Document 0Jg2OJqN0M8Vx1G07EgqYRKeR

C O V /H H > THE DEVELOPMENT SERVICES COMPANY Sponsor: 3M St. Paul, Minnesota FINAL REPORT Study Title: 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys Author: Peter J. Thomford, PhD Study Completion Date: January 11, 2002 Testing Facility: Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Laboratory Study Identification: Covance 6329-223 Sponsor Study Identification: 3M Study No. T-6295.7 Volume I of II Page 1 o f 1086 Covance 6329-223 3M T-6295.7 COMPLIANCE STATEMENT 26-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 Regulations, 40 CFR 792, with the exception that the analysis of fecal samples for urobilinogen at the Mayo Clinic were not done in compliance with Good Laboratory Practice Regulations. Andrew M. Seacat, PhD Study Monitor 3M Date 2 Covance 6329-223 3M T-6295.7 QUALITY ASSURANCE STATEMENT This report has been reviewed by the Quality Assurance Unit of Covance Laboratories Inc., in accordance with the Environmental Protection Agency (EPA) Good Laboratory Practice Standards, 40 CFR 792. The following inspections were conducted and findings reported to the study director and study director management. Inspection Date Reported to Dates_______ Study Director and From To Phase Study Director Management 08/06/98 08/06/98 Test Article Preparation 08/06/98 08/24/98 08/24/98 Protocol Review 08/24/98 11/25/98 11/25/98 Body Weight 11/25/98 03/03/99 03/03/99 Analytical Laboratory Inspection 03/03/99 04/09/99 04/12/99 Protocol Amendment Review 04/12/99 05/23/99 05/23/99 Protocol Amendment Review 05/23/99 09/27/99 09/27/99 Protocol Amendment Review 09/27/99 10/22/99 10/25/99 Data Review 10/27/99 10/20/99 10/27/99 Data Review 10/27/99 02/11/00 02/13/00 Protocol Amendment Review 02/13/00 03/16/00 03/16/00 Protocol Amendment Review 03/16/00 03/13/00 03/23/00 Data Review 03/23/00 04/04/00 04/04/00 Protocol Amendment Review 04/04/00 04/18/00 05/05/00 Report Review 05/09/00 05/31/00 05/31/00 Protocol Amendment Review 05/31/00 10/23/01 10/23/01 Protocol Amendment Review 10/23/01 12/18/01 12/18/01 Report Review 12/18/01 3 Covance 6329-223 3M T-6295.7 STUDY IDENTIFICATION 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys Test Material Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) Sponsor 3M Toxicology Services Building 220-2E-02, 3M Center St. Paul, Minnesota 55144-1000 Study Monitor Andrew M. Seacat, PhD 3M 651.575.3161 Alternate Study Monitor Marvin T. Case, DVM, PhD 3M Toxicology Services 651.733.5180 Study Location Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Study Director Peter J. Thomford, PhD Covance Laboratories Inc. PO Box 7545 Madison, Wisconsin 53707-7545 608.241.7207 Study Timetable Study Initiation Date In-Life (Experimental) Start Date In-Life Termination Date Experimental Termination Date August 20, 1998 August 26, 1998 March 8, 2000 December 21, 2001 4 Covance 6329-223 3M T-6295.7 KEY PERSONNEL 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys Study Director Study Toxicologist Study Coordinator Manager, Large Animal Toxicology Supervisor, Dose Formulation Associate Director, Laboratory Animal Medicine Clinical Pathologist Supervisor, Clinical Pathology Anatomic Pathologist Supervisor, Anatomic Pathology Supervisor, Anatomic Pathology Consultant Consultant Consultant Consultant Consultant Peter J. Thomford, PhD Dale Aldridge, BS Elizabeth A. Disch, BA Sharon Dunn, LATG, AT 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) Robert A. Leedle, DVM, PhD Diplomate, ACVP Laurie J. Schuller, BA, LAT Kimberly W. Durland, BS, HT Stephen I. Bistner, DVM Diplomate, ACVO Veterinary Ophthalmologist Dr. Saroj Das AniLytics Inc. Sandra R. Eldridge, PhD Pathology Associates North Carolina Division, A Charles River Company Sharon Ambrose Pathology Associates North Carolina Division, A Charles River Company Dr. Joe McConnell Mayo Clinic 5 Covance 6329-223 3M T-6295.7 VOLUME I OF II CONTENTS Page ABSTRACT.......................................................................................................................11 PURPOSE.......................................................................................................................... 14 REGULATORY COMPLIANCE..................................................................................... 14 TEST MATERIAL, VEHICLE, AND SOLVENT........................................................... 14 Test Material..................................................................................................................14 Vehicle........................................................................................................................... 14 Solvent........................................................................................................................... 15 Gelatin Capsules............................................................................................................ 15 Reserve (Archive) Samples............................................................................................15 Disposition.....................................................................................................................15 TEST ANIMALS AND HUSBANDRY........................................................................... 15 Animals.......................................................................................................................... 15 Identification..................................................................................................................16 Justification....................................................................................................................16 Husbandry......................................................................................................................16 Acclimation....................................................................................................................17 PROCEDURES..................................................................................................................17 Group Designations and Dosage Levels........................................................................ 17 Dosing Procedures......................................................................................................... 18 Dose Analyses............................................................................................................... 19 Observation of Animals.................................................................................................19 Clinical Pathology.........................................................................................................20 Blood Hormone Determination..................................................................................... 21 Serum PFOS Level Determination................................................................................21 Additional Serum Collection........................................................................................ 22 Urine and Feces PFOS Level Determination................................................................ 22 Additional Fecal Samples............................................................................................. 23 Interim Liver Biopsy Samples...................................................................................... 23 Terminal Liver Biopsy Samples.................................................................................... 23 Anatomic Pathology - Terminal Sacrifice.................................................................... 24 Anatomic Pathology - Recovery Sacrifice.................................................................... 26 Statistical Analyses........................................................................................................27 Record Retention...........................................................................................................28 6 Covance 6329-223 3M T-6295.7 VOLUME I OF II CONTENTS (Continued) Page RESULTS AND DISCUSSION....................................................................................... 28 Observation of Animals................................................................................................ 28 Clinical Pathology.........................................................................................................30 Palmitoyl CoA Oxidase Determination.........................................................................31 Blood Hormone Determination..................................................................................... 31 Anatomic Pathology......................................................................................................31 CONCLUSION................................................................................................................. 33 SIGNATURES.................................................................................................................. 34 REFERENCES.................................................................................................................. 35 OPHTHALMOLOGY REPORT...................................................................................... 36 PATHOLOGY REPORT...................................................................................................37 COMMENTS ON THE DATA........................................................................................ 45 CODES, ABBREVIATIONS, AND UNITS.................................................................... 47 General Codes and Abbreviations.................................................................................48 Codes for Clinical Pathology........................................................................................ 49 Abbreviations and Units for Clinical Hematology........................................................ 52 Abbreviations and Units for Clinical Chemistry........................................................... 54 Abbreviations and Units for Clinical Urinalysis........................................................... 56 Codes for Anatomic Pathology..................................................................................... 57 FIGURES 1 Mean Body Weight Data (kg) - Males.....................................................................59 2 Mean Body Weight Data (kg) - Females................................................................ 60 TABLES 1 Summary of Clinical Observations - Treatment.....................................................61 2 Summary of Clinical Observations - Recovery (Days 186 through365)...............65 3 Summary of Clinical Observations - Recovery (Days 366 through561).............. 66 4 Summary of Ophthalmic Observations - Treatment...............................................68 5 Summary of Ophthalmic Observations - Recovery.................................................70 6 Summary of Body Weight Data (kg) - Treatment...................................................71 7 Summary of Body Weight Data (kg) - Recovery....................................................76 8 Summary of Clinical Hematology Data - Day -27..................................................84 9 Summary of Clinical Hematology Data - Day 37...................................................88 10 Summary of Clinical Hematology Data - Day 62...................................................92 11 Summary of Clinical Hematology Data - Day 91...................................................96 7 Covance 6329-223 3M T-6295.7 VOLUME I OF II CONTENTS (Continued) Page TABLES 12 Summary of Clinical Hematology Data - Day153.............................................. 100 13 Summary of Clinical Hematology Data - Day182.............................................. 104 14 Summary of Clinical Hematology Data - Day217..............................................108 15 Summary of Clinical Hematology Data - Day245..............................................112 16 Summary of Clinical Hematology Data - Day274..............................................116 17 Summary of Clinical Hematology Data - Day322..............................................120 18 Summary of Clinical Hematology Data - Day364..............................................124 19 Summary of Clinical Hematology Data - Day456..............................................128 20 Summary of Clinical Hematology Data - Day546.............................................. 132 21 Summary of Clinical Chemistry Data - Day -27................................................... 136 22 Summary of Clinical Chemistry Data - Day 37 .................................................... 142 23 Summary of Clinical Chemistry Data - Day 62 .................................................... 148 24 Summary of Clinical Chemistry Data - Day 91 .................................................... 154 25 Summary of Clinical Chemistry Data - Day 153.................................................. 160 26 Summary of Clinical Chemistry Data - Day 182.................................................. 166 27 Summary of Clinical Chemistry Data - Day 217.................................................. 172 28 Summary of Clinical Chemistry Data - Day 245.................................................. 178 29 Summary of Clinical Chemistry Data - Day 274.................................................. 184 30 Summary of Clinical Chemistry Data - Day 322.................................................. 190 31 Summary of Clinical Chemistry Data - Day 364................................................. 196 32 Summary of Clinical Chemistry Data - Day 456..................................................202 33 Summary of Clinical Chemistry Data - Day 546..................................................208 34 Summary of Clinical Urinalysis Data - Day -27...................................................214 35 Summary of Clinical Urinalysis Data - Day 3 7 ....................................................216 36 Summary of Clinical Urinalysis Data - Day 6 2 ....................................................218 37 Summary of Clinical Urinalysis Data - Day 9 1 ....................................................220 38 Summary of Clinical Urinalysis Data - Day 153 ..................................................222 39 Summary of Clinical Urinalysis Data - Day 182..................................................224 40 Summary of Clinical Urinalysis Data - Day 2 17..................................................226 41 Summary of Clinical Urinalysis Data - Day 245 ..................................................228 42 Summary of Clinical Urinalysis Data - Day 2 74..................................................230 43 Summary of Clinical Urinalysis Data - Day 322..................................................232 44 Summary of Clinical Urinalysis Data - Day 364..................................................234 45 Summary of Clinical Urinalysis Data - Day 4 56..................................................236 46 Summary of Clinical Urinalysis Data - Day 546..................................................238 47 Summary of Palmitoyl CoA Oxidase Determinations - Terminal Sacrifice........ 240 48 Summary of Organ Weight Data - Terminal Sacrifice......................................... 242 49 Incidence of Macroscopic Observations - Terminal Sacrifice.............................. 272 50 Incidence of Macroscopic Observations - Recovery Sacrifice............................. 275 8 Covance 6329-223 3M T-6295.7 VOLUME I OF II CONTENTS (Continued) Page TABLES 51 Incidence of Microscopic Observations - Terminal Sacrifice............................... 276 52 Incidence of Microscopic Observations - Recovery Sacrifice.............................. 286 APPENDIX 1.................................................................................................................. 287 Protocol Deviations.....................................................................................................288 Protocol....................................................................................................................... 293 Protocol Amendment No. 1 ........................................................................................ 311 Protocol Amendment No. 2 ........................................................................................ 320 Protocol Amendment No. 3 ........................................................................................ 328 Protocol Amendment No. 4 ........................................................................................ 334 APPENDIX 2 .................................................................................................................. 336 Individual Animal Fate Data....................................................................................... 337 Individual Clinical Observations................................................................................. 339 Individual Ophthalmic Observations...........................................................................481 APPENDIX 3.................................................................................................................. 496 Individual Body Weight Data (kg)..............................................................................497 VOLUME II OF II APPENDIX 4 .................................................................................................................. 511 Individual Clinical Hematology Data..........................................................................512 Individual Clinical Chemistry Data.............................................................................614 Individual Clinical Urinalysis Data.............................................................................728 APPENDIX 5.................................................................................................................. 818 Individual Palmitoyl CoA Oxidase Determinations.................................................... 819 Individual Anatomic Pathology Data..........................................................................823 APPENDIX 6.................................................................................................................. 907 AniLytics Inc. Quality Assurance Statements............................................................ 908 Summary and Individual Blood Hormone Determination...........................................917 APPENDIX 7.................................................................................................................. 963 Cell Proliferation Report............................................................................................ 964 APPENDIX 8.................................................................................................................. 977 Electron Microscopic Evaluation of Liver in Cynomolgus Monkeys.........................978 9 Covance 6329-223 3M T-6295.7 VOLUME II OF II CONTENTS (Continued) Page APPENDIX 9................................................................................................................ 1069 Urobilinogen Analysis Report.................................................................................. 1070 APPENDIX 10.............................................................................................................. 1072 Dose Confirmation Analysis Report.........................................................................1073 Compound Stability Report...................................................................................... 1078 Analytical Laboratory Report................................................................................... 1080 Certificate of Analysis...............................................................................................1083 Quality Assurance Statement.................................................................................... 1086 10 ABSTRACT Covance 6329-223 3M T-6295.7 The purpose of this study was to assess the effect of the test material, Perfluorooctane Sulfonic Acid Potassium Salt [PFOS; T-6295 (hereafter referred to as PFOS)] on critical enzyme levels, hormones, and other selected biochemical parameters when administered daily by oral capsule to cynomolgus monkeys for at least 26 weeks. The treatment period was followed by an approximate 52-week recovery period. Male and female cynomolgus monkeys were assigned to four groups (six animals/sex in Groups 1, 3, and 4; four animals/sex in Group 2). Each group received dose preparations containing the vehicle, lactose, or 0.03, 0.15, or 0.75 mg of PFOS/kg of body weight/day (mg/kg/day). Two animals/group in Groups 1, 3, and 4 were in a recovery period and were not treated for at least 52 weeks following the 26 week treatment period. Food was provided ad libitum, except when animals were fasted. Water was provided ad libitum. The animals were observed twice daily (a.m. and p.m.) for mortality and moribundity. At least once daily, animals were examined for abnormalities and signs of toxicity, and food consumption was assessed qualitatively. Ophthalmic examinations were done before initiation of treatment and during Weeks 26 and 52. Body weight data were recorded weekly before initiation of treatment, on Days -1 and 1, and weekly thereafter. Blood and urine samples were collected for clinical hematology, clinical chemistry, and urinalysis tests before initiation of treatment and at specified intervals during treatment and recovery. Blood was also collected for blood hormone and PFOS level determinations before, during, and after treatment at specified intervals. Feces and liver samples were also collected at specified intervals. On Day 155 (Week 23), one male given 0.75 mg/kg/day died, and on Day 179 (Week 26), one male given 0.75 mg/kg/day was sacrificed due to poor health. On Days 184 and 185 (Week 27), four animals/sex/group (Groups 1 through 3) and four females and two males (Group 4) were anesthetized, weighed, exsanguinated, and necropsied. At necropsy at the scheduled and unscheduled sacrifices, a serum sample was collected, macroscopic observations were recorded, selected organs were weighed, and selected tissues were collected and preserved. Microscopic examinations were done on tissues from each animal in the control and high-dose groups and selected tissues from animals in the low-and mid-dose groups. Tissues were also collected for palmitoyl CoA oxidase determination, cell proliferation evaluation, PFOS determination, and electron microscopy. Additionally, the bile was collected from the gallbladder, and the gallbladder was preserved. At the recovery sacrifice on Day 549, the remaining Group 4 11 Covance 6329-223 3M T-6295.7 animals were anesthetized, weighed, exsanguinated, and necropsied. Macroscopic observations were recorded and specified tissues and serum were collected. Remaining animals in Groups 1 and 3 were transferred to Covance stock or transferred to a follow-up study, Covance 6329-268. At all dose levels, clinical observations, ophthalmic observations, and palmitoyl CoA oxidase determinations do not appear to be affected by treatment with PFOS. Two males given 0.75 mg/kg/day did not survive to scheduled termination. These deaths were preceded by some adverse clinical observations (constricted pupil, pale gums, abnormal feces, excessive salivation, labored respiration, dehydrated appearance, hypoactive, ataxic, recumbent, low food consumption) and appeared to be related to the administration of PFOS. When compared with animals given the control material, covariate adjusted mean body weights (CAM) for males given 0.75 mg/kg/day were slightly lower beginning at Week 21, and for females given 0.75 mg/kg/day CAM body weights were, in general, significantly lower beginning at Week 11. Similar decreases were not seen in the other treated groups; therefore, this finding is likely test material-related. Test material-related effects on body weights were not apparent during recovery. Low food consumption was noted sporadically for animals in the groups given the control material and 0.03 mg/kg/day throughout treatment. The incidence of low food consumption was generally higher in the groups given 0.15 or 0.75 mg/kg/day as compared to animals given the control material and appeared to be test material-related. During recovery, effects on food consumption were reversed. Estradiol values were generally lower on Days 62, 91, and 182 in males given 0.75 mg/kg/day, although because of the variation in the data only the Day 182 value was significant. Estrone values were generally higher in all of the treated females on Days 37, 62, and 91, although because of the variation in the data none of these values were significantly different, and this difference was not apparent on Day 182. Triiodothyronine values were notably lower in both males and females given 0.15 and 0.75 mg/kg/day on Days 91 and 182. With the single exception of males given 0.15 mg/kg/day on Day 91, all values were significantly lower. During recovery were occasional instances in which the hormone values in treated groups differed slightly from those of controls, but those differences were not consistent over time or between sexes, were not clearly dose-related, and did not appear to be clearly related to the administration of the test material. Apparent differences in the sexual maturity of both males and females used in this study complicates the interpretation of the hormone data. 12 Covance 6329-223 3M T-6295.7 The only clinical pathology parameters considered related to the test material were lower total cholesterol for animals given 0.75 mg/kg/day and lower high density lipoprotein cholesterol for animals given 0.15 or 0.75 mg/kg/day. These effects were reversed within the first 5 and 9 weeks of recovery, respectively. At the terminal sacrifice, increased liver weights, macroscopic observations of mottled liver, hepatocellular hypertrophy, and hepatocellular vacuolation in animals given 0.75 mg/kg/day were considered related to PFOS treatment. However, the microscopic examination liver biopsies taken during recovery did not indicate any test material-related findings and none of the macroscopic observations made at the recovery sacrifice were considered test material-related. There were no microscopic findings in the liver from the animals in the high-dose recovery group. This indicates that the hepatic test material-related effects were reversible. Treatment with PFOS by oral capsule for at least 26 weeks is generally well-tolerated in male and female cynomolgus monkeys at doses up to 0.15 mg/kg/day. Clinical and pathological findings considered to be associated with the treatment of PFOS after at least 26 weeks of treatment were found to be reversible during a 52-week recovery period. Based on the data presented in this report, the no-observable-adverse-effect level is 0.15 mg/kg/day. Dose analyses (provided by the Sponsor), fecal analysis results (provided by the Mayo Clinic) and electron microscopy results (provided by Pathology Associates North Carolina Division, A Charles River Company), were provided for inclusion in the final report. 13 PURPOSE Covance 6329-223 3M T-6295.7 The purpose of this study was to assess the effect of the test material on critical enzyme levels, hormones, and other selected biochemical parameters when administered daily by capsule to cynomolgus monkeys for at least 26 weeks. The treatment period was followed by an approximate 52-week recovery period. REGULATORY COMPLIANCE All aspects of this study were done in accordance with the Environmental Protection Agency Good Laboratory Practice Regulations, 40 CFR 792, with the exception that the analysis of fecal samples for urobilinogen at the Mayo Clinic were not done in compliance with Good Laboratory Practice Regulations. TEST MATERIAL, VEHICLE, AND SOLVENT Test Material The test material, Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295), Lot No. 217 (expiration date: August 31, 2001), 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, composition, or other characteristics that define the test material is on file with the Sponsor. 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, stability, composition, or other characteristics that define the vehicle is on file with the manufacturer. 14 Covance 6329-223 3M T-6295.7 Solvent The solvent was acetone (Spectrum, Gardena, California), Lot No. LH0253, (expiration date June 2000). It was received at Covance on June 23, 1997. The solvent was stored at room temperature. Information on synthesis methods, composition, or other characteristics that define the solvent is on file with the manufacturer. Gelatin Capsules Gelatin capsules, Size Nos. 2 (Lot No. 122932, expiration date June 12, 2003) and 4 (Lot No. 544043, expiration date August 1, 2002) were manufactured by Torpac Inc., (Fairfield, New Jersey). Lot No. 122932 was received at Covance on June 12, 1998, and Lot No. 544043 was received on September 1 and November 10, 1998. The capsules were stored at room temperature. A copy of the Certificate of Analysis provided by the manufacturer is maintained in the data. Reserve (Archive) Samples A reserve sample (1 g) of each lot of the test material, vehicle, and each test material/lactose dilution was taken and stored at room temperature. These samples were transferred to the Sponsor after completion of the treatment phase (see Protocol Deviations). Disposition Remaining test material will be retained at Covance for use in possible future studies. TEST ANIMALS AND HUSBANDRY Animals Young adult to adult cynomolgus monkeys were obtained from Covance Research Products Inc. (Denver, Pennsylvania) on June 30, 1998. The animals weighed 2.4 to 4.4 kg at initiation of treatment. 15 Covance 6329-223 3M T-6295.7 Identification Each animal was assigned a permanent number upon arrival and identified with a collar tag before initiation of treatment. All data for an animal are recorded under this number. Justification PFOS is a known hepatic peroxisome proliferator (PP) in the rat. When exposed to a 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. Husbandry Animal Rooms 251, 258, 259, and 527 were used for this study. Environmental controls for the animal rooms 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 suspended, stainless-steel cages. Certified primate diet (#8726C, Harlan Teklad) was provided once or twice daily, unless otherwise specified. 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. 16 Covance 6329-223 3M T-6295.7 Acclimation Twenty-four males and 24 females were received on June 30, 1998, and acclimated in Animal Room 251 for 57 days before initiation of treatment. In general, animals in this 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 performed on each animal. PROCEDURES This study was conducted in accordance with the Protocol dated August 20, 1998, and Protocol Amendment Nos. 1, 2, 3, and 4. The protocol, protocol amendments, and protocol deviations are in Appendix 1. Group Designations and Dosage Levels Selection of animals for the study was based on data collected during acclimation. 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 Level Number of Animals Group (mg/kg/day)a (mg/kg/day)b Males Females 1 0a 30a 6" 6" 2 0.03 3 0.15 15b 4 4 6c 6d 6d 4 0.75 30c 6d 6d a The control group (Group 1) received the equivalent amount of lactose in gelatin capsules as the total material administered to Group 4. b The low-dose (Group 2) received the test material diluted with lactose (1:499, w:w). c The mid-dose (Group 3) and high-dose (Group 4) groups received the test material diluted with lactose (1:39, w:w). d Two animals in Groups 1,3, and 4 designated as recovery animals were treated for at least 26 weeks, then treatment was discontinued, and the animals were observed for reversibility, persistence, or delayed occurrence of toxic effects for at least 52 weeks posttreatment. 17 Covance 6329-223 3M T-6295.7 Dosing Procedures Vehicle. Dose levels were based on the vehicle as supplied for Group 1. For Group 1 dose preparations, the specified amount of lactose was weighed, transferred into gelatin capsules, and the top and bottom halves of each capsule were joined. Capsules were prepared at least once weekly. Test Material. The test material/lactose preparations for Groups 2 through 4 were diluted once before initiation of treatment; capsules were prepared at least once weekly. A specified amount of test material was weighed, placed into a labeled mixing container, and the appropriate volume of acetone was added. After stirring manually until the test material was dissolved, the required amount of lactose was weighed and transferred to the container. The components were mixed thoroughly using a spatula. The prepared test material dilution was stirred periodically while allowed to stand exposed to the air until the acetone had evaporated. Preparations were diluted to facilitate capsule preparation. Samples of the finished mixture for dose analyses were taken directly from the container. The dose preparations were stored at room temperature between capsule preparations. The appropriate amount of prepared test material was weighed and transferred into Size 2 (Days 1 through 8) or 4 (Days 9 through 184) gelatin capsules and the top and bottom halves of each capsule were joined. Size 4 capsules were used instead of Size 2 to better facilitate dose administration. Individual daily doses were based on the most recently recorded body weight, with the exception of doses given on days when body weight measurements were performed; on those days, the previous body weight was used. All capsule preparations were stored at room temperature until used for dosing. Method of Administration. Gelatin capsules were used to facilitate comparison with data from previous toxicology studies that used the oral route. Also, oral is the most likely route of exposure in humans. Partial or intact capsules were noted in the vomitus of several animals on occasion; however, this is not considered to have adversely affected the results of the study. The dose preparations were administered orally in gelatin capsules once daily 7 days/week for at least 26 weeks (see Protocol Deviations for exceptions). 18 Covance 6329-223 3M T-6295.7 Dose Analyses Homogeneity and stability analyses were the responsibility of the Sponsor. Samples (approximately 1 g each) were taken from the top, middle, and bottom of the test material/lactose preparations on Day -15 for homogeneity analysis. Samples collected from the middle of the preparations were also designated for prestudy stability analysis. A set of samples (approximately 1 g each) were taken from the low- and high-dose test material/lactose preparations at the end of the treatment phase for test material content analysis. All samples were stored at room temperature until sent under ambient conditions to the Sponsor for analysis. Results of dose analyses were provided for inclusion in the final report. Observation of Animals Clinical Observations. The animals were observed twice daily (a.m. and p.m.) for mortality and moribundity. Animals were also observed at least once daily (a.m.) for signs of poor health or abnormal behavior, and food consumption was assessed qualitatively; only abnormal findings were recorded. Once weekly and on the day of scheduled sacrifice, each animal was observed; abnormal findings or an indication of normal was recorded (see Protocol Deviations for exceptions). Additionally, postdose observations were recorded during treatment approximately 30 to 90 minutes after the last dose administration; only abnormal findings were recorded. Ophthalmology. Ophthalmic examinations were done on each animal before initiation of treatment, before the scheduled terminal sacrifice during Week 26, and during Week 52 (see Protocol Deviations). The pupils were dilated with 1% Mydriacyl and the anterior portion of the eye, optic media, and ocular fundus were examined with an indirect ophthalmoscope by a board-certified ophthalmologist. Body Weights. Individual body weight data were recorded weekly before initiation of treatment, on Day -1, on the first day of treatment, and weekly thereafter. 19 Covance 6329-223 3M T-6295.7 Clinical Pathology Blood and urine samples were collected from each animal once before initiation of treatment (Day -27); on Days 37, 62, 91, 153, and 182 of treatment; and on Days 217, 245, 274, 322, 364, 456, and 546 during recovery (see Protocol Deviations). Animals were fasted overnight, and urine was collected overnight on wet ice before blood sampling; water was provided ad libitum. Blood was collected from the femoral vein. Potassium EDTA was the anticoagulant used for hematology tests; no anticoagulant was used for the chemistry tests. Blood samples were collected from the animal that was sacrificed at an unscheduled interval. Animals were bled in sequential order on Days 37, 62, and 91 and in random order at all other scheduled collections; this is not expected to have an impact on the clinical pathology results. The following were evaluated (see Protocol Deviations for exceptions). Hematology red blood cell (erythrocyte) count differential blood cell count hemoglobin segmented neutrophil count hematocrit lymphocyte count mean corpuscular volume monocyte count mean corpuscular hemoglobin eosinophil count mean corpuscular hemoglobin basophil count concentration blood cell morphology platelet count reticulocyte count white blood cell (leukocyte) count glucose urea nitrogen creatinine total protein albumin globulin total bilirubin cholesterol triglycerides alanine aminotransferase alkaline phosphatase aspartate aminotransferase gamma glutamyltransferase Clinical Chemistry sorbitol dehydrogenase creatine kinase calcium inorganic phosphorus sodium potassium chloride bile acids amylase lipase pancreatic-specific amylase high density lipoprotein (HDL) (effective with collection on Day 153) 20 Covance 6329-223 3M T-6295.7 volume (approximately 16 hours) specific gravity pH protein glucose ketones Urinalysis bilirubin blood urobilinogen microscopic examination of sediment appearance Blood Hormone Determination Blood samples (approximately 5 mL) were collected from each animal three times before initiation of treatment (Days -50, -40, and -27); on Days 37, 62, 91, and 182 of treatment; and on Days 217, 245, 274, 322, 364, 456, and 546 during recovery (see Protocol Deviations). Animals were fasted overnight. Blood was collected from a femoral vein without using an anticoagulant. Samples were allowed to clot and centrifuged within 1 hour after collection; serum was harvested. The serum was divided into two approximately equal aliquots and stored in a freezer, set to maintain -60 to -80oC, until packed on dry ice and shipped to AniLytics Inc. for analysis of cortisol, testosterone, estradiol, estrone, estriol, thyroid stimulating hormone, total triiodothyronine, and total thyroxin. Beginning with the collection on Day 322 the samples were also analyzed for free triiodothyronine and free thyroxin. Serum PFOS Level Determination Blood samples (approximately 2 mL) were collected from each animal once before initiation of treatment (Day -27); during Weeks 1 (Day 7), 2, 4, 6, 8, 12, 16, 20, 24, and 26, and 27 (Day 183) of treatment; and during Weeks 27 (Days 184, 185, and 187), 28 (Day 190), 29 (Day 198), 30 (Day 204), 31 (Day 211), 35, 39, 43, 47, 51, 53, 57, 61, 65, 69, 73, 77, and 79 (see Protocol Deviations). Animals were fasted overnight and water was provided ad libitum. Blood was collected from a femoral vein without using an anticoagulant. Samples were centrifuged within 1 hour after collection and serum was harvested. Serum samples were stored in a freezer, set to maintain -60 to -80oC, until packed on dry ice and shipped to the Sponsor for analysis. Results will reported separately. 21 Covance 6329-223 3M T-6295.7 Additional Serum Collection At the scheduled terminal necropsy and the necropsy of Animal No. I05506 (Group 4 male), blood samples (approximately 20 mL) were collected from the vena cava at the time of exsanguination. Samples were collected without using an anticoagulant and centrifuged within 1 hour of collection. 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 possible future analysis. An aliquot (0.8 ml) of the additional serum collection samples collected from all animals from Groups 1, 2, 3, and 4 sacrificed at the terminal necropsy were sent on dry ice by the Sponsor to AniLytics for total triiodothyronine, total thyroxin, free triiodothyronine, and free thyroxin determinations. Additional serum samples collected at the terminal and recovery sacrifices were transferred by the Sponsor to Anilytics for analysis of estradiol, follicle stimulating hormone (FSH), and lutenizing hormone (LH) for females, and estradiol in males. Results were provided for inclusion in the final report. Additionally, samples were transferred by the Sponsor to the Mayo Clinic for analysis of triiodothyronine (T3), total thyroxin (T4), free thyroxin (free T4), and thyroid stimulating hormone (TSH). Additional reserve samples of serum were transferred for possible future anlaysis for estradiol. Any unused serum will be returned to the Sponsor. Results were provided for inclusion in the final report. Urine and Feces PFOS Level Determination Urine [at least 2 mL (see Protocol Deviations)] and feces (at least 5 g) were collected overnight on the first day of recovery (Day 184) and on Days 189, 216, 275, 321, and 366 during recovery. In addition, a 24-hour sample of urine and feces was collected before the completion of 52 weeks of recovery. Except for the first day of recovery, animals were not fasted. Samples were stored in a freezer set to maintain -10 to -30oC, until they were packed on dry ice and shipped to the Sponsor. The samples will be analyzed for PFOS. Results will be reported separately. 22 Covance 6329-223 3M T-6295.7 Additional Fecal Samples During Week 23, a fresh fecal sample (up to 5 g) was collected from all animals in the control and high-dose groups. Samples were collected in white polypropylene containers after pans were cleaned in the morning to ensure that the fecal samples were not more than 6 hours old (see Protocol Deviations). Samples were packed on dry ice and shipped to the Mayo Clinic for analysis of urobilinogen using a routine, standardized, colormetric assay. Results were provided for inclusion in the final report. Interim Liver Biopsy Samples A sample of liver (approximately 1 to 2 g) was collected by biopsy from animals in Group 4 only during recovery [Week 57 (Day 393), on the same day as the serum PFOS blood collection]. This sample was divided into four portions as follows. One subsample was preserved in 10% neutral-buffered formalin, embedded in paraffin, sectioned, stained with hematoxylin and eosin (duplicate slides were prepared), and examined microscopically. The second subsample was flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80oC, until shipped to the Sponsor for analysis (see Protocol Deviations). Results will be reported separately. The third subsample was processed to block stage for electron microscopic evaluation. The tissue blocks and a hematoxylin and eosin-stained slide for light microscopy were transferred to Pathology Associates. Tissues were processed and evaluated by electron microscopy by Pathology Associates. A report was provided by Pathology Assoicates for inclusion in the final report. The fourth subsample was flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80oC, until transferred to the Sponsor for possible future analysis. Terminal Liver Biopsy Samples A sample of liver (approximately 1 g) was collected by biopsy from all animals in Group 3 during recovery [Week 80 (Day 554), one week after the serum PFOS blood collection (see Protocol Deviations)]. This sample was flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80oC, until shipped to the Sponsor for analysis. Results will be reported separately. 