Document 5Ln4gNY7z5E84R5vxkqkGKjk4

Sponsor: 3M St. Paul, Minnesota FINAL REPORT Study Title: 4-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys Author: Peter J. Thomford, PhD Study Completion Date: April 9, 2002 Performing Laboratory: Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Laboratory Project Identification: Covance 6329-222 Sponsor Project Identification: 3M Study No. T-6295.6 Page 1 of 235 Covance 6329-222 3M T-6295.6 COMPLIANCE STATEMENT 4-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys All aspects of this study were in accordance with the Environmental Protection Agency Good Laboratory Practice (GLP) Standards, 40 CFR 792. However, during the timeframe of March 10, 1998, through April 16, 1998, prestudy procedures such as general husbandry, health screening activities, and testing for assignment to study were conducted. The protocol was finalized on April 17, 1998. While the performance of these prestudy events without a final protocol represents a GLP deviation, they did not affect either the outcome or the interpretation of the data. Andrew M. Seacat, PhD Date Study Monitor 3M 2 Covance 6329-222 3M T-6295.6 QUALITY ASSURANCE STATEMENT This report has been reviewed by the Quality Assurance Unit of Covance Laboratories Inc. The following inspections were conducted and findings reported to the study director (SD) and associated management. Inspection Dates From To 04/21/98 04/21/98 05/20/98 05/20/98 05/20/98 05/20/98 05/21/98 05/21/98 06/01/98 06/01/98 07/08/98 07/13/98 08/14/98 08/14/98 08/10/98 08/18/98 06/04/99 06/04/99 03/27/02 03/27/02 03/27/02 03/27/02 Phase Protocol Review Protocol Amendment Review Protocol Amendment Review Clinical Laboratory Inspection Postlife Data Review Protocol Amendment Review Report Review Protocol Amendment Review Protocol Amendment Review Report Review Date Reported to Study Director and Study Director Management 04/21/98 05/20/98 05/20/98 05/21/98 06/01/98 07/13/98 08/14/98 08/18/98 06/04/99 03/27/02 03/27/02 3 Covance 6329-222 3M T-6295.6 STUDY IDENTIFICATION 4-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys Test Material Sponsor Study Monitor Alternate Study Monitor Study Location Study Director Study Timetable Study Initiation Date In-Life (Experimental) Start Date In-Life Termination Date Experimental Termination Date Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) 3M Toxicology Services Building 220-2E-02, 3M Center St. Paul, Minnesota 55144-1000 Andrew M. Seacat, PhD 3M 651.575.3161 Marvin T. Case, DVM, PhD 3M 651.733.5180 Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Peter J. Thomford, PhD Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 608.241.7207 April 17, 1998 April 23, 1998 May 22, 1998 April 8, 2002 4 KEY PERSONNEL Covance 6329-222 3M T-6295.6 Study Director Study Toxicologist Study Coordinator Supervisor, Large Animal Toxicology Supervisor, Dose Formulation Supervisor, Laboratory Animal Medicine Clinical Pathologist Supervisor, Clinical Pathology Anatomical Pathologist Anatomical Pathologist Supervisor, Anatomical Pathology Peter J. Thomford, PhD Dale Aldridge, BS Patricia K. McKee Pesik, BS, LAT Meechelle Bordeaux, LAT Dixie Bushee, BS, LATG Donna J. Clemons, DVM, MS Diplomate, ACLAM Robert L. Hall, DVM, PhD Diplomate, ACVP (Clinical Pathology) Ronald Markevitch, BS, MT (ASCP) Dawn G. Goodman, VMD Diplomate, ACVP Director of Pathology Thomas E. Palmer, PhD Kimberly W. Durland, BS, HT 5 Covance 6329-222 3M T-6295.6 CONTENTS Page ABSTRACT.......................................................................................................................10 PURPOSE ..........................................................................................................................12 REGULATORY COMPLIANCE......................................................................................12 TEST MATERIAL, VEHICLE, AND SOLVENT............................................................12 Test Material ..................................................................................................................12 Vehicle ...........................................................................................................................12 Solvent ...........................................................................................................................13 Reserve (Archive) Samples............................................................................................13 Disposition .....................................................................................................................13 TEST SYSTEM .................................................................................................................13 Test Animal....................................................................................................................13 Identification ..................................................................................................................13 Acclimation....................................................................................................................13 Housing and Maintenance..............................................................................................14 Justification ....................................................................................................................15 PROCEDURES .................................................................................................................15 Group Designations and Dose Levels............................................................................15 Dose Preparation............................................................................................................15 Dose Analyses................................................................................................................17 Method of Administration .............................................................................................17 Clinical Observations.....................................................................................................17 Body Weights.................................................................................................................18 Rectal Body Temperatures.............................................................................................18 Blood Hormone Determination......................................................................................18 Serum PFOS Level Determination ................................................................................18 Clinical Pathology..........................................................................................................19 Additional Blood Collection..........................................................................................19 Necropsy ........................................................................................................................20 Palmitoyl CoA Oxidase Determinations........................................................................20 Cell Proliferation Evaluation .........................................................................................20 Liver PFOS Determination ............................................................................................20 Tissue Preservation ........................................................................................................21 Histopathology ...............................................................................................................21 Statistical Analyses ........................................................................................................22 RECORD RETENTION ....................................................................................................22 6 Covance 6329-222 3M T-6295.6 CONTENTS (Continued) Page RESULTS ..........................................................................................................................23 Dose Analyses................................................................................................................23 Clinical Observations.....................................................................................................23 Body Weights.................................................................................................................23 Food Consumption.........................................................................................................24 Rectal Body Temperatures.............................................................................................24 Blood Hormone Analyses ..............................................................................................24 Clinical Pathology..........................................................................................................25 Cell Proliferation Evaluation .........................................................................................25 Anatomical Pathology....................................................................................................25 CONCLUSIONS................................................................................................................25 SIGNATURES...................................................................................................................26 REFERENCES ..................................................................................................................27 PATHOLOGY REPORT...................................................................................................28 COMMENTS ON THE DATA .........................................................................................31 CODES, ABBREVIATIONS, AND UNITS .....................................................................32 General Codes and Abbreviations .................................................................................33 Codes for Clinical Pathology.........................................................................................34 Abbreviations and Units for Clinical Hematology ........................................................36 Abbreviations and Units for Clinical Chemistry ...........................................................38 Codes for Anatomical Pathology ...................................................................................40 TABLES 1 Summary of Clinical Observations A.M./Weekly......................................................41 2 Summary of Clinical Observations 30 Minutes Postdose...........................................42 3 Summary of Clinical Observations 60 Minutes Postdose...........................................43 4 Summary of Clinical Observations 90 Minutes Postdose...........................................44 5 Summary of Clinical Observations Unscheduled .......................................................45 6 Summary of Body Weight Data (kg) ..........................................................................46 7 Summary of Rectal Body Temperature Data (oC) ......................................................49 8 Summary of Clinical Hematology Data - Day -7........................................................51 9 Summary of Clinical Hematology Data - Day 29 .......................................................55 10 Summary of Clinical Chemistry Data - Day -7.........................................................59 11 Summary of Clinical Chemistry Data - Day 2 ..........................................................65 12 Summary of Clinical Chemistry Data - Day 7 ..........................................................71 13 Summary of Clinical Chemistry Data - Day 14 ........................................................77 7 Covance 6329-222 3M T-6295.6 CONTENTS (Continued) Page TABLES 14 Summary of Clinical Chemistry Data - Day 29 ........................................................83 15 Summary of Clinical Chemistry Data - Day 30 ........................................................89 16 Incidence of Macroscopic Observations ...................................................................91 17 Incidence of Microscopic Observations....................................................................92 APPENDIX 1.....................................................................................................................94 Protocol Deviations........................................................................................................95 Protocol ..........................................................................................................................97 Protocol Amendment No. 1 .........................................................................................115 Protocol Amendment No. 2 .........................................................................................117 Protocol Amendment No. 3 .........................................................................................120 Protocol Amendment No. 4 .........................................................................................123 Material Safety Data Sheet ..........................................................................................125 APPENDIX 2...................................................................................................................131 Individual Animal Fate Data........................................................................................132 Individual Clinical Observations .................................................................................133 Individual Rectal Body Temperature Data (oC)...........................................................140 APPENDIX 3...................................................................................................................142 Individual Body Weight Data (kg)...............................................................................143 APPENDIX 4...................................................................................................................145 Individual Clinical Hematology Data ..........................................................................146 Individual Clinical Chemistry Data .............................................................................158 APPENDIX 5...................................................................................................................190 Individual Animal Pathology Data ..............................................................................191 APPENDIX 6...................................................................................................................203 Quality Assurance Statement - AniLytics....................................................................204 Summary and Individual Hormone Analyses Data......................................................205 Figure 1 - Mean Estradiol Data (pg/mL) - Males ........................................................209 Figure 2 - Mean Estradiol Data (pg/mL) - Females .....................................................210 Figure 3 - Mean Triiodothyronine Data (ng/dL) - Males.............................................211 Figure 4 - Mean Triiodothyronine Data (ng/dL) - Females .........................................212 APPENDIX 7...................................................................................................................213 Dose Confirmation Analysis Report ............................................................................214 Compound Stability Report .........................................................................................219 8 Covance 6329-222 3M T-6295.6 CONTENTS (Continued) Page Certificate of Analysis .................................................................................................221 Quality Assurance Statement - 3M ..............................................................................226 APPENDIX 8...................................................................................................................227 Cell Proliferation Report..............................................................................................228 9 ABSTRACT Covance 6329-222 3M T-6295.6 The purpose of this study was to provide data for determining an estimated maximum-tolerated dose and lower dose levels to be used in a chronic