.7517 0.7500 0.7848 0.8125 0.8029 6 0.8049 0.0654 0.7741 0.5888 0.8183 0.7821 0.8350 0.7124 6 0.7518 0.0904 0.9372 0.7590 0.6947 TE 3.4698 2.9808 2.8478 3.2911 2.9317 2.8137 6 3.0558 0.2644 2.8943 2.7400 3.0946 2.7896 2.9111 3.2586 6 2.9480 0.1952 3.3072 2.8135 3.1618 TH 0.5026 0.5711 0.4336 0.6600 0.9318 0.5241 6 0.6039 0.1774 0.5496 0.6983 0.9560 0.8007 0.5562 0.5391 6 0.6833 0.1692 0.7104 0.8812 0.6890 APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 2 TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L DEATH=T ;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, OV - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP TE TH M 3 C94506 M 3 C94507 M 3 C94508 322.1 298.0 357.8 0.0479 0.0676 0.0567 1.8990 2.0294 2.0861 0.9847 0.8627 1.1055 3.3090 2.9125 3.3758 12.2100 11.2672 13.4521 0.7515 0.6989 0.8250 2.6611 3.2209 2.8780 0.5349 0.5221 0.7962 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 337.2 25.3 6 0.0608 0.0088 6 2.0175 0.1200 6 0.9760 0.0886 6 3.3466 0.2597 6 12.7132 0.8627 6 0.7777 0.0914 6 3.0071 0.2583 6 0.6890 0.1418 M 4 C94509 M 4 C94510 M 4 C94511 M 4 C94512 M 4 C94513 M 4 C94514 301.9 282.3 308.5 365.6 330.7 349.8 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 323.1 31.3 M 5 C94515 M 5 C94516 M 5 C94517 M 5 C94518 331.8 295.2 337.9 316.7 ** CONTINUED ON NEXT PAGE ** 0.0566 0.0478 0.0530 0.0377 0.0538 0.0630 6 0.0520 0.0086 0.0545 0.0456 0.0725 0.0549 2.1850 2.0063 2.0354 1.9763 2.2273 2.3348 6 2.1275 0.1430 2.1887 2.0552 1.9646 2.0189 0.9372 0.7471 0.8228 0.9490 0.8336 0.9083 6 0.8663 0.0785 0.8303 0.7772 1.1014 0.7763 3.0753 2.9461 2.9192 3.1823 3.5906 3.6837 6 3.2329 0.3284 3.4080 3.1619 3.6453 3.1469 10.1043 10.3504 12.4616 13.9926 13.3383 13.7000 6 12.3245 1.7057 17.4565 16.0421 15.5417 19.5437 0.5576 0.7116 0.6977 0.7251 0.6600 0.8910 6 0.7072 0.1085 0.6778 0.7592 0.6331 0.7817 3.0521 2.6666 2.6572 3.1206 2.9338 3.1234 6 2.9256 0.2156 3.0282 3.0667 3.1028 2.7821 0.6354 0.4856 0.5913 0.5207 0.5986 0.6808 6 0.5854 0.0721 0.7223 0.7229 0.5009 0.7942 000 VI 181 C'i APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 3 TABLE INCLUDES: SEX=ALL ;GROUP=ALL ;WEEKS=ALL DEATH=T ;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, OV - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP TE TH M 5 C94519 M 5 C94520 317.4 325.4 0.0522 0.0485 2.1524 2.1764 0.7815 0.8017 3.0339 3.3572 14.5708 17.1128 0.7127 0.4740 2.8462 3.0040 0.5508 0.6690 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 320.7 15.0 6 0.0547 0.0094 6 2.0927 0.0928 6 0.8447 0.1274 6 3.2922 0.2223 6 16.7113 1.7399 6 0.6731 0.1114 6 2.9717 0.1282 6 0.6600 0.1124 M 6 C94521 M 6 C94522 M 6 C94524 M 6 C94525 M 6 C94526 226.3 243.9 211.8 228.0 229.1 0.0436 0.0735 0.0573 0.0507 0.0596 1.8883 1.9366 1.9767 2.1492 2.0535 0.6830 0.7866 0.6364 0.7775 0.7748 2.3557 2.8945 2.4286 2.5308 2.7529 20.2477 19.4615 18.0054 19.5937 20.7386 0.6046 0.5137 0.6151 0.6822 0.4943 3.1040 3.2106 2.4897 3.1146 3.0650 0.6047 0.4000 0.3243 0.4146 0.5015 NUMBER IN GROUP : MEAN: STANDARD DEV: 5 227.8 11.4 5 0.0569 0.0112 5 2.0009 0.1027 5 0.7317 0.0679 5 2.5925 0.2256 5 19.6094 1.0341 5 0.5820 0.0775 5 2.9968 0.2885 5 0.4490 0.1074 >1 182 APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E ATH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT M 1 C94491 M 1 C94492 M 1 C94493 M 1 C94494 M 1 C94495 M 1 C94496 335.4 361.6 339.1 379.4 343.5 291.7 0.0223 0.0177 0.0177 0.0299 0.0189 0.0172 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 341.8 29.6 6 0.0206 0.0049 M 2 C94497 M 2 C94498 M 2 C94499 M 2 C94500 M 2 C94501 M 2 C94502 345.7 321.0 384.3 320.2 332.4 323.8 0.0295 0.0252 0.0216 0.0213 0.0155 0.0273 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 337.9 24.7 6 0.0234 0.0050 M 3 C94503 M 3 C94504 M 3 C94505 338.4 369.1 337.9 0.0198 0.0231 0.0230 ** CONTINUED ON NEXT PAGE ** Covance 6329-224 3M T-6314.2 PAGE: 4 APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT M 3 C94506 M 3 C94507 M 3 C94508 322.1 298.0 357.8 0.0189 0.0224 0.0282 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 337.2 25.3 6 0.0226 0.0033 M 4 C94509 M 4 C94510 M 4 C94511 M 4 C94512 M 4 C94513 M 4 C94514 301.9 282.3 308.5 365.6 330.7 349.8 0.0160 0.0192 0.0111 0.0254 0.0216 0.0304 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 323.1 31.3 6 0.0206 0.0068 M 5 C94515 M 5 C94516 M 5 C94517 M 5 C94518 331.8 295.2 337.9 316.7 0.0252 0.0201 0.0207 0.0203 ** CONTINUED ON NEXT PAGE ** Covance 6329-224 3M T-6314.2 PAGE: 5 APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E A TH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT M 5 C94519 M 5 C94520 317.4 325.4 0.0172 0.0278 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 320.7 15.0 6 0.0219 0.0039 M 6 C94521 M 6 C94522 M 6 C94524 M 6 C94525 M 6 C94526 226.3 243.9 211.8 228.0 229.1 0.0149 0.0172 0.0191 0.0303 0.0172 NUMBER IN GROUP : MEAN: STANDARD DEV: 5 227.8 11.4 5 0.0197 0.0061 Covance 6329-224 3M T-6314.2 PAGE: 6 o o 185 L APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL D E A TH=T;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, OV - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP F 1 C94527 F 1 C94528 F 1 C94529 F 1 C94530 F 1 C94531 F 1 C94532 213.0 210.0 228.8 235.2 207.8 184.7 0.0715 0.0706 0.1022 0.0605 0.0655 0.0682 2.0013 1.9160 1.9228 2.0288 1.9550 1.9062 2.0130 1.9295 2.6260 2.1802 2.0538 1.7582 7.4326 7.8862 8.7876 8.2680 7.5010 6.6326 0.1162 0.0945 0.1418 0.1644 0.1314 0.1150 0.5561 0.3804 0.6896 0.5085 0.4679 0.4453 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 213.3 17.8 6 0.0731 0.0148 6 1.9550 0.0500 6 2.0935 0.2961 6 7.7513 0.7450 6 0.1272 0.0243 6 0.5080 0.1069 F 2 C94533 F 2 C94534 F 2 C94535 F 2 C94536 F 2 C94537 F 2 C94538 200.3 197.5 217.3 204.4 223.4 192.6 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 205.9 12.0 F 3 C94539 F 3 C94540 F 3 C94541 217.8 174.2 234.2 ** CONTINUED ON NEXT PAGE ** 0.0639 0.0655 0.0683 0.0803 0.0733 0.0606 6 0.0687 0.0071 0.1090 0.0624 0.0850 2.0393 2.0617 2.0698 1.8203 2.0384 1.8703 6 1.9833 0.1088 2.0113 1.9367 2.0657 1.9056 1.9166 1.8145 2.0013 2.2858 1.8873 6 1.9685 0.1666 2.6878 1.9136 2.5187 8.3329 7.1556 7.8013 6.8621 8.2008 6.9707 6 7.5539 0.6425 8.3813 6.6088 8.8330 0.1402 0.1380 0.1276 0.1446 0.1269 0.1094 6 0.1311 0.0128 0.1454 0.1402 0.1394 0.5051 0.4487 0.5174 0.6338 0.4833 0.4307 6 0.5032 0.0719 0.5526 0.3929 0.6589 o o 0 01 186 Covance 6329-224 3M T-6314.2 PAGE: 7 TE TH 0.4566 0.6013 0.6188 0.5445 0.5398 0.5121 6 0.5455 0.0592 0.4569 0.3874 0.4819 0.5764 0.5223 0.7123 6 0.5229 0.1124 0.4936 0.3952 0.6495 i APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL ;GROUP=ALL ;WEEKS=ALL DEATH=T ;SUBSET:=ALL : AD - ADRENAL : KD - KIDNEY, ORGAN ABBREVIATION: SP - SPLEEN, BR - BRAIN, EP - EPIDIDYMIDES LI - LIVER, OV - OVARY TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP F 3 C94542 F 3 C94543 F 3 C94544 242.5 167.9 185.5 0.0880 0.0487 0.0563 2.0048 1.8660 2.0395 2.5368 1.7414 2.1156 9.4944 6.4505 8.2267 0.1565 0.0986 0.1453 0.5490 0.3354 0.4673 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 203.7 32.0 6 0.0749 0.0229 6 1.9873 0.0735 6 2.2523 0.3837 6 7.9991 1.2215 6 0.1376 0.0200 6 0.4927 0.1181 F 4 C94545 F 4 C94546 F 4 C94547 F 4 C94548 F 4 C94549 F 4 C94550 187.2 219.7 237.1 186.8 207.7 187.0 0.0585 0.0634 0.0794 0.0536 0.0653 0.0630 1.8832 2.0493 2.1499 2.0980 2.0569 1.9038 2.0151 2.1332 2.2587 1.9018 2.1431 1.8946 7.1725 9.5768 9.8392 6.8828 8.7554 7.7017 0.1228 0.1006 0.1338 0.0940 0.1636 0.0960 0.4640 0.5830 0.5588 0.4053 0.5145 0.4316 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 204.3 21.1 6 0.0639 0.0087 6 2.0235 0.1071 6 2.0578 0.1457 6 8.3214 1.2523 6 0.1185 0.0273 6 0.4929 0.0710 F 5 C94551 F 5 C945B2 F 5 C94553 F 5 C94554 171.1 201.4 206.3 184.4 0.0661 0.0660 0.0679 0.0582 1.8855 2.0531 2.0290 1.8946 1.9419 2.3079 2.2091 1.9402 8.7911 10.2382 10.4906 8.6778 0.1289 0.1255 0.1087 0.0972 0.4517 0.4772 0.4567 0.3575 ** CONTINUED ON NEXT PAGE ** Covance 6329-224 3M T-6314.2 PAGE: 8 TE TH 0.6078 0.5563 0.4899 6 0.5321 0.0918 0.4712 0.6427 0.5987 0.6280 0.4439 0.5060 6 0.5484 0.0854 0.3160 0.3988 0.6089 0.3711 O o o C/l 187  APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET=ALL : AD - ADRENAL : KD - KIDNEY, ORGAN ABBREVIATION: SP - SPLEEN, BR - BRAIN, EP - EPIDIDYMIDES LI - LIVER, OV - OVARY TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP F 5 C94555 F 5 C94556 192.5 206.1 0.0605 0.0777 2.0725 2.0897 2.1591 2.6036 10.0252 9.4436 0.1028 0.1349 0.4944 0.6082 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 193.6 13.9 6 0.0661 0.0068 6 2.0041 0.0906 6 2,1936 0.2491 6 9.6111 0.7628 6 0.1163 0.0155 6 0.4743 0.0810 F 6 C94557 F 6 C94558 F 6 C94559 F 6 C94560 F 6 C94561 F 6 C94562 151.5 154.4 134.5 172.6 161.3 165.1 0.0381 0.0453 0.0351 0.0389 0.0618 0.0589 1.9430 2.1101 1.7981 2.0925 1.9670 2.0415 1.6979 1.7106 1.4107 1.6771 1.9650 1.8903 12.4887 12.6860 9.8766 14.9295 13.3315 10.9656 0.0758 0.0777 0.0511 0.0671 0.0797 0.1065 0.3143 0.4358 0.4295 0.5289 0.4122 0.4382 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 156.6 13.2 6 0.0464 0.0114 6 1.9920 0.1159 6 1.7253 0.1934 6 12.3797 1.7764 6 0.0763 0.0181 6 0.4265 0.0686 Covance 6329-224 3M T-6314.2 PAGE: 9 TE TH 0.8204 0.5221 6 0.5062 0.1873 0.3376 0.4256 0.4142 0.6468 0.4100 0.5178 6 0.4587 0.1086 o o c <1 188 N APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L DEATH=T; SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT F 1 C94527 F 1 C94528 F 1 C94529 F 1 C94530 F 1 C94531 F 1 C94532 213.0 210.0 228.8 235.2 207.8 184.7 0.0155 0.0141 0.0177 0.0133 0.0173 0.0175 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 213.3 17.8 6 0.0159 0.0019 F 2 C94533 F 2 C94534 F 2 C94535 F 2 C94536 F 2 C94537 F 2 C94538 NUMBER IN GROUP: MEAN: STANDARD DEV: 200.3 197.5 217.3 204.4 223.4 192.6 6 205.9 12.0 0.0197 0.0217 0.0196 0.0140 0.0192 0.0143 6 0.0181 0.0032 F 3 C94539 F 3 C94540 F 3 C94541 217.8 174.2 234.2 ** CONTINUED ON NEXT PAGE ** 0.0066EX 0.0217 0.0164 Covance 6329-224 3M T-6314.2 PAGE: 10 APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E A TH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT F 3 C94542 F 3 C94543 F 3 C94544 242.5 167.9 185.5 0.0250 0.0192 0.0140 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 203.7 32.0 5 0.0193 0.0043 F 4 C94545 F 4 C94546 F 4 C94547 F 4 C94548 F 4 C94549 F 4 C94550 NUMBER IN GROUP: MEAN: STANDARD DEV: 187.2 219.7 237.1 186.8 207.7 187.0 6 204.3 21.1 0.0131 0.0293 0.0129 0.0167 0.0221 0.0165 6 0.0184 0.0063 F 5 C94551 F 5 C94552 F 5 C94553 F 5 C94554 171.1 201.4 206.3 184.4 1e CONTINUED ON NEXT PAGE ** 0.0126 0.0244 0.0237 0.0149 o o o C/ 190 Covance 6329-224 3M T-6314.2 PAGE: 11 APPENDIX 6 Individual Absolute Organ Weight Data (g) Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E ATH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL - GROUP NUMBER BODY WT (g) TT F 5 C94555 F 5 C94556 192.5 206.1 0.0177 0.0150 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 193.6 13.9 6 0.0181 0.0049 F 6 C94557 F 6 C94558 F 6 C94559 F 6 C94560 F 6 C94561 F 6 C94562 NUMBER IN GROUP : MEAN: STANDARD DEV: 151.5 154.4 134.5 172.6 161.3 165.1 6 156.6 13.2 0.0152 0.0122 0.0118 0.0095 0.0182 0.0154 6 0.0137 0.0031 o o 0 -.1 1. 01 191 Covance 6329-224 3M T-6314.2 PAGE: 12 APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 1 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, OV - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP M 1 C94491 M 1 C94492 M 1 C94493 M 1 C94494 M 1 C94495 M 1 C94496 335.4 361.6 339.1 379.4 343.5 291.7 0.0182 0.0142 0.0166 0.0167 0.0121 0.0249 0.6294 0.5488 0.5667 0.5598 0.6400 0.6903 0.3085 0.2429 0.2575 0.2680 0.2459 0.3019 1.0770 0.9001 1.0785 0.9903 0.9325 0.9961 4.1863 3.7862 3.6591 3.7820 3.8783 3.3119 0.2766 0.2079 0.2212 0.2069 0.2365 0.2752 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 341.8 29.6 6 0.0171 0.0044 6 0.6058 0.0562 6 0.2708 0.0282 6 0.9957 0.0730 6 3.7673 0.2855 6 0.2374 0.0317 M 2 C94497 M 2 C94498 M 2 C94499 M 2 C94500 M 2 C94501 M 2 C94502 NUMBER IN GROUP : MEAN: STANDARD DEV: 345.7 321.0 384.3 320.2 332.4 323.8 6 337.9 24.7 0.0167 0.0196 0.0118 0.0180 0.0187 0.0174 6 0.0170 0.0027 0.5447 0.6374 0.5437 0.6634 0.6224 0.6175 6 0.6049 0.0496 0.2594 0.2953 0.2153 0.2648 0.2924 0.2761 6 0.2672 0.0292 0.7429 0.8759 0.9094 1.1167 0.9218 0.9593 6 0.9210 0.1214 3.3996 3.7372 3.7142 3.7469 3.5089 4.0284 6 3.6892 0.2180 0.2239 0.1834 0.2129 0.2443 0.2512 0.2200 6 0.2226 0 .0242 M 3 C94503 M 3 C94504 M 3 C94505 338.4 369.1 337.9 ** CONTINUED ON NEXT PAGE ** 0.0212 0.0174 0.0166 0.5472 0.5608 0.6419 0.2980 0.2408 0.2978 1.0263 1.0039 0.9777 3.7365 3.6000 3.9710 0.2770 0.2056 0.2056 TE 1.0345 0.8243 0.8398 0.8674 0.8535 0.9646 6 0.8974 0.0834 0.8372 0.8536 0.8053 0.8712 0.8758 1.0064 6 0.8749 0.0693 0.9773 0.7623 0.9357 TH 0.1499 0.1579 0.1279 0.1740 0.2713 0.1797 6 0.1768 0.0498 0.1590 0.2175 0.2488 0.2501 0.1673 0.1665 6 0.2015 0.0425 0.2099 0.2387 0.2039 00075 192 (?) ) i APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 2 TABLE INCLUDES: SEX=ALL ;GROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, O V - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP M 3 C94506 M 3 C94507 M 3 C94508 322.1 298.0 357.8 0.0149 0.0227 0.0158 0.5896 0.6810 0.5830 0.3057 0.2895 0.3090 1.0273 0.9773 0.9435 3.7907 3.7809 3.7597 0.2333 0.2345 0.2306 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 337.2 25.3 6 0.0181 0.0031 6 0.6006 0.0511 6 0.2901 0.0251 6 0.9927 0.0327 6 3.7731 0.1192 6 0.2311 0.0261 M 4 C94509 M 4 C94510 M 4 C94511 M 4 C94512 M 4 C94513 M 4 C94514 NUMBER IN GROUP : MEAN: STANDARD DEV: 301.9 282.3 308.5 365.6 330.7 349.8 6 323.1 31.3 0.0187 0.0169 0.0172 0.0103 0.0163 0.0180 6 0.0162 0.0030 0.7237 0.7107 0.6598 0.5406 0.6735 0.6675 6 0.6626 0.0650 0.3104 0.2646 0.2667 0.2596 0.2521 0.2597 6 0.2688 0.0210 1.0186 1.0436 0.9463 0.8704 1.0858 1.0531 6 1.0030 0.0801 3.3469 3.6665 4.0394 3.8273 4.0334 3.9165 6 3.8050 0.2642 0.1847 0.2521 0.2262 0.1983 0.1996 0.2547 6 0.2193 0.0297 M 5 C94515 M 5 C94516 M 5 C94517 M 5 C94518 331.8 295.2 337.9 316.7 ** CONTINUED ON NEXT PAGE ** 0.0164 0.0154 0.0215 0.0173 0.6596 0.6962 0.5814 0.6375 0.2502 0.2633 0.3260 0.2451 1.0271 1.0711 1.0788 0.9937 5.2612 5.4343 4.5995 6.1710 0.2043 0.2572 0.1874 0.2468 TE 0.8262 1.0808 0.8044 6 0.8978 0.1212 1.0110 0.9446 0.8613 0.8536 0.8871 0.8929 6 0.9084 0.0596 0.9127 1.0389 0.9183 0.8785 TH 0.1661 0.1752 0.2225 6 0.2027 0.0277 0.2105 0.1720 0.1917 0.1424 0.1810 0.1946 6 0.1820 0.0234 0.2177 0.2449 0.1482 0.2508 193 000757 APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 3 TABLE INCLUDES: SEX=ALL ;GROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET==ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, OV - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP M 5 C94519 M 5 C94520 317.4 325.4 0.0164 0.0149 0.6781 0.6688 0.2462 0.2464 0.9559 1.0317 4.5907 5.2590 0.2245 0.1457 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 320.7 15.0 6 0.0170 0.0023 6 0.6536 0.0404 6 0.2629 0.0316 6 1.0264 0.0465 6 5.2193 0.5890 6 0.2110 0.0412 M 6 C94521 M 6 C94522 M 6 C94524 M 6 C94525 M 6 C94526 NUMBER IN GROUP : MEAN: STANDARD DEV: 226.3 243.9 211.8 228.0 229.1 5 227.8 11.4 0.0193 0.0301 0.0271 0.0222 0.0260 5 0.0249 0.0042 0.8344 0.7940 0.9333 0.9426 0.8963 5 0.8801 0.0642 0.3018 0.3225 0.3005 0.3410 0.3382 5 0.3208 0.0193 1.0410 1.1868 1.1466 1.1100 1.2016 5 1.1372 0.0646 8.9473 7.9793 8.5011 8.5937 9.0522 5 8.6147 0.4240 0.2672 0.2106 0.2904 0.2992 0.2158 5 0.2566 0.0414 TE 0.8967 0.9232 6 0.9280 0.0567 1.3716 1.3164 1.1755 1.3661 1.3378 5 1.3135 0.0803 TH 0.1735 0.2056 6 0.2068 0.0401 0.2672 