23 Covance 6329-223 3M T-6295.7 Anatomic Pathology - Terminal Sacrifice Necropsy. A necropsy was done on Animal No. I05509 (Group 4 male) that died on Day 155 (Week 23) and Animal No. I05506 (Group 4 male) that was sacrificed in a moribund condition on Day 179 (Week 26). During Week 27 (Days 184 and 185) four animals/sex/group (Groups 1through 3) and four females and two males (Group 4) were fasted overnight, 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 external surface of the brain; the nasal cavity and paranasal sinuses; cervical tissues and organs; and the thoracic, abdominal, and pelvic cavities and viscera. Organ Weights. At scheduled and unscheduled sacrifices, the following organs (when present) were weighed; paired organs were weighed separately. adrenal (2) brain epididymis (2) kidney (2) liver ovary (2) pancreas testis (2) thyroid (2) with parathyroid Organ-to-body weight percentages and organ-to-brain weight ratios were calculated. Palmitoyl CoA Oxidase Determinations. Representative samples of the right lateral lobe of liver were collected from each animal at the scheduled sacrifice, weighed, 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 left lateral lobe of the liver, left and right testes, and pancreas were collected and preserved in zinc formalin. A second set of tissues (representative samples of the left lateral lobe of the liver, left and right testes, and pancreas) preserved in formalin without zinc were also prepared. After fixation, samples were embedded in paraffin and shipped to Pathology Associates North Carolina Division, A Charles River Company (Pathology Associates) for proliferation cell nuclear antigen (PCNA) evaluation, including the examination of slides stained with 24 Covance 6329-223 3M T-6295.7 hematoxylin and eosin (see Protocol Deviations). Results were provided by Pathology Associates for inclusion in the final report (Appendix 7). Liver PFOS Determination. A section of liver (approximately 20 g) was collected from each animal at the scheduled sacrifice, weighed, flash-frozen in liquid nitrogen, and stored in a freezer, set to maintain -60 to -80oC, until shipped with plasma samples to the Sponsor. Results will be reported separately. Gallbladder and Bile Collection. At the scheduled terminal sacrifice for each animal, bile was collected from the gallbladder, measured, transferred into a cryovial, and flash-frozen in liquid nitrogen. The gallbladder, once emptied, was weighed, and a section (approximately 4 to 5 mm) from the mid-portion was collected. The remaining gallbladder was placed in a cryovial and flash-frozen in liquid nitrogen. The bile and gallbladder samples were stored on dry ice until transferred to a freezer set to maintain -60 to -80oC. Samples were packed on dry ice and shipped to the Sponsor for possible future analysis. Tissue Preservation. The following tissues (when present) or representative samples were collected and preserved in 10% neutral-buffered formalin, unless otherwise specified (see Protocol Deviations). adrenal (2) aorta brain cecum cervix colon duodenum epididymis (2) esophagus eyes [(2) preserved in Davidson's fixative for all sacrificed animals] femur with bone marrow (articular surface of the distal end) gallbladder heart ileum jejunum kidney (2) lesions liver lung mammary gland mesenteric lymph node ovary (2) pancreas pituitary prostate rectum salivary gland [mandibular (2)] sciatic nerve seminal vesicle (2) skeletal muscle (thigh) skin spinal cord (cervical, thoracic, and lumbar) spleen 25 sternum with bone marrow stomach testis [(2) preserved in Bouin's solution for all sacrificed animals] thymus Covance 6329-223 3M T-6295.7 thyroid (2) with parathyroid trachea urinary bladder uterus vagina Histopathology. Tissues (as appropriate) were embedded in paraffin, sectioned, stained with hematoxylin and eosin, and examined microscopically from each animal in the control and high-dose groups (see Protocol Deviations for exceptions). In addition, liver and thymus for all animals in the low- and mid-dose groups and spinal cord gray matter from females in the low- and mid-dose groups were embedded in paraffin, sectioned, stained with hematoxylin and eosin, and examined microscopically. Other tissues, as appropriate, will be retained for possible future examination. Bone marrow smears from the sternum of each animal at scheduled and unscheduled sacrifices were prepared, stained with Wright's stain, and retained for possible examination. Electron Microscopy. A sample of the liver was collected from each animal at the scheduled terminal sacrifice. Tissues were processed into blocks and, along with a hematoxylin and eosin-stained slide, were shipped to Pathology Associates for analysis. Results were provided for inclusion in the final report. Anatomic Pathology - Recovery Sacrifice Termination. Remaining animals in Group 1 were transferred to Covance stock on Day 549 and remaining animals in Group 3 were transferred to Covance 6329-268 on Day 561. On Day 549, remaining animals in Group 4 were fasted overnight, anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. The necropsy of the animals in Group 4 included a macroscopic examination of the external surface of the body; all orifices; the cranial cavity; the external surface of the brain; the nasal cavity and paranasal sinuses; cervical tissues and organs; and the thoracic, abdominal, and pelvic cavities and viscera. Liver Samples. Samples of liver were collected from animals in Group 4 as follows. 26 Covance 6329-223 3M T-6295.7 One sample was preserved in 10% neutral-buffered formalin, embedded in paraffin, sectioned, stained with hematoxylin and eosin (duplicate slides were prepared), and examined microscopically. The second sample was flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80oC, until shipped to the Sponsor for analysis. Results will be reported separately. The third sample was processed to block stage for electron microscopic evaluation. The tissue blocks and a hematoxylin and eosin-stained slide for light microscopy were transferred to Pathology Associates. Tissues were processed and evaluated by electron microscopy by Pathology Associates. A report was provided by Pathology Associates for inclusion in the final report. Additional Tissue and Serum Samples. Samples of lung, kidney, spleen, thyroid, brain, abdominal fat, heart, (approximately 3 g each, if possible), and bile and serum (each as much as possible) were collected. These samples were flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80oC, until shipped to the Sponsor for possible future analysis. Statistical Analyses 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. Comparison tests took variance heterogeneity into consideration. One-way analysis of variance [ANOVA (Winer, 1971a)] was used (if applicable) to analyze initial body weights, organ weights, palmitoyl CoA oxidase activities, continuous clinical pathology values, and blood hormone determinations. 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. If the ANCOVA was significant, covariate-adjusted means were used for control versus treated group comparisons. 27 Covance 6329-223 3M T-6295.7 Group comparisons (Groups 2 through 4 versus Group 1) were evaluated at the 5.0%, two-tailed probability level. Only data collected on or after the first day of treatment were analyzed statistically. Statistical analyses were not performed on data collected during recovery. 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 at least 1 year. At least 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 the protocol, study correspondence, and an original copy of the final report will be retained by Covance-Madison. Within 1 year after submission of the final report, all of the aforementioned materials from the Sponsor's designees (AniLytics Inc., 3M E. T. & S, Mayo Clinic, and Pathology Associates) will be sent to the Sponsor (Andrew Seacat, PhD, 3M) by the Sponsor's designees. RESULTS AND DISCUSSION Observation of Animals Clinical Observations. Clinical observations are summarized in Tables 1, 2, and 3; individual data are presented in Appendix 2. Individual animal fate data are also presented in Appendix 2. Animal Nos. I05506 and I05509 given 0.75 mg/kg/day (Group 4 males) did not survive to the scheduled terminal sacrifice. All other animals survived to the scheduled study termination. No clinical observations noted in the animals that survived to the terminal sacrifice or recovery were attributable to the administration of PFOS. Animal No. I05509 (Group 4 male) died after dosing on Day 155 (Week 23). On Day 154 (Week 22) observations of constricted pupil in both eyes and pale gums were noted. Observations noted on Day 155 prior to dosing included few, mucoid, liquid, and black-colored feces and low food consumption. Approximately 15 minutes after dosing, the animal was observed as hypoactive with labored respiration and pale gums. This 28 Covance 6329-223 3M T-6295.7 animal also appeared dehydrated and was cold to the touch. These observations persisted until approximately 30 minutes postdose when the animal was also noted as recumbent. Shortly thereafter, the animal died during an examination by a laboratory animal veterinarian. An enlarged liver was detected by palpation. The cause of death was determined to be pulmonary necrosis with severe acute inflammation. On Day 179 (Week 26), Animal No. I05506 (Group 4 male) was sacrificed in a moribund condition. Low food consumption was noted on Day 178 (Week 26) and at the a.m. observation interval on Day 179. Approximately 5 to 10 minutes postdose on Day 179, the animal had excessive salivation, labored respiration, and hypoactive and ataxic behavior. With the exception of excessive salivation, these findings continued to be observed approximately 3 hours postdose. The cause of the moribund condition was not determined. Two additional animals had noteworthy observations during treatment. One female in the group given the control material, Animal No. I05529, was examined by a laboratory animal veterinarian on Day 5 (Week 1) due to observations of dehydration, thin appearance, clear oral and nasal discharge, excessive salivation, and audible respiration. This animal was diagnosed with pneumonia and treated with Lactated Ringer's solution and antibiotics. This animal had recovered by Day 14 (Week 2). Animal No. I05534 (Group 4 female) was diagnosed with a tapeworm infection during Week 23 and was treated with praziquantel. Neither infection was test material-related. Clinical observations during recovery were typical of laboratory primates. Ophthalmology. Ophthalmic observations are summarized in Tables 4 and 5; individual data are presented in Appendix 2. There were no ophthalmic observations at the Week 26 or Week 52 examinations that were test material-related. Animal No. I05529 (Group 1 female) was noted as having increased myelination of the right optic nerve at the baseline and Week 52 ophthalmic examinations. Because this is a permanent, congenital condition, it was noted at the baseline and recovery examinations only and is not related to treatment with PFOS. Body Weights. Body weight data are illustrated in Figures 1 and 2 and summarized in Tables 6 and 7; individual data are presented in Appendix 3. 29 Covance 6329-223 3M T-6295.7 Covariate-adjusted mean (CAM) body weights were slightly lower in males given 0.75 mg/kg/day when compared with males given the control material beginning at Week 21; the difference was significant at Weeks 23 and 27. In females given 0.75 mg/kg/day, CAM body weights were significantly lower at Weeks 11 through 16, 19 through 23, and 25 through 27 when compared with females given the control material. These decreases were likely test material-related. Differences in body weights were not apparent during the recovery period. Food Consumption. Food consumption data are summarized in Tables 1, 2, and 3 (Summary of Clinical Observations); individual data are included in the individual clinical observations in Appendix 2. Low food consumption was noted sporadically for animals in the groups given the control material and 0.03 mg/kg/day. The incidence of low food consumption was generally higher in the groups given 0.15 and 0.75 mg/kg/day as compared to animals given the control material and appeared to be test material-related. During recovery, instances of low food consumption were sporadic and were similar for animals in the control and treated groups. Clinical Pathology Hematology, clinical chemistry, and urinalysis data are summarized in Tables 8 through 46; individual data are presented in Appendix 4. Administration of PFOS was associated with moderately to markedly lower total cholesterol for males and females given 0.75 mg/kg/day and high density lipoprotein cholesterol for males and females given 0.15 or 0.75 mg/kg/day. During the treatment period, the effect on total cholesterol became progressively worse over time. The effect on cholesterol was reversed within 5 weeks of the end of treatment, and the effect on high density lipoprotein cholesterol was reversed within 9 weeks of the end of treatment. Of uncertain relationship to administration of PFOS was lower total bilirubin concentration for males given 0.75 mg/kg/day and higher serum bile acid concentration for males given 0.75 mg/kg/day. These potential effects of the test material were very mild, and neither was considered adverse. 30 Covance 6329-223 3M T-6295.7 Palmitoyl CoA Oxidase Determination Palmitoyl CoA oxidase determinations are summarized in Table 47; individual data are presented in Appendix 5. Results of palmitoyl CoA oxidase determinations were not considered to be related to the test material. Blood Hormone Determination Summary and Individual Blood Hormone Data are presented in Appendix 6. Estradiol values were generally lower on Days 62, 91, and 182 in males given 0.75 mg/kg/day, although because of the variation in the data only the Day 182 value was significant. Estrone values were generally higher in all of the treated females on Days 37, 62, and 91, although because of the variation in the data none of these values were significantly different, and this difference was not apparent on Day 182. Triiodothyronine values were notably lower on Days 91 and 182 in both males and females given 0.15 or 0.75 mg/kg/day. With the single exception on Day 91 of males given 0.15 mg/kg/day, all values were significantly lower. There were several other instances in which the hormone values in treated groups differed from those of controls, but these differences were not consistent over time or between sexes, were not clearly dose-related, and did not appear to be related to the administration of the test material. During recovery were occasional instances in which the hormone values in treated groups differed slightly from those of controls, but those differences were not consistent over time or between sexes, were not clearly dose-related, and did not appear to be clearly related to the administration of the test material. Apparent differences in the sexual maturity of both males and females used in this study complicates the interpretation of the hormone data. Anatomic Pathology Terminal body weights, absolute organ weights, organ-to-body weight percentages, and organ-to-brain weight ratios are summarized in Table 48; incidences of macroscopic and microscopic observations are summarized in Tables 49 through 52. Individual data are presented in Appendix 5. 31 Covance 6329-223 3M T-6295.7 Two of four males receiving 0.75 mg/kg/day (high dose) did not survive to the scheduled terminal sacrifice at Week 27. At the terminal sacrifice, females in the group receiving 0.75 mg/kg/day had increased absolute liver weight, liver-to-body weight percentages, and liver-to-brain weight ratios. In males, liver-to-body weight percentages were increased in the high-dose group compared to the control group. Absolute and relative liver weight increases were regarded as test material-related. Among the macroscopic observations, only "mottled" liver was considered test material-related. "Mottled" livers were observed in the two high-dose males and in one high-dose female. Of the two males not surviving until the scheduled terminal sacrifice, one had "mottled" and "large" liver. Microscopic examination of animals sacrificed at Week 27 and of the two males sacrificed at an unscheduled interval yielded test material-related observations in the liver. In four of four high-dose males there was hepatocellular hypertrophy, occurring either centrilobullary or without regard to location within hepatic lobules. Hypertrophy, as described in the males, was observed in all high-dose females. The microscopic observations of hepatocellular hypertrophy were reflected in higher liver weights in the high-dose females. Hypertrophy was regarded as test material-dependent in high-dose animals. Centrilobular or diffuse hepatocellular vacuolation was also test material-dependent in high-dose animals, occurring in two of four females and two of four males. Multifocal hepatic vacuoles were not regarded as test material-dependent because they were found in one of four low-dose males, and in a control and a low-dose female. Microscopic examination of liver taken at biopsy on Week 57 from the high-dose animal did not have any test material-related findings. At the recovery sacrifice, one of two males and one of two females did not have macroscopic observations. The observations in the other animals were of adhesions on the lungs or liver and nodules in the thoracic cavity. None of these observations was considered test material-related. Only livers were examined microscopically, and no test material-related observations were made. The hepatic vacuolation observed in terminal sacrifice and unscheduled death animals was not present, indicating that the hepatic test material-related effects were reversible. 32 CONCLUSION Covance 6329-223 3M T-6295.7 Treatment with PFOS by oral capsule for at least 26 weeks is generally well-tolerated in male and female cynomolgus monkeys at doses up to 0.15 mg/kg/day. Clinical and pathological findings considered to be associated with the treatment of PFOS after at least 26 weeks of treatment were found to be reversible during a 52-week recovery period. Based on the data presented in this report, the no-observable-adverse-effect level is 0.15 mg/kg/day. Dose analysis results (provided by the Sponsor), fecal analysis results (provided by the Mayo Clinic), and electron microscopy results (provided by Pathology Associates), were provided for inclusion in the final report. 33 SIGNATURES Covance 6329-223 3M T-6295.7 Elir^beilli A. D .m:>i, Ti A tudy G'Qrdm^tor Cbvaflce Laboratorio nc Studv tetar Cvancc LLburatoni.^ Irte. ->L-i-k7--A / -yi >O.-2 LXi.te 34 Covance 6329-223 3M T-6295.7 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). 35 OPHTHALMOLOGY REPORT Covance 6329-223 3M T-6295.7 Ophthalmic examinations were done before initiation of treatment and during Weeks 26 and 52. There were no ophthalmic observations at the Week 26 or Week 52 examinations that were test material-related. Animal No. I05529 (Group 1 female) was noted as having increased myelination of the right optic nerve at the baseline and Week 52 ophthalmic examinations. Because this is a permanent, congenital condition, it was noted at the baseline and recovery examinations only and is not related to treatment with PFOS. There were no test material-related observations at any of the examinations. fS ^^ Stephen I. Bistner, DVM Diplomate, ACVO Veterinary Ophthalmologist i ZUQOf Date 36 PATHOLOGY REPORT Covance 6329-223 3M T-6295.7 SUMMARY The purpose of the study was to assess the effect of the test material, Perfluorooctane Sulfonic Acid Potassium Salt (PFOS), on critical enzyme levels, hormones, and other selected biochemical parameters when administered daily by capsule to cynomolgus monkeys for at least 26 weeks. The test material was administered at dose levels of 0.03, 0.15, and 0.75 mg/kg/day. One male given 0.75 mg/kg/day died on Day 155 after dose administration and one male given 0.75 mg/kg/day was sacrificed on Day 179 due to poor health. The treatment period was followed by an approximate 52-week recovery period. Administration of PFOS was associated with moderately to markedly lower total cholesterol for males and females given 0.75 mg/kg/day and high density lipoprotein cholesterol for males and females given 0.15 or 0.75 mg/kg/day. During the treatment period, the effect on total cholesterol became progressively worse over time. The effect on cholesterol was reversed within 5 weeks of the end of treatment, and the effect on high density lipoprotein cholesterol was reversed within 9 weeks of the end of treatment. Of uncertain relationship to administration of PFOS was lower total bilirubin concentration for males given 0.75 mg/kg/day and higher serum bile acid concentration for males given 0.75 mg/kg/day. These potential effects of the test material were very mild, and neither was considered adverse. Two of four males receiving 0.75 mg/kg/day did not survive to the scheduled terminal sacrifice at Week 27. At the terminal sacrifice, females in the group receiving 0.75 mg/kg/day had increased absolute liver weight, liver-to-body weight percentages, and liver-to-brain weight ratios. In males, liver-to-body weight percentages were increased in the high-dose group compared to controls. These absolute and relative liver weight increases were regarded as test material-related. Among the macroscopic observations, only "mottled" liver was considered test material-related. "Mottled" livers were observed in the two high-dose males and in one high-dose female. Of the two males not surviving until the scheduled terminal sacrifice, one had "mottled" and "large" liver. 37 Covance 6329-223 3M T-6295.7 Microscopic examination of animals sacrificed at Week 27 and the two unscheduled sacrifice males yielded test material-related observations in the liver. In four of four high-dose males there was hepatocellular hypertrophy, occurring either centrilobullary or without regard to location within hepatic lobules. Hypertrophy, as described in the males, was also observed in four of four high-dose females. The microscopic observations of hepatocellular hypertrophy were reflected in higher liver weights in the high-dose females. Hypertrophy was regarded as test material-dependent in high-dose animals. Centrilobular or diffuse hepatocellular vacuolation was also test material-dependent in high-dose animals, occurring in two of four females and two of four males. Multifocal hepatic vacuoles were not regarded as test material-dependent because they were found in one of four low-dose males, and in a control and a low-dose female. Microscopic examination of liver taken at biopsy on Week 57 from the high-dose animal did not have any test material-related findings. For the recovery sacrifice at Week 79, only high-dose animals were necropsied. One of two males and one of two females did not have macroscopic observations. The observations in the other animals were of adhesions on the lungs or liver and nodules in the thoracic cavity. None of these observations was considered test material-related. Only livers were examined microscopically. No test material-related observations were made. The hepatic vacuolation observed in terminal sacrifice and unscheduled death animals was not present, indicating that the hepatic test material-related effects were reversible. METHODS Four groups of male and female cynomolgus monkeys were administered the test material daily by capsule at a dose level of 0 (control group; received capsules containing lactose), 0.03, 0.15, or 0.75 mg/kg of body weight/day (mg/kg/day). There were six animals/sex in the control group and the groups given 0.15 or 0.75 mg/kg/day; two animals/sex in these groups were designated as recovery animals to be observed for approximately 26 weeks posttreatment. The recovery period was later extended an additional 26 weeks. There were four animals/sex in the group given 0.03 mg/kg/day. 38 Covance 6329-223 3M T-6295.7 One male given 0.75 mg/kg/day died on Day 155 following dose administration, and one male given 0.75 mg/kg/day was sacrificed on Day 179 due to poor health. Blood and urine were collected for hematology, clinical chemistry, and urinalysis tests once before initiation of treatment (Week -4), on Days 37, 62, 91, 153, and 182 and on Days 217, 245, 274, 322, 364, 456, and 546 (recovery animals). High density lipoprotein cholesterol was not measured at the clinical pathology intervals before Day 153. The terminal sacrifice and necropsy occurred on Days 184/185; macroscopic observations were recorded, organ weights were obtained, and tissues were placed in fixative as specified by the protocol. Samples of the right lateral lobe of the liver from each animal were frozen for analysis of palmitoyl CoA oxidase activity. Sections of liver from each animal were processed to block for electron microscopy and shipped to the Sponsor's designee for ultrastructural evaluation. Samples of liver from each animal were frozen and shipped to the Sponsor for PFOS determination. The gallbladders and bile from each animal were collected, frozen, and shipped to the Sponsor. Samples of pancreas, left and right testes, and the left lateral lobe of the liver were preserved for cell proliferation evaluation by the Sponsor's designee using proliferation cell nuclear antigen. Light microscopic examinations were done on collected tissues from control animals and animals given 0.75 mg/kg/day. In addition, liver and thymus from all animals given 0.03 or 0.15 mg/kg/day and spinal cord gray matter from females given 0.03 or 0.15 mg/kg/day were examined by light microscopy. During Week 57, liver biopsies were performed on the recovery animals that had been given 0.75 mg/kg/day. The tissue was divided into four samples. Three of the samples were used for light microscopic examination, ultrastructural examination by the Sponsor's designee, and PFOS analysis by the Sponsor, respectively. The fourth sample was frozen and shipped to the Sponsor for possible analysis. At the end of the recovery period (Week 79), the control animals were returned to the Covance stock colony, the animals that had been given 0.15 mg/kg/day were transferred to a subsequent study for the Sponsor (Covance 6329-268) following liver biopsy for PFOS analysis by the Sponsor, and the animals that had been given 0.75 mg/kg/day were sacrificed and necropsied. At this recovery necropsy, macroscopic observations were recorded, and three samples of liver were collected for light microscopic examination, ultrastructural examination by the Sponsor's designee, and PFOS analysis by the Sponsor, respectively. 39 Covance 6329-223 3M T-6295.7 Statistically significant differences cited in the Results and Discussion are based on comparisons between the control and treated groups. RESULTS AND DISCUSSION Mortality Two of four males receiving 0.75 mg/kg/day (high dose) of the test material did not survive to the scheduled terminal sacrifice at Week 27. One was found dead on Day 155. The other was sacrificed on Day 179 due to poor health. The cause of death in the animal found dead was judged to be pulmonary necrosis with severe acute inflammation. Microscopically, the pulmonary lesion appeared to be an acute exacerbation of a chronic lesion. The cause of death in the moribund animal was not determined. All other animals survived to their scheduled sacrifices. Clinical Pathology Week -4. Results of clinical pathology tests indicated no obvious group or individual health abnormalities. Several animals, however, had mildly elevated alanine aminotransferase activities at Week -4. These animals were primarily females and were dispersed among all of the groups. By Day 37, their alanine aminotransferase activities were no longer elevated. The transient increase in this liver enzyme was considered likely due to subclinical infection with Hepatitis A virus, a common infection in cynomolgus monkeys, and did not negatively impact evaluation of the test material. Days 37, 62, 91,153, and 182. Although there were several statistically significant or otherwise notable differences for clinical pathology test results between the control and treated animals, most of the differences were inconsistent over time or similar to differences present before initiation of treatment (i.e., Week -4). The only differences considered to represent effects of the test material were lower total cholesterol for males and females given 0.75 mg/kg/day and lower high density lipoprotein cholesterol for males and females given 0.15 or 0.75 mg/kg/day. The effect on total cholesterol became progressively worse over time. At Day 182, the mean total cholesterol concentrations for the males and females given 0.75 mg/kg/day were approximately 68% and 49% lower, respectively, than those for the control males and females. The effect on high density lipoprotein cholesterol, measured only at Days 153 and 182, was proportionately greater than that for total cholesterol. At Day 182, the mean high density lipoprotein cholesterol 40 Covance 6329-223 3M T-6295.7 concentrations for the males and females given 0.75 mg/kg/day were approximately 79% and 62% lower, respectively, than those for the control males and females. Of uncertain relationship to administration of PFOS was lower total bilirubin concentration for males given 0.75 mg/kg/day (statistically lower on Days 91, 153, and 182) and higher serum bile acid concentration for males given 0.75 mg/kg/day (statistically higher on Day 182 only). These potential effects of the test material were very mild, and neither was considered adverse. Statistically significant differences for other test results were considered incidental and unrelated to administration of the test material. These differences were inconsistent over time or were similar to differences that existed before the initiation of treatment. Unscheduled sacrifice Animal No. I05506, a male given 0.75 mg/kg/day, was sacrificed on Day 179. The most notable findings for this animal were a moderate neutrophilic leukocytosis, mildly increased serum bile acid and globulin concentrations, and moderately to markedly decreased total cholesterol and high density lipoprotein cholesterol. Days 217, 245, 274, 322, 364, 456, and 546 (Recovery animals). The effect on cholesterol was reversed by Day 217, and the effect on high density lipoprotein cholesterol was reversed by Day 245. There were no other findings considered to represent persistent or delayed occurrence of toxic effects. Anatomic Pathology Organ Weights. At the terminal sacrifice (Week 27) females in the group receiving 0.75 mg/kg/day (high-dose) had increased absolute liver weight, liver-to-body weight percentages, and liver-to-brain weight ratios. This increase was regarded as test material-related. In females the absolute pancreas weights were higher in animals receiving 0.03 mg/kg/day (low-dose) than in those receiving 0 mg/kg/day (control). Increased pancreatic weights were not regarded as test material-related. In males, liver-to-body weight percentages were increased in the high-dose group compared to controls. The increase was regarded as test material-related. Left adrenal-to-body weight percentages were also increased in high dose males compared to controls. The significance of the increase left adrenal weight percentage was not known. 41 Organ weights were not taken at the recovery sacrifice at Week 79. Covance 6329-223 3M T-6295.7 Macroscopic Observations. Twenty one of 30 animals at the terminal sacrifice had at least one macroscopic observation. One of the observations was obesity; it was not regarded as pathologic. Thus, 20 animals had macroscopic observations. Of all the macroscopic observations, only "mottled" liver was considered test material-related. "Mottled" liver was observed in the two high-dose males and in one high-dose female. The other observations included adhesions and dark or red foci in any of several organs. Among high-dose females, each had at least one observation of a dark or red focus. In addition, adrenal cortices of the two high-dose males and two of four high dose females were recorded as dark. In one high-dose female (Animal No. I05540), the red focus in the lung correlated microscopically with hemorrhage. There were no microscopic correlates for the other observations. Hence, dark or red foci were considered too non-specific to be considered test material-related. Additionally, dark and red foci were observed in animals in other dose groups. Dark adrenal cortices did not have a microscopic correlate; they, too, were not considered test material-related. Of the two males not surviving until the scheduled terminal sacrifice, one did not have any macroscopic observations. The other (Animal No. I05509) had several observations. Of these observations, those in the liver were considered test material-related. The liver observations were "mottled" and "large". For the recovery sacrifice at Week 79, only high dose animals were necropsied. One of two males and one of two females did not have macroscopic observations. The observations in the other animals were of adhesions on the lungs or liver and nodules in the thoracic cavity. None of these observations was considered test material-related. Microscopic Observations. At the terminal sacrifice, all tissues from the control and high dose groups were examined. All tissues were examined on the two high-dose males not surviving until the terminal sacrifice; the microscopic data were grouped with that of the terminal sacrifice animals. Liver, thymus, and spinal cord (females only) were examined from animals in the low and intermediate dose groups. In four of four high-dose males there was hepatocellular hypertrophy, occurring either centrilobullary or without regard to location within hepatic lobules. Hypertrophy, as described in the males, was observed in four of four high-dose females. The microscopic observations of 42 Covance 6329-223 3M T-6295.7 hepatocellular hypertrophy were reflected in higher liver weights in the high-dose females. Hypertrophy was regarded as test material-dependent in high dose animals. Centrilobular or diffuse hepatocellular vacuolation was also test material-dependent in high-dose animals, occurring in two of four females and two of four males. Multifocal hepatic vacuoles were not regarded as test material-dependent. Multifocal hepatic vacuoles were found in one of four low dose males, and in a control and a low-dose female. Two other observations were suggestive of possible test material effects upon examination of only control and high-dose animals. When tissues were examined from the low and intermediate dose groups as well, test material-dependency was not supported. In females, thymic atrophy was more pronounced in dosed animals than in controls. However, there is no clear dose-dependent pattern and thus, thymic atrophy cannot be considered test material-dependent. Intraneuronal pigment was observed in the spinal cord gray matter of two of four high dose, four of four mid-dose, three of four low-dose and one of four control females. And thus, spinal cord pigment was considered unrelated to the test material. Microscopic examination of liver taken at biopsy on Week 57 from the high-dose animal did not have any test material related findings. At the recovery sacrifice, livers were examined from high-dose animals. No test material-related observations were made. The hepatic vacuolation observed in terminal sacrifice and unscheduled death animals was not present, indicating that the hepatic test material-related effects were reversible. In those animals from which all tissues were examined, the width of the femoral growth plates were assessed as a general indication of the maturity of the animals. Based on this indicator, males were less mature than females. 43 Covance 6329-223 3M T-6295.7 44 Covance 6329-223 3M T-6295.7 COMMENTS ON THE DATA 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 units for the dose levels on the data collection system (PTS) summary tables are mg/kg/day. The number of animals listed in the heading of the summary table for clinical observations reflects the number of animals assigned to each group at the start of the study. The summary table for clinical observations indicates 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 of clinical observations table. The specific details for comments in the individual clinical observations tables that are indicated with a "C" can be found at the end of each group for each sex. The day of initiation of treatment is "Day 1, Week 1." Body weight data are entered at the start of a study week (e.g., a body weight recorded on Day 1 is considered a Week 1 body weight, a body weight recorded on Day 8 is considered a Week 2 body weight). Differences in the population size (N) on the summary tables for clinical and anatomic pathology are explained on the individual data tables. Results of clinical pathology samples collected for animals sacrificed at an unscheduled interval appear on the individual clinical pathology tables for the next scheduled interval. These results are not on the summary tables and are not included in the statistical analyses. Statistical analyses were not done when there were two or fewer values for a parameter. 45 Covance 6329-223 3M T-6295.7 COMMENTS ON THE DATA (continued) Bile volume is located on the individual anatomic pathology table under the heading of "absolute organ weight (grams)". The value listed for bile is not a weight and is designated with a unit of mL. Some clinical observations discussed in the report were documented on the Request for Veterinary Services form and will be archived with the raw data, but they do not appear on the individual clinical observations tables. 46 CODES, ABBREVIATIONS, AND UNITS Covance 6329-223 3M T-6295.7 General Codes and Abbreviations Codes for Clinical Pathology Abbreviations and Units for Clinical Hematology Abbreviations and Units for Clinical Chemistry Abbreviations and Units for Clinical Urinalysis Codes for Anatomic Pathology 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. 47 General Codes and Abbreviations Covance 6329-223 3M T-6295.7 WK N Mean; MEAN CAM SD; S.D.; STAND DEV; STANDARD DEV; sd * -;NA P C UNSCHED DISPATCH TBW # VET EXAM AMOBS 30-90 OB E2 FSH LH T3 T4 FREE T4 TSH Week Number of measurements in a group Arithmetic mean Covariate-adjusted mean Standard deviation Group mean is significantly different from the mean of the control group (Group 1) at p < 0.05 No value; not applicable; not present Present Comment found at the end of each group for each sex Unscheduled Observations transferred from the in-life module of the data collection system to the necropsy module for reference during necropsy. Observations are duplicates of the last in-life observations. Terminal body weight Number Veterinary examination Observations recorded during the daily, morning observation interval. Observations recorded during the 30 to 90 minute postdose observation interval. Estradiol Follicle stimulating hormone Lutenizing hormone Triiodothyronine Total thyroxin Free thyroxin Thyroid stimulating hormone 48 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 6329-223 3M T-6295.7 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 49 Covance 6329-223 3M T-6295.7 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 URINE APPEARANCE A Pale B Straw C Yellow D Dark yellow Color E Amber F Brown G Red H Green I Black P Blue/green Q Blue R Orange Clarity J Clear K Hazy L Cloudy Miscellaneous M Debris O Feces 50 Covance 6329-223 3M T-6295.7 Codes for Clinical Pathology (Continued) URINE CHEMISTRY MULTISTIX STRIP Urine Glucose + ++ +++ ++++ +++++ Negative 100 mg/dL 250 mg/dL 500 mg/dL 1,000 mg/dL >2,000 mg/dL Urine Ketone + ++ +++ ++++ +++++ Negative 5 mg/dL 15 mg/dL 40 mg/dL 80 mg/dL 160 mg/dL Urine Blood - Negative + Small ++ Moderate +++ Large Urine Urobilinogen + ++ +++ ++++ 0.2 mg/dL 1 mg/dL 2 mg/dL 4 mg/dL 8 mg/dL (1 mg = approximately 1 Ehrlich unit) Urine Bilirubin - Negative + Small ++ Moderate +++ Large URINE SEDIMENT Cells, Crystals, Casts, and Comments A Amorphous urates B Amorphous phosphates C Uric acid D Triple phosphates E Calcium oxalate F Calcium carbonate G Granular casts H Hyaline casts I Cellular casts J Waxy casts K Unknown crystal P Mucous threads Q Sperm R Fecal contamination S Pinworm ova found T Pinworm larvae found U Parasite ova found 0 Not present 1 1-5 per field 2 6-10 per field 3 11-20 per field 4 >20 per field Bacteria 0 Not present 1 Few 2 Moderate 3 Many 51 Covance 6329-223 3M T-6295.7 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 Poikilocytosis Abbreviation (Units) RBC (E6/UL or X106/mcL) HGB (G/DL) HCT (%) MCV (FL) MCH (PG) MCHC (%) PLT (E3/UL or X103/mcL) MPV (FL) RETIC (%) RETIC (e 3/UL or X103/mcL) 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/mcL) NRBC (/100 WBC) COR WBC (E3/UL or X103/mcL) N-SEG (E3/UL or X103/mcL) and % N-BAND (E3/UL or X103/mcL) and % LYMPH (E3/UL or X103/mcL) and % MONO (E3/UL or X103/mcL) and % EOSIN (E3/UL or X103/mcL) and % BASO (E3/UL or X103/mcL) and % ANISO (-,1,2,3) POLY (-,1,2,3) POIK (-,1,2,3) 52 Covance 6329-223 3M T-6295.7 Abbreviations and Units for Clinical Hematology (Continued) Test 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) 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) 53 Covance 6329-223 3M T-6295.7 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) 54 Covance 6329-223 3M T-6295.7 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 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) CK-BB (U/L) CK-MB (U/L) CK-MM (U/L) 55 Covance 6329-223 3M T-6295.7 Abbreviations and Units for Clinical Urinalysis Test Urine volume 8 hour urine volume Specific gravity Urine osmolality Quantitative urinary/cerebrospinal fluid protein Urine protein excretion Urine chemistry Multistix strip Urine pH Urine protein Urine glucose Urine ketones Urine bilirubin Urine blood Urine urobilinogen Urine reducing substances Microscopic examination of urine sediment Red blood cells per high-power field White blood cells per high-power field Epithelial cells per high-power field Bacteria per high-power field Casts per low-power field Crystals per low-power field Urine appearance Comments Abbreviation (Units) U VOL (ML) 8 HR VOL (ML) SPGR U OSMO (MOSM/KG) QUAN PRO (MG/DL) PRO EXC (MG) UPH U PRO (MG/DL) U GLU UKET UBILI U BLOOD UROBILI U RE SUB RBC (PER HPF) WBC (PER HPF) EPITH (PER HPF) BACT (PER HPF) CASTS (PER LPF) CRYSTALS (PERLPF1 or PER LPF2) URINE APP1 or URINE APP2 COMMENTS Miscellaneous Codes and Abbreviations for Clinical Pathology Fecal occult blood Not applicable Fecal parasite detection Not applicable Hemolytic potential Not applicable 56 Code T U D M P/O 6 Codes for Anatomic Pathology Definition ANIMAL DEATH CODES Terminal sacrifice Recovery sacrifice Found dead Moribund Transferred to Covance stock Transferred to Covance 6329-268 Covance 6329-223 3M T-6295.7 EX NOT TAKEN MISSING UNSUITABLE AUTOLYTIC EXCLUDE MACROSCOPIC CODES Indicates that organ weight is excluded from calculations Organ weight not taken; explanation given in necropsy notes Organ missing or lost Organ technically unsuitable for weighing Organ autolyzed and could not be weighed Weight was taken, but was excluded from all calculations MICROSCOPIC CODES Codes Prefacing Neoplastic Findings B- Primary, benign neoplasm M- Primary, malignant neoplasm N- Metastatic neoplasm I- Locally invasive neoplasm X- Other neoplasm Distribution of Findings Focal Diffuse Multifocal 57 Covance 6329-223 3M T-6295.7 Codes for Anatomic Pathology (Continued) Code Definition 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 Other Microscopic Codes TL Total P Finding present - Finding not present TISSUE ABBREVIATIONS Abbreviation LF RT LN GL STOMACH, GL STOMACH, NONGL SALIV GL, MANDIB LN, ANT MES/PANC AUDITORY SEB GL LACRIMAL GLAND, EX HEMATO NEOPLASIA LACRIMAL GL, INT CAVITY, ABDOM SALIV GL,PAROTID LN, TRACHEOBRON THYROID/PARA Definition Left Right Lymph node Gland Glandular stomach Nonglandular Mandibular salivary gland Anterior mesenteric/pancreatic lymph node Auditory sebaceous gland Exorbital lacrimal gland Hematopoietic neoplasia Internal lacrimal gland Abdominal cavity Parotid salivary gland Tracheobronchial lymph node Thyroid with parathyroid 58 59 60 DAYS 1-185 CATEGORY KEYWORD QUALIFIER *** TOP OF LIST *** APPEARANCE APPEARS DEHYDRATED RECUMBENT BEHAVIOR ATAXIC HYPOACTIVE DISCHARGE NASAL CLEAR ORAL CLOUDY VOMITUS WHITE IN COLOR CONTAINING FOOD INTACT CAPSULE PARTIAL CAPSULE EXCESSIVE SALIVATION APPEARS TO BE MENSTRUATING DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR Table 1 Summary of Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS SEX: GROUP : DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED --- MALE --- --- ---FEMALE-12341234 0 0.03 0. 