toxicity study and to assess the effect of the test material, Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295), on critical enzyme levels, hormones, and other selected biochemical parameters. Male and female cynomolgus monkeys were assigned to three groups (two animals/sex in Group 1, three animals/sex in Group 2, and one animal/sex in Group 3). Animals in Groups 2 and 3 received gelatin capsules containing 0.02 and 2.0 PFOS/kg of body weight/day (mg/kg/day), respectively, triturated with lactose (1:999 and 1:9, w:w, respectively). Animals in Group 1 received gelatin capsules containing lactose only. The total material dose level for each group was 20.0 mg/kg/day. Food was provided once or twice daily. Water was provided ad libitum. The animals were observed twice daily (a.m. and p.m.) for mortality and moribundity. At least once daily, animals were examined for abnormalities and signs of toxicity, and food consumption was assessed qualitatively. In addition, animals were observed approximately 30, 60, and 90 minutes postdose for signs of poor health or abnormal behavior. Body weight data were collected twice weekly beginning 2 weeks before initiation of treatment, on Day -1, on the first day of treatment, and twice weekly thereafter. Rectal body temperatures were recorded twice weekly beginning 2 weeks before initiation of treatment. Blood samples for hormone analyses [estradiol, estrone, estriol, thyroid stimulating hormone, triiodothyronine (T3), and thyroxin (T4)] were collected before initiation of treatment and predose on Day 29. Serum was harvested, and the samples were sent to Ani Lytics Inc., for analyses. Blood samples for serum PFOS concentration analyses were collected before initiation of treatment and predose on Days 2, 3 (approximately 24 hours after the first and second dose, respectively), 7, 14, and 29. Serum was harvested, and samples were sent to the Sponsor for analyses. Blood samples were collected for hematology and clinical chemistry tests before initiation of treatment and on Day 29. In addition, blood for clinical chemistry tests was collected predose on Days 2, 7, and 14. Additional blood was collected at the time of exsanguination, and samples were shipped to the Sponsor for possible future analysis. On Day 30, the animals were anesthetized, weighed, exsanguinated, and necropsied. At necropsy, macroscopic observations were recorded, and selected tissues were collected 10 Covance 6329-222 3M T-6295.6 and preserved. In addition, a sample of liver was collected from each animal for palmitoyl CoA oxidase activity analyses. Representative samples of liver, testes, and pancreas were collected from each animal and sent to Pathology Associates International for proliferation cell nuclear antigen evaluation. A sample of liver was collected from each animal and sent to the Sponsor for PFOS concentration analyses. Microscopic examinations were done on the adrenals, eye, femoral bone marrow, lung, liver, kidney, pancreas, spleen, testes, and thymus from each animal. All animals survived to the scheduled sacrifice. There were no test material-related effects on clinical observations, body weights, food consumption, rectal body temperatures, clinical pathology, or macroscopic or microscopic findings. There were no apparent test material-related effects on estrone, estriol, thyroid stimulating hormone, or thyroxin. There were no apparent test material-related effects on estradiol or triiodothyronine at 0.02 mg/kg/day. Given the low number of animals in this study, it is not possible to determine conclusively whether there was a test material-related effect on estradiol or triiodothyronine. Estradiol levels for the male and female given 2.0 mg/kg/day were numerically lower than those of the control animals on Day 29 and their respective prestudy values. Triiodothyronine levels for the male and female given 2.0 mg/kg/day were numerically lower than those of the control animals on Day 29; however, their prestudy values were also considerably lower than the control values. Triiodothyronine levels for animals given 0 or 0.02 mg/kg/day were numerically higher on Day 29 compared with their prestudy levels while triiodothyronine levels for animals given 2.0 mg/kg/day were numerically lower compared with their prestudy levels. Cell proliferation, as determined by measuring the proliferating index, was not increased in the liver, testes, or pancreas of monkeys. In cynomolgus monkeys treated with 0, 0.02, or 2.0 mg PFOS/kg/day orally for at least 4 weeks, there were no apparent test material-related effects on clinical observations, body weights, food consumption, rectal body temperatures, or clinical or anatomical pathology findings. The one male and one female treated with 2.0 mg PFOS/kg/day appeared to have lower levels of estradiol on Day 29. 11 PURPOSE Covance 6329-222 3M T-6295.6 The purpose of this study was to provide data for determining an estimated maximum-tolerated dose and lower dose levels to be used in a chronic toxicity study and to assess the effect of the test material, Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295), on critical enzyme levels, hormones, and other selected biochemical parameters. REGULATORY COMPLIANCE All aspects of this study were done in accordance with the Environmental Protection Agency Good Laboratory Practice Standards, 40 CFR 792. TEST MATERIAL, VEHICLE, AND SOLVENT Test Material The test material, Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295), Lot No. 217, is a white to off-white powder and is 86.9% pure. It was received at Covance on September 4, 1997. The test material was stored at room temperature. Information on synthesis methods, stability, purity, composition, or other characteristics that define the test material is on file with the Sponsor. The Certificate of Analysis is in Appendix 7. Vehicle The vehicle was lactose (Spectrum, New Brunswick, New Jersey), Lot No. NN0192 (expiration date February 13, 1999). It was received at Covance on March 30, 1998. The vehicle was stored at room temperature. Information on synthesis methods, purity, composition, or other characteristics that define the vehicle is on file with the manufacturer. 12 Covance 6329-222 3M T-6295.6 Solvent The solvent was acetone, USP (Spectrum, Gardena, California), Lot No. LH0253 (expiration date June 2000), and is 99.8% pure. It was received at Covance on June 23, 1997. The vehicle was stored at room temperature. Information on synthesis methods, purity, composition, or other characteristics that define the solvent is on file with the manufacturer. Reserve (Archive) Samples A reserve sample (10 g each) of each lot of the test material, vehicle, and each test material/lactose trituration was taken before initiation of treatment and stored at room temperature. These samples were transferred to the Sponsor after completion of the in-life phase. Disposition Remaining test material will be retained at Covance for use in possible future studies. TEST SYSTEM Test Animal Young adult to adult cynomolgus monkeys were obtained from Covance Research Products Inc. (Alice, Texas), on March 10, 1998. The animals weighed 2.0 to 2.5 kg at initiation of treatment. Identification Each animal was assigned a permanent number upon arrival and identified with collar tag before initiation of treatment. All data for an animal are recorded under this number. Acclimation Seven males and seven females were received on March 10, 1998, transferred from the Covance in-house stock colony on March 16, 1998, and acclimated in Animal Room 2015 for 38 days before initiation of treatment. In general, animals in this 13 Covance 6329-222 3M T-6295.6 shipment appeared healthy. During acclimation, the animals were examined for abnormalities indicative of health problems. In addition, three tuberculosis tests, a physical examination, and a fecal flotation for parasites were done on each animal. The physical examination done after the animals were received revealed no major abnormalities. Results of the tuberculosis tests were negative for all animals; the results are recorded in the data. The results of the fecal flotation tests indicated the animals were negative for parasite ova. One male and one female were eliminated from study consideration based on clinical pathology findings or abnormal fecal observations during acclimation. There were six males and six females in the randomization for assignment to groups (two animals/sex in Group 1, three animals/sex in Group 2, and one animal/sex in Group 3). Animals not selected for the study were transferred to the Covance stock colony. Housing and Maintenance Animal Room 2015 was used for this study. Environmental controls for the animal room were set to maintain 18 to 29oC, a relative humidity of 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 of the study. The animals were housed individually in stainless steel cages. Certified primate diet (#8726C, Harlan Teklad) was provided once or twice daily. The lot numbers are recorded in the data. The diet is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Results of specified nutrient and contaminant analyses are on file with Covance-Madison. Fruits or additional supplements were provided, but did not require analysis. Water was provided ad libitum. Samples of 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. 14 Covance 6329-222 3M T-6295.6 Justification PFOS is a known hepatic peroxisome proliferator (PP) in the rat. When exposed to PP, nonhuman primates (such as the cynomolgus monkey) respond similarly to humans (i.e., low to no hepatic response) and therefore are an appropriate human surrogate species. PROCEDURES This study was conducted in accordance with the Protocol dated April 17, 1998, and Protocol Amendment Nos. 1 through 4. The protocol, protocol amendments, and protocol deviations are in Appendix 1. Group Designations and Dose Levels Selection of animals for the study was based on clinical observations, clinical pathology, 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. Dose Level Total Material Dose Number of Animals Group 1 (Control) 2 (Low dose) 3 (High dose) (mg/kg/day) 0a 0.02 2.0 Level (mg/kg/day) 20.0a 20.0b 20.0c Males 2 3 1 Females 2 3 1 a The control group (Group 1) received an equivalent amount of lactose in gelatin capsules as the total material administered to Group 3. b The low-dose group received the test material triturated with lactose (1:999, w:w). c The high-dose group received the test material triturated with lactose (1:9, w:w). Dose Preparation Gelatin capsules (Torpac, Inc., Fairfield, New Jersey), Size No. 2, Lot No. 122630 (expiration date June 26, 2002), were used for dose administration. The test material triturated with lactose and lactose only (control group) were dispensed into capsules twice weekly and stored at room temperature. 15 Covance 6329-222 3M T-6295.6 Vehicle. Lactose was used as the vehicle in the dose preparations. Dose levels were based on the vehicle as supplied for Group 1. For Group 1 dose preparations, the specified amount of lactose was weighed and transferred into the gelatin capsule. The top and bottom halves of each capsule were joined, and the capsule was placed into the appropriate container labeled with study number, group number, animal number, and dose level. Test Material. For Group 2 and 3 dose preparations, the test material was dissolved in acetone and triturated with lactose (1:999 and 1:9, w:w, respectively) once before initiation of treatment. Acetone (Spectrum, Gardena, California), Lot No. LH0253 (expiration date June 2000) was used to dilute the test material with lactose. Trituration with lactose was necessary to facilitate capsule preparation. For Group 3 dose preparations, the specified amount of test material was weighed, placed into a labeled mixing container, and the appropriate volume of acetone was added to the container. The preparation was stirred manually until the test material was dissolved. The specified amount of lactose was weighed, placed into the mixing container, and thoroughly mixed using a spatula. This preparation was exposed to air until the acetone was evaporated and stirred periodically. Samples of the finished preparation for dose analyses were taken directly from the container. The triturated test material was transferred to a container and stored at room temperature and protected from light and moisture. For Group 2 preparations, the required amount of the Group 3 preparation was measured and placed into a labeled mixing container. The specified amount of lactose was weighed, placed into the mixing container, and thoroughly mixed using a spatula for approximately 5 minutes. Samples of the finished preparation for dose analyses were taken directly from the container. The triturated test material was transferred to a container and stored at room temperature and protected from light and moisture. The specified amount of triturated test material was weighed and transferred into the gelatin capsule. The top and bottom halves of each capsule were joined, and the capsule was placed into the appropriate container labeled with study number, group number, animal number, and dose level. 16 Covance 6329-222 3M T-6295.6 Dose Analyses Samples (1 g each) were collected from the top, middle, and bottom of the test material/lactose preparations for the low- and high-dose groups and stored at room temperature. The samples were shipped under ambient conditions to the Sponsor for analysis (see Protocol Deviations for exceptions). Homogeneity samples collected from the middle of the preparations were used for the prestudy stability analysis. One set of samples (1 g each) were taken from the low- and high-dose test material/lactose preparations at the end of the in-life phase and shipped to the Sponsor for analysis (see Protocol Deviations for exceptions). Results of the homogeneity, stability, and dose confirmation analyses provided by the Sponsor are in Appendix 7. Method of Administration Gelatin capsules were used for test material preparation administration to compare with data from previous toxicology studies using the oral route, which is the most likely route of exposure. The dose preparations were administered orally in gelatin capsules once daily (7 days/week) for 29 days (see Protocol Deviations for exceptions). The dosing tubes were flushed with 5 mL of reverse osmosis water. Individual doses were calculated based on the most recently recorded body weights, with the exception of body weight collection days when the previous body weight was used. Animals were dosed at approximately the same time each day. Clinical Observations The animals were observed twice daily (a.m. and p.m.) for mortality and moribundity. Each animal was observed daily, and food consumption was assessed qualitatively; abnormal findings were recorded. Animals were observed approximately 30, 60, and 90 minutes postdose for signs of poor health or abnormal behavior. Effects were recorded as they were observed. Animals were observed once weekly; abnormal findings or an indication of normal was recorded. 17 Covance 6329-222 3M T-6295.6 Body Weights Individual body weight data were recorded twice weekly beginning 2 weeks before initiation of treatment (Monday and Thursday), on the first day of treatment, and twice weekly thereafter. An additional body weight was recorded on Day -1 for the Day 1 dose calculations. Rectal Body Temperatures Rectal body temperatures were taken at approximately 11:00 twice weekly beginning 2 weeks before initiation of treatment [Monday and Thursday (see Protocol Deviations for exceptions)]. Animals were not anesthetized for the procedure. Blood Hormone Determination Approximately 5 mL of whole blood were collected from a femoral vein of each animal before initiation of treatment (Day -7) and predose on Day 29. Blood was collected between 07:00 and 09:00. Animals were fasted overnight before collections. All samples were collected without anticoagulant, maintained at room temperature, and allowed to clot. Samples were centrifuged within 1 hour after collection, and serum samples were harvested. Serum was divided into two approximately equal aliquots (blood collected on Day 29 only) and stored in a freezer set to maintain -60 to -80oC until packed on dry ice and shipped to Ani Lytics Inc., for analyses. The samples were analyzed for estradiol, estrone, estriol, thyroid stimulating hormone, triiodothyronine (T3), and thyroxin (T4). Results of these analyses were provided by Ani Lytics Inc., and are in Appendix 6. Serum PFOS Level Determination Approximately 5 (Day -7 only) or 2 mL of whole blood were collected from a femoral vein of each animal before initiation of treatment (Day -7) and predose on Days 2, 3 (approximately 24 hours after the first and second dose, respectively), 7, 14, and 29. Animals were fasted overnight before collections. All samples were collected without anticoagulant, maintained at room temperature, and allowed to clot. Samples were centrifuged within 1 hour after collection, and serum was harvested and stored in a freezer set to maintain -60 to -80oC until packed on dry ice and shipped to the Sponsor for analyses. The samples were analyzed for PFOS. Results of these analyses will be reported separately by the Sponsor. 