0.1640 0.1531 0.1818 0.2189 5 0.1970 0.0465 o o o Cl APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY W T (g) TT M 1 C94491 M 1 C94492 M 1 C94493 M 1 C94494 M 1 C94495 M 1 C94496 335.4 361.6 339.1 379.4 343.5 291.7 0.0066 0.0049 0.0052 0.0079 0.0055 0.0059 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 341.8 29.6 6 0.0060 0.0011 M 2 C94497 M 2 C94498 M 2 C94499 M 2 C94500 M 2 C94501 M 2 C94502 NUMBER IN GROUP : MEAN: STANDARD DEV: 345.7 321.0 384.3 320.2 332.4 323.8 6 337.9 24.7 0.0085 0.0079 0.0056 0.0067 0.0047 0.0084 6 0.0070 0.0016 M 3 C94503 M 3 C94504 M 3 C94505 338.4 369.1 337.9 0.0059 0.0063 0.0068 ** CONTINUED ON NEXT PAGE ** o o ^ 195 Covance 6329-224 3M T-6314.2 PAGE: 4 APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT M 3 C94506 M 3 C94507 M 3 C94508 322.1 298.0 357.8 0.0059 0.0075 0.0079 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 337.2 25.3 6 0.0067 0.0009 M 4 C94509 M 4 C94510 M 4 C94511 M 4 C94512 M 4 C94513 M 4 C94514 NUMBER IN GROUP: MEAN: STANDARD DEV: 301.9 282.3 308.5 365.6 330.7 349.8 6 323.1 31.3 0.0053 0.0068 0.0036 0.0069 0.0065 0.0087 6 0.0063 0.0017 M 5 C94515 M 5 C94516 M 5 C94517 M 5 C94518 331.8 295.2 337.9 316.7 ** CONTINUED ON NEXT PAGE ** 0.0076 0.0068 0.0061 0.0064 o o <7> 196 o Covance 6329-224 3M T-6314.2 PAGE: 5 0007 APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL ;GROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT M 5 C94519 M 5 C94520 317.4 325.4 0.0054 0.0085 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 320.7 15.0 6 0.0068 0.0011 M 6 C94521 M 6 C94522 M 6 C94524 M 6 C94525 M 6 C94526 NUMBER IN GROUP : MEAN: STANDARD DEV: 226.3 243.9 211.8 228.0 229.1 5 227.8 11.4 0.0066 0.0071 0.0090 0.0133 0.0075 5 0.0087 0.0027 Covance 6329-224 3M T-6314.2 PAGE: 6 APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, : KD - KIDNEY, LI - LIVER, ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, EP - EPIDIDYMIDES OV - OVARY TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP F 1 C94527 F 1 C94528 F 1 C94529 F 1 C94530 F 1 C94531 F 1 C94532 213.0 210.0 228.8 235.2 207.8 184.7 0.0336 0.0336 0.0447 0.0257 0.0315 0.0369 0.9396 0.9124 0.8404 0.8626 0.9408 1.0321 0.9451 0.9188 1.1477 0.9270 0.9884 0.9519 3.4895 3.7553 3.8407 3.5153 3.6097 3.5910 0.0546 0.0450 0.0620 0.0699 0.0632 0.0623 0.2611 0.1811 0.3014 0.2162 0.2252 0.2411 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 213.3 17.8 6 0.0343 0.0063 6 0.9213 0.0679 6 0.9798 0.0858 6 3.6336 0.1378 6 0.0595 0.0086 6 0.2377 0.0411 F 2 C94533 F 2 C94534 F 2 C94535 F 2 C94536 F 2 C94537 F 2 C94538 NUMBER IN GROUP : MEAN: STANDARD DEV: 200.3 197.5 217.3 204.4 223.4 192.6 6 205.9 12.0 0.0319 0.0332 0.0314 0.0393 0.0328 0.0315 6 0.0333 0.0030 1.0181 1.0439 0.9525 0.8906 0.9124 0.9711 6 0.9648 0.0592 0.9514 0.9704 0.8350 0.9791 1.0232 0.9799 6 0.9565 0.0640 4.1602 3.6231 3.5901 3.3572 3.6709 3.6193 6 3.6701 0.2643 0.0700 0.0699 0.0587 0.0707 0.0568 0.0568 6 0.0638 0.0070 0.2522 0.2272 0.2381 0.3101 0.2163 0.2236 6 0.2446 0.0344 F 3 C94539 F 3 C94540 F 3 C94541 217.8 174.2 234.2 ** CONTINUED ON NEXT PAGE ** 0.0500 0.0358 0.0363 0.9235 1.1118 0.8820 1.2341 1.0985 1.0754 3.8482 3.7938 3.7716 0.0668 0.0805 0.0595 0.2537 0.2255 0.2813 Covance 6329-224 3M T-6314.2 PAGE: 7 TE TH 0.2144 0.2863 0.2705 0.2315 0.2598 0.2773 6 0.2566 0.0280 0.2281 0.1962 0.2218 0.2820 0.2338 0.3698 6 0.2553 0.0627 0.2266 0.2269 0.2773 APPENDIX 6 Individual Organ-to-Body weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL D E ATH=T;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, : KD - KIDNEY, LI - LIVER, ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, EP - EPIDIDYMIDES OV - OVARY TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP F 3 C94542 F 3 C94543 F 3 C94544 242.5 167.9 185.5 0.0363 0.0290 0.0304 0.8267 1.1114 1.0995 1.0461 1.0372 1.1405 3.9152 3.8419 4.4349 0.0645 0.0587 0.0783 0.2264 0.1998 0.2519 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 203.7 32.0 6 0.0363 0.0075 6 0.9925 0.1298 6 1.1053 0.0733 6 3.9342 0.2503 6 0.0681 0.0093 6 0.2398 0.0285 F 4 C94545 F 4 C94546 F 4 C94547 F 4 C94548 F 4 C94549 F 4 C94550 187.2 219.7 237.1 186.8 207.7 187.0 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 204.3 21.1 F 5 C94551 F 5 C94552 F 5 C94553 F 5 C94554 171.1 201.4 206.3 184.4 ** CONTINUED ON NEXT PAGE ** 0.0313 0.0289 0.0335 0.0287 0.0314 0.0337 6 0.0312 0.0022 0.0386 0.0328 0.0329 0.0316 1.0060 0.9328 0.9067 1.1231 0.9903 1.0181 6 0.9962 0.0758 1.1020 1.0194 0.9835 1.0274 1.0764 0.9710 0.9526 1.0181 1.0318 1.0132 6 1.0105 0.0442 1.1350 1.1459 1.0708 1.0522 3.8315 4.3590 4.1498 3.6846 4.2154 4.1186 6 4.0598 0.2523 5.1380 5.0835 5.0851 4.7060 0.0656 0.0458 0.0564 0.0503 0.0788 0.0513 6 0.0580 0.0122 0.0753 0.0623 0.0527 0.0527 0.2479 0.2654 0.2357 0.2170 0.2477 0.2308 6 0.2407 0.0167 0.2640 0.2369 0.2214 0.1939 o o o Co 199 Covance 6329-224 3M T-6314.2 PAGE: 8 TE TH 0.2506 0.3313 0.2641 6 0.2628 0.0391 0.2517 0.2925 0.2525 0.3362 0.2137 0.2706 6 0.2695 0.0417 0.1847 0.1980 0.2952 0.2012 APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L DEATH=T;SUBSET=ALL : AD - ADRENAL : KD - KIDNEY, ORGAN ABBREVIATION: SP - SPLEEN, BR - BRAIN, EP - EPIDIDYMIDES LI - LIVER, OV - OVARY TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP F 5 C94555 F 5 C94556 192.5 206.1 0.0314 0.0377 1.0766 1.0139 1.1216 1.2633 5.2079 4.5820 0.0534 0.0655 0.2568 0.2951 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 193.6 13.9 6 0.0342 0.0032 6 1.0372 0.0438 6 1.1315 0.0744 6 4.9671 0.2573 6 0.0603 0.0092 6 0.2447 0.0353 F 6 C94557 F 6 C94558 F 6 C94559 F 6 C94560 F 6 C94561 F 6 C94562 NUMBER IN GROUP: MEAN: STANDARD DEV: 151.5 154.4 134.5 172.6 161.3 165.1 6 156.6 13.2 0.0251 0.0293 0.0261 0.0225 0.0383 0.0357 6 0.0295 0.0062 1.2825 1.3666 1.3369 1.2123 1.2195 1.2365 6 1.2757 0.0644 1.1207 1.1079 1.0488 0.9717 1.2182 1.1449 6 1.1021 0.0843 8.2434 8.2163 7.3432 8.6498 8.2650 6.6418 6 7.8932 0.7492 0.0500 0.0503 0.0380 0.0389 0.0494 0.0645 6 0.0485 0.0097 0.2075 0.2823 0.3193 0.3064 0.2555 0.2654 6 0.2727 0.0400 Covance 6329-224 3M T-6314.2 PAGE: 9 TE TH 0.4262 0.2533 6 0.2598 0.0915 0.2228 0.2756 0.3080 0.3747 0.2542 0.3136 6 0.2915 0.0530 c c o vi eS 200 0007 APPENDIX 6 individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E A T H = T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT F 1 C94527 F 1 C94528 F 1 C94529 F 1 C94530 F 1 C94531 F 1 C94532 213.0 210.0 228.8 235.2 207.8 184.7 0.0073 0.0067 0.0077 0.0057 0.0083 0.0095 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 213.3 17.8 6 0.0075 0.0013 F 2 C94533 F 2 C94534 F 2 C94535 F 2 C94536 F 2 C94537 F 2 C94538 NUMBER IN GROUP : MEAN: STANDARD DEV: 200.3 197.5 217.3 204.4 223.4 192.6 6 205.9 12.0 0.0098 0.0110 0.0090 0.0068 0.0086 0.0074 6 0.0088 0.0015 F 3 C94539 F 3 C94540 F 3 C94541 217.8 174.2 234.2 ** CONTINUED ON NEXT PAGE ** 0.0030EX 0.0125 0.0070 C/T 201 Covance 6329-224 3M T-6314.2 PAGE: 10 APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL; WEEKS=ALL DEATH=T; SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL - GROUP NUMBER BODY WT (g) TT F 3 C94542 F 3 C94543 F 3 C94544 242.5 167.9 185.5 0.0103 0.0114 0.0075 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 203.7 32.0 5 0.0098 0.0024 F 4 C94545 F 4 C94546 F 4 C94547 F 4 C94548 F 4 C94549 F 4 C94550 NUMBER IN GROUP: MEAN: STANDARD DEV: 187.2 219.7 237.1 186.8 207.7 187.0 6 204.3 21.1 0.0070 0.0133 0.0054 0.0089 0.0106 0.0088 6 0.0090 0.0028 F 5 C94551 F 5 C94552 F 5 C94553 F 5 C94554 171.1 201.4 206.3 184.4 ** CONTINUED ON NEXT PAGE ** 0.0074 0.0121 0.0115 0.0081 o o & 202 Covance 6329-224 3M T-6314.2 PAGE: 11 APPENDIX 6 Individual Organ-to-Body Weight Percentages Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL ;GROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY VT (g) TT F 5 C94555 F 5 C94556 192.5 206.1 0.0092 0.0073 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 193.6 13.9 6 0.0093 0.0021 F 6 C94557 F 6 C94558 F 6 C94559 F 6 C94560 F 6 C94561 F 6 C94562 NUMBER IN GROUP : MEAN: STANDARD DEV: 151.5 154.4 134.5 172.6 161.3 165.1 6 156.6 13.2 0.0100 0.0079 0.0088 0.0055 0.0113 0.0093 6 0.0088 0.0020 o o o c> 203 Covance 6329-224 3M T-6314.2 PAGE: 12 > APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 1 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, : KD - KIDNEY, LI - LIVER, ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, EP - EPIDIDYMIDES OV - OVARY TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP M 1 C94491 M 1 C94492 M 1 C94493 M 1 C94494 M 1 C94495 M 1 C94496 335.4 361.6 339.1 379.4 343.5 291.7 0.0290 0.0260 0.0293 0.0299 0.0189 0.0360 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 0.4902 0.4427 0.4543 0.4787 0.3842 0.4373 1.7113 1.6402 1.9030 1.7690 1.4570 1.4429 6.6515 6.8996 6.4565 6.7562 6.0595 4.7975 0.4394 0.3788 0.3903 0.3695 0.3696 0.3987 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 341.8 29.6 6 0.0282 0.0056 6 1.0000 0.0000 6 0.4479 0.0374 6 1.6539 0.1800 6 6.2701 0.7779 6 0.3911 0.0264 M 2 C94497 M 2 C94498 M 2 C94499 M 2 C94500 M 2 C94501 M 2 C94502 NUMBER IN GROUP : MEAN: STANDARD DEV: 345.7 321.0 384.3 320.2 332.4 323.8 6 337.9 24.7 0.0307 0.0308 0.0217 0.0271 0.0300 0.0283 6 0.0281 0.0035 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 6 1.0000 0.0000 0.4762 0.4632 0.3961 0.3992 0.4697 0.4471 6 0.4419 0.0357 1.3637 1.3741 1.6728 1.6832 1.4810 1.5536 6 1.5214 0.1402 6.2406 5.8628 6.8319 5.6477 5.6379 6.5240 6 6.1241 0.4911 0.4111 0.2878 0.3917 0.3682 0.4036 0.3563 6 0.3698 0.0453 M 3 C94503 M 3 C94504 M 3 C94505 338.4 369.1 337.9 ** CONTINUED ON NEXT PAGE ** 0.0388 0.0311 0.0259 1.0000 1.0000 1.0000 0.5446 0.4294 0.4639 1.8756 1.7902 1.5233 6.8284 6.4197 6.1865 0.5061 0.3667 0.3203 TE 1.6438 1.5022 1.4818 1.5496 1.3335 1.3973 6 1.4847 0.1098 1.5369 1.3391 1.4812 1.3132 1.4071 1.6298 6 1.4512 0.1214 1.7860 1.3593 1.4578 TH 0.2381 0.2878 0.2256 0.3108 0.4238 0.2603 6 0.2911 0.0722 0.2918 0.3413 0.4576 0.3769 0.2689 0.2696 6 0.3343 0.0739 0.3836 0.4257 0.3177 204 000768 APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 2 TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L DEATH=T; SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, OV - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL - GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP M 3 C94506 M 3 C94507 M 3 C94508 322.1 298.0 357.8 0.0252 0.0333 0.0272 1.0000 1.0000 1.0000 0.5185 0.4251 0.5299 1.7425 1.4352 1.6182 6.4297 5.5520 6.4484 0.3957 0.3444 0.3955 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 337.2 25.3 6 0.0303 0.0052 6 1.0000 0.0000 6 0.4852 0.0526 6 1.6641 0.1680 6 6.3108 0.4252 6 0.3881 0.0648 M 4 C94509 M 4 C94510 M 4 C94511 M 4 C94512 M 4 C94513 M 4 C94514 NUMBER IN GROUP : MEAN: STANDARD DEV: 301.9 282.3 308.5 365.6 330.7 349.8 6 323.1 31.3 0.0259 0.0238 0.0260 0.0191 0.0242 0.0270 6 0.0243 0.0028 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 6 1.0000 0.0000 0.4289 0.3724 0.4042 0.4802 0.3743 0.3890 6 0.4082 0.0411 1.4075 1.4684 1.4342 1.6102 1.6121 1.5777 6 1.5184 0.0923 4.6244 5.1589 6.1224 7.0802 5.9886 5.8677 6 5.8070 0.8457 0.2552 0.3547 0.3428 0.3669 0.2963 0.3816 6 0.3329 0.0479 TE 1.4013 1.5871 1.3796 6 1.4952 0.1644 1.3968 1.3291 1.3055 1.5790 1.3172 1.3378 6 1.3776 0.1037 TH 0.2817 0.2573 0.3817 6 0.3413 0.0659 0.2908 0.2420 0.2905 0.2635 0.2688 0.2916 6 0.2745 0.0201 M 5 C94515 M 5 C94516 M 5 C94517 M 5 C94518 331.8 295.2 337.9 316.7 ** CONTINUED ON NEXT PAGE ** 0.0249 0.0222 0.0369 0.0272 1.0000 1.0000 1.0000 1.0000 0.3794 0.3782 0.5606 0.3845 1.5571 1.5385 1.8555 1.5587 7.9757 7.8056 7.9109 9.6804 o o o 0.3097 0.3694 0.3223 0.3872 1.3836 1.4922 1.5794 1.3780 0.3300 0.3517 0.2550 0.3934 a 205  APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS Covance 6329-224 3M T-6314.2 PAGE: 3 TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E ATH=T;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, ov - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP M 5 C94519 M 5 C94520 317.4 325.4 0.0243 0.0223 1.0000 1.0000 0.3631 0.3684 1.4095 1.5425 6.7696 7.8629 0.3311 0.2178 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 320.7 15.0 6 0.0263 0.0055 6 1.0000 0.0000 6 0.4057 0.0763 6 1.5770 0.1476 6 8.0008 0.9384 6 0.3229 0.0593 M 6 C94521 M 6 C94522 M 6 C94524 M 6 C94525 M 6 C94526 NUMBER IN GROUP: MEAN: STANDARD DEV: 226.3 243.9 211.8 228.0 229.1 5 227.8 11.4 0.0231 0.0380 0.0290 0.0236 0.0290 5 0.0285 0.0060 1.0000 1.0000 1.0000 1.0000 1.0000 5 1.0000 0.0000 0.3617 0.4062 0.3220 0.3618 0.3773 5 0.3658 0.0305 1.2475 1.4946 1.2286 1.1776 1.3406 5 1.2978 0.1248 10.7227 10.0493 9.1088 9.1167 10.0991 5 9.8193 0.6974 0.3202 0.2653 0.3112 0.3174 0.2407 5 0.2909 0.0359 TE 1.3223 1.3803 6 1.4226 0.0946 1.6438 1.6579 1.2595 1.4492 1.4926 5 1.5006 0.1628 TH 0.2559 0.3074 6 0.3156 0.0545 0.3202 0.2065 0.1641 0.1929 0.2442 5 0.2256 0.0603 206 000771 APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R 0 U P = A L L ;W E E K S = A L L D E ATH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT M 1 C94491 M 1 C94492 M 1 C94493 M 1 C94494 M 1 C94495 M 1 C94496 335.4 361.6 339.1 379.4 343.5 291.7 0.0106 0.0089 0.0092 0.0141 0.0086 0.0085 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 341.8 29.6 6 0.0100 0.0021 M 2 C94497 M 2 C94498 M 2 C94499 M 2 C94500 M 2 C94501 M 2 C94502 NUMBER IN GROUP : MEAN: STANDARD DEV: 345.7 321.0 384.3 320.2 332.4 323.8 6 337.9 24.7 0.0157 0.0123 0.0103 0.0100 0.0075 0.0137 6 0.0116 0.0029 M 3 C94503 M 3 C94504 M 3 C94505 338.4 369.1 337.9 ** CONTINUED ON NEXT PAGE ** 0.0107 0.0112 0.0106 207 Covance 6329-224 3M T-6314.2 PAGE: 4 APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L DEATH=T; SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT M 3 C94506 M 3 C94507 M 3 C94508 322.1 298.0 357.8 0.0100 0.0110 0.0135 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 337.2 25.3 6 0.0112 0.0012 M 4 C94509 M 4 C94510 M 4 C94511 M 4 C94512 M 4 C94513 M 4 C94514 NUMBER IN GROUP : MEAN: STANDARD DEV: 301.9 282.3 308.5 365.6 330.7 349.8 6 323.1 31.3 0.0073 0.0096 0.0055 0.0129 0.0097 0.0130 6 0.0097 0.0030 M 5 C94515 M 5 C94516 M 5 C94517 M 5 C94518 331.8 295.2 337.9 316.7 ** CONTINUED ON NEXT PAGE ** 0.0115 0.0098 0.0105 0.0101 Covance 6329-224 3M T-6314.2 PAGE: 5 APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL ;GROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT M 5 C94519 M 5 C94520 317.4 325.4 0.0080 0.0128 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 320.7 15.0 6 0.0104 0.0016 M 6 C94521 M 6 C94522 M 6 C94524 M 6 C9452S M 6 C94526 NUMBER IN GROUP : MEAN: STANDARD DEV: 226.3 243.9 211.8 228.0 229.1 5 227.8 11.4 0.0079 0.0089 0.0097 0.0141 0.0084 5 0.0098 0.0025 Covance 6329-224 3M T-6314.2 PAGE: 6 APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL ;GROUP=ALL, WEEKS=ALL DEATH=T ;SUBSET=ALL : AD - ADRENAL : KD - KIDNEY, ORGAN ABBREVIATION: SP - SPLEEN, BR - BRAIN, EP - EPIDIDYMIDES LI - LIVER, OV - OVARY TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT <g) AD BR EP KD LI OV SP F 1 C94527 F 1 C94528 F 1 C94529 F 1 C94530 F 1 C94531 F 1 C94532 213.0 210.0 228.8 235.2 207.8 184.7 0.0357 0.0368 0.0532 0.0298 0.0335 0.0358 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 1.0058 1.0070 1.3657 1.0746 1.0505 0.9224 3.7139 4.1160 4.5702 4.0753 3.8368 3.4795 0.0581 0.0493 0.0737 0.0810 0.0672 0.0603 0.2779 0.1985 0.3586 0.2506 0.2393 0.2336 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 213.3 17.8 6 0.0375 0.0081 6 1.0000 0.0000 6 1.0710 0.1534 6 3.9653 0.3785 6 0.0650 0.0114 6 0.2598 0.0548 F 2 C94533 F 2 C94534 F 2 C94535 F 2 C94536 F 2 C94537 F 2 C94538 NUMBER IN GROUP : MEAN: STANDARD