15 0.75 0 0.03 0.15 0.75 64666466 00011000 00010000 00010000 0 0 02 1 0 0 0 00001000 00001000 00000100 11312 021 0 0 0 01 0 02 01033003 00011000 00004424 10001000 Covance 6329-223 3M T-6295.7 PAGE: 1 61 DAYS 1-185 CATEGORY KEYWORD QUALIFIER EXCRETION DISCOLORED FECES BLACK IN COLOR RED IN COLOR YELLOW IN COLOR DISCOLORED URINE GREEN IN COLOR RED IN COLOR FEW FECES LIQUID FECES MUCOID FECES NO FECES NON-FORMED FECES SMALL FECES EYES CONSTRICTED PUPIL EYES RESPIRATION LABORED SKIN & PELAGE ALOPECIA DORSAL DORSAL-THORACIC Table 1 Summary of Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS SEX: GROUP : DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED -- --- MALE --- --- ---FEMALE-12341234 0 0.03 0. 15 0.75 0 0.03 0.15 0.75 64666466 00010000 00001003 00000001 00000001 00100000 0002 0235 11012 002 0 0 02 1 0 02 0002 0111 32 1 12 1 02 00000001 00010000 0002 0000 00000001 00000001 62 Covance 6329-223 3M T-6295.7 PAGE: 2 DAYS 1-185 CATEGORY KEYWORD QUALIFIER SKIN & PELAGE ALOPECIA DORSAL-THORACIC-LEFT FEET HEAD-ENTIRE HEAD-CRANIAL HEAD-MAXILLARY-LEFT HEAD-MAXILLARY-RIGHT LIMB-HIND-LEFT LIMBS-ALL LIMBS-FRONT LIMBS-HIND TAIL BROKEN SKIN HAND-LEFT DIGIT(S)-FRONT-LEFT HEAD-CRANIAL HEAD-MAXILLARY-LEFT HEAD-MAXILLARY-RIGHT MOUTH PERI-ORBITAL-LEFT PERI-ORBITAL-RIGHT TAIL TAIL-DISTAL COLD TO TOUCH BODY-ENTIRE Table 1 Summary of Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS SEX: GROUP: DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED --- MALE --- --- ---FEMALE-12341234 0 0.03 0. 15 0.75 0 0.03 0.15 0.75 64666466 00000001 00001000 00000001 00000001 00000001 00000001 00000001 00000002 00000001 00001000 00001001 10000000 00010000 00001010 00000100 00000100 00001000 00001101 01 0 0 02 1 0 10100000 10000000 00010000 63 Covance 6329-223 3M T-6295.7 PAGE: 3 DAYS 1-185 CATEGORY KEYWORD QUALIFIER SKIN & PELAGE PALE SKIN HEAD-ENTIRE GUMS RED SKIN LIMB-FRONT-RIGHT SCAB(S) HEAD-MAXILLARY-LEFT LIMB-FRONT-LEFT LIMB-FRONT-RIGHT BRUISED SKIN PERI-ORBITAL-LEFT QUALITATIVE FOOD CONSUMPTION LOW *** END OF LIST *** Table 1 Summary of Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS SEX: GROUP: DOSE: NUMBER: NUMBER OF ANIMALS AFFECTED --- MALE------- --- ---FEMALE-12341234 0 0.03 0.15 0.75 0 0.03 0.15 0.75 64666466 00000001 00010000 00001000 00000100 00001000 00001000 00000001 33665366 Covance 6329-223 3M T-6295.7 PAGE: 4 64 DAYS 186-365 CATEGORY KEYWORD QUALIFIER *** TOP OF LIST *** DISCHARGE APPEARS TO BE MENSTRUATING EXCRETION FEW FECES LIQUID FECES NON-FORMED FECES SKIN & PELAGE ALOPECIA FEET TAIL BROKEN SKIN DIGIT(S)-FRONT-LEFT QUALITATIVE FOOD CONSUMPTION LOW *** END OF LIST *** Table 2 Summary of Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS SEX: GROUP: DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED --- MALE------- --- ---FEMALE-12341234 0 0.03 0.15 0.75 0 0.03 0.15 0.75 2 0222 022 00001011 00000010 00001000 00100001 00001000 00001000 10000000 10212 022 Covance 6329-223 3M T-6295.7 PAGE: 1 65 DAYS 368-558 CATEGORY KEYWORD QUALIFIER *** TOP OF LIST *** APPEARANCE SWOLLEN HEAD-MAXILLARY-RIGHT DISCHARGE VOMITUS CONTAINING FOOD APPEARS TO BE MENSTRUATING DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR EXCRETION FEW FECES LIQUID FECES NO FECES NON-FORMED FECES SKIN & PELAGE ALOPECIA LIMB-HIND-RIGHT Table 3 Summary of Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS SEX: GROUP : DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED --- MALE --- --- ---FEMALE-12341234 0 0.03 0. 15 0.75 0 0.03 0.15 0.75 2 0222 022 00100000 102 01010 00001001 00000011 0010002 0 00001001 0010002 0 10111001 00001000 Covance 6329-223 3M T-6295.7 PAGE: 1 66 DAYS 368-558 CATEGORY KEYWORD QUALIFIER QUALITATIVE FOOD CONSUMPTION LOW NONE *** END OF LIST *** Table 3 Summary of Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS SEX: GROUP : DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED --- MALE---1234 0 0.03 0.15 0 .75 ---FEMALE- 1234 0 0.03 0.15 0.75 2 0222 022 10212 022 0000002 0 Covance 6329-223 3M T-6295.7 PAGE: 2 67 Table 4 Summary of Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK -4 CATEGORY KEYWORD QUALIFIER *** TOP OF LIST *** NO VISIBLE LESIONS NO VISIBLE LESIONS EYE-LEFT EYES MISCELLANEOUS OPHTHALMICS INCREASED MYELINATION OF OPTIC NERVE EYE-RIGHT *** END OF LIST *** SEX: GROUP : DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED --- MALE --- --- --- ---FEMALE-12341234 0 0.03 0. 15 0.75 0 0.03 0.15 0.75 64666466 00001000 64665466 00001000 Covance 6329-223 3M T-6295.7 PAGE: 1 68 WEEK 26 CATEGORY KEYWORD QUALIFIER *** TOP OF LIST *** NO VISIBLE LESIONS NO VISIBLE LESIONS EYES *** END OF LIST *** Table 4 Summary of Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS SEX: GROUP : DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED --- MALE---- --- --- ---FEMALE-12341234 0 0.03 0.15 0 .75 0 0.03 0.15 0.75 64656466 64656466 Covance 6329-223 3M T-6295.7 PAGE: 2 69 Table 5 Summary of Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK 52 CATEGORY KEYWORD QUALIFIER *** TOP OF LIST *** NO VISIBLE LESIONS NO VISIBLE LESIONS EYES EYE-LEFT MISCELLANEOUS OPHTHALMICS INCREASED MYELINATION OF OPTIC NERVE EYE-RIGHT *** END OF LIST *** SEX: GROUP : DOSE: NUMBER : NUMBER OF ANIMALS AFFECTED --- MALE--- --- --- ---FEMALE-12341234 0 0.03 0.15 0.75 0 0.03 0.15 0.75 2 0222 022 2 0221022 00001000 00001000 Covance 6329-223 T-6295.7 PAGE: 3 70 Table 6 Summary of Body Weight Data (kg) Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: --------------------- MALE---------------------- -------------------- FEMALE--------------------- GROUP: 1 2 3 4 1 2 3 4 DOSE: 0 0.03 0.15 0.75 0 0.03 0.15 0.75 UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY 1a N MEAN S.D. 1b N MEAN S.D. 1N MEAN S.D. 2N CAM MEAN S.D. 3N CAM MEAN S.D. 4N CAM MEAN S.D. 5N CAM MEAN S.D. 6 3.2 0.43 6 3.3 0.45 6 3.3 0.45 6 3.3 3.3 0.44 6 3.3 3.3 0.41 6 3.3 3.3 0.38 6 3.3 3.3 0.39 4 3.4 0.73 4 3.4 0.65 4 3.4 0.70 4 3.2 3.4 0.64 4 3.3 3.4 0.68 4 3.4 3.5 0.64 4 3.4 3.5 0.64 6 3.0 0.33 6 3.1 0.34 6 3.1 0.35 6 3.3 3.1 0.34 6 3.3 3.2 0.32 6 3.4 3.2 0.34 6 3.4 3.2 0.34 6 3.3 0.59 6 3.4 0.55 6 3.4 0.55 6 3.2 3.4 0.62 6 3.3 3.4 0.59 6 3.4 3.5 0.58 6 3.4 3.5 0.60 6 2.8 0.33 6 2.8 0.29 6 2.8 0.29 6 2.9 2.8 0.26 6 2.9 2.8 0.38 6 3.0 2.9 0.34 6 2.9 2.8 0.35 4 3.0 0.55 4 3.0 0.55 4 3.1 0.60 4 3.0 3.1 0.59 4 3.0 3.1 0.59 4 3.0 3.1 0.65 4 2.9 3.1 0.60 6 3.0 0.38 6 3.0 0.41 6 3.0 0.41 6 3.0 3.0 0.43 6 2.9 3.0 0.43 6 2.9 3.0 0.43 6 2.9 3.0 0.44 6 2.9 0.54 6 2.9 0.52 6 2.9 0.52 6 2.9 2.9 0.49 6 2.9 2.9 0.49 6 2.9 2.9 0.52 6 2.8 2.8 0.55 a Day -7. b Day -1. Covance 6329-223 3M T-6295.7 PAGE: 1 71 Table 6 Summary of Body Weight Data (kg) Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: --------------------- MALE---------------------- -------------------- FEMALE--------------------- GROUP: 1 2 3 4 1 2 3 4 DOSE: 0 0.03 0.15 0.75 0 0.03 0.15 0.75 UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY 6N CAM MEAN S.D. 7N CAM MEAN S.D. 8N CAM MEAN S.D. 9N CAM MEAN S.D. 10 N CAM MEAN S.D. 11 N CAM MEAN S.D. 12 N CAM MEAN S.D. 6 3.3 3.3 0.41 6 3.3 3.3 0.42 6 3.3 3.3 0.39 6 3.4 3.4 0.43 6 3.4 3.4 0.43 6 3.4 3.4 0.46 6 3.4 3.4 0.47 4 3.4 3.5 0.63 4 3.4 3.5 0.64 4 3.4 3.5 0.64 4 3.4 3.6 0.60 4 3.4 3.6 0.60 4 3.5 3.7 0.68 4 3.5 3.7 0.68 6 3.4 3.2 0.34 6 3.4 3.2 0.33 6 3.3 3.2 0.30 6 3.4 3.2 0.29 6 3.3 3.2 0.33 6 3.4 3.2 0.33 6 3.4 3.2 0.29 6 3.4 3.5 0.60 6 3.4 3.5 0.63 6 3.4 3.5 0.65 6 3.5 3.5 0.65 6 3.4 3.5 0.65 6 3.5 3.6 0.66 6 3.4 3.5 0.65 6 2.9 2.8 0.36 6 3.0 2.8 0.38 6 2.9 2.8 0.39 6 3.0 2.9 0.40 6 3.0 2.9 0.36 6 3.0 2.9 0.35 6 3.1 3.0 0.37 4 3.0 3.1 0.57 4 3.0 3.1 0.61 4 3.0 3.1 0.61 4 3.0 3.2 0.66 4 3.0 3.1 0.62 4 3.0 3.1 0.60 4 3.0 3.2 0.59 6 2.9 3.0 0.48 6 2.9 3.0 0.47 6 2.9 3.0 0.47 6 3.0 3.0 0.46 6 3.0 3.0 0.44 6 3.0 3.0 0.46 6 3.0 3.0 0.48 6 2.8 2.8 0.55 6 2.9 2.9 0.48 6 2.9 2.9 0.50 6 2.9 2.9 0.55 6 2.9 2.9 0.55 6 2.8* 2.8 0.51 6 2.9* 2.9 0.50 Covance 6329-223 3M T-6295.7 PAGE: 2 72 Table 6 Summary of Body Weight Data (kg) Treatment 26- WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --------MALE------------ 23 0.03 0.15 MG/KG/DAY MG/KG/DAY 4 0.75 MG/KG/DAY --------FEMALE----------- 123 0 0.03 0.15 MG/KG/DAY MG/KG/DAY MG/KG/DAY 4 0.75 MG/KG/DAY 13 N CAM MEAN S.D. 14 N CAM MEAN S.D. 15 N CAM MEAN S.D. 16 N CAM MEAN S.D. 17 N CAM MEAN S.D. 18 N CAM MEAN S.D. 19 N CAM MEAN S.D. 6 3.5 3.5 0.46 6 3.5 3.5 0.44 6 3.5 3.5 0.46 6 3.4 3.4 0.48 6 3.5 3.5 0.49 6 3.5 3.5 0.50 6 3.6 3.6 0.50 4 3.6 3.7 0.65 4 3.5 3.7 0.57 4 3.6 3.7 0.61 4 3.6 3.8 0.60 4 3.7 3.8 0.56 4 3.6 3.7 0.56 4 3.7 3.8 0.59 6 3.4 3.3 0.27 6 3.4 3.2 0.31 6 3.4 3.3 0.30 6 3.4 3.3 0.27 6 3.4 3.3 0.26 6 3.4 3.3 0.23 6 3.5 3.3 0.19 6 3.5 3.6 0.66 6 3.4 3.5 0.67 6 3.4 3.5 0.68 6 3.3 3.4 0.71 6 3.4 3.5 0.75 6 3.4 3.5 0.69 6 3.4 3.5 0.73 6 3.1 3.0 0.36 6 3.0 2.9 0.37 6 3.0 2.9 0.38 6 3.0 2.9 0.34 6 3.1 3.0 0.37 6 3.1 2.9 0.38 6 3.1 3.0 0.34 4 3.1 3.2 0.62 4 3.1 3.2 0.62 4 3.1 3.2 0.63 4 3.1 3.2 0.63 4 3.1 3.2 0.70 4 3.1 3.2 0.68 4 3.1 3.3 0.66 6 3.0 3.1 0.47 6 3.0 3.1 0.48 6 3.1 3.1 0.49 6 3.0 3.1 0.45 6 3.1 3.1 0.45 6 3.0 3.1 0.48 6 3.1 3.1 0.50 6 2.8* 2.8 0.46 6 2.8* 2.8 0.44 6 2.8* 2.8 0.38 6 2.8* 2.8 0.38 6 2.9 2.9 0.44 6 2.9 2.9 0.45 6 2.9* 2.9 0.39 Covance 6329-223 3M T-6295.7 PAGE: 3 73 Table 6 Summary of Body Weight Data (kg) Treatment 26- WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --------MALE------------ 23 0.03 0.15 MG/KG/DAY MG/KG/DAY 4 0.75 MG/KG/DAY --------FEMALE----------- 123 0 0.03 0.15 MG/KG/DAY MG/KG/DAY MG/KG/DAY 4 0.75 MG/KG/DAY 20 N CAM MEAN S.D. 21 N CAM MEAN S.D. 22 N CAM MEAN S.D. 23 N CAM MEAN S.D. 24 N CAM MEAN S.D. 25 N CAM MEAN S.D. 26 N CAM MEAN S.D. 6 3.5 3.5 0.53 6 3.6 3.6 0.55 6 3.6 3.6 0.56 6 3.6 3.6 0.58 6 3.6 3.6 0.63 6 3.7 3.7 0.61 6 3.7 3.7 0.67 4 3.7 3.8 0.59 4 3.6 3.8 0.64 4 3.7 3.8 0.56 4 3.7 3.8 0.55 4 3.7 3.9 0.60 4 3.8 3.9 0.55 4 3.8 3.9 0.55 6 3.5 3.3 0.22 6 3.4 3.2 0.26 6 3.5 3.3 0.25 6 3.5 3.3 0.25 6 3.5 3.3 0.26 6 3.6 3.4 0.20 6 3.5 3.3 0.20 6 3.3 3.4 0.73 6 3.2 3.3 0.72 6 3.3 3.4 0.62 6 3.2* 3.3 0.67 5 3.3 3.4 0.69 5 3.3 3.5 0.72 5 3.3 3.4 0.73 6 3.1 3.0 0.34 6 3.0 2.9 0.34 6 3.1 3.0 0.37 6 3.0 2.9 0.31 6 3.0 2.9 0.32 6 3.1 3.0 0.37 6 3.1 3.0 0.37 4 3.1 3.2 0.67 4 3.1 3.2 0.70 4 3.1 3.2 0.68 4 3.1 3.2 0.68 4 3.1 3.2 0.76 4 3.2 3.3 0.76 4 3.1 3.2 0.79 6 3.1 3.2 0.48 6 3.0 3.0 0.46 6 3.1 3.1 0.44 6 3.1 3.1 0.46 6 3.1 3.1 0.46 6 3.1 3.2 0.46 6 3.1 3.1 0.46 6 2.8* 2.8 0.38 6 2.8* 2.8 0.33 6 2.8* 2.8 0.31 6 2.8* 2.8 0.35 6 2.8 2.8 0.32 6 2.8* 2.8 0.31 6 2.8* 2.8 0.35 Covance 6329-223 3M T-6295.7 PAGE: 4 74 Table 6 Summary of Body Weight Data (kg) Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: --------------------- MALE---------------------- -------------------- FEMALE--------------------- GROUP: 1 2 3 4 1 2 3 4 DOSE: 0 0.03 0.15 0.75 0 0.03 0.15 0.75 UNITS: MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY MG/KG/DAY N CAM MEAN S.D. 6 3.7 3.7 0.68 4 3.8 3.9 0.56 6 3.5 3.3 0.26 4 3.0* 3.2 0.83 6 3.1 3.0 0.35 4 3.1 3.2 0.72 6 3.0 3.1 0.51 6 2.8* 2.8 0.37 Covance 6329-223 3M T-6295.7 PAGE: 5 75 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --MALE----3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 1 0 MG/KG/DAY -FEMALE---3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 28 N MEAN S.D. 29 N MEAN S.D. 30 N MEAN S.D. 31 N MEAN S.D. 32 N MEAN S.D. 33 N MEAN S.D. 34 N MEAN S.D. 2 3.5 0.42 2 3.6 0.42 2 3.6 0.42 2 3.7 0.42 2 3.8 0.42 2 3.8 0.42 2 3.8 0.42 2 3.1 0.21 2 3.1 0.28 2 3.0 0.28 2 3.1 0.35 2 3.2 0.35 2 3.2 0.28 2 3.2 0.21 2 3.1 0.57 2 3.3 0.64 2 3.3 0.57 2 3.5 0.71 2 3.6 0.85 2 3.7 0.78 2 3.8 0.99 2 2.7 0.35 2 2.7 0.42 2 2.7 0.35 2 2.7 0.42 2 2.8 0.35 2 2.8 0.42 2 2.8 0.35 2 3.3 0.71 2 3.4 0.71 2 3.3 0.71 2 3.4 0.78 2 3.5 0.78 2 3.5 0.78 2 3.4 0.85 2 2.6 0.14 2 2.7 0.14 2 2.7 0.14 2 2.8 0.21 2 2.9 0.35 2 3.0 0.28 2 3.0 0.28 76 Covance 6329-223 3M T-6295.7 PAGE: 1 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --MALE----3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 1 0 MG/KG/DAY -FEMALE---3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 35 N MEAN S.D. 36 N MEAN S.D. 37 N MEAN S.D. 38 N MEAN S.D. 39 N MEAN S.D. 40 N MEAN S.D. 41 N MEAN S.D. 2 3.8 0.35 2 3.8 0.42 2 3.9 0.42 2 3.9 0.42 2 3.9 0.35 2 3.9 0.35 2 4.0 0.42 2 3.1 0.28 2 3.3 0.21 2 3.2 0.28 2 3.2 0.21 2 3.1 0.28 2 3.1 0.28 2 3.3 0.21 2 3.7 0.99 2 3.9 1.06 2 3.9 1.06 2 3.8 0.99 2 3.7 0.99 2 3.7 1.06 2 3.8 0.99 2 2.8 0.35 2 2.8 0.35 2 2.8 0.42 2 2.8 0.35 2 2.7 0.42 2 2.6 0.42 2 2.8 0.42 2 3.5 0.92 2 3.6 0.92 2 3.6 0.78 2 3.5 0.85 2 3.5 0.85 2 3.4 0.85 2 3.6 0.85 2 3.0 0.21 2 3.1 0.35 2 3.1 0.35 2 3.0 0.42 2 2.9 0.35 2 3.0 0.21 2 3.1 0.35 77 Covance 6329-223 3M T-6295.7 PAGE: 2 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --MALE----3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 1 0 MG/KG/DAY -FEMALE---3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 42 N MEAN S.D. 43 N MEAN S.D. 44 N MEAN S.D. 45 N MEAN S.D. 46 N MEAN S.D. 47 N MEAN S.D. 48 N MEAN S.D. 2 4.0 0.28 2 4.0 0.28 2 4.2 0.28 2 4.3 0.21 2 4.4 0.21 2 4.2 0.14 2 4.2 0.18 2 3.2 0.21 2 3.2 0.21 2 3.3 0.21 2 3.3 0.28 2 3.3 0.28 2 3.2 0.28 2 3.2 0.25 2 3.8 1.06 2 3.8 0.99 2 3.8 0.92 2 3.8 0.92 2 4.0 0.92 2 3.8 0.85 2 3.9 0.78 2 2.7 0.42 2 2.7 0.42 2 2.8 0.35 2 2.8 0.42 2 2.8 0.42 2 2.7 0.42 2 2.6 0.35 2 3.6 0.78 2 3.6 0.78 2 3.7 0.92 2 3.7 0.78 2 3.6 0.85 2 3.6 0.92 2 3.6 0.94 2 2.9 0.35 2 3.0 0.42 2 3.1 0.35 2 3.1 0.35 2 3.1 0.42 2 3.1 0.49 2 3.1 0.49 78 Covance 6329-223 3M T-6295.7 PAGE: 3 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --MALE----3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 1 0 MG/KG/DAY -FEMALE---3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 49 N MEAN S.D. 50 N MEAN S.D. 51 N MEAN S.D. 52 N MEAN S.D. 53 N MEAN S.D. 54 N MEAN S.D. 55 N MEAN S.D. 2 4.3 0.21 2 4.3 0.21 2 4.3 0.21 2 4.4 0.21 2 4.4 0.21 2 4.4 0.28 2 4.5 0.28 2 3.3 0.21 2 3.2 0.28 2 3.3 0.21 2 3.3 0.21 2 3.2 0.28 2 3.3 0.21 2 3.3 0.21 2 4.1 0.78 2 4.0 0.71 2 4.1 0.64 2 4.1 0.57 2 4.1 0.49 2 4.2 0.49 2 4.1 0.42 2 2.8 0.35 2 2.7 0.35 2 2.7 0.42 2 2.7 0.28 2 2.6 0.28 2 2.6 0.28 2 2.7 0.35 2 3.7 0.92 2 3.6 0.92 2 3.7 0.92 2 3.7 0.92 2 3.6 0.99 2 3.6 0.92 2 3.5 0.99 2 3.2 0.35 2 3.1 0.35 2 3.1 0.35 2 3.1 0.42 2 3.1 0.49 2 3.1 0.49 2 3.1 0.64 79 Covance 6329-223 3M T-6295.7 PAGE: 4 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 56 N MEAN S.D. 57 N MEAN S.D. 58 N MEAN S.D. 59 N MEAN S.D. 60 N MEAN S.D. 61 N MEAN S.D. 62 N MEAN S.D. 1 0 MG/KG/DAY --MALE----3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 2 4.4 0.35 2 3.3 0.14 2 4.1 0.35 2 4.4 0.35 2 3.3 0.21 2 4.0 0.28 2 4.4 0.35 2 3.3 0.14 2 4.1 0.35 2 4.4 0.42 2 3.3 0.14 2 4.1 0.42 2 4.6 0.49 2 3.4 0.14 2 4.3 0.42 2 4.6 0.49 2 3.4 0.14 2 4.3 0.42 2 4.5 0.49 2 3.5 0.21 2 4.4 0.49 1 0 MG/KG/DAY -FEMALE---3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 2 2.7 0.35 2 3.6 0.92 2 3.1 0.57 2 2.6 0.35 2 3.6 0.92 2 3.0 0.57 2 2.7 0.28 2 3.6 0.78 2 3.0 0.57 2 2.7 0.35 2 3.5 0.71 2 3.0 0.57 2 2.8 0.35 2 3.6 0.85 2 3.2 0.49 2 2.7 0.28 2 3.6 0.78 2 3.2 0.49 2 2.7 0.42 2 3.6 0.78 2 3.2 0.57 Covance 6329-223 3M T-6295.7 PAGE: 5 80 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --MALE----3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 1 0 MG/KG/DAY -FEMALE---3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 63 N MEAN S.D. 64 N MEAN S.D. 65 N MEAN S.D. 66 N MEAN S.D. 67 N MEAN S.D. 68 N MEAN S.D. 69 N MEAN S.D. 2 4.5 0.57 2 4.4 0.64 2 4.4 0.57 2 4.4 0.64 2 4.5 0.57 2 4.6 0.57 2 4.7 0.57 2 3.4 0.14 2 3.4 0.14 2 3.4 0.07 2 3.3 0.14 2 3.4 0.14 2 3.5 0.21 2 3.5 0.14 2 4.4 0.42 2 4.5 0.21 2 4.4 0.21 2 4.3 0.28 2 4.4 0.21 2 4.5 0.21 2 4.5 0.28 2 2.8 0.35 2 2.7 0.35 2 2.7 0.35 2 2.6 0.28 2 2.7 0.35 2 2.7 0.35 2 2.7 0.28 2 3.6 0.71 2 3.6 0.78 2 3.5 0.78 2 3.5 0.78 2 3.6 0.71 2 3.6 0.78 2 3.6 0.85 2 3.2 0.57 2 3.2 0.64 2 3.1 0.57 2 3.1 0.57 2 3.2 0.57 2 3.2 0.64 2 3.2 0.71 81 Covance 6329-223 3M T-6295.7 PAGE: 6 Table 7 Summary of Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --MALE----3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 1 0 MG/KG/DAY -FEMALE---3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY 70 N MEAN S.D. 71 N MEAN S.D. 72 N MEAN S.D. 73 N MEAN S.D. 74 N MEAN S.D. 75 N MEAN S.D. 76 N MEAN S.D. 2 4.6 0.57 2 4.7 0.64 2 4.8 0.71 2 4.7 0.71 2 4.8 0.85 2 4.8 0.78 2 4.8 0.85 2 3.5 0.07 2 3.5 0.07 2 3.6 0.07 2 3.5 0.07 2 3.6 0.07 2 3.6 0.07 2 3.6 0.07 2 4.5 0.21 2 4.4 0.28 2 4.5 0.21 2 4.4 0.21 2 4.5 0.21 2 4.5 0.21 2 4.5 0.21 2 2.7 0.35 2 2.7 0.35 2 2.7 0.35 2 2.7 0.35 2 2.7 0.42 2 2.7 0.28 2 2.7 0.28 2 3.6 0.78 2 3.6 0.85 2 3.7 0.78 2 3.6 0.85 2 3.7 0.78 2 3.7 0.78 2 3.7 0.71 2 3.2 0.71 2 3.2 0.71 2 3.3 0.78 2 3.2 0.78 2 3.3 0.78 2 3.3 0.78 2 3.4 0.78 82 Covance 6329-223 3M T-6295.7 PAGE: 7 Table 7 Summary of Body Weight Data (kg) Recovery 26 -WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK SEX: GROUP: DOSE: UNITS: 1 0 MG/KG/DAY --MALE---3 0.15 MG/KG/DAY 4 0.75 MG/KG/DAY --- FEMALE---13 0 0.15 MG/KG/DAY MG/KG/DAY 4 0.75 MG/KG/DAY 77 N MEAN S.D. 78 N MEAN S.D. 79 N MEAN S.D. 80 N MEAN S.D. 2 4.7 0.85 2 4.7 0.92 2 4.7 0.92 0 2 3.5 0.07 2 3.5 0.07 2 3.5 0.00 2 3.3 0.21 2 4.4 0.14 2 4.4 0.14 2 4.4 0.07 0 2 2.7 0.35 2 2.6 0.28 2 2.7 0.35 0 2 3.7 0.78 2 3.5 0.85 2 3.6 0.85 2 3.4 0.85 2 3.3 0.78 2 3.2 0.85 2 3.3 0.85 0 Covance 6329-223 3M T-6295.7 PAGE: 8 83 Table 8 Summary of Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.45 .275 6 6.99 .688 4 6.76 .315 6 6.88 .575 6 12.2 .36 6 12.4 .46 4 12.6 .41 6 12.5 .82 6 41.2 1.30 6 42.9 2.95 4 42.9 1.88 6 43.1 2.06 6 63.9 2.32 6 61.5 2.51 4 63.5 2.38 6 62.8 3.44 6 19.0 .87 6 17.8 1.13 4 18.7 .76 6 18.2 1.01 6 29.8 .56 6 29.0 1.34 4 29.5 .41 6 29.0 .61 6 530 125.0 6 574 210.3 4 493 109.0 6 415 202.6 6 .3 .19 6 .4 .24 4 .5 .53 6 .5 .47 6 20 12 6 24 14 4 32 34 6 33 27 6 84 Table 8 Summary of Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62 95) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 8.6 1.76 6 11.0 1.00 4 11.9 1.95 6 9.4 2.53 6 3.9 1.28 6 5.2 1.88 4 6.6 2.42 6 3.7 1.40 6 4.0 .90 6 4.6 1.05 4 4.1 1.14 6 4.3 1.25 6 .6 .24 6 .8 .48 4 .9 .25 6 1.1 .53 6 .1 .08 6 .2 .17 4 .2 .31 6 .2 .25 6 0 44 47 7 1 0 05 8.9 9.2 2.4 .8 .5 666666 0 47 43 8 2 0 00 15.2 9.4 4.4 1.3 .0 444444 0 54 36 8 2 0 04 13.4 10.9 3.3 2.1 .4 666666 1 39 46 12 2 1 08 10.9 9.5 3.3 3.3 .8 666666 85 Table 8 Summary of Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.09 .681 6 6.31 .522 4 6.54 .320 6 6.50 .195 6 12.0 .97 6 11.5 1.06 4 12.0 .49 6 12.1 .50 6 39.3 3.93 6 39.5 3.26 4 40.1 1.97 6 41.5 1.68 6 64.7 4.51 6 62.7 4.49 4 61.4 2.79 6 63.9 1.14 6 19.7 1.81 6 18.3 1.73 4 18.3 .50 6 18.7 .50 6 30.4 .87 6 29.2 .71 4 29.8 .68 6 29.2 .52 6 539 79.5 6 482 72.4 4 481 100.9 6 435 108.9 6 .6 .46 6 .4 .31 4 .4 .26 6 .2 .18 6 35 24 6 27 17 4 29 16 6 16 11 6 86 Table 8 Summary of Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62 95) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 10.2 4.6 4.5 .8 .3 S.D. 2.52 1.14 1.36 .24 .28 N 66666 0.03 MEAN 8.7 5.0 2.9 .6 .1 S.D. 2.41 2.52 .79 .17 .05 N 44444 0.15 MEAN 10.1 5.1 3.8 .8 .3 S.D. 2.94 2.81 .40 .20 .27 N 66666 0.75 MEAN 9.0 4.8 3.2 .8 .1 S.D. 3.08 1.70 1.66 .32 .18 N 66666 0 45 44 7 3 0 05 8.3 7.6 1.2 2.1 .5 666666 0 55 35 8 2 0 05 14.3 11.6 2.8 .6 .5 444444 0 48 40 93 0 04 13.0 8.4 3.8 3.0 .4 666666 0 54 35 9 1 0 04 10.7 9.7 4.2 1.4 .4 666666 87 Table 9 Summary of Clinical Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.45 .221 6 6.86 .501 4 6.66 .385 6 6.53 .431 6 12.4 .55 6 12.5 .38 4 12.5 .27 6 11.8 .57 6 40.6 1.44 6 42.4 3.93 4 41.2 .76 6 40.2 1.74 6 63.0 2.74 6 61.9 4.61 4 62.0 2.96 6 61.7 2.63 6 19.1 .97 6 18.2 1.17 4 18.8 1.06 6 18.1 .85 6 30.4 .58 6 29.5 1.69 4 30.3 .53 6 29.4 .57 6 486 117.8 6 532 146.1 4 476 59.6 6 383 164.3 6 .2 .16 6 .4 .35 4 .4 .14 6 .4 .10 6 14 10 6 29 23 4 25 10 6 25 5 6 88 Table 9 Summary of Clinical Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62 95) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 7.6 3.9 3.1 .5 .0 S.D. 1.98 2.01 .67 .31 .08 N 66666 0.03 MEAN 10.8 6.3 3.7 .5 .2 S.D. 1.89 2.40 1.26 .17 .05 N 44444 0.15 MEAN 10.0 6.0 3.2 .6 .2 S.D. 2.06 2.23 .91 .24 .32 N 66666 0.75 MEAN 10.3 6.6 2.9 .6 .1 S.D. 4.16 3.69 .52 .18 .11 N 66666 0 50 43 7 1 0 08 14.4 12.8 3.4 1.2 .8 666666 0 58 36 5 2 0 00 15.9 14.2 1.7 .5 .0 444444 0 58 33 6 2 0 05 12.5 10.4 3.6 2.3 .4 666666 0 62 30 7 1 1 05 9.8 7.5 2.7 1.2 .4 666666 89 Table 9 Summary of Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.41 .351 6 6.60 .664 4 6.55 .343 6 6.21 .280 6 12.2 .69 6 11.8 .97 4 11.8 .41 6 11.6 .38 6 40.5 2.42 6 40.6 2.92 4 39.7 1.06 6 39.1 1.96 6 63.1 2.31 6 61.8 6.28 4 60.7 2.68 6 63.0 1.48 6 19.0 .83 6 18.1 1.80 4 18.1 .75 6 18.6 .44 6 30.2 .29 6 29.2 .48 4 29.7 .29 6 29.6 .89 6 538 84.2 6 417 23.6 4 431 85.3 6 469 95.4 6 .3 .16 6 .3 .28 4 .3 .12 6 .3 .23 6 22 10 6 18 15 4 19 8 6 20 13 6 90 Table 9 Summary of Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 12.7 7.8 3.6 1.1 .3 .0 59 30 8 2 0 S.D. 4.75 3.77 1.59 .67 .26 .08 18.2 16.2 2.3 1.7 .5 N 66666666666 0.03 MEAN 9.6 5.7 2.8 .8 .2 .0 60 29 8 3 0 S.D. 2.37 1.90 .82 .24 .17 .05 10.6 6.0 2.1 2.2 1.0 N 44444444444 0.15 MEAN 9.1 5.5 2.9 .5 .2 .0 56 35 6 3 0 S.D. 2.66 2.48 .72 .13 .18 .00 17.0 15.7 1.6 1.2 .0 N 66666666666 0.75 MEAN 8.9 5.3 2.9 .6 .1 .0 56 35 7 1 0 S.D. 2.85 3.19 1.06 .20 .08 .00 15.1 13.7 2.7 1.2 .4 N 66666666666 91 Table 10 Summary of Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.49 .292 6 6.84 .437 4 6.60 .315 6 6.73 .516 6 12.5 .53 6 12.4 .33 4 12.5 .52 6 12.3 .75 6 41.1 1.78 6 41.4 1.36 4 40.7 1.42 6 41.2 2.31 6 63.3 3.03 6 60.7 2.92 4 61.7 2.56 6 61.3 3.02 6 19.2 .95 6 18.2 .91 4 18.9 .87 6 18.3 .72 6 30.4 .84 6 29.9 .62 4 30.6 .50 6 29.8 .52 6 522 126.9 6 536 152.1 4 504 97.3 6 437 217.8 6 .3 .27 6 .4 .45 4 .3 .25 6 .3 .19 6 18 17 6 25 29 4 21 17 6 19 12 6 92 Table 10 Summary of Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62 95) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 7.3 3.0 3.5 .6 .1 S.D. .81 .68 .87 .26 .08 N 66666 0.03 MEAN 10.5 6.1 * 3.4 .8 .2 S.D. 1.79 1.51 .82 .38 .05 N 44444 0.15 MEAN 11.8 * 7.0 * 3.9 .7 .2 S.D. 3.02 3.16 1.18 .40 .13 N 66666 0.75 MEAN 9.6 5.3 3.4 .6 .2 S.D. 2.97 2.52 .52 .23 .21 N 66666 0 42 48 8 2 0 05 10.5 8.2 3.2 .8 .8 666666 0 58 32 8 2 0 00 9.5 6.5 3.5 .5 .0 444444 0 56 35 7 2 0 05 16.3 14.6 4.0 .8 .4 666666 0 52 38 6 2 0 08 10.0 11.2 1.0 2.1 .5 666666 93 Table 10 Summary of Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.23 .766 6 6.48 .593 4 7.00 1.068 6 6.28 .397 6 12.3 .66 6 12.0 .83 4 12.8 2.17 6 11.8 .29 6 40.2 3.27 6 40.2 2.39 4 42.3 6.70 6 40.2 1.96 6 64.9 4.33 6 62.4 6.25 4 60.5 2.31 6 64.0 1.27 6 19.9 1.87 6 18.5 2.02 4 18.3 .76 6 18.9 .72 6 30.6 1.01 6 29.7 .67 4 30.3 .57 6 29.5 .70 6 572 74.6 6 462 83.8 4 436 133.5 6 504 148.3 6 .4 .22 6 .4 .37 4 .4 .28 6 .3 .25 6 27 11 6 28 24 4 24 18 6 17 14 6 94 Table 10 Summary of Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62 95) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 11.1 5.8 4.3 .6 .3 S.D. 2.93 3.08 1.73 .48 .18 N 66666 0.03 MEAN 8.7 4.4 3.4 .6 .2 S.D. 1.42 1.59 1.16 .13 .17 N 44444 0.15 MEAN 8.8 4.3 3.6 .5 .3 S.D. 1.78 1.75 .93 .16 .15 N 66666 0.75 MEAN 9.3 5.6 3.0 .6 .1 S.D. 4.59 3.89 1.07 .40 .08 N 66666 0 50 40 6 2 0 08 17.6 15.9 4.6 2.0 .5 666666 0 50 40 8 2 0 06 14.5 14.9 .5 1.7 .6 444444 0 48 42 6 3 0 05 13.1 11.2 2.9 1.6 .5 666666 0 56 36 7 1 0 05 13.2 14.2 2.7 1.0 .4 666666 95 Table 11 Summary of Clinical Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.43 .314 6 7.00 .628 4 6.50 .295 6 6.66 .488 6 12.4 .53 6 12.7 .55 4 12.3 .16 6 12.2 .81 6 40.3 2.17 6 42.5 1.78 4 40.4 .93 6 41.0 2.23 6 62.8 3.11 6 61.0 3.13 4 62.1 2.53 6 61.6 2.47 6 19.3 1.06 6 18.2 1.02 4 19.0 .76 6 18.2 .77 6 30.7 1.00 6 29.8 .43 4 30.6 .49 6 29.6 * .65 6 490 124.3 6 512 208.8 4 496 82.6 6 431 198.6 6 .3 .26 6 .7 .54 4 .5 .54 6 .4 .19 6 21 16 6 47 33 4 33 32 6 26 11 6 96 Table 11 Summary of Clinical Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62 95) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 6.7 2.4 3.7 .4 .1 S.D. 1.99 .64 1.24 .16 .08 N 66666 0.03 MEAN 8.5 4.4 3.3 .6 .2 S.D. 1.60 1.79 .88 .00 .10 N 44444 0.15 MEAN 10.3 5.7 * 3.7 .6 .2 S.D. 3.21 1.85 1.61 .27 .18 N 66666 0.75 MEAN 9.4 5.1 * 3.5 .6 .2 S.D. 2.56 2.06 .71 .28 .16 N 66666 0 37 55 6 2 0 04 4.1 2.8 2.1 1.3 .5 666666 0 50 40 * 7 2 0 00 13.9 12.6 1.0 1.4 .0 444444 0 56 * 36 * 7 2 0 05 9.3 8.4 2.6 1.8 .5 666666 0 52 * 38 * 6 2 0 05 9.8 7.8 3.2 1.6 .5 666666 97 Table 11 Summary of Clinical Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.31 .565 6 6.20 .472 4 6.50 .298 6 6.32 .210 6 12.3 .77 6 11.7 .97 4 12.0 .42 6 11.9 .36 6 40.3 2.79 6 39.2 2.18 4 39.4 1.44 6 40.3 1.54 6 64.1 3.90 6 63.6 7.19 4 60.7 2.35 6 63.8 1.37 6 19.5 1.21 6 19.0 2.78 4 18.6 .78 6 18.8 .51 6 30.4 .33 6 29.9 1.21 4 30.6 .57 6 29.4 .54 6 562 83.6 6 467 33.4 4 442 78.9 6 504 124.1 6 .3 .08 6 .5 .13 4 .2 .10 6 .2 .15 6 20 5 6 30 7 4 14 6 6 12 9 6 98 Table 11 Summary of Clinical Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 9.4 4.0 4.3 .6 .4 .0 44 46 7 4 0 S.D. 1.89 1.31 1.59 .10 .27 .04 12.5 10.3 1.0 2.4 .5 N 66666666666 0.03 MEAN 8.7 4.4 3.2 .8 .2 .0 48 39 9 2 0 S.D. 3.42 2.74 1.22 .41 .10 .10 13.2 11.2 3.9 1.0 1.0 N 44444444444 0.15 MEAN 8.7 4.4 3.4 .6 .2 .0 51 39 7 2 0 S.D. 1.25 .82 .69 .18 .12 .00 6.4 6.6 1.5 1.0 .4 N 66666666666 0.75 MEAN 8.1 4.6 2.9 .6 .1 .0 56 36 7 2 0 S.D. 1.91 1.75 1.02 .26 .08 .05 13.1 10.4 3.5 1.2 .5 N 66666666666 99 Table 12 Summary of Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.68 .421 6 7.08 .513 4 6.78 .479 6 6.65 .641 6 12.5 .54 6 12.6 .46 4 12.6 .38 6 11.8 1.04 6 40.9 2.28 6 41.7 1.91 4 41.3 1.47 6 40.0 3.32 6 61.4 2.74 6 59.0 2.70 4 61.1 2.82 6 60.3 2.43 6 18.7 .88 6 17.8 .90 4 18.7 .95 6 17.7 .87 6 30.6 .62 6 30.2 .82 4 30.6 .40 6 29.4 * .50 6 464 131.6 6 483 167.0 4 519 146.4 6 398 199.1 6 .2 .26 6 .2 .16 4 .4 .15 6 .6 .48 6 17 18 6 14 10 4 30 9 6 39 30 6 100 Table 12 Summary of Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62 95) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 7.3 2.7 3.9 .5 .2 S.D. 2.62 1.64 .91 .29 .15 N 66666 0.03 MEAN 9.9 5.6 3.5 .6 .2 S.D. 1.04 1.70 1.08 .22 .08 N 44444 0.15 MEAN 10.1 5.2 4.0 .7 .3 S.D. 2.44 2.81 1.17 .12 .21 N 66666 0.75 MEAN 9.0 4.3 3.6 .8 .2 S.D. 2.87 3.02 1.08 .44 .18 N 66666 0 35 54 7 2 0 08 8.6 8.3 2.9 2.7 .8 666666 0 56 36 6 2 0 00 15.0 13.5 1.8 1.0 .0 444444 0 49 42 7 2 0 05 18.2 16.4 2.5 2.0 .5 666666 0 45 44 92 0 04 16.3 16.1 3.7 1.5 .4 666666 101 Table 12 Summary of Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.60 .559 6 6.66 .641 4 6.66 .257 6 6.33 .288 6 12.4 .85 6 12.0 .92 4 12.1 .45 6 11.7 .44 6 40.6 2.96 6 40.4 2.44 4 39.9 1.31 6 39.5 1.98 6 61.7 2.45 6 61.1 6.52 4 59.8 2.12 6 62.4 2.21 6 18.8 .77 6 18.1 2.23 4 18.2 .64 6 18.5 .70 6 30.6 .46 6 29.6 * .82 4 30.4 .18 6 29.7 * .65 6 520 73.1 6 387 52.3 4 460 83.7 6 492 144.0 6 .4 .31 6 .6 .61 4 .3 .24 6 .2 .12 6 24 20 6 39 33 4 20 16 6 11 7 6 102 Table 12 Summary of Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 9.7 4.6 4.1 .8 .2 .0 44 44 93 0 S.D. 2.44 2.98 1.08 .30 .18 .05 18.7 15.9 3.9 2.3 .5 N 66666666666 0.03 MEAN 9.3 5.0 2.9 1.1 .2 .1 50 36 11 2 1 S.D. 4.49 3.55 .62 1.00 .14 .08 12.6 15.6 3.6 1.4 1.0 N 44444444444 0.15 MEAN 8.1 3.7 3.4 .6 .3 .0 44 44 8 3 0 S.D. 2.23 1.98 .96 .14 .15 .00 14.5 14.4 2.2 1.9 .5 N 66666666666 0.75 MEAN 9.5 4.4 4.0 .8 .2 .0 46 43 92 1 S.D. 2.99 2.33 2.19 .35 .13 .05 17.4 16.5 4.3 .9 .5 N 66666666666 103 Table 13 Summary of Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.60 .354 6 6.96 .627 4 6.65 .372 6 6.32 .387 4 12.5 .50 6 41.1 2.07 6 12.5 .45 4 42.1 1.79 4 12.5 .31 6 41.0 1.15 6 11.4 * .83 4 38.8 2.45 4 62.3 2.53 6 60.7 2.81 4 61.8 2.76 6 61.5 2.72 4 18.9 .78 6 18.0 1.05 4 18.8 .80 6 17.9 1.08 4 30.3 .79 6 29.6 .88 4 30.4 .30 6 29.2 * .48 4 467 90.4 6 466 183.0 4 470 63.1 6 401 228.0 4 .2 .08 6 .2 .17 4 .3 .04 6 .2 .24 4 11 5 6 12 11 4 19 3 6 12 14 4 104 Table 13 Summary of Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-62 95) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 9.7 4.2 4.4 .7 .2 S.D. 1.76 1.66 1.46 .46 .18 N 66666 0.03 MEAN 8.4 4.8 2.8 .6 .2 S.D. .74 1.46 .74 .26 .06 N 44444 0.15 MEAN 10.0 5.2 4.1 .5 .2 S.D. 2.44 2.10 1.39 .14 .20 N 66666 0.75 MEAN 7.6 2.9 4.0 .5 .1 S.D. 2.09 1.13 1.16 .12 .10 N 44444 0 45 46 7 2 0 05 16.1 12.4 4.1 2.0 .5 666666 0 57 34 6 2 0 00 15.1 10.6 3.8 1.0 .5 444444 0 50 42 5 2 0 00 15.2 13.6 2.4 2.1 .0 666666 0 38 53 7 2 0 06 6.9 9.1 2.9 1.7 .6 444444 105 Table 13 Summary of Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.40 .461 6 6.15 .798 4 6.57 .256 6 6.09 .360 6 12.1 .64 6 11.2 1.66 4 11.9 .62 6 11.3 .37 6 40.8 2.67 6 38.3 5.67 4 39.9 1.78 6 39.2 2.17 6 63.8 2.49 6 62.3 6.23 4 60.8 2.50 6 64.3 1.46 6 19.0 .70 6 18.2 2.09 4 18.2 .73 6 18.6 .71 6 29.7 .65 6 29.3 .94 4 29.9 .35 6 29.0 1.09 6 484 100.1 6 429 54.7 4 412 74.4 6 490 166.0 6 .4 .24 6 .2 .13 4 .2 .12 6 .2 .21 6 27 15 6 13 5 4 12 7 6 12 12 6 106 Table 13 Summary of Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 10.4 5.0 4.3 .7 .2 .0 46 44 8 3 0 S.D. 3.59 3.41 1.96 .15 .19 .05 17.5 15.1 3.4 1.8 .5 N 66666666666 0.03 MEAN 8.5 4.3 3.2 .7 .3 .0 50 38 8 3 0 S.D. 2.05 1.45 .57 .32 .15 .10 9.3 10.1 2.2 1.4 1.0 N 44444444444 0.15 MEAN 9.2 4.5 3.8 .6 .3 .0 48 43 6 3 0 S.D. 1.61 1.73 .61 .18 .24 .04 13.0 11.7 2.1 2.0 .8 N 66666666666 0.75 MEAN 9.7 4.2 4.6 .7 .2 .1 46 45 8 2 0 S.D. 2.73 1.10 2.70 .32 .08 .05 14.6 14.8 3.4 .8 .5 N 66666666666 107 Table 14 Summary of Clinical Hematology Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.26 .007 2 6.49 .057 2 5.90 .042 2 12.0 .21 2 12.7 .42 2 11.6 .07 2 38.1 .28 2 40.7 1.27 2 37.8 .64 2 60.8 .35 2 62.8 1.34 2 64.0 .71 2 19.1 .28 2 19.6 .42 2 19.5 .07 2 31.5 .35 2 31.2 .07 2 30.6 .42 2 483 193.7 2 488 118.8 2 469 22.6 2 .4 .07 2 .3 .14 2 .4 .21 2 22 4 2 20 9 2 26 12 2 108 Table 14 Summary of Clinical Hematology Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 7.3 2.4 4.0 .6 .2 .0 34 54 93 1 S.D. 1.70 .14 1.63 .14 .07 .00 4.9 9.9 4.2 .0 .0 N 22222222222 0.15 MEAN 11.5 6.2 4.5 .6 .3 .0 53 38 6 3 0 S.D. 3.82 2.05 2.12 .21 .14 .00 .0 5.7 3.5 2.8 .0 N 22222222222 0.75 MEAN 11.8 6.0 4.4 .9 .4 .0 50 39 7 4 0 S.D. 4.10 2.69 .78 .57 .07 .00 5.7 7.1 2.8 .0 .0 N 22222222222 109 Table 14 Summary of Clinical Hematology Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 5.94 .714 2 6.14 .092 2 6.42 .417 2 11.8 1.20 2 11.9 .14 2 12.0 .28 2 36.9 4.81 2 37.6 .57 2 40.2 2.90 2 62.0 .64 2 61.4 .07 2 62.6 .57 2 19.8 .35 2 19.5 .07 2 18.7 .71 2 32.0 .99 2 31.7 .14 2 29.8 1.34 2 468 111.0 2 408 37.5 2 444 160.5 2 .3 .28 2 .4 .21 2 .5 .28 2 18 19 2 22 13 2 32 20 2 110 Table 14 Summary of Clinical Hematology Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 8.2 4.6 2.8 .6 .1 .0 55 36 8 2 0 S.D. 2.76 2.12 .35 .28 .00 .00 7.1 7.8 .7 .7 .0 N 22222222222 0.15 MEAN 7.6 2.6 4.0 .6 .4 .0 34 53 8 4 1 S.D. 1.06 1.20 .35 .14 .21 .07 10.6 11.3 2.8 2.1 .0 N 22222222222 0.75 MEAN 9.3 2.6 5.8 .6 .2 .0 28 64 6 3 0 S.D. 2.26 .64 1.20 .35 .07 .07 .7 2.1 2.8 1.4 .7 N 22222222222 111 Table 15 Summary of Clinical Hematology Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.52 .332 2 6.78 .049 2 6.20 .191 2 12.6 .57 2 13.3 .00 2 11.9 .71 2 39.2 1.91 2 42.2 .49 2 39.5 .64 2 60.2 .07 2 62.1 1.13 2 63.7 .99 2 19.4 .07 2 19.6 .28 2 19.2 .49 2 32.1 .00 2 31.6 .21 2 30.1 1.27 2 556 181.7 2 493 36.8 2 532 43.1 2 .2 .14 2 .2 .07 2 .6 .28 2 13 8.5 2 10 4.9 2 36 16.3 2 112 Table 15 Summary of Clinical Hematology Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 10.0 3.2 6.1 .4 .3 .0 32 60 4 3 0 S.D. 2.90 .78 2.12 .07 .00 .00 1.4 3.5 .7 1.4 .0 N 22222222222 0.15 MEAN 11.4 5.5 4.8 .6 .4 .0 48 42 6 3 0 S.D. 1.13 .42 1.06 .28 .07 .00 .7 4.9 3.5 1.4 .0 N 22222222222 0.75 MEAN 13.4 5.6 6.2 1.0 .5 .1 41 47 8 4 1 S.D. 5.52 2.83 1.77 .64 .14 .00 4.2 5.7 2.1 .0 .0 N 22222222222 113 Table 15 Summary of Clinical Hematology Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.22 .735 2 6.74 .191 2 6.70 .453 2 12.3 1.41 2 12.7 .28 2 12.5 .42 2 38.4 4.95 2 40.7 .35 2 42.0 2.97 2 61.6 .71 2 60.3 1.27 2 62.7 .21 2 19.8 .07 2 18.8 .14 2 18.7 .71 2 32.1 .49 2 31.2 .28 2 29.8 1.20 2 519 82.0 2 425 48.1 2 440 149.2 2 .2 .07 2 .2 .07 2 .2 .21 2 16 6 2 10 4 2 17 15 2 114 Table 15 Summary of Clinical Hematology Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 11.4 7.1 3.4 .7 .2 .0 62 30 6 2 0 S.D. 1.56 2.83 .85 .28 .14 .00 16.3 12.0 2.8 1.4 .0 N 22222222222 0.15 MEAN 9.4 3.0 5.0 1.0 .4 .0 28 56 11 4 0 S.D. 2.76 2.97 .49 .00 .28 .07 23.3 21.9 2.8 1.4 .7 N 22222222222 0.75 MEAN 11.0 3.6 6.2 .9 .2 .1 32 56 8 2 1 S.D. .21 1.34 1.77 .28 .07 .00 12.7 14.8 2.8 1.4 .0 N 22222222222 115 Table 16 Summary of Clinical Hematology Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.72 .198 2 6.78 .106 2 6.45 .495 2 12.6 .49 2 13.1 .42 2 12.3 1.13 2 40.1 2.12 2 41.8 2.05 2 41.0 2.40 2 59.6 1.34 2 61.5 1.98 2 63.6 1.13 2 18.8 .21 2 19.3 .28 2 19.1 .21 2 31.6 .42 2 31.4 .49 2 29.9 .92 2 504 228.4 2 496 105.4 2 519 60.8 2 .2 .07 2 .4 .28 2 .3 .14 2 17 4 2 27 19 2 19 7 2 116 Table 16 Summary of Clinical Hematology Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 7.3 2.6 3.7 .8 .1 .0 36 51 10 2 1 S.D. .42 .28 .42 .35 .00 .07 6.4 2.8 4.2 .0 .0 N 22222222222 0.15 MEAN 11.5 6.6 4.1 .4 .2 .0 58 36 4 2 0 S.D. 2.26 2.05 .14 .21 .14 .00 6.4 8.5 1.4 1.4 .0 N 22222222222 0.75 MEAN 11.6 5.0 5.4 .8 .4 .0 40 49 7 2 1 S.D. 6.22 3.54 1.91 .49 .21 .07 9.2 9.9 .0 .7 .0 N 22222222222 117 Table 16 Summary of Clinical Hematology Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.32 1.082 2 6.64 .071 2 6.78 .410 2 12.3 1.70 2 12.6 .07 2 12.5 .35 2 39.0 7.57 2 40.1 .57 2 40.8 1.56 2 61.7 1.41 2 60.3 .21 2 60.2 1.34 2 19.5 .71 2 18.8 .35 2 18.4 .64 2 31.6 1.91 2 31.2 .64 2 30.5 .35 2 510 135.8 2 423 5.7 2 440 137.9 2 .4 .00 2 .4 .21 2 .4 .35 2 25 4.2 2 23 14.1 2 30 21.9 2 118 Table 16 Summary of Clinical Hematology Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 8.8 5.4 2.8 .5 .0 .0 60 33 6 1 0 S.D. 1.13 2.40 .99 .14 .07 .00 19.1 15.6 2.8 1.4 .7 N 22222222222 0.15 MEAN 7.8 2.9 3.8 .6 .4 .0 34 53 8 5 1 S.D. 2.26 2.55 .64 .07 .28 .07 22.6 22.6 .7 1.4 .0 N 22222222222 0.75 MEAN 9.2 4.4 4.1 .6 .1 .0 48 44 6 0 0 S.D. 2.26 .92 .85 .49 .00 .07 2.1 2.1 3.5 .7 .7 N 22222222222 119 Table 17 Summary of Clinical Hematology Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.72 .078 2 6.80 .127 2 6.22 .198 2 12.6 .35 2 13.2 .57 2 11.8 .42 2 40.2 .57 2 41.9 1.84 2 38.1 .35 2 59.8 .07 2 61.5 1.48 2 61.1 1.34 2 18.8 .28 2 19.4 .49 2 19.0 .07 2 31.5 .42 2 31.5 .07 2 31.0 .71 2 544 209.3 2 491 80.6 2 572 43.1 2 .3 .28 2 .2 .07 2 .6 .35 2 20 19.1 2 10 4.9 2 34 21.2 2 120 Table 17 Summary of Clinical Hematology Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 8.6 4.2 3.8 .6 .1 .0 48 42 8 1 0 S.D. 1.20 .21 1.06 .07 .00 .00 4.9 6.4 1.4 .0 .0 N 22222222222 0.15 MEAN 12.8 8.2 3.7 .8 .2 .0 64 30 6 1 0 S.D. 1.34 2.05 .99 .21 .07 .00 9.2 10.6 1.4 .0 .0 N 22222222222 0.75 MEAN 9.0 4.0 3.9 .8 .2 .0 43 44 10 2 0 S.D. 3.75 2.55 1.13 .07 .07 .07 9.9 6.4 2.8 1.4 .7 N 22222222222 121 Table 17 Summary of Clinical Hematology Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.32 .403 2 6.76 .071 2 6.50 .431 2 12.3 .64 2 12.5 .00 2 11.9 .42 2 38.4 2.12 2 40.1 .78 2 39.5 2.19 2 60.8 .49 2 59.4 1.77 2 60.8 .64 2 19.6 .21 2 18.4 .21 2 18.4 .64 2 32.1 .07 2 31.0 .64 2 30.2 .71 2 546 140.0 2 472 103.9 2 424 155.6 2 .2 .14 2 .4 .07 2 .3 .28 2 13 9.9 2 24 4.9 2 20 19.8 2 122 DOSE WBC mg/kg/day X103/mcL Table 17 Summary of Clinical Hematology Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 11.8 7.2 3.2 1.0 .2 .0 59 30 8 2 0 S.D. 4.38 3.96 .07 .57 .07 .00 11.3 11.3 2.1 1.4 .0 N 22222222222 0.15 MEAN 9.4 4.2 4.2 .6 .4 .0 42 48 7 4 0 S.D. 2.83 3.18 .42 .21 .28 .00 21.2 19.1 4.2 1.4 .0 N 22222222222 0.75 MEAN 8.9 2.7 5.6 .6 .2 .0 30 62 6 2 0 S.D. 1.56 .57 .78 .07 .07 .00 1.4 1.4 .7 .7 .0 N 22222222222 123 Table 18 Summary of Clinical Hematology Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.53 .042 2 6.72 .283 2 6.23 .198 2 12.4 .07 2 13.0 .64 2 12.2 .21 2 39.5 .07 2 41.2 2.97 2 38.9 .28 2 60.5 .49 2 61.3 1.91 2 62.5 2.40 2 19.2 .21 2 19.4 .28 2 19.5 .28 2 31.6 .07 2 31.7 .57 2 31.2 .85 2 514 179.6 2 448 68.6 2 508 17.7 2 .1 .14 2 .1 .14 2 .8 1.06 2 6 9 2 7 9 2 46 64 2 124 Table 18 Summary of Clinical Hematology Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 10.8 6.6 3.4 .7 .0 .0 61 32 6 0 0 S.D. .14 .99 .92 .14 .07 .07 8.5 9.2 .7 .7 .7 N 22222222222 0.15 MEAN 12.5 8.2 3.5 .8 .1 .0 64 28 6 0 0 S.D. 1.84 1.98 .71 .49 .14 .00 6.4 10.6 2.8 .7 .0 N 22222222222 0.75 MEAN 12.2 6.4 4.2 1.1 .4 .0 52 36 93 0 S.D. 3.96 2.69 .78 .42 .07 .07 4.9 5.7 .0 .0 .7 N 22222222222 125 Table 18 Summary of Clinical Hematology Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.28 .453 2 6.77 .113 2 6.54 .028 2 12.4 .78 2 12.6 .14 2 12.2 .07 2 38.1 2.90 2 40.8 1.34 2 40.1 .57 2 60.8 .35 2 60.2 .92 2 61.3 1.13 2 19.8 .14 2 18.6 .07 2 18.6 .14 2 32.6 .42 2 31.0 .64 2 30.4 .78 2 534 142.8 2 456 67.9 2 448 181.7 2 .2 .07 2 .2 .07 2 .2 .07 2 10 4.9 2 10 4.2 2 10 4.2 2 126 Table 18 Summary of Clinical Hematology Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 7.4 3.4 2.8 1.0 .2 .0 46 37 14 3 0 S.D. 1.48 1.13 .42 .28 .14 .00 6.4 1.4 6.4 1.4 .0 N 22222222222 0.15 MEAN 8.1 3.0 3.7 .9 .4 .0 38 46 11 5 0 S.D. .57 .71 .99 .42 .14 .07 10.6 9.2 4.2 2.8 .7 N 22222222222 0.75 MEAN 10.8 4.7 5.2 .8 .1 .0 43 48 8 1 0 S.D. .78 .57 .21 .42 .14 .00 1.4 4.9 3.5 1.4 .0 N 22222222222 127 Table 19 Summary of Clinical Hematology Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.63 .269 2 7.16 .049 2 6.30 .530 2 12.9 .57 2 14.0 .21 2 12.6 .92 2 40.2 1.34 2 45.6 .99 2 40.6 2.69 2 60.7 .42 2 63.7 .92 2 64.5 1.13 2 19.4 .00 2 19.5 .14 2 19.9 .21 2 32.0 .28 2 30.6 .21 2 31.0 .14 2 460 174.7 2 490 106.8 2 510 92.6 2 .3 .14 2 .3 .28 2 .7 .99 2 20 9 2 22 20 2 42 58 2 128 Table 19 Summary of Clinical Hematology Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 11.6 6.4 4.4 .6 .1 .0 55 38 6 1 0 S.D. .57 1.48 .78 .07 .00 .07 9.9 8.5 .7 .0 .7 N 22222222222 0.15 MEAN 11.6 4.9 5.9 .6 .2 .0 42 50 6 2 0 S.D. 1.27 1.13 .42 .21 .00 .00 4.9 2.1 2.1 .7 .0 N 22222222222 0.75 MEAN 16.6 10.3 4.8 1.2 .4 .1 62 28 6 2 0 S.D. 6.51 3.96 1.77 .64 .21 .00 .7 .7 .7 1.4 .7 N 22222222222 129 Table 19 Summary of Clinical Hematology Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.26 .884 2 6.66 .064 2 7.06 .629 2 12.4 1.56 2 12.7 .00 2 13.1 .57 2 38.5 5.23 2 40.8 .85 2 42.9 3.18 2 61.6 .35 2 61.4 .71 2 60.8 .92 2 19.8 .35 2 19.2 .21 2 18.5 .78 2 32.2 .49 2 31.2 .78 2 30.6 .92 2 494 122.3 2 451 14.1 2 446 215.7 2 .5 .14 2 .3 .14 2 .2 .21 2 31 4 2 20 9 2 12 16 2 130 Table 19 Summary of Clinical Hematology Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 8.8 4.4 3.4 .7 .3 .0 50 38 8 3 0 S.D. .78 .14 .64 .14 .14 .00 6.4 3.5 .7 1.4 .0 N 22222222222 0.15 MEAN 9.9 3.8 4.6 .9 .6 .0 37 48 96 0 S.D. 1.70 1.70 .07 .14 .28 .00 11.3 6.4 .0 4.2 .0 N 22222222222 0.75 MEAN 10.6 3.0 6.2 1.0 .3 .2 29 58 93 2 S.D. .92 .71 1.56 .07 .14 .07 9.9 9.9 1.4 1.4 .7 N 22222222222 131 Table 20 Summary of Clinical Hematology Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.56 .035 2 6.90 .141 2 6.42 .000 2 12.6 .00 2 13.6 .21 2 12.6 .14 2 40.7 1.06 2 43.9 .42 2 42.4 1.56 2 61.9 1.27 2 63.6 .71 2 66.0 2.33 2 19.2 .07 2 19.8 .00 2 19.6 .14 2 31.0 .71 2 31.1 .28 2 29.8 .78 2 434 96.9 2 373 5.7 2 520 59.4 2 .5 .28 2 .7 .00 2 .6 .42 2 33 18.4 2 48 .7 2 38 27.6 2 132 Table 20 Summary of Clinical Hematology Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0 MEAN 8.4 3.1 4.2 .8 .1 .2 36 52 91 2 S.D. 1.77 1.56 .14 .42 .00 .21 11.3 12.0 2.8 .0 2.1 N 22222222222 0.15 MEAN 10.9 5.0 4.7 .8 .4 .1 46 42 8 2 1 S.D. 3.96 1.70 2.12 .14 .21 .00 1.4 4.2 4.2 .7 .0 N 22222222222 0.75 MEAN 16.0 9.8 4.4 1.2 .2 .2 62 28 8 2 2 S.D. .35 1.48 1.41 .07 .21 .14 11.3 7.8 .7 .7 .7 N 22222222222 133 Table 20 Summary of Clinical Hematology Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T--6295) IN CYNOMOLGUS MONKEYS DOSE RBC mg/kg/day X106/mcL HGB G/DL HCT % MCV FL MCH PG MCHC % PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 6.02 .700 2 6.46 .191 2 6.72 .134 2 11.8 1.06 2 12.3 .42 2 12.4 .14 2 37.5 4.17 2 40.2 1.34 2 40.8 .28 2 62.5 .21 2 62.2 .21 2 60.8 1.56 2 19.8 .49 2 19.0 .14 2 18.5 .57 2 31.6 .71 2 30.6 .14 2 30.4 .14 2 508 35.4 2 406 2.1 2 396 146.4 2 .4 .21 2 .4 .21 2 .3 .14 2 26 9 2 29 12 2 20 9 2 134 Table 20 Summary of Clinical Hematology Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE WBC N-SEG LYMPH MONO EOSIN BASO N-SEG% mg/kg/day X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO 0 MEAN 11.2 7.0 2.8 1.0 .3 .2 58 28 10 2 1 S.D. 6.15 4.95 .49 .42 .14 .07 12.0 11.3 .7 .7 .0 N 22222222222 0.15 MEAN 11.5 5.4 