18 Covance 6329-222 3M T-6295.6 Clinical Pathology Blood samples were collected from each animal on Days -7 and 29 for hematology and clinical chemistry tests. In addition, blood for clinical chemistry tests was collected from each animal predose on Days 2, 7, and 14. Animals were fasted overnight; water was provided ad libitum. Blood was collected from the femoral vein. The following were evaluated: 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 blood cell morphology reticulocyte count glucose urea nitrogen creatinine total protein albumin globulin total bilirubin cholesterol triglycerides aspartate aminotransferase alanine aminotransferase alkaline phosphatase Clinical Chemistry gamma glutamyl transferase sorbitol dehydrogenase creatine kinase calcium inorganic phosphorus sodium potassium chloride serum bile acids amylase lipase pancreatic-specific amylase Additional Blood Collection Whole blood (approximately 20 mL) was collected from the vena cava of each animal at the time of exsanguination (See Protocol Deviations for exceptions). The anticoagulant was potassium EDTA. Samples were transferred into containers (approximately 5 mL each) and stored in a freezer set to maintain -60 to -80oC until packed on dry ice and shipped to the Sponsor possible future analysis. 19 Covance 6329-222 3M T-6295.6 Necropsy On Day 30, animals that were fasted overnight were anesthetized with ketamine and xylazine, weighed, bled for required tests, exsanguinated, and necropsied. Animals were necropsied in random order. The necropsy included a macroscopic examination of the external surface of the body; all orifices; the cranial cavity; the brain and spinal cord; the nasal cavity and paranasal sinuses; cervical tissues and organs; and the thoracic, abdominal, and pelvic cavities and viscera. Palmitoyl CoA Oxidase Determinations A sample of the right lateral lobe of liver was collected from each animal at scheduled sacrifice. The sample was flash-frozen in liquid nitrogen and stored in a freezer set to maintain -60 to -80oC until analyzed for palmitoyl CoA oxidase activity. Cell Proliferation Evaluation Representative samples of the liver, testes, and pancreas were collected and preserved in zinc formalin. After fixation, samples for proliferation cell nuclear antigen (PCNA) evaluation were embedded in paraffin and shipped to Pathology Associates International for PCNA evaluation. PCNA evaluation (including examination of slides stained with hematoxylin and eosin) was done on the samples. Results of the evaluation provided by Pathology Associates International are in Appendix 8. Liver PFOS Determination A sample of liver was collected from each animal at sacrifice, weighed, flash-frozen in liquid nitrogen, and stored in a freezer set to maintain -60 to -80oC until packed on dry ice and shipped with plasma samples to the Sponsor for PFOS analysis. Results of these analyses will be reported separately by the Sponsor. 20 Covance 6329-222 3M T-6295.6 Tissue Preservation The following tissues (when present) or representative samples were collected and preserved in 10% neutral-buffered formalin, unless otherwise specified, for possible future microscopic examination: adrenal (2) aorta brain cecum cervix colon duodenum epididymis (2) esophagus eyes [preserved in Davidson's fixative (2)] femur with bone marrow (articular surface of the distal end) gallbladder heart ileum jejunum kidney (2) liver lung lymph node (mesenteric) mammary gland muscle (thigh) ovary (2) pancreas pituitary prostate rectum salivary gland [mandibular (2)] sciatic nerve seminal vesicle (2) skin spinal cord (cervical, thoracic, and lumbar) spleen sternum with bone marrow stomach testis (2) thymus thyroid (2) with parathyroid trachea urinary bladder uterus vagina Histopathology The adrenals, eye, femoral bone marrow, lung, liver, kidney, pancreas, spleen, testes, and thymus were embedded in paraffin, sectioned, stained with hematoxylin and eosin, and examined microscopically from each animal (see Protocol Deviations for exceptions). Bone marrow smears from the sternum of each animal at the scheduled sacrifice were prepared, stained with Wright's stain, and retained for possible examination. 21 Covance 6329-222 3M T-6295.6 Statistical Analyses Only data collected on or after the first day of treatment were analyzed statistically. Statistical analyses were not done on data collected for Group 3 due to the small number of animals. One-way analysis of variance [ANOVA (Winer, 1971a)] was used to analyze initial body weights, rectal body temperature, palmitoyl CoA oxidase activities, and continuous clinical pathology values. Levene's test (Levene, 1960) was done to test for variance homogeneity. In the case of heterogeneity of variance at p < 0.05, transformations were used to stabilize the variance. ANOVA was done on the homogeneous or transformed data. If the ANOVA was significant, Dunnett's t-test (Dunnett, 1964) was used for control versus treated group comparisons. One-way analysis of covariance [ANCOVA (Winer, 1971b)] was used to analyze body weights, with initial body weights as the covariate. Although Levene's test for variance homogeneity was done (see above), no transformations were used because covariance adjustment removed extraneous heterogeneity. If the ANCOVA was significant, least squares means t-test was used for control versus treated group comparisons. For each sex, Group 2 was compared with Group 1 (Control). Group comparisons were evaluated at the 5.0% two-tailed probability level. RECORD RETENTION All raw data, documentation, records, protocol, and specimens generated as a result of this study will be archived in the storage facilities of Covance-Madison for a period of 1 year. One year after the submission of the final report, the Sponsor will determine the final disposition of the materials. All raw data stored on magnetic media and an original copy of the final report will be retained by Covance-Madison. 22 Covance 6329-222 3M T-6295.6 Within 1 year after submission of the final report, all of the aforementioned materials (as appropriate) from the Sponsor's designees (3M E.T. & S and Ani Lytics Inc.) will be sent to the Sponsor (Andrew Seacat, PhD, 3M). Pathology Associates International (PAI) is responsible for the maintenance of any raw data or specimens produced by PAI. RESULTS Dose Analyses Results of analyses provided by the Sponsor are in Appendix 7. Dose analysis results indicate that the average + standard deviation for the 2.0 mg/kg/day dose level prepared at a 1:9 dilution was 80 + 02% of target. The average + standard deviation for the 0.02 mg/kg/day dose level prepared at a 1:999 dilution was 54% + 02% of target. The stability samples obtained from the middle of each mixture on May 22, 1998, were 79% and 71% of target for the 2.0 and 0.02 mg/kg/day preparations, respectively. Inherent variability and lack of sufficient sensitivity in the analytical method for measuring (PFOS; T-6295) resulted in stability and routine analysis data that were outside of the generally recognized as acceptable standard limits of + 15%. Clinical Observations Clinical observations are summarized in Tables 1 through 5; individual data are in Appendix 2. All animals survived to the scheduled sacrifice. There were no test material-related clinical observations. Body Weights Body weight data are summarized in Table 6; individual data are in Appendix 3. There were no apparent test material-related effects on body weights. 23 Covance 6329-222 3M T-6295.6 Food Consumption Food consumption data are summarized in Table 1 (Summary of Clinical Observations - A.M./Weekly); individual data are included in the individual clinical observations in Appendix 2. There were no test material-related effects on food consumption. Rectal Body Temperatures Rectal body temperature data are summarized in Tables 7; individual data are in Appendix 2. There were no test material-related effects on rectal body temperatures. Blood Hormone Analyses Summary and individual hormone analyses data are in Appendix 6. Estradiol and triiodothyronine analyses data are illustrated in Figures 1 through 4 (Appendix 6). There were no apparent test material-related effects on estrone, estriol, thyroid stimulating hormone, or thyroxin. There were no apparent test material-related effects on estradiol or triiodothyronine at 0.02 mg/kg/day. Given the low number of animals in this study, it is not possible to determine conclusively whether there was a test material-related effect on estradiol or triiodothyronine. Estradiol levels for the male and female given 2.0 mg/kg/day were numerically lower than those of the control animals on Day 29 and their respective prestudy values. Triiodothyronine levels for the male and female given 2.0 mg/kg/day were numerically lower than those of the control animals on Day 29; however, their prestudy values were also considerably lower than the control values. Triiodothyronine levels for animals given 0 or 0.02 mg/kg/day were numerically higher on Day 29 compared with their prestudy levels while triiodothyronine levels for animals given 2.0 mg/kg/day were numerically lower compared with their prestudy levels. 24 Covance 6329-222 3M T-6295.6 Clinical Pathology Hematology and clinical chemistry data are summarized in Tables 8 through 15; individual data are in Appendix 4. The Pathology Report contains a discussion of the data. Administration of PFOS had no effects on clinical pathology test results. Cell Proliferation Evaluation Results of cell proliferation evaluation provided by Pathology Associates International are in Appendix 8. Cell proliferation, as determined by measuring the proliferating index, was not increased in the liver, testes, or pancreas of monkeys. Anatomical Pathology Incidences of macroscopic and microscopic observations are summarized in Tables 16 and 17. Individual data are in Appendix 5. The Pathology Report contains a discussion of the data. There were no test material-related macroscopic or microscopic changes in the organs and tissues examined. CONCLUSIONS In cynomolgus monkeys treated with 0, 0.02, or 2.0 mg PFOS/kg/day orally for at least 4 weeks, there were no apparent test material-related effects on clinical observations, body weights, food consumption, rectal body temperatures, or clinical or anatomical pathology findings. The one male and one female treated with 2.0 mg PFOS/kg/day appeared to have lower levels of estradiol on Day 29. 25 SIGNATURES Covance 6329-222 3M T-6295.6 26 Covance 6329-222 3M T-6295.6 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 of 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 of Covariance," Statistical Principles in Experimental Design, Second Ed., Ch. 10, pp. 752-812, McGraw-Hill: New York, New York (1971b). 27 PATHOLOGY REPORT Covance 6329-222 3M T-6295.6 SUMMARY The purpose of this study was to provide data for determining an estimated maximum-tolerated dose and lower dose levels to be used in a chronic toxicity study and to assess the effect of the test material, Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295), on critical enzyme levels, hormones, and other selected biochemical parameters. Administration of PFOS had no effects on clinical pathology test results and caused no test material-related macroscopic or microscopic changes in the organs and tissues examined. METHODS Three groups of male and female cynomolgus monkeys were administered the test material orally via capsule at a dose level of 0 (control group; received the vehicle, lactose), 0.02, or 2.0 mg/kg of body weight/day (mg/kg/day) for 29 days. The control group had two animals/sex, the low-dose group had three animals/sex, and the high-dose group had one animal/sex. Blood was collected for hematology and clinical chemistry tests before initiation of treatment (Day -7) and on Day 29. In addition, blood for clinical chemistry tests was collected on Days 2, 7, and 14. The animals were sacrificed and necropsied on Day 30; macroscopic observations were recorded, and tissues were preserved in fixative as specified by the protocol. Samples of liver were collected and frozen for determination of hepatic palmitoyl CoA oxidase activity and for determination of PFOS content (by the Sponsor). Samples of liver, testes, and pancreas were collected and preserved in zinc formalin for evaluation of proliferation cell nuclear antigen (PCNA; by Pathology Associates International). Microscopic examinations were done on adrenals, eye, femoral bone marrow, lung, liver, kidney, pancreas, spleen, testes, and thymus from all animals. Results of clinical pathology tests for the control and low-dose groups were compared statistically. 28 RESULTS AND DISCUSSION Mortality All animals survived to the scheduled sacrifice. Covance 6329-222 3M T-6295.6 Clinical Pathology Individual values for hematology and clinical chemistry tests are in Appendix 4. Mean values and the results of statistical comparisons are in Tables 8 through 15. Day -7. Clinical pathology test results indicated no obvious group or individual health abnormalities. Days 2, 7, and 14. Administration of the test material had no effects on clinical chemistry test results at these collection intervals. Statistically significant differences for clinical chemistry results between the control and low-dose groups were inconsistent over time and between the sexes. Several of the differences were similar to differences present at Day -7, and none of the differences exhibited a strong dose relationship (i.e., the high-dose animals did not exhibit notable differences for the same parameters). Day 29. Administration of the test material had no effects on hematology or clinical chemistry test results at Day 29. Statistically significant differences for red blood cell count, neutrophil count, monocyte count, and hepatic palmitoyl CoA oxidase were inconsistent between the sexes and exhibited no dose relationship. Statistically significant differences for triglycerides and alkaline phosphatase were similar to differences observed at Day -7. Anatomical Pathology Anatomical pathology findings for each animal are in Appendix 5. Incidence summaries of the macroscopic and microscopic observations are in Tables 16 and 17. 29 Covance 6329-222 3M T-6295.6 30 COMMENTS ON THE DATA Covance 6329-222 3M T-6295.6 Various models of 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. Some tabular data were compiled using Excel Version 7.0 software. The summary tables for clinical observations indicate the number of 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. The day of initiation of treatment is "Day 1." 31 CODES, ABBREVIATIONS, AND UNITS General Codes and Abbreviations Codes for Clinical Pathology Abbreviations and Units for Clinical Hematology Abbreviations and Units for Clinical Chemistry Codes for Anatomical Pathology Covance 6329-222 3M T-6295.6 Note: The following lists of codes, abbreviations, and units are used by Covance. Some, but not necessarily all, of this information may be needed for this report. 32 Covance 6329-222 3M T-6295.6 General Codes and Abbreviations WK N Mean; MEAN CAM SD; S.D.; STAND DEV; STANDARD DEV; sd * -; NA P UNSCHED DISPATCH MIN OBS Week. Number of measurements in a group. Arithmetic mean. Covariate-adjusted mean. Standard deviation. Group 2 mean is significantly different from the mean of the control group (Group 1) at p < 0.05. No value; not applicable; not present. Present. 