DEV: 200.3 197.5 217.3 204.4 223.4 192.6 6 205.9 12.0 0.0313 0.0318 0.0330 0.0441 0.0360 0.0324 6 0.0348 0.0049 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 6 1.0000 0.0000 0.9344 0.9296 0.8767 1.0994 1.1214 1.0091 6 0.9951 0.0990 4.0862 3.4707 3.7691 3.7698 4.0232 3.7270 6 3.8077 0.2222 0.0687 0.0669 0.0616 0.0794 0.0623 0.0585 6 0.0663 0.0075 0.2477 0.2176 0.2500 0.3482 0.2371 0.2303 6 0.2551 0.0471 F 3 C94539 F 3 C94540 F 3 C94541 217.8 174.2 234.2 ** CONTINUED ON NEXT PAGE ** 0.0542 0.0322 0.0411 1.0000 1.0000 1.0000 1.3363 0.9881 1.2193 4.1671 3.4124 4.2760 0.0723 0.0724 0.0675 0.2747 0.2029 0.3190 Covance 6329-224 3M T-6314.2 PAGE: 7 TE TH 0.2282 0.3138 0.3218 0.2684 0.2761 0.2686 6 0.2795 0.0342 0.2240 0.1879 0.2328 0.3167 0.2562 0.3808 6 0.2664 0.0704 0.2454 0.2041 0.3144 00077 210 APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E A TH=T;SUBSET=ALL : AD - ADRENAL, BR - BRAIN, EP - EPIDIDYMIDES : KD - KIDNEY, LI - LIVER, O V - OVARY ORGAN ABBREVIATION: SP - SPLEEN, TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP F 3 C94542 F 3 C94543 F 3 C94544 242.5 167.9 185.5 0.0439 0.0261 0.0276 1.0000 1.0000 1.0000 1.2654 0.9332 1.0373 4.7358 3.4569 4.0337 0.0781 0.0528 0.0712 0.2738 0.1797 0.2291 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 203.7 32.0 6 0.0375 0.0109 6 1.0000 0.0000 6 1.1299 0.1651 6 4.0137 0.5071 6 0.0691 0.0086 6 0.2466 0.0519 F 4 C94545 F 4 C94546 F 4 C94547 F 4 C94548 F 4 C94549 F 4 C94550 NUMBER IN GROUP : MEAN: STANDARD DEV: 187.2 219.7 237.1 186.8 207.7 187.0 6 204.3 21.1 0.0311 0.0309 0.0369 0.0255 0.0317 0.0331 6 0.0316 0.0037 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 6 1.0000 0.0000 1.0700 1.0409 1.0506 0.9065 1.0419 0.9952 6 1.0175 0.0597 3.8087 4.6732 4.5766 3.2806 4.2566 4.0454 6 4.1069 0.5175 0.0652 0.0491 0.0622 0.0448 0.0795 0.0504 6 0.0586 0.0130 0.2464 0.2845 0.2599 0.1932 0.2501 0.2267 6 0.2435 0.0310 F 5 C94551 F 5 C94552 F 5 C94553 F 5 C94554 171.1 201.4 206.3 184.4 ** CONTINUED ON NEXT PAGE ** 0.0351 0.0321 0.0335 0.0307 1.0000 1.0000 1.0000 1.0000 1.0299 1.1241 1.0888 1.0241 4.6625 4.9867 5.1703 4.5803 0.0684 0.0611 0.0536 0.0513 0.2396 0.2324 0.2251 0.1887 o o o Cl 211 Covance 6329-224 3M T-6314.2 PAGE: 8 TE TH 0.3032 0.2981 0.2402 6 0.2676 0.0440 0.2502 0.3136 0.2785 0.2993 0.2158 0.2658 6 0.2705 0.0352 0.1676 0.1942 0.3001 0.1959 APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: S E X = A L L ;G R O U P = A L L ;W E E K S = A L L D E A T H = T;SUBSET=ALL : AD - ADRENAL : KD - KIDNEY, ORGAN ABBREVIATION: SP - SPLEEN, BR - BRAIN, EP - EPIDIDYMIDES LI - LIVER, OV - OVARY TE - TESTIS, TH - THYMUS SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) AD BR EP KD LI OV SP F 5 C94555 F 5 C94556 192.5 206.1 0.0292 0.0372 1.0000 1.0000 1.0418 1.2459 4.8372 4.5191 0.0496 0.0646 0.2386 0.2910 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 193.6 13.9 6 0.0330 0.0029 6 1.0000 0.0000 6 1.0924 0.0845 6 4.7927 0.2526 6 0.0581 0.0077 6 0.2359 0.0329 F 6 C94557 F 6 C94558 F 6 C94559 F 6 C94560 F 6 C94561 F 6 C94562 NUMBER IN GROUP : MEAN: STANDARD DEV: 151.5 154.4 134.5 172.6 161.3 165.1 6 156.6 13.2 0.0196 0.0215 0.0195 0.0186 0.0314 0.0289 6 0.0232 0.0055 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 6 1.0000 0.0000 0.8739 0.8107 0.7846 0.8015 0.9990 0.9259 6 0.8659 0.0839 6.4275 6.0120 5.4928 7.1348 6.7776 5.3713 6 6.2027 0.7044 0.0390 0.0368 0.0284 0.0321 0.0405 0.0522 6 0.0382 0.0082 0.1618 0.2065 0.2389 0.2528 0.2096 0.2146 6 0.2140 0.0314 Covance 6329-224 3M T-6314.2 PAGE: 9 TE TH 0.3959 0.2498 6 0.2506 0.0856 0.1738 0.2017 0.2304 0.3091 0.2084 0.2536 6 0.2295 0.0474 o o q CD 212 APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;G ROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT F 1 C94527 F 1 C94528 F 1 C94529 F 1 C94530 F 1 C94531 F 1 C94532 213.0 210.0 228.8 235.2 207.8 184.7 0.0077 0.0074 0.0092 0.0066 0.0088 0.0092 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 213.3 17.8 6 0.0081 0.0011 F 2 C94533 F 2 C94534 F 2 C94535 F 2 C94536 F 2 C94537 F 2 C94538 NUMBER IN GROUP: MEAN: STANDARD DEV: 200.3 197.5 217.3 204.4 223.4 192.6 6 205.9 12.0 0.0097 0.0105 0.0095 0.0077 0.0094 0.0076 6 0.0091 0.0012 F 3 C94539 F 3 C94540 F 3 C94541 217.8 174.2 234.2 * CONTINUED ON NEXT PAGE ** 0.0033EX 0.0112 0.0079 Covance 6329-224 3M T-6314.2 PAGE: 10  r >j Q APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT F 3 C94542 F 3 C94543 F 3 C94544 242.5 167.9 185.5 0.0125 0.0103 0.0069 NUMBER IN GROUP: MEAN: STANDARD DEV: 6 203.7 32.0 5 0.0098 0.0023 F 4 C94545 F 4 C94546 F 4 C94547 F 4 C94548 F 4 C94549 F 4 C94550 NUMBER IN GROUP: MEAN: STANDARD DEV: 187.2 219.7 237.1 186.8 207.7 187.0 6 204.3 21.1 0.0070 0.0143 0.0060 0.0080 0.0107 0.0087 6 0.0091 0.0030 F 5 C94551 F 5 C94552 F 5 C94553 F 5 C94554 171.1 201.4 206.3 184.4 ** CONTINUED ON NEXT PAGE ** 0.0067 0.0119 0.0117 0.0079 214 Covanee 6329-224 3M T-6314.2 PAGE: 11 I II t APPENDIX 6 Individual Organ-to-Brain Weight Ratios Terminal Sacrifice 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS TABLE INCLUDES: SEX=ALL ;GROUP=ALL;WEEKS=ALL DEATH=T ;SUBSET=ALL ORGAN ABBREVIATION: TT - THYROID/PARATHYR SEX DOSE ANIMAL TERMINAL GROUP NUMBER BODY WT (g) TT F 5 C94555 F 5 C94556 192.5 206.1 0.0085 0.0072 NUMBER IN GROUP : MEAN: STANDARD DEV: 6 193.6 13.9 6 0.0090 0.0023 F 6 C94557 F 6 C94558 F 6 C94559 F 6 C94560 F 6 C94561 F 6 C94562 NUMBER IN GROUP: MEAN: STANDARD DEV: 151.5 154.4 134.5 172.6 161.3 165.1 6 156.6 13.2 0.0078 0.0058 0.0066 0.0045 0.0093 0.0075 6 0.0069 0.0017 Covance 6329-224 3M T-6314.2 PAGE: 12 6/-/-.000 215 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 1 ANIMAL NUMBER: C94491 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 335.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:01 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0612 2.1109 1.0347 3.6123 14.0407 .9276 3.4698 .5026 .0223 .0182 % .6294 % .3085 % 1.0770 % 4.1863 % .2766 % 1.0345 % .1499 % .0066 % .0290 1.0000 .4902 1.7113 6.6515 .4394 1.6438 .2381 .0106 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATI O N ,-MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUT E ,-MINIMAL P t APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 2 ANIMAL NUMBER: C94491 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH:!: 32 STUDY WEEK OIFF DEATH: 5 TERMINAL BODY WEIGHT: 335.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:01 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) o o o 217 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 3 ANIMAL NUMBER: C94492 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 361.6 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:46 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0515 1.9843 .8785 3.2546 13.6908 .7517 2.9808 .5711 .0177 .0142 % .5488 % .2429 % .9001 % 3.7862 % .2079 % .8243 % .1579 % .0049 % .0260 1.0000 .4427 1.6402 6.8996 .3788 1.5022 .2878 .0089 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -V ACUOLATION,-MINIMAL APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 4 ANIMAL NUMBER: C94492 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 361.6 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:46 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR), KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW. FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 0007S3 219 I* APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 5 ANIMAL NUMBER: C94493 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 339.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:30 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0563 1.9218 .8731 3.6572 12.4081 .7500 2.8478 .4336 .0177 .0166 % .5667 % .2575 % 1.0785 % 3.6591 % .2212 % .8398 % .1279 % .0052 % .0293 1.0000 .4543 1.9030 6.4565 .3903 1.4818 .2256 .0092 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY STOMACH, GL (ST) : -DARK FOCUS (I)/AREA(S) ; MUCOSA: 1 MM IN DIAMETER GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN MULTIPLE BROWN AREAS, UP TO BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL ADRENAL, CORTEX (AC) : -VACUOLATION, -MINIMAL STOMACH, GL (ST) : >UNREMARKABLE 000 GO 2 2 0 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 6 ANIMAL NUMBER: C94493 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 339.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:30 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA (MA), TESTIS (TE), STOMACH, NONGL (SU) o o 0 GO 01 221 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 7 ANIMAL NUMBER: C94494 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 379.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:02 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0634 2.1238 1.0167 3,7571 14.3488 .7848 3.2911 .6600 .0299 .0167 % .5598 % .2680 % .9903 % 3.7820 % .2069 % .8674 % .1740 % .0079 % .0299 1.0000 .4787 1.7690 6.7562 .3695 1.5496 .3108 .0141 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -DEGENERATION, TUBULAR,-MINIMAL -HYALINE DROPLETS, TUBULAR EPITHELIUM,-SLIGHT LIVER (LI) : -INFLAMMATION, SUBACU T E ,-MINIMAL ADRENAL, CORTEX (AC) : -VACUOLATION, -MINIMAL o qo GC o 222 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 8 ANIMAL NUMBER: C94494 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 379.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:02 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR(MN), SKIN (SK), URINARY BLADDER (UB),PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA (MA), TESTIS (TE) o o GO 223 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 9 ANIMAL NUMBER: C94495 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 DATE AND TIME OF NECROPSY: 07/13/98 8: 26 PROSECTOR: DONIA MEYER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 343..5 GRAMS RECORDER: JODI THIEREN WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0416 2.1985 .8446 3.2033 13.3219 .8125 2.9317 .9318 .0189 .0121 % .6400 % .2459 % .9325 % 3.8783 % .2365 % .8535 % .2713 % .0055 % .0189 1.0000 .3842 1.4570 6.0595 .3696 1.3335 .4238 .0086 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY O B SERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL o o o 05 00 224 III APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 10 ANIMAL NUMBER: C94495 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 343.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:26 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL), LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) o o o GS C5 225 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 11 ANIMAL NUMBER: C94496 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 291.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:34 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0725 2.0137 .8805 2.9056 9.6607 .8029 2.8137 .5241 .0172 .0249 % .6903 % .3019 % .9961 % 3.3119 % .2752 % .9646 % .1797 % .0059 % .0360 1.0000 .4373 1.4429 4.7975 .3987 1.3973 .2603 .0085 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, S U B ACU T E ,-MINIMAL oo o n J o 226 Ii APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 12 ANIMAL NUMBER: C94496 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 291.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:34 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 000791 227 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 13 ANIMAL NUMBER: C94497 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 345.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:23 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0579 1.8832 .8967 2.5682 11.7523 .7741 2.8943 .5496 .0295 .0167 % .5447 % .2594 % .7429 % 3.3996 % .2239 % .8372 % .1590 % .0085 % .0307 1.0000 .4762 1.3637 6.2406 .4111 1.5369 .2918 .0157 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -INFLAMMATION, C H R O N I C ,-MINIMAL LIVER (LI) : -INFLAMMATION, SUBACU T E ,-MINIMAL o to 228 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 14 ANIMAL NUMBER: C94497 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 345.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:23 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR),KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) ,BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB),PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 15 ANIMAL NUMBER: C94498 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 321.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:20 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0630 2.0462 .9478 2.8116 11.9965 .5888 2.7400 .6983 .0252 .0196 % .6374 % .2953 % .8759 % 3.7372 % .1834 % .8536 % .2175 % .0079 % .0308 1.0000 .4632 1.3741 5.8628 .2878 1.3391 .3413 .0123 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL 000734 230 APPENDIX 6 Individual Animal Pathology Data C o v a n c e 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 16 ANIMAL NUMBER: C94498 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 321.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:20 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR),KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP), CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB),PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 17 ANIMAL NUMBER: C94499 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 384.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:48 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0454 2.0893 .8275 3.4950 14.2738 .8183 3.0946 .9560 .0216 .0118 % .5437 % .2153 % .9094 % 3.7142 % .2129 % .8053 % .2488 % .0056 % .0217 1.0000 .3961 1.6728 6.8319 .3917 1.4812 .4576 .0103 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL KIDNEY (KD) : -INFLAMMATION, CHRONIC,-SLIGHT LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL o c p si Ci 232 (i i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 18 ANIMAL NUMBER: C94499 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 384.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:48 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR(MN), SKIN (SK), URINARY BLADDER (UB),PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) c c 233 v! APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 19 ANIMAL NUMBER: C94500 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 320.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:29 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (T T ) .0575 2.1243 .8480 3.5756 11.9975 .7821 2.7896 .8007 .0213 .0180 % .6634 % .2648 % 1.1167 % 3.7469 % .2443 % .8712 % .2501 % .0067 % .0271 1.0000 .3992 1.6832 5.6477 .3682 1.3132 .3769 .0100 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -HYALINE DROPLETS, TUBULAR EPITHELIUM,-MINIMAL -PYELITIS,-MODERATE LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL ADRENAL, CORTEX (AC) : -VACUOLATION,-MINIMAL o c q "Vi Q 234 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 20 ANIMAL NUMBER: C94500 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH:l: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 320.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:29 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA (MA) , TESTIS (TE) o oo 235 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 21 ANIMAL NUMBER: C94501 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 332.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:14 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0621 2.0688 .9718 3.0639 11.6636 .8350 2.9111 .5562 .0155 .0187 % .6224 % .2924 % .9218 % 3.5089 % .2512 % .8758 % .1673 % .0047 % .0300 1.0000 .4697 1.4810 5.6379 .4036 1.4071 .2689 .0075 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -HYALINE DROPLETS, TUBULAR EPITHELIUM,-MINIMAL 00080 236 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 22 ANIMAL NUMBER: C94501 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH:[: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 332.