4.2 1.0 .6 .2 46 37 10 5 2 S.D. 3.25 2.33 1.20 .07 .21 .00 7.1 .0 2.8 2.8 .0 N 22222222222 0.75 MEAN 10.4 3.1 6.4 .5 .2 .2 30 61 5 2 2 S.D. .85 .14 .92 .00 .14 .07 3.5 4.2 .0 .7 .7 N 22222222222 135 DOSE mg/kg/day GLU MG/DL Table 21 Summary of Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL 0 MEAN S.D. N 76 12.5 6 20 3.8 6 1.2 .10 6 9.0 .32 6 4.9 .21 6 4.1 .26 6 .6 .45 6 9 138 2.0 33.7 66 70 13.3 6 0.03 MEAN S.D. N 70 8.3 4 20 6.2 4 1.2 .17 4 9.6 .58 4 5.2 .46 4 4.4 .48 4 .4 .18 4 9 110 1.4 20.1 44 61 35.0 4 0.15 MEAN S.D. N 82 30.4 6 21 3.3 6 1.2 .22 6 9.5 .44 6 5.1 .34 6 4.4 .26 6 .6 10 151 56 .37 2.2 26.1 4.9 6666 0.75 MEAN S.D. N 73 15.4 6 20 2.0 6 1.3 .11 6 9.4 .38 6 5.2 .28 6 4.3 .37 6 .5 .29 6 9 138 1.3 29.3 66 67 11.0 6 136 Table 21 Summary of Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 56 16.5 6 44 6.3 4 72 23.5 6 68 11.7 6 32 9.7 6 36 11.2 4 69 35.7 6 80 54.2 6 711 252.6 6 700 265.6 4 770 210.3 6 840 360.9 6 134 42.8 6 141 34.5 4 160 68.4 6 171 53.3 6 7 1133 1.9 535.3 66 3 936 1.0 709.0 44 8 1087 5.4 322.3 66 6 1094 1.5 497.4 66 395 93.4 6 476 164.6 4 386 94.5 6 529 135.6 6 55 84.4 6 35 20.6 4 51 42.4 6 41 31.8 6 247 54.0 6 302 107.4 4 242 62.4 6 324 72.2 6 137 Table 21 Summary of Clinical Chemistry Data Males Day -27 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.8 .60 6 11.6 .53 4 11.5 .62 6 11.3 .54 6 6.2 .84 6 6.6 .44 4 7.1 .99 6 6.9 1.06 6 159 4.6 6 164 6.0 4 163 5.3 6 161 4.8 6 5.4 .58 6 5.9 .32 4 6.4 .60 6 5.8 .62 6 109 2.9 6 111 2.2 4 112 2.7 6 108 2.9 6 Covance 6329-223 3M T-6295.7 138 DOSE mg/kg/day GLU MG/DL Table 21 Summary of Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL 0 MEAN S.D. N 76 22.2 6 22 1.6 6 1.2 .08 6 9.6 .78 6 4.9 .35 6 4.7 .83 6 .5 .34 6 7 149 1.9 37.2 66 73 32.4 6 0.03 MEAN S.D. N 73 10.7 4 22 1.3 4 1.2 .08 4 9.3 .50 4 4.7 .18 4 4.6 .41 4 .5 .17 4 6 130 1.7 12.4 44 62 7.5 4 0.15 MEAN S.D. N 76 12.0 6 23 3.9 6 1.1 .10 6 9.6 .62 6 4.7 .57 6 4.9 .38 6 .6 12 144 58 .21 12.1 14.0 11.7 6666 0.75 MEAN S.D. N 78 16.3 6 24 3.9 6 1.2 .18 6 9.4 .78 6 4.8 .40 6 4.6 .65 6 .6 .37 6 9 154 1.4 10.1 66 61 16.6 6 139 Table 21 Summary of Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 64 6.7 6 54 10.2 4 74 35.5 6 72 15.4 6 140 76.9 6 103 29.4 4 110 41.0 6 123 54.2 6 291 130.1 6 201 12.5 4 257 118.5 6 310 141.4 6 123 54.0 6 94 48.5 4 87 32.9 6 75 24.3 6 4 979 1.6 384.3 66 3 484 .8 156.7 44 4 844 2.4 306.4 66 4 1624 2.0 1251.5 66 374 121.9 6 378 153.7 4 416 121.0 6 384 88.6 6 28 12.5 6 26 15.9 4 35 21.2 6 19 15.4 6 220 73.1 6 237 79.9 4 244 81.3 6 247 54.1 6 140 Table 21 Summary of Clinical Chemistry Data Females Day -27 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 11.4 1.10 6 10.9 .58 4 11.0 .59 6 11.3 .59 6 6.2 .63 6 4.7 .99 4 5.9 .78 6 5.5 .50 6 163 7.1 6 163 3.4 4 162 6.1 6 163 4.9 6 6.2 .96 6 5.9 .70 4 6.1 .63 6 6.1 .80 6 114 5.0 6 115 3.3 4 115 3.1 6 114 1.5 6 Covance 6329-223 3M T-6295.7 141 DOSE mg/kg/day GLU MG/DL Table 22 Summary of Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 60 5.9 6 62 8.3 4 61 9.8 6 65 7.8 6 20 3.3 6 18 3.9 4 21 4.9 6 21 2.3 6 1.1 .12 6 1.2 .18 4 1.2 .23 6 1.3 .12 6 8.9 .56 6 9.3 1.02 4 9.2 .33 6 9.3 .37 6 4.7 .13 6 5.0 .46 4 4.8 .25 6 5.1 .36 6 4.2 .49 6 4.3 .85 4 4.4 .32 6 4.2 .40 6 .8 .43 6 .4 .16 4 .6 .27 6 .4 .17 6 9 140 1.5 22.1 66 8 118 1.3 28.4 44 8 146 .8 21.5 66 7 130 1.5 18.0 66 69 18.7 6 47 4.6 4 58 5.3 6 91 27.3 6 142 Table 22 Summary of Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 45 15.9 6 37 6.3 4 48 15.9 6 43 10.0 6 39 19.5 6 40 13.0 4 50 23.8 6 46 23.0 6 888 339.5 6 876 384.3 4 896 267.3 6 996 417.0 6 134 42.9 6 120 35.4 4 136 57.3 6 142 39.9 6 7 354 2.6 461.0 66 3 191 1.5 58.2 44 5 184 3.2 59.7 66 2 * 283 .4 149.7 66 374 106.3 6 459 149.3 4 369 78.9 6 522 124.7 6 22 12.5 6 24 13.6 4 40 21.7 6 26 10.9 6 222 58.4 6 282 93.3 4 221 55.5 6 307 55.9 6 143 Table 22 Summary of Clinical Chemistry Data Males Day 37 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.6 .25 6 11.2 1.12 4 11.0 .39 6 10.9 .43 6 6.7 .80 6 6.9 1.58 4 6.8 1.00 6 6.6 1.29 6 160 3.6 6 165 10.1 4 160 3.1 6 162 3.4 6 5.4 .28 6 5.8 .74 4 5.6 .38 6 5.4 .29 6 115 3.4 6 116 4.2 4 115 .9 6 114 2.7 6 Covance 6329-223 3M T-6295.7 144 DOSE mg/kg/day GLU MG/DL Table 22 Summary of Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 58 14.7 6 67 15.2 4 60 8.4 6 70 11.5 6 22 4.4 6 21 3.0 4 20 3.6 6 22 5.4 6 1.1 .16 6 1.1 .05 4 1.0 .04 6 1.1 .14 6 9.3 .71 6 9.0 .41 4 9.2 .26 6 9.1 .31 6 4.4 .26 6 4.5 .15 4 4.3 .37 6 4.4 .10 6 4.9 .80 6 4.5 .39 4 4.9 .40 6 4.7 .38 6 .6 .34 6 .5 .25 4 .6 .14 6 .4 .15 6 8 147 .5 26.9 66 9 124 2.5 11.1 44 8 133 3.2 22.4 66 7 123 1.2 14.1 66 71 25.7 6 64 12.0 4 57 11.3 6 66 23.0 6 145 Table 22 Summary of Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 44 12.1 6 49 15.9 4 36 6.6 6 36 8.0 6 59 30.2 6 70 13.3 4 68 30.9 6 46 7.5 6 362 125.6 6 240 48.7 4 319 129.0 6 415 188.9 6 102 42.9 6 88 54.7 4 76 20.3 6 58 20.0 6 5 240 2.4 146.6 66 3 378 1.3 262.2 44 3 198 1.5 101.3 66 2 * 331 .9 242.1 66 339 89.9 6 384 110.9 4 414 115.1 6 373 83.3 6 18 13.2 6 28 15.2 4 34 17.4 6 23 5.9 6 194 58.2 6 237 55.5 4 230 70.7 6 230 66.0 6 146 Table 22 Summary of Clinical Chemistry Data Females Day 37 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.4 .39 6 10.2 .42 4 9.7 .73 6 10.4 .25 6 5.7 .73 6 4.2 * .37 4 5.1 .65 6 5.0 .48 6 161 4.9 6 161 5.4 4 157 2.5 6 160 5.3 6 5.7 .38 6 5.2 .92 4 5.2 .39 6 5.9 .42 6 115 4.4 6 116 4.3 4 114 1.1 6 116 3.0 6 Covance 6329-223 3M T-6295.7 147 DOSE mg/kg/day GLU MG/DL Table 23 Summary of Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL 0 MEAN S.D. N 59 9.1 6 20 3.9 6 1.1 .08 6 8.6 .50 6 4.6 .17 6 4.0 .42 6 .7 .42 6 9 153 1.5 23.0 66 62 19.0 6 0.03 MEAN 59 20 1.2 9.0 4.7 4.3 .4 10 114 * 60 S.D. 2.9 3.7 .14 .69 .36 .58 .10 2.2 25.1 14.8 N 4444444444 0.15 MEAN 67 18 1.2 8.8 4.6 4.1 .5 10 144 57 S.D. 13.3 3.9 .19 .42 .48 .44 .23 1.7 19.7 13.4 N 6666666666 0.75 MEAN 74 19 1.3 8.8 4.8 4.0 .3 10 125 76 S.D. 10.6 2.6 .12 .41 .53 .59 .06 2.7 20.6 16.6 N 6666666666 148 Table 23 Summary of Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 36 7.9 6 35 7.2 4 40 9.4 6 34 6.3 6 34 15.2 6 35 17.5 4 37 11.7 6 43 16.2 6 839 321.9 6 750 369.9 4 806 237.8 6 823 367.0 6 130 46.2 6 116 25.0 4 128 39.4 6 125 29.9 6 7 132 371 2.3 27.8 115.8 666 4 149 428 1.5 47.7 143.3 444 5 153 344 3.8 19.9 89.3 666 3 203 * 499 .8 57.2 119.4 666 22 13.9 6 21 13.8 4 20 11.3 6 22 13.4 6 224 64.2 6 270 92.9 4 213 61.7 6 301 53.4 6 149 Table 23 Summary of Clinical Chemistry Data Males Day 62 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.4 .39 6 10.5 .44 4 10.4 .26 6 10.5 .60 6 7.1 .66 6 6.8 .88 4 6.6 1.08 6 6.8 1.31 6 160 2.9 6 166 12.5 4 160 3.5 6 159 6.4 6 5.4 .44 6 5.6 .92 4 5.4 .50 6 5.6 .63 6 120 2.5 6 122 9.3 4 120 3.5 6 120 2.8 6 Covance 6329-223 3M T-6295.7 150 DOSE mg/kg/day GLU MG/DL Table 23 Summary of Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL 0 MEAN S.D. N 57 10.2 6 21 3.5 6 1.1 .13 6 9.0 .57 6 4.4 .21 6 4.7 .75 6 .5 .24 6 9 155 .8 45.4 66 86 49.4 6 0.03 MEAN 66 22 1.1 8.8 4.3 4.5 .6 10 127 76 S.D. 17.3 3.4 .05 .44 .10 .46 .26 3.7 11.2 21.5 N 4444444444 0.15 MEAN 62 20 1.0 9.0 4.3 4.7 .6 10 137 64 S.D. 12.6 2.7 .10 .15 .33 .24 .18 3.2 19.5 18.0 N 6666666666 0.75 MEAN S.D. N 74 7.2 6 20 5.0 6 1.2 .13 6 9.0 .44 6 4.4 .17 6 4.6 .39 6 .4 .10 6 9 127 1.9 18.9 66 61 10.5 6 151 Table 23 Summary of Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 38 3.4 6 45 9.9 4 37 7.8 6 31 7.8 6 53 16.7 6 77 15.8 4 60 29.3 6 42 6.2 6 360 152.5 6 241 45.3 4 305 134.0 6 398 200.5 6 106 47.7 6 84 44.5 4 75 20.8 6 58 20.0 6 4 262 1.8 123.6 66 4 276 2.2 67.9 44 4 194 1.0 76.1 66 2 * 243 .4 130.1 66 342 86.9 6 358 108.3 4 410 129.7 6 385 89.4 6 14 14.7 6 19 16.7 4 28 19.6 6 27 9.9 6 198 55.5 6 228 55.8 4 234 82.3 6 246 56.7 6 152 Table 23 Summary of Clinical Chemistry Data Females Day 62 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.0 .34 6 9.9 .22 4 9.6 .48 6 10.2 .60 6 6.0 .36 6 4.6 * .30 4 5.1 * .51 6 5.0 * .30 6 162 6.5 6 160 2.9 4 160 3.6 6 161 3.5 6 5.8 .59 6 5.2 .43 4 5.5 .60 6 5.8 .67 6 120 5.1 6 120 2.2 4 123 3.0 6 120 1.8 6 Covance 6329-223 3M T-6295.7 153 DOSE mg/kg/day GLU MG/DL Table 24 Summary of Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 60 8.0 6 64 7.6 4 75 18.5 6 73 19.1 6 20 4.3 6 20 4.9 4 19 4.6 6 19 1.3 6 1.1 .14 6 1.3 .22 4 1.2 .16 6 1.4 .19 6 8.7 .40 6 9.6 .98 4 9.0 .19 6 9.4 .36 6 4.8 .12 6 5.3 * .39 4 5.0 .14 6 5.2 * .31 6 3.9 .33 6 4.2 .75 4 4.0 .21 6 4.2 .35 6 .7 .38 6 .4 .13 4 .4 .22 6 .3 * .05 6 8 1.2 6 8 .6 4 9 2.7 6 10 3.6 6 154 24.6 6 126 14.9 4 150 18.8 6 112 * 27.0 6 68 20.4 6 54 9.8 4 50 10.4 6 73 21.0 6 154 Table 24 Summary of Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 39 7.7 6 35 7.0 4 42 12.2 6 36 6.3 6 35 15.8 6 60 55.8 4 45 22.4 6 44 21.0 6 866 296.2 6 789 401.7 4 851 265.3 6 807 428.6 6 136 50.1 6 131 34.5 4 140 58.6 6 127 27.4 6 7 168 2.6 32.4 66 4 175 1.4 42.5 44 6 164 4.3 36.2 66 2 * 214 .6 75.7 66 392 111.8 6 465 185.6 4 377 94.9 6 468 149.1 6 33 30.3 6 48 57.9 4 27 18.3 6 32 17.5 6 265 71.2 6 318 125.4 4 258 70.1 6 350 70.4 6 155 Table 24 Summary of Clinical Chemistry Data Males Day 91 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.3 .77 6 10.5 .79 4 10.6 .51 6 10.8 .41 6 6.8 .37 6 6.7 .70 4 6.8 1.05 6 6.4 .94 6 160 7.1 6 167 4.9 4 161 4.6 6 163 5.0 6 5.1 .56 6 5.7 1.04 4 5.4 .35 6 5.4 .45 6 117 5.3 6 120 4.1 4 118 7.0 6 117 4.2 6 Covance 6329-223 3M T-6295.7 156 DOSE mg/kg/day GLU MG/DL Table 24 Summary of Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL 0 MEAN S.D. N 66 20.5 6 20 2.7 6 1.2 .10 6 9.2 .51 6 4.7 .38 6 4.6 .51 6 .4 .16 6 8 166 1.5 42.0 66 67 10.9 6 0.03 MEAN S.D. N 68 14.7 4 22 3.3 4 1.1 .08 4 9.0 .69 4 4.6 .19 4 4.4 .54 4 .5 .27 4 8 134 1.4 15.6 44 61 14.0 4 0.15 MEAN 60 20 1.0 9.1 4.4 4.6 .4 10 140 56 S.D. 12.4 4.2 .05 .24 .41 .32 .10 5.8 13.1 18.0 N 6666666666 0.75 MEAN 79 22 1.2 9.5 4.8 4.7 .3 11 111 * 60 S.D. 15.5 6.3 .19 .45 .29 .33 .08 7.0 26.6 14.4 N 6666666666 157 Table 24 Summary of Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 44 9.1 6 43 14.6 4 37 11.1 6 34 9.8 6 54 17.9 6 79 26.6 4 67 42.8 6 45 13.0 6 329 128.7 6 233 57.5 4 324 140.3 6 388 150.1 6 110 46.5 6 103 78.3 4 74 19.2 6 63 22.3 6 6 786 2.2 947.2 66 4 220 4.4 39.4 44 4 209 2.5 81.8 66 2 * 416 .5 377.0 66 370 87.4 6 390 99.8 4 442 127.6 6 379 96.5 6 15 17.5 6 18 10.9 4 40 46.1 6 19 13.6 6 236 62.7 6 269 62.5 4 282 87.7 6 263 59.4 6 158 Table 24 Summary of Clinical Chemistry Data Females Day 91 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 1.11 6 10.2 1.21 4 10.0 .53 6 10.6 .58 6 5.7 .66 6 4.2 * .44 4 5.2 .63 6 5.1 .53 6 161 5.9 6 161 7.5 4 160 3.4 6 162 4.7 6 5.6 .74 6 5.2 .93 4 5.7 .45 6 5.8 .54 6 118 6.1 6 117 6.8 4 120 4.2 6 118 3.9 6 Covance 6329-223 3M T-6295.7 159 DOSE mg/kg/day GLU MG/DL Table 25 Summary of Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 60 8.0 6 61 4.3 4 63 9.4 6 76 17.0 6 20 3.0 6 19 2.2 4 22 4.5 6 20 2.2 6 1.1 .12 6 1.2 .19 4 1.2 .18 6 1.3 .20 6 8.2 .45 6 8.8 .83 4 8.8 .55 6 9.0 .23 6 4.8 .19 6 5.2 .24 4 5.0 .31 6 4.9 .48 6 3.4 .34 6 3.6 .66 4 3.8 .61 6 4.1 .43 6 .7 .41 6 .4 .08 4 .5 .20 6 .2 * .05 6 10 1.5 6 7 1.0 4 10 2.3 6 14 5.5 6 154 29.9 6 120 16.3 4 149 22.8 6 65 * 20.3 6 60 18.3 6 60 24.9 4 65 9.5 6 60 26.3 6 69 10.6 6 46 * 4.5 4 55 * 12.5 6 19 * 6.5 6 160 Table 25 Summary of Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 31 4.9 6 30 6.3 4 40 15.7 6 39 8.8 6 43 27.3 6 36 19.8 4 55 17.2 6 52 26.6 6 792 305.3 6 684 348.2 4 853 207.5 6 646 384.1 6 142 53.1 6 123 32.2 4 148 63.8 6 112 36.1 6 3 165 392 2.6 28.5 112.8 666 23 10.5 6 276 74.9 6 2 133 470 1.5 42.6 165.2 444 41 40.0 4 339 123.2 4 4 193 429 166 312 3.1 38.4 69.9 339.9 67.7 66666 2 352 * 517 1.2 297.5 124.5 666 32 17.2 6 364 59.9 6 161 Table 25 Summary of Clinical Chemistry Data Males Day 153 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.1 .73 6 10.8 .56 4 10.4 .64 6 10.8 .76 6 6.6 .31 6 6.3 1.09 4 6.8 1.01 6 6.8 1.66 6 157 6.1 6 159 3.9 4 158 3.2 6 158 7.9 6 5.4 .48 6 5.5 .67 4 5.5 .43 6 5.8 .73 6 116 4 6 117 4 4 115 4 6 113 7 6 Covance 6329-223 3M T-6295.7 162 DOSE mg/kg/day GLU MG/DL Table 25 Summary of Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 58 9.9 6 20 4.0 6 1.1 .14 6 8.9 .80 6 4.7 .47 6 4.2 .63 6 .5 .27 6 9 163 1.3 48.5 66 80 47.1 6 59 16.8 6 0.03 MEAN S.D. N 64 12.1 4 20 6.0 4 1.1 .17 4 8.6 .25 4 4.4 .40 4 4.2 .29 4 .5 .34 4 8 110 * 1.7 22.1 44 82 28.5 4 47 9.5 4 0.15 MEAN 57 22 1.1 8.8 4.5 4.2 .5 10 130 69 41 * S.D. 4.9 3.1 .08 .33 .37 .48 .12 3.1 23.2 13.7 9.2 N 66666666666 0.75 MEAN 70 18 1.2 8.9 4.5 4.4 .3 15 91 * 64 23 * S.D. 14.6 5.3 .14 .43 .41 .40 .08 13.8 23.1 13.5 4.3 N 66666666666 163 Table 25 Summary of Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 36 8.2 6 38 16.2 4 36 13.4 6 40 18.1 6 77 43.3 6 80 52.8 4 66 34.1 6 48 10.0 6 315 143.3 6 262 42.2 4 308 120.9 6 336 146.9 6 112 51.2 6 108 97.8 4 72 20.3 6 61 24.2 6 2 235 .8 105.0 66 2 255 .8 131.7 44 3 242 2.5 116.5 66 2 695 2.3 1217.1 66 373 74.3 6 378 108.8 4 432 165.5 6 380 104.1 6 18 17.7 5 18 13.5 4 25 15.2 6 26 10.9 6 256 55.7 6 275 67.7 4 293 129.4 6 281 76.1 6 164 Table 25 Summary of Clinical Chemistry Data Females Day 153 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 .87 6 9.8 1.04 4 9.8 .42 6 10.5 .67 6 5.6 .34 6 4.1 * .84 4 5.0 .96 6 4.9 .71 6 158 8.5 6 155 6.9 4 154 2.2 6 158 5.0 6 6.0 .81 6 5.6 .46 4 5.4 .52 6 6.3 .75 6 119 7 6 116 6 4 116 3 6 116 4 6 Covance 6329-223 3M T-6295.7 165 DOSE mg/kg/day GLU MG/DL Table 26 Summary of Clinical Chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 60 6.1 6 64 9.1 4 70 8.3 6 76 12.6 4 18 3.9 6 18 6.3 4 17 2.6 6 22 4.5 4 1.1 .16 6 1.2 .16 4 1.1 .17 6 1.2 .24 4 8.2 .54 6 8.8 .65 4 8.5 .30 6 9.0 .77 4 4.8 .23 6 5.0 .34 4 4.9 .31 6 4.9 .53 4 3.5 .40 6 3.8 .47 4 3.6 .17 6 4.1 .44 4 .6 .23 6 .3 * .08 4 .4 .10 6 .2 * .05 4 6 .8 6 5* .5 4 6 1.3 6 18 * 8.6 4 152 27.5 6 110 * 17.0 4 147 24.0 6 48 * 18.8 4 45 8.7 6 33 6.6 4 36 10.4 6 30 11.8 4 63 11.1 6 42 * 3.7 4 48 14.3 6 13 * 5.4 4 166 Table 26 Summary of Clinical Chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 32 6.2 6 27 6.2 4 36 13.3 6 34 5.3 4 39 17.9 6 29 8.8 4 47 16.9 6 47 19.7 4 735 318.7 6 604 353.5 4 688 178.3 6 389 155.7 4 150 65.6 6 126 42.6 4 148 55.8 6 104 25.3 4 6 210 393 3.7 158.7 102.8 666 4 138 442 1.9 58.8 136.5 444 6 174 381 3.8 101.5 82.3 666 3 182 446 1.0 64.5 65.3 444 29 13.4 6 24 10.6 4 30 11.8 6 36 22.2 4 280 68.5 6 314 96.4 4 270 59.0 6 320 25.2 4 167 Table 26 Summary of Clinical Chemistry Data Males Day 182 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 .43 6 10.0 .20 4 10.1 .41 6 10.3 .62 4 6.4 .82 6 5.8 .96 4 6.2 .82 6 6.1 1.22 4 154 4.8 6 156 1.5 4 154 4.7 6 153 6.4 4 5.1 .23 6 5.0 .32 4 5.0 .25 6 5.4 .17 4 111 1 6 109 2 4 110 2 6 106 5 4 Covance 6329-223 3M T-6295.7 168 DOSE mg/kg/day GLU MG/DL Table 26 Summary of Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 58 15.2 6 54 7.8 4 64 9.0 6 73 11.0 6 20 3.7 6 20 3.4 4 19 3.1 6 20 4.7 6 1.1 .18 6 1.0 .17 4 1.0 .09 6 1.2 .16 6 8.9 .66 6 8.6 .76 4 8.9 .47 6 9.2 .37 6 4.7 .42 6 4.4 .47 4 4.5 .35 6 4.6 .31 6 4.2 .55 6 4.2 .38 4 4.4 .67 6 4.7 .63 6 .4 .25 6 .5 .24 4 .4 .08 6 .2 .08 6 6 160 .6 46.5 66 5 122 1.5 21.6 44 8 129 2.0 22.3 66 7 82 * 3.4 14.7 66 56 13.3 6 49 14.7 4 49 15.8 6 53 15.8 6 56 16.0 6 42 9.1 4 36 * 12.1 6 21 * 7.2 6 169 Table 26 Summary of Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 41 25.0 6 42 14.6 4 37 13.0 6 33 6.2 6 87 85.9 6 72 26.3 4 53 36.1 6 44 9.9 6 283 137.1 6 239 39.7 4 254 85.3 6 316 172.4 6 114 53.3 6 111 99.5 4 71 19.7 6 64 22.7 6 5 212 3.1 123.4 66 6 823 6.0 1281.8 44 7 182 5.2 84.7 66 3 284 1.5 119.3 66 378 84.6 6 358 100.7 4 439 140.9 6 375 64.9 6 32 37.1 6 19 15.0 4 33 21.6 6 31 21.2 6 258 64.1 6 260 64.4 4 294 111.7 6 273 43.1 6 170 Table 26 Summary of Clinical Chemistry Data Females Day 182 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 .68 6 9.6 .84 4 9.8 .16 6 10.3 .69 6 5.3 .84 6 4.4 .39 4 4.8 1.10 6 5.2 .76 6 156 6.8 6 152 7.2 4 154 3.3 6 156 4.9 6 5.3 .56 6 4.8 .94 4 5.0 .37 6 5.4 .82 6 111 5.0 6 109 3.6 4 110 1.8 6 110 3.1 6 Covance 6329-223 3M T-6295.7 171 DOSE GLU mg/kg/day MG/DL Table 27 Summary of Clinical Chemistry Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN 57 16 1.0 8.0 4.6 3.4 .5 12 132 44 58 S.D. 2.8 4.9 .07 .21 .07 .14 .14 1.4 28.3 .7 12 7 N 22222222222 0.15 MEAN S.D. N 70 17 .9 9.0 5.1 3.9 12.0 .0 .14 .42 .00 .42 222222 .6 16 158 39 61 .21 .0 37.5 2.8 19 8 22222 0.75 MEAN 73 14 1.0 8.7 4.6 4.2 .6 14 137 69 28 S.D. 4.2 2.1 .07 .00 .35 .35 .00 3.5 4.2 32.5 7 8 N 22222222222 172 Table 27 Summary of Clinical Chemistry Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 22 3.5 2 37 8.5 2 32 4.9 2 26 3.5 2 44 2.1 2 48 28.3 2 932 316.1 2 793 175.4 2 518 27.6 2 150 123.7 2 138 68.6 2 143 22.6 2 4 .7 2 12 1.4 2 2 .7 2 139 77.8 2 162 21.9 2 200 32.5 2 338 87.7 2 454 42.4 2 505 53.7 2 36 7.8 2 46 2.1 2 38 21.2 2 250 58.7 2 288 62.2 2 346 23.3 2 173 Table 27 Summary of Clinical Chemistry Data Males Day 217 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.0 .57 2 11.0 .78 2 10.8 .21 2 6.3 1.13 2 6.6 .00 2 6.2 1.13 2 152 2.8 2 155 1.4 2 159 2.8 2 5.0 .49 2 5.3 .28 2 5.4 .07 2 111 1 2 108 2 2 111 1 2 Covance 6329-223 3M T-6295.7 174 DOSE GLU mg/kg/day MG/DL Table 27 Summary of Clinical Chemistry Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN 59 16 .8 8.6 4.6 4.0 .4 14 119 72 54 S.D. 11.3 4.9 .14 .42 .21 .21 .42 1.4 46.7 50.2 29 0 N 22222222222 0.15 MEAN 76 18 1.0 8.7 4.0 4.6 .6 14 145 56 44 S.D. .7 2.1 .00 .14 .07 .21 .00 .7 4.2 4.9 24 7 N 22222222222 0.75 MEAN S.D. N 75 9.9 2 23 2.8 2 1.0 .21 2 9.3 .42 2 4.6 .57 2 4.7 .14 2 .6 19 133 78 34 .07 7.1 2.8 21.9 12 0 22222 175 Table 27 Summary of Clinical Chemistry Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 34 .7 2 26 9.9 2 23 .0 2 103 24.0 2 48 7.8 2 50 16.3 2 184 33.2 2 182 97.6 2 220 29.0 2 61 28 3 2 70 21 2 94 37 5 2 4 137 343 .7 28.3 48.1 222 4 657 486 4.2 763.7 244.0 222 4 165 345 2.1 29.7 69.3 222 13 18.4 2 32 21.9 2 38 4.2 2 244 17 2 350 163 2 256 47 2 176 Table 27 Summary of Clinical Chemistry Data Females Day 217 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 9.8 .14 2 9.8 .14 2 10.3 .14 2 4.8 1.56 2 5.5 .28 2 5.8 .64 2 148 4.9 2 152 3.5 2 152 .0 2 5.4 .64 2 5.5 .00 2 5.0 .21 2 108 6.4 2 110 2.1 2 110 2.1 2 Covance 6329-223 3M T-6295.7 177 DOSE GLU mg/kg/day MG/DL Table 28 Summary of Clinical Chemistry Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 101 21.2 2 16 1.4 2 1.1 .14 2 8.7 .14 2 4.8 .07 2 3.8 .07 2 .4 .07 2 8 134 .7 29.0 22 33 7.1 2 77 57 2 0.15 MEAN S.D. N 81 2.8 2 17 .0 2 1.1 .14 2 9.0 .14 2 5.2 .07 2 3.8 .07 2 .6 .28 2 8 160 4.2 46.0 22 48 5.7 2 84 26 9 2 0.75 MEAN 72 17 1.0 8.8 4.6 4.2 .4 11 136 64 52 S.D. 16.3 1.4 .00 .35 .35 .00 .00 5.7 4.9 10.6 2 1 N 22222222222 178 Table 28 Summary of Clinical Chemistry Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 27 4.2 2 34 21.2 2 46 4.9 2 28 .7 2 40 .0 2 53 28.3 2 900 334.5 2 838 62.9 2 680 78.5 2 144 107.5 2 142 62.2 2 166 14.1 2 4 177 358 2.8 45.3 72.1 222 4 156 462 3.5 46.0 57.3 222 4 257 544 3.5 111.7 118.8 222 42 13.4 2 37 21.2 2 32 21.9 2 270 50.9 2 297 79.2 2 372 54.4 2 179 Table 28 Summary of Clinical Chemistry Data Males Day 245 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 .35 2 10.9 .57 2 10.8 .64 2 6.6 .64 2 6.6 .21 2 7.0 1.13 2 154 3.5 2 160 .7 2 162 3.5 2 5.0 .00 2 5.2 .07 2 5.2 .28 2 117 .0 2 117 1.4 2 116 2.8 2 Covance 6329-223 3M T-6295.7 180 DOSE GLU mg/kg/day MG/DL Table 28 Summary of Clinical Chemistry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 58 14.1 2 18 3.5 2 1.0 .35 2 9.0 .64 2 4.6 .14 2 4.4 .49 2 .6 .35 2 9 131 1.4 52.3 22 57 5.7 2 70 25.5 2 0.15 MEAN 87 20 1.0 9.0 4.1 4.9 .4 11 150 71 72 S.D. 5.7 1.4 .14 .28 .14 .14 .14 1.4 17.7 1.4 27.6 N 22222222222 0.75 MEAN S.D. N 92 .7 2 22 .0 2 1.2 .07 2 9.4 .57 2 4.7 .42 2 4.7 .14 2 .2 15 149 95 64 .07 5.7 2.8 48.1 13.4 22222 181 Table 28 Summary of Clinical Chemistry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N MEAN S.D. N 0.75 MEAN S.D. N 36 9.2 2 30 9.2 2 25 4.2 2 116 59.4 2 66 7.1 2 40 1.4 2 182 30.4 2 188 105.4 2 236 17.7 2 58 20.5 2 80 4.2 2 98 33.2 2 2 168 329 .7 50.9 48.1 222 3 392 482 2.8 384.0 242.5 222 2 148 331 .7 27.6 76.4 222 10 14.8 2 34 17.7 2 66 66.5 2 242 27.6 2 346 157.7 2 250 54.4 2 182 Table 28 Summary of Clinical Chemistry Data Females Day 245 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 9.7 .14 2 9.8 .49 2 10.6 .57 2 4.6 .28 2 5.4 .28 2 5.4 .71 2 150 4.2 2 152 4.9 2 160 7.8 2 4.6 .21 2 5.4 .71 2 5.5 .99 2 114 4 2 118 2 2 120 6 2 Covance 6329-223 3M T-6295.7 183 DOSE GLU mg/kg/day MG/DL Table 29 Summary of Clinical Chemistry Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 67 18.4 2 74 2.8 2 70 9.2 2 16 3.5 2 19 1.4 2 18 3.5 2 1.2 .14 2 1.0 .14 2 1.2 .21 2 8.5 .42 2 8.8 .21 2 8.8 .07 2 4.7 .14 2 5.0 .21 2 4.8 .42 2 3.8 .28 2 3.8 .00 2 4.0 .35 2 .4 .42 2 .4 .14 2 .3 .14 2 2 130 .7 26.2 22 9 168 2.8 50.2 22 8 139 3.5 5.7 22 36 15.6 2 48 13.4 2 74 23.3 2 64 14.8 2 76 26.2 2 40 7.1 2 184 Table 29 Summary of Clinical Chemistry Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 28 12.7 2 26 6.4 2 38 3.5 2 35 5.7 2 39 4.2 2 54 21.2 2 842 409.4 2 850 105.4 2 689 186.7 2 124 90.5 2 146 70.0 2 164 7.8 2 7 176 318 4.2 35.4 71.4 222 4 141 444 2.8 22.6 43.1 222 4 230 .7 89.8 22 512 84.1 2 36 7.1 2 39 2.8 2 35 24.0 2 239 53.7 2 285 75.0 2 354 32.5 2 185 Table 29 Summary of Clinical Chemistry Data Males Day 274 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 .21 2 11.2 1.20 2 11.2 .57 2 6.0 1.13 2 6.4 .21 2 6.4 .92 2 154 4.9 2 159 7.1 2 160 3.5 2 5.8 .21 2 5.6 .35 2 5.6 .35 2 116 .7 2 118 6.4 2 114 2.1 2 Covance 6329-223 3M T-6295.7 186 DOSE GLU mg/kg/day MG/DL Table 29 Summary of Clinical Chemistry Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N MEAN S.D. N 0.75 MEAN S.D. N 56 15.6 2 74 4.9 2 92 3.5 2 20 4.9 2 21 2.8 2 23 4.2 2 .8 .00 2 .9 .14 2 1.0 .14 2 8.7 .85 2 8.9 .28 2 9.0 .35 2 4.4 .28 2 4.0 .00 2 4.4 .42 2 4.3 .57 2 4.9 .28 2 4.6 .07 2 .6 .57 2 .4 .21 2 .1 .00 2 8 129 2.1 58.0 22 5 144 .0 6.4 22 6 144 2.1 .7 22 48 7.8 2 59 11.3 2 70 31.8 2 62 26.2 2 52 22.6 2 56 4.2 2 187 Table 29 Summary of Clinical Chemistry Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 40 9.9 2 37 14.1 2 29 18.4 2 104 34.6 2 58 2.1 2 44 10.6 2 163 35.4 2 172 94.0 2 226 25.5 2 58 17.7 2 76 .7 2 87 29.7 2 3 301 1.4 189.5 22 9 1214 7.1 1557.8 22 5 142 1.4 31.8 22 309 26.9 2 468 256.0 2 316 113.8 2 9 12.7 2 74 33.9 2 32 2.1 2 225 9.9 2 340 177.5 2 236 83.4 2 188 Table 29 Summary of Clinical Chemistry Data Females Day 274 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 9.8 .78 2 9.5 .00 2 10.4 .00 2 4.4 .28 2 5.2 .07 2 5.2 .85 2 150 7.8 2 150 2.8 2 156 2.1 2 5.0 .92 2 4.8 .92 2 6.0 .07 2 110 4.9 2 111 5.7 2 119 2.8 2 Covance 6329-223 3M T-6295.7 189 DOSE GLU mg/kg/day MG/DL Table 30 Summary of Clinical Chemistry Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 71 4.2 2 62 23.3 2 66 14.8 2 18 2.1 2 28 2.8 2 18 .7 2 1.2 .07 2 1.4 .21 2 1.4 .35 2 8.6 .07 2 8.7 .42 2 8.6 .49 2 4.8 .14 2 5.1 .14 2 4.7 .42 2 3.8 .07 2 3.6 .28 2 3.8 .07 2 .4 .57 2 .7 .71 2 .4 .28 2 6 134 .7 34.6 22 7 163 1.4 65.1 22 8 136 2.1 .7 22 52 21.9 2 61 18.4 2 90 51.6 2 69 17 0 2 72 26 2 2 39 71 2 190 Table 30 Summary of Clinical Chemistry Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 38 5.7 2 53 9.9 2 61 21.2 2 38 6.4 2 68 7.1 2 76 23.3 2 772 386.8 2 882 159.1 2 708 191.6 2 124 105.4 2 140 68.6 2 157 1.4 2 4 966 487 1.4 149.2 35.4 222 6 570 1297 .0 77.1 454.0 222 2 1048 1.4 368.4 22 625 144.2 2 94 5.7 2 710 227.7 2 30 7.8 2 366 19.8 2 962 326.7 2 442 85.6 2 191 Table 30 Summary of Clinical Chemistry Data Males Day 322 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.4 .49 2 11.0 .92 2 10.6 .92 2 5.4 .57 2 5.8 .64 2 5.8 1.13 2 150 3.5 2 154 .0 2 154 4.9 2 5.0 .14 2 5.0 .07 2 5.4 .35 2 106 .7 2 106 2.8 2 108 .0 2 Covance 6329-223 3M T-6295.7 192 DOSE GLU mg/kg/day MG/DL Table 30 Summary of Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN 54 15 1 . 2 8.4 4.4 4.1 .5 10 118 42 58 S.D. 14.1 1.4 .21 .07 .07 .14 .57 4.9 41.7 8.5 23.3 N 22222222222 0.15 MEAN S.D. N 64 7.8 2 28 .7 2 1.3 .14 2 8.8 .78 2 3.9 .14 2 4.8 .64 2 .5 .00 2 8 148 3.5 9.2 22 86 23.3 2 60 19.8 2 0.75 MEAN S.D. N 85 1.4 2 18 9.2 2 1.5 .14 2 8.7 .64 2 4.3 .42 2 4.4 .21 2 .0 .07 2 6 129 2 . 1 14.1 22 74 9.2 2 60 .0 2 193 Table 30 Summary of Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 56 14.1 2 48 17.0 2 44 2.1 2 87 14.1 2 78 9.9 2 112 60.1 2 156 18.4 2 160 64.3 2 235 21.2 2 60 30.4 2 73 8.5 2 80 35.4 2 4 2.1 2 6 3.5 2 2 .7 2 1118 132.9 2 1058 644.2 2 1065 574.2 2 366 33.9 2 554 237.6 2 449 1.4 2 0 .0 2 73 14.1 2 64 43.1 2 268 12.0 2 406 166.9 2 338 1.4 2 194 Table 30 Summary of Clinical Chemistry Data Females Day 322 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 9.7 .14 2 9.8 .57 2 10.3 .00 2 4.7 .42 2 5.2 .49 2 4.2 .21 2 147 1.4 2 151 4.2 2 156 2.8 2 5.0 .21 2 5.2 .07 2 5.5 .42 2 104 4.9 2 108 1.4 2 110 1.4 2 Covance 6329-223 3M T-6295.7 195 DOSE GLU mg/kg/day MG/DL Table 31 Summary of Clinical Chemistry Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 72 2.1 2 74 2.1 2 70 9.2 2 20 4.9 2 26 3.5 2 18 1.4 2 1.3 .00 2 1.2 .07 2 1.2 .14 2 8.9 .00 2 8.6 .64 2 8.4 .14 2 5.2 .21 2 5.2 .35 2 4.8 .35 2 3.8 .21 2 3.4 .28 2 3.6 .21 2 .5 .28 2 .8 .42 2 .4 .21 2 6 .7 2 6 .7 2 4 2.1 2 126 30.4 2 166 55.9 2 119 4.2 2 40 7.8 2 48 21.9 2 51 21.2 2 61 14 1 2 74 27 6 2 38 49 2 196 Table 31 Summary of Clinical Chemistry Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 50 4.9 2 60 6.4 2 60 2.8 2 42 4.9 2 66 4.9 2 66 25.5 2 714 461.7 2 820 134.4 2 622 202.2 2 138 119.5 2 143 63.6 2 155 1.4 2 6 3.5 2 8 .7 2 4 2.8 2 2137 19.8 2 1495 356.4 2 1310 980.8 2 376 17.7 2 1294 489.3 2 516 142.1 2 38 .7 2 579 302.6 2 33 2.8 2 272 36 2 958 351 2 358 79 2 197 Table 31 Summary of Clinical Chemistry Data Males Day 364 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.6 .49 2 10.9 1.41 2 10.6 .49 2 4.7 .71 2 5.6 .14 2 4.9 .42 2 156 2.1 2 155 7.1 2 154 2.1 2 5.4 .14 2 5.4 .49 2 5.4 .64 2 111 .0 2 111 2.8 2 110 3.5 2 Covance 6329-223 3M T-6295.7 198 DOSE mg/kg/day GLU MG/DL Table 31 Summary of Clinical Chemistry Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 55 1.4 2 73 9.9 2 88 4.2 2 20 2.1 2 24 2.8 2 23 2.8 2 1.0 .14 2 1.0 .07 2 1.2 .07 2 9.0 .07 2 8.7 .57 2 8.7 .78 2 4.7 .00 2 3.9 .14 2 4.4 .64 2 4.2 .07 2 4.8 .42 2 4.2 .14 2 .8 .49 2 .8 .07 2 .4 .07 2 6 .7 2 6 .0 2 9 5.7 2 137 35.4 2 137 1.4 2 142 14.8 2 49 9.9 2 54 16.3 2 75 28.3 2 60 27.6 2 54 24.7 2 60 7.8 2 199 Table 31 Summary of Clinical Chemistry Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 86 34.6 2 50 17.7 2 56 15.6 2 202 135.1 2 78 24.0 2 80 3.5 2 162 7.1 2 148 55.9 2 228 21.2 2 77 45.3 2 79 1.4 2 86 43.1 2 6 1.4 2 12 4.9 2 4 1.4 2 2408 806.1 2 871 195.2 2 1797 786.3 2 398 85.6 2 467 230.5 2 479 67.9 2 16 23.3 2 47 7.1 2 47 .0 2 300 50.2 2 345 161.2 2 370 58.7 2 200 Table 31 Summary of Clinical Chemistry Data Females Day 364 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 9.9 .28 2 9.4 .64 2 10.2 .35 2 4.9 .99 2 4.8 .07 2 4.4 .21 2 148 4.9 2 148 3.5 2 155 2.8 2 5.0 .92 2 5.4 .71 2 5.4 .21 2 106 4.2 2 110 2.1 2 112 1.4 2 Covance 6329-223 3M T-6295.7 201 DOSE GLU mg/kg/day MG/DL Table 32 Summary of Clinical Chemistry Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 74 8.5 2 91 4.2 2 70 7.8 2 14 2.8 2 16 1.4 2 14 .7 2 1.2 .00 2 1.2 .07 2 1.2 .21 2 8.7 .28 2 9.1 .28 2 8.9 .57 2 5.0 .21 2 5.4 .07 2 5.0 .64 2 3.6 .07 2 3.6 .35 2 4.0 .07 2 .6 .35 2 .4 .21 2 .6 .35 2 3 .0 2 6 .7 2 4 .7 2 132 14.1 2 178 54.4 2 118 5.7 2 32 .7 2 41 2.8 2 59 31.1 2 58 35 2 80 36 1 2 35 12 7 2 202 Table 32 Summary of Clinical Chemistry Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 24 7.1 2 25 5.7 2 34 4.9 2 24 3.5 2 46 .7 2 41 12.7 2 620 320.3 2 871 141.4 2 418 55.9 2 124 91.9 2 150 68.6 2 138 13.4 2 6 5.7 2 2 .7 2 0 .7 2 102 34.6 2 141 31.1 2 202 32.5 2 298 30.4 2 450 52.3 2 422 82.0 2 16 7.1 2 16 2.1 2 16 4.9 2 233 18.4 2 294 83.4 2 294 44.5 2 203 Table 32 Summary of Clinical Chemistry Data Males Day 456 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.2 .21 2 11.8 1.20 2 10.6 .78 2 6.0 .49 2 6.9 .42 2 5.3 1.98 2 153 4.2 2 164 4.2 2 155 4.2 2 5.4 .42 2 6.0 .49 2 5.0 .57 2 111 2.8 2 116 3.5 2 111 2.8 2 Covance 6329-223 3M T-6295.7 204 DOSE mg/kg/day GLU MG/DL Table 32 Summary of Clinical Chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 64 21.9 2 78 .7 2 100 2.1 2 17 .0 2 17 1.4 2 19 2.8 2 1.0 .07 2 1.0 .07 2 1.0 .07 2 8.5 .28 2 8.7 .42 2 8.7 .64 2 4.6 .00 2 4.1 .00 2 4.5 .57 2 3.9 .28 2 4.6 .42 2 4.2 .07 2 .6 .49 2 .6 .07 2 .2 .07 2 6 2.1 2 5 1.4 2 4 1.4 2 120 30.4 2 144 .0 2 138 1.4 2 56 5.7 2 71 17.0 2 78 50.9 2 50 23 3 2 47 15 6 2 64 12 0 2 205 Table 32 Summary of Clinical Chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 43 18.4 2 32 10.6 2 25 .0 2 134 69.3 2 50 22.6 2 54 14.8 2 156 24.7 2 140 65.1 2 232 22.6 2 72 33.2 2 78 3.5 2 94 43.1 2 4 222 268 2 . 1 31.1 34.6 222 7 183 339 4.2 100.4 137.2 222 2 124 296 2 . 1 14.1 89.8 222 10 2.1 2 13 2.8 2 18 7.1 2 204 17.0 2 250 87.0 2 230 66.5 2 206 Table 32 Summary of Clinical Chemistry Data Females Day 456 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 9.9 .42 2 9.8 .42 2 10.4 .14 2 5.2 .35 2 5.2 .21 2 5.4 .35 2 148 5.7 2 152 1.4 2 154 .7 2 5.0 .14 2 5.6 .35 2 6.2 .85 2 108 3.5 2 112 .7 2 116 2.8 2 Covance 6329-223 3M T-6295.7 207 DOSE GLU mg/kg/day MG/DL Table 33 Summary of Clinical Chemistry Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 82 4.9 2 79 2.8 2 79 5.7 2 16 2.8 2 19 .0 2 16 .0 2 1.2 .07 2 1.2 .07 2 1.4 .00 2 8.8 .14 2 8.8 .28 2 9.4 .14 2 4.7 .14 2 5.1 .28 2 5.1 .14 2 4.1 .00 2 3.7 .00 2 4.3 .28 2 .4 .21 2 .4 .21 2 .6 .35 2 6 .7 2 4 1.4 2 7 4.2 2 134 21.9 2 166 48.1 2 138 9.2 2 31 1.4 2 36 6.4 2 44 10.6 2 70 99 2 92 31 8 2 57 14 1 2 208 Table 33 Summary of Clinical Chemistry Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 24 6.4 2 30 .7 2 36 12.7 2 25 7.1 2 34 2.1 2 40 3.5 2 505 277.2 2 754 130.1 2 404 88.4 2 116 94 2 136 60 2 148 1 2 10 12.7 2 3 2.8 2 0 .0 2 111 46.7 2 171 58.0 2 165 .0 2 262 4.2 2 402 62.9 2 440 111.0 2 14 4.9 2 12 .7 2 16 7.8 2 202 1.4 2 264 81.3 2 297 52.3 2 209 Table 33 Summary of Clinical Chemistry Data Males Day 546 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.6 .21 2 11.2 .28 2 11.9 .14 2 6.6 .07 2 7.0 .92 2 5.8 .57 2 160 3.5 2 166 3.5 2 172 3.5 2 6.0 .57 2 6.4 .78 2 6.1 .14 2 116 6 2 120 3 2 118 3 2 Covance 6329-223 3M T-6295.7 210 DOSE mg/kg/day GLU MG/DL Table 33 Summary of Clinical Chemistry Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL HDL MG/DL 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 60 9.9 2 72 2.1 2 96 4.9 2 16 .7 2 18 1.4 2 19 .0 2 1.0 .07 2 1.0 .21 2 1.2 .00 2 8.5 .42 2 8.4 .21 2 8.4 .78 2 4.4 .00 2 3.8 .21 2 4.3 .42 2 4.1 .42 2 4.6 .00 2 4.2 .35 2 .6 .35 2 .6 .07 2 .3 .00 2 6 .7 2 5 .0 2 5 1.4 2 124 39.6 2 138 12.7 2 146 1.4 2 53 2.8 2 60 19.1 2 76 50.9 2 64 27 6 2 62 34 6 2 74 78 2 211 Table 33 Summary of Clinical Chemistry Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 42 16.3 2 26 .7 2 28 12.0 2 120 100.4 2 34 4.2 2 59 28.3 2 151 28.3 2 146 70.0 2 213 38.2 2 69 33.9 2 79 4.2 2 89 39.6 2 0 .0 2 2 .7 2 2 2.1 2 154 87.0 2 94 20.5 2 130 47.4 2 280 50.2 2 353 142.8 2 311 86.3 2 12 .7 2 11 4.2 2 15 4.2 2 212 28.3 2 261 93.3 2 240 64.3 2 212 Table 33 Summary of Clinical Chemistry Data Females Day 546 26-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 S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 10.1 .00 2 10.0 .28 2 10.5 .28 2 5.4 .28 2 5.2 .35 2 5.6 .35 2 151 1.4 2 156 1.4 2 162 4.2 2 5.2 .14 2 5.8 .49 2 6.2 .78 2 110 2.1 2 114 3.5 2 120 6.4 2 Covance 6329-223 3M T-6295.7 213 Table 34 Summary of Clinical Urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 41.5 17.76 6 52.5 10.15 4 97.8 71.41 6 83.5 46.63 6 1.026 .0050 6 1.021 .0021 4 1.019 .0078 6 1.018 .0066 6 7.3 .75 6 7.4 .48 4 7.1 .20 6 7.2 .26 6 Covance 6329-223 3M T-6295.7 214 Table 34 Summary of Clinical Urinalysis Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 90.7 75.84 6 92.5 88.38 4 71.8 33.80 6 88.0 78.91 6 1.018 .0060 6 1.019 .0082 4 1.021 .0052 6 1.020 .0068 6 7.3 .41 6 7.1 .25 4 7.8 .42 6 7.3 .41 6 Covance 6329-223 3M T-6295.7 215 Table 35 Summary of Clinical Urinalysis Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 50.2 13.75 6 72.5 29.73 4 94.3 105.16 6 79.0 42.12 6 1.018 .0071 6 1.021 .0048 4 1.019 .0092 6 1.018 .0082 6 7.5 .45 6 7.5 .41 4 7.2 .27 6 7.3 .75 6 Covance 6329-223 3M T-6295.7 216 Table 35 Summary of Clinical Urinalysis Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 118.5 218.53 6 86.8 56.91 4 83.7 53.05 6 100.2 155.27 6 1.014 .0103 6 1.018 .0056 4 1.017 .0076 6 1.022 .0094 6 8.0 .32 6 7.8 .29 4 7.5 .32 6 7.8 .61 6 Covance 6329-223 3M T-6295.7 217 Table 36 Summary of Clinical Urinalysis Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 77.5 50.66 6 62.2 34.86 4 94.5 59.43 6 68.0 26.39 6 1.018 .0054 6 1.018 .0076 4 1.015 .0095 6 1.017 .0051 6 8.0 .32 6 8.0 .41 4 7.8 .42 6 7.9 .38 6 Covance 6329-223 3M T-6295.7 218 Table 36 Summary of Clinical Urinalysis Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 74.3 61.32 6 53.5 32.58 4 62.3 28.86 6 81.0 51.27 6 1.019 .0076 6 1.020 .0056 4 1.020 .0061 6 1.017 .0091 6 8.2 .26 6 7.6 .48 4 7.8 .26 6 7.6 * .38 6 Covance 6329-223 3M T-6295.7 219 Table 37 Summary of Clinical Urinalysis Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 47.5 7.31 6 65.8 40.43 4 101.2 73.16 6 54.0 19.47 6 1.024 .0046 6 1.018 .0062 4 1.014 * .0061 6 1.020 .0066 6 7.5 .77 6 7.8 .29 4 7.4 .49 6 7.2 .88 6 Covance 6329-223 3M T-6295.7 220 Table 37 Summary of Clinical Urinalysis Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 93.3 68.15 6 64.8 30.02 4 63.2 22.56 6 120.5 125.14 6 1.015 .0053 6 1.018 .0034 4 1.018 .0073 6 1.017 .0096 6 8.0 .00 6 7.4 .48 4 7.5 .63 6 7.8 .42 6 Covance 6329-223 3M T-6295.7 221 Table 38 Summary of Clinical Urinalysis Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 131.3 110.42 6 55.0 21.32 4 137.8 114.54 6 180.0 136.48 6 1.013 .0072 6 1.020 .0052 4 1.011 .0062 6 1.011 .0082 6 7.1 .49 6 7.4 .48 4 7.1 .20 6 7.1 .58 6 Covance 6329-223 3M T-6295.7 222 Table 38 Summary of Clinical Urinalysis Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 85.2 53.91 6 60.5 36.93 4 40.7 11.15 6 89.0 93.46 6 1.016 .0084 6 1.016 .0029 4 1.022 .0040 6 1.017 .0085 6 7.5 .32 6 7.0 .41 4 7.1 .20 6 7.1 .66 6 Covance 6329-223 3M T-6295.7 223 Table 39 Summary of Clinical Urinalysis Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 116.2 79.33 6 75.5 26.20 4 122.3 125.43 6 121.0 108.83 4 1.014 .0072 6 1.017 .0022 4 1.013 .0053 6 1.013 .0059 4 7.9 .20 6 7.9 .25 4 7.5 1.00 6 7.2 .65 4 Covance 6329-223 3M T-6295.7 224 Table 39 Summary of Clinical Urinalysis Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 85.7 40.59 6 76.2 31.48 4 73.3 25.33 6 131.8 156.54 6 1.016 .0050 6 1.016 .0054 4 1.017 .0055 6 1.014 .0058 6 8.1 .20 6 7.6 .48 4 7.9 .20 6 7.8 .26 6 Covance 6329-223 3M T-6295.7 225 Table 40 Summary of Clinical Urinalysis Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 179.5 24.75 2 239.5 79.90 2 87.5 36.06 2 1.010 .0000 2 1.007 .0028 2 1.013 .0028 2 7.2 .35 2 7.5 .00 2 7.0 .71 2 Covance 6329-223 3M T-6295.7 226 Table 40 Summary of Clinical Urinalysis Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 143.0 77.78 2 121.0 80.61 2 89.0 36.77 2 1.014 .0078 2 1.015 .0000 2 1.015 .0000 2 7.8 .35 2 7.2 .35 2 7.5 .71 2 Covance 6329-223 3M T-6295.7 227 Table 41 Summary of Clinical Urinalysis Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 195.5 9.19 2 196. 0 132. 94 2 83.0 29.70 2 1.009 .0014 2 1.010 .0064 2 1.017 .0042 2 7.8 .35 2 7.5 .00 2 7.8 .35 2 Covance 6329-223 3M T-6295.7 228 Table 41 Summary of Clinical Urinalysis Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 117.0 100.41 2 131.5 62.93 2 91.5 48.79 2 1.018 .0113 2 1.016 .0021 2 1.016 .0035 2 8.0 .00 2 7.2 .35 2 7.8 .35 2 Covance 6329-223 3M T-6295.7 229 Table 42 Summary of Clinical Urinalysis Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 284.0 50.91 2 234.0 169.71 2 67.5 50.20 2 1.004 .0007 2 1.007 .0042 2 1.018 .0106 2 6.8 .35 2 7.2 .35 2 7.0 .71 2 Covance 6329-223 3M T-6295.7 230 Table 42 Summary of Clinical Urinalysis Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 141.5 33.23 2 63.5 37.48 2 64.5 58.69 2 1.006 .0014 2 1.020 .0050 2 1.010 .0007 2 7.8 .35 2 7.5 .00 2 7.2 1.06 2 Covance 6329-223 3M T-6295.7 231 Table 43 Summary of Clinical Urinalysis Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 296.0 254.56 2 99.5 94.05 2 47.5 4.95 2 1.008 .0092 2 1.016 .0099 2 1.020 .0092 2 6.8 .35 2 6.5 .71 2 6.0 .00 2 Covance 6329-223 3M T-6295.7 232 Table 43 Summary of Clinical Urinalysis Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 220.5 188.80 2 59. 0 24. 04 2 92.0 29.70 2 1.006 .0050 2 1.018 .0042 2 1.014 .0035 2 8.0 .00 2 6.5 .71 2 6.8 .35 2 Covance 6329-223 3M T-6295.7 233 Table 44 Summary of Clinical Urinalysis Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 206.5 81.32 2 74.5 10.61 2 90.0 14.14 2 1.017 .0028 2 1.018 .0000 2 1.018 .0050 2 7.8 .35 2 7.5 .71 2 6.8 1.06 2 Covance 6329-223 3M T-6295.7 234 Table 44 Summary of Clinical Urinalysis Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 158.0 11.31 2 68.5 13.44 2 76.0 46.67 2 1.011 .0000 2 1.021 .0014 2 1.018 .0007 2 8.0 .00 2 7.0 .00 2 7.0 .71 2 Covance 6329-223 3M T-6295.7 235 Table 45 Summary of Clinical Urinalysis Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 185.0 120.21 2 182. 0 147. 08 2 84.0 8.49 2 1.010 .0028 2 1.008 .0050 2 1.012 .0050 2 8.0 .00 2 8.0 .00 2 8.0 .00 2 Covance 6329-223 3M T-6295.7 236 Table 45 Summary of Clinical Urinalysis Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 214. 0 164. 05 2 145.0 74.95 2 118.0 82.02 2 1.009 .0057 2 1.011 .0042 2 1.005 .0042 2 8.0 .00 2 7.8 .35 2 8.0 .00 2 Covance 6329-223 3M T-6295.7 237 Table 46 Summary of Clinical Urinalysis Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 430. 0 70. 