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. Minute. Observation. Animal Death Codes: T Terminal sacrifice. 33 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 6329-222 3M T-6295.6 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 of 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 34 Covance 6329-222 3M T-6295.6 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), and toxic neutrophils (TOXNEUT): Scale 1 2 3 4 Degree Normal for the species Slight Moderate Marked Not applicable Presence Not present Rare Few Moderate Many 35 Covance 6329-222 3M T-6295.6 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 X106/mL) HGB (G/DL) HCT (%) MCV (FL) MCH (PG) MCHC (%) PLT (E3/UL or X103/mL) MPV (FL) RETIC (%) RETIC (E3/UL or X103/mL) 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/mL) NRBC (/100 WBC) COR WBC (E3/UL or X103/mL) N-SEG (E3/UL or X103/mL) and % N-BAND (E3/UL or X103/mL) and % LYMPH (E3/UL or X103/mL) and % MONO (E3/UL or X103/mL) and % EOSIN (E3/UL or X103/mL) and % BASO (E3/UL or X103/mL) and % ANISO (-,1,2,3) POLY (-,1,2,3) 36 Covance 6329-222 3M T-6295.6 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) 37 Covance 6329-222 3M T-6295.6 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) ALK PHOS (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) I PHOS (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) 38 Covance 6329-222 3M T-6295.6 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 Alpha-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 Pancreatic-specific amylase 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-1 (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) P AMYL (U/L) CK-BB (U/L) CK-MB (U/L) CK-MM (U/L) 39 Covance 6329-222 3M T-6295.6 Codes for Anatomical Pathology MICROSCOPIC CODES Distribution of Findings Focal Diffuse Multifocal 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 of change, but readily discernible as abnormal 3 Moderate - the average amount of change that is expected for a lesion 4 Moderately severe (marked) - a marked amount of change with possible loss of function of the affected cells or organs 5 Severe - a great amount of change with probable loss of function of the affected cell or organs and frequently involves large areas of the organ 40 Table 1 Summary of Clinical Observations A.M./Weekly Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED DAYS 1-30 SEX: -----MALE---- ----FEMALE--- GROUP: 1 2 3 1 2 3 CATEGORY DOSE: 0 0.02 2 0 0.02 2 KEYWORD QUALIFIER NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------------------- *** TOP OF LIST *** APPEARANCE SWOLLEN LIP(S) 0 0 0 1 0 0 DISCHARGE VOMITUS CONTAINING FOOD APPEARS TO BE MENSTRUATING 0 0 1 0 0 0 0 0 0 0 1 0 DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR 0 0 1 0 0 0 EXCRETION FEW FECES NON-FORMED FECES 0 0 0 0 0 1 0 0 0 2 0 0 SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH 0 0 0 1 0 0 0 0 0 1 0 0 QUALITATIVE FOOD CONSUMPTION LOW *** END OF LIST *** 0 1 0 1 0 1 41 Table 2 Summary of Clinical Observations 30 Minutes Postdose Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED DAYS 1-29 SEX: -----MALE---- ----FEMALE--- GROUP: 1 2 3 1 2 3 CATEGORY DOSE: 0 0.02 2 0 0.02 2 KEYWORD QUALIFIER NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------------------- *** TOP OF LIST *** APPEARANCE SWOLLEN LIP(S) 0 0 0 1 0 0 EXCRETION NON-FORMED FECES 0 0 0 1 0 0 SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH *** END OF LIST *** 0 0 0 1 0 0 0 0 0 1 0 0 42 Table 3 Summary of Clinical Observations 60 Minutes Postdose Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------------ NUMBER OF ANIMALS AFFECTED DAYS 1-29 SEX: -----MALE---- ----FEMALE--- GROUP: 1 2 3 1 2 3 CATEGORY DOSE: 0 0.02 2 0 0.02 2 KEYWORD QUALIFIER NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------------------------ *** TOP OF LIST *** APPEARANCE SWOLLEN LIP(S) 0 0 0 1 0 0 EXCRETION MUCOID FECES 1 0 0 0 0 0 SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH *** END OF LIST *** 0 0 0 1 0 0 0 0 0 1 0 0 43 Table 4 Summary of Clinical Observations 90 Minutes Postdose Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ----------------------------------------------------------------------------------------------------------------------------- NUMBER OF ANIMALS AFFECTED DAYS 1-29 SEX: -----MALE---- ----FEMALE--- GROUP: 1 2 3 1 2 3 CATEGORY DOSE: 0 0.02 2 0 0.02 2 KEYWORD QUALIFIER NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------------------- *** TOP OF LIST *** APPEARANCE SWOLLEN LIP(S) 0 0 0 1 0 0 SKIN & PELAGE RED SKIN LIP(S) SCAB(S) MOUTH *** END OF LIST *** 0 0 0 1 0 0 0 0 0 1 0 0 44 Table 5 Summary of Clinical Observations Unscheduled Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------ NUMBER OF ANIMALS AFFECTED DAYS 1-30 SEX: -----MALE---- ----FEMALE--- GROUP: 1 2 3 1 2 3 CATEGORY DOSE: 0 0.02 2 0 0.02 2 KEYWORD QUALIFIER NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------------------------------------------------------------ *** TOP OF LIST *** DISCHARGE VOMITUS CONTAINING FOOD 0 1 0 0 0 0 *** END OF LIST *** 45 Table 6 Summary of Body Weight Data (kg) Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------- SEX: ---------------MALE--------------- --------------FEMALE-------------- GROUP: 1 2 3 1 2 3 DOSE: 0 0.02 2 0 0.02 2 DAY UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ------------------------------------------------------------------------------------------------------------------------------- -14 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.00 0.21 2 3 1 2.1 2.1 2.2 0.07 0.17 -10 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.07 0.21 2 3 1 2.1 2.1 2.1 0.07 0.10 -7 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.07 0.21 2 3 1 2.1 2.1 2.2 0.00 0.15 -3 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.07 0.21 2 3 1 2.1 2.1 2.1 0.00 0.15 -1 N 2 3 1 MEAN 2.3 2.4 2.2 S.D. 0.00 0.25 2 3 1 2.1 2.1 2.2 0.00 0.20 1 N 2 3 1 MEAN 2.3 2.3 2.2 S.D. 0.14 0.21 2 3 1 2.1 2.2 2.2 0.00 0.15 5 N 2 3 1 CAM 2.3 2.3 MEAN 2.3 2.3 2.2 S.D. 0.07 0.17 2 3 1 2.0 2.1 2.0 2.1 2.1 0.00 0.15 46 Table 6 Covance 6329-222 3M T-6295.6 Summary of Body Weight Data (kg) 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 2 ------------------------------------------------------------------------------------------------------------------------------- SEX: ---------------MALE--------------- --------------FEMALE-------------- GROUP: 1 2 3 1 2 3 DOSE: 0 0.02 2 0 0.02 2 DAY UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ------------------------------------------------------------------------------------------------------------------------------- 8 N 2 3 1 CAM 2.5 2.4 MEAN 2.5 2.4 2.3 S.D. 0.07 0.12 2 3 1 2.2 2.2 2.2 2.2 2.2 0.07 0.20 12 N 2 3 1 CAM 2.5 2.3* MEAN 2.5 2.3 2.2 S.D. 0.07 0.12 2 3 1 2.1 2.1 2.1 2.2 2.2 0.00 0.15 15 N 2 3 1 CAM 2.4 2.4 MEAN 2.4 2.4 2.3 S.D. 0.14 0.06 2 3 1 2.2 2.2 2.2 2.2 2.1 0.07 0.20 19 N 2 3 1 CAM 2.5 2.4 MEAN 2.5 2.4 2.3 S.D. 0.07 0.06 2 3 1 2.1 2.3 2.1 2.3 2.3 0.00 0.17 22 N 2 3 1 CAM 2.5 2.4 MEAN 2.5 2.4 2.1 S.D. 0.07 0.10 2 3 1 2.2 2.2 2.2 2.2 2.1 0.07 0.15 26 N 2 3 1 CAM 2.5 2.4 MEAN 2.5 2.4 2.1 S.D. 0.07 0.10 2 3 1 2.2 2.2 2.2 2.2 2.1 0.07 0.15 29 N 2 3 1 CAM 2.4 2.4 MEAN 2.4 2.4 2.0 S.D. 0.07 0.06 2 3 1 2.1 2.1 2.1 2.1 2.1 0.00 0.15 47 48 Table 7 Summary of Rectal Body Temperature Data (oC) Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------- SEX: ---------------MALE--------------- --------------FEMALE-------------- GROUP: 1 2 3 1 2 3 DOSE: 0 0.02 2 0 0.02 2 DAY UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ------------------------------------------------------------------------------------------------------------------------------- -14 N MEAN S.D. 2 39.8 0.28 3 39.2 0.57 1 39.6 2 40.2 0.28 3 40.1 0.50 1 40.0 -10 N MEAN S.D. 2 40.0 0.35 3 39.2 0.40 1 39.5 2 39.8 0.49 3 39.7 0.55 1 39.8 -7 N MEAN S.D. 2 39.8 0.57 3 39.0 0.72 1 39.1 2 39.9 0.21 3 40.0 0.38 1 39.9 -3 N MEAN S.D. 2 39.6 0.28 3 39.2 0.45 1 39.2 2 39.8 0.49 3 39.8 0.10 1 39.7 1 N MEAN S.D. 2 39.0 0.57 3 39.4 0.30 1 39.4 2 39.6 0.35 3 39.9 0.29 1 39.5 5 N MEAN S.D. 2 38.9 0.07 3 39.1 0.59 1 39.9 2 39.0 0.35 3 39.8 0.25 1 39.7 8 N MEAN S.D. 2 38.5 0.35 3 39.2 0.40 1 39.6 2 39.1 0.42 3 39.8 0.21 1 39.9 49 Table 7 Summary of Rectal Body Temperature Data (oC) Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 2 ------------------------------------------------------------------------------------------------------------------------------- SEX: ---------------MALE--------------- --------------FEMALE-------------- GROUP: 1 2 3 1 2 3 DOSE: 0 0.02 2 0 0.02 2 DAY UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY ------------------------------------------------------------------------------------------------------------------------------- 12 N MEAN S.D. 2 39.0 0.07 3 39.1 0.47 1 40.0 2 39.2 0.14 3 39.8 0.25 1 39.7 15 N MEAN S.D. 2 39.7 0.00 3 39.7 0.42 1 39.7 2 39.7 0.57 3 40.0 0.20 1 39.8 19 N MEAN S.D. 2 38.7 0.21 3 38.7 0.64 1 38.9 2 39.0 0.35 3 39.3 0.21 1 39.3 22 N MEAN S.D. 2 39.4 0.21 3 39.5 0.57 1 39.4 2 39.6 0.42 3 39.8 0.25 1 39.4 26 N MEAN S.D. 2 38.8 0.07 3 39.2 0.38 1 39.2 2 39.0 0.35 3 39.6 0.15 1 39.1 29 N MEAN S.D. 2 38.5 0.42 3 38.8 0.35 1 38.9 2 38.8 0.14 3 39.1 0.38 1 39.2 50 Table 8 Summary of Clinical Hematology Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day ------ RBC X106/mL -------- HGB G/DL -------- HCT % -------- MCV FL -------- MCH PG -------- MCHC % -------- PLT X103/mL -------- RETIC RETIC % X103/mL -------- -------- 0 MEAN 5.64 14.0 42.6 75.4 24.8 32.9 502 .9 S.D. .332 1.41 3.82 2.26 1.06 .42 138.6 .00 N 2 2 2 2 2 2 2 2 51 2.8 2 0.02 MEAN 5.18 12.6 39.1 75.4 24.4 32.4 454 .9 S.D. .272 .31 .90 2.21 1.10 .91 88.1 .53 N 3 3 3 3 3 3 3 3 46 26.1 3 2.0 MEAN 5.91 12.8 41.0 69.4 21.7 31.2 531 .7 41 N 1 1 1 1 1 1 1 1 1 51 Table 8 Summary of Clinical Hematology Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day WBC X103/mL N-SEG X103/mL LYMPH X103/mL MONO X103/mL EOSIN X103/mL BASO X103/mL N-SEG% LYMPH% MONO% EOSIN% BASO% ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 8.4 3.4 4.6 .4 .1 .0 40 54 4 1 0 S.D. .99 1.06 .07 .07 .14 .00 7.8 7.1 .7 1.4 .0 N 2 2 2 2 2 2 2 2 2 2 2 0.02 MEAN 9.2 2.9 5.8 .4 .1 .0 31 63 4 1 0 S.D. 1.00 1.33 1.46 .20 .10 .00 16.5 14.6 2.0 1.0 .0 N 3 3 3 3 3 3 3 3 3 3 3 2.0 MEAN 8.2 2.8 4.8 .6 .0 .0 34 58 8 0 0 N 1 1 1 1 1 1 1 1 1 1 1 52 Table 8 Summary of Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE RBC HGB HCT MCV MCH MCHC PLT RETIC RETIC mg/kg/day X106/mL G/DL % FL PG % X103/mL % X103/mL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 5.25 13.3 40.4 76.9 25.4 33.1 478 .8 S.D. .325 1.34 3.96 2.69 .92 .00 180.3 .21 N 2 2 2 2 2 2 2 2 45 14.1 2 0.02 MEAN 5.00 12.8 39.1 78.2 25.6 32.7 430 .7 S.D. .241 .21 .21 3.30 1.55 .56 121.3 .17 N 3 3 3 3 3 3 3 3 35 8.5 3 2.0 MEAN 5.53 13.4 40.2 72.7 24.2 33.3 505 .8 44 N 1 1 1 1 1 1 1 1 1 53 Table 8 Summary of Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day -----0 MEAN S.D. N WBC X103/mL -------- 9.0 1.48 2 N-SEG X103/mL -------- 3.6 1.91 2 LYMPH X103/mL -------- 5.1 .14 2 MONO X103/mL -------- .2 .28 2 EOSIN X103/mL -------- .0 .07 2 BASO X103/mL -------- .0 .00 2 N-SEG% LYMPH% MONO% EOSIN% BASO% -------- -------- -------- -------- -------- 38 58 2 0 0 14.8 11.3 3.5 .7 .0 2 2 2 2 2 0.02 MEAN 10.2 3.5 6.2 .4 .1 .0 36 59 4 1 0 S.D. 1.97 3.29 4.05 .12 .10 .00 34.2 32.9 1.5 1.0 .0 N 3 3 3 3 3 3 3 3 3 3 3 2.0 MEAN 11.7 6.2 4.8 .4 .2 .0 53 42 4 1 0 N 1 1 1 1 1 1 1 1 1 1 1 54 Table 9 Summary of Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE RBC HGB HCT MCV MCH MCHC PLT RETIC RETIC mg/kg/day X106/mL G/DL % FL PG % X103/mL % X103/mL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 6.02 14.0 44.0 72.9 23.3 31.9 440 .8 S.D. .035 .64 1.84 2.69 .99 .21 116.7 .14 N 2 2 2 2 2 2 2 2 48 8.5 2 0.02 MEAN 5.12 * 12.6 39.1 76.4 24.6 32.2 392 .5 S.D. .262 .78 2.18 1.69 .61 .26 92.1 .35 N 3 3 3 3 3 3 3 3 28 19.8 3 2.0 MEAN 5.69 13.2 41.5 73.1 23.1 31.7 503 .2 11 N 1 1 1 1 1 1 1 1 1 55 Table 9 Summary of Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day WBC X103/mL N-SEG X103/mL LYMPH X103/mL MONO X103/mL EOSIN X103/mL BASO X103/mL N-SEG% LYMPH% MONO% EOSIN% BASO% ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 9.2 1.6 6.8 .6 .2 .0 18 74 6 2 0 S.D. .21 .49 .78 .21 .14 .00 5.7 7.1 2.8 1.4 .0 N 2 2 2 2 2 2 2 2 2 2 2 0.02 MEAN 8.8 1.0 6.9 .6 .2 .0 13 78 6 2 0 S.D. 2.44 .15 2.27 .38 .10 .00 6.1 5.5 2.3 1.0 .0 N 3 3 3 3 3 3 3 3 3 3 3 2.0 MEAN 5.8 .9 4.4 .4 .0 .0 16 77 7 0 0 N 1 1 1 1 1 1 1 1 1 1 1 56 Table 9 Summary of Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE RBC HGB HCT MCV MCH MCHC PLT RETIC RETIC mg/kg/day X106/mL G/DL % FL PG % X103/mL % X103/mL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 5.14 13.2 40.5 78.9 25.6 32.5 S.D. .170 .78 2.33 2.12 .71 .00 N 2 2 2 2 2 2 511 182.4 2 1.2 .21 2 59 12.7 2 0.02 MEAN 5.13 13.1 41.1 80.1 25.5 31.9 425 .8 S.D. .116 .87 1.74 3.93 1.80 .81 116.7 .26 N 3 3 3 3 3 3 3 3 41 14.0 3 2.0 MEAN 4.81 12.3 36.7 76.4 25.6 33.6 529 1.0 48 N 1 1 1 1 1 1 1 1 1 57 Table 9 Summary of Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day WBC X103/mL N-SEG X103/mL LYMPH X103/mL MONO X103/mL EOSIN X103/mL BASO X103/mL N-SEG% LYMPH% MONO% EOSIN% BASO% ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 11.1 3.8 6.2 1.0 .0 .0 36 54 10 0 0 S.D. 2.69 .14 2.55 .21 .00 .00 10.6 10.6 .7 .0 .0 N 2 2 2 2 2 2 2 2 2 2 2 0.02 MEAN 10.0 2.2 * 7.1 .6 * .1 .0 22 70 6 1 0 S.D. 2.55 .45 2.67 .06 .00 .00 7.6 9.2 2.1 .0 .0 N 3 3 3 3 3 3 3 3 3 3 3 2.0 MEAN 15.7 7.2 7.9 .5 .1 .0 46 50 3 1 0 N 1 1 1 1 1 1 1 1 1 1 1 58 Table 10 Summary of Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 82 24 1.0 8.2 5.2 3.0 .2 S.D. 19.1 1.4 .07 .00 .00 .00 .07 N 2 2 2 2 2 2 2 8 155 .7 62.2 2 2 64 24.7 2 0.02 MEAN 61 29 1.0 7.7 4.8 3.0 .3 S.D. 13.2 2.0 .06 .06 .29 .32 .06 N 3 3 3 3 3 3 3 9 161 1.5 35.4 3 3 85 22.2 3 2.0 MEAN 54 28 1.0 8.2 5.0 3.2 .4 10 150 68 N 1 1 1 1 1 1 1 1 1 1 59 Table 10 Summary of Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 48 4.9 2 40 9.2 2 612 36.1 2 88 4.9 2 4 228 424 .7 102.5 99.7 2 2 2 64 37.5 2 291 69.3 2 0.02 MEAN S.D. N 50 7.6 3 58 13.0 3 681 81.1 3 101 36.7 3 6 214 315 1.2 17.2 63.1 3 3 3 62 61.2 3 223 50.1 3 2.0 MEAN 54 N 1 50 1086 117 1 1 1 5 220 244 1 1 1 7 144 1 1 60 Table 10 Summary of Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 10.7 S.D. .14 N 2 7.2 .57 2 162 2.1 2 5.8 .07 2 110 .0 2 0.02 MEAN S.D. N 10.6 .52 3 7.7 .71 3 159 5.0 3 5.6 .47 3 112 4.6 3 2.0 MEAN 11.4 8.7 162 5.9 111 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 61 Table 10 Summary of Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 76 24 1.0 8.0 5.1 2.8 .5 S.D. 8.5 .0 .14 .49 .42 .07 .28 N 2 2 2 2 2 2 2 4 142 5.7 15.6 2 2 76 14.1 2 0.02 MEAN 64 26 .9 7.9 4.9 3.0 .4 S.D. 9.0 4.6 .06 .30 .26 .10 .06 N 3 3 3 3 3 3 3 9 154 2.1 34.6 3 3 69 35.8 3 2.0 MEAN 71 27 1.0 8.2 4.9 3.3 .3 12 141 67 N 1 1 1 1 1 1 1 1 1 1 62 Table 10 Summary of Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 99 76.4 2 53 21.2 2 593 66.5 2 80 2.1 2 6 1907 4.9 2286.8 2 2 334 31.1 2 10 10.6 2 232 21.9 2 0.02 MEAN S.D. N 58 6.7 3 58 14.2 3 828 65.5 3 74 10.1 3 4 385 324 1.0 163.0 44.1 3 3 3 64 81.8 3 215 19.4 3 2.0 MEAN 53 N 1 55 683 110 1 1 1 3 1094 315 1 1 1 89 224 1 1 63 Table 10 Summary of Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 11.0 S.D. .49 N 2 7.4 1.27 2 159 2.8 2 7.2 1.91 2 113 2.8 2 0.02 MEAN S.D. N 11.0 .59 3 8.0 1.72 3 158 6.7 3 5.8 .64 3 114 4.0 3 2.0 MEAN 11.3 6.8 165 6.0 115 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 64 Table 11 Summary of Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 57 25 .9 7.4 5.0 2.4 .4 16 142 80 S.D. 7.1 5.7 .00 .07 .07 .00 .07 4.2 64.3 48.8 N 2 2 2 2 2 2 2 2 2 2 0.02 MEAN 62 24 .8 7.0 * 4.5 * 2.6 .3 10 * 163 69 S.D. 6.0 2.3 .06 .12 .12 .23 .06 .6 18.3 18.6 N 3 3 3 3 3 3 3 3 3 3 2.0 MEAN 58 21 .9 7.3 4.7 2.6 .4 N 1 1 1 1 1 1 1 9 151 50 1 1 1 65 Table 11 Summary of Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 75 14.1 2 56 21.2 2 726 48.8 2 84 6.4 2 2 899 412 .7 5.7 69.3 2 2 2 31 5.7 2 256 40.3 2 0.02 MEAN S.D. N 41 2.5 3 56 14.8 3 599 82.7 3 88 31.8 3 2 579 289 .0 391.1 51.3 3 3 3 40 19.6 3 180 30.7 3 2.0 MEAN 54 N 1 55 1028 105 1 1 1 2 219 302 1 1 1 11 139 1 1 66 Table 11 Summary of Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 10.2 S.D. .14 N 2 6.8 1.06 2 152 1.4 2 5.2 .07 2 106 .7 2 0.02 MEAN S.D. N 9.5 * .26 3 6.7 .31 3 147 2.5 3 4.7 .25 3 108 4.0 3 