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:14 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) OOOSOl 237 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 23 ANIMAL NUMBER: C94502 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 323.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:18 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0565 1.9994 .8940 3.1062 13.0440 .7124 3.2586 .5391 .0273 .0174 % .6175 % .2761 % .9593 % 4.0284 % .2200 % 1.0064 % .1665 % .0084 % .0283 1.0000 .4471 1.5536 6.5240 .3563 1.6298 .2696 .0137 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN EYE (EY) : -VASCULARIZATION, CORNEAL,-MINIMAL BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL 000802 238 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 24 ANIMAL NUMBER: C94502 SEX: MALE DATE OF DEATH: 07/13/98 STUDY DAY OF DATE AND TIME OF NECROPSY: 07/13/98 8:18 POST-FIX WEIGHER: NOT AVAILABLE DOSE GROUP: 2 SACRIFICE STATUS: DEATH:l ; 32 OS Ti. UU DU YI WVYCEj EEjKIx. KOJFC UDlEATH: 5 PROSECTOR: NANCY DIEDRICH PATHOLOGIST: HAMP, BRUNER SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 323.8 GRAMS RECORDER: JODI THIEREN WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 00080 C.J 2 3 9 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 25 ANIMAL NUMBER: C94503 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 338.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:27 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0719 1.8517 1.0084 3.4730 12.6442 .9372 3.3072 .7104 .0198 .0212 % .5472 % .2980 % 1.0263 % 3.7365 % .2770 % .9773 % .2099 % .0059 % .0388 1.0000 .5446 1.8756 6.8284 .5061 1.7860 .3836 .0107 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY SKIN (SK) : -CRUSTED A R E A ( S ) ; BILATERAL, SHOULDER REGION: TWO DRY, RED CRUSTED AREAS, LEFT IS 12 X 9 MM (CAP 21), RIGHT IS 10 X 4 MM (CAP 22) GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BRAIN (BR) : -V A CUOLATION,-MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL SKIN (SK) : -INFLAMMATION, CHRONIC-ACTIVE,-MODERATE > N O T E :>WITH ACANTHOSIS. 000804 240 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 26 ANIMAL NUMBER: C94503 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 338.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:27 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , URINARY BLADDER (UB) , PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 000805 241 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 27 ANIMAL NUMBER: C94504 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 369.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:13 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0644 2.0698 .8887 3.7053 13.2875 .7590 2.8135 .8812 .0231 .0174 % .5608 % .2408 % 1.0039 % 3.6000 % .2056 % .7623 % .2387 % .0063 % .0311 1.0000 .4294 1.7902 6.4197 .3667 1.3593 .4257 .0112 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL ADRENAL, CORTEX (AC) : -VACUOLATION, -MINIMAL OOOSO 242 Vj APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 28 ANIMAL NUMBER: C94504 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH:I: 32 STUDY WEEK OF DEATH: 5 DATE AND TIME OF NECROPSY: 07/13/98 11:13 PROSECTOR: DONIA MEYER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 369.1 GRAMS RECORDER: JODI THIEREN WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), URINARY BLADDER (UB) , PROSTATE (PR), SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA (MA), TESTIS (TE) 00080 Vi 243 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 29 ANIMAL NUMBER: C94505 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 337.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:38 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0562 2.1689 1.0062 3.3038 13.4179 .6947 3.1618 .6890 .0230 .0166 % .6419 % .2978 % .9777 % 3.9710 % .2056 % .9357 % .2039 % .0068 % .0259 1.0000 .4639 1.5233 6.1865 .3203 1.4578 .3177 .0106 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN EYE (EY) : -ONE EXAMINED,-PRESENT >NOTE:>ONE OF PAIR PRESENT. ooosos 244 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 30 ANIMAL NUMBER: C94505 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 337.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:38 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB) ,PROSTATE (PR) , SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 000809 245 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 31 ANIMAL NUMBER: C94506 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 322.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:53 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) ABSOLUTE ORGAN WEIGHT (GRAMS) .0479 1.8990 .9847 3.3090 12.2100 .7515 2.6611 .5349 .0189 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0149 % .5896 % .3057 % 1.0273 % 3.7907 % .2333 % .8262 % .1661 % .0059 % ORGAN TO BRAIN WEIGHT RATIO .0252 1.0000 .5185 1.7425 6.4297 .3957 1.4013 .2817 .0100 ORGAN STATUS WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN EYE (EY) : -ONE EXAMINED,-PRESENT > N O T E :>ONE OF PAIR PRESENT. BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL -NECROSIS,-MINIMAL ADRENAL, CORTEX (AC) : -VACUOLATION,-MINIMAL OTSOOO 246 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 32 ANIMAL NUMBER: C94506 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 322.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:53 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA (MA), TESTIS (TE) Q0311 O 247 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 33 ANIMAL NUMBER: C94507 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 298.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:41 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0676 2.0294 .8627 2.9125 11.2672 .6989 3.2209 .5221 .0224 .0227 % .6810 % .2895 % .9773 % 3.7809 % .2345 % 1.0808 % .1752 % .0075 % .0333 1.0000 .4251 1.4352 5.5520 .3444 1.5871 .2573 .0110 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, S U B A C U T E ,-MINIMAL 000812 248 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 34 ANIMAL NUMBER: C94507 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 298.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:41 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, G L (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 000813 249 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 35 ANIMAL NUMBER: C94508 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 357.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:23 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) ABSOLUTE ORGAN WEIGHT (GRAMS) .0567 2.0861 1.1055 3.3758 13.4521 .8250 2.8780 .7962 .0282 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0158 % .5830 % .3090 % .9435 % 3.7597 % .2306 % .8044 % .2225 % .0079 % ORGAN TO BRAIN WEIGHT RATIO .0272 1.0000 .5299 1.6182 6.4484 .3955 1.3796 .3817 .0135 ORGAN STATUS WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL 000814 250 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 36 ANIMAL NUMBER: C94508 SEX: MALE DATE OF DEATH: 07/13/98 STUDY DAY OF DATE AND TIME OF NECROPSY: 07/13/98 11:23 POST-FIX WEIGHER: NOT AVAILABLE DOSE GROUP: 3 SACRIFICE STATUS: DEATH:I: 32 STUDY WEEK OF DEATH: 5 PROSECTOR: JAMES T. CALLEN PATHOLOGIST: HAMP, BRUNER SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 357.8 GRAMS RECORDER: JODI THIEREN WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 000815 251 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLU0R00CTANESULF0NAMID0 ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 37 ANIMAL NUMBER: C94509 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 301.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:52 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0566 2.1850 .9372 3.0753 10.1043 .5576 3.0521 .6354 .0160 .0187 % .7237 % .3104 % 1.0186 % 3.3469 % .1847 % 1.0110 % .2105 % .0053 % .0259 1.0000 .4289 1.4075 4.6244 .2552 1.3968 .2908 .0073 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -CYST, -MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MINIMAL 000816 252 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 38 ANIMAL NUMBER: C94509 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 301.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:52 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 00081 253 APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 39 ANIMAL NUMBER: C94510 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 282.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:36 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0478 2.0063 .7471 2.9461 10.3504 .7116 2.6666 .4856 .0192 .0169 % .7107 % .2646 % 1.0436 % 3.6665 % .2521 % .9446 % .1720 % .0068 % .0238 1.0000 .3724 1.4684 5.1589 .3547 1.3291 .2420 .0096 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -INFLAMMATION, SUBAC U T E ,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR, -MINIMAL 000818 254 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 40 ANIMAL NUMBER: C94510 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH:: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 282.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:36 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG),AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), URINARY BLADDER (UB),PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 000819 255 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 41 ANIMAL NUMBER: C94511 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 308.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:45 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0530 2.0354 .8228 2.9192 12.4616 .6977 2.6572 .5913 .0111 .0172 % .6598 % .2667 % .9463 % 4.0394 % .2262 % .8613 % .1917 % .0036 % .0260 1.0000 .4042 1.4342 6.1224 .3428 1.3055 .2905 .0055 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL KIDNEY (KD) : -INFLAMMATION, CHR O N I C ,-MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SLIGHT ADRENAL, CORTEX (AC) : -VACUOLATION, -MINIMAL 000820 256 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLU0R00CTANESULF0NAMID0 ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 42 ANIMAL NUMBER: C94511 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 308.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:45 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB) ,PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA (MA), TESTIS (TE) 000821 257 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 43 ANIMAL NUMBER: C94512 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 365.6 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:44 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0377 1.9763 .9490 3.1823 13.9926 .7251 3.1206 .5207 .0254 .0103 % .5406 % .2596 % .8704 % 3.8273 % .1983 % .8536 % .1424 % .0069 % .0191 1.0000 .4802 1.6102 7.0802 .3669 1.5790 .2635 .0129 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY ADRENAL, CORTEX (AC) : -SMALL; RIGHT: 3 X 2 X 1 MM 2 MM) GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN (FOR COMPARISON, LEFT IS 5 X 3 X BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, ADRENAL, CORTEX (AC) : >UNREMARKABLE CENTRILOBULAR,-MINIMAL APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 44 ANIMAL NUMBER: C94512 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 365.6 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:44 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) (MA) , THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA (MA), TESTIS (TE) 00082 259 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 45 ANIMAL NUMBER: C94513 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 330.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:24 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) ABSOLUTE ORGAN WEIGHT (GRAMS) .0538 2.2273 .8336 3.5906 13.3383 .6600 2.9338 .5986 .0216 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0163 % .6735 % .2521 % 1.0858 % 4.0334 % .1996 % .8871 % .1810 % .0065 % ORGAN TO BRAIN WEIGHT RATIO .0242 1.0000 .3743 1.6121 5.9886 .2963 1.3172 .2688 .0097 ORGAN STATUS WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MINIMAL 0008 I'W. M- 2 6 0 APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 46 ANIMAL NUMBER: C94513 SEX: MALE DATE OF DEATH: 07/13/98 STUDY DAY OF DATE AND TIME OF NECROPSY: 07/13/98 11:24 POST-FIX WEIGHER: NOT AVAILABLE DOSE GROUP: 4 SACRIFICE STATUS: DEATH:1: 32 STUDY WEEK OF DEATH: 5 PROSECTOR: JILL PAUS PATHOLOGIST: HAMP, BRUNER SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 330.7 GRAMS RECORDER: JODI THIEREN WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), URINARY BLADDER (UB) , PROSTATE (PR), SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 00 i\3 Q\ 261 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 47 ANIMAL NUMBER: C94514 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 349.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:22 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/ PARATHYR (TT) .0630 2.3348 .9083 3.6837 13.7000 .8910 3.1234 .6808 .0304 .0180 % .6675 % .2597 % 1.0531 % 3.9165 % .2547 % .8929 % .1946 % .0087 % .0270 1.0000 .3890 1.5777 5.8677 .3816 1.3378 .2916 .0130 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY O B S E R V A T I C )N S HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-SLIGHT -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR, -MINIMAL APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 48 ANIMAL NUMBER: C94514 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 349.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:22 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), URINARY BLADDER (UB) , PROSTATE (PR), SEMINAL VESICLES (SV) , EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 000827 263 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 49 ANIMAL NUMBER: C94515 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 331.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:25 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0545 2.1887 .8303 3.4080 17.4565 .6778 3.0282 .7223 .02 52 .0164 % .6596 % .2502 % 1.0271 % 5.2612 % .2043 % .9127 % .2177 % .0076 % .0249 1.0000 .3794 1.5571 7.9757 .3097 1.3836 .3300 .0115 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, SUBAC U T E ,-SLIGHT -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATE -NECROSIS, -MINIMAL ooos tN3 00 264 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 50 ANIMAL NUMBER: C94515 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 331.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:25 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) o o o GO M 265 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE , T-6314) IN RATS PAGE: 51 ANIMAL NUMBER: C94516 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH : 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 295-.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8: 27 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) ABSOLUTE ORGAN WEIGHT (GRAMS) .0456 2.0552 .7772 3.1619 16.0421 .7592 3.0667 .7229 .0201 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0154 % .6962 % .2633 % 1.0711 % 5.4343 % .2572 % 1.0389 % .2449 % .0068 % ORGAN TO BRAIN WEIGHT RATIO .0222 1.0000 .3782 1.5385 7.8056 .3694 1.4922 .3517 .0098 ORGAN STATUS WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATE 000830 266 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-63I4) IN RATS PAGE: 52 ANIMAL NUMBER: C94516 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 295.