71 2 300.0 148.49 2 222.5 173.24 2 1.005 .0000 2 1.006 .0028 2 1.010 .0071 2 8.0 .00 2 7.8 .35 2 8.0 .00 2 Covance 6329-223 3M T-6295.7 238 Table 46 Summary of Clinical Urinalysis Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS DOSE mg/kg/day U VOL ML SP GR U PH 0 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 132.5 38.89 2 67.5 24.75 2 99.0 80.61 2 1.011 .0057 2 1.018 .0014 2 1.014 .0050 2 8.0 .00 2 8.0 .00 2 8.0 .00 2 Covance 6329-223 3M T-6295.7 239 Table 47 Summary of Palmitoyl CoA Oxidase Determinations Terminal Sacrifice Males 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 5 1.5 4 5 1.0 4 6 .6 4 7 1.4 2 Covance 6329-223 3M T-6295.7 240 Table 47 Summary of Palmitoyl CoA Oxidase Determinations Terminal Sacrifice Females 26-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 S.D. N 0.03 MEAN S.D. N 0.15 MEAN S.D. N 0.75 MEAN S.D. N 4 .8 4 4 1.3 4 6 1.0 4 6* .8 4 Covance 6329-223 3M T-6295.7 241 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 0.2858 0.0195 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 0.3105 0.0367 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 0.2692 0.0298 LEFT ADRENAL ORGAN-TOBODY WT (%) 4 0.0083 0.0012 ORGAN-TOBRAIN WT RATIO 4 0 .0045 0 .0 0 0 2 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0087 0.0015 4 0 .0051 0 .0008 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0084 0.0006 4 0 .0043 0 .0003 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) 4 0.2933 0.0650 4 0.3815 0.0508 4 0.3400 0.0589 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 0.0103 0.0016 4 0 .0052 0 .0014 4 0.0132 0.0033 4 0 .0063 0 .0 0 1 0 4 0.0122 0.0012 4 0 .0058 0 .0 0 1 0 242 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) LEFT ADRENAL ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 0.3665 0.1237 2 0 .0 1 2 0 * 0.0003 2 0.0055 0.0012 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 0.3468 0.0265 4 0.0134 0.0029 4 0.0061 0.0004 243 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 0.2093 0.0503 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 0.2240 0.0243 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 0.2135 0.0484 RIGHT ADRENAL ORGAN-TOBODY WT (%) 4 0.0059 0.0011 ORGAN-TOBRAIN WT RATIO 4 0 .0033 0 .0008 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0063 0.0012 4 0 .0036 0 .0005 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0067 0.0014 4 0 .0033 0 .0006 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) 4 0.2178 0.0772 4 0.2768 0.0356 4 0.2425 0.0377 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 0.0076 0.0021 4 0 .0039 0 .0016 4 0.0095 0.0020 4 0 .0046 0 .0005 4 0.0088 0.0008 4 0 .0042 0 .0006 244 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) RIGHT ADRENAL ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 0.2725 0.0686 2 0.0090 0.0011 2 0.0041 0.0006 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 0.2535 0.0306 4 0.0098 0.0025 4 0.0044 0.0004 245 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 5 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) ORGAN WEIGHT (g) 4 3540.0 765.9 4 63.1425 1.1363 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 61.7943 5.5692 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 63.3520 5.3720 BRAIN ORGAN-TOBODY WT (%) 4 1.8330 0.3051 ORGAN-TOBRAIN WT RATIO 4 1.0000 0.0000 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 1.7415 0.3701 4 1.0000 0.0000 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 1.9873 0.1406 4 1.0000 0.0000 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) ORGAN WEIGHT (g) 4 2821.3 304.9 4 56.6408 4.1710 4 2988.8 723.4 4 60.6083 2.6726 4 2768.8 335.9 4 58.3910 3.2163 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 2.0307 0.3056 4 1.0000 0.0000 4 2.1053 0.4471 4 1.0000 0.0000 4 2.1321 0.2735 4 1.0000 0.0000 246 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 6 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) BRAIN ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TO BRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 66.2635 7.8154 2 2.2566 0.5678 2 1.0000 0.0000 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 57.0957 2.2179 4 2.1883 0.3459 4 1.0000 0.0000 247 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 7 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP: MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 1.1407 0.5031 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 1.4208 0.9897 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 0.9760 0.0910 LF EPIDIDYMIS ORGAN-TOBODY WT (%) 4 0.0314 0.0076 ORGAN-TOBRAIN WT RATIO 4 0 .0180 0 .0076 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0371 0.0196 4 0 .0243 0 .0197 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0306 0.0027 4 0 .0155 0 .0025 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 248 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 8 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) LF EPIDIDYMIS ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 1.3095 1.0812 2 0.0387 0.0210 2 0.0189 0.0141 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 249 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 9 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP: MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 1.2160 0.4066 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 1.3563 0.9663 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 1.0213 0.0786 RT EPIDIDYMIS ORGAN-TOBODY WT (%) 4 0.0340 0.0063 ORGAN-TOBRAIN WT RATIO 4 0 .0192 0 .0061 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0353 0.0191 4 0 .0232 0 .0192 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0322 0.0039 4 0 .0163 0 .0025 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 250 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 10 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) RT EPIDIDYMIS ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 1.3805 1.3371 2 0.0396 0.0290 2 0.0198 0.0178 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 251 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 11 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 6.2305 0.8729 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 6.6015 0.4812 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 5.8875 0.6683 LF KIDNEY ORGAN-TOBODY WT (%) 4 0.1780 0.0147 ORGAN-TOBRAIN WT RATIO 4 0.0985 0.0120 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.1838 0.0231 4 0.1078 0.0163 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.1844 0.0157 4 0.0936 0.0150 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) 4 5.5023 0.9665 4 5.8693 0.9019 4 5.5955 0.4375 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 0.1943 0.0191 4 0.0978 0.0214 4 0.1993 0.0191 4 0 .0972 0 .0166 4 0.2033 0.0174 4 0 .0960 0 .0090 1 ^1 1 1 1 1 OJ 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 252 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 12 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) LF KIDNEY ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 5.5310 1.3916 2 0.1837 0.0217 2 0.0828 0.0112 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 5.7638 0.9586 4 0.2190 0.0364 4 0.1007 0.0138 253 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 13 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 6.0052 0.9353 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 6.7495 0.6929 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 5.7358 0.6730 RT KIDNEY ORGAN-TOBODY WT (%) 4 0.1712 0.0127 ORGAN-TOBRAIN WT RATIO 4 0.0949 0.0130 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.1875 0.0228 4 0.1104 0.0206 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.1795 0.0140 4 0.0910 0.0131 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) 4 5.2995 0.7814 4 5.7718 0.8467 4 5.4028 0.4663 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 0.1876 0.0168 4 0.0941 0.0173 4 0.1966 0.0260 4 0 .0956 0 .0163 4 0.1965 0.0210 4 0 .0926 0 .0067 1 ^1 1 1 1 1 OJ 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 254 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 14 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) RT KIDNEY ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 5.4045 1.2594 2 0.1801 0.0247 2 0.0810 0.0095 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 5.7878 1.1793 4 0.2191 0.0375 4 0.1011 0.0181 255 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 15 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV: TERMINAL BODY WT (g) ORGAN WEIGHT (g) 4 3540.0 765.9 4 54.9200 8.1496 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 62.0868 5.2757 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 57.3325 5.5102 LIVER ORGAN-TOBODY WT (%) 4 1.5733 0.2144 ORGAN-TOBRAIN WT RATIO 4 0.8689 0.1203 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 1.7413 0.3311 4 1.0090 0.0994 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 1.7955 0.0901 4 0.9059 0.0581 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) ORGAN WEIGHT (g) 4 2821.3 304.9 4 51.0925 9.4330 4 2988.8 723.4 4 56.8278 12.5811 4 2768.8 335.9 4 57.0393 3.1240 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 1.8015 0.1518 4 0.9104 0.2199 4 1.9074 0.0398 4 0.9392 0.2089 4 2.0747 0.1801 4 0.9783 0.0629 256 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 16 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) LIVER ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 85.2815 38.3782 2 2.7247* 0.2548 2 1.2616 0.4304 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 75.2997* 13.3835 4 2.8466* 0.3447 4 1.3189* 0.2262 257 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 17 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 LF OVARY ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: F2 NUMBER IN GROUP: MEAN: STANDARD DEV: F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) 4 0.1688 0.0679 4 0.1723 0.0729 4 0.1873 0.0847 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 0.0059 0.0022 4 0 .0030 0 .0013 4 0.0056 0.0011 4 0 .0028 0 .0 0 1 2 4 0.0067 0.0028 4 0 .0032 0 .0015 258 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 18 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) LF OVARY ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 0.1590 0.0563 4 0.0063 0.0031 4 0.0028 0.0009 259 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 19 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 RT OVARY ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: F2 NUMBER IN GROUP: MEAN: STANDARD DEV: F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) 4 0.1423 0.0491 4 0.1788 0.0453 4 0.1367 0.0353 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 0.0050 0.0012 4 0 .0025 0 .0 0 1 0 4 0.0061 0.0014 4 0 .0029 0 .0007 4 0.0049 0.0010 4 0 .0024 0 .0007 260 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 20 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) RT OVARY ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 0.1498 0.0169 4 0.0058 0.0015 4 0.0026 0.0003 261 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 21 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 6.9795 3.7391 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 7.8848 7.4545 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 5.0977 0.6925 LF TESTIS ORGAN-TOBODY WT (%) 4 0.1918 0.0803 ORGAN-TOBRAIN WT RATIO 4 0.1100 0.0572 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.2009 0.1587 4 0.1369 0.1434 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.1600 0.0215 4 0.0814 0.0173 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 262 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 22 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) LF TESTIS ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 7.0340 7.9238 2 0.1946 0.1866 2 0.0998 0.1078 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 263 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 23 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 6.7453 3.3813 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 8.1230 7.2175 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 5.0045 0.7091 RT TESTIS ORGAN-TOBODY WT (%) 4 0.1868 0.0764 ORGAN-TOBRAIN WT RATIO 4 0.1064 0.0518 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.2089 0.1504 4 0.1403 0.1403 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.1568 0.0194 4 0.0798 0.0163 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 264 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 24 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) RT TESTIS ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 6.9155 7.8977 2 0.1906 0.1872 2 0.0980 0.1076 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 265 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 25 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 5.4570 0.8021 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 4.8133 1.3674 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 4.3790 1.1403 PANCREAS ORGAN-TOBODY WT (%) 4 0.1576 0.0319 ORGAN-TOBRAIN WT RATIO 4 0 .0863 0 .0119 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.1309 0.0234 4 0 .0799 0 .0298 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.1365 0.0294 4 0 .0687 0 .0138 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 4.4270 0.4797 4 0.1571 0.0097 4 0 .0787 0 .0125 4 5.9108* 1.0351 4 0.2030 0.0437 4 0 .0982 0 .0216 4 4.6248 0.4099 4 0.1678 0.0126 4 0 .0792 0 .0059 266 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 26 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) PANCREAS ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 4.1355 1.5450 2 0.1341 0.0014 2 0.0615 0.0161 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 4.3725 0.4273 4 0.1659 0.0119 4 0.0768 0.0089 267 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 27 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 0.1675 0.0479 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 0.2750 0.1374 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 0.2075 0.0792 LF THYROID/PARA ORGAN-TOBODY WT (%) 4 0.0047 0.0004 ORGAN-TOBRAIN WT RATIO 4 0 .0026 0 .0007 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0074 0.0028 4 0 .0046 0 .0027 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0064 0.0022 4 0 .0032 0 .0 0 1 1 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) 4 0.2567 0.1415 4 0.2138 0.0751 4 0.1542 0.0382 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 0.0088 0.0037 4 0 .0047 0 .0029 4 0.0071 0.0013 4 0 .0035 0 .0 0 1 2 4 0.0057 0.0018 4 0 .0027 0 .0007 268 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 28 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) LF THYROID/PARA ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 0.2020 0.1174 2 0.0063 0.0015 2 0.0030 0.0014 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 0.1872 0.0463 4 0.0071 0.0017 4 0.0033 0.0008 269 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 29 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M1 NUMBER IN GROUP MEAN: STANDARD DEV TERMINAL BODY WT (g) 4 3540.0 765.9 ORGAN WEIGHT (g) 4 0.1690 0.0711 M2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3631.3 524.0 4 0.2632 0.1614 M3 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 3190.0 199.8 4 0.2575 0.1150 RT THYROID/PARA ORGAN-TOBODY WT (%) 4 0.0046 0.0009 ORGAN-TOBRAIN WT RATIO 4 0 .0027 0 .0 0 1 1 SEX DOSE GROUP F1 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0070 0.0035 4 0 .0045 0 .0031 F2 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 0.0080 0.0032 4 0 .0040 0 .0016 F3 NUMBER IN GROUP: MEAN: STANDARD DEV: TERMINAL BODY WT (g) 4 2821.3 304.9 4 2988.8 723.4 4 2768.8 335.9 ORGAN WEIGHT (g) 4 0.2455 0.1300 4 0.2350 0.0815 4 0.1332 0.0279 ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO 4 0.0084 0.0034 4 0 .0044 0 .0027 4 0.0078 0.0016 4 0 .0039 0 .0013 4 0.0048 0.0007 4 0 .0023 0 .0005 270 TABLE 48 Summary of Organ Weight Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 30 TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;SUBSET=ALL SEX DOSE GROUP M4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) RT THYROID/PARA ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO SEX DOSE GROUP F4 TERMINAL BODY WT (g) ORGAN WEIGHT (g) ORGAN-TOBODY WT (%) ORGAN-TOBRAIN WT RATIO NUMBER IN GROUP: MEAN: STANDARD DEV: 2 3077.5 1120.8 2 0.2360 0.1556 2 0.0072 0.0024 2 0.0034 0.0019 NUMBER IN GROUP: MEAN: STANDARD DEV: 4 2653.8 403.1 4 0.1945 0.0633 4 0.0073 0.0019 4 0.0034 0.0011 271 TABLE 49 Incidence of Macroscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 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- -4- -1 - -2 - -3- -4- ORGAN AND KEYWORD(S) OR PHRASE -- -- NUMBER: 4 4 4 2 4 4 4 4 -=- -=- -=- -=- -=- -=- -=- -=- ** TOP OF LIST ** GENERAL COMMENT (GC) ..................... ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 0 0 0 0 0 0 0 0 BONE MARROW SMEAR TAKEN EYES - DAVIDSONS NO MACROSCOPIC LESIONS ANIMAL OBESE 4442 4444 4442 4444 2 2 30 1 0 1 0 000001 00 LUNG (LU) ................................. ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 3 3 3 2 2 1 1 0 ADHESION(S) RED FOCUS(I)/AREA(S) DARK FOCUS(I)/AREA(S) LIGHT FOCUS(I)/AREA(S) 0 1 1 0 2 31 0 1 000 0 012 000002 12 00000001 LIVER (LI) ................................ ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 4 4 4 0 3 3 4 3 MOTTLED ADHESION(S) LIGHT FOCUS(I)/AREA(S) 0002 0001 000001 00 00001 000 SPLEEN (SP) ............................... ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 3 3 4 2 4 4 3 4 LARGE ** CONTINUED ON NEXT PAGE ** 11000000 272 TABLE 49 Incidence of Macroscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 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- -4- -1 - -2 - -3- -4- ORGAN AND KEYWORD(S) OR PHRASE -- -- NUMBER: 4 4 4 2 4 4 4 4 -=- -=- -=- -=- -=- -=- -=- -=- ** FROM PREVIOUS PAGE ** SPLEEN (SP) ............................... ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 3 3 4 2 4 4 3 4 LIGHT FOCUS(I)/AREA(S) 0000001 0 LN, MESENTERIC (MS) ...................... ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 4 4 4 1 4 4 4 4 DIFFUSELY RED 0001 0 0 0 0 ADRENAL, CORTEX (AC) ..................... ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 4 4 4 0 4 4 4 2 DIFFUSELY DARK 0002 0002 STOMACH, GL (ST) ......................... ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 4 4 4 2 3 4 4 4 RED FOCUS(I)/AREA(S) 00001 000 CECUM (CE) ................................ ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 4 4 4 2 4 4 2 3 RED FOCUS(I)/AREA(S) DARK FOCUS(I)/AREA(S) 0000002 0 00000001 273 TABLE 49 Incidence of Macroscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 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- -4- -1 - -2 - -3- -4- ORGAN AND KEYWORD(S) OR PHRASE -- NUMBER: 4 4 4 2 4 4 4 4 ------------------------------ -=- -=- -=- -=- -=- -=- -=- -=- COLON (CO) ................................ ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 4 4 4 2 4 4 4 3 DARK FOCUS(I)/AREA(S) 00000001 SKIN (SK) ................................. ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 3 4 4 2 4 4 4 2 ABRASION(S)/ULCERATION(S) ALOPECIA-DIFFUSE ALOPECIA-FOCAL 10000000 00000001 00000001 TESTIS (TE) ............................... ............ NUMBER EXAMINED: 4 4 4 2 0 0 0 0 NOT REMARKABLE: 4 3 4 2 0 0 0 0 LARGE 01 00 0 0 0 0 ADIPOSE TISSUE (AT) ...................... ............ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 4 4 3 2 4 4 4 3 RAISED FOCUS(I)/AREA(S) ** END OF LIST ** 001 0 0 0 01 274 TABLE 50 Incidence of Macroscopic Observations Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 TABLE INCLUDES: SEX=ALL;GROUP=4;WEEKS=ALL DEATH=U;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: -4- -4- ORGAN AND KEYWORD(S) OR PHRASE NUMBER: 2 2 ** TOP OF LIST ** GENERAL COMMENT (GC) ..................... ............ NUMBER EXAMINED: NOT REMARKABLE: 2 1 2 1 NO MACROSCOPIC LESIONS 11 LUNG (LU) ................................. ............ NUMBER EXAMINED: NOT REMARKABLE: 2 1 2 2 ADHESION(S) 10 LIVER (LI) ................................ ............ NUMBER EXAMINED: NOT REMARKABLE: 2 2 2 1 ADHESION(S) 01 CAVITY, THORACIC (TA) .................... ............ NUMBER EXAMINED: NOT REMARKABLE: 2 1 2 2 NODULE(S) ** END OF LIST ** 10 275 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 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- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION -- NUMBER: 4 4 4 2 4 4 4 4 -- -=- -=- -=- -=- -=- -=- -=- -=- ** TOP OF LIST ** BONE, FEMUR (FE) ...................................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 0 0 0 0 3 0 0 3 --GROWTH PLATE OPEN 40 02 1 0 01 MARROW, FEMUR (FM) .................................... NUMBER EXAMINED: 1 0 0 0 2 0 0 1 NOT REMARKABLE: 1 0 0 0 2 0 0 1 MARROW, STERNUM (SE) .................................. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 3 0 0 4 --HYPOCELLULAR, MARROW 00001 000 BONE, STERNUM (SB) .................................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 EYE (EY) ............................................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 BRAIN (BR) ............................................. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 2 0 0 0 1 0 0 1 --INFILTRATE, LYMPHOHISTIOCYTIC, PERIVASCULAR --INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR --INFLAMMATION, LYMPHOHISTIOCYTIC 0001 0 0 0 0 2 0 02 30 02 00000001 276 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 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- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION -- NUMBER: 4 4 4 2 4 4 4 4 -=- -=- -=- -=- -=- -=- -=- -=- KIDNEY (KD) ............................................ NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 2 0 0 1 2 0 0 2 --INFILTRATE, LYMPHOHISTIOCYTIC --GLOMERULOSCLEROSIS --MINERALIZATION, CORTEX --MINERALIZATION, MEDULLA 2 0011000 1 0001 000 0001 0 0 0 0 0 0 0 0 0 0 02 LUNG (LU) .............................................. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 0 0 0 2 2 0 0 2 --HYPERPLASIA, LYMPHOCYTIC, PERIBRONCHIOLAR/PERIVASCULAR --FIBROSIS, PLEURAL/SUBPLEURAL --FIBROSIS, INTERSTITIAL --INFILTRATE, MACROPHAGE, ALVEOLAR --HEMORRHAGE 40 0 01 0 01 00002 000 00001 000 00000001 00000001 HEART (HT) ............................................. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 LIVER (LI) ..... --INFILTRATE, LYMPHOHISTIOCYTIC --GRANULOMA --HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR --HYPERTROPHY, HEPATOCELLULAR ** CONTINUED ON NEXT PAGE ** ... NUMBER EXAMINED: 4 4 4 2 NOT REMARKABLE: 0 1 3 0 431 0 1000 0001 0011 4444 001 0 4433 0000 0003 0001 277 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL -- NUMB E R -O F -A N IM A L S SEX: --- MALE --- --- --- -- FEMALE-- GROUP: -1 - -2 - -3- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION NUMBER: 4 4 4 2 4 4 4 4 ** FROM PREVIOUS PAGE ** LIVER (LI) ............................................. NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 0 1 3 0 0 0 1 0 --VACUOLATION, HEPATOCELLULAR, CENTRILOBULAR --VACUOLATION, HEPATOCELLULAR --STASIS, BILE --DEGENERATION/NECROSIS, HEPATOCELLULAR 0001 0 0 01 01 001 1 01 01 00 0 0 0 0 0000001 0 GALLBLADDER (GB) ...................................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 3 0 0 1 3 0 0 2 --INFILTRATE, LYMPHOHISTIOCYTIC 1 0011 002 SPLEEN (SP) ............................................ NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 THYMUS (TH) ............................................ NUMBER EXAMINED: 4 4 4 2 4 4 4 4 NOT REMARKABLE: 3 1 1 0 4 0 0 1 --CYST --ATROPHY 01 01 01 12 1 2 32 0 443 LN, MESENTERIC (MS) ................................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 2 0 0 1 3 0 0 4 --HEMORRHAGE --INFILTRATE, MACROPHAGE, PIGMENTED 1 001 0 0 0 0 1 0001 000 Covance 6329-223 3M T-6295.7 PAGE: 3 278 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL -- NUMB E R -O F -A N IM A L S SEX: --- MALE --- --- --- ---FEMALE-- GROUP: -1 - -2 - -3- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION -- -- NUMBER: 4 4 4 2 4 4 4 4 -=- -=- -=- -=- -=- -=- -=- -=- TRACHEA (TR) ...................... ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 1 0 0 0 2 0 0 0 --INFILTRATE, LYMPHOHISTIOCYTIC --INFLAMMATION, ACUTE 30 02 2 0 04 0001 0 0 0 0 ESOPHAGUS (ES) .................... ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 3 0 0 4 --INFILTRATE, LYMPHOHISTIOCYTIC 00001 000 THYROID (TY) ...................... ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 3 0 0 1 --INFILTRATE, LYMPHOHISTIOCYTIC --CYST, ULTIMOBRANCHIAL 00001 001 0 0 0 0 0 0 02 PARATHYROID (PT) .................. ................... NUMBER EXAMINED: 4 0 0 2 3 0 0 4 NOT REMARKABLE: 3 0 0 2 3 0 0 4 --CYST 10000000 ADRENAL, CORTEX (AC) .............. ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 2 0 0 2 3 0 0 3 --HYPERTROPHY, CORTICAL CELL --INFILTRATE, LYMPHOHISTIOCYTIC --PIGMENT 1 0001 001 10000000 00000001 Covance 6329-223 3M T-6295.7 PAGE: 4 279 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL -- NUMB E R -O F -A N IM A L S SEX: --- MALE --- --- --- ---FEMALE-- GROUP: -1 - -2 - -3- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION -- -- NUMBER: 4 4 4 2 4 4 4 4 -=- -=- -=- -=- -=- -=- -=- -=- ADRENAL, MEDULLA (MA) ............. ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 AORTA (AO) ........................ ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 3 --PROLIFERATION, INTIMAL 00000001 PITUITARY (PI) .................... ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 SALIV GL, MANDIB (SG) ............. ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 0 0 0 1 2 0 0 2 --INFILTRATE, LYMPHOHISTIOCYTIC 40 012 0 02 MUSCLE, SKELETAL (SM) ............. ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 3 0 0 2 2 0 0 2 --INFILTRATE, LYMPHOHISTIOCYTIC --DEGENERATION --INFLAMMATION, GRANULOMATOUS --REGENERATION, MYOFIBER --PARASITES, CYST 1 000 0 0 01 00001 000 00001 000 00001 000 00001 001 Covance 6329-223 3M T-6295.7 PAGE: 5 280 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL -- NUMB E R -O F -A N IM A L S SEX: ---MALE --- --- --- ---FEMALE-- GROUP: -1 - -2 - -3- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION -- -- NUMBER: 4 4 4 2 4 4 4 4 -=- -=- -=- -=- -=- -=- -=- -=- SPINAL CORD (SC) ...................... ............... NUMBER EXAMINED: 4 0 0 2 4 4 4 4 NOT REMARKABLE: 4 0 0 2 3 1 0 2 --PIGMENT, NEURONAL 0 0 0 0 1 342 NERVE, SCIATIC (SN) ................... ............... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 STOMACH, GL (ST) ...................... ............... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 DUODENUM (DU) ......................... ............... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 3 0 0 2 2 0 0 1 --INFILTRATE, MACROPHAGE, PIGMENTED 1 0002 003 PANCREAS (PA) ......................... ............... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 3 0 0 2 4 0 0 4 --INFILTRATE, LYMPHOHISTIOCYTIC 10000000 JEJUNUM (JE) .......................... ............... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 3 0 0 0 1 0 0 1 --INFILTRATE, MACROPHAGE, PIGMENTED 1 0 02 30 0 3 Covance 6329-223 3M T-6295.7 PAGE: 6 281 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION -- NUMB E R -O F -A N IM A L S SEX: --- MALE --- --- --- -- FEMALE-- GROUP: -1 - -2 - -3- -4- -1 - -2 - -3- -4- NUMBER: 4 4 4 2 4 4 4 4 ILEUM (IL) ............................... ............. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 2 0 0 1 1 0 0 2 --INFILTRATE, MACROPHAGE, PIGMENTED 2 0 0 1 30 02 CECUM (CE) ............................... ............. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 3 0 0 2 3 0 0 2 --INFILTRATE, MACROPHAGE, PIGMENTED --PARASITISM 1 0001 001 00000001 COLON (CO) ............................... ............. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 2 0 0 2 4 0 0 3 --INFILTRATE, EOSINOPHILIC --PARASITISM, INTRAMUSCULAR 10000000 1 000 0 0 01 RECTUM (RE) .............................. ............. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 4 0 0 2 4 0 0 4 SKIN (SK) ................................ ............. NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 3 0 0 2 4 0 0 2 --HYPERPLASIA, EPIDERMAL (ACANTHOSIS) --INFLAMMATION, CHRONIC-ACTIVE --ULCERATION --HAIR FOLLICLES, DECREASED 10000000 10000000 10000000 0 0 0 0 0 0 02 Covance 6329-223 3M T-6295.7 PAGE: 7 282 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL -- NUMB E R -O F -A N IM A L S SEX: --- MALE --- --- --- -- FEMALE-- GROUP: -1 - -2 - -3- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION -- NUMBER: 4 4 4 2 4 4 4 4 ------------------------------------- -=- -=- -=- -=- -=- -=- -=- -=- MAMMARY, FEMALE (MF) .............. ................... NUMBER EXAMINED: 0 0 0 0 4 0 0 4 NOT REMARKABLE: 0 0 0 0 2 0 0 4 --INFLAMMATION, ACUTE --INFILTRATE, LYMPHOHISTIOCYTIC 00001 000 00001 000 MAMMARY, MALE (MM) ................ ................... NUMBER EXAMINED: 2 0 0 1 0 0 0 0 NOT REMARKABLE: 2 0 0 1 0 0 0 0 URINARY BLADDER (UB) .............. ................... NUMBER EXAMINED: 4 0 0 2 4 0 0 4 NOT REMARKABLE: 3 0 0 2 1 0 0 3 --INFILTRATE, LYMPHOHISTIOCYTIC 1 0 0 0 30 0 1 UTERUS (UT) ....................... ................... NUMBER EXAMINED: 0 0 0 0 4 0 0 4 NOT REMARKABLE: 0 0 0 0 2 0 0 3 --AMYLOID 00002 001 OVARY (OV) ........................ ................... NUMBER EXAMINED: 0 0 0 0 4 0 0 4 NOT REMARKABLE: 0 0 0 0 3 0 0 2 --MINERALIZATION --AMYLOID --ONE EXAMINED 00001 001 00000001 00000001 Covance 6329-223 3M T-6295.7 PAGE: 8 283 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL -- NUMB E R -O F -A N IM A L S SEX: --- MALE --- --- --- ---FEMALE-- GROUP: -1 - -2 - -3- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION -- -- NUMBER: 4 4 4 2 4 4 4 4 -=- -=- -=- -=- -=- -=- -=- -=- VAGINA (VA) ......................... ................. NUMBER EXAMINED: 0 0 0 0 4 0 0 4 NOT REMARKABLE: 0 0 0 0 4 0 0 4 CERVIX (CV) ......................... ................. NUMBER EXAMINED: 0 0 0 0 4 0 0 4 NOT REMARKABLE: 0 0 0 0 4 0 0 4 PROSTATE (PR) ....................... ................. NUMBER EXAMINED: 4 0 0 2 0 0 0 0 NOT REMARKABLE: 2 0 0 0 0 0 0 0 --INFLAMMATION, LYMPHOHISTIOCYTIC 2 002 0000 SEMINAL VESICLES (SV) ............... ................. NUMBER EXAMINED: 4 0 0 2 0 0 0 0 NOT REMARKABLE: 4 0 0 2 0 0 0 0 EPIDIDYMIDES (EP) ................... ................. NUMBER EXAMINED: 4 0 0 2 0 0 0 0 NOT REMARKABLE: 3 0 0 1 0 0 0 0 --HYPOSPERMIA 1 001 0 0 0 0 TESTIS (TE) ......................... ................. NUMBER EXAMINED: 4 0 0 2 0 0 0 0 NOT REMARKABLE: 3 0 0 1 0 0 0 0 --IMMATURE 1 001 0 0 0 0 Covance 6329-223 3M T-6295.7 PAGE: 9 284 TABLE 51 Incidence of Microscopic Observations Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TABLE INCLUDES: SEX=ALL;GROUP=ALL;WEEKS=ALL DEATH=T;FIND=ALL;SUBSET=ALL -- N U M BE R -O F -A N IMA L S SEX: ---MALE--- --- --- -- FEMALE-- GROUP: -1 - -2- -3- -4- -1 - -2 - -3- -4- ORGAN AND FINDING DESCRIPTION NUMBER: 4 4 4 2 4 4 4 4 -- ------------------------------------------- -=- -=- -=- -=- -=- -=- -=- -=- ADIPOSE TISSUE (AT) ......... ........................ NUMBER EXAMINED: 0 0 0 0 0 0 0 1 NOT REMARKABLE: 0 0 0 0 0 0 0 0 --LYMPHOID TISSUE 00000001 CAUSE OF DEATH (CD) ......... ........................ NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 LN, TRACHEOBRON (TB) ................ ................. NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 ** END OF LIST ** Covance 6329-223 3M T-6295.7 PAGE: 10 T E D -- 285 TABLE 52 Incidence of Microscopic Observations Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 TABLE INCLUDES: SEX=ALL;GROUP=4;WEEKS=ALL DEATH=U;FIND=ALL;SUBSET=ALL ORGAN AND FINDING DESCRIPTION -- 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: -4- -4- NUMBER: 2 2 ** TOP OF LIST ** 2 2LIVER, BIOPSYa (LI0) ................................. ... NUMBER EXAMINED: 1 2NOT REMARKABLE: --PIGMENT, HEPATOCELLULAR 10 2 2LIVER (LI) ......................................... ... NUMBER EXAMINED: 0 0NOT REMARKABLE: --INFILTRATE, LYMPHOHISTIOCYTIC --PIGMENT, HEPATOCELLULAR --HYPERPLASIA, BILE DUCT --INFLAMMATION, EOSINOPHILIC, PERI-BILE DUCT --FIBROSIS, CAPSULAR 21110 11000 ** END OF LIST ** a The liver biopsy was taken during Week 57 of recovery. 286 APPENDIX 1 Protocol Deviations Protocol Protocol Amendment No. 1 Protocol Amendment No. 2 Protocol Amendment No. 3 Protocol Amendment No. 4 Covance 6329-223 3M T-6295.7 287 Protocol Deviations Covance 6329-223 3M T-6295.7 Protocol. Reserve (Archive) Samples. "These samples will be transferred to the Sponsor after completion of the in-life phase." Actual Procedure. These samples were shipped to the Sponsor after the dosing phase was competed, which was prior to the end of the in-life phase. Protocol. Dosing Procedures. Method of Administration. "Orally by gelatin capsules, daily (7 days/week) for at least 26 weeks." Actual Procedure. On Day 3, Animal Nos. I05520 (Group 1 male) and I05529 (Group 1 female) did not receive a dose administration due to bleeding and irritation in the throat. Dosing was discontinued for Animal No. I05530 (Group 1 female) from Days 10 through 14 due to a sore inside its mouth. Protocol. Observation of Animals. Clinical Observations. "Once weekly, each animal will be observed; abnormal findings or an indication that the animal was normal will be recorded." Actual Procedure. During the course of the study, several animals did not have a weekly observation of normal of abnormal recorded on various scheduled days. Protocol. Observation of Animals. Ophthalmic Examinations. Before initiation of treatment and before each scheduled sacrifice; the anterior portion of the eye, optic media, and ocular fundus will be examined using an indirect ophthalmoscope by a boardcertified ophthalmologist. Actual Procedure. An ophthalmic examination was completed during Week 52 instead of prior to the recovery sacrifice during Week 79. 288 Protocol Deviations (Continued) Covance 6329-223 3M T-6295.7 Protocol. Clinical Pathology. Frequency. Scheduled Collections. "Once before initiation of treatment; after at least 30, 60, 90, 150, and 180 days of treatment (before the daily dose); and after at least 30, 60, 90, 135, 180, 274, and 365 days of recovery" Actual Procedure. On Day 184, urine samples were collected for several animals; however, these samples were not required by the protocol and were discarded. Samples were collected on Days 273 and 363 of recovery. Protocol. Clinical Pathology. Tests. Hematology. Eleven hematological parameters were to be tested at all intervals. Actual Procedure. In addition to the required hematology tests at the pretreatment interval, mean platelet volume, red blood cell distribution width, platelet distribution width, and plateletcrit were also inadvertently tested for. Protocol. Blood Hormone Determination. Frequency. "Three times before initiation of treatment; after at least 30, 60, 90, and 180 days of treatment; and after at least 30, 60, 90, 135, 180, 274, and 365 days of recovery." Actual Procedure. Samples were collected on Days 273 and 363 of recovery. Protocol. Serum PFOS Level Determination. Method of Collection. "Animals will be fasted overnight; blood (approximately 2 mL) will be collected from a femoral vein without an anticoagulant." Actual Procedure. Animals were not fasted overnight for the scheduled collection on Day 197; however, animals were fasted the following night and collection was done on Day 198. 289 Protocol Deviations (Continued) Covance 6329-223 3M T-6295.7 Protocol. Urine and Feces PFOS Level Determination. Method of Collection. "Animals will not be fasted (except for the first day of recovery); urine (at least 2 mL) and feces (at least 5 g) will be collected overnight." Actual Procedure. The amount of urine collected was not documented at the time of each collection and therefore cannot be verified. Protocol. Additional Fecal Samples. "The samples will be collected in the early afternoon after pans are cleaned in the morning to ensure that they are no more than 6 hours old." Actual Procedure. On Day 160, some fecal samples were collected in the late morning rather than the early afternoon. Protocol. Interim Liver Biopsy Samples. "Kris J. Hansen or her alternate will be notified regarding the shipment of the samples." Actual Procedure. The phone call made to notify Kris J. Hansen prior to shipment of these samples was not documented and therefore cannot be verified. Protocol. Terminal Liver Biopsy Samples. "A sample of liver (approximately 1 g) will be collected by biopsy from all animals in Groups 3 during recovery (Week 79, within 1 day of the serum PFOS blood collection)." Actual Procedure. These samples were collected during Week 80, and were not collected within one day of the serum PFOS blood collection. Protocol. Postmortem Procedures. Cell Proliferation Evaluation. "After fixation, samples for proliferation cell nuclear antigen (PCNA) evaluation will be embedded in paraffin and shipped to:" 290 Protocol Deviations (Continued) Covance 6329-223 3M T-6295.7 Actual Procedure. PCNA analysis was not done for Animal No. I05509 (Group 4 male). Protocol. Termination. Postmortem Procedures. Additional Lung Tissue Samples. "At the terminal necropsy, a sample of lung (approximately 5 g) will be collected from an animal in the high-dose group. This sample will be weighed, flash-frozen in liquid nitrogen, and stored in a freezer, set to maintain -60 to -80 C, until shipped. This frozen sample, and a sample of lung (approximately 1 g, stored in formalin) from Animal No. I05509 (Group 4 male, died January 27, 1999) will be sent separately under appropriate conditions (ambient or packed on dry ice) to: Kris J. Hansen, PhD 3ME. T. & S. Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone: 651.778.6018 Facsimile: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples." Actual Procedure. This procedure was inadvertently not done at the terminal sacrifice; thus no samples were available for shipment to Kris J. Hansen, PhD. Protocol. Termination. 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." 291 Protocol Deviations (Continued) Covance 6329-223 3M T-6295.7 Actual Procedure. Femoral bone marrow from Animal Nos. I05517,105519,105527 (Group 1 males), I05507, I05509, I05512 (Group 4 males), I05531, I05535 (Group 1 females), I05536, I05540, and I05551 (Group 4 females); mammary gland from Animal Nos. I05508, I05519 (Group 1 males), and I05512 (Group 4 male); and parathyroid from Animal No. I05544 (Group 1 female) were insufficient. These tissues, therefore, were not examined microscopically. Additionally, one ovary of a possible two was examined from Animal No. I05536 (Group 4 female). Missing tissues are listed with appropriate comments in the pathology data sheets for individual animals. Summary tables do not include them as having been examined. These deviations are not expected to have affected the results of the study. 292 293 Covance 6329-223 3M T-6295.7 ________________________________________________________ _______________ _________ Page 2 Study 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys Purpose To assess the effect of the test material on critical enzyme levels, hormones, and other selected biochemical parameters when administered daily by capsule to cynomolgus monkeys for at least 26 weeks Sponsor 3M Toxicology Services Building 220-2E-02, 3M Center St. Paul, Minnesota 55144-1000 Study Monitor Andrew M. Seacat, PhD 3M Telephone No.: 651.575.3161 Facsimile No.: 651.733.1773 Alternate Study Monitor Marvin T. Case, DVM, PhD 3M Toxicology Services Telephone No.: 651.733.5180 Facsimile No.: 651.733.1773 Study Location Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Mailing Address: PO Box 7545 Madison, Wisconsin 53707-7545 294 Covance 6329-223 3M T-6295.7 _____________________________________ _____________________________ ______________ Page 3 Study Director Peter J. Thomford, PhD Covance Laboratories Inc. Telephone No.: 608.241.7207 Facsimile No.: 608.242.2736 Study Toxicologist Dale Aldridge, BS Covance Laboratories Inc. Proposed Study Timetable Experimental Start Date: August 26, 1998 In-life Start Date: August 26, 1998 In-life Termination Date: To be determined Audited Draft Report Date: To be determined Experimental Termination Date: To be determined Regulatory Compliance This study will be conducted in compliance with the Environmental Protection Agency Good Laboratory Practice Regulations as set forth in Title 40 of the US Code of Federal Regulations, Part 792, issued November 29, 1983 (effective December 29, 1983), and with any applicable amendments. Animal Care and Use Statement All procedures in this protocol are in compliance with the Animal Welfare Act Regulations, 9 CFR 1-4. In the opinion of the Sponsor and study director, the study does not unnecessarily duplicate any previous work. Quality Assurance The protocol, study conduct, and final report will be audited by the Covance Quality Assurance Unit (QAU). The proliferation cell nuclear antigen evaluation data and report will be audited by the QAU of Pathology Associates International. The dose analysis and serum and liver PFOS analysis and report will be audited by the QAU of 3M Environmental Laboratories. The blood hormone determinations and report will be audited by the QAU of Ani Lytics Inc. 295 Covance 6329-223 3M T-6295.7 _____ ___________________________________ ______________________ ________________ Page 4 Test Material Identification Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) Lot Number The lot number will be maintained in the raw data. Purity Responsibility of the Sponsor Stability Responsibility of the Sponsor Storage Conditions At room temperature Characteristics Information on synthesis methods, composition, or other characteristics that define the test material is on file with the Sponsor. Vehicle Identification Lactose Lot Number The lot number will be maintained in the raw data. Purity On file with the manufacturer Stability On file with the manufacturer Storage Conditions At room temperature 296 Covance 6329-223 3M T-6295.7 _____________________________________ ___________________________________________ Page 5 Gelatin Capsules Capsules (Size No. 2) obtained from Torpac, Inc. (Fairfield, New Jersey); lot number will be supplied by the manufacturer. Gelatin capsules will be stored at room temperature. A copy of the Certificate of Analysis provided by the manufacturer will be maintained in the data. Reserve (Archive) Samples A reserve sample of each lot of test material, vehicle, and each test material/lactose dilution (1 g each) will be taken and stored at room temperature. These samples will be transferred to the Sponsor after completion of the in-life phase. Disposition of Test Material Any remaining test material will be retained at Covance for use in possible future studies. Animals Species Cynomolgus monkey Source Covance Research Products Inc. Age at Initiation of Treatment Young adult/adult Weight at Initiation of Treatment Approximately 2 to 5 kg Number and Sex 22 males and 22 females Identification Collar tag Husbandry Housing Individual; animals will be housed in suspended, stainless steel cages. 297 Covance 6329-223 3M T-6295.7 ___________________________ ______________________________________ ___ _________ Page 6 Diet Certified primate diet (#8726C, Harlan Teklad) once or twice daily. The diet is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Results of specified nutrient and contaminant analyses are on file at Covance-Madison. Fruit, vegetables, or other supplements may be provided but will not require analysis. Water Ad libitum. Samples of the water are routinely analyzed for specified microorganisms and environmental contaminants. The results are on file at Covance-Madison. Contaminants There are no known contaminants in the diet or water at levels that might interfere with this study. Environment Environmental controls for the animal room will be set to maintain 18 to 29C, a relative humidity of 30 to 70%, and a 12-hour light/12-hour dark cycle. The dark cycle may be interrupted to accommodate in-life procedures. Acclimation Minimum of 4 weeks Randomization Animals will be weighed, stratified by body weight, and allocated to the number of blocks equal to the number of animals to be selected for each group. Animals in each block will then be assigned to groups using computer-generated random numbers. 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. 298 Covance 6329-223 3M T-6295.7 __________________________________________________________________ ____________ Page 7 Group Designations and Dosage Levels a Dose levels will be provided. The control group (Group 1) will receive an equivalent amount of lactose in gelatin capsules as the total material administered to Group 4. b The low-dose (Group 2) will receive the test material diluted with lactose (1:499, w:w). c The mid-dose (Group 3) and high-dose (Group 4) groups will receive the test material diluted with lactose (1:39, w:w). d Two animals in Groups 1, 3, and 4 designated as recovery animals will be treated for at least 26 weeks, then treatment will be discontinued, and the animals will be observed for reversibility, persistence, or delayed occurrence of toxic effects for at least 13 weeks posttreatment. Based on plasma test material levels and clinical pathology findings, the recovery may be reduced or extended, at the discretion of the study director and after consultation with the Sponsor. Dosing Procedures Method of Administration Orally by gelatin capsules, daily (7 days/week) for at least 26 weeks Reason for Dosing Route To compare with data from previous toxicology studies using the oral route, which is the most likely route of exposure Dose Preparation Capsules will be prepared at least weekly. The size and number of capsules will depend on the physical characteristics of the test material, the dose level, and the weight of the monkey. Individual daily doses will be based on the most recent individual body weights, with the exception of body weight collection days when the previous body weight will be used. Dose levels will be based on the vehicle as supplied for Group 1. 299 Covance 6329-223 3M T-6295.7 _____________________________________________________ _ _ _ _ _ _ ____________________Page 8 For the Groups 2 through 4 dose preparations, the test material will be dissolved in acetone and diluted with lactose (1:499, 1:39, and 1:39, w:w, respectively) once before initiation of treatment. Dilution with lactose is necessary to facilitate capsule preparation. All dose preparations will be stored at room temperature until dosed. Dose Analyses Dose analyses will be done by the Sponsor. Homogeneity Samples (approximately 1 g each) will be collected from the top, middle, and bottom of the test material/lactose preparations for the low- and high-dose groups and analyzed for test material content. All samples will be stored at room temperature until analyzed. Stability Homogeneity samples collected from the middle of the preparations will be used for the prestudy stability analysis. 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. Sample Shipping Samples will be shipped under ambient conditions to: Kris J. Hansen, PhD 3M E. T. & S Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone: 651.778.6018 Facsimile: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Analysis of for test material content will be done on the samples. Results will be provided for inclusion in the final report. Observation of Animals Clinical Observations Each animal will be observed twice daily (a.m. and p.m.) for mortality and moribundity; findings will be recorded as they are observed. 