2.0 MEAN 10.0 7.0 152 5.0 104 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 67 Table 11 Summary of Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 70 19 .8 7.4 4.9 2.5 .4 S.D. 14.1 .0 .07 .42 .28 .14 .07 N 2 2 2 2 2 2 2 8 145 .7 2.8 2 2 42 11.3 2 0.02 MEAN 57 24 .8 7.3 4.7 2.6 .5 16 * 133 69 S.D. 3.5 3.5 .06 .15 .30 .23 .06 1.0 28.2 33.7 N 3 3 3 3 3 3 3 3 3 3 2.0 MEAN 68 27 1.0 7.5 4.7 2.8 .4 17 136 47 N 1 1 1 1 1 1 1 1 1 1 68 Table 11 Summary of Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 58 18.4 2 72 43.1 2 578 123.0 2 81 5.7 2 2 523 502 .7 15.6 138.6 2 2 2 39 5.7 2 324 96.9 2 0.02 MEAN S.D. N 54 4.5 3 57 16.9 3 805 65.3 3 69 8.1 3 2 426 351 .6 133.3 46.2 3 3 3 31 9.2 3 208 24.7 3 2.0 MEAN 46 N 1 55 672 100 1 1 1 2 308 291 1 1 1 84 184 1 1 69 Table 11 Summary of Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 10.2 S.D. .71 N 2 6.7 .28 2 153 4.2 2 5.4 .64 2 108 .0 2 0.02 MEAN S.D. N 10.0 .25 3 7.6 .85 3 151 6.2 3 4.9 .21 3 105 2.3 3 2.0 MEAN 10.0 6.5 151 4.7 106 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 70 Table 12 Summary of Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 81 20 .8 7.8 4.8 3.0 .2 10 138 52 S.D. 4.2 .0 .07 .28 .21 .07 .07 4.9 65.8 7.1 N 2 2 2 2 2 2 2 2 2 2 0.02 MEAN 68 * 21 .8 7.5 4.5 * 3.1 .3 10 156 51 S.D. 3.1 1.5 .06 .25 .06 .25 .00 1.2 19.3 1.5 N 3 3 3 3 3 3 3 3 3 3 2.0 MEAN 63 18 .8 7.5 4.6 2.9 .4 N 1 1 1 1 1 1 1 7 137 50 1 1 1 71 Table 12 Summary of Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 51 15.6 2 46 13.4 2 770 78.5 2 80 .0 2 0 249 397 .0 79.2 67.9 2 2 2 33 7.1 2 272 48.1 2 0.02 MEAN S.D. N 39 3.8 3 57 15.0 3 556 106.4 3 85 34.6 3 0 399 327 .0 415.4 35.6 3 3 3 31 13.5 3 225 24.1 3 2.0 MEAN 46 49 1012 98 N 1 1 1 1 0 270 260 1 1 1 0 139 1 1 72 Table 12 Summary of Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 10.2 S.D. .35 N 2 7.0 .49 2 156 3.5 2 5.2 .21 2 112 .0 2 0.02 MEAN S.D. N 9.8 .32 3 7.0 .35 3 152 3.6 3 4.8 .29 3 112 2.5 3 2.0 MEAN 10.3 6.6 156 5.1 112 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 73 Table 12 Summary of Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 86 20 .8 8.0 4.6 3.5 .2 S.D. 9.2 6.4 .00 .07 .49 .42 .07 N 2 2 2 2 2 2 2 7 130 1.4 2.1 2 2 32 13.4 2 0.02 MEAN 73 19 .8 8.0 4.8 3.2 .3 S.D. 4.6 1.5 .10 .17 .31 .15 .06 N 3 3 3 3 3 3 3 8 147 .0 31.3 3 3 38 6.8 3 2.0 MEAN 73 18 .8 7.9 4.6 3.3 .3 12 117 44 N 1 1 1 1 1 1 1 1 1 1 74 Table 12 Summary of Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 46 .7 2 52 13.4 2 558 94.0 2 69 8.5 2 0 142 434 .7 55.2 26.9 2 2 2 30 10.6 2 303 26.9 2 0.02 MEAN S.D. N 49 8.1 3 57 6.9 3 775 108.2 3 68 9.6 3 0 218 356 * .6 27.8 18.9 3 3 3 25 5.1 3 231 34.1 3 2.0 MEAN 45 57 674 90 N 1 1 1 1 0 166 349 101 238 1 1 1 1 1 75 Table 12 Summary of Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 11.0 S.D. .78 N 2 6.1 .57 2 156 2.1 2 6.4 .92 2 112 .7 2 0.02 MEAN S.D. N 10.7 .40 3 7.3 .78 3 155 6.1 3 5.5 .20 3 113 1.5 3 2.0 MEAN 10.6 6.4 155 5.3 113 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 76 Table 13 Summary of Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 80 19 .8 7.7 5.0 2.7 .4 S.D. 13.4 1.4 .07 .42 .28 .14 .00 N 2 2 2 2 2 2 2 8 141 2.1 58.0 2 2 38 7.1 2 0.02 MEAN 63 19 .7 7.2 4.5 2.7 .4 S.D. 3.8 1.0 .23 .45 .17 .32 .00 N 3 3 3 3 3 3 3 8 150 2.1 12.2 3 3 44 9.5 3 2.0 MEAN 64 15 .7 7.4 4.8 2.6 .4 N 1 1 1 1 1 1 1 6 132 27 1 1 1 77 Table 13 Summary of Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 47 7.1 2 40 9.2 2 761 33.9 2 80 7.8 2 4 162 394 2.1 43.8 30.4 2 2 2 35 8.5 2 262 20.5 2 0.02 MEAN S.D. N 36 5.7 3 49 8.0 3 519 131.9 3 77 37.0 3 3 111 306 .6 35.2 40.8 3 3 3 35 18.6 3 203 28.9 3 2.0 MEAN 39 45 908 89 N 1 1 1 1 2 245 242 1 1 1 2 123 1 1 78 Table 13 Summary of Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 10.2 S.D. .21 N 2 7.6 1.63 2 151 1.4 2 4.8 .28 2 106 .7 2 0.02 MEAN S.D. N 9.7 * .15 3 6.7 .64 3 148 1.0 3 4.5 .30 3 107 1.0 3 2.0 MEAN 10.1 6.4 153 4.8 108 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 79 Table 13 Summary of Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 80 19 .6 7.5 4.6 2.8 .4 S.D. 3.5 4.2 .07 .14 .21 .35 .07 N 2 2 2 2 2 2 2 7 119 .0 11.3 2 2 24 4.9 2 0.02 MEAN 58 20 .7 7.7 4.8 2.9 .5 S.D. 9.0 2.5 .20 .25 .30 .06 .15 N 3 3 3 3 3 3 3 8 139 1.5 24.1 3 3 35 7.0 3 2.0 MEAN 59 18 .8 7.8 4.6 3.2 .4 N 1 1 1 1 1 1 1 8 107 41 1 1 1 80 Table 13 Summary of Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 46 8.5 2 46 7.8 2 499 58.0 2 64 .7 2 4 259 428 .7 144.2 40.3 2 2 2 30 16.3 2 288 36.1 2 0.02 MEAN S.D. N 47 7.5 3 55 11.3 3 800 * 68.6 3 63 10.4 3 3 307 320 * .6 97.5 27.2 3 3 3 39 24.6 3 200 * 18.8 3 2.0 MEAN 40 51 727 86 N 1 1 1 1 3 462 440 309 283 1 1 1 1 1 81 Table 13 Summary of Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 10.4 S.D. .49 N 2 6.8 .28 2 154 3.5 2 6.0 .71 2 110 .7 2 0.02 MEAN S.D. N 10.4 .46 3 6.7 .69 3 151 6.8 3 5.2 .25 3 108 3.6 3 2.0 MEAN 10.4 6.1 152 5.4 108 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 82 Table 14 Summary of Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 81 24 .8 7.6 4.6 3.0 .2 S.D. 8.5 .0 .07 .14 .00 .14 .07 N 2 2 2 2 2 2 2 7 140 1.4 65.8 2 2 36 6.4 2 0.02 MEAN 73 24 .8 7.5 4.3 3.2 .2 10 151 53 * S.D. 7.0 4.0 .15 1.04 .44 .65 .06 3.1 21.5 4.7 N 3 3 3 3 3 3 3 3 3 3 2.0 MEAN 80 15 1.1 8.2 4.8 3.4 .3 N 1 1 1 1 1 1 1 8 91 25 1 1 1 83 Table 14 Summary of Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 52 12.7 2 46 14.1 2 755 60.8 2 96 9.2 2 4 410 424 2.8 93.3 87.0 2 2 2 37 .0 2 285 62.2 2 0.02 MEAN S.D. N 42 7.5 3 62 26.6 3 564 127.2 3 94 42.9 3 3 314 334 1.2 255.2 57.7 3 3 3 35 33.9 3 228 39.5 3 2.0 MEAN 31 38 815 88 N 1 1 1 1 1 202 285 1 1 1 3 156 1 1 84 Table 14 Summary of Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 10.5 S.D. .14 N 2 7.5 .99 2 154 2.1 2 5.6 .92 2 111 1.4 2 0.02 MEAN S.D. N 10.2 .29 3 6.3 .40 3 152 3.0 3 5.1 .79 3 110 2.0 3 2.0 MEAN 11.0 6.4 156 6.0 107 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 85 Table 14 Summary of Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE mg/kg/day GLU MG/DL UN MG/DL CREAT MG/DL T PRO G/DL ALB G/DL GLOB G/DL T BILI MG/DL SBA umol/L CHOL MG/DL TRIG MG/DL ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN 86 25 .8 7.6 4.4 3.3 .2 S.D. .7 1.4 .07 .35 .07 .42 .00 N 2 2 2 2 2 2 2 9 121 2.8 19.8 2 2 38 3.5 2 0.02 MEAN 62 24 .9 7.9 4.6 3.3 .3 S.D. 10.8 3.8 .12 .57 .38 .20 .10 N 3 3 3 3 3 3 3 9 143 1.7 24.8 3 3 46 6.0 3 2.0 MEAN 78 24 1.0 8.2 4.6 3.6 .2 17 62 27 N 1 1 1 1 1 1 1 1 1 1 86 Table 14 Summary of Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-222 3M T-6295.6 DOSE AST/SGOT ALT/SGPT ALK PHOS mg/kg/day IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE IU/L LIPASE IU/L P AMYL U/L ------ -------- -------- -------- -------- -------- -------- -------- -------- -------- 0 MEAN S.D. N 53 9.9 2 46 9.2 2 467 69.3 2 72 3.5 2 6 298 538 130 370 3.5 51.6 133.6 157.7 99.0 2 2 2 2 2 0.02 MEAN S.D. N 45 7.1 3 54 5.7 3 908 * 68.8 3 76 7.6 3 3 273 340 1.2 79.2 46.1 3 3 3 23 14.7 3 218 34.0 3 2.0 MEAN 36 47 637 93 N 1 1 1 1 2 341 326 1 1 1 18 221 1 1 87 Table 14 Summary of Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L ------ -------- -------- -------- -------- -------- 0 MEAN 10.4 S.D. .21 N 2 6.4 1.06 2 152 1.4 2 5.7 .42 2 111 2.8 2 0.02 MEAN S.D. N 10.9 .46 3 6.9 .89 3 155 4.4 3 5.5 .10 3 111 2.1 3 2.0 MEAN 11.1 6.5 158 5.7 110 N 1 1 1 1 1 Covance 6329-222 3M T-6295.6 88 Table 15 Summary of Clinical Chemistry Data Males Day 30 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day PCOAO IU/G ------ -------- 0 MEAN 0 S.D. .7 N 2 0.02 MEAN 4 * S.D. .6 N 3 2.0 MEAN 1 S.D. .0 N 1 Covance 6329-222 3M T-6295.6 89 Table 15 Summary of Clinical Chemistry Data Females Day 30 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day PCOAO IU/G ------ -------- 0 MEAN 2 S.D. 2.8 N 2 0.02 MEAN 3 S.D. 3.5 N 3 2.0 MEAN 1 S.D. .0 N 1 Covance 6329-222 3M T-6295.6 90 TABLE 16 Incidence of Macroscopic Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------------ TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=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: -----MALE---- ----FEMALE--GROUP: -1- -2- -3- -1- -2- -3- ORGAN AND KEYWORD(S) OR PHRASE NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------ -=- -=- -=- -=- -=- -=- ** TOP OF LIST ** GENERAL COMMENT (GC) ................................. NUMBER EXAMINED: 2 3 1 2 3 1 BONE MARROW SMEAR TAKEN EYES - DAVIDSONS STAINS-PERINEUM/PERIANAL NO MACROSCOPIC LESIONS ** END OF LIST ** 2 3 1 2 3 1 2 3 1 2 3 1 0 0 0 0 1 0 2 3 1 2 2 1 91 TABLE 17 Incidence of Microscopic Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------------ TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;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: -----MALE---- ----FEMALE--GROUP: -1- -2- -3- -1- -2- -3- ORGAN AND FINDING DESCRIPTION NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------ -=- -=- -=- -=- -=- -=- ** TOP OF LIST ** EYE (EY) ............................................. NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 3 1 2 3 1 BONE, FEMUR (FE) ..................................... NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 3 1 2 3 1 MARROW, FEMUR (FM) ................................... NUMBER EXAMINED: 0 1 0 1 2 1 NOT REMARKABLE: 0 1 0 1 2 1 KIDNEY (KD) .......................................... NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 2 1 1 1 1 --INFILTRATE, LYMPHOPLASMACYTIC 0 1 0 1 2 0 LUNG (LU) ............................................ NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 3 1 2 3 1 LIVER (LI) ........................................... NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 2 1 0 1 1 --INFILTRATE, LYMPHOPLASMACYTIC --INFLAMMATION, LYMPHOHISTIOCYTIC --LIPIDOSIS, SUBCAPSULAR (TENSION LIPIDOSIS) 0 1 0 1 2 0 0 0 0 1 0 0 0 0 0 1 0 0 92 TABLE 17 Incidence of Microscopic Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 2 ------------------------------------------------------------------------------------------------------------------------------------ TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;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: -----MALE---- ----FEMALE--GROUP: -1- -2- -3- -1- -2- -3- ORGAN AND FINDING DESCRIPTION NUMBER: 2 3 1 2 3 1 ------------------------------------------------------------------------ -=- -=- -=- -=- -=- -=- SPLEEN (SP) .......................................... NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 3 1 2 3 1 PANCREAS (PA) ........................................ NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 3 1 2 3 1 ADRENAL, CORTEX (AC) ................................. NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 3 1 2 2 1 --HEMORRHAGE --THROMBUS 0 0 0 0 1 0 0 0 0 0 1 0 ADRENAL, MEDULLA (MA) ................................ NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 3 1 2 3 1 THYMUS (TH) .......................................... NUMBER EXAMINED: 2 3 1 2 3 1 NOT REMARKABLE: 2 3 1 2 3 1 TESTIS (TE) .......................................... NUMBER EXAMINED: 2 3 1 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 --IMMATURE 2 3 1 0 0 0 ** END OF LIST ** 93 APPENDIX 1 Protocol Deviations Protocol Protocol Amendment No. 1 Protocol Amendment No. 2 Protocol Amendment No. 3 Protocol Amendment No. 4 Material Safety Data Sheet Covance 6329-222 3M T-6295.6 94 Covance 6329-222 3M T-6295.6 Protocol Deviations Protocol. Group Designations and Dosage Levels. Dose levels were 0, 0.02, and 2.0 mg/kg/day. The control group (Group 1) was to receive an equivalent amount of lactose in gelatin capsules as the total material administered to Group 3. The total material was 20.0 mg/kg/day for each group; however, the low- and high-dose groups were to receive test material triturated with lactose (1:999, w:w, and 1:9, w:w, respectively). Actual Procedure. Because the capsule broke during dose administration, the following animals may not have received the full amount of dose preparation: Animal No. I05350 (Group 1 male) on Day 1; Animal No. I05367 (Group 1 female) on Days 2, 7, and 14; Animal No. I05344 (Group 2 male) on Day 7; and Animal No. I05369 (Group 3 female) on Day 2. Protocol. Dose Analysis. Stability. "One set of samples (approximately 1 g each) will be taken from the low- and high-dose test material/lactose preparations at the end of the in-life phase and analyzed for test material content." Actual Procedure. Two reserve samples (10 g) were shipped to the sponsor for stability analysis. The samples for stability analysis (1 g) were retained as reserve samples, until shipped to the Sponsor on March 19, 2002. Protocol. Observation of Animals. Rectal Body Temperatures. "Beginning 2 weeks before initiation of treatment, rectal body temperatures will be taken at approximately 11:00 on two days/week (Monday and Thursday)." Actual Procedure. Rectal body temperatures were recorded between 12:50 and 13:30 on Day -14 and between 08:17 and 08:40 on Day -10. Protocol. Serum PFOS Level Determination. Frequency. "Before initiation of treatment (Day -7 or -6), and prior to treatment on Days 2 (approximately 24 hours after the first dose), 7, 14, and 29." 95 Protocol Deviations (Continued) Covance 6329-222 3M T-6295.6 Actual Procedure. On Day 2, incorrect blood collection tubes were used for the collection of blood for clinical chemistry test; therefore, blood collected for serum PFOS level determinations was used for clinical chemistry tests. Remaining serum from clinical chemistry tests was used as the Day 2 sample for serum PFOS level determinations. In addition, whole blood (approximately 2 mL) was collected from a femoral vein of each animal before treatment on Day 3 (approximately 24 hours after the second dose). Protocol. Additional Blood Collection. "At scheduled and unscheduled necropsies, blood (as much as possible, up to 20 mL) will be collected from animals at the time of exsanguination." Actual Procedure. Additional blood was not collected from Animal Nos. I05364 (Group 2 female), I05365 (Group 2 female), and I05369 (Group 3 female). Protocol. Postmortem Procedures. Tissue Preservation. "The following tissues (when present) from each animal will be preserved in 10% neutral-buffered formalin, unless otherwise specified, for possible future microscopic examination:" Actual Procedure. Femoral bone marrow from Animal Nos. I05349 and I05350 (Group 1 males), I05344 and I05348 (Group 2 males), I05345 (Group 3 male), I05366 (Group 1 female), and I05364 (Group 2 female) were insufficient; therefore, these tissues were not examined microscopically. This tissue is listed with the appropriate comments in the pathology data sheets for each individual animal. Summary tables do not include it as having been examined. These deviations are not expected to have affected the results of the study. 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 PROTOCOL AMENDMENT NO. 3 Covance 6329-222 4-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys 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 April 17, 1998 1. Page 5, Vehicle, Storage Conditions. To include the solvent used to dissolve the test material before mixing with the lactose, add the following after this section. Solvent Identification 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 Characteristics Information on synthesis methods, composition, or other characteristics that define the solvent is on file with the manufacturer. 120 Covance 6329-222 Protocol Amendment No. 3 Page 2 2. Page 7, Dosing Procedures, Dose Preparation, Sentence 5. To include the use of acetone in the preparation of the doses, delete this sentence and replace with the following. For the Group 2 and 3 dose preparations, the test material will be dissolved in acetone and triturated with lactose (1:999 and 1:9, w:w, respectively) once before initiation of treatment. Effective April 17, 1998 and April 26, 1999 3. Page 16, Record Retention. To correct an omission in the protocol and to specify the record retention requirements for Ani Lytics Inc. and 3M E.T. & S (effective April 17, 1998) and to clarify the requirement for Pathology Associates International (effective April 26, 1999), add the following. Within 1 year after submission of the final report, all of the aforementioned materials (as appropriate) from Ani Lytics Inc. and 3M E.T. & S will be sent to the Sponsor (Andrew Seacat, PhD, 3M). Pathology Associates International (PAI) is responsible for the maintenance of any raw data or specimens produced by PAI. Effective December 15, 1998 4. Page 13, Postmortem Procedures, Cell Proliferation Evaluation, Paragraph 3, Sentence 2. To include evaluation of slides stained with hematoxylin and eosin in the PCNA evaluation, delete this sentence and replace with the following. PCNA evaluation (including examination of slides stained with hematoxylin and eosin) will be done on the samples. 