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:27 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB),PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) TCSOOO 267 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 53 ANIMAL NUMBER: C94517 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 337.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:57 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0725 1.9646 1.1014 3.6453 15.5417 .6331 3.1028 .5009 .0207 .0215 % .5814 % .3260 % 1.0788 % 4.5995 % .1874 % .9183 % .1482 % .0061 % .0369 1.0000 .5606 1.8555 7.9109 .3223 1.5794 .2550 .0105 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : - V A C U O L A T I O N ,- M I N I M A L LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR, -MODERATE -VACUOLATION, HEPATOCELLULAR, -MINIMAL APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 54 ANIMAL NUMBER: C94517 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 337.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:57 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN. MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 00083 CJ 269 * APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 55 ANIMAL NUMBER: C94518 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 316.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:19 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0549 2.0189 .7763 3.1469 19.5437 .7817 2.7821 .7942 .0203 .0173 % .6375 % .2451 % .9937 % 6.1710 % .2468 % .8785 % .2508 % .0064 % .0272 1.0000 .3845 1.5587 9.6804 .3872 1.3780 .3934 .0101 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -DEGENERATION, TUB U L A R ,-MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR, -MODERATELY SEVERE -VACUOLATION, HEPATOCELLULAR,-MINIMAL 00083 270 fi i i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 56 ANIMAL NUMBER: C94518 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 316.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:19 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR), KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU) , JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CE C U M (CE) , COLON (CO) , RECTUM (RE), THYROID (TY), PARATHYROID <PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL C ORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) C8000 C/I 271 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 57 ANIMAL NUMBER: C94519 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 317.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:16 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0522 2.1524 .7815 3.0339 14.5708 .7127 2.8462 .5508 .0172 .0164 % .6781 % .2462 % .9559 % 4.5907 % .2245 % .8967 % .1735 % .0054 % .0243 1.0000 .3631 1.4095 6.7696 .3311 1.3223 .2559 .0080 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, S U B ACUT E ,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATE 00083 & 272 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 58 ANIMAL NUMBER: C94519 SEX: MALE DATE OF DEATH: 07/13/98 STUDY DAY OF DATE AND TIME OF NECROPSY: 07/13/98 11:16 POST-FIX WEIGHER: NOT AVAILABLE DOSE GROUP : 5 SACRIFICE STATUS: DEATH:i. 32 So xTuUiDj iY WnEEiE&rKk OFr DEATH: 5 PROSECTOR: NANCY DIEDRICH PATHOLOGIST: HAMP, BRUNER SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 317.4 RECORDER: JODI THIEREN WEIGHER: MATTHEW AXTMAN GRAMS THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR), KIDNEY <KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 000S3 273 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 59 ANIMAL NUMBER: C94520 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 325.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:50 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0485 2.1764 .8017 3.3572 17.1128 .4740 3.0040 .6690 .0278 .0149 % .6688 % .2464 % 1.0317 % 5.2590 % .1457 % .9232 % .2056 % .0085 % .0223 1.0000 .3684 1.5425 7.8629 .2178 1.3803 .3074 .0128 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, S U B A C U T E ,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR, -MODERATELY SEVERE PANCREAS (PA) : -INFLAMMATION, C H R O N I C ,-SLIGHT -HEMORRHAGE, -MINIMAL 00083 00 274 :i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 60 ANIMAL NUMBER: C94520 SEX: MALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH:1: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 325.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:50 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN <SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU) , JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , C E C U M (CE) , COLON (CO) , RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR(MN) , SKIN (SK) , URINARY BLADDER (UB),PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 00083 cD 275 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 61 ANIMAL NUMBER: C94521 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 226.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:03 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) ABSOLUTE ORGAN WEIGHT (GRAMS) .0436 1.8883 .6830 2.3557 20.2477 .6046 3.1040 .6047 .0149 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0193 % .8344 % .3018 % 1.0410 % 8.9473 % .2672 % 1.3716 % .2672 % .0066 % ORGAN TO BRAIN WEIGHT RATIO .0231 1.0000 .3617 1.2475 10.7227 .3202 1.6438 .3202 .0079 ORGAN STATUS WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY LIVER (LI) : -LARGE; ALL LOBES: THICKENED STOMACH, GL (ST) : -RED FOCUS (I)/AREA(S) ; MUCOSA: DIAMETER GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -ANIMAL THIN SINGLE FOCUS, 1 MM IN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, SEVERE LN, MESENTERIC (MS) : -HEMORRHAGE,-MINIMAL STOMACH, GL (ST) : UNREMARKABLE CENTRILOBULAR,-MODERATELY APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLU0R00CTANESULF0NAMID0 ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 62 ANIMAL NUMBER: C94521 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 226.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:03 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, NQNGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , C E C U M (CE) , COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) (SB), THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 000841 277 APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 63 ANIMAL NUMBER: C94522 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 243.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:17 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0735 1.9366 .7866 2.8945 19.4615 .5137 3.2106 .4000 .0172 .0301 % .7940 % .3225 % 1.1868 % 7.9793 % .2106 % 1.3164 % .1640 % .0071 % .0380 1.0000 .4062 1.4946 10.0493 .2653 1.6579 .2065 .0089 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY LIVER (LI) : -LARGE; ALL LOBES, THICKENED -LIGHT FOCUS(I)/AREA(S): ALL LOBES: MULTIPLE TO 3 X 4 MM; COLLECTED ON ROUTINE SECTION -DIFFUSELY DARK; ALL LOBES: BROWN LN, MANDIBULAR (MN) : -MOTTLED; BILATERAL: RED AND TAN TAN AREAS, UP GENERAL COMMENT (GC) : -MALOCCLUSION; BILATERAL UPPER INCISORS -BONE MARROW SMEAR TAKEN -DISCHARGE-OCULAR; BILATERAL: DARK RED AND DRY BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, -NECROSIS,-MODERATE CENTRILOBULAR,-SEVERE LN, MANDIBULAR (MN) : TISSUE MISSING NOTE: MANDIBULAR LYMPH NODE MISSING IN RETRIM. 000S42 278 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 64 ANIMAL NUMBER: C94522 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 243.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:17 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS) , SALIV GL, MANDIB (SG) , SKIN (SK) , URINARY BLADDER (UB) , PROSTATE (PR) , SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) 000843 279 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 65 ANIMAL NUMBER: C94523 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: UNSCHEDULED (D) DATE OF DEATH: 07/06/98 STUDY DAY OF DEATH: 25 STUDY WEEK OF DEATH: 4 TERMINAL BODY WEIGHT: NOT ENTERED DATE AND TIME OF NECROPSY: 07/06/98 12:17 PROSECTOR: TODD ACKER RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: NOT AVAILABLE *** ORGAN WEIGHTS WERE NOT RECORDED *** NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -MALOCCLUSION; BILATERAL, UPPER INCISORS -DISCHARGE-NASAL; DARK RED AND DRY MATERIAL BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, -NECROSIS,-MODERATELY SEVERE CENTRILOBULAR,-SEVERE THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) ,KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) ,MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE,STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB),PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 0008 ki.3 280 I)> t APPENDIX 6 Individual Animal Pathology Data Covante 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 66 ANIMAL NUMBER: C94524 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 211.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:57 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) ABSOLUTE ORGAN WEIGHT (GRAMS) .0573 1.9767 .6364 2.4286 18.0054 .6151 2.4897 .3243 .0191 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0271 % .9333 % .3005 % 1.1466 % 8.5011 % .2904 % 1.1755 % .1531 % .0090 % ORGAN TO BRAIN WEIGHT RATIO .0290 1.0000 .3220 1.2286 9.1088 .3112 1.2595 .1641 .0097 ORGAN STATUS WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY SEMINAL VESICLES (SV) : -SMALL; BILATERAL: EACH IS 7 X 4 X 1 MM GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BRAIN <BR) : - V A C U O L A T I O N ,- M I N I M A L LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SEVERE -NECROSIS,-MODERATE SEMINAL VESICLES (SV) : -SECRETION, DECREASED,-MODERATE oo o 03 H-* C/I 281 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 67 ANIMAL NUMBER: C94524 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 211.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:57 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL), LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) o o o GO o 282 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 68 ANIMAL NUMBER: C94525 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 228.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:54 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0507 2.1492 .7775 2.5308 19.5937 .6822 3.1146 .4146 .0303 .0222 % .9426 % .3410 % 1.1100 % 8.5937 % .2992 % 1.3661 % .1818 % .0133 % .0236 1.0000 .3618 1.1776 9.1167 .3174 1.4492 .1929 .0141 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY ADRENAL, CORTEX (AC) : -DIFFUSELY RED; BILATERAL GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATELY SEVERE ADRENAL, CORTEX (AC) : >UNREMARKABLE 000847 283 >i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 69 ANIMAL NUMBER: C94525 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 228.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:54 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY <KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU) , TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) (MA) , THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, MEDULLA (MA), TESTIS (TE) 000848 284 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 70 ANIMAL NUMBER: C94526 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 229.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:24 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) EPIDIDYMIDES (EP) KIDNEY (KD) LIVER (LI) SPLEEN (SP) TESTIS (TE) THYMUS (TH) THYROID/PARATHYR (TT) .0596 2.0535 .7748 2.7529 20.7386 .4943 3.0650 .5015 .0172 .0260 % .8963 % .3382 % 1.2016 % 9.0522 % .2158 % 1.3378 % .2189 % .0075 % .0290 1.0000 .3773 1.3406 10.0991 .2407 1.4926 .2442 .0084 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY STOMACH, GL (ST) : -DARK FOCUS(I)/AREA(S); MUCOSA: IS 2 X 1 MM GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN TWO DARK BROWN AREAS, EACH BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, SEVERE STOMACH, GL (ST) : -EROSION,-SLIGHT CENTRILOBULAR,-MODERATELY 00084 285 *i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 71 ANIMAL NUMBER: C94526 SEX: MALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 229.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:24 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , TESTIS (TE) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), TESTIS (TE) 000850 286 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 72 ANIMAL NUMBER: C94527 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 213.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:48 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0715 2.0013 2.0130 7.4326 .1162 .5561 .4566 .0155 .0336 % .9396 % .9451 % 3.4895 % .0546 % .2611 % .2144 % .0073 % .0357 1.0000 1.0058 3.7139 .0581 .2779 .2282 .0077 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY UTERUS <UT) : -LUMEN FILLED WITH FLUID; GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BILATERAL: CLEAR FLUID LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL UTERUS (UT) : -DILATATION,-SLIGHT 000851 287 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 73 ANIMAL NUMBER: C94527 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 213.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:48 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE <EY> , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000852 288 ii t APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 74 ANIMAL NUMBER: C94528 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 210.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:53 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) ABSOLUTE ORGAN WEIGHT (GRAMS) .0706 1.9160 1.9295 7.8862 .0945 .3804 .6013 .0141 ORGAN WEIGHT RELATIVE T O BODY WEIGHT (%) .0336 % .9124 % .9188 % 3.7553 % .0450 % .1811 % .2863 % .0067 % ORGAN TO BRAIN WEIGHT RATIO .0368 1.0000 1.0070 4.1160 .0493 .1985 .3138 .0074 ORGAN STATUS WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -VACUOLATION, HEPATOCELLULAR,-MINIMAL 000853 289 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 75 ANIMAL NUMBER: C94528 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 210.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:53 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY <KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS) , SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000854 290 APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 76 ANIMAL NUMBER: C94529 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 228.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:27 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .1022 1.9228 2.6260 8.7876 .1418 .6896 .6188 .0177 .0447 % .8404 % 1.1477 % 3.8407 % .0620 % .3014 % .2705 % .0077 % .0532 1.0000 1.3657 4.5702 .0737 .3586 .3218 .0092 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, S U B ACUT E ,-MINIMAL -VACUOLATION, HEPATOCELLULAR,-MINIMAL OOOSI W ! 291 Cl ?i APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 77 ANIMAL NUMBER: C94529 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH:[: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 228.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:27 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU) , JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , C E C U M (CE) , COLON (CO) , RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 00085 292 CD ' i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 78 ANIMAL NUMBER: C94530 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 235.