300 Covance 6329-223 3M T-6295.7 _________ Page 9 Each animal will be observed daily and food consumption will be assessed qualitatively; abnormal findings will be recorded. Once weekly, each animal will be observed; abnormal findings, or an indication that the animal is normal will be recorded. During treatment, each animal will be observed for signs of poor health or abnormal behavior approximately 30 to 90 minutes after the last animal on test has been dosed; abnormal findings will be recorded. Additional findings will be recorded as they are observed. Body Weights Weekly before initiation of treatment, on the first day of treatment, and weekly thereafter. An additional body weight will be recorded on Day -1 for the Day 1 dose calculations. Ophthalmic Examinations Before initiation of treatment and before each scheduled sacrifice; the anterior portion of the eye, optic media, and ocular fundus will be examined using an indirect ophthalmoscope by a board-certified ophthalmologist. Clinical Pathology Frequency Unscheduled Collections When possible, blood will be collected for clinical pathology tests from animals sacrificed at unscheduled intervals Scheduled Collections Once before initiation of treatment; and (before the daily dose) after at least 30, 60, 90, and 180 days of treatment; and after at least 30, 60, and 90 days of recovery Method of Collection Animals will be fasted overnight; blood will be collected from a femoral vein. Anticoagulant will be potassium EDTA for hematology tests. No anticoagulant is required for clinical chemistry tests. Urine will be collected overnight on wet ice: 301 Covance 6329-223 3M T-6295.7 ________ Page 10 Tests 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 blood cell morphology reticulocyte count Clinical Chemistry glucose urea nitrogen creatinine total protein albumin globulin total bilirubin direct bilirubin (if total bilirubin is greater than 2.0 mg/dL) cholesterol triglycerides alanine aminotransferase alkaline phosphatase aspartate aminotransferase gamma glutamyltransferase sorbitol dehydrogenase creatine kinase calcium inorganic phosphorus sodium potassium chloride bile acids amylase lipase pancreatic-specific amylase Urinalysis appearance glucose volume (approximately 16 hours) ketones specific gravity bilirubin pH blood protein microscopic examination of sediment urobilinogen Blood Hormone Determination Frequency Three times before initiation of treatment; after at least 30, 60, 90, and 180 days of treatment; and after at least 30, 60, and 90 days of recovery 302 Covance 6329-223 3M T-6295.7 _____________________________________________ ________________________________ Page 11 Number of Animals All Method of Collection Animals will be fasted overnight; blood will be collected from a femoral vein. Approximately 5 mL of blood will be collected without anticoagulant and allowed to clot for serum samples. Sample Handling Samples for serum will be centrifuged within 1 hour after collection, and serum will be harvested. Serum will be divided into two approximately equal aliquots and stored in a freezer set to maintain -60 to -80C until packed on dry ice and shipped to: Dr. Saroj Das Ani Lytics Inc. 200 Girard Street, Suite 200 Gaithersburg, Maryland 20877 Telephone No.: 301.921.0168 Facsimile No.: 301.977.0433 Ani Lytics Inc. will be notified regarding shipment of samples. Tests Samples will be analyzed by Ani Lytics Inc., for cortisol, testosterone, estradiol, estrone, estriol, thyroid stimulating hormone, triiodothyronine (T3), and thyroxin (T4). Serum PFOS Level Determination Frequency Before initaition of treatment, and during Weeks 1 (Day 7), 2, 4, 6, 8, 12, 16, 20, 24, 26, 28, 30, 32, 34, and 39. Number of Animals All Method of Collection Animals will be fasted overnight; blood (approximately 2 mL) will be collected from a femoral vein without an anticoagulant. 303 Covance 6329-223 3M T-6295.7 _____________________________________ ___ ____________________ __________________Page 12 Sample Handling Samples will be centrifuged within 1hour after collection, and serum will be harvested. Serum samples will be stored in a freezer set to maintain -60 to -80C. Sample Shipping Serum samples will be packed on dry ice and shipped to: Kris J. Hansen, PhD 3M E. T. & S Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone: 651.778.6018 Facsimile: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Analysis of serum for PFOS will be done on the samples. Results will be provided for inclusion in the final report. Additional Serum Collection At scheduled and unscheduled necropsies, blood (as much as possible, up to 20 mL) will be collected from the vena cava without an anticoagulant from animals at the time of exsanguination. Samples will be centrifuged within 1hour after collection, and serum will be harvested. Serum from each animal will be transferred into an appropriate container and stored in a freezer set to maintain -60 to -80C until shipped to the Sponsor (Kris J. Hansen) for possible future analysis. Urine and Feces PFOS Level Determination Frequency On the first day of recovery and after at least 6,30, and 90 days of recovery Number of Animals All Method of Collection Animals will not be fasted; urine (approximately 2 mL) and feces (approximately 5 grams) will be collected overnight. 304 Covance 6329-223 3M T-6295.7 ______________________________________ _________________ ______________________ Page 13 Sample Handling Samples will be stored in a freezer set to maintain -10 to -30C. Sample Shipping Samples will be packed on dry ice and shipped to: Kris J. Hansen, PhD 3M E. T. & S Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone: 651.778.6018 Facsimile: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Analysis of urine and feces for PFOS will be done on the samples. Results will be provided for inclusion in the final report. Termination Unscheduled Sacrifices and Deaths Necropsies will be done. Animals to be sacrificed will be anesthetized with ketamine and xylazine, weighed, bled for required tests, and exsanguinated. Scheduled Sacrifices After at least 26 weeks of treatment, four animals/sex/group will be fasted overnight, then anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. After at least 26 weeks of treatment and at least 13 weeks without treatment, the remaining animals will be fasted overnight, then anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. Postmortem Procedures Necropsy The necropsy will include examination of: all orifices cranial cavity external surface of the brain; the external surface of the spinal cord and cut surfaces of the brain and spinal cord will be examined when tissue trimming is performed, cervical tissues and organs 305 Covance 6329-223 3M T-6295.7 ______________________________________________________________________________ Page 14 thoracic, abdominal, and pelvic cavities and viscera external surface of the body nasal cavity and paranasal sinuses Organ Weights From each animal at scheduled and unscheduled sacrifices, the following organs (when present) will be weighed; paired organs will be weighed separately: adrenal(2) brain epididymis (2) kidney (2) liver ovary (2) pancreas testis (2) thyroid (2) with parathyroid Organ-to-body weight percentages and organ-to-brain weight ratios will be calculated. Palmitoyl CoA Oxidase Determinations Representative samples of the right lateral lobe of liver will be collected from each animal at the scheduled sacrifice, weighed, flash-frozen in liquid nitrogen, and stored in a freezer set to maintain -60 to -80C until analyzed for palmitoyl CoA oxidase activity. Cell Proliferation Evaluation Representative samples of the left lateral lobe of the liver, left and right testes, and pancreas will be collected and preserved in zinc formalin. After fixation, samples for proliferation cell nuclear antigen (PCNA) evaluation will be embedded in paraffin and shipped to: Sandra R. Eldridge, PhD Pathology Associates International 15 Worman's Mill Court Suite I Frederick, Maryland 21701 Telephone: 301.663.1644 ext. 2036 Facsimile: 301.663.8994 Pathology Associates International will be notified regarding shipment of samples. PCNA evaluation will be done on the samples. Results will be provided for inclusion in the final report. 306 Covance 6329-223 3M T-6295.7 _______________________________________________________ ______________________Page 15 Liver PFOS Determination A section (approximately 20 g) of liver will be collected from each animal at the scheduled sacrifice, weighed, flash-frozen in liquid nitrogen, and stored in a freezer set to maintain -60 to -80C until shipped with plasma samples to 3M (Kris Hansen) for analysis. Results will be provided for inclusion in the final report. 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: adrenal (2) aorta brain cecum cervix colon duodenum epididymis (2) esophagus eye [(2) to be preserved in Davidson's fixative for sacrificed animals only] femur with bone marrow (articular surface of the distal end) gallbladder heart ileum jejunum kidney (2) lesions liver lung mammary gland ovary (2) mesenteric lymph node pancreas pituitary prostate rectum salivary gland [mandibular (2)] sciatic nerve seminal vesicle (2) skeletal muscle (thigh) skin spinal cord (cervical, thoracic, and lumbar) spleen sternum with bone marrow stomach testis [(2) to be preserved in Bouins' solution for sacrificed animals only] thymus thyroid (2) with parathyroid trachea urinary bladder uterus vagina Bone Marrow Smear From the sternum of each animal at unscheduled and scheduled sacrifices (made and held for possible future examination). 307 Covance 6329-223 3M T-6295.7 ________ Page 16 Histopathology Tissues from each animal in the control and high-dose groups will be embedded in paraffin, sectioned, stained with hematoxylin and eosin, and examined microscopically, Tissues from all other animals will be retained for possible future examination. Reports Letter Report A letter report will be prepared following the terminal sacrifice. Final Report A draft report that includes the following information will be prepared and submitted: Experimental Design and Methods Results mortality clinical observations body weights food consumption ophthalmic examinations clinical pathology results palmitoyl CoA oxidase activities hormone analyses (provided by Ani Lytics) serum, urine, feces, and liver PFOS levels (provided by 3M) cell proliferation evaluations (provided by Pathology Associates International) dose analyses (provided by 3M) organ weights organ-to-body weight percentages organ-to-brain weight ratios macroscopic observations microscopic observations Statistical Evaluation Levene's test will be done to test for variance homogeneity. In the case of heterogeneity of variance at p < 0.05, transformations will be used to stabilize the variance. Comparison tests will take variance heterogeneity into consideration. 308 Covance 6329-223 3M T-6295.7 __________________________________ ________________________ ____________________ Page 17 One-way analysis of variance (ANOVA) will be used (if applicable) to analyze initial body weights, palmitoyl CoA oxidase activities, and continuous clinical pathology values. If the ANOVA is significant, Dunnett's t-test will be used for control versus treated group comparisons. One-way analysis of covariance (ANCOVA) will be used to analyze body weights, with initial body weights as the covariate. If the ANCOVA is significant, covariateadjusted means will be used for control versus treated group comparisons. Group comparisons (Groups 2 through 4 versus Group 1) will be evaluated at the 5.0% two-tailed probability level. Only data collected on or after the first day of treatment will be analyzed statistically. At the end of 1 year after issuance of the audited draft report, if no requested revisions or instructions to finalize have been communicated by the Sponsor, then the audited draft report will be considered 'final' and issued as the final report, signed by the study director, and submitted to the Sponsor. Any modifications or changes to the audited draft report requested 1 year after issuance will be performed at additional cost to the Sponsor. Record Retention All raw data, documentation, records, protocol, specimens, and final report generated as a result of this study generated by Covance will be archived in the storage facilities of Covance for a period of 1 year following submission of the final report to the Sponsor. One year after submission of the final report, all of the aforementioned materials will be sent to the Sponsor, and a return fee will be charged. The Sponsor may elect to have the materials retained in the Covance archives for an additional period of time, and Covance will charge a storage fee. If the Sponsor chooses to have Covance dispose of the materials, a disposal fee will be charged. All raw data stored on magnetic media will be retained by Covance. Within 1 year after submission of the final report, all of the aforementioned materials from the Sponsor's designees (Ani Lytics Inc., 3M E. T. & S, and Pathology Associates International) will be sent to the Sponsor (Andrew Seacat, PhD, 3M) by the Sponsor's designees. 309 310 CO VAitf> THE DEVELOPMENT SERVICES COMPANY PROTOCOL AMENDMENT NO. 1 Covance 6329-223 3M T-6295.7 This amendment modifies the following portions of the protocol. Effective August 20,1998 1. Page 4, 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 311 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 1 __________________________________________________________ _________________ Page 2 Characteristics Information on synthesis methods, composition, or other characteristics that define the solvent is on file with the manufacturer. 2. Page 7, Group Designations and Dosage Levels, Footnote a, Sentence 1. To correct an error, delete this sentence. Effective September 2,1998 3. PageS, Gelatin Capsules, Sentence 1. To change the size of the gelatin capsules, delete this sentence and replace with the following. Capsules (Size Nos. 2 or 4) obtained from Torpac, Inc. (Fairfield, New Jersey); lot number will be supplied by the manufacturer. Effective December 15,1998 4. Page 14, 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. Effective January 21,1999 5. Page 10, Clinical Pathology, Tests, Clinical Chemistry. To include an additional clinical chemistry test, add the following. High density lipoprotein (HDL) Effective January 21 and 28 and February 2,1999 6. Page 12, Urine and Feces PFOS Level Determination, Sample Shipping. At the request of the Sponsor to collect additional fecal samples (effective January 21, 1999) and to clarify the sample collection requirements (effective January 28 and February 2, 1999), add the following after this section. 312 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 1 _____________________________________________________ _____________________ Page 3 Additional Fecal Samples During Week 23, a fresh fecal sample of at least 5 g, if possible, will be collected from 6 males and 6 females each in the control and high-dose groups, survival permitting. The samples will be collected in the early afternoon after pans are cleaned in the morning to ensure that they are no more than 6 hours old. The samples will be collected in white polypropylene containers and sent on dry ice to: Joe McConnell Porphyrins and Nutritional Chemistry Group Mayo Clinic 200 First Street SW Rochester, Minnesota 55905 Telephone: 507.284.2150 Lab Telephone: 507.284.3232 Dr. McConnell will be contacted before shipping the samples. Effective January 21 and February 12 and 16,1999 7. Page 9, Clinical Pathology, Frequency, Scheduled Collections. To reflect the decision of the Sponsor and the Study Director to add a collection interval after 150 days of treatment (effective January 21, 1999), to extend the length of recovery (effective February 12, 1999), and to clarify the collection requirement (effective February 12, 1999), delete the text in this section and replace with the following. Once before initiation of treatment; and after at least 30, 60, 90, 150, and 180 days of treatment (before the daily dose); and after at least 30, 60, 90, 135, and 180 days of recovery Effective February 10 and 16,1999 8. Page 12, Urine and Feces PFOS Level Determination, Method of Collection. To modify the amount of sample to be collected (effective February 10, 1999) and to permit collection of samples from fasted animals on the first day of recovery (effective February 16, 1999), delete the text in this section and replace with the following. Animals will not be fasted (except for the first day of recovery); urine (at least 2 mL) and feces (at least 5 g) will be collected overnight. 313 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 1 ________________ __________________________________________ ____________ Page 4 Effective February 12,1999 9. Page 7, Group Designations and Dosage Levels, Footnote d. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery, delete the text in this footnote and replace with the following. d Two animals in Groups 1,3, and 4 designated as recovery animals will be treated for at least 26 weeks, then treatment will be discontinued, and the animals will be observed for reversibility, persistence, or delayed occurrence of toxic effects for at least 26 weeks posttreatment. Effective February 12 and 15,1999 10. Page 11, Serum PFOS Level Determination, Frequency. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery (effective February 12, 1999) and to revise the requirements for these collections during recovery (effective February 15, 1999), delete the text in this section and replace with the following. Before initiation of treatment; during Weeks 1 (Day 7), 2, 4, 6, 8, 12, 16, 20, 24, 26, and 27 (Day 183) during treatment; and during Weeks 27 (Days 184, 185, and 187), 28 (Day 190), 29 (Day 197), 30 (Day 204), 31 (Day 211), 35, 39, 43, 47, 51, and 53. 11. Page 13, Termination, Scheduled Sacrifices. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery (effective February 12, 1999) and to prioritize the number of animals designated for recovery (effective February 15, 1999), delete the text in this section and replace with the following. After at least 26 weeks of treatment, up to four animals/sex/group will be fasted overnight, then anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. After at least 26 weeks of treatment and at least 26 weeks without treatment, two animals/sex/group will be fasted overnight, then anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. 314 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 1 ______________________ _______________________________________________________Page 5 Effective February 12 and 16,1999 12. Page 10, Blood Hormone Determination, Frequency. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery (effective February 12, 1999) and to clarify the requirements (effective February 16, 1999), delete the text in this section and replace with the following. Three times before initiation of treatment; after at least 30, 60, 90, and 180 days of treatment; and after at least 30, 60, 90, 135, and 180 days of recovery 13. Page 12, Urine and Feces PFOS Level Determination, Frequency. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery (effective February 12, 1999) and to clarify the requirements (effective February 16, 1999), delete the text in this section and replace with the following. On the first day of recovery and after at least 6, 30, 90, 135, and 180 days of recovery Effective February 15,17, and 18,1999 14. Page 13, Postmortem Procedures. To facilitate a request by the Sponsor to transfer samples of lung tissue (effective February 15 and 18, 1999) and gallbladder and bile (effective February 17, 1999), add the following. Additional Lung Tissue Samples At the terminal necropsy, a sample of lung (approximately 5g) will be collected from an animal in the high-dose group. This sample will be weighed, flash-frozen in liquid nitrogen, and stored in a freezer, set to maintain -60 to -80C, until shipped. This frozen sample and a sample of lung (approximately 1 g, stored in formalin) from Animal No. 105509 (Group 4 male, died January 27, 1999) will be sent separately under appropriate conditions (ambient or packed on dry ice) to: Kris J. Hansen, PhD 3M E. T. & S. Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone: 651.778.6018 Facsimile: 651.778.6176 315 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 1 ______________________________________________________________ __ _________Page 6 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Additional Gallbladder and Bile Samples At the scheduled necropsies, the gallbladder and bile will be collected and stored according to a special collection and fixation procedure. Frozen gallbladder and bile samples will be packed on dry ice and transferred to: Kris J. Hansen, PhD 3M E. T. & S Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone: 651.778.6018 Facsimile: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Effective February 24 and March 9,1999 15. Page 13, Postmortem Procedures. To facilitate a request by the Sponsor to prepare (effective February 24, 1999) and transfer (effective March 9, 1999) samples of liver for electron microscopy and to prepare and transfer hematoxylin and eosin-stained slides for light microscopy (effective March 9, 1999), add the following. Electron Microscopy At the terminal necropsy, samples of liver will be collected and processed to block stage for electron microscopic evaluation. The tissue blocks and a hematoxylin and eosin-stained slide for light microscopy will be transferred to: Sharon Ambrose Division Director Pathology Associates International 4915 D. Prospectus Drive Durham, North Carolina 27713 Telephone: 919.544.5257 Facsimile: 919.544.3218 316 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 1 __________________________________ __________________________________________ Page 7 Tissues will be processed and evaluated by electron microscopy by Pathology Associates International (PAI). A report will be provided by PAI for inclusion in the final report. PAI is responsible for the quality assurance auditing and maintenance of any raw data or specimens produced by PAI. Sharon Ambrose or her alternate will be notified regarding the shipment of the samples. Effective April 22,1999 16. Page 16, Reports, Statistical Evaluation, Paragraph 2, Sentence 1. To add statistical analysis of organ weight and hormone values, delete this sentence and replace with the following. One-way analysis of variance (ANOVA) will be used (if applicable) to analyze initial body weights, palmitoyl CoA oxidase activities, continuous clinical pathology values, hormone values, and organ weight data. Effective April 26,1999 17. Page 14, Postmortem Procedures, Cell Proliferation Evaluation, Paragraph 1. To add a second set of tissues for cell proliferation evaluation, add the following to this paragraph. A second set of tissues (representative samples of the left lateral lobe of the liver, left and right testes, and pancreas) preserved in formalin without zinc will also be prepared. Effective April 28,1999 18. Page 8, Dose Analyses, Stability, Sentence 2. To change the schedule for the return of the samples, delete this sentence and replace with the following. 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 treatment phase and will be analyzed for test material content. 317 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 1 ____________________________________________________________________________ Page 8 Effective May 6,1999 19. Page 16, Reports, Letter Report. To change the letter report to an interim report, delete the text in this section and replace with the following. Interim Report An interim report, including all items from the final report as appropriate, will be prepared following the terminal sacrifice. Effective May 17,1999 20. Page 16, Postmortem Procedures, Histopathology, Sentence 2. To include target organs for animals in the low- and mid-dose groups, delete this sentence and replace with the following. In addition, liver and thymus for all animals in the low- and mid-dose groups and spinal cord gray matter from females in the low- and mid-dose groups will be embedded in paraffin, sectioned, stained with hematoxylin and eosin, and examined microscopically. Other tissues, as appropriate, will be retained for possible future examination. Effective May 18,1999 21. Page 3, Proposed Study Timetable. To include proposed dates for in-life termination, the unaudited draft interim report, and the audited draft report, delete the text in this section and replace with the following. Experimental Start Date: August 26, 1998 In-life Start Date: August 26,1998 In-life Termination Date: August 27,1999 Unaudited Draft Interim Report Date: May 11, 1999 Audited Draft Report Date: December 28, 1999 Experimental Termination Date: To be determined 318 319 PROTOCOL AMENDMENT NO. 2 Covance 6329-223 3M T-6295.7 26-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 February 19, 1999 1. Page 9, Observation of Animals, Clinical Observations, Paragraph 2, Sentence 2. To add an observation on the day of scheduled sacrifice, delete this sentence and replace with the following. Once weekly and on the day of scheduled sacrifice, each animal will be observed; abnormal findings or an indication that the animal is normal will be recorded. Effective June 11, 1999 2. Page 11, Blood Hormone Determination, Tests. To add free triiodothyronine (T3) and free thyroxin (T4) tests, delete the text in this section and replace with the following. Samples will be analyzed by Ani Lytics Inc. for cortisol, testosterone, estradiol, estrone, estriol, thyroid stimulating hormone, total and free triiodothyronine (T3), and total and free thyroxin (T4). 320 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 2 _________________Page 2 3. Page 16, Reports, Final Report, Statistical Evaluation. To add repeated measure statistical analysis of cholesterol and total and free triiodothyronine (T3), add the following to the end of the section. Cholesterol and total and free triiodothyronine (T3) will be analyzed by repeated measures analysis of covariance (ANCOVA) procedure with average pretreatment measurements for the parameters as covariates. Treatment effects under ANOVA or ANCOVA procedures will be evaluated at p = 0.05 level. All post-hoc control-versus-treated-group mean comparisons (including values during recovery) will be conducted using Dunnett's many-on-one t procedure. Analyses will be carried out with SAS procedure PROC MIXED or BMDP, or both. Effective August 24, 1999 4. Page 7, Group Designations and Dosage Levels, Footnote d. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery, delete the text in this footnote and replace with the following. d Two animals in Groups 1,3, and 4 designated as recovery animals will be treated for at least 26 weeks, then treatment will be discontinued, and the animals will be observed for reversibility, persistence, or delayed occurrence of toxic effects for at least 52 weeks posttreatment. 5. Page 9, Clinical Pathology, Frequency, Scheduled Collections. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery, delete the text in this section and replace with the following. Once before initiation of treatment; after at least 30, 60, 90, 150, and 180 days of treatment (before the daily dose); and after at least 30, 60, 90, 135, 180, 274, and 365 days of recovery 6. Page 10, Blood Hormone Determination, Frequency. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery, delete the text in this section and replace with the following. Three times before initiation of treatment; after at least 30, 60, 90, and 180 days of treatment; and after at least 30, 60, 90, 135, 180, 274, and 365 days of recovery 321 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 2 _________________Page 3 7. Page 11, Serum PFOS Level Determination, Frequency. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery, delete the text in this section and replace with the following. Before initiation of treatment; during Weeks 1 (Day 7), 2, 4, 6, 8, 12, 16, 20, 24, 26, and 27 (Day 183) during treatment; and during Weeks 27 (Days 184, 185, and 187), 28 (Day 190), 29 (Day 197), 30 (Day 204), 31 (Day 211), 35, 39, 43, 47, 51, 53, 57, 61, 65, 69, 73, 77, and 79 Effective August 24, 1999, and January 12 and 21, 2000 8. Page 13, Termination, Scheduled Sacrifices. To reflect the decision of the Sponsor and the Study Director to extend the length of recovery (effective August 24, 1999), to reflect the decision of the Sponsor to cancel the recovery necropsy (effective January 12, 2000), and to subsequently clarify the requirement (effective January 21, 2000), delete the text in this section and replace with the following. After at least 26 weeks of treatment, up to four animals/sex/group will be fasted overnight, then anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. After at least 26 weeks of treatment and at least 52 weeks without treatment, the remaining animals will be removed from the study as follows. Two animals/sex in Group 1 will be returned to the Covance stock. Two animals/sex in Group 3 will be transferred to a subsequent study (Covance 6329-268). Two animals/sex in Group 4 will be fasted overnight, then anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. Effective August 24 and September 22, 1999 9. Page 12, Additional Fecal Samples. At the request of the Sponsor to collect liver samples by biopsy (effective August 24, 1999) and to modify the procedures (effective September 22, 1999), add the following after this section. 322 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 2 _________________Page 4 Interim Liver Biopsy Samples A sample ofliver (approximately 1 to 2 g) will be collected by biopsy from animals in Group 4 only during recovery (Week 57, within 1 day of the serum PFOS blood collection). This sample will be divided into four portions as follows. One subsample will be preserved in 10% neutral-buffered formalin, embedded in paraffin, sectioned, stained with hematoxylin and eosin (duplicate slides will be prepared), and examined microscopically. The second subsample will be flash-frozen in liquid nitrogen, and stored in a freezer, set to maintain -60 to -80C, until shipped for analysis to: Kris J. Hansen, PhD 3ME. T. & S. Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone No.: 651.778.6018 Facsimile No.: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Results will be provided for inclusion in the final report. The third subsample will be processed to block stage for electron microscopic evaluation. The tissue blocks and a hematoxylin and eosin-stained slide for light microscopy will be transferred to: Sharon Ambrose Division Director Pathology Associates International 4915 D. Prospectus Drive Durham, North Carolina 27713 Telephone No.: 919.544.5257 Facsimile No.: 919.544.3218 Tissues will be processed and evaluated by electron microscopy by Pathology Associates International (PAI). A report will be provided by PAI for inclusion in the final report. Sharon Ambrose or her alternate will be notified regarding the shipment of the samples. 323 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 2 _________________Page 5 The fourth subsample will be flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80 C, and transferred to the Sponsor for possible future analysis. Effective January 12 and 21, 2000 10. Page 12, Interim Liver Biopsy Samples. At the request of the Sponsor to collect liver samples by biopsy, then terminate the study and transfer the animals to a subsequent study (effective January 12, 2000) and to modify the requirement (effective January 21, 2000), add the following after this section. Terminal Liver Biopsy Samples A sample of liver (approximately 1 g) will be collected by biopsy from all animals in Groups 3 during recovery (Week 79, within 1 day of the serum PFOS blood collection). This sample will be flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80C, until shipped for analysis to: Kris J. Hansen, PhD 3ME. T. & S. Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone No.: 651.778.6018 Facsimile No.: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Results will be provided for inclusion in the final report. Effective January 21, 2000 11. Page 12, Additional Serum Collection. To reflect the decision of the Sponsor to analyze additional serum samples for specified thyroid hormones, add following to the end of this section. An aliquot (0.8 ml) of the additional serum collection samples collected from all animals from Groups 1, 2, 3 and 4 sacrificed at the terminal necropsy will be sent on dry ice by the Sponsor to Dr. Saroj Das, Ani Lytics, for free T3, free T4, total T3, and total T4 determinations. 324 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 2 _________________Page 6 12. Page 12, Urine and Feces PFOS Level Determination, Frequency. To reflect the decision of the Sponsor to collect a 24-hour urine and fecal sample after one year of recovery, delete the text in this section and replace with the following. On the first day of recovery and after at least 6, 30, 90, 135, and 180 days of recovery. In addition, a 24-hour sample of urine and feces will be collected before the completion of 52 weeks of recovery. 13. Page 16, Postmortem Procedures, Histopathology. To define the postmortem procedures for recovery animals in the high-dose group, add the following after this section. Postmortem Procedures for Recovery Animals in the High-Dose Group At necropsy of the recovery animals in the high-dose group, procedures (including organ weights and collection of tissues for histopathological examination) described previously are not required. The following procedures will be done. Necropsy The necropsy will include examination of: all orifices cranial cavity external surface of the brain; the external surface of the spinal cord and cut surfaces of the brain and spinal cord will be examined when tissue trimming is performed cervical tissues and organs thoracic, abdominal, and pelvic cavities and viscera external surface of the body nasal cavity and paranasal sinuses Liver Samples A sample of liver (approximately 1 to 2 g) will be collected. This sample will be divided into three portions as follows. One subsample will be preserved in 10% neutral-buffered formalin, embedded in paraffin, sectioned, stained with hematoxylin and eosin (duplicate slides will be prepared), and examined microscopically. The second subsample will be flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80C, until shipped for analysis to: 325 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 2 _________________Page 7 Kris J. Hansen, PhD 3ME. T. & S. Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone No.: 651.778.6018 Facsimile No.: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Results will be provided for inclusion in the final report. The third subsample will be processed to block stage for electron microscopic evaluation. The tissue blocks and a hematoxylin and eosin-stained slide for light microscopy will be transferred to: Sharon Ambrose Division Director Pathology Associates International 4915 D. Prospectus Drive Durham, North Carolina 27713 Telephone No.: 919.544.5257 Facsimile No.: 919.544.3218 Tissues will be processed and evaluated by electron microscopy by Pathology Associates International (PAI). A report will be provided by PAI for inclusion in the final report. Sharon Ambrose or her alternate will be notified regarding the shipment of the samples. Additional Tissue and Serum Samples Samples of lung, kidney, spleen, thyroid, brain, abdominal fat, heart, bile, (approximately 3 g each), and serum (as much as possible) will be collected. These samples will be flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80C, until shipped for possible future analysis to: Kris J. Hansen, PhD 3ME. T. & S. Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone No.: 651.778.6018 Facsimile No.: 651.778.6176 326 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 2 _________________Page 8 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Effective February 11 and 15, 2000 14. Page 3, Proposed Study Timetable. To change proposed dates for in-life termination (effective February 11, 2000) and the audited draft report (effective February 15, 2000), delete the text in this section and replace with the following. Experimental Start Date: August 26, 1998 In-life Start Date: August 26, 1998 In-life Termination Date: March 7, 2000 Unaudited Draft Interim Report Date: May 11, 1999 Audited Draft Report Date: May 29, 2000 Experimental Termination Date: To be determined AMENDMENT APPROVAL 327 cov/v*rcl> THE DEVELOPMENT SERVICES COMPANY PROTOCOL AMENDMENT NO. 3 Covance 6329-223 3M T-6295.7 26-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 August 20,1998 1. Page 16, Reports, Final Report, Statistical Evaluation, Paragraph 4. To correct an omission, add the following to the end of the section. Data collected during recovery will not be analyzed statistically due to the small sample size. Effective January 21,2000 2. Protocol Amendment No. 2, Item 13. To correct a typographical error, change the font to bold on the following heading. Postmortem Procedures for Recovery Animals in the High-Dose Group Effective February 18, 2000 3. Page 12, Serum PFOS Level Determinations, Sample Shipping, Paragraph 3, Sentence 3. To indicate that the results of the Sponsor's analysis of serum samples for PFOS will be reported separately, delete this sentence and replace with the following. Results will be reported separately. 328 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 3 ______________________________________________ __________________________ Page 2 4. Page 12, Interim Liver Biopsy Samples, Paragraph 3, Sentence 2. To indicate that the results of the Sponsor's analysis of the interim liver biopsy samples will be reported separately, delete this sentence and replace with the following. Results will be reported separately. 5. Page 12, Terminal Liver Biopsy Samples, Paragraph 2, Sentence 2. To indicate that the results of the Sponsor's analysis of the terminal liver biopsy samples will be reported separately, delete this sentence and replace with the following. Results will be reported separately. 6. Page 15, Postmortem Procedures, Liver PFOS Determinations, Sentence 2. To indicate that the results of the Sponsor's analysis of the liver samples will be reported separately, delete this sentence and replace with the following. Results will be reported separately. 7. Page 16, Reports, Final Report, Statistical Evaluation, Paragraph 4. To remove repeated measure statistical analysis of cholesterol and total and free triiodothyronine (T3) at the request of the Sponsor, delete the following. Cholesterol and total and free triiodothyronine (T3) will be analyzed by repeated measures analysis of covariance (ANCOVA) procedure with average pretreatment measurements for the parameters as covariates. Treatment effects under ANOVA or ANCOVA procedures will be evaluated at p = 0.05 level. All post-hoc control-versus-treated-group mean comparisons (including values during recovery) will be conducted using Dunnett's many-on-one t procedure. Analyses will be carried out with SAS procedure PROC MIXED or BMDP, or both. Effective February 18 and 22,2000 8. Page 16, Reports, Final Report, Results. To indicate that the results of the Sponsor's analysis of the serum and liver samples (effective February 18, 2000) and urine and feces samples (effective February 22, 2000) will be reported separately, delete the following. serum, urine, feces, and liver PFOS levels (provided by 3M) 329 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 3 ________________ Page 3 Page 16, Postmortem Procedures for Recovery Animals in the High-Dose Group, Liver Samples. To indicate that the results of the Sponsor's analysis of the liver samples will be reported separately (effective February 18,2000) and to modify the amount of liver collected at necropsy (effective February 22, 2000), delete the text in this section and replace with the following. Samples of liver will be collected as follows. One sample will be preserved in 10% neutral-buffered formalin, embedded in paraffin, sectioned, stained with hematoxylin and eosin (duplicate slides will be prepared), and examined microscopically. The second sample will be flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80C, until shipped for analysis to: Kris J. Hansen, PhD 3M E. T. & S. Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone No.: 651.778.6018 Facsimile No.: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Results will be reported separately. The third sample will be processed to block stage for electron microscopic evaluation. The tissue blocks and a hematoxylin and eosin-stained slide for light microscopy will be transferred to: Sharon Ambrose Division Director Pathology Associates International 4915 D. Prospectus Drive Durham, North Carolina 27713 Telephone No.: 919.544.5257 Facsimile No.: 919.544.3218 Tissues will be processed and evaluated by electron microscopy by Pathology Associates International (PAI). A report will be provided by PAI for inclusion in the final report. Sharon Ambrose or her alternate will be notified regarding the shipment of the samples. 330 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 3 ________ ____________________________________________________________________ Page 4 Effective February 22, 2000 10. Page 13, Urine and Feces PFOS Determination, Sample Shipping, Paragraph 2, Sentence 3. To indicate that the results of the Sponsor's analysis of the urine and feces samples will be reported separately, delete this sentence and replace with the following. Results will be reported separately. 11. Page 16, Postmortem Procedures for Recovery Animals in the High-Dose Group, Additional Tissue and Serum Samples, Paragraph 1. To modify the amount of tissue collected at necropsy, delete this paragraph and replace with the following. Samples of lung, kidney, spleen, thyroid, brain, abdominal fat, heart, (approximately 3 g each, if possible), and bile and serum (each as much as possible) will be collected. These samples will be flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80C, until shipped for possible future analysis to: Kris J. Hansen, PhD 3M E. T. & S. Bldg. 2-3E-09 935 Bush Avenue St. Paul, Minnesota 55106 Telephone No.: 651.778.6018 Facsimile No.: 651.778.6176 Kris J. Hansen or her alternate will be notified regarding the shipment of the samples. Effective April 6,2000 12. Page 3, Regulatory Compliance. To include a compliance exception for the fecal analysis done at the Mayo Clinic, delete the text in this section and replace with the following. 331 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 3 ________________________ .____________________ _________________ Page 5 This study will be conducted in compliance with the Environmental Protection Agency Good Laboratory Practice Regulations as set forth in Title 40 of the US Code of Federal Regulations, Part 792, issued November 29, 1983 (effective December 29, 1983), and with any applicable amendments with the following exception. Analysis of fecal samples for urobilinogen at the Mayo Clinic will not be done in compliance with GLPs. 13. Page 3, Quality Assurance. To include an exception for the fecal analysis done at the Mayo Clinic, add the following to the end of the section. Analysis of fecal samples for urobilinogen at the Mayo Clinic will not be done in compliance with GLPs and will not be audited by a Quality Assurance Unit. 14. Page 12, Additional Fecal Samples. To clarify analysis and reporting requirements for fecal analysis, add the following to the end of this section. The samples will be analyzed for urobilinogen using a routine standardized colormetric assay. The results of these analyses will be provided for inclusion in the final report. 