121 AMENDMENT APPROVAL Covance 6329-222 Protocol Amendment No. 3 Page 3 122 123 124 Covance 6329-222 3M T-6295.6 125 Covance 6329-222 3M T-6295.6 126 Covance 6329-222 3M T-6295.6 127 Covance 6329-222 3M T-6295.6 128 Covance 6329-222 3M T-6295.6 129 Covance 6329-222 3M T-6295.6 130 APPENDIX 2 Individual Animal Fate Data Individual Clinical Observations Individual Rectal Body Temperature Data (C) Covance 6329-222 3M T-6295.6 131 APPENDIX 2 Individual Animal Fate Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------- ANIMAL NUMBER -----I05349 I05350 I05344 I05347 I05348 I05345 I05366 I05367 I05364 I05365 I05370 I05369 DOSE GROUP ----- 1 1 2 2 2 3 1 1 2 2 2 3 SEX ------ MALE MALE MALE MALE MALE MALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE DEATH CODE ----- 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 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 DATE OF DEATH -------05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 05/22/98 DAY OF STUDY ------30 30 30 30 30 30 30 30 30 30 30 30 WEEK OF STUDY ------5 5 5 5 5 5 5 5 5 5 5 5 132 Appendix 2 Individual Clinical Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M1 DOSE: 0 MG/KG/DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP ANIMAL DEATH WK OF KEYWORD AM OBS 30MIN 90MIN UNSCHED NUMBER CODE DEATH QUALIFIER DAYS 1-30 DAY PM CHECK 60MIN DISPATCH =============================================================================================================================== I05349 T 5 NORMAL NO REMARKABLE OBSERVATIONS 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - I05350 T 5 EXCRETION MUCOID FECES NORMAL NO REMARKABLE OBSERVATIONS 12 - - - P - - - 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - 133 Appendix 2 Individual Clinical Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 2 ------------------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M2 DOSE: 0.02 MG/KG/DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP ANIMAL DEATH WK OF KEYWORD AM OBS 30MIN 90MIN UNSCHED NUMBER CODE DEATH QUALIFIER DAYS 1-30 DAY PM CHECK 60MIN DISPATCH =============================================================================================================================== I05344 T 5 NORMAL NO REMARKABLE OBSERVATIONS 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - I05347 T 5 DISCHARGE VOMITUS CONTAINING FOOD NORMAL NO REMARKABLE OBSERVATIONS 4 - - - - - - P 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - I05348 T 5 NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE FOOD CONSUMPTION LOW 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - 15 P - - - - - - 134 Appendix 2 Individual Clinical Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 3 ------------------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: M3 DOSE: 2 MG/KG/DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP ANIMAL DEATH WK OF KEYWORD AM OBS 30MIN 90MIN UNSCHED NUMBER CODE DEATH QUALIFIER DAYS 1-30 DAY PM CHECK 60MIN DISPATCH =============================================================================================================================== I05345 T 5 DISCHARGE VOMITUS CONTAINING FOOD DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR NORMAL NO REMARKABLE OBSERVATIONS 24 P - - - - - - 15 P - - - - - - 1 P - - - - - - 8 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - 135 Appendix 2 Individual Clinical Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 4 ------------------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: F1 DOSE: 0 MG/KG/DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP ANIMAL DEATH WK OF KEYWORD AM OBS 30MIN 90MIN UNSCHED NUMBER CODE DEATH QUALIFIER DAYS 1-30 DAY PM CHECK 60MIN DISPATCH =============================================================================================================================== I05366 T 5 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 23 P - P - - - - 27 P - - - - - - 29 P - - - - - - 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 30 P - - - - P - I05367 T 5 APPEARANCE SWOLLEN LIP(S) EXCRETION NON-FORMED FECES 11 - - P P P - - 13 - - P P P - - 14 P - - - P - - 15 P - P P P - - 19 P - P P P - - 20 P - P P P - - 21 P - P P P - - 22 P - P P P - - 23 P - - - - - - 24 - - P P P - - 25 - - - P P - - 26 P - P P P - - 30 P - - - - P - 15 P - - - - - - 27 P - - - - - - 136 Appendix 2 Individual Clinical Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 5 ------------------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: F1 DOSE: 0 MG/KG/DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP ANIMAL DEATH WK OF KEYWORD AM OBS 30MIN 90MIN UNSCHED NUMBER CODE DEATH QUALIFIER DAYS 1-30 DAY PM CHECK 60MIN DISPATCH =============================================================================================================================== (CONTINUED FROM PREVIOUS PAGE) I05367 T 5 SKIN & PELAGE RED SKIN LIP(S) 11 - - P P P - - 13 - - P P P - - 14 P - - - P - - 15 P - P P P - - 19 P - P P P - - 20 P - P P P - - SCAB(S) MOUTH 29 P - P P P - - NORMAL NO REMARKABLE OBSERVATIONS 1 P - - - - - - 8 P - - - - - - QUALITATIVE FOOD CONSUMPTION LOW 4 P - - - - - - 137 Appendix 2 Individual Clinical Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 6 ------------------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: F2 DOSE: 0.02 MG/KG/DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP ANIMAL DEATH WK OF KEYWORD AM OBS 30MIN 90MIN UNSCHED NUMBER CODE DEATH QUALIFIER DAYS 1-30 DAY PM CHECK 60MIN DISPATCH =============================================================================================================================== I05364 T 5 NORMAL NO REMARKABLE OBSERVATIONS 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - I05365 T 5 DISCHARGE APPEARS TO BE MENSTRUATING NORMAL NO REMARKABLE OBSERVATIONS 29 P - - - - - - 30 P - - - - P - 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - I05370 T 5 NORMAL NO REMARKABLE OBSERVATIONS 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - 138 Appendix 2 Individual Clinical Observations Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 7 ------------------------------------------------------------------------------------------------------------------------------- CATEGORY GROUP: F3 DOSE: 2 MG/KG/DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP ANIMAL DEATH WK OF KEYWORD AM OBS 30MIN 90MIN UNSCHED NUMBER CODE DEATH QUALIFIER DAYS 1-30 DAY PM CHECK 60MIN DISPATCH =============================================================================================================================== I05369 T 5 EXCRETION FEW FECES NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE FOOD CONSUMPTION LOW 17 P - - - - - - 1 P - - - - - - 8 P - - - - - - 15 P - - - - - - 22 P - - - - - - 29 P - - - - - - 30 P - - - - P - 26 P - - - - - - 139 Appendix 2 Individual Rectal Body Temperature Data (oC) Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 --------------------------------------------------------------------------------------------------------------------------- ANIMAL DAY DAY DAY DAY DAY DAY DAY DAY DAY DAY NUMBER -14 -10 -7 -3 1 5 8 12 15 19 ------------------------------------------------------------------------------------------------------------------------------- GROUP: MALE 1 - 0 MG/KG/DAY I05349 I05350 40.0 39.6 40.2 39.7 40.2 39.4 39.8 39.4 39.4 38.6 38.8 38.9 38.2 38.7 38.9 39.0 39.7 39.7 38.5 38.8 GROUP: MALE 2 - 0.02 MG/KG/DAY I05344 I05347 I05348 39.0 39.8 38.7 39.0 39.7 39.0 38.4 39.8 38.8 39.2 39.7 38.8 39.7 39.4 39.1 39.3 39.5 38.4 39.4 39.4 38.7 39.3 39.5 38.6 39.8 40.0 39.2 39.2 39.0 38.0 GROUP: MALE 3 - 2 MG/KG/DAY I05345 39.6 39.5 39.1 39.2 39.4 39.9 39.6 40.0 39.7 38.9 GROUP: FEMALE 1 - 0 MG/KG/DAY I05366 I05367 40.0 40.4 39.4 40.1 39.7 40.0 39.4 40.1 39.3 39.8 38.7 39.2 38.8 39.4 39.1 39.3 39.3 40.1 38.7 39.2 GROUP: FEMALE 2 - 0.02 MG/KG/DAY I05364 I05365 I05370 40.6 39.6 40.1 40.1 39.1 40.0 40.3 39.6 40.2 39.9 39.7 39.8 40.2 39.7 39.7 40.0 39.5 39.8 40.0 39.6 39.9 40.0 39.5 39.8 40.2 40.0 39.8 39.5 39.1 39.4 GROUP: FEMALE 3 - 2 MG/KG/DAY I05369 40.0 39.8 39.9 39.7 39.5 39.7 39.9 39.7 39.8 39.3 140 Appendix 2 Individual Rectal Body Temperature Data (oC) Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 2 --------------------------------------------------------------------------------------------------------------------------- ANIMAL DAY DAY DAY NUMBER 22 26 29 ------------------------------------------------------------------------------------------------------------------------------- GROUP: MALE 1 - 0 MG/KG/DAY I05349 I05350 39.2 39.5 38.7 38.8 38.2 38.8 GROUP: MALE 2 - 0.02 MG/KG/DAY I05344 I05347 I05348 40.0 39.7 38.9 39.4 39.5 38.8 38.8 39.1 38.4 GROUP: MALE 3 - 2 MG/KG/DAY I05345 39.4 39.2 38.9 GROUP: FEMALE 1 - 0 MG/KG/DAY I05366 I05367 39.3 39.9 38.7 39.2 38.7 38.9 GROUP: FEMALE 2 - 0.02 MG/KG/DAY I05364 I05365 I05370 40.1 39.6 39.8 39.8 39.5 39.6 39.3 38.7 39.4 GROUP: FEMALE 3 - 2 MG/KG/DAY I05369 39.4 39.1 39.2 141 APPENDIX 3 Individual Body Weight Data (kg) Covance 6329-222 3M T-6295.6 142 Appendix 3 Individual Body Weight Data (kg) Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 --------------------------------------------------------------------------------------------------------------------------- ANIMAL DAY DAY DAY DAY DAY DAY DAY DAY DAY DAY NUMBER -14 -10 -7 -3 -1 1 5 8 12 15 ------------------------------------------------------------------------------------------------------------------------------- GROUP: MALE 1 - 0 MG/KG/DAY I05349 I05350 2.3 2.2 2.2 2.2 2.3 2.2 2.2 2.4 2.4 2.3 2.3 2.3 2.3 2.3 2.3 2.4 2.3 2.5 2.5 2.5 GROUP: MALE 2 - 0.02 MG/KG/DAY I05344 I05347 I05348 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 2.4 2.4 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 2.2 2.3 2.5 2.5 2.5 2.5 2.6 2.5 2.4 2.5 2.4 2.4 GROUP: MALE 3 - 2 MG/KG/DAY I05345 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 2.2 2.3 GROUP: FEMALE 1 - 0 MG/KG/DAY I05366 I05367 2.0 2.0 2.1 2.1 2.1 2.1 2.0 2.2 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.0 2.1 2.1 2.2 GROUP: FEMALE 2 - 0.02 MG/KG/DAY I05364 I05365 I05370 2.2 2.1 2.1 2.1 2.1 2.2 2.1 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.4 2.3 2.4 1.9 2.0 1.9 1.9 1.9 2.0 2.0 2.0 2.0 2.0 GROUP: FEMALE 3 - 2 MG/KG/DAY I05369 2.2 2.1 2.2 2.1 2.2 2.2 2.1 2.2 2.2 2.1 143 Appendix 3 Individual Body Weight Data (kg) Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 2 --------------------------------------------------------------------------------------------------------------------------- ANIMAL DAY DAY DAY DAY NUMBER 19 22 26 29 ------------------------------------------------------------------------------------------------------------------------------- GROUP: MALE 1 - 0 MG/KG/DAY I05349 I05350 2.4 2.4 2.4 2.3 2.5 2.5 2.5 2.4 GROUP: MALE 2 - 0.02 MG/KG/DAY I05344 I05347 I05348 2.4 2.5 2.4 2.4 2.3 2.3 2.3 2.3 2.4 2.4 2.5 2.4 GROUP: MALE 3 - 2 MG/KG/DAY I05345 2.3 2.1 2.1 2.0 GROUP: FEMALE 1 - 0 MG/KG/DAY I05366 I05367 2.1 2.1 2.1 2.1 2.1 2.2 2.2 2.1 GROUP: FEMALE 2 - 0.02 MG/KG/DAY I05364 I05365 I05370 2.2 2.2 2.2 2.1 2.5 2.4 2.4 2.3 2.2 2.1 2.1 2.0 GROUP: FEMALE 3 - 2 MG/KG/DAY I05369 2.3 2.1 2.1 2.1 144 APPENDIX 4 Individual Clinical Hematology Data Individual Clinical Chemistry Data Covance 6329-222 3M T-6295.6 145 Appendix 4 Individual Clinical Hematology Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ RBC HGB X106/mL G/DL -------- -------- HCT % -------- MCV FL -------- MCH PG -------- MCHC % -------- PLT RETIC X103/mL % -------- -------- RETIC X103/mL -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 I05350 5.41 13.0 39.9 73.8 24.0 32.6 404 .9 49 5.88 15.0 45.3 77.0 25.5 33.2 600 .9 53 MEAN S.D. N 5.64 14.0 42.6 75.4 24.8 32.9 502 .9 .332 1.41 3.82 2.26 1.06 .42 138.6 .00 2 2 2 2 2 2 2 2 51 2.8 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 I05347 I05348 4.97 12.3 38.5 77.5 24.8 32.0 473 1.3 65 5.49 12.7 40.1 73.1 23.2 31.7 358 .3 16 5.09 12.9 38.6 75.7 25.3 33.4 531 1.1 56 MEAN S.D. N 5.18 12.6 39.1 75.4 24.4 32.4 454 .9 .272 .31 .90 2.21 1.10 .91 88.1 .53 3 3 3 3 3 3 3 3 46 26.1 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 5.91 12.8 41.0 69.4 21.7 31.2 531 .7 41 Covance 6329-222 3M T-6295.6 146 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Hematology Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS WBC X103/mL -------- N-SEG X103/mL -------- LYMPH X103/mL -------- MONO X103/mL -------- EOSIN X103/mL -------- BASO X103/mL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSIN% -------- BASO% -------- Dose Level: 0 Dosage Unit: mg/kg/day 9.1 4.1 4.5 .4 .0 .0 45 49 5 0 0 7.7 2.6 4.6 .3 .2 .0 34 59 4 2 0 8.4 3.4 4.6 .4 .1 .0 40 54 4 1 0 .99 1.06 .07 .07 .14 .00 7.8 7.1 .7 1.4 .0 2 2 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 10.3 3.2 6.3 .6 .2 .0 31 61 6 2 0 8.8 1.4 7.0 .4 .1 .0 15 79 4 1 0 8.4 4.0 4.2 .2 .0 .0 48 50 2 0 0 9.2 2.9 5.8 .4 .1 .0 31 63 4 1 0 1.00 1.33 1.46 .20 .10 .00 16.5 14.6 2.0 1.0 .0 3 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 8.2 2.8 4.8 .6 .0 .0 34 58 8 0 0 147 Appendix 4 Individual Clinical Hematology Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 - - - - - I05350 - - - - - Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 - - - - - I05347 - - - - - I05348 - - - - - Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 - - - - - Covance 6329-222 3M T-6295.6 148 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mL -------- HGB G/DL -------- HCT % -------- MCV FL -------- MCH PG -------- MCHC % -------- PLT X103/mL -------- RETIC % -------- RETIC X103/mL -------- Dose Level: 0 Dosage Unit: mg/kg/day 5.02 12.4 37.6 75.0 24.8 33.1 351 .7 35 5.48 14.3 43.2 78.8 26.1 33.1 606 1.0 55 5.25 13.3 40.4 76.9 25.4 33.1 478 .8 .325 1.34 3.96 2.69 .92 .00 180.3 .21 2 2 2 2 2 2 2 2 45 14.1 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 4.77 13.0 38.9 81.5 27.2 33.3 355 .6 29 4.98 12.7 39.0 78.3 25.5 32.6 365 .9 45 5.25 12.6 39.3 74.9 24.1 32.2 570 .6 32 5.00 12.8 39.1 78.2 25.6 32.7 430 .7 .241 .21 .21 3.30 1.55 .56 121.3 .17 3 3 3 3 3 3 3 3 35 8.5 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 5.53 13.4 40.2 72.7 24.2 33.3 505 .8 44 149 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS WBC X103/mL -------- N-SEG X103/mL -------- LYMPH X103/mL -------- MONO X103/mL -------- EOSIN X103/mL -------- BASO X103/mL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSIN% -------- BASO% -------- Dose Level: 0 Dosage Unit: mg/kg/day 7.9 2.2 5.2 .4 .1 .0 28 66 5 1 0 10.0 4.9 5.0 .0 .0 .0 49 50 0 0 0 9.0 3.6 5.1 .2 .0 .0 38 58 2 0 0 1.48 1.91 .14 .28 .07 .00 14.8 11.3 3.5 .7 0 2 2 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 8.6 1.6 6.2 .5 .2 .0 19 73 6 2 0 12.4 1.6 10.2 .5 .1 .0 13 82 4 1 0 9.6 7.3 2.1 .3 .0 .0 75 21 3 0 0 10.2 3.5 6.2 .4 .1 .0 36 59 4 1 0 1.97 3.29 4.05 .12 .10 .00 34.2 32.9 1.5 1.0 .0 3 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 11.7 6.2 4.8 .4 .2 .0 53 42 4 1 0 150 Appendix 4 Individual Clinical Hematology Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 - - - - - I05367 - - - - - Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 - - - - - I05365 - - - - - I05370 - - - - - Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 - - - - - Covance 6329-222 3M T-6295.6 151 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mL -------- HGB G/DL -------- HCT % -------- MCV FL -------- MCH PG -------- MCHC % -------- PLT X103/mL -------- RETIC % -------- RETIC X103/mL -------- Dose Level: 0 Dosage Unit: mg/kg/day 6.00 13.6 42.7 71.0 22.6 31.8 357 .9 54 6.05 14.5 45.3 74.8 24.0 32.1 522 .7 42 6.02 14.0 44.0 72.9 23.3 31.9 440 .8 .035 .64 1.84 2.69 .99 .21 116.7 .14 2 2 2 2 2 2 2 2 48 8.5 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 4.90 12.2 38.1 77.8 24.9 32.0 448 .5 24 5.05 12.1 37.6 74.5 23.9 32.1 286 .2 10 5.41 13.5 41.6 76.8 25.0 32.5 443 .9 49 5.12 12.6 39.1 76.4 24.6 32.2 392 .5 .262 .78 2.18 1.69 .61 .26 92.1 .35 3 3 3 3 3 3 3 3 28 19.8 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 5.69 13.2 41.5 73.1 23.1 31.7 