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:13 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0605 2.0288 2.1802 8.2680 .1644 .5085 .5445 .0133 .0257 % .8626 % .9270 % 3.5153 % .0699 % .2162 % .2315 % .0057 % .0298 1.0000 1.0746 4.0753 .0810 .2506 .2684 .0066 WEIGHT TAKEN WEIGHT TAKE* WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -VACUOLATION, HEPATOCELLULAR,-MINIMAL 000857 293 t APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 79 ANIMAL NUMBER: C94530 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 235.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:13 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000S5 Q 2 94 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 80 ANIMAL NUMBER: C94531 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 207.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:43 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0655 1.9550 2.0538 7.5010 .1314 .4679 .5398 .0173 .0315 % .9408 % .9884 % 3.6097 % .0632 % .2252 % .2598 % .0083 % .0335 1.0000 1.0505 3.8368 .0672 .2393 .27 61 .0088 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN GENERAL INFORMATION (XX) : > N O T E :>ANIMAL IDENTIFICATION TRANSPONDER DAMAGED AT NECROPSY BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -VACUOLATION, HEPATOCELLULAR, -MINIMAL 00085 295 II APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 81 ANIMAL NUMBER: C94531 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 207.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:43 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV) O o o 0 296 o APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 82 ANIMAL NUMBER: C94532 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 184.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:04 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0682 1.9062 1.7582 6.6326 .1150 .4453 .5121 .0175 .0369 % 1.0321 % .9519 % 3.5910 % .0623 % .2411 % .2773 % .0095 % .0358 1.0000 .9224 3.4795 .0603 .2336 .2686 .0092 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -CYST,-MINIMAL 0008G 297 ii APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 83 ANIMAL NUMBER: C94532 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 184.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:04 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000SG2 298 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 84 ANIMAL NUMBER: C94533 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 200.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:52 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0639 2.0393 1.9056 8.3329 .1402 .5051 .4569 .0197 .0319 % 1.0181 % .9514 % 4.1602 % .0700 % .2522 % .2281 % .0098 % .0313 1.0000 .9344 4.0862 .0687 .2477 .2240 .0097 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -VACUOLATION, HEPATOCELLULAR, -MINIMAL 0008G t o 299 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 85 ANIMAL NUMBER: C94533 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 200.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:52 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 0008G 300 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 86 ANIMAL NUMBER: C94534 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 197.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:50 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0655 2.0617 1.9166 7.1556 .1380 .4487 .3874 .0217 .0332 % 1.0439 % .9704 % 3.6231 % .0699 % .2272 % .1962 % .0110 % .0318 1.0000 .9296 3.4707 .0669 .2176 .1879 .0105 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -DEGENERATION, TUBULAR,-MINIMAL LIVER (LI) : -VACUOLATION, HEPATOCELLULAR,-MINIMAL LN, MESENTERIC (MS) : >TISSUE MISSING > N O T E :>MESENTERIC LYMPH NODE MISSING IN RETRIM. 000S6 301 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 87 ANIMAL NUMBER: C94534 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 197.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:50 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) o o o GO (?) 302 APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 88 ANIMAL NUMBER: C94535 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 217.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:18 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0683 2.0698 1.8145 7.8013 .1276 .5174 .4819 .0196 .0314 % .9525 % .8350 % 3.5901 % .0587 % .2381 % .2218 % .0090 % .0330 1.0000 .8767 3.7691 .0616 .2500 .2328 .0095 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -VACUOLATION, HEPATOCELLULAR,-MINIMAL O0O8G7 303 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 89 ANIMAL NUMBER: C94535 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 217.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:18 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) SOOO GO 3 0 4 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 90 ANIMAL NUMBER: C94536 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 204.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:26 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0803 1.8203 2.0013 6.8621 .1446 .6338 .5764 .0140 .0393 % .8906 % .9791 % 3.3572 % .0707 % .3101 % .2820 % .0068 % .0441 1.0000 1.0994 3.7698 .0794 .3482 .3167 .0077 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL 0008? u> 305 ?i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 91 ANIMAL NUMBER: C94536 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 204.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:26 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV) 000870 306 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 92 ANIMAL NUMBER: C94537 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 223.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:03 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0733 2.0384 2.2858 8.2008 .1269 .4833 .5223 .0192 .0328 % .9124 % 1.0232 % 3.6709 % .0568 % .2163 % .2338 % .0086 % .0360 1.0000 1.1214 4.0232 .0623 .2371 .2562 .0094 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL KIDNEY (KD) : -PYELITIS,-SLIGHT LIVER (LI) : -VACUOLATION, HEPATOCELLULAR,-MINIMAL 00087 307 APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 93 ANIMAL NUMBER: C94537 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 223.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:03 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 0008 *vl 3 0 8 0 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 94 ANIMAL NUMBER: C94538 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 192.6 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:25 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE T O BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0606 1.8703 1.8873 6.9707 .1094 .4307 .7123 .0143 .0315 % .9711 % .9799 % 3.6193 % .0568 % .2236 % .3698 % .0074 % .0324 1.0000 1.0091 3.7270 .0585 .2303 .3808 .0076 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY KIDNEY (KD) : -LARGE PELVIS(ES); LEFT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUO LATI O N ,-MINIMAL KIDNEY (KD) : -DILATATION, PELVIC,-MODERATE LIVER (LI) : -VACUOLATION, HEPATOCELLULAR, -MINIMAL 00087 CO 309 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 95 ANIMAL NUMBER: C94538 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 192.6 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:25 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN <BR) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL STOMACH, NONGL (SU) , DUODENUM (DU) , JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , C E C U M (CE) , COLON (CO) , RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) (SB), (ST), THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000874 310 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 96 ANIMAL NUMBER: C94539 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 217.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:30 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .1090 2.0113 2.6878 8.3813 .1454 .5526 .4936 .0066 .0500 % .9235 % 1.2341 % 3.8482 % .0668 % .2537 % .2266 % .0030 % .0542 1.0000 1.3363 4.1671 .0723 .2747 .2454 .0033 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN EXCLUDE NECROPSY OBSERVATIONS HISTOPATHOLOGY THYROID (TY) : >NOTE :>ONE THYROID/PARATHYROID LOST PRIOR TO WEIGHING GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLAT IO N ,-MINIMAL KIDNEY (KD) : -PYELITIS,-SLIGHT LIVER (LI) : -VACUOLATION, HEPATOCELLULAR,-MINIMAL THYROID (TY) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL  APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 97 ANIMAL NUMBER: C94539 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 217.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:30 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS <UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 9,8000 312 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 98 ANIMAL NUMBER: C94540 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 174.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:35 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0624 1.9367 1.9136 6.6088 .1402 .3929 .3952 .0217 .0358 1.1118 1.0985 3.7938 .0805 .2255 .2269 .0125 % % % % % % % % .0322 1.0000 .9881 3.4124 .0724 .2029 .2041 .0112 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL o o o QS ^2 313 vi APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 99 ANIMAL NUMBER: C94540 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 174.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:35 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000878 314 i # >^ I 1 ^ APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 100 ANIMAL NUMBER: C94541 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 234.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:06 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0850 2.0657 2.5187 8.8330 .1394 .6589 .6495 .0164 .0363 % .8820 % 1.0754 % 3.7716 % .0595 % .2813 % .2773 % .0070 % .0411 1.0000 1.2193 4.2760 .0675 .3190 .3144 .0079 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -PYELITIS,-MINIMAL 000879 315 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 101 ANIMAL NUMBER: C94541 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 234.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:06 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) o o 00 OC 316 t APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 102 ANIMAL NUMBER: C94542 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 242.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:53 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0880 2.0048 2.5368 9.4944 .1565 .5490 .6078 .0250 .0363 .8267 1.0461 3.9152 .0645 .2264 .2506 .0103 % % % % % % % % .0439 1.0000 1.2654 4.7358 .0781 .2738 .3032 .0125 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -VACUOLATION, HEPATOCELLULAR,-MINIMAL 0008S1 317 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 103 ANIMAL NUMBER: C94542 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 242.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:53 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG), AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG), LN, MANDIBULAR (MN), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT). VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV) 0008S O 318 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 104 ANIMAL NUMBER: C94543 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 167.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:33 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY <KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0487 1.8660 1.7414 6.4505 .0986 .3354 .5563 .0192 .0290 % 1.1114 % 1.0372 % 3.8419 % .0587 % .1998 % .3313 % .0114 % .0261 1.0000 .9332 3.4569 .0528 .1797 .2981 .0103 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY UTERUS (UT) : -LUMEN FILLED WITH FLUID; GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BILATERAL: CLEAR FLUID BRAIN (BR) : -VACUOLATION, -MINIMAL UTERUS (UT) : -DILATATION,-MODERATE 0008S3 319 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 105 ANIMAL NUMBER: C94543 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 167.9 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:33 PROSECTOR: JILL PAUS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV) 0008S4 320 > si APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 106 ANIMAL NUMBER: C94544 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 185.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:29 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0563 2.0395 2.1156 8.2267 .1453 .4673 .4899 .0140 .0304 % 1.0995 % 1.1405 % 4.4349 % .0783 % .2519 % .2641 % .0075 % .0276 1.0000 1.0373 4.0337 .0712 .2291 .2402 .0069 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL OO0SS5 321  APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 107 ANIMAL NUMBER: C94544 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 185.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:29 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV) 0Q08SG 322 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 108 ANIMAL NUMBER: C94545 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 187.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:43 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0585 1.8832 2.0151 7.1725 .1228 .4640 .4712 .0131 .0313 % 1.0060 % 1.0764 % 3.8315 % .0656 % .2479 % .2517 % .0070 % .0311 1.0000 1.0700 3.8087 .0652 .2464 .2502 .0070 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -PYELITIS,-MODERATE 00083 323 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 109 ANIMAL NUMBER: C94545 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 187.2 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:43 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BRAIN (BR), KIDNEY (KD), LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 0008S8 324  ) i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 110 ANIMAL NUMBER: C94546 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 219.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:48 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0634 2.0493 2.1332 9.5768 .1006 .5830 .6427 .0293 .0289 % .9328 % .9710 % 4.3590 % .0458 % .2654 % .2925 % .0133 % .0309 1.0000 1.0409 4.6732 .0491 .2845 .3136 .0143 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -VACUOLATION, HEPATOCELLULAR, -MINIMAL OG08S9 325 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 111 ANIMAL NUMBER: C94546 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 219.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:48 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000890 326 it APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 112 ANIMAL NUMBER: C94547 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 237.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:19 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0794 2.1499 2.2587 9.8392 .1338 .5588 .5987 .0129 .0335 % .9067 % .9526 % 4.1498 % .0564 % .2357 % .2525 % .0054 % .0369 1.0000 1.0506 4.5766 .0622 .2599 .2785 .0060 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -DILATATION, P E LVIC,-SLIGHT 000891 327 >t APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 113 ANIMAL NUMBER: C94547 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 237.