15. Page 17, Record Retention, Paragraph 2. To include the record retention requirements for fecal analysis, delete this paragraph and replace with the following. Within 1 year after submission of the final report, all of the aforementioned materials from the Sponsor's designees (Ani Lytics Inc., 3M E. T. & S, Mayo Clinic, and Pathology Associates International) will be sent to the Sponsor (Andrew Seacat, PhD, 3M) by the Sponsor's designees. Effective April 7,2000 16. Page 2, Purpose. To modify the purpose of the study, delete the text in this section and replace with the following. To assess the effect of the test material on critical enzyme levels, hormones, and other selected biochemical parameters when administered daily by capsule to cynomolgus monkeys for at least 26 weeks. The treatment period will be followed by an approximate 52-week recovery period. 332 333 covAfsrcir^ THE DEVELOPMENT SERVICES COMPANY PROTOCOL AMENDMENT NO. 4 Covance 6329-223 3M T-6295.7 26-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 24 May 2001 1. Page 13, Postmortem Procedures, Electron Microscopy, and all other occurrences of "Pathology Associates International." To reflect a change in the name of the subcontractor, delete all occurrences of "Pathology Associates International" in the protocol and replace with the following. Pathology Associates North Carolina Division, A Charles River Company Effective 27 August 2001 2. Page 12, Additional Serum Collection To reflect the Sponsor's decision to do additional hormone analyses at Ani Lytics, Inc. on serum samples, add the following to the end of the section. At the request of the sponsor, serum samples collected at the terminal and recovery sacrifices will be transferred by the sponsor to Ani Lytics, Inc. for analysis of estradiol, follicle stimulating hormone (FSH), and lutenizing hormone (LH) for females, and estradiol in males. Results of these analyses will be provided for inclusion in the final report. 334 Covance 6329-223 3M T-6295.7 Protocol Amendment No. 4 __________________________________________________________ _____________ Page 2 Effective 17 September 2001 3. Page 12, Additional Serum Collection To reflect the Sponsor's decision to do additional analyses at Mayo Clinic on serum samples, add the following to the end of the section. At the request of the sponsor, specified serum samples will be transferred by the sponsor to R. Singh, PhD, Hilton 730, Mayo Clinic, Rochester, MN for analysis of triiodothyronine (T3), total thyroxin (T4), free thyroxin (free T4), and thyroid stimulating hormone (TSH). Additional reserve samples of serum will be transferred for possible future analysis for estradiol. Any unused serum will be returned to the sponsor. Results of these analyses will be provided for inclusion in the final report. AMENDMENT APPROVAL Andrew M. Seacat, PhD Study Monitor 3M Date 335 APPENDIX 2 Individual Animal Fate Data Individual Clinical Observations Individual Ophthalmic Observations Covance 6329-223 3M T-6295.7 336 APPENDIX 2 Individual Animal Fate Data Covance 6329-223 3M T-6295.7 26 -WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL DOSE NUMBER GROUP SEX I05508 1 MALE I05517 1 MALE I05519 1 MALE I05520 1 MALE I05526 1 MALE I05527 1 MALE I05514 2 MALE I05515 2 MALE I05516 2 MALE I05521 2 MALE I05505 3 MALE I05510 3 MALE I05518 3 MALE I05523 3 MALE I05524 3 MALE I05528 3 MALE I05506 4 MALE I05507 4 MALE I05509 4 MALE I05511 4 MALE I05512 4 MALE I05522 4 MALE I05529 1 FEMALE I05530 1 FEMALE I05531 1 FEMALE I05535 1 FEMALE I05544 1 FEMALE I05549 1 FEMALE I05537 2 FEMALE I05541 2 FEMALE I05547 2 FEMALE I05550 2 FEMALE I05532 3 FEMALE I05538 3 FEMALE DEATH CODE TYPE OF DEATH DESCRIPTION OF DEATH T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE O UNSCHEDULED UNSCHEDULED DEATH O UNSCHEDULED UNSCHEDULED DEATH T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE 6 SCHEDULED SIXTH INTERIM SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE 6 SCHEDULED SIXTH INTERIM SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE M UNSCHEDULED UNSCHEDULED DEATH T SCHEDULED TERMINAL SACRIFICE D UNSCHEDULED UNSCHEDULED DEATH U SCHEDULED FIRST POST-RECOV SAC T SCHEDULED TERMINAL SACRIFICE U SCHEDULED FIRST POST-RECOV SAC P UNSCHEDULED UNSCHEDULED DEATH T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE P UNSCHEDULED UNSCHEDULED DEATH T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE T SCHEDULED TERMINAL SACRIFICE DATE OF DEATH 02/25/99 02/25/99 02/25/99 02/25/00 02/25/00 02/25/99 02/25/99 02/26/99 02/26/99 02/26/99 03/08/00 02/26/99 02/26/99 03/08/00 02/26/99 02/26/99 02/20/99 02/25/99 01/27/99 02/25/00 02/25/99 02/25/00 02/25/00 02/25/99 02/26/99 02/26/99 02/25/99 02/25/00 02/25/99 02/26/99 02/26/99 02/26/99 02/25/99 02/25/99 DAY OF STUDY 184 184 184 549 549 184 184 185 185 185 561 185 185 561 185 185 179 184 155 549 184 549 549 184 185 185 184 549 184 185 185 185 184 184 WEEK OF STUDY 27 27 27 79 79 27 27 27 27 27 81 27 27 81 27 27 26 27 23 79 27 79 79 27 27 27 27 79 27 27 27 27 27 27 PAGE: 1 337 APPENDIX 2 Individual Animal Fate Data Covance 6329-223 3M T-6295.7 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER I05539 I05545 I05548 I05552 I05533 I05534 I05536 I05540 I05542 I05551 DOSE GROUP 3 3 3 3 4 4 4 4 4 4 SEX FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE FEMALE DEATH CODE 6 T T 6 U T T T U T TYPE OF DEATH SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED SCHEDULED DESCRIPTION OF DEATH SIXTH INTERIM SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE SIXTH INTERIM SACRIFICE FIRST POST-RECOV SAC TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE FIRST POST-RECOV SAC TERMINAL SACRIFICE DATE OF DEATH 03/08/00 02/25/99 02/25/99 03/08/00 02/25/00 02/26/99 02/25/99 02/26/99 02/25/00 02/26/99 DAY OF STUDY 561 184 184 561 549 185 184 185 549 185 WEEK OF STUDY 81 27 27 81 79 27 27 27 79 27 PAGE: 2 338 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05508 T 27 NORMAL NO REMARKABLE OBSERVATIONS 1P 8P - - - 15 P - - - 22 P - - - 29 P - - - 36 P - - - 43 P - - - 50 P - - - 57 P - - - 64 P - - - 71 P - - - 78 P - - - 85 P - - - 92 P - - - 99 P - - - 106 P - - - 113 P - - - 120 P - - - 127 P - - - 134 P - - - 141 P - - - 148 P - - - 155 P - - - 162 P - - - 169 P - - - 176 P - - - 183 P - -- 184 P - -P 339 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05517 T 27 NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE FOOD CONSUMPTION LOW 1P 8P 15 P 22 P 29 P 36 P 43 P 50 P 57 P 64 P 71 P 78 P 85 P 92 P 99 P 106 P 113 P 120 P 127 P 134 P 141 P 148 P 155 P 162 P 169 P 176 P 183 P 184 P 102 P 340 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05517 T 27 QUALITATIVE FOOD CONSUMPTION LOW 141 176 177 179 I05519 T 27 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 113 120 127 134 141 148 155 162 169 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--- P--P P P P P P P P P P P P P P P P P P P P P P P P 341 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05519 T 27 NORMAL NO REMARKABLE OBSERVATIONS 176 183 184 I05520 O 79 DISCHARGE VOMITUS CONTAINING FOOD 141 EXCRETION LIQUID FECES NON-FORMED FECES 29 29 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 36 43 50 57 64 71 78 85 92 99 106 113 120 127 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P P--- P P-P- P P P P P P P P P P P P P P P P P P 342 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 5 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05520 O 79 NORMAL NO REMARKABLE OBSERVATIONS 134 148 155 162 169 176 183 QUALITATIVE FOOD CONSUMPTION LOW 122 I05526 O 79 EXCRETION NON-FORMED FECES 179 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P 343 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 6 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) 105526 O 79 NORMAL NO REMARKABLEOBSERVATIONS 113 120 127 134 141 148 155 162 169 176 183 105527 T 27 DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED INCOLOR 144 EXCRETION NON-FORMEDFECES 2 SKIN & PELAGE BROKEN SKIN HAND-LEFT TAIL 37 38 39 40 43 168 169 170 176 177 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P--P-PP-PP--P----PP----PP----P- 344 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 7 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05527 T 27 SKIN & PELAGE BROKEN SKIN TAIL TAIL-DISTAL 178 179 180 181 183 184 145 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 50 57 64 71 78 85 92 99 106 113 120 127 134 141 148 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP--P----PP--P--P --P- P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 345 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 8 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05527 T 27 NORMAL NO REMARKABLE OBSERVATIONS 155 162 QUALITATIVE FOOD CONSUMPTION LOW 43 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P 346 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 9 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05514 T 27 EXCRETION LIQUID FECES NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 91 P - - 105 - - P 132 - - P - 1P 8P 15 P 22 P 29 P 36 P 43 P 50 P 57 P 64 P 71 P 78 P 85 P 92 P 99 P 106 P 113 P 120 P 127 P 134 P 141 P 148 P 155 P 162 P 169 P 176 P 347 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 10 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05514 T 27 NORMAL NO REMARKABLE OBSERVATIONS 183 184 QUALITATIVE FOOD CONSUMPTION LOW 102 179 I05515 T 27 EXCRETION NON-FORMED FECES 69 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 113 120 127 134 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P P--P--- --P- P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 348 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 11 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05515 T 27 NORMAL NO REMARKABLE OBSERVATIONS 141 148 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 141 162 I05516 T 27 DISCHARGE VOMITUS CONTAINING FOOD PARTIAL CAPSULE 179 85 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P P--P--- P----P- P--P--P--P--P--P--P--P--P--P--P--P--- 349 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 12 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05516 T 27 NORMAL NO REMARKABLE OBSERVATIONS 85 92 99 106 113 120 127 134 141 148 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 179 I05521 T 27 SKIN & PELAGE BROKEN SKIN PERI-ORBITAL-RIGHT 20 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P-P- P--P--P--P--P--P--- 350 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 13 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05521 T 27 NORMAL NO REMARKABLE OBSERVATIONS 43 50 57 64 71 78 85 92 99 106 113 120 127 134 141 148 155 162 169 176 183 185 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P 351 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 14 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY I05505 6 81 DISCHARGE VOMITUS CONTAINING FOOD NORMAL NO REMARKABLE OBSERVATIONS 141 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 113 120 127 134 148 155 162 169 176 183 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-- P P P P P P P P P P P P P P P P P P P P P P P P P P 352 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 15 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05505 6 81 QUALITATIVE FOOD CONSUMPTION LOW 80 141 180 I05510 T 27 EXCRETION DISCOLORED URINE RED IN COLOR 97 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 113 120 134 141 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P 353 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 16 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) T 27 NORMAL NO REMARKABLE OBSERVATIONS 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 67 73 109 127 141 142 148 154 180 183 I05518 T 27 DISCHARGE VOMITUS CONTAINING FOOD 179 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P--- P--P--P--P--P--P--P--- 354 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 17 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05518 T 27 NORMAL NO REMARKABLE OBSERVATIONS 50 57 64 71 78 85 92 99 106 113 120 127 134 141 148 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 141 179 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P P P--- 355 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 18 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05523 6 81 SKIN & PELAGE BROKEN SKIN TAIL NORMAL NO REMARKABLE OBSERVATIONS 149 - - P 1P 8P 15 P 22 P 29 P 36 P 43 P 50 P 57 P 64 P 71 P 78 P 85 P 92 P 99 P 106 P 113 P 120 P 127 P 134 P 141 P 148 P 155 P 162 P 169 P 176 P 183 P 356 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 19 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05523 6 81 QUALITATIVE FOOD CONSUMPTION LOW 6 141 179 I05524 T 27 DISCHARGE VOMITUS CONTAINING FOOD 141 EXCRETION NON-FORMED FECES 179 180 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 50 57 64 71 78 85 92 99 106 113 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P 357 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 20 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05524 T 27 NORMAL NO REMARKABLE OBSERVATIONS 120 127 134 148 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 43 65 141 179 180 I05528 T 27 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 85 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P P--P--P--P--P--- P--P--P--P--P--P--P--P--P--P--P--P--- 358 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 21 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05528 T 27 NORMAL NO REMARKABLE OBSERVATIONS 92 99 106 120 134 141 148 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 78 113 116 127 134 162 176 179 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P 359 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 22 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05506 M 26 BEHAVIOR ATAXIC <UNSPECIFIED> HYPOACTIVE <UNSPECIFIED> DISCHARGE EXCESSIVE SALIVATION RESPIRATION LABORED NORMAL NO REMARKABLE OBSERVATIONS 179 - P - P 179 - P - P 179 - P - - 179 - P - P 1P 8P - - - 15 P - - - 22 P - - - 29 P - - - 36 P - - - 43 P - - - 50 P - - - 57 P - - - 64 P - - - 71 P - - - 78 P - - - 85 P - - - 92 P - - - 99 P - - - 106 P - - - 113 P - - - 120 P - - - 127 P - - - 360 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 23 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05506 M 26 NORMAL NO REMARKABLE OBSERVATIONS 134 141 148 155 162 169 176 QUALITATIVE FOOD CONSUMPTION LOW 3 141 178 179 T 27 DISCHARGE VOMITUS PARTIAL CAPSULE 11 111 178 SKIN & PELAGE BROKEN SKIN DIGIT(S)-FRONT-LEFT 97 98 99 100 101 102 104 106 107 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-P-P-P-P-P-P-- P-P-P-P-- --P --P --P --P P-P P-P P---P P-P-P P-P P-P 361 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 24 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05507 T 27 SKIN & PELAGE BROKEN SKIN DIGIT(S)-FRONT-LEFT 108 111 112 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 113 120 127 134 141 148 155 162 169 176 183 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P P 362 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 25 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05507 T 27 NORMAL NO REMARKABLE OBSERVATIONS 184 QUALITATIVE FOOD CONSUMPTION LOW 141 I05509 D 23 APPEARANCE APPEARS DEHYDRATED OTHER 155 155 BEHAVIOR HYPOACTIVE <UNSPECIFIED> 155 EXCRETION DISCOLORED FECES BLACK IN COLOR FEW FECES LIQUID FECES MUCOID FECES NO FECES 155 152 155 155 155 154 EYES CONSTRICTED PUPIL EYES 154 RESPIRATION LABORED 155 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P P--- PP PC -P-P P P--P--P--P--P --- --P- PP 363 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 26 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05509 D 23 SKIN & PELAGE COLD TO TOUCH BODY-ENTIRE PALE SKIN GUMS 155 154 155 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 113 120 127 134 141 148 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH -P-P --P-P-P P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 364 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 27 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05509 D 23 QUALITATIVE FOOD CONSUMPTION LOW 141 152 154 155 I05511 U 79 DISCHARGE VOMITUS CONTAINING FOOD PARTIAL CAPSULE 100 155 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 113 120 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-P-P-- P-- P-- P P P P P P P P P P P P P P P P P P P - 365 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 28 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05511 U 79 NORMAL NO REMARKABLE OBSERVATIONS 127 134 141 148 155 162 169 176 183 QUALITATIVE FOOD CONSUMPTION LOW 57 60 100 102 141 145 148 154 155 170 171 172 173 174 175 176 177 179 180 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P P 366 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 29 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05512 T 27 DISCHARGE VOMITUS PARTIAL CAPSULE EXCRETION FEW FECES NO FECES NON-FORMED FECES 32 - - P 37 - - P - 100 P - - - 102 P - - - 105 P - - - 106 P - - - 110 P - - - 125 P - - - 126 P - - - 127 P - - - 128 P - - - 129 P - - - 130 P - - - 133 P - - - 134 P - - - 155 P - - - 156 P - - - 157 P - - - 158 P - - - 159 P - - - 161 P - - - 181 P - - - 183 P - - - 184 P - - - 99 P - - - 131 P - - - 132 P - - - 130 P - - - 367 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 30 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05512 T 27 EXCRETION NON-FORMED FECES 133 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 113 120 141 148 162 169 176 184 QUALITATIVE FOOD CONSUMPTION LOW 17 98 99 100 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--- P P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P-----P P--P--P--P--- 368 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 31 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05512 T 27 QUALITATIVE FOOD CONSUMPTION LOW 102 105 110 116 125 126 127 128 129 130 131 132 133 134 155 156 157 158 159 160 161 162 164 168 174 175 176 178 179 180 181 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P 369 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 32 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05512 T 27 QUALITATIVE FOOD CONSUMPTION LOW 183 I05522 U 79 EXCRETION MUCOID FECES 179 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 113 120 127 134 141 148 155 162 169 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--- P P P P P P P P P P P P P P P P P P P P P P P P P P 370 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 33 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05522 U 79 NORMAL NO REMARKABLE OBSERVATIONS 176 183 QUALITATIVE FOOD CONSUMPTION LOW 102 180 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--- P--P--- 371 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 34 STUDY ANIMAL GROUP DAY WK CATEGORY KEYWORD QUALIFIER FREE-TEXT COMMENT I05509 M4 155 23 APPEARANCE OTHER AFTER DOSING ANIMAL BECAME RECUMBENT. VET WAS CALLED. ANIMAL DIED PRIOR TO VET EXAM. 372 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 35 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05529 P 79 APPEARANCE APPEARS DEHYDRATED BEHAVIOR HYPOACTIVE <UNSPECIFIED> DISCHARGE NASAL CLEAR ORAL CLOUDY EXCESSIVE SALIVATION EXCRETION LIQUID FECES 5- - P 6P - - 7P - - - 6- - P 7P - - 8P - P - 5- - P 6P - P 7P - - 8P - P 9P - - - 6- - P 7P - - 8P - - 5- - P 6P - P 7P - - 8P - - - 29 P - - 30 P - - 38 P - P 39 P - - - 373 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 36 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 EXCRETION LIQUID FECES NON-FORMED FECES 40 41 42 43 44 65 66 67 68 69 70 99 100 101 102 115 71 73 77 103 115 SKIN & PELAGE ALOPECIA FEET 105 106 107 108 109 110 111 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH --PP--P-PP--P----PP--P--P--P--P----PP-PP--P----PP--P--P--P--P--- P-PP-PP-PP-PP-PP-PP-P- 374 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 37 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA FEET GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 112 113 114 115 117 118 119 120 121 122 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 142 143 146 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-P--P--PP-PP-PP-PP-P--PP-PP-PP-PP-PP-PP-PP-PP-PP--P-PP-PP-PP-PP-P- 375 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 38 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA FEET GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 147 148 149 150 151 152 153 154 155 156 157 158 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P -P P -P -P P -P P -P P -P P -P P -P -P -P -P - -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P 376 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 39 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA FEET LIMBS-HIND TAIL 180 181 182 183 184 185 92 93 94 95 96 98 99 100 101 102 142 144 134 135 136 137 138 139 140 142 143 146 147 148 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-P--PP-PP-PP--P----P--PP-PP-PP-PP-PP-PP-PP--P-P--P--PP-PP-PP-PP-PP--P-PP-PP-PP-PP-PP-PP--- 377 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 40 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA TAIL GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 149 150 151 152 153 154 155 156 157 158 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P -P P -P P -P P -P P -P P -P -P -P -P - -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P P -P - -P 378 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 41 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA TAIL 182 183 184 185 NORMAL NO REMARKABLE OBSERVATIONS 1 15 22 36 50 57 64 78 85 92 141 QUALITATIVE FOOD CONSUMPTION LOW 5 8 41 42 69 72 73 75 102 174 179 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP--P--- P--P--P--P--P--P--P--P--P--P--P--- P--P--P--P--P--P--P--P--P--P--P--- 379 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 42 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05530 T 27 DISCHARGE VOMITUS PARTIAL CAPSULE APPEARS TO BE MENSTRUATING EXCRETION DISCOLORED FECES RED IN COLOR LIQUID FECES MUCOID FECES NON-FORMED FECES 97 - - P 39 - - P 40 P - - 92 P - - 176 P - - 180 P 28 P - - 27 P - - 28 P - P 29 P - - 31 - - P 32 P - - 33 P - - 34 P - P 35 P - - 36 P - - 37 P - - 38 P - P 39 - - P 40 P - - 49 P - - 50 P - - 51 P - P 55 P - - 28 P - - 12 P - - 31 P - - - 380 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 43 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05530 T 27 EXCRETION NON-FORMED FECES 41 54 55 57 SKIN & PELAGE BROKEN SKIN MOUTH 10 12 15 22 23 25 26 27 28 29 30 31 NORMAL NO REMARKABLE OBSERVATIONS 1 8 43 64 71 78 85 99 106 113 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--- --PP--P--P--P--P-PP-PP-PP-PP-PP-PP-P- P P P P P P P P P P 381 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 44 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) T 27 NORMAL NO REMARKABLE OBSERVATIONS 120 127 134 141 148 155 162 169 183 184 QUALITATIVE FOOD CONSUMPTION LOW 26 27 29 141 I05531 T 27 DISCHARGE VOMITUS CONTAINING FOOD APPEARS TO BE MENSTRUATING 179 176 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P--P--- P--P--P--P--P--P--P--P--- 382 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 45 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05531 T 27 NORMAL NO REMARKABLE OBSERVATIONS 57 64 71 78 85 92 99 106 113 120 127 134 141 148 155 162 169 183 185 QUALITATIVE FOOD CONSUMPTION LOW 141 179 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P P P--- 383 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 46 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05535 T 27 DISCHARGE APPEARS TO BE MENSTRUATING SKIN & PELAGE RED SKIN LIMB-FRONT-RIGHT SCAB(S) LIMB-FRONT-LEFT LIMB-FRONT-RIGHT NORMAL NO REMARKABLE OBSERVATIONS 37 - - P 38 P - - 108 P - P 137 P - P 138 P - - 166 P - P - 167 P - P - 22 - - P - 23 - - P 24 P - P - 21283 P - - P - 23 - - P - 24 P - P - 18 P P - - - 2125 P P - - - 29 P - - - 36 P - - - 43 P - - - 50 P - - - 57 P - - - 64 P - - - 71 P - - - 384 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 47 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05535 T 27 NORMAL NO REMARKABLE OBSERVATIONS 78 85 92 99 106 113 120 127 134 141 148 155 162 169 176 185 I05544 T 27 DISCHARGE VOMITUS CONTAINING FOOD PARTIAL CAPSULE 141 29 33 34 66 117 141 DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR 112 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- P--P P--- --P- --P- --P- --P- --P- P -- - P 385 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 48 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05544 T 27 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 50 57 64 71 78 85 92 99 106 113 120 134 148 155 162 169 176 183 184 QUALITATIVE FOOD CONSUMPTION LOW 6 36 38 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P P P--P--- 386 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 49 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05544 T 27 QUALITATIVE FOOD CONSUMPTION 42 43 127 171 174 176 I05549 P 79 DISCHARGE VOMITUS INTACT CAPSULE PARTIAL CAPSULE APPEARS TO BE MENSTRUATING 111 97 175 SKIN & PELAGE BROKEN SKIN HEAD-CRANIAL PERI-ORBITAL-LEFT 3 7 8 15 NORMAL NO REMARKABLE OBSERVATIONS 1 22 29 36 43 50 57 64 71 78 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-P-P-P-P-P-- - -P - -P P -- - -P - -P P -P P -P P P P P P P P P P P - 387 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 50 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05549 P 79 NORMAL NO REMARKABLE OBSERVATIONS 85 92 99 106 113 120 127 134 141 148 155 162 169 176 183 QUALITATIVE FOOD CONSUMPTION LOW 141 175 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- P P--- 388 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 51 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05537 T 27 DISCHARGE VOMITUS WHITE IN COLOR APPEARS TO BE MENSTRUATING SKIN & PELAGE BROKEN SKIN HEAD-MAXILLARY-RIGHT PERI-ORBITAL-LEFT PERI-ORBITAL-RIGHT 1- - P - 45 - - P - 46 - - P - 47 P - - - 48 P - - - 49 - - P - 72 P - P - 73 P - P - 74 P - P - 75 P - - - 104 P - - - 105 P - P - 106 P - P - 107 P - - - 168 P - P - 169 P P 50 - - P 52 - - P 8P - P 9P - P - 10 P - P - 3P - P 4P - - 6P - P - 7- - P - 389 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 52 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05537 T 27 NORMAL NO REMARKABLE OBSERVATIONS 1 15 22 29 36 43 50 57 64 71 78 85 92 99 113 120 127 134 141 148 155 162 176 183 184 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P 390 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 53 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05541 T 27 DISCHARGE APPEARS TO BE MENSTRUATING EXCRETION FEW FECES SKIN & PELAGE BROKEN SKIN PERI-ORBITAL-RIGHT NORMAL NO REMARKABLE OBSERVATIONS 99 - - P - 102 P - - - 152 - - P - 154 - - P - 141 P - - - 98 - - P - 99 P - P - 102 P - - - 1P - - - 8P - - - 15 P - - - 36 P - - - 50 P - - - 57 P - - - 64 P - - - 71 P - - - 78 P - - - 85 P - - - 92 P - - - 106 P - - - 120 P - - - 127 P - - - 134 P - - - 148 P - - - 391 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 54 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05541 T 27 NORMAL NO REMARKABLE OBSERVATIONS 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 3 22 28 29 43 55 57 76 87 113 140 169 174 179 I05547 T 27 DISCHARGE APPEARS TO BE MENSTRUATING 129 164 165 167 EXCRETION FEW FECES 150 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P P--P--P--P--P--P--P--P--P--P--P--P--P--P--- P----PP--P--- P--- 392 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 55 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05547 T 27 EXCRETION FEW FECES NO FECES NON-FORMED FECES 151 152 156 168 154 155 178 181 SKIN & PELAGE BROKEN SKIN HEAD-MAXILLARY-LEFT SCAB(S) HEAD-MAXILLARY-LEFT 170 171 172 173 174 175 176 178 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 50 57 64 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P----P- P-PP-PP-P--PP-PP--- P--P-P- P--P--P--P--P--P--P--P--P--- 393 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 56 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05547 T 27 NORMAL NO REMARKABLE OBSERVATIONS 71 78 85 92 106 113 134 141 148 162 169 183 185 QUALITATIVE FOOD CONSUMPTION LOW 17 41 43 55 57 66 99 120 121 127 134 141 148 150 151 152 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P 394 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 57 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05547 T 27 QUALITATIVE FOOD CONSUMPTION LOW 154 155 156 160 161 162 165 167 168 169 170 171 174 175 179 184 I05550 T 27 DISCHARGE APPEARS TO BE MENSTRUATING 91 92 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- --PP--- P--P--P--P--P--P--P--P--P--- 395 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 58 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05550 T 27 NORMAL NO REMARKABLE OBSERVATIONS 64 71 78 85 99 106 113 120 127 134 141 148 155 162 169 176 183 185 QUALITATIVE FOOD CONSUMPTION LOW 3 141 179 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P P P--P--- 396 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 59 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05532 T 27 SKIN & PELAGE BROKEN SKIN HEAD-CRANIAL PERI-ORBITAL-RIGHT NORMAL NO REMARKABLE OBSERVATIONS 2P 3P 31 32 P 33 - 1P 8P 15 P 22 P 36 P 43 P 50 P 57 P 64 P 71 P 92 P 99 P 106 P 113 P 127 P 134 P 141 P 148 P 155 P 162 P 169 P 176 P 183 P -P -P -P -P -P ------------------------ - 397 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 60 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05532 T 27 NORMAL NO REMARKABLE OBSERVATIONS 184 QUALITATIVE FOOD CONSUMPTION LOW 26 29 32 41 55 57 58 65 78 85 115 116 120 126 141 143 147 150 155 162 164 169 170 174 175 176 179 183 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH PP P P P P P P P P P P P P P P P P P P P P P P P P P P P P 398 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 61 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05538 T 27 DISCHARGE VOMITUS CONTAINING FOOD EXCRETION FEW FECES NORMAL NO REMARKABLE OBSERVATIONS 141 P - - 179 P - - 43 P - - 1P 8P 15 P 22 P 29 P 36 P 50 P 57 P 64 P 71 P 78 P 85 P 92 P 99 P 106 P 113 P 120 P 127 P 134 P 148 P 155 P 162 P 169 P 399 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 62 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05538 T 27 NORMAL NO REMARKABLE OBSERVATIONS 176 183 184 QUALITATIVE FOOD CONSUMPTION LOW 27 41 42 43 141 160 167 174 178 179 I05539 6 81 DISCHARGE APPEARS TO BE MENSTRUATING 71 EXCRETION FEW FECES 141 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P P--P--P--P--P--P--P--P--P--P--- P-P- P P--P--P--P--P--P--P--P--- 400 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 63 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05539 6 81 NORMAL NO REMARKABLE OBSERVATIONS 57 64 78 92 99 106 120 134 148 155 162 169 176 183 QUALITATIVE FOOD CONSUMPTION LOW 17 18 24 57 60 70 85 109 113 116 127 132 133 138 139 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P P P 401 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 64 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05539 6 81 QUALITATIVE FOOD CONSUMPTION LOW 150 155 158 159 162 171 174 179 I05545 T 27 DISCHARGE APPEARS TO BE MENSTRUATING 136 EXCRETION NO FECES 51 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 50 57 64 71 85 92 99 106 127 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--- P-P- P--- P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 402 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 65 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05545 T 27 NORMAL NO REMARKABLE OBSERVATIONS 134 141 148 155 162 176 183 184 QUALITATIVE FOOD CONSUMPTION LOW 25 30 35 43 74 78 86 113 116 120 141 149 150 155 161 169 171 174 175 176 179 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P 403 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 66 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05545 T 27 QUALITATIVE FOOD CONSUMPTION LOW 180 183 I05548 T 27 DISCHARGE VOMITUS CONTAINING FOOD 141 EXCRETION FEW FECES 178 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 99 106 113 120 127 134 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--- P--- P--- P P P P P P P P P P P P P P P P P P P P 404 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 67 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05548 T 27 NORMAL NO REMARKABLE OBSERVATIONS 148 155 162 169 176 183 184 QUALITATIVE FOOD CONSUMPTION LOW 18 28 58 141 142 174 I05552 6 81 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 29 36 43 50 57 64 71 78 85 92 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P P--P--P--P--P--P--- P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 405 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 68 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05552 6 81 NORMAL NO REMARKABLE OBSERVATIONS 99 106 113 120 127 134 141 148 155 162 169 176 183 QUALITATIVE FOOD CONSUMPTION LOW 20 141 156 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P 406 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 69 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05533 U 79 DISCHARGE APPEARS TO BE MENSTRUATING SKIN & PELAGE ALOPECIA HEAD-CRANIAL 39 P - P 40 P --- 22 P 24 - - P 27 P - P 28 - - P 29 P - P 30 P - P 31 P - P 32 P - P 33 - - P 34 P - P 35 P - P 36 P - P 37 - - P 38 P - P 39 P - P 40 P - - 41 P - P 42 P - P 43 P - P 44 - - P 45 - - P 48 - - P 49 - - P 50 P - P 51 P - P 52 P - P - 407 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 70 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05533 U 79 SKIN & PELAGE ALOPECIA HEAD-CRANIAL HEAD-MAXILLARY-LEFT 53 54 55 56 57 58 59 60 61 62 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 48 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-P--P--PP----P--PP-PP-PP-PP-P--PP-PP-PP-P--PP-PP-PP--P-PP-PP-P--P--P--P- 408 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 71 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05533 U 79 SKIN & PELAGE ALOPECIA HEAD-MAXILLARY-LEFT HEAD-MAXILLARY-RIGHT 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH --PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P--P--PP-PP-P--P--PP-PP-PP-PP-P--PP-PP-PP-P--PP-PP-PP--P-P- 409 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 72 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05533 U 79 SKIN & PELAGE ALOPECIA HEAD-MAXILLARY-RIGHT 42 43 44 45 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 NORMAL NO REMARKABLE OBSERVATIONS 1 8 15 22 64 71 78 85 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-P--P--P--P--PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P--P--PP-PP-P- P--P--P--P--P--P--P--P--- 410 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 73 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) 105533 U 79 NORMAL NO REMARKABLE OBSERVATIONS 92 99 106 113 120 127 134 141 148 155 162 169 176 183 QUALITATIVE FOOD CONSUMPTION LOW 141 105534 T 27 DISCHARGE VOMITUS PARTIAL CAPSULE APPEARS TO BE MENSTRUATING 6 10 72 59 98 133 134 EXCRETION DISCOLORED FECES RED IN COLOR 149 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P --P--P--PP--P--P--P P--- 411 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 74 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05534 T 27 EXCRETION DISCOLORED FECES RED IN COLOR YELLOW IN COLOR FEW FECES LIQUID FECES MUCOID FECES NO FECES NON-FORMED FECES 150 156 102 105 107 109 113 127 163 92 93 136 137 138 139 141 142 143 144 156 185 150 49 110 113 127 137 140 144 145 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P-PP--P--P-PP--P--P--P--P--P--P--P--P--P--P--P--P--P--- 412 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 75 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05534 T 27 EXCRETION NON-FORMED FECES 146 147 148 149 150 SKIN & PELAGE BROKEN SKIN PERI-ORBITAL-LEFT OTHER 70 71 9 10 12 15 NORMAL NO REMARKABLE OBSERVATIONS 1 29 36 50 57 64 85 99 106 155 162 169 176 183 185 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH PPPPP PPC PC PC PC - P P P P P P P P P P P P P P - ----- P PPC PC -PC - 413 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 76 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05534 T 27 QUALITATIVE FOOD CONSUMPTION 2 3 8 10 22 24 38 43 49 60 63 66 78 80 81 92 93 98 100 102 105 109 113 116 120 122 125 127 128 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 414 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 77 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05534 T 27 QUALITATIVE FOOD CONSUMPTION LOW 129 133 134 137 138 141 148 149 150 154 155 156 157 162 164 167 170 174 175 176 180 184 I05536 T 27 DISCHARGE VOMITUS CONTAINING FOOD PARTIAL CAPSULE 141 30 EXCRETION DISCOLORED FECES RED IN COLOR 69 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- P----P- --P- 415 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 78 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05536 T 27 EXCRETION FEW FECES LIQUID FECES NON-FORMED FECES 8888 179 183 NORMAL NO REMARKABLE OBSERVATIONS 18 2125 29 36 43 50 57 64 71 78 85 92 99 106 112103 134 148 155 162 169 176 184 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--- P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P 416 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 79 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05536 T 27 QUALITATIVE FOOD CONSUMPTION 3 65 72 81 88 114 117 126 127 129 130 141 149 156 157 160 180 181 I05540 T 27 DISCHARGE VOMITUS INTACT CAPSULE 99 EXCRETION DISCOLORED FECES RED IN COLOR DISCOLORED URINE GREEN IN COLOR 27 28 71 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- P P P P-- 417 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 80 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 EXCRETION DISCOLORED URINE GREEN IN COLOR FEW FECES MUCOID FECES 72 28 29 28 29 SKIN & PELAGE ALOPECIA DORSAL DORSAL-THORACIC 1 141 1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P----PP--- P----P--PP-P--P--PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 418 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 81 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP--P-PP-PP-P--P--PP-PP-P--P--PP-PP--- 419 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 82 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC 142 143 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 420 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 83 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC DORSAL-THORACIC-LEFT 174 175 176 177 178 179 180 181 182 183 184 185 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP--P --PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 421 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 84 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC-LEFT 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP--P-PP-PP-PP-PP-PP-PP-PP-PP-PP--P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P--PP-PP-PP-PP-P- 422 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 85 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC-LEFT 106 107 108 109 110 111 112 113 114 115 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P--P--P--PP-PP-PP-PP-PP-P- 423 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 86 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA DORSAL-THORACIC-LEFT HEAD-ENTIRE 137 138 139 140 1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-P--P--PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 424 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 87 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA HEAD-ENTIRE LIMB-HIND-LEFT 28 29 30 31 32 33 34 35 36 37 38 39 40 41 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP--P-P--PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 425 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 88 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA LIMB-HIND-LEFT 73 74 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP--P-PP-PP-PP-PP-PP-PP-PP-PP-PP--P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P--PP-PP-P- 426 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 89 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA LIMB-HIND-LEFT LIMBS-ALL LIMBS-FRONT 104 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 1 2 3 5 6 7 8 9 10 11 12 13 14 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P-PP-P--P--PP-PP-P--P--PP-PP-PP-PP-PP-PP-PP--P--P-PP-P--P--PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 427 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 90 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA LIMBS-FRONT TAIL 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 145 146 147 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP--P-P--PP-PP-P- 428 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 91 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA TAIL GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 429 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 92 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05540 T 27 SKIN & PELAGE ALOPECIA TAIL 178 179 180 181 182 183 184 185 QUALITATIVE FOOD CONSUMPTION LOW 17 20 25 27 69 71 73 74 78 80 85 87 120 132 137 141 155 179 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP--P P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 430 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 93 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05542 U 79 DISCHARGE VOMITUS INTACT CAPSULE PARTIAL CAPSULE APPEARS TO BE MENSTRUATING EXCRETION FEW FECES SKIN & PELAGE PALE SKIN HEAD-ENTIRE NORMAL NO REMARKABLE OBSERVATIONS 136 P - P 65 - - P 78 - - P 126 - - P 131 - - P 71 P - P 115 P - - 161 P - - - 155 P - - 161 P - - 162 P - - - 182 - - P 183 P - - 184 P - - - 1P - - 8P - - 15 P - - 22 P - - 29 P - - 50 P - - 57 P - - 64 P - - 85 P - - - 431 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 94 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05542 U 79 NORMAL NO REMARKABLE OBSERVATIONS 99 106 113 120 127 134 141 148 169 176 QUALITATIVE FOOD CONSUMPTION LOW 14 36 43 49 57 59 60 65 78 92 98 125 134 139 141 142 143 154 155 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P P P 432 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 95 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05542 U 79 QUALITATIVE FOOD CONSUMPTION LOW 161 162 175 I05551 T 27 DISCHARGE APPEARS TO BE MENSTRUATING 43 44 45 73 74 75 76 80 112 113 137 138 139 140 141 166 167 168 EXCRETION FEW FECES SMALL FECES 161 49 SKIN & PELAGE ALOPECIA LIMBS-ALL 1 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--- --P--P--PP-PP-PP-PP-PP--P-PP-P--PP-PP-PP-PP-PP-PP-PP--- P--P-P- P-P- 433 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 96 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05551 T 27 SKIN & PELAGE ALOPECIA LIMBS-ALL GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-P--P--P--PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 434 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 97 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05551 T 27 SKIN & PELAGE ALOPECIA LIMBS-ALL GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P--P--PP-PP-P--PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 435 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 98 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05551 T 27 SKIN & PELAGE ALOPECIA