503 .2 11 152 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS WBC X103/mL -------- N-SEG X103/mL -------- LYMPH X103/mL -------- MONO X103/mL -------- EOSIN X103/mL -------- BASO X103/mL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSIN% -------- BASO% -------- Dose Level: 0 Dosage Unit: mg/kg/day 9.1 2.0 6.3 .7 .1 .0 22 69 8 1 0 9.4 1.3 7.4 .4 .3 .0 14 79 4 3 0 9.2 1.6 6.8 .6 .2 .0 18 74 6 2 0 .21 .49 .78 .21 .14 .00 5.7 7.1 2.8 1.4 .0 2 2 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 10.9 .9 8.8 1.0 .2 .0 9 81 9 1 0 9.3 1.0 7.6 .4 .3 .0 10 82 5 3 0 6.1 1.2 4.4 .3 .1 .0 20 72 5 2 0 8.8 1.0 6.9 .6 .2 .0 13 78 6 2 0 2.44 .15 2.27 .38 .10 .00 6.1 5.5 2.3 1.0 .0 3 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 5.8 .9 4.4 .4 .0 .0 16 77 7 0 0 153 Appendix 4 Individual Clinical Hematology Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 - - - - - I05350 - - - - - Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 - - - - - I05347 - - - - - I05348 - - - - - Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 - - - - - Covance 6329-222 3M T-6295.6 154 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mL -------- HGB G/DL -------- HCT % -------- MCV FL -------- MCH PG -------- MCHC % -------- PLT X103/mL -------- RETIC % -------- RETIC X103/mL -------- Dose Level: 0 Dosage Unit: mg/kg/day 5.02 12.6 38.9 77.4 25.1 32.5 382 1.0 50 5.26 13.7 42.2 80.4 26.1 32.5 640 1.3 68 5.14 .170 2 13.2 .78 2 40.5 2.33 2 78.9 2.12 2 25.6 .71 2 32.5 .00 2 511 182.4 2 1.2 .21 2 59 12.7 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 5.15 14.1 43.1 83.7 27.4 32.8 377 1.1 57 5.01 12.7 40.5 80.7 25.4 31.4 340 .7 35 5.24 12.5 39.8 75.9 23.8 31.4 558 .6 31 5.13 13.1 41.1 80.1 25.5 31.9 425 .8 .116 .87 1.74 3.93 1.80 .81 116.7 .26 3 3 3 3 3 3 3 3 41 14.0 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 4.81 12.3 36.7 76.4 25.6 33.6 529 1.0 48 155 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS WBC X103/mL -------- N-SEG X103/mL -------- LYMPH X103/mL -------- MONO X103/mL -------- EOSIN X103/mL -------- BASO X103/mL -------- N-SEG% -------- LYMPH% -------- MONO% -------- EOSIN% -------- BASO% -------- Dose Level: 0 Dosage Unit: mg/kg/day 9.2 3.9 4.4 .9 .0 .0 43 47 10 0 0 13.0 3.7 8.0 1.2 .0 .0 28 62 9 0 0 11.1 3.8 6.2 1.0 .0 .0 36 54 10 0 0 2.69 .14 2.55 .21 .00 .00 10.6 10.6 .7 .0 .0 2 2 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 8.7 1.7 6.2 .6 .1 .0 19 72 7 1 0 12.9 2.2 10.1 .5 .1 .0 17 78 4 1 0 8.3 2.6 5.0 .6 .1 .0 31 60 8 1 0 10.0 2.2 7.1 .6 .1 .0 22 70 6 1 0 2.55 .45 2.67 .06 .00 .00 7.6 9.2 2.1 .0 .0 3 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 15.7 7.2 7.9 .5 .1 .0 46 50 3 1 0 156 Appendix 4 Individual Clinical Hematology Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ ANISO POLY POIK HYPO TOXNEUT -------- -------- -------- -------- -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 - - - - - I05367 - - - - - Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 - - - - - I05365 - - - - - I05370 - - - - - Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 - - - - - Covance 6329-222 3M T-6295.6 157 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 95 25 1.0 8.2 5.2 3.0 .2 68 23 1.1 8.2 5.2 3.0 .3 8 111 46 9 199 81 82 24 1.0 8.2 5.2 3.0 .2 19.1 1.4 .07 .00 .00 .00 .07 2 2 2 2 2 2 2 8 155 .7 62.2 2 2 64 24.7 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 46 29 .9 7.7 4.6 3.1 .3 11 137 65 71 27 1.0 7.7 5.1 2.6 .4 9 202 82 66 31 1.0 7.8 4.6 3.2 .3 8 145 109 61 29 1.0 7.7 4.8 3.0 .3 13.2 2.0 .06 .06 .29 .32 .06 3 3 3 3 3 3 3 9 161 1.5 35.4 3 3 85 22.2 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 54 28 1.0 8.2 5.0 3.2 .4 10 150 68 158 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 52 33 638 91 45 46 587 84 4 156 353 3 301 494 37 242 90 340 48 4.9 2 40 9.2 2 612 36.1 2 88 4.9 2 4 228 424 .7 102.5 99.7 2 2 2 64 37.5 2 291 69.3 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 58 45 606 78 43 71 767 143 48 59 670 81 7 200 376 132 275 5 208 318 38 220 5 233 250 17 175 50 7.6 3 58 13.0 3 681 81.1 3 101 36.7 3 6 214 315 1.2 17.2 63.1 3 3 3 62 61.2 3 223 50.1 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 54 50 1086 117 5 220 244 7 144 159 Appendix 4 Individual Clinical Chemistry Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 I05350 10.6 7.6 161 5.7 110 10.8 6.8 164 5.8 110 MEAN S.D. N 10.7 .14 2 7.2 .57 2 162 2.1 2 5.8 .07 2 110 .0 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 I05347 I05348 10.3 7.8 159 5.1 111 11.2 6.9 164 5.8 117 10.3 8.3 154 6.0 108 MEAN S.D. N 10.6 .52 3 7.7 .71 3 159 5.0 3 5.6 .47 3 112 4.6 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 11.4 8.7 162 5.9 111 Covance 6329-222 3M T-6295.6 160 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 70 24 .9 7.6 4.8 2.8 .3 I05367 SH 82 24 1.1 8.3 5.4 2.9 .7 8 131 66 0 153 86 MEAN S.D. N 76 24 1.0 8.0 5.1 2.8 .5 8.5 .0 .14 .49 .42 .07 .28 2 2 2 2 2 2 2 4 142 5.7 15.6 2 2 76 14.1 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 I05365 I05370 55 23 .9 8.2 5.2 3.0 .4 7 114 47 73 23 .8 7.9 4.8 3.1 .4 8 169 49 64 31 .9 7.6 4.7 2.9 .3 11 178 110 MEAN S.D. N 64 26 .9 7.9 4.9 3.0 .4 9.0 4.6 .06 .30 .26 .10 .06 3 3 3 3 3 3 3 9 154 2.1 34.6 3 3 69 35.8 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 71 27 1.0 8.2 4.9 3.3 .3 12 141 67 161 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 45 38 546 81 3 290 356 17 247 I05367 SH 153 68 640 78 10 3524 312 2 216 MEAN S.D. N 99 76.4 2 53 21.2 2 593 66.5 2 80 2.1 2 6 1907 4.9 2286.8 2 2 334 31.1 2 10 10.6 2 232 21.9 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 I05365 I05370 60 45 755 62 64 73 849 80 51 55 881 79 5 253 281 21 193 4 567 369 158 228 3 334 321 12 225 MEAN S.D. N 58 6.7 3 58 14.2 3 828 65.5 3 74 10.1 3 4 385 324 1.0 163.0 44.1 3 3 3 64 81.8 3 215 19.4 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 53 55 683 110 3 1094 315 89 224 162 Appendix 4 Individual Clinical Chemistry Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 10.6 6.5 161 5.9 111 I05367 SH 11.3 8.3 157 8.6 115 MEAN S.D. N 11.0 .49 2 7.4 1.27 2 159 2.8 2 7.2 1.91 2 113 2.8 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 I05365 I05370 10.6 6.4 154 5.1 110 10.8 7.7 155 6.1 114 11.7 9.8 166 6.3 118 MEAN S.D. N 11.0 .59 3 8.0 1.72 3 158 6.7 3 5.8 .64 3 114 4.0 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 11.3 6.8 165 6.0 115 Covance 6329-222 3M T-6295.6 163 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 52 29 .9 7.4 5.0 2.4 .4 19 97 45 62 21 .9 7.3 4.9 2.4 .3 13 188 114 57 25 .9 7.4 5.0 2.4 .4 7.1 5.7 .00 .07 .07 .00 .07 2 2 2 2 2 2 2 16 142 80 4.2 64.3 48.8 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 56 21 .8 7.1 4.4 2.7 .3 10 149 60 68 25 .8 6.9 4.6 2.3 .3 9 184 56 62 25 .9 7.1 4.4 2.7 .4 10 157 90 62 24 .8 7.0 4.5 2.6 .3 10 163 69 6.0 2.3 .06 .12 .12 .23 .06 .6 18.3 18.6 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 58 21 .9 7.3 4.7 2.6 .4 9 151 50 164 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 65 41 692 88 85 71 761 79 2 903 363 3 895 461 35 227 27 284 75 14.1 2 56 21.2 2 726 48.8 2 84 6.4 2 2 899 412 .7 5.7 69.3 2 2 2 31 5.7 2 256 40.3 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 44 40 531 68 39 69 691 125 41 60 575 72 2 139 325 2 888 311 2 709 230 62 205 35 190 24 146 41 2.5 3 56 14.8 3 599 82.7 3 88 31.8 3 2 579 289 .0 391.1 51.3 3 3 3 40 19.6 3 180 30.7 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 54 55 1028 105 2 219 302 11 139 165 Appendix 4 Individual Clinical Chemistry Data Males Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 I05350 10.1 7.6 151 5.2 107 10.3 6.1 153 5.1 106 MEAN S.D. N 10.2 .14 2 6.8 1.06 2 152 1.4 2 5.2 .07 2 106 .7 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 I05347 I05348 9.7 7.0 147 5.0 110 9.6 6.6 150 4.5 110 9.2 6.4 145 4.7 103 MEAN S.D. N 9.5 .26 3 6.7 .31 3 147 2.5 3 4.7 .25 3 108 4.0 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 10.0 7.0 152 5.0 104 Covance 6329-222 3M T-6295.6 166 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 80 19 .8 7.1 4.7 2.4 .4 60 19 .9 7.7 5.1 2.6 .5 8 143 34 9 147 50 70 19 .8 7.4 4.9 2.5 .4 14.1 .0 .07 .42 .28 .14 .07 2 2 2 2 2 2 2 8 145 .7 2.8 2 2 42 11.3 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 60 24 .9 7.5 5.0 2.5 .5 15 102 42 57 28 .8 7.3 4.4 2.9 .5 16 140 59 53 21 .8 7.2 4.7 2.5 .4 17 157 107 57 24 .8 7.3 4.7 2.6 .5 16 133 69 3.5 3.5 .06 .15 .30 .23 .06 1.0 28.2 33.7 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 68 27 1.0 7.5 4.7 2.8 .4 17 136 47 167 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 45 42 491 77 71 103 665 85 1 534 404 2 512 600 43 256 35 393 58 18.4 2 72 43.1 2 578 123.0 2 81 5.7 2 2 523 502 .7 15.6 138.6 2 2 2 39 5.7 2 324 96.9 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 54 43 730 60 59 76 833 74 50 53 851 74 2 281 298 3 543 376 2 455 380 21 185 33 204 39 234 54 4.5 3 57 16.9 3 805 65.3 3 69 8.1 3 2 426 351 .6 133.3 46.2 3 3 3 31 9.2 3 208 24.7 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 46 55 672 100 2 308 291 84 184 168 Appendix 4 Individual Clinical Chemistry Data Females Day 2 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 I05367 9.7 6.5 150 5.0 108 10.7 6.9 156 5.9 108 MEAN S.D. N 10.2 .71 2 6.7 .28 2 153 4.2 2 5.4 .64 2 108 .0 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 I05365 I05370 10.2 6.7 146 5.1 104 9.7 7.6 149 4.7 104 10.0 8.4 158 4.8 108 MEAN S.D. N 10.0 .25 3 7.6 .85 3 151 6.2 3 4.9 .21 3 105 2.3 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 10.0 6.5 151 4.7 106 Covance 6329-222 3M T-6295.6 169 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 84 20 .8 7.6 4.7 2.9 .3 7 92 47 78 20 .9 8.0 5.0 3.0 .2 14 185 57 81 20 .8 7.8 4.8 3.0 .2 10 138 52 4.2 .0 .07 .28 .21 .07 .07 4.9 65.8 7.1 2 2 2 2 2 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 67 20 .8 7.5 4.4 3.1 .3 11 134 49 71 21 .7 7.3 4.5 2.8 .3 9 171 51 65 23 .8 7.8 4.5 3.3 .3 9 162 52 68 21 .8 7.5 4.5 3.1 .3 10 156 51 3.1 1.5 .06 .25 .06 .25 .00 1.2 19.3 1.5 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 63 18 .8 7.5 4.6 2.9 .4 7 137 50 170 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 62 37 714 80 40 56 825 80 0 305 349 0 193 445 28 238 38 306 51 15.6 2 46 13.4 2 770 78.5 2 80 .0 2 0 249 397 .0 79.2 67.9 2 2 2 33 7.1 2 272 48.1 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 42 40 477 65 41 66 677 125 35 66 514 65 0 110 361 0 875 330 0 212 290 42 250 35 222 16 202 39 3.8 3 57 15.0 3 556 106.4 3 85 34.6 3 0 399 327 .0 415.4 35.6 3 3 3 31 13.5 3 225 24.1 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 46 49 1012 98 0 270 260 0 139 171 Appendix 4 Individual Clinical Chemistry Data Males Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 I05350 10.0 7.3 153 5.0 112 10.5 6.6 158 5.3 112 MEAN S.D. N 10.2 .35 2 7.0 .49 2 156 3.5 2 5.2 .21 2 112 .0 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 I05347 I05348 9.4 7.3 151 4.5 112 9.9 7.0 156 5.0 114 10.0 6.6 149 5.0 109 MEAN S.D. N 9.8 .32 3 7.0 .35 3 152 3.6 3 4.8 .29 3 112 2.5 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 10.3 6.6 156 5.1 112 Covance 6329-222 3M T-6295.6 172 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 80 25 .8 8.1 4.9 3.2 .3 93 16 .8 8.0 4.2 3.8 .2 6 128 42 8 131 23 86 20 .8 8.0 4.6 3.5 .2 9.2 6.4 .00 .07 .49 .42 .07 2 2 2 2 2 2 2 7 130 1.4 2.1 2 2 32 13.4 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 74 18 .8 8.1 5.1 3.0 .3 68 21 .7 7.8 4.5 3.3 .4 77 19 .9 8.1 4.9 3.2 .3 8 111 30 8 162 43 8 168 40 73 19 .8 8.0 4.8 3.2 .3 4.6 1.5 .10 .17 .31 .15 .06 3 3 3 3 3 3 3 8 147 .0 31.3 3 3 38 6.8 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 73 18 .8 7.9 4.6 3.3 .3 12 117 44 173 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 45 43 492 75 46 62 625 63 1 181 415 0 103 453 23 284 38 322 46 .7 2 52 13.4 2 558 94.0 2 69 8.5 2 0 142 434 .7 55.2 26.9 2 2 2 30 10.6 2 303 26.9 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 58 65 655 57 45 53 805 72 43 53 865 75 0 240 364 1 228 334 0 187 369 21 251 31 192 24 251 49 8.1 3 57 6.9 3 775 108.2 3 68 9.6 3 0 218 356 .6 27.8 18.9 3 3 3 25 5.1 3 231 34.1 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 45 57 674 90 0 166 349 101 238 174 Appendix 4 Individual Clinical Chemistry Data Females Day 7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 I05367 10.4 6.5 155 5.7 112 11.5 5.7 158 7.0 113 MEAN S.D. N 11.0 .78 2 6.1 .57 2 156 2.1 2 6.4 .92 2 112 .7 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 I05365 I05370 10.7 6.8 151 5.7 111 10.3 6.9 152 5.3 113 11.1 8.2 162 5.5 114 MEAN S.D. N 10.7 .40 3 7.3 .78 3 155 6.1 3 5.5 .20 3 113 1.5 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 10.6 6.4 155 5.3 113 Covance 6329-222 3M T-6295.6 175 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 89 18 .9 8.0 5.2 2.8 .4 70 20 .8 7.4 4.8 2.6 .4 6 100 33 9 182 43 80 19 .8 7.7 5.0 2.7 .4 13.4 1.4 .07 .42 .28 .14 .00 2 2 2 2 2 2 2 8 141 2.1 58.0 2 2 38 7.1 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 60 18 .6 7.2 4.4 2.8 .4 10 136 37 61 20 .6 6.7 4.4 2.3 .4 7 158 55 67 19 1.0 7.6 4.7 2.9 .4 6 156 41 63 19 .7 7.2 4.5 2.7 .4 3.8 1.0 .23 .45 .17 .32 .00 3 3 3 3 3 3 3 8 150 2.1 12.2 3 3 44 9.5 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 64 15 .7 7.4 4.8 2.6 .4 6 132 27 176 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 52 34 785 86 42 47 737 75 6 131 372 3 193 415 41 248 29 277 47 7.1 2 40 9.2 2 761 33.9 2 80 7.8 2 4 162 394 2.1 43.8 30.4 2 2 2 35 8.5 2 262 20.5 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 42 41 431 58 34 48 671 120 31 57 456 54 3 97 351 4 85 294 3 151 272 52 236 37 188 15 184 36 5.7 3 49 8.0 3 519 131.9 3 77 37.0 3 3 111 306 .6 35.2 40.8 3 3 3 35 18.6 3 203 28.9 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 39 45 908 89 2 245 242 2 123 177 Appendix 4 Individual Clinical Chemistry Data Males Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 I05350 10.1 8.8 152 4.6 105 10.4 6.5 150 5.0 106 MEAN S.D. N 10.2 .21 2 7.6 1.63 2 151 1.4 2 4.8 .28 2 106 .7 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 I05347 I05348 9.7 7.4 148 4.5 108 9.5 6.4 149 4.2 107 9.8 6.2 147 4.8 106 MEAN S.D. N 9.7 .15 3 6.7 .64 3 148 1.0 3 4.5 .30 3 107 1.0 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 10.1 6.4 153 4.8 108 Covance 6329-222 3M T-6295.6 178 Covance 6329-222 Appendix 4 3M T-6295.6 Individual Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 I05367 77 22 .7 7.4 4.8 2.6 .4 82 16 .6 7.6 4.5 3.1 .3 7 127 27 7 111 20 MEAN S.D. N 80 19 .6 7.5 4.6 2.8 .4 3.5 4.2 .07 .14 .21 .35 .07 2 2 2 2 2 2 2 7 119 .0 11.3 2 2 24 4.9 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 I05365 I05370 49 20 .9 7.9 5.1 2.8 .5 57 22 .5 7.4 4.5 2.9 .7 67 17 .7 7.7 4.8 2.9 .4 6 111 28 8 150 42 9 155 36 MEAN S.D. N 58 20 .7 7.7 4.8 2.9 .5 9.0 2.5 .20 .25 .30 .06 .15 3 3 3 3 3 3 3 8 139 1.5 24.1 3 3 35 7.0 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 59 18 .8 7.8 4.6 3.2 .4 8 107 41 179 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 40 41 458 64 52 52 540 63 5 157 399 4 361 456 18 262 41 313 46 8.5 2 46 7.8 2 499 58.0 2 64 .7 2 4 259 428 .7 144.2 40.3 2 2 2 30 16.3 2 288 36.1 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 46 48 722 51 55 68 852 69 40 49 825 69 3 341 289 3 383 335 4 197 337 31 190 67 189 20 222 47 7.5 3 55 11.3 3 800 68.6 3 63 10.4 3 3 307 320 .6 97.5 27.2 3 3 3 39 24.6 3 200 18.8 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 40 51 727 86 3 462 440 309 283 180 Appendix 4 Individual Clinical Chemistry Data Females Day 14 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 I05367 10.1 6.6 152 5.5 110 10.8 7.0 157 6.5 109 MEAN S.D. N 10.4 .49 2 6.8 .28 2 154 3.5 2 6.0 .71 2 110 .7 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 I05365 I05370 10.5 6.3 146 5.2 105 9.9 6.3 149 5.0 107 10.8 7.5 159 5.5 112 MEAN S.D. N 10.4 .46 3 6.7 .69 3 151 6.8 3 5.2 .25 3 108 3.6 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 10.4 6.1 152 5.4 108 Covance 6329-222 3M T-6295.6 181 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 75 24 .8 7.5 4.6 2.9 .3 87 24 .9 7.7 4.6 3.1 .2 6 93 40 8 186 31 81 24 .8 7.6 4.6 3.0 .2 8.5 .0 .07 .14 .00 .14 .07 2 2 2 2 2 2 2 7 140 1.4 65.8 2 2 36 6.4 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 66 22 .8 7.2 4.0 3.2 .2 9 129 48 73 22 .7 6.7 4.1 2.6 .2 7 151 55 80 29 1.0 8.7 4.8 3.9 .3 13 172 57 73 24 .8 7.5 4.3 3.2 .2 10 151 53 7.0 4.0 .15 1.04 .44 .65 .06 3.1 21.5 4.7 3 3 3 3 3 3 3 3 3 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 