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:19 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000892 328 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 114 ANIMAL NUMBER: C94548 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 186.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:29 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0536 2.0980 1.9018 6.8828 .0940 .4053 .6280 .0167 .0287 % 1.1231 % 1.0181 % 3.6846 % .0503 % .2170 % .3362 % .0089 % .0255 1.0000 .9065 3.2806 .0448 .1932 .2993 .0080 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN KIDNEY (KD) : -INFLAMMATION, C H R O N I C ,-MINIMAL 000893 329  APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 115 ANIMAL NUMBER: C94548 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 186.8 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:29 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , BRAIN (BR) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV) 000894 330 f APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 116 ANIMAL NUMBER: C94549 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 207.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:47 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYRO ID/ PARATHYR (TT) .0653 2.0569 2.1431 8.7554 .1636 .5145 .4439 .0221 .0314 % .9903 % 1.0318 % 4.2154 % .0788 % .2477 % .2137 % .0106 % .0317 1.0000 1.0419 4.2566 .0795 .2501 .2158 .0107 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY O B S E R V A T I C )N S HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -NECROSIS, -MINIMAL 000895 331 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 117 ANIMAL NUMBER: C94549 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 207.7 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 11:47 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) ,SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC(MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000S96 332 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 118 ANIMAL NUMBER: C94550 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 187.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:46 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO O RGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID /PARATHYR (TT) .0630 1.9038 1.8946 7.7017 .0960 .4316 .5060 .0165 .0337 % 1.0181 % 1.0132 % 4.1186 % .0513 % .2308 % .2706 % .0088 % .0331 1.0000 .9952 4.0454 .0504 .2267 .2658 .0087 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY O B S E R V A T I C )N S HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL KIDNEY (KD) : -PYELITIS,-SLIGHT LIVER (LI) : -INFLAMMATION, S U B ACUT E ,-MINIMAL 000897 333 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 119 ANIMAL NUMBER: C94550 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 187.0 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:46 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV) , UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV) 0 0 0 8 38 334 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 120 ANIMAL NUMBER: C94551 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 171.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:54 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0661 1.8855 1.9419 8.7911 .1289 .4517 .3160 .0126 .0386 % 1.1020 % 1.1350 % 5.1380 % .0753 % .2640 % .1847 % .0074 % .0351 1.0000 1.0299 4.6625 .0684 .2396 .1676 .0067 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY UTERUS (UT) : -LUMEN FILLED WITH FLUID; GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BILATERAL: CLEAR FLUID BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SLIGHT -VACUOLATION, HEPATOCELLULAR, -MINIMAL UTERUS (UT) : -DILATATION,-SLIGHT 000899 335 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 121 ANIMAL NUMBER: C94551 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 171.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:54 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU) , TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) ooosoo 336 ii APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 122 ANIMAL NUMBER: C94552 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 201.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:53 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0660 2.0531 2.3079 10.2382 .1255 .4772 .3988 .0244 .0328 % 1.0194 % 1.1459 % 5.0835 % .0623 % .2369 % .1980 % .0121 % .0321 1.0000 1.1241 4.9867 .0611 .2324 .1942 .0119 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SLIGHT 000901 337 ii APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 123 ANIMAL NUMBER: C94552 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 201.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:53 PROSECTOR: MICHELE ZIMA RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000902 338 * > APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 124 ANIMAL NUMBER: C94553 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 206.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:58 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) T H Y R O I D / PA R A T H Y R (T T ) .0679 2.0290 2.2091 10.4906 .1087 .4567 .6089 .0237 .0329 % .9835 % 1.0708 % 5.0851 % .0527 % .2214 % .2952 % .0115 % .0335 1.0000 1.0888 5.1703 .0536 .2251 .3001 .0117 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATE 000903 339 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 125 ANIMAL NUMBER: C94553 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 206.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 12:58 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000904 340 > APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 126 ANIMAL NUMBER: C94554 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 184.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:19 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0582 1.8946 1.9402 8.6778 .0972 .3575 .3711 .0149 .0316 % 1.0274 % 1.0522 % 4.7060 % .0527 % .1939 % .2012 % .0081 % .0307 1.0000 1.0241 4.5803 .0513 .1887 .1959 .0079 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY UTERUS (UT) : -LUMEN FILLED WITH FLUID; GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BILATERAL: CLEAR FLUID BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -INFLAMMATION, SUBACUT E ,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SLIGHT UTERUS (UT) : -DILATATION,-SLIGHT 000905 341 # APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 127 ANIMAL NUMBER: C94554 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 184.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:19 PROSECTOR: WENDY CHERRY RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), OVARY (OV), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 0009QG 342 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 128 ANIMAL NUMBER: C94555 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 192.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:54 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY <KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0605 2.0725 2.1591 10.0252 .1028 .4944 .8204 .0177 .0314 % 1.0766 % 1.1216 % 5.2079 % .0534 % .2568 % .4262 % .0092 % .0292 1.0000 1.0418 4.8372 .0496 .2386 .3959 .0085 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY UTERUS (UT) : -LUMEN FILLED WITH FLUID; GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN BILATERAL: CLEAR FLUID BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATE -VACUOLATION, HEPATOCELLULAR,-MINIMAL UTERUS (UT) : -DILATATION, -MINIMAL 000907 343 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 129 ANIMAL NUMBER: C94555 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 192.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:54 PROSECTOR: JAMES T. CALLEN RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP), CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS) , SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL,CORTEX(AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 00090 GO 3 4 4  APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 130 ANIMAL NUMBER: C94556 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 206.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:56 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0777 2.0897 2.6036 9.4436 .1349 .6082 .5221 .0150 .0377 1.0139 1.2633 4.5820 .0655 .2951 .2533 .0073 % % % % % % % % .0372 1.0000 1.2459 4.5191 .0646 .2910 .2498 .0072 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATI O N ,-MINIMAL KIDNEY (KD) : -PYELITIS,-SLIGHT LIVER (LI) : -INFLAMMATION, SUBACUTE,-MINIMAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SLIGHT 000909 345 t > APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 131 ANIMAL NUMBER: C94556 SEX: FEMALE DOSE GROUP: 5 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 206.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:56 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 00091 o 346 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 132 ANIMAL NUMBER: C94557 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 151.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:00 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0381 1.9430 1.6979 12.4887 .0758 .3143 .3376 .0152 .0251 % 1.2825 % 1.1207 % 8.2434 % .0500 % .2075 % .2228 % .0100 % .0196 1.0000 .8739 6.4275 .0390 .1618 .1738 .0078 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN EYE (EY) : -INFILTRATE, LYMPHOCYTIC,-MINIMAL BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR, -MODERATELY SEVERE LN, MESENTERIC (MS) : >TISSUE MISSING >N O T E :>MESENTERIC LYMPH NODE MISSING IN RETRIM. 000911 347 i APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 133 ANIMAL NUMBER: C94557 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 151.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:00 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU) , JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO) , RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: KIDNEY (KD), SPLEEN (SP) , PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000912 348 )) t it APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 134 ANIMAL NUMBER: C94558 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 154.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:37 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0453 2.1101 1.7106 12.6860 .0777 .4358 .4256 .0122 .0293 1.3666 % 1.1079 % 8.2163 % .0503 % .2823 % .2756 % .0079 % .0215 1.0000 .8107 6.0120 .0368 .2065 .2017 .0058 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATE 000913 349  APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 135 ANIMAL NUMBER: C94558 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 154.4 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 8:37 PROSECTOR: NANCY DIEDRICH RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: MATTHEW AXTMAN THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CE C U M (CE) , COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) ,AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000914 350 APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 136 ANIMAL NUMBER: C94559 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 134.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:17 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0351 1.7981 1.4107 9.8766 .0511 .4295 .4142 .0118 .0261 % 1.3369 % 1.0488 % 7.3432 % .0380 % .3193 % .3080 % .0088 % .0195 1.0000 .7846 5.4928 .0284 .2389 .2304 .0066 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, SEVERE CENTRILOBULAR,-MODERATELY 00091: 351  APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 137 ANIMAL NUMBER: C94559 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 134.5 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:17 PROSECTOR: DONIA MEYER RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) ,LN, MANDIBULAR (MN) ,SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 00091G 352  APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 138 ANIMAL NUMBER: C94560 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 172.6 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:39 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: STEVE VAN ADESTINE ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0389 2.0925 1.6771 14.9295 .0671 .5289 .6468 .0095 .0225 % 1.2123 % .9717 % 8.6498 % .0389 % .3064 % .3747 % .0055 % .0186 1.0000 .8015 7.1348 .0321 .2528 .3091 .0045 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATION,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, SEVERE CENTRILOBULAR,-MODERATELY 000917 353 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 139 ANIMAL NUMBER: C94560 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 172.6 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 9:39 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: STEVE VAN ADESTINE THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR) , ESOPHAGUS (ES) , HEART (HT) , MUSCLE, SKELETAL (SM) , NERVE, SCIATIC (SN) , STOMACH, GL (ST), STOMACH, NONGL (SU) , DUODENUM (DU), JEJUNUM (JE) , ILEUM (IL) , LN, POPLITEAL (PP) , CECUM (CE) , COLON (CO), RECTUM (RE), THYROID (TY) , PARATHYROID (PT) , AORTA (AO), PITUITARY (PI), THYMUS (TH) , SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF), URINARY BLADDER (UB), CERVIX (CV), UTERUS (UT), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) <?T6000 354 i i ii APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 140 ANIMAL NUMBER: C94561 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 161.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:36 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY <KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0618 1.9670 1.9650 13.3315 .0797 .4122 .4100 .0182 .0383 % 1.2195 % 1.2182 % 8.2650 % .0494 % .2555 % .2542 % .0113 % .0314 1.0000 .9990 6.7776 .0405 .2096 .2084 .0093 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY SKIN (SK) : -ALOPECIA-FOCAL; RIGHT AND LEFT HIP REGIONS: SINGLE AREA ON EACH; LEFT IS 45 X 29 MM, RIGHT IS 42 X 30 MM (CAPS 21 AND 22) GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -ANIMAL THIN BRAIN (BR) : -VACUOLATION, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATELY SEVERE SKIN (SK) : -INVOLUTION, FOLLICULAR,-SLIGHT 000319 355 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 141 ANIMAL NUMBER: C94561 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 161.3 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 13:36 PROSECTOR: TERRI L. WILLIAMS RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE <EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) ,LN, MANDIBULAR (MN) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , KIDNEY (KD) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 000920 356  APPENDIX 6 individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 142 ANIMAL NUMBER: C94562 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 165.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:52 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN STATUS ADRENAL (AD) BRAIN (BR) KIDNEY (KD) LIVER (LI) OVARY (OV) SPLEEN (SP) THYMUS (TH) THYROID/PARATHYR (TT) .0589 2.0415 1.8903 10.9656 .1065 .4382 .5178 .0154 .0357 % 1.2365 % 1.1449 % 6.6418 % .0645 % .2654 % .3136 % .0093 % .0289 1.0000 .9259 5.3713 .0522 .2146 .2536 .0075 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS -BONE MARROW SMEAR TAKEN BRAIN (BR) : -VACUOLATI O N ,-MINIMAL KIDNEY (KD) : -PYELITIS, -MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, SEVERE CENTRILOBULAR, -MODERATELY 000921 357 APPENDIX 6 Individual Animal Pathology Data Covance 6329-224 3M T-6314.2 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MEFOSE, T-6314) IN RATS PAGE: 143 ANIMAL NUMBER: C94562 SEX: FEMALE DOSE GROUP: 6 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 07/13/98 STUDY DAY OF DEATH: 32 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 165.1 GRAMS DATE AND TIME OF NECROPSY: 07/13/98 10:52 PROSECTOR: JOHN S. HALFORD RECORDER: JODI THIEREN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: HAMP, BRUNER WEIGHER: LYNN HORNER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY) , BRAIN (BR) , KIDNEY (KD) , LIVER (LI), SPLEEN (SP), PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) , BONE, FEMUR (FE) , MARROW, FEMUR (FM) , MARROW, STERNUM (SE) , BONE, STERNUM (SB), LUNG (LU), TRACHEA (TR), ESOPHAGUS (ES), HEART (HT), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), STOMACH, NONGL (SU), DUODENUM (DU), JEJUNUM (J E ) , ILEUM (IL), LN, POPLITEAL (PP), CECUM (CE), COLON (CO), RECTUM (RE), THYROID (TY), PARATHYROID (PT), AORTA (AO), PITUITARY (PI), THYMUS (TH), SPINAL CORD (SC), HARDERIAN GLAND (HG) , AUDITORY SEB GL (AS), SALIV GL, MANDIB (SG) , LN, MANDIBULAR (MN) , SKIN (SK) , MAMMARY, FEMALE (MF) , URINARY BLADDER (UB) , CERVIX (CV) , UTERUS (UT) , VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY) , SPLEEN (SP) , PANCREAS (PA), LN, MESENTERIC (MS), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA) , OVARY (OV) 0009: fs) 358 APPENDIX 7 Cell Proliferation Report Covance 6329-224 3M T-6314.2 Note: This appendix of the report contains information supplied by Pathology Associates International and has been reviewed by the Quality Assurance Unit of Pathology Associates International. 359 000923 Covance 6329-224 3M T-6314.2 Ceil Proliferation Report Pathology Aaaodataa International A Com pany o f Science Applications International Corporation Am A n l n M f t A M t i M i a i i v FINAL CELL PROLIFERATION REPORT 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MeFOSE, T-6314) IN RATS COVANCE STUDY NUMBER 6329-224 PREPARED FOR: 3M TOXICOLOGY SERVICES BUILDING 220-2E-02,3M CENTER ST. PAUL, MN 55144-1000 PREPARED BY: PATHOLOGY ASSOCIATES INTERNATIONAL 15 WORMAN'S MILL COURT, SUITE I FREDERICK, MD 21701 MAY 12,2000 15Woman**MfllConrt,SuiteI Frederick, Maryland21701 *(301) 643-1644 * (301) 663-8994FAX 360 000924 Covance 6329-224 3M T-6314.2 K ni CanProUftnttaiRapart Covance StudyNumber6329-224 Page 2 TABLE OF CONTENTS l. CELL PROLIFERATION REPORT n . TABLES m . SIGNATURE PACT IV. QUALITY ASSURANCE STATEMENT V. APPENDIX I 361 00092 Covance 6329-224 3M T-6314.2 Find CeUProliferationReport Covance StudyNumber 6329*224 Page 3 CELL PROLIFERATION REPORT 4-WEEK RANGE-FINDING DIETARY TOXICITY STUDY WITH N-METHYL PERFLUOROOCTANESULFONAMIDO ETHANOL (N-MeFOSE, T-6314) IN RATS COVANCE STUDY NUMBER 6329-224 PURPOSE The purpose o f the study was to a sm s the toxicity o f the test material when administered in the diet to rats for at least 4 weeks. Tins report, submitted by Pafootogy Associates International (PAI) to the study Sponsor, 3M , Hipresenls the ceti proli&iatitn findings and inteqxetation for Covance Study Number 6329-224 entitled M4-Week Range Finding Dietary Toxicity Study with N-Methy! PerfoMxoectanearifonanado Ethanol (N-MeFOSE, T-6314) In Rats" . A ll aspects o f foe tasks associated with PAI's portion o f tins study were conducted in compliance with the Food and Drug Adariaistestion Good laboratory Practice (GLP) Regulations as set forth in Title 21 o f foe US Code o f Federal Regulation, Part 58, issued December 22, 1978 (effective June 2 0 ,1 9 7 9 ), and w ifo any applicable amendments. MATERIALS AND METHODS Tisane C ollection for CeB ProM eration Six per sex per group in p o o p s 1 through 6 were sacrificed during week 4 for hqjoleceihriarpsofifotstien. A section o f foe left lateral lobe o f the liver from each o f 6 rats per sex per group (grasps 1-6) was fixed and processed to paraffin block by Covance per protocol specifications. Tissue blocks were shipped to PAI far sectioning and staining. From each block, a slide w as prepared for H&E evaluation and irnmunohiBtochcmical detection o f proliferating cell nuclear antigen (PCNA), a marker o f cell proliferation. Insagw ohlstoebem lsti y for CeB Prolifera tlee Sections o f pantffin-efobedded tissues w ere cut at 5 pm and placed on positively charged slides (Superfrost Plus, Fisher Scientific, Pittsburgh, PA) to ensure adhesion during processing for PCNA. Standard immgBohiatochcmical methods were used to stain tissues for PCNA (PAI's SOP for inanunnhwitochcmistry). Briefly, tissue sections were incubated with a monoclonal antibody to PCNA (DAKO, lot #016, PAI N o. A1723) and reagents required for foe avidin-biotin peroxidase (ABC Elite Kit, lot #PK-610Q, PAI No. K 324) method for foe detection o f foe antigen-antibody complex. PCNA expression in cells in all phases o f the cell cycle (G,, S, G2 and M) w as localized by the chromageu 3,3'-diaminabenzidine (DAB; Sigma Chemical Co., lot #18H 8201). Tissue sections were counterstained with hematoxylin. A negative control slide was included in the staining run and consisted o f study tissue that was not incubated with foe primary antibody. 362 000926 Covance 6329-224 3M T-6314.2 C ell F n M fe n tlo i M easurements FinalCell Prottfcntion Report Covance StudyNumber6329-224 Page4 Far cell proliferation evaluations, slides were first perused at law magnification (LOOX) to judge quality o f *""*% preow ing and sectioning, pattern o f cell labeling (e.g., centrilobular or proliferation, such as Kupffer cells, bile duct epithelium , enAnhafam ), andhistomarphologic changes. Cell proliferation was then quantified at higher m agnification (20QX). The percentage o f hepatocytes in S phase o f the cell cycle (labeling index, LI) w as determined by scoring at le n t 3000 hepatocytes in 10 randomly selected fields per arrimaL Hlatcnnoiphelogy was Anther assessed by evaluating the serial H&E slide fin: each 8nimai evaluated for cell proliferation. Statistical Analysis The Student's M est (two-sided, unequal variance) was used to test for statistical significance in PI between control and treatment groups using Microsoft Excel version 5.0. A P value o f 0.05 was judged to he statistically significant. RESULTS Cell ProHfferatien Individual animal and group mean cell protifcration data ate presented in S ection g (Tables 1 and 2). The percentage o f proh&nting hepatocytes as determined by the labeling index (LI) did not differ significantly between control and treated groups o f male or female rats. hi gro up 6 m ales, there was no PCNA slide present for animal C94523; therefore, five out o f six animate w ere reported far this group. H btopstbology Sections from the same tisane blocks used for preparation o f PCNA-stained slides w ere stained with hem atoxylin and costs (H&E) for histopathologic evaluation to facilitate the interpretation o f the iranramoatamed slides. Individual animal findings and group summaries w e presented in Appendix I. The results stow ed no change in the liver tissue o f male and female rats that would alto- tire interpretation o f the PCNA in this study. The livers from one mid-high dose mid two high dose m ale rats, and two high dose female rats each contained focal necrosis without a concomitant inflammatory response. This necrosis was not accompanied by a secondary regenerative effect as determined by an increased PCNA LI. 363 000927 Covance 6329-224 3M T-6314.2 SUM M ARY Fnal CeHProliferation Report Covance StudyNumber6329-224 PageS In the present study, cxii proliferation w h measured within die liver o f male and fem ale rats from control (0 ppm ), low dose (1 ppm), low-raid dose (10 ppm), mid dose (30 ppm ), m id-high dose (100 ppm), and high dose (500 ppm) groups after 4 w eeks on study. N o statistically iyWW>Kt increases in ceH proliferation, as deterauned by die PCNA labeling index (LI) were observed in male or female rats after 4 weeks ofN -m etbyl perflirarooctanesulfonamido etbimoL 364 000928 Covance 6329-224 3M T-6314.2 Final Cell Proliferation Report Covunce Study Number 6329-224 Page 6 1L TABLES Legend SEM Standard Error o f the M ean 365 000929 Covance 6329-224 3M T-6314.2 Covano Study No. 6239-224 Tablo 11-1. Coll Premaratlon InUvrof Malo Rata Aftar4 Wks of N-MaFOSE 9CM Ofoup 1 -0 ppm (Control) Animal Labalktg Sox i Humbar Indax M , C94491 0.188% M C94492 0.136% M C94493 ! NP 2 -1 ppm (Low) M : C94494 ; 0.196% M ; C9449S 0.407% M ; C94496 0.156% Moan 0460% 8EM 0.048% M I C94497 0.427% M ! C94498 ! 0.082% M ; C94499 I 0.726% M 1 C94500 ! 0.170% M ! C94501 I 0.067% M ' C94502 I 0.616% ! Moan | 0.330% 3 -1 0 pom (Low-Mid) SEM 0.110% M CM603 0.377% M C94504 0.325% 4 - 30 ppm (MM) M C94606 M 094608 M C94507 jjf | cmbob Moan t SEM M ! C94509 M C94610 M ; C94611 M ! C94512 M j C94513 0.879% 0.168% 0.084% 0.167% 0.300% 0988% 0.027% 0.064% 0425% 0.329% 0.378% 5-100 ppm (MM-HtSh) 6 SCOppm (High) M ! C94514 0481% Mean 0416% SEM 0.069% M i C94515 0480% M ; C94616 0.337% M ! C94517 0.263% M : C94518 0495% M i C94519 0.384% M C94520 0.055% Mam 0484% SEM 0.060% M : C94521 j 0.196% M C94522 ! 0.054% !M M C94523 ! NP C94524 0.112% M | C94S25 M ! C94528 0.085% 0.191% Moan 0.127% SEM 0.028% Sl NP; tissue not present on i8de for#094493 NP; slid not present for#094523 ! 1 Page 11-1 366 0003JQ Covance 6329-224 3MT-6314.2 Covane Study No. 6238-224 Tabi 11-2. CH Proliferation In Uver of Fornai Rata Altar 4 Weeks of N-MeFOSE i---------------- 1-- PCH'A I Animal ( Labeling (brow Sax ; Humber i index 1 -0 ppm (Control) F I C84527 | ND F ! C84528 I 0.082% F . C84828 ) 0.138% F ; C84830 0.666% F ! C84831 0.084% F ! C84832 Mean 0.138% 0.201% SEM 0.082% 2 -1 ppm (tow) F ! C84533 F | C84534 0.136% 0.136% F C84535 F : C84536 F i C84637 F ; C84S38 0.111% 0.401% 0.347% 0.272% Mean 0.234% 3 10 ppm (Low-Mkt) SEM ; 0.081% F C84539 0.160% F j C84540 0.064% F ; C84541 0.080% F i C84542 0.110% 4 - 3 0 ppm (Mid) F : C84543 F ; C84544 | Mean; SEM F C94545 F C84546 F C94547 F C94548 F C84549 F C94550 0.168% 0.168% 6t3% 0.020% 0.137% 0.110% 0.192% 0.112% 0.181% 0.080% Mean 0.132% 5 -1 0 0 ppm (Mid-High) F F F F F SEM C94551 C94552 C94553 C94554 C84565 0.016% 0.356% 0.080% 0.062% 0.081% 0.083% F ! C84556 0.055% M nn 0.123% 6 - 500 ppm (High) SEM j 0.047% F C94557 0.193% F C9455S 0.027% F C84558 0.081% F ; C94560 I 0.193% F C84561 0.161% F ; C94562 0.142% M ean 0.133% SEM 0.027% ND: not determined due to insufficient tissue on slide I Page 11-2 367 000931 Covance 6329-224 3M T-6314.2 Fini CfcUProliferationReport Covance StudyNumber 6329-224 Fat 7 IH . SIGNATURE PAGE Sobmittod by: Project Manager; Project Pathologist* ^ / S -0 0 Date Carolyn M< llmate, A.C.V.P. Date ^ ^ 368 000932 Covance 6329-224 3M T-6314.2 Fine! CdlProhfenrtkm Report Covance Study Number 6329-224 P tie S IV. QUALITY ASSURANCE STATEMENT 369 000933 Pathology Aaeodatea International A ^ * - M 1 U ^ y B B f W y O W W K i^ P P M IM lIH ifB W n B W BJJQIIM i Covance 6329-224 3M T-6314.2 C ell Proliferation Report 4-W eek Range-Finding D ietary Toxicity Study w ith N-M ethyl Perfluoroctaneeulfonam ido Ethanol (N-M eFOSE, T-6314) in Rate Covance StudyNumber 6329-224 QUALITY ASSURANCE STATEMENT This cell proiiftration project ime been inspected and audited by die PAI Quality Asaonmee Unit (QAU) as required by die Good Laboratory Practice (OLP) regulations inieindfli il by the U.S. Fe< and Drug Administration (FDA). The cell proliferation report is aa accasatereflection ofthe recoded data. The following table is a record ofthe impcctices/aadrts performed andrepotted by the QAU. Date of Date FiswUngs Reported to PAI 08/12/98 03/31;04/04/00 03/3L04/04/00 05/12/00 Microtomy StudyData and SupportingDocnmentatkm Draft Cefl PiettferaticmReport Final Cefl Proliferation Report 08/13/98 04/04/00 04/04/00 05/12/00 KarenE. Bader Quality Assarance Officer Date 15 W o rm a i'3 Milt Court, Suite I F re d e ric * , Maryland 21701 (301) 663-1644 (301) 663-8994 FAX 370 000934 Covance 6329-224 3M T -63I4.2 Final Cell Proliferation Report Covance Study Number 6329-224 Page9 A PPEN D IX I 371 00093 Covance 6329-224 3M T-6314.2 Final DraftCdl ProHfaatfemReport Covance StudyNo. 6329-224 Irnttridwri Antami HatoaaerplMiofieFladiigi ta liver: 4-Week R ^ i T laittn Dhtary TmdsjtyStsdy with N-Metbyl P a ftw r o w tiiiiiftiin iM i Ethanol (N-MeFOSI, T-6314) ia Rats Aai-- IN w obw 04491 04492 04493 04494 04495 04496 04497 OM 99 04499 04504 04501 04502 04503 04504 04505 04506 04507 04509 04599 04510 0*511 04512 04513 04514 04515 04516 04517 04519 04519 04520 04521 04522 C94523 C94524 04525 04526 Sax M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M P w Grump_________________ Histologic Findings I-Oppm (Control) Ho Significant Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 2-1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 2*1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 3-10 ppm (Low-raid) No Significant Findings 3-10 ppm (Low-mid) No Significant Findings 3-10 ppm (Low-mid) No Significant Findings 3-10 ppm (Low-mid) No Significant Findings 3-10 ppm (Low-mid) No SignificantFindings 3-10 ppm (Low-mid) No SignificantFindings 4-30 ppm (Mid) No SignificantFindings 4-30 ppm (MU) No Significant Foldings 4-30 ppm (Mid) No Significant Findings 4-30 ppm (hfid) No SignificantFindings 4-30 ppm (Mid) No SignificantFindings 4-30 ppm (Mid) No Significant Findings 5-100 ppm (Mid-high) No Significant Findings 5-100 ppm(Mid-high) No Significant Findings 5-100 ppm (Mid-high) No Significant Findings 5-100 ppm (Mid-high) Focsl Necrosis 5-100 ppm (Mid-high) No Significant Findings 5-100 ppm (Mid-high) No Significant Findings 6-500 ppm (High) No SignificantFindings 6-500 ppm (High) No Significant Findings 6-500 ppm (High) 6-500 ppm (High) Focal Necrosis Focal Necrosis 6-500 ppm (High) No Significant Findings 6-500 ppm (High) No Significant Findings 372 000936 Covance 6329-224 3M T-6314.2 Final DraftCell ProliftnboB Report Covuce StudyNo. 6329-224 iBdWftwdAnimal Hbtanarphologk Findings in Liver: 4WwkHay Hi ilagDietaryTnaddtyStady wtthN-Mthyi Pi i flanrnnttm n ilft-- idi Ethanol (N-MeFOSE, T-6314) InRats AatamlNmabsr 04527 04528 04529 04530 04531 C94S32 C94533 04534 04535 04536 04537 0453 04539 04540 04541 04542 04543 04544 04545 04546 04547 04548 04549 04556 04551 04552 04553 04554 04555 04556 04557 04558 04559 04560 04561 04562 Sax F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F PostGroap________________Histologic Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 1-0 ppm (Control) No Significant Findings 2-1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 2-1 ppm (Low) No Significant Findings 3-10 ppm (Low-mid) No Significant Findings 3-10 ppm (Low-mid) No Significant Findings 3-10ppm (Low-mid) No Significant Findings 3-10 ppm (Low-mid) No Significant Findings 3-10 ppm (Low-mid) No Significant Findings 3-10 ppm (Low-mid) No Significant Findings 4-30 ppm (Mid) No Significant Findings 4-30 ppm (Mid) No Significant Findings 4-30 ppm (Mid) No Significant Findings 4-30 ppm (Mid) No Significant Findings 4-30 ppm (Mid) No Significant Findings 4-30 ppm (Mid) No Significant Findings 5-100 ppm (Mid-high) No Significant Findings 5-100 ppm (Mid-high) No Significant Findings 5-100 ppm (Mid-high) No Significant Findings 5-100 ppm (Mid-high) No SignificantFindings 5-100 ppm (Mid-high) No Significant Findings 5-100 ppm (Mid-high) No Significant Findings 6-500 ppm (High) No Significant Findings 6-500 ppm (High) No Significant Findings 6-500 ppm (High) Focal Necrosis 6-500 ppm (High) Focal Necrosis 6-500 ppm (High) No Significant Findings 6-500 ppm (High) No Significant Findings 373 00033