80 15 1.1 8.2 4.8 3.4 .3 8 91 25 182 ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 61 36 798 103 43 56 712 90 6 476 362 2 344 485 37 241 37 329 52 12.7 2 46 14.1 2 755 60.8 2 96 9.2 2 4 410 424 2.8 93.3 87.0 2 2 2 37 .0 2 285 62.2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 42 45 477 73 34 49 710 143 49 93 505 65 2 134 382 4 202 350 2 606 270 73 263 24 235 8 185 42 7.5 3 62 26.6 3 564 127.2 3 94 42.9 3 3 314 334 1.2 255.2 57.7 3 3 3 35 33.9 3 228 39.5 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 31 38 815 88 1 202 285 3 156 183 Appendix 4 Individual Clinical Chemistry Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 I05350 10.4 8.2 152 6.3 112 10.6 6.8 155 5.0 110 MEAN S.D. N 10.5 .14 2 7.5 .99 2 154 2.1 2 5.6 .92 2 111 1.4 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 I05347 I05348 10.0 6.7 149 4.8 108 10.0 5.9 152 4.5 112 10.5 6.3 155 6.0 110 MEAN S.D. N 10.2 .29 3 6.3 .40 3 152 3.0 3 5.1 .79 3 110 2.0 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 11.0 6.4 156 6.0 107 Covance 6329-222 3M T-6295.6 184 ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Covance 6329-222 3M T-6295.6 Individual Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS GLU MG/DL -------- UN MG/DL -------- CREAT MG/DL -------- T PRO G/DL -------- ALB G/DL -------- GLOB G/DL -------- T BILI MG/DL -------- SBA umol/L -------- CHOL MG/DL -------- TRIG MG/DL -------- Dose Level: 0 Dosage Unit: mg/kg/day 87 26 .8 7.4 4.4 3.0 .2 11 107 41 86 24 .9 7.9 4.3 3.6 .2 7 135 36 86 25 .8 7.6 4.4 3.3 .2 .7 1.4 .07 .35 .07 .42 .00 2 2 2 2 2 2 2 9 121 2.8 19.8 2 2 38 3.5 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 50 28 1.0 8.5 5.0 3.5 .4 8 114 45 71 22 .8 7.7 4.4 3.3 .3 8 156 40 65 21 .8 7.4 4.3 3.1 .2 11 158 52 62 24 .9 7.9 4.6 3.3 .3 10.8 3.8 .12 .57 .38 .20 .10 3 3 3 3 3 3 3 9 143 1.7 24.8 3 3 46 6.0 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 78 24 1.0 8.2 4.6 3.6 .2 17 62 27 185 Covance 6329-222 ANIMAL NUMBER -----Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 Appendix 4 Individual Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT IU/L -------- ALT/SGPT IU/L -------- ALK PHOS IU/L -------- GGT IU/L -------- SDH IU/L -------- CK IU/L -------- AMYLASE IU/L -------- LIPASE IU/L -------- P AMYL U/L -------- Dose Level: 0 Dosage Unit: mg/kg/day 46 39 418 70 60 52 516 75 9 335 444 18 300 4 262 633 241 440 53 9.9 2 46 9.2 2 467 69.3 2 72 3.5 2 6 298 538 130 370 3.5 51.6 133.6 157.7 99.0 2 2 2 2 2 Dose Level: 0.02 Dosage Unit: mg/kg/day 53 49 926 67 44 60 966 79 39 52 832 81 4 215 290 2 363 348 2 240 381 10 193 39 205 20 257 45 7.1 3 54 5.7 3 908 68.8 3 76 7.6 3 3 273 340 1.2 79.2 46.1 3 3 3 23 14.7 3 218 34.0 3 Dose Level: 2.0 Dosage Unit: mg/kg/day 36 47 637 93 2 341 326 18 221 3M T-6295.6 186 Appendix 4 Individual Clinical Chemistry Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ CA MG/DL -------- I PHOS MG/DL -------- NA MMOL/L -------- K MMOL/L -------- CL MMOL/L -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 I05367 10.3 5.6 151 5.4 109 10.6 7.1 153 6.0 113 MEAN S.D. N 10.4 .21 2 6.4 1.06 2 152 1.4 2 5.7 .42 2 111 2.8 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 I05365 I05370 11.2 7.9 152 5.5 109 10.4 6.6 153 5.4 112 11.2 6.2 160 5.6 113 MEAN S.D. N 10.9 .46 3 6.9 .89 3 155 4.4 3 5.5 .10 3 111 2.1 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 11.1 6.5 158 5.7 110 Covance 6329-222 3M T-6295.6 187 Appendix 4 Individual Clinical Chemistry Data Males Day 30 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ PCOAO IU/G -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05349 0 I05350 1 MEAN 0 S.D. .7 N 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05344 4 I05347 4 I05348 3 MEAN 4 S.D. .6 N 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05345 1 Covance 6329-222 3M T-6295.6 188 Appendix 4 Individual Clinical Chemistry Data Males Day 30 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ PCOAO IU/G -------- Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05366 0 I05367 4 MEAN 2 S.D. 2.8 N 2 Group: 2 Dose Level: 0.02 Dosage Unit: mg/kg/day I05364 7 I05365 0 I05370 3 MEAN 3 S.D. 3.5 N 3 Group: 3 Dose Level: 2.0 Dosage Unit: mg/kg/day I05369 1 Covance 6329-222 3M T-6295.6 189 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 190 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 1 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05349 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2235.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 9:44 PROSECTOR: JILL PAUS RECORDER: WENDY CHERRY POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 191 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 2 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05350 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2295.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 11:00 PROSECTOR: JILL PAUS RECORDER: DONIA MEYER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 192 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 3 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05344 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2330.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 10:25 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIEDRICH POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 193 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 4 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05347 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2125.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 11:00 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIEDRICH POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- LIVER (LI) : -INFILTRATE, LYMPHOPLASMACYTIC,-MINIMAL TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 194 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 5 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05348 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2285.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 10:19 PROSECTOR: DENNIS HOFFMAN RECORDER: DONIA MEYER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT KIDNEY (KD) : -INFILTRATE, LYMPHOPLASMACYTIC,-SLIGHT, FOCAL TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 195 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 6 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05345 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 1870.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 11:10 PROSECTOR: WENDY CHERRY RECORDER: DENNIS HOFFMAN POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT TESTIS (TE) : -IMMATURE,-PRESENT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), TESTIS (TE), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, MALE (MM), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 196 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 7 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05366 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2000.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 9:40 PROSECTOR: DENNIS HOFFMAN RECORDER: DONIA MEYER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT LIVER (LI) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-SLIGHT, FOCAL GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), KIDNEY (KD), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 197 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 8 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05367 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2085.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 9:47 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIEDRICH POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- KIDNEY (KD) : -INFILTRATE, LYMPHOPLASMACYTIC,-MINIMAL LIVER (LI) : -INFILTRATE, LYMPHOPLASMACYTIC,-MINIMAL -LIPIDOSIS, SUBCAPSULAR (TENSION LIPIDOSIS),-SLIGHT, FOCAL GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 198 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 9 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05364 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2080.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 8:09 PROSECTOR: DENNIS HOFFMAN RECORDER: DONIA MEYER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT KIDNEY (KD) : -INFILTRATE, LYMPHOPLASMACYTIC,-SLIGHT ADRENAL, CORTEX (AC) : -HEMORRHAGE,-MODERATE, FOCAL -THROMBUS,-PRESENT >NOTE:>UNILATERAL MICROSCOPIC FINDINGS GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 199 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 10 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05365 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 2245.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 8:08 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIEDRICH POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- KIDNEY (KD) : -INFILTRATE, LYMPHOPLASMACYTIC,-MODERATE LIVER (LI) : -INFILTRATE, LYMPHOPLASMACYTIC,-MINIMAL GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -STAINS-PERINEUM/PERIANAL; DARK RED AND MOIST - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 200 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 11 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05370 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 1940.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 10:18 PROSECTOR: JILL PAUS RECORDER: WENDY CHERRY POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- LIVER (LI) : -INFILTRATE, LYMPHOPLASMACYTIC,-SLIGHT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 201 APPENDIX 5 Individual Animal Pathology Data Covance 6329-222 3M T-6295.6 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE: 12 ------------------------------------------------------------------------------------------------------------------------------------ ANIMAL NUMBER: I05369 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 05/22/98 STUDY DAY OF DEATH: 30 STUDY WEEK OF DEATH: 5 TERMINAL BODY WEIGHT: 1970.0 GRAMS DATE AND TIME OF NECROPSY: 05/22/98 8:08 PROSECTOR: JILL PAUS RECORDER: WENDY CHERRY POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: DR. TOM PALMER WEIGHER: NOT AVAILABLE ------------------------------------------------------------------------------------------------------------------------------------ O B S E R V A T I O N S NECROPSY HISTOPATHOLOGY ---------------------------------------------------------------- ---------------------------------------------------------------- GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH), MARROW, STERNUM (SE), BONE, STERNUM (SB), BRAIN (BR), SPINAL CORD (SC), NERVE, SCIATIC (SN), HEART (HT), MUSCLE, SKELETAL (SM), TRACHEA (TR), ESOPHAGUS (ES), GALLBLADDER (GB), PITUITARY (PI), AORTA (AO), LN, MESENTERIC (MS), THYROID (TY), PARATHYROID (PT), SALIV GL, MANDIB (SG), SKIN (SK), MAMMARY, FEMALE (MF), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), URINARY BLADDER (UB), OVARY (OV), UTERUS (UT), CERVIX (CV), VAGINA (VA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: EYE (EY), BONE, FEMUR (FE), MARROW, FEMUR (FM), KIDNEY (KD), LUNG (LU), LIVER (LI), SPLEEN (SP), PANCREAS (PA), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), THYMUS (TH) ------------------------------------------------------------------------------------------------------------------------------------ 202 Covance 6329-222 3M T-6295.6 APPENDIX 6 Quality Assurance Statement Summary and Individual Hormone Analyses Data Figure 1 - Mean Estradiol Data (pg/mL) - Males Figure 2 - Mean Estradiol Data (pg/mL) - Females Figure 3 - Mean Triiodothyronine Data (ng/dL) - Males Figure 4 - Mean Triiodothyronine Data (ng/dL) - Females NOTE: This appendix of the report contains information supplied by Ani Lytics Inc. and has been reviewed by the Quality Assurance Unit of Ani Lytics Inc. 203 Covance 6329-222 3M T-6295.6 204 Appendix 6 Summary and Individual Hormone Analyses Data Males Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- Dose Level: 0 34.86 29.20 38.62 17.83 32.03 4.002 2 28.23 14.701 2 Dose Level: 0.02 24.95 34.14 26.73 18.44 17.74 15.79 28.61 4.874 3 17.32 1.373 3 Dose Level: 2.0 28.71 13.98 ESTRIOL ng/mL ------- THYROID STIMULATING mIU/mL ------------------- Dosage Unit: mg/kg/day 0.00 0.00 2.33 3.30 0.00 0.000 2 2.82 0.686 2 Dosage Unit: mg/kg/day 0.00 0.00 0.00 2.62 2.49 1.21 0.00 0.000 3 2.11 0.779 3 Dosage Unit: mg/kg/day 0.00 1.71 TRIIODOTHYRONINE ng/dL ---------------- 160.41 119.07 139.74 29.232 2 152.65 148.40 66.41 122.49 48.610 3 97.61 THYROXIN mg/dL -------- 4.01 6.84 5.43 2.001 2 3.90 4.43 4.52 4.28 0.335 3 3.86 Covance 6329-222 3M T-6295.6 205 Appendix 6 Summary and Individual Hormone Analyses Data Females Day -7 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- Dose Level: 0 45.43 45.13 25.12 32.42 45.28 0.212 2 28.77 5.162 2 Dose Level: 0.02 28.17 70.25 45.95 21.98 26.58 42.65 48.12 21.124 3 30.40 10.852 3 Dose Level: 2.0 37.37 29.50 ESTRIOL ng/mL ------- THYROID STIMULATING mIU/mL ------------------- Dosage Unit: mg/kg/day 0.00 0.00 1.26 7.48 0.00 0.000 2 4.37 4.398 2 Dosage Unit: mg/kg/day 0.00 0.00 0.00 3.07 3.65 0.80 0.00 0.000 3 2.51 1.506 3 Dosage Unit: mg/kg/day 0.00 1.41 TRIIODOTHYRONINE ng/dL ---------------- 172.31 92.99 132.65 56.088 2 148.92 176.45 67.89 131.09 56.434 3 122.38 THYROXIN mg/dL -------- 5.55 4.21 4.88 0.948 2 5.71 4.94 3.62 4.76 1.057 3 3.60 Covance 6329-222 3M T-6295.6 206 Appendix 6 Summary and Individual Hormone Analyses Data Males Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ Group: 1 I05349 I05350 MEAN S.D. N Group: 2 I05344 I05347 I05348 MEAN S.D. N Group: 3 I05345 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- Dose Level: 0 33.04 32.75 25.02 18.84 32.90 0.205 2 21.93 4.370 2 Dose Level: 0.02 25.19 37.25 40.32 10.24 14.20 19.73 34.25 7.998 3 14.72 4.767 3 Dose Level: 2.0 18.16 20.12 ESTRIOL ng/mL ------- THYROID STIMULATING mIU/mL ------------------- Dosage Unit: mg/kg/day 0.00 0.00 0.73 3.57 0.00 0.000 2 2.15 2.008 2 Dosage Unit: mg/kg/day 0.00 0.00 0.00 3.27 3.58 2.45 0.00 0.000 3 3.10 0.584 3 Dosage Unit: mg/kg/day 0.00 0.95 TRIIODOTHYRONINE ng/dL ---------------- 181.44 191.25 186.35 6.937 2 195.89 209.96 159.16 188.34 26.229 3 90.73 THYROXIN mg/dL -------- 3.32 5.31 4.32 1.407 2 3.86 3.82 4.90 4.19 0.612 3 3.18 Covance 6329-222 3M T-6295.6 207 Appendix 6 Summary and Individual Hormone Analyses Data Females Day 29 4-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER ------ Group: 1 I05366 I05367 MEAN S.D. N Group: 2 I05364 I05365 I05370 MEAN S.D. N Group: 3 I05369 ESTRADIOL pg/mL --------- ESTRONE pg/mL ------- Dose Level: 0 67.67 39.27 24.46 27.47 53.47 20.082 2 25.97 2.128 2 Dose Level: 0.02 31.90 87.09 57.17 32.66 30.94 31.23 58.72 27.628 3 31.61 0.921 3 Dose Level: 2.0 19.82 25.85 ESTRIOL ng/mL ------- THYROID STIMULATING mIU/mL ------------------- Dosage Unit: mg/kg/day 0.00 0.00 2.57 3.32 0.00 0.000 2 2.95 0.530 2 Dosage Unit: mg/kg/day 0.00 0.00 0.00 2.50 4.64 1.14 0.00 0.000 3 2.76 1.764 3 Dosage Unit: mg/kg/day 0.00 3.92 TRIIODOTHYRONINE ng/dL ---------------- 141.93 183.46 162.70 29.366 2 179.61 196.25 165.89 180.58 15.203 3 90.17 THYROXIN mg/dL -------- 4.57 3.95 4.26 0.438 2 5.26 3.79 3.09 4.05 1.108 3 3.38 Covance 6329-222 3M T-6295.6 208 209 210 211 212 APPENDIX 7 Dose Confirmation Analysis Report Compound Stability Report Certificate of Analysis Quality of Assurance Statement Covance 6329-222 3M T-6295.6 NOTE: This appendix of the report contains information supplied by the Sponsor and has been reviewed by the Quality Assurance Unit of 3M. 213 Covance 6329-222 3M T-6295.6 214 Covance 6329-222 3M T-6295.6 215 Covance 6329-222 3M T-6295.6 216 Covance 6329-222 3M T-6295.6 217 Covance 6329-222 3M T-6295.6 218 Covance 6329-222 3M T-6295.6 219 Covance 6329-222 3M T-6295.6 220 Covance 6329-222 3M T-6295.6 221 Covance 6329-222 3M T-6295.6 222 Covance 6329-222 3M T-6295.6 223 Covance 6329-222 3M T-6295.6 224 Covance 6329-222 3M T-6295.6 225 Covance 6329-222 3M T-6295.6 226 APPENDIX 8 Cell Proliferation Report Covance 6329-222 3M T-6295.6 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. 227 Covance 6329-222 3M T-6295.6 228 Covance 6329-222 3M T-6295.6 229 Covance 6329-222 3M T-6295.6 230 Covance 6329-222 3M T-6295.6 231 Covance 6329-222 3M T-6295.6 232 Covance 6329-222 3M T-6295.6 233 Covance 6329-222 3M T-6295.6 234 Covance 6329-222 3M T-6295.6 235 Covance 6329-222 3M T-6295.6 236 Covance 6329-222 3M T-6295.6 237 Covance 6329-222 3M T-6295.6 238