LIMBS-ALL GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 436 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 99 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05551 T 27 SKIN & PELAGE ALOPECIA LIMBS-ALL GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-P--PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P--PP-PP-PP-PP-PP-P- 437 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 100 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05551 T 27 SKIN & PELAGE ALOPECIA LIMBS-ALL GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-P--P--P--PP-PP-PP-PP-PP-PP-PP-PP-PP-P--PP-PP-P--P--PP-PP-PP-PP-PP-PP-P- 438 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 101 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05551 T 27 SKIN & PELAGE ALOPECIA LIMBS-ALL GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-PP-P- 439 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 102 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 1-185 DAY (CONTINUED FROM PREVIOUS PAGE) I05551 T 27 SKIN & PELAGE ALOPECIA LIMBS-ALL 182 183 184 185 QUALITATIVE FOOD CONSUMPTION LOW 72 85 102 146 162 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P-PP-PP-PP--P P--P--P--P--P--- 440 Appendix 2 Individual Clinical Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS STUDY ANIMAL GROUP DAY WK CATEGORY KEYWORD QUALIFIER FREE-TEXT COMMENT I05534 F4 9 2 TO 15 3 SKIN & PELAGE OTHER BRUISED SKIN PERI-ORBITAL LEFT EYE Covance 6329-223 3M T-6295.7 PAGE: 103 441 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05520 O 79 SKIN & PELAGE BROKEN SKIN DIGIT(S)-FRONT-LEFT NORMAL NO REMARKABLE OBSERVATIONS 361 P - - 362 P - - - 190 P - - - 197 P - - - 204 P - - - 211 P - - - 218 P - - - 225 P - - - 232 P - - - 239 P - - - 246 P - - - 253 P - - - 260 P - - - 267 P - - - 274 P - - - 281 P - - - 288 P - - - 295 P - - - 302 P - - - 309 P - - - 316 P - - - 323 P - - - 330 P - - - 337 P - - - 344 P - - - 351 P - - - 358 P - - - 365 P - - - 442 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05520 O 79 QUALITATIVE FOOD CONSUMPTION LOW 273 I05526 O 79 NORMAL NO REMARKABLE OBSERVATIONS 190 197 204 211 218 225 232 239 246 253 260 267 274 281 288 295 302 309 316 323 330 337 344 351 358 365 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P 443 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05505 6 81 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 191 P - - - 190 P 197 P - - - 204 P - - - 211 P - - - 218 P - - - 225 P - - - 232 P - - - 239 P - - - 246 P - - - 253 P - - - 260 P - - - 267 P - - - 274 P - - - 281 P - - - 288 P - - - 295 P - - - 302 P - - - 309 P - - - 316 P - - - 323 P - - - 330 P - - - 337 P - - - 344 P - - - 351 P - - - 358 P - - - 365 P - - - 444 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05505 6 81 QUALITATIVE FOOD CONSUMPTION LOW 240 I05523 6 81 NORMAL NO REMARKABLE OBSERVATIONS 190 197 204 211 218 225 232 239 246 253 260 267 274 281 288 295 302 309 316 323 330 337 344 351 358 365 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P 445 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 5 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05523 6 81 QUALITATIVE FOOD CONSUMPTION LOW 247 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P 446 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 6 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05511 U 79 NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE FOOD CONSUMPTION LOW 190 P 197 P 204 P 211 P 218 P 225 P 232 P 239 P 246 P 253 P 260 P 267 P 274 P 281 P 288 P 295 P 302 P 309 P 316 P 323 P 330 P 337 P 344 P 351 P 358 P 365 P 255 P 447 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 7 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05522 U 79 NORMAL NO REMARKABLE OBSERVATIONS 190 P 197 P 204 P 211 P 218 P 225 P 232 P 239 P 246 P 253 P 260 P 267 P 274 P 281 P 288 P 295 P 302 P 309 P 316 P 323 P 330 P 337 P 344 P 351 P 358 P 365 P 448 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 8 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05529 P 79 EXCRETION LIQUID FECES SKIN & PELAGE ALOPECIA FEET 277 P - - 278 P - - 306 P - - 308 P - - - 186 P - - - 187 P - - - 188 P - - - 189 P - - - 190 P - - - 191 P - - - 192 P - - - 193 P - - - 194 P - - - 195 P - - - 197 P - - - 200 P - - - 201 P - - - 203 P - - - 204 P - - - 206 P - - - 210 P - - - 211 P - - - 213 P - - - 216 P - - - 217 P - - - 218 P - - - 219 P - - - 220 P - - - 449 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 9 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA FEET GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 221 222 223 225 226 229 230 231 232 233 234 235 236 237 238 239 240 241 244 245 246 247 248 251 252 253 254 255 257 258 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 450 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 10 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA FEET GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 259 260 261 263 264 265 266 267 268 269 272 273 274 275 276 277 278 279 280 281 288 289 294 295 298 301 302 305 306 308 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 451 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 11 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA FEET TAIL GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 186-365 DAY 309 310 311 314 186 187 188 189 190 191 192 193 194 195 197 200 201 203 204 206 210 211 213 216 217 218 219 220 221 222 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- 452 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 12 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 SKIN & PELAGE ALOPECIA TAIL 223 225 226 229 230 231 232 233 234 235 236 237 238 239 240 241 244 245 246 247 NORMAL NO REMARKABLE OBSERVATIONS 316 323 330 337 344 351 358 365 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- P--P--P--P--P--P--P--P--- 453 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 13 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 QUALITATIVE FOOD CONSUMPTION LOW 195 210 247 248 260 272 273 294 P 79 DISCHARGE APPEARS TO BE MENSTRUATING 261 NORMAL NO REMARKABLE OBSERVATIONS 190 197 204 211 218 225 232 239 246 253 260 267 274 281 288 295 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P 454 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 14 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05549 P 79 NORMAL NO REMARKABLE OBSERVATIONS 302 309 316 323 330 337 344 351 358 365 QUALITATIVE FOOD CONSUMPTION LOW 195 231 248 272 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P 455 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 15 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05539 6 81 DISCHARGE APPEARS TO BE MENSTRUATING EXCRETION FEW FECES NORMAL NO REMARKABLE OBSERVATIONS 216 P 217 P 246 P 275 P 191 P 195 P 190 P 197 P 204 P 211 P 218 P 225 P 232 P 239 P 253 P 260 P 267 P 274 P 281 P 288 P 295 P 302 P 309 P 316 P 323 P 330 P 337 P 456 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 16 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05539 6 81 NORMAL NO REMARKABLE OBSERVATIONS 344 351 358 365 QUALITATIVE FOOD CONSUMPTION LOW 191 195 213 218 251 254 259 269 316 346 I05552 6 81 NORMAL NO REMARKABLE OBSERVATIONS 190 197 204 211 218 225 232 239 246 253 260 267 274 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P 457 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 17 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05552 6 81 NORMAL NO REMARKABLE OBSERVATIONS 281 288 295 302 309 316 323 330 337 344 351 358 365 QUALITATIVE FOOD CONSUMPTION LOW 220 343 344 346 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P 458 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 18 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 186-365 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH I05533 U 79 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 245 P - - - 190 P 197 P - - - 204 P - - - 211 P - - - 218 P - - - 225 P - - - 232 P - - - 239 P - - - 246 P - - - 253 P - - - 260 P - - - 267 P - - - 274 P - - - 281 P - - - 288 P - - - 295 P - - - 302 P - - - 309 P - - - 316 P - - - 323 P - - - 330 P - - - 337 P - - - 344 P - - - 351 P - - - 358 P - - - 365 P - - - 459 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 19 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05533 U 79 QUALITATIVE FOOD CONSUMPTION LOW 241 244 343 U 79 DISCHARGE APPEARS TO BE MENSTRUATING 260 299 NORMAL NO REMARKABLE OBSERVATIONS 190 197 204 211 218 225 232 239 246 253 267 274 288 295 302 309 316 323 330 337 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P 460 Appendix 2 Individual Clinical Observations Recovery (Days 186 through 365) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 20 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 186-365 DAY (CONTINUED FROM PREVIOUS PAGE) I05542 U 79 NORMAL NO REMARKABLE OBSERVATIONS 344 351 358 365 QUALITATIVE FOOD CONSUMPTION LOW 269 273 275 281 302 343 344 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCHED 30-90 OB DISPATCH P P P P P P P P P P P 461 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 368-558 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH I05520 O 79 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 533 P - - 534 P - - - 372 P - - 379 P - - 386 P - - 393 P - - 400 P - - 407 P - - 414 P - - 421 P - - 428 P - - 435 P - - 442 P - - 449 P - - 456 P - - 463 P - - 470 P - - 477 P - - 484 P - - 491 P - - 498 P - - 505 P - - 512 P - - 519 P - - 526 P - - 540 P - - 547 P - - - 462 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05520 O 79 QUALITATIVE FOOD CONSUMPTION LOW 541 I05526 O 79 DISCHARGE VOMITUS CONTAINING FOOD 535 541 NORMAL NO REMARKABLE OBSERVATIONS 372 379 386 393 400 407 414 421 428 435 442 449 456 463 470 477 484 491 498 505 512 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P 463 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: Ml DOSE: 0 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05526 O 79 NORMAL NO REMARKABLE OBSERVATIONS 519 526 533 540 547 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P P P P P 464 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH I05505 6 81 APPEARANCE SWOLLEN HEAD-MAXILLARY-RIGHT DISCHARGE VOMITUS CONTAINING FOOD EXCRETION FEW FECES NORMAL NO REMARKABLE OBSERVATIONS 390 391 393 394 395 397 400 P P P P P P P 535 555 372 379 386 407 414 421 428 435 442 449 456 463 470 477 P P P P P P P P P P P P P P P P 465 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 5 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05505 6 81 NORMAL NO REMARKABLE OBSERVATIONS 484 491 498 505 512 519 526 533 540 547 554 QUALITATIVE FOOD CONSUMPTION LOW 375 376 555 I05523 6 81 DISCHARGE VOMITUS CONTAINING FOOD 535 EXCRETION NO FECES NON-FORMED FECES 555 556 557 NORMAL NO REMARKABLE OBSERVATIONS 372 386 393 400 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P P P P P P P P P P P P P P P P P P P P P P 466 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 6 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05523 6 81 NORMAL NO REMARKABLE OBSERVATIONS 407 414 421 428 435 442 449 456 463 470 477 484 491 498 505 512 519 526 533 540 547 554 QUALITATIVE FOOD' CONSUMPTION LOW 375 379 553 555 558 'C ' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--P--- P--P--PP-P--P--- 467 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 7 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 368-558 DAY 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH I05511 U 79 NORMAL NO REMARKABLE OBSERVATIONS 372 P 379 P - - 386 P - - 393 P - - 400 P - - 407 P - - 414 P - - 421 P - - 428 P - - 435 P - - 442 P - - 449 P - - 456 P - - 463 P - - 470 P - - 477 P - - 484 P - - 491 P - - 498 P - - 505 P - - 512 P - - 519 P - - 526 P - - 533 P - - 540 P - - 547 P - - 549 P - - P 468 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 8 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 368-558 DAY 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH I05522 U 79 EXCRETION NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 402 P 403 P 372 P 379 P - - 386 P - - 393 P - - 400 P - - 407 P - - 414 P - - 421 P - - 428 P - - 435 P - - 442 P - - 449 P - - 456 P - - 463 P - - 470 P - - 477 P - - 484 P - - 491 P - - 498 P - - 505 P - - 512 P - - 519 P - - 526 P - - 533 P - - 540 P - - 547 P - - 549 P - - P 469 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 9 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05522 U 79 QUALITATIVE FOOD CONSUMPTION LOW 394 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P 470 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 10 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 368-558 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH I05529 P 79 EXCRETION LIQUID FECES NON-FORMED FECES SKIN & PELAGE ALOPECIA LIMB-HIND-RIGHT NORMAL NO REMARKABLE OBSERVATIONS 489 P - - 491 P - - 492 P - - 493 P - - 494 P - - 496 P - - - 368 P - - 369 P - - 372 P - - 376 P - - 377 P - - 378 P - - 549 P - - - 379 P - - 386 P - - 393 P - - 400 P - - 407 P - - 414 P - - 421 P - - 428 P - - 435 P - - 442 P - - 449 P - - 456 P - - 463 P - - - 471 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 11 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05529 P 79 NORMAL NO REMARKABLE OBSERVATIONS 470 477 484 498 505 512 519 526 533 540 547 QUALITATIVE FOOD CONSUMPTION LOW 372 376 452 I05549 P 79 DISCHARGE VOMITUS CONTAINING FOOD APPEARS TO BE MENSTRUATING 535 372 400 456 484 541 NORMAL NO REMARKABLE OBSERVATIONS 379 386 393 407 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P P P P P P P P P P P P P P P--P--P--P--P--P--- P--P--P--P--- 472 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 12 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05549 P 79 NORMAL NO REMARKABLE OBSERVATIONS 414 421 428 435 442 449 463 470 477 491 498 505 512 519 526 533 540 547 QUALITATIVE FOOD CONSUMPTION LOW 372 452 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P P P P P P P P P P P P P P P P P P P P 473 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 13 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH I05539 6 81 DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR EXCRETION FEW FECES NO FECES NORMAL NO REMARKABLE OBSERVATIONS 555 P 556 P 404 P 558 P 555 P 556 P 557 P 372 P 379 P 386 P 393 P 400 P 407 P 414 P 421 P 428 P 435 P 442 P 449 P 456 P 463 P 470 P 477 P 484 P 491 P 498 P 474 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 14 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05539 6 81 NORMAL NO REMARKABLE OBSERVATIONS 505 512 519 526 533 540 547 554 QUALITATIVE FOOD CONSUMPTION LOW NONE 375 376 399 404 407 553 556 557 558 555 I05552 6 81 DISCHARGE VOMITUS CONTAINING FOOD 535 EXCRETION FEW FECES NO FECES 555 557 558 556 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P P P P P P P P PPPPP- -P PPPP- P P P P P 475 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 15 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05552 6 81 NORMAL NO REMARKABLE OBSERVATIONS 372 379 386 393 400 407 414 421 428 435 442 449 456 463 470 477 484 491 498 505 512 519 526 533 540 547 554 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P P P P P P P P P P P P P P P P P P P P P P P P P P P 476 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 16 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05552 6 81 QUALITATIVE FOOD CONSUMPTION LOW NONE 372 557 558 555 556 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P--P--P--P--- P--- 477 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 17 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 368-558 DAY 'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH I05533 U 79 EXCRETION LIQUID FECES NON-FORMED FECES NORMAL NO REMARKABLE OBSERVATIONS 399 P - - 400 P - - 402 P - - - 372 P - - 379 P - - 386 P - - 393 P - - 407 P - - 414 P - - 421 P - - 428 P - - 435 P - - 442 P - - 449 P - - 456 P - - 463 P - - 470 P - - 477 P - - 484 P - - 491 P - - 498 P - - 505 P - - 512 P - - 519 P - - 526 P - - 533 P - - 540 P - - 547 P - - 549 P - - P 478 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 18 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05533 U 79 QUALITATIVE FOOD CONSUMPTION LOW 394 I05542 U 79 DISCHARGE APPEARS TO BE MENSTRUATING 496 DISCHARGE UNKNOWN SOURCE FOUND IN PAN RED IN COLOR 375 NORMAL NO REMARKABLE OBSERVATIONS 372 379 386 393 400 407 414 421 428 435 442 449 456 463 470 477 484 491 498 'C'1 - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P P P P P P P P P P P P P P P P P P P P P P 479 Appendix 2 Individual Clinical Observations Recovery (Days 366 through 561) 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 19 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY DAYS 368-558 DAY (CONTINUED FROM PREVIOUS PAGE) I05542 U 79 NORMAL NO REMARKABLE OBSERVATIONS 505 512 519 526 533 540 547 549 QUALITATIVE FOOD CONSUMPTION LOW 375 394 395 1'C' - COMMENTS LISTED AT END OF OBSERVATIONS FOR SEX/GROUP AM OBS UNSCH EXTRA DISPATCH P --P --P --P --P --P --P --P - -P P P P 480 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M1 DOSE: 0 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05508 T I05517 T I05519 T I05520 O I05526 O I05527 T 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 481 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M2 DOSE: 0.03 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05514 T I05515 T I05516 T I05521 T 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4, 26 482 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05505 6 I05510 T I05518 T I05523 6 I05524 T I05528 T 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 483 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05506 M I05507 T I05509 D I05511 U I05512 T I05522 U 26 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 23 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4 -4, 26 -4, 26 -4, 26 484 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 5 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05529 P I05530 T I05531 T I05535 T I05544 T I05549 P 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYE-LEFT EYES MISCELLANEOUS OPHTHALMICS INCREASED MYELINATION OF OPTIC NERVE EYE-RIGHT 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4 26 -4 -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 485 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 6 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F2 DOSE: 0.03 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05537 T I05541 T I05547 T I05550 T 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4, 26 486 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 7 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05532 T I05538 T I05539 6 I05545 T I05548 T I05552 6 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 487 Appendix 2 Individual Ophthalmic Observations Treatment 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 8 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY WEEKS -4 AND 26 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05533 U I05534 T I05536 T I05540 T I05542 U I05551 T 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 27 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 -4, 26 488 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M1 DOSE: 0 MG/KG/DAY WEEK 52 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05520 O 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES I05526 O 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 52 489 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M3 DOSE: 0.15 MG/KG/DAY WEEK 52 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05505 6 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES I05523 6 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 52 490 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: M4 DOSE: 0.75 MG/KG/DAY WEEK 52 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05511 U 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES I05522 U 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 52 491 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F1 DOSE: 0 MG/KG/DAY WEEK 52 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05529 P 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYE-LEFT MISCELLANEOUS OPHTHALMICS OTHER EYE-RIGHT I05549 P 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 52C 52 492 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 5 STUDY ANIMAL GROUP DAY WK CATEGORY KEYWORD QUALIFIER FREE-TEXT COMMENT I05529 F1 363 52 MISCELLANEOUS OPHTHALMICS OTHER EYE-RIGHT INCREASED MYELINATION OF OPTIC NERVE HEAD THAT MAY BE ASSOCIATED WITH OPTIC NEURITIS. MACULA NORMAL. 493 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 6 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F3 DOSE: 0.15 MG/KG/DAY WEEK 52 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05539 6 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES I05552 6 81 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 52 494 Appendix 2 Individual Ophthalmic Observations Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 7 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: F4 DOSE: 0.75 MG/KG/DAY WEEK 52 - OBSERVED DURING THE WEEKS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS I05533 U 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES I05542 U 79 NO VISIBLE LESIONS NO VISIBLE LESIONS EYES 52 52 495 APPENDIX 3 Individual Body Weight Data (kg) Covance 6329-223 3M T-6295.7 496 ANIMAL NUMBER a WEEK -1 Appendix 3 Individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS b WEEK -1 WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 GROUP: MALE 1 - 0 MG/KG/DAY I05508 I05517 I0 5519 I05520 I05526 I05527 3.0 3.1 3.1 3.1 3.2 3.2 3.2 3.4 3.4 3.4 3.3 3.2 3.2 3.3 2.9 3.0 3.0 3.0 3.0 3.1 3.1 2.9 2.9 2.9 2.9 3.0 3.1 3.0 3.0 3.0 3.0 3.1 3.2 3.3 3.3 4.0 4.1 4.1 4.1 4.1 4.1 4.1 GROUP: MALE 2 - 0.03 MG/KG/DAY I05514 I05515 I05516 I05521 3.1 3.1 3.1 3.2 3.2 3.3 3.3 3.3 3.3 3.3 3.2 3.3 3.4 3.4 2.7 2.8 2.8 2.8 2.8 2.9 2.9 4.4 4.3 4.4 4.3 4.4 4.4 4.4 GROUP: MALE 3 - 0.15 MG/KG/DAY I05505 I05510 I05518 I05523 I05524 I05528 3.1 3.2 3.2 3.2 3.3 3.3 3.3 2.9 3.0 2.9 2.9 2.9 3.0 3.0 3.0 3.1 3.1 3.1 3.1 3.2 3.2 2 . 6 2.7 2.7 2.7 2 . 8 2 . 8 2 . 8 2.9 2.9 2.9 3.0 3.1 3.1 3.1 3.6 3.7 3.7 3.7 3.7 3.8 3.8 GROUP: MALE 4 - 0.75 MG/KG/DAY I05506 I05507 I05509 I05511 I05512 I05522 3.3 3.4 3.4 3.4 3.5 3.5 3.6 4.4 4.4 4.4 4.5 4.5 4.5 4.5 3.1 3.2 3.2 3.1 3.2 3.2 3.3 2 . 8 2.9 2.9 2.9 2.9 2.9 2 . 8 2 . 8 2.9 2.9 2 . 8 2.9 3.0 3.0 3.4 3.4 3.4 3.4 3.5 3.6 3.6 a Day -7. b Day -1. WEEK 6 3.2 3.3 3.0 3.0 3.3 4.1 3.3 3.5 2.9 4.4 3.3 3.0 3.2 2.8 3.1 3.8 3.7 4.5 3.3 2.8 3.0 3.6 Covance 6329-223 3M T-6295.7 PAGE: 1 WEEK 7 3.2 3.3 3.0 2.9 3.3 4.1 3.3 3.4 2.9 4.4 3.3 3.1 3.2 2.8 3.1 3.8 3.7 4.6 3.2 2.8 3.1 3.6 WEEK 8 3.2 3.3 3.1 3.0 3.3 4.1 3.3 3.4 2.9 4.4 3.2 3.1 3.2 2.8 3.0 3.7 3.7 4.6 3.2 2.8 3.0 3.6 497 ANIMAL NUMBER a WEEK -1 Appendix 3 Individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS/T-6295) IN CYNOMOLGUS MONKEYS b WEEK -1 WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 GROUP: FEMALE 1 - 0 MG/KG/DAY I05529 I05530 I05531 I05535 I05544 I05549 2.5 2.5 2.5 2.7 2.3 2.4 2.4 2.9 2.9 2.9 2 . 8 2.9 2.9 2.7 2.6 2.6 2.6 2.6 2.6 2.7 2.6 3.4 3.3 3.3 3.3 3.4 3.4 3.4 2 . 6 2.7 2.7 2 . 6 2 . 6 2.7 2.7 2.9 2.9 2.9 2.9 3.0 3.0 3.0 GROUP: FEMALE 2 - 0.03 MG/KG/DAY I05537 I05541 I05547 I05550 3.8 3.8 3.9 3.9 3.9 4.0 3.9 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.9 2.9 2.9 3.0 3.0 3.0 3.0 2.9 2.9 2.9 2.9 2.9 2 . 8 2 . 8 GROUP: FEMALE 3 - 0.15 MG/KG/DAY I05532 I05538 I05539 I05545 I05548 I05552 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.2 3.2 3.2 3.1 3.1 3.0 3.0 3.6 3.7 3.7 3.8 3.8 3.8 3.8 2 . 6 2 . 6 2 . 6 2.7 2.7 2.7 2 . 6 2 . 8 2.9 2.9 3.0 2.9 3.0 3.0 2 . 8 2 . 8 2 . 8 2.7 2.7 2.7 2.7 GROUP: FEMALE 4 - 0.75 MG/KG/DAY I05533 I05534 I05536 I05540 I05542 I05551 2.6 2.8 3.9 2.9 2.8 2.3 2.6 2.8 3.9 3.0 2.9 2.4 2.6 2.8 3.9 3.0 2.8 2.4 2.6 2.8 3.8 3.1 2.8 2.4 2.6 2.8 3.8 3.1 2.8 2.4 2.6 2.8 3.9 2.8 2.8 2.4 2.5 2.8 3.9 2.6 2.8 2.4 a Day -7. b Day -1. WEEK 6 2.4 2.7 2.6 3.4 2.6 3.0 3.9 2.6 3.0 2.8 2.7 3.0 3.9 2.6 3.0 2.7 2.6 2.8 3.9 2.6 2.8 2.3 Covance 6329-223 3M T-6295.7 PAGE: 2 WEEK 7 2.4 2.8 2.7 3.5 2.6 3.0 4.0 2.6 3.0 2.9 2.8 3.0 3.9 2.6 3.0 2.7 2.6 2.8 3.8 2.8 2.8 2.4 WEEK 8 2.4 2.8 2.6 3.5 2.6 3.0 4.0 2.6 3.0 2.9 2.8 3.0 3.9 2.6 3.0 2.7 2.5 2.8 3.8 2.9 2.8 2.4 498 Appendix 3 Individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK 14 WEEK 15 GROUP: MALE 1 - 0 MG/KG/DAY I05508 I05517 I0 5519 I05520 I05526 I05527 3.2 3.2 3.2 3.3 3.3 3.3 3.3 3.4 3.3 3.3 3.3 3.3 3.3 3.3 3.1 3.1 3.1 3.1 3.2 3.2 3.2 3.0 3.0 3.1 3.0 3.0 3.1 3.0 3.4 3.4 3.5 3.5 3.6 3.5 3.6 4.2 4.2 4.3 4.3 4.3 4.3 4.3 GROUP: MALE 2 - 0.03 MG/KG/DAY I05514 I05515 I05516 I05521 3.3 3.3 3.4 3.4 3.4 3.4 3.5 3.5 3.5 3.6 3.7 3.7 3.6 3.6 3.0 3.0 3.0 3.0 3.1 3.2 3.2 4.4 4.4 4.6 4.6 4.6 4.5 4.6 GROUP: MALE 3 - 0.15 MG/KG/DAY I05505 I05510 I05518 I05523 I05524 I05528 3.3 3.2 3.3 3.3 3.3 3.2 3.3 3.1 3.1 3.2 3.2 3.3 3.1 3.2 3.3 3.2 3.2 3.3 3.3 3.2 3.2 2.8 2.7 2.8 2.8 2.9 2.9 2.9 3.2 3.0 3.1 3.1 3.1 3.1 3.1 3.7 3.7 3.8 3.7 3.7 3.8 3.8 GROUP: MALE 4 - 0.75 MG/KG/DAY I05506 I05507 I05509 I05511 I05512 I05522 3.8 3.7 3.9 3.8 3.9 3.8 3.9 4.7 4.6 4.7 4.7 4.7 4.6 4.6 3.2 3.2 3.2 3.2 3.2 3.1 3.1 2.9 2.8 2.9 2.9 2.9 2.9 2.9 3.1 3.0 3.1 3.1 3.1 2.9 2.9 3.6 3.6 3.7 3.6 3.7 3.7 3.7 WEEK 16 3.3 3.1 3.2 3.0 3.6 4.3 3.5 3.7 3.2 4.6 3.3 3.2 3.3 2.9 3.1 3.7 3.9 4.5 3.0 2.8 2.7 3.6 Covance 6329-223 3M T-6295.7 PAGE: 3 WEEK 17 WEEK 18 3.4 3.4 3.3 3.3 3.3 3.2 3.0 3.0 3.7 3.7 4.4 4.4 3.6 3.5 3.8 3.7 3.3 3.2 4.6 4.5 3.3 3.3 3.3 3.3 3.3 3.3 3.0 2.9 3.0 3.2 3.7 3.6 4.0 3.9 4.6 4.5 3.1 3.0 2.7 2.8 2.8 2.8 3.7 3.7 499 Appendix 3 Individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK 14 WEEK 15 GROUP: FEMALE 1 - 0 MG/KG/DAY I05529 I05530 I05531 I05535 I05544 I05549 2.5 2.5 2.5 2 . 6 2 . 6 2 . 6 2.4 2.9 2.9 3.0 3.1 3.0 3.0 3.0 2.7 2.6 2.7 2.7 2.7 2.7 2.7 3.6 3.5 3.5 3.6 3.6 3.6 3.5 2 . 6 2.7 2.7 2.7 2 . 8 2.7 2.7 3.0 3.0 2.9 3.0 3.0 3.0 3.0 GROUP: FEMALE 2 - 0.03 MG/KG/DAY I05537 I05541 I05547 I05550 4.1 4.0 4.0 4.0 4.1 4.1 4.1 2 . 6 2 . 6 2.7 2.7 2.7 2.7 2.7 3.0 3.0 3.0 3.1 3.1 3.1 3.0 2.9 2.8 2.8 2.8 2.9 2.9 2.9 GROUP: FEMALE 3 - 0.15 MG/KG/DAY I05532 I05538 I05539 I05545 I05548 I05552 2.8 2.8 2.8 2.8 2.8 2.8 2.8 3.0 3.0 3.2 3.2 3.3 3.2 3.3 3.9 3.9 3.9 3.9 3.9 4.0 4.0 2 . 6 2.7 2.7 2 . 6 2 . 6 2.7 2.7 3.0 3.0 3.0 3.1 3.1 3.1 3.1 2 . 8 2 . 8 2.7 2.7 2 . 8 2 . 8 2 . 8 GROUP: FEMALE 4 - 0.75 MG/KG/DAY I05533 I05534 I05536 I05540 I05542 I05551 2 . 6 2 . 6 2 . 6 2.7 2.7 2 . 6 2 . 6 2.9 2.8 2.8 2.8 2.8 2.8 2.8 3.9 3.9 3.8 3.8 3.7 3.6 3.5 3.1 3.0 2 . 8 2 . 8 2 . 8 2.7 2.9 2 . 8 2.7 2.7 2.7 2.7 2.7 2 . 6 2.3 2.3 2.3 2.3 2.3 2.3 2.4 WEEK 16 2.5 3.0 2.7 3.5 2.8 3.0 4.1 2.7 3.0 2.9 2.8 3.3 3.9 2.7 3.0 2.8 2.6 2.8 3.4 3.0 2.6 2.3 Covance 6329-223 3M T-6295.7 PAGE: 4 WEEK 17 WEEK 18 2.5 2.5 3.0 3.0 2.8 3.6 2.8 3.6 2 . 8 2.7 3.1 3.0 4.2 4.2 2 . 6 2.7 3.0 3.0 2.9 2.9 2.9 3.4 3.9 2.7 3.1 2.8 2.8 3.4 3.9 2.6 3.0 2.8 2.7 2.6 2.9 2.9 3.7 3.6 3.1 3.1 2 . 8 2.7 2.4 2.3 500 Appendix 3 Individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 19 WEEK 20 WEEK 21 WEEK 22 WEEK 23 WEEK 24 WEEK 25 GROUP: MALE 1 - 0 MG/KG/DAY I05508 I05517 I0 5519 I05520 I05526 I05527 3.4 3.4 3.4 3.4 3.4 3.4 3.6 3.4 3.4 3.3 3.3 3.3 3.4 3.4 3.3 3.2 3.2 3.2 3.3 3.3 3.4 3.1 3.0 3.1 3.1 3.1 3.0 3.2 3.7 3.7 3.7 3.8 3.7 3.7 3.8 4.5 4.5 4.6 4.6 4.7 4.8 4.9 GROUP: MALE 2 - 0.03 MG/KG/DAY I05514 I05515 I05516 I05521 3.6 3.6 3.6 3.6 3.7 3.7 3.8 3.8 3.8 3.6 3.7 3.7 3.7 3.8 3.2 3.2 3.2 3.3 3.3 3.3 3.4 4.6 4.6 4.7 4.6 4.6 4.7 4.7 GROUP: MALE 3 - 0.15 MG/KG/DAY I05505 I05510 I05518 I05523 I05524 I05528 3.3 3.3 3.2 3.3 3.3 3.3 3.4 3.3 3.3 3.2 3.3 3.3 3.4 3.5 3.3 3.3 3.2 3.3 3.3 3.3 3.3 3.0 3.0 2.9 2.9 2.9 2.9 3.1 3.3 3.3 3.2 3.3 3.3 3.3 3.4 3.6 3.7 3.7 3.7 3.7 3.7 3.7 GROUP: MALE 4 - 0.75 MG/KG/DAY I05506 I05507 I05509 I05511 I05512 I05522 4.0 4.0 3.9 3.9 3.9 4.0 4.0 4.5 4.4 4.3 4.2 4.2 4.1 4.2 3.0 3.1 2.9 3.0 2 . 8 2.9 2.8 2.6 2.7 2.7 2 . 8 2.7 2.6 2.5 2.6 2.8 2.7 2.6 2.7 3.7 3.6 3.6 3.6 3.6 3.6 3.7 WEEK 26 3.6 3.3 3.4 3.2 3.9 5.0 3.8 3.8 3.4 4.7 3.3 3.4 3.4 3.0 3.4 3.6 3.9 4.2 2.6 2.7 3.7 Covance 6329-223 3M T-6295.7 PAGE: 5 WEEK 27 3.6 3.3 3.4 3.1 3.8 5.0 3.8 3.7 3.4 4.7 3.2 3.4 3.3 2.9 3.3 3.7 4.2 2.5 2.5 3.5 501 Appendix 3 Individual Body Weight Data (kg) Treatment Phase 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 19 WEEK 20 WEEK 21 WEEK 22 WEEK 23 WEEK 24 WEEK 25 GROUP: FEMALE 1 - 0 MG/KG/DAY I05529 I05530 I05531 I05535 I05544 I05549 2.5 2.5 2.5 2.5 2.5 2 . 6 2.5 3.0 3.0 2.9 3.0 3.0 3.0 3.1 2.8 2.8 2.7 2.8 2.7 2.7 2 . 8 3.5 3.5 3.5 3.6 3.4 3.5 3.6 2.8 2.8 2.8 2.8 2.8 2.8 2.9 3.1 3.1 3.0 3.1 3.0 3.0 3.0 GROUP: FEMALE 2 - 0.03 MG/KG/DAY I05537 I05541 I05547 I05550 4.2 4.2 4.2 4.2 4.2 4.3 4.4 2.7 2.7 2.6 2.7 2.8 2.7 2.8 3.1 3.0 3.0 2.9 2 . 8 2.7 2 . 8 3.0 3.0 2.9 3.0 2.9 3.0 3.1 GROUP: FEMALE 3 - 0.15 MG/KG/DAY I05532 I05538 I05539 I05545 I05548 I05552 2.8 2.8 2.7 2.8 2.8 2.8 2.8 3.4 3.4 3.3 3.5 3.5 3.4 3.5 4.0 4.0 3.8 3.8 3.8 3.9 3.9 2.7 2.8 2.6 2.7 2.6 2.7 2.7 3.1 3.1 3.0 3.1 3.1 3.1 3.1 2.8 2.8 2.7 2.8 2.8 2.8 2.9 GROUP: FEMALE 4 - 0.75 MG/KG/DAY I05533 I05534 I05536 I05540 I05542 I05551 2 . 6 2 . 6 2 . 6 2 . 6 2 . 6 2.7 2.7 2.9 2.8 2.7 2.9 2 . 8 2.9 2.8 3.5 3.5 3.3 3.3 3.4 3.3 3.3 3.1 3.0 3.0 2.9 2.9 3.0 3.0 2.7 2.7 2.6 2.7 2.6 2.6 2.7 2.4 2.4 2.4 2.4 2.4 2.4 2.4 WEEK 26 2.5 3.0 2.8 3.6 2.9 3.1 4.4 2.8 2.7 3.0 2.8 3.4 3.9 2.7 3.1 2.8 2.7 2.7 3.4 3.0 2.6 2.4 Covance 6329-223 3M T-6295.7 PAGE: 6 WEEK 27 2.4 3.0 2.9 3.5 2.9 3.0 4.3 2.8 2.8 3.0 2.7 3.5 3.9 2.7 3.1 2.7 2.5 2.8 3.4 3.0 2.6 2.4 502 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 28 WEEK 29 WEEK 30 WEEK 31 WEEK 32 WEEK 33 WEEK 34 GROUP: MALE 1 - 0 MG/KG/DAY I05520 I05526 3.2 3.3 3.3 3.4 3.5 3.5 3.5 3.8 3.9 3.9 4.0 4.1 4.1 4.1 GROUP: MALE 3 - 0.15 MG/KG/DAY I05505 I05523 3.2 3.3 3.2 3.3 3.4 3.4 3.3 2.9 2.9 2 . 8 2 . 8 2.9 3.0 3.0 GROUP: MALE 4 - 0.75 MG/KG/DAY I05511 I05522 2.7 2.8 2.9 3.0 3.0 3.1 3.1 3.5 3.7 3.7 4.0 4.2 4.2 4.5 GROUP: FEMALE 1 - 0 MG/KG/DAY I05529 I05549 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.9 3.0 2.9 3.0 3.0 3.1 3.0 GROUP: FEMALE 3 - 0 .15 MG/KG/DAY I05539 I05552 3.8 3.9 3.8 3.9 4.0 4.0 4.0 2.8 2.9 2.8 2.8 2.9 2.9 2 . 8 GROUP: FEMALE 4 - 0 .75 MG/KG/DAY I05533 I05542 2.5 2.6 2.6 2.6 2.7 2.8 2.8 2.7 2.8 2.8 2.9 3.2 3.2 3.2 WEEK 35 3.5 4.0 3.3 2.9 3.0 4.4 2.5 3.0 4.1 2.8 2.8 3.1 Covance 6329-223 3M T-6295.7 PAGE: 1 WEEK 36 WEEK 37 3.5 3.6 4.1 4.2 3.4 3.4 3.1 3.0 3.1 3.1 4.6 4.6 2.5 2.5 3.0 3.1 4.2 4.1 2.9 3.0 2.8 3.3 2.8 3.3 503 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 38 WEEK 39 WEEK 40 WEEK 41 WEEK 42 WEEK 43 WEEK 44 WEEK 45 GROUP: MALE 1 - 0 MG/KG/DAY I05520 3.6 3.6 3.6 3.7 3.8 3.8 4.0 4.1 I05526 4.2 4.1 4.1 4.3 4.2 4.2 4.4 4.4 GROUP: MALE 3 - 0.15 MG/KG/DAY I05505 I05523 3.3 3.3 3.3 3.4 3.3 3.3 3.4 3.5 3.0 2.9 2.9 3.1 3.0 3.0 3.1 3.1 GROUP: MALE 4 - 0.75 MG/KG/DAY I05511 I05522 3.1 3.0 2.9 3.1 3.0 3.1 3.2 3.2 4.5 4.4 4.4 4.5 4.5 4.5 4.5 4.5 GROUP: FEMALE 1 - 0 MG/KG/DAY I05529 I05549 2.5 2.4 2.3 2.5 2.4 2.4 2.5 2.5 3.0 3.0 2.9 3.1 3.0 3.0 3.0 3.1 GROUP: FEMALE 3 - 0 .15 MG/KG/DAY I05539 I05552 4.1 4.1 4.0 4.2 4.1 4.1 4.3 4.2 2.9 2.9 2.8 3.0 3.0 3.0 3.0 3.1 GROUP: FEMALE 4 - 0 .75 MG/KG/DAY I05533 I05542 2.7 2.7 2.8 2.8 2.7 2.7 2 . 8 2.8 3.3 3.2 3.1 3.3 3.2 3.3 3.3 3.3 Covance 6329-223 3M T-6295.7 PAGE: 2 WEEK 46 4.2 4.5 3.5 3.1 3.3 4.6 2.5 3.1 4.2 3.0 2.8 3.4 WEEK 47 4.1 4.3 3.4 3.0 3.2 4.4 2.4 3.0 4.2 2.9 2.7 3.4 504 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 48 WEEK 49 WEEK 50 WEEK 51 WEEK 52 WEEK 53 WEEK 54 GROUP: MALE 1 - 0 MG/KG/DAY I05520 4.1 4.1 4.1 4.1 4.2 4.2 4.2 I05526 4.3 4.4 4.4 4.4 4.5 4.5 4.6 GROUP: MALE 3 - 0.15 MG/KG/DAY: I05505 I05523 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.0 3.1 3.0 3.1 3.1 3.0 3.1 GROUP: MALE 4 - 0.75 MG/KG/DAY: I05511 I05522 3.3 3.5 3.5 3.6 3.7 3.7 3.8 4.4 4.6 4.5 4.5 4.5 4.4 4.5 GROUP: FEMALE 1 - 0 MG/KG/DAY: I05529 I05549 2.3 2.5 2.4 2.4 2.5 2.4 2.4 2 . 8 3.0 2.9 3.0 2.9 2 . 8 2 . 8 GROUP: FEMALE 3 - 0 .15 MG/KG/DAY: I05539 I05552 4.3 4.3 4.2 4.3 4.3 4.3 4.2 2.9 3.0 2.9 3.0 3.0 2.9 2.9 GROUP: FEMALE 4 - 0 .75 MG/KG/DAY: I05533 I05542 2.7 2.9 2.8 2.8 2.8 2.7 2.7 3.4 3.4 3.3 3.3 3.4 3.4 3.4 WEEK 55 4.3 4.7 3.4 3.1 3.8 4.4 2.4 2.9 4.2 2.8 2.6 3.5 Covance 6329-223 3M T-6295.7 PAGE: 3 WEEK 56 4.2 4.7 3.4 3.2 3.9 4.4 2.4 2.9 4.2 2.9 2.7 3.5 WEEK 57 4.1 4.6 3.4 3.1 3.8 4.2 2.3 2.8 4.2 2.9 2.6 3.4 505 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 58 WEEK 59 WEEK 60 WEEK 61 WEEK 62 WEEK 63 WEEK 64 WEEK 65 GROUP: MALE 1 - 0 MG/KG/DAY I05520 I05526 4.2 4.1 4.2 4.2 4.1 4.1 4.0 4.0 4.7 4.7 4.9 4.9 4.8 4.9 4.9 4.8 GROUP: MALE 3 - 0.15 MG/KG/DAY: I05505 I05523 3.4 3.4 3.5 3.5 3.6 3.5 3.5 3.4 3.2 3.2 3.3 3.3 3.3 3.3 3.3 3.3 GROUP: MALE 4 - 0.75 MG/KG/DAY: I05511 I05522 3.9 3.8 4.0 4.0 4.0 4.1 4.3 4.2 4.4 4.4 4.6 4.6 4.7 4.7 4.6 4.5 GROUP: FEMALE 1 - 0 MG/KG/DAY: I05529 I05549 2.5 2.4 2.5 2.5 2.4 2.5 2.4 2.4 2.9 2.9 3.0 2.9 3.0 3.0 2.9 2.9 GROUP: FEMALE 3 - 0 .15 MG/KG/DAY: I05539 I05552 4.1 4.0 4.2 4.1 4.1 4.1 4.1 4.0 3.0 3.0 3.0 3.0 3.0 3.1 3.0 2.9 GROUP: FEMALE 4 - 0 .75 MG/KG/DAY: I05533 I05542 2.6 2.6 2.8 2.8 2.8 2.8 2.7 2.7 3.4 3.4 3.5 3.5 3.6 3.6 3.6 3.5 Covance 6329-223 3M T-6295.7 PAGE: 4 WEEK 66 WEEK 67 4.0 4.1 4.9 4.9 3.4 3.5 3.2 3.3 4.1 4.2 4.5 4.5 2.4 2.4 2 . 8 2.9 4.0 4.1 2.9 3.1 2.7 2.8 3.5 3.6 506 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 68 WEEK 69 WEEK 70 WEEK 71 WEEK 72 WEEK 73 WEEK 74 GROUP: MALE 1 - 0 MG/KG/DAY I05520 4.2 4.3 4.2 4.2 4.3 4.2 4.2 I05526 5.0 5.1 5.0 5.1 5.3 5.2 5.4 GROUP: MALE 3 - 0.15 MG/KG/DAY: I05505 I05523 3.6 3.6 3.5 3.5 3.6 3.5 3.6 3.3 3.4 3.4 3.4 3.5 3.4 3.5 GROUP: MALE 4 - 0.75 MG/KG/DAY: I05511 I05522 4.3 4.3 4.3 4.2 4.3 4.2 4.3 4.6 4.7 4.6 4.6 4.6 4.5 4.6 GROUP: FEMALE 1 - 0 MG/KG/DAY: I05529 I05549 2.4 2.5 2.4 2.4 2.4 2.4 2.4 2.9 2.9 2.9 2.9 2.9 2.9 3.0 GROUP: FEMALE 3 - 0.15 MG/KG/DAY: I05539 I05552 4.1 4.2 4.1 4.2 4.2 4.2 4.2 3.0 3.0 3.0 3.0 3.1 3.0 3.1 GROUP: FEMALE 4 - 0.75 MG/KG/DAY: I05533 I05542 2.7 2.7 2.7 2.7 2.7 2 . 6 2.7 3.6 3.7 3.7 3.7 3.8 3.7 3.8 WEEK 75 4.2 5.3 3.6 3.5 4.3 4.6 2.5 2.9 4.2 3.1 2.7 3.8 Covance 6329-223 3M T-6295.7 PAGE: 5 WEEK 76 4.2 5.4 3.6 3.5 4.3 4.6 2.5 2.9 4.2 3.2 2.8 3.9 WEEK 77 4.1 5.3 3.5 3.4 4.3 4.5 2.4 2.9 4.2 3.1 2.7 3.8 507 Appendix 3 Individual Body Weight Data (kg) Recovery 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER WEEK 78 WEEK 79 WEEK 80 GROUP: I05520 I05526 GROUP: I05505 I05523 GROUP: I05511 I05522 GROUP: I05529 I05549 GROUP: I05539 I05552 GROUP: I05533 I05542 MALE 1 - 0 MG/KG/DAY 4.0 4.0 5.3 5.3 MALE 3 - 0.15 MG/KG/DAY 3.5 3.5 3.4 3.5 MALE 4 - 0.75 MG/KG/DAY 4.3 4.4 4.5 4.5 FEMALE 1 - 0 MG/KG/DAY 2.4 2.4 2 . 8 2.9 FEMALE 3 - 0 .15 MG/KG/DAY 4.1 4.2 2.9 3.0 FEMALE 4 - 0 .75 MG/KG/DAY 2 . 6 2.7 3.8 3.9 Covance 6329-223 3M T-6295.7 PAGE: 6 508 C O V /H H > THE DEVELOPMENT SERVICES COMPANY Sponsor: 3M St. Paul, Minnesota FINAL REPORT Study Title: 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys Author: Peter J. Thomford, PhD Study Completion Date: January 11, 2002 Testing Facility: Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595 Laboratory Study Identification: Covance 6329-223 Sponsor Study Identification: 3M Study No. T-6295.7 Volume II of II Page 509 o f 1086 Covance 6329-223 3M T-6295.7 VOLUME II OF II CONTENTS Page APPENDIX 4 .................................................................................................................. 511 Individual Clinical Hematology Data..........................................................................512 Individual Clinical Chemistry Data.............................................................................614 Individual Clinical Urinalysis Data.............................................................................728 APPENDIX 5.................................................................................................................. 818 Individual Palmitoyl CoA Oxidase Determinations.................................................... 819 Individual Anatomic Pathology Data..........................................................................823 APPENDIX 6.................................................................................................................. 907 AniLytics Inc. Quality Assurance Statements............................................................ 908 Summary and Individual Blood Hormone Determination...........................................917 APPENDIX 7.................................................................................................................. 963 Cell Proliferation Report............................................................................................ 964 APPENDIX 8.................................................................................................................. 977 Electron Microscopic Evaluation of Liver in Cynomolgus Monkeys.........................978 APPENDIX 9................................................................................................................ 1069 Urobilinogen Analysis Report.................................................................................. 1070 APPENDIX 10.............................................................................................................. 1072 Dose Confirmation Analysis Report.........................................................................1073 Compound Stability Report...................................................................................... 1078 Analytical Laboratory Report................................................................................... 1080 Certificate of Analysis...............................................................................................1083 Quality Assurance Statement.................................................................................... 1086 510 APPENDIX 4 Individual Clinical Hematology Data Individual Clinical Chemistry Data Individual Clinical Urinalysis Data Covance 6329-223 3M T-6295.7 511 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL 0Dose Level: 6.48 6.25 6.97 6.27 6.48 6.27 6.45 .2765 1122..83 11112122....8015 12.2 .636 Dose Level: 0.03 76..2228 6.67 7.79 1121..85 12.5 12.9 6..69898 4 12.4 .46 4 Dose Level: 6.45 6.58 7.36 6.73 6.76 6.67 6.76 .3165 0.15 12.6 11.9 1132..80 1132..60 12.6 .641 Dosage Unit: mg/kg/day 40.3 42.4 42.9 39.4 41.1 40.9 62.2 67.8 61.5 62.9 63.5 65.3 19.0 20.5 17.9 18.8 18.6 19.3 41.2 1.360 63.9 2.362 19.0 .687 Dosage Unit: mg/kg/day 45.5 39.8 40.9 45.3 62.5 64.0 61.3 58.1 17.2 18.9 18.7 16.6 42.9 2.95 4 61.5 2.51 4 17.8 1.13 4 Dosage Unit: mg/kg/day 42.0 39.7 44.8 43.1 44.6 43.1 65.2 60.3 60.9 6646..11 64.6 19.6 18.1 17.6 19.0 19.3 18.9 421..8968 63.5 2.368 18.7 .676 30.5 30.2 29.0 29.9 29.3 29.6 29.8 .656 27.5 29.6 30.6 28.5 29.0 1.34 4 30.0 29.9 29.0 29.7 29.2 29.3 29.5 .641 419 380 577 681 472 652 530 1256. 0 .3 .5 ...025 .3 .3 .619 469 675 341 813 257140.3 4 ....6215 .4 .24 4 469 546 375 569 635 366 493 1096. 0 1.4 .5 ...007 .3 .5 .653 Covance 6329-223 3M T-6295.7 RETIC X103/mcL 19 31 350 13 19 21062.6 36 37 7 16 24 14.9 4 90 33 250200 32 346.5 512 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 7.63 6.94 6.89 5.90 7.20 6.73 13.4 12.0 11.9 11.4 13.1 13.1 6.88 .575 6 12.5 .82 6 Dosage Unit: mg/kg/day 45.8 41.5 42.3 40.3 44.5 44.1 60.0 59.7 61.4 68.4 61.8 65.5 17.6 17.3 17.3 19.4 18.1 19.5 43.1 2.06 6 62.8 3.44 6 18.2 1.01 6 29.3 28.9 28.1 28.4 29.3 29.7 29.0 .61 6 519 58 409 528 342 636 415 202.6 6 .6 .3 .4 1.4 .2 .1 .5 .47 6 46 21 28 83 14 7 33 27.8 6 513 ANIMAL NUMBER WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05508 I05517 I05519 I05520 I05526 I05527 6 . 6 2 . 1 4.0 .4 9.2 3.3 4.7 1 . 0 6.7 3.1 3.1 .4 9.0 5.1 3.0 .8 11.3 5.4 5.3 .5 8.9 4.4 3.7 .7 0 .0 32 61 6 1 .1 36 52 1 1 2 .0 46 46 5 0 .1 56 34 9 1 .0 48 47 5 1 .0 49 41 8 0 1 2 0 1 1 0 1 0 1 0 0 MEAN S.D. N 8.6 1.76 6 3.9 1.28 6 4.0 .90 6 .6 .24 6 1 .0 44 47 71 0 08 .05 8.9 9.2 2.4 .8 .5 6666666 Group: 2 Dose Level: 0 .03 Dosage Unit: mg/kg/day I05514 I05515 I05516 I05521 11.7 7.2 4.0 .4 11.5 3.2 6 . 2 1.5 9.5 4.0 4.4 .9 11.1 6.3 4.0 .6 2 .0 62 34 3 5 .0 28 54 13 1 .0 42 47 1 0 2 .0 56 36 6 2 4 1 2 0 0 0 0 MEAN S.D. N 11.0 1.00 4 5.2 1.88 4 4.6 1.05 4 .8 .48 4 2 .0 47 43 8 2 0 17 .00 15.2 9.4 4.4 1.3 .0 4444444 Group: 3 Dose Level: 0 .15 Dosage Unit: mg/kg/day I05505 I05510 I05518 I05523 I05524 I05528 12.5 9.4 2.4 .6 11.1 5.8 4.2 1.0 10.7 4.8 4.6 1.3 15.0 9.8 3.7 .8 9.4 4.2 4.0 1 . 1 12.7 5.3 5.9 .8 1 .0 75 19 5 1 .0 52 38 9 0 .0 45 43 1 2 6 .0 6 6 25 5 0 .1 45 42 1 2 7 .0 42 46 6 1 1 0 4 0 5 0 0 0 0 1 0 MEAN S.D. N 11.9 1.95 6 6.6 2.42 6 4.1 1.14 6 .9 .25 6 2 .0 54 36 8 2 0 31 .04 13.4 10.9 3.3 2.1 .4 6666666 514 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level 0.75 Dosage Unit: mg/kg/day 9.3 3.0 5.0 1 . 1 .2 .1 32 54 12 2 1 13.7 4.9 6.3 2 . 1 .1 .2 36 46 15 1 2 7.5 3.3 2 . 8 .7 .7 .0 44 37 9 9 0 8 . 0 3.9 3.3 .6 .1 .0 49 41 8 1 0 7.1 1 . 6 4.3 1 . 2 .0 .0 2 2 60 16 0 1 11.0 5.5 4.1 1 . 1 .2 .1 50 37 10 2 1 9.4 3.7 4.3 1 . 1 .2 .1 39 46 12 2 1 2.53 1.40 1.25 .53 .25 .08 10.9 9.5 3.3 3.3 .8 66666666666 515 Appendix 4 Individual Clinical Hematology Data Males Day -27 26-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 I05508 I05517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 I05505 I05510 I05518 105523 105524 I05528 Group: 4 105506 105507 I05509 105511 105512 I05522 Dose Level: 0 ------------ Dose Level: 0.03 --------- Dose Level: 0.15 ------------- Dose Level: 0.75 ------------- Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 516 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 5.96 6.78 5.72 6.66 4.98 6.45 11.5 13.3 10.5 12.2 11.6 12.6 6.09 .681 6 12.0 .97 6 Dose Level: 0.03 6.13 5.78 6.30 7.02 10.6 12.0 10.7 12.8 6.31 .522 4 11.5 1.06 4 Dose Level: 0.15 6.95 6.16 6.23 6.72 6.76 6.39 12.7 11.3 11.7 12.3 11.8 12.0 6.54 .320 6 12.0 .49 6 Dosage Unit: mg/kg/day 37.1 45.0 34.7 40.8 36.2 41.9 62.2 66.4 60.6 61.3 72.7 65.0 19.3 19.6 18.3 18.3 23.2 19.5 39.3 3.93 6 64.7 4.51 6 19.7 1.81 6 Dosage Unit: mg/kg/day 36.7 40.0 37.4 43.9 59.9 69.1 59.3 62.5 17.3 20.8 17.0 18.2 39.5 3.26 4 62.7 4.49 4 18.3 1.73 4 Dosage Unit: mg/kg/day 43.2 38.3 39.2 40.7 38.0 41.1 62.2 62.1 62.9 60.6 56.2 64.2 18.2 18.4 18.8 18.3 17.4 18.7 40.1 1.97 6 61.4 2.79 6 18.3 .50 6 31.0 29.5 30.2 29.9 31.9 30.1 30.4 .87 6 28.8 30.2 28.6 29.1 29.2 .71 4 29.3 29.6 29.9 30.1 31.0 29.1 29.8 .68 6 631 552 584 577 471 417 539 79.5 6 529 426 558 414 482 72.4 4 433 475 477 325 615 560 481 100.9 6 .4 .3 .1 .5 1.3 1.0 .6 .46 6 .3 .9 .4 .2 .4 .31 4 .4 .3 .8 .1 .4 .7 .4 .26 6 24 20 6 33 65 64 35 24.2 6 18 52 25 14 27 17.1 4 28 18 50 7 27 45 29 16.2 6 517 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 6.46 6.72 6.67 6.21 6.57 6.35 12.1 13.1 12.1 11.8 12.0 11.7 6.50 .195 6 12.1 .50 6 Dosage Unit: mg/kg/day 41.2 44.2 41.7 39.6 42.4 40.0 63.8 65.8 62.6 63.8 64.5 63.0 18.7 19.5 18.2 19.0 18.2 18.5 41.5 1.68 6 63.9 1.14 6 18.7 .50 6 29.3 29.6 29.1 29.8 28.3 29.4 29.2 .52 6 337 438 606 433 492 304 435 108.9 6 .2 .4 .1 .0 .4 .4 .2 .18 6 13 27 7 0 26 25 16 11.4 6 518 ANIMAL NUMBER Group: 1 105529 105530 105531 I05535 105544 105549 MEAN S.D. N Group: 2 105537 I05541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 I05552 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 7.4 11.7 8.4 12.6 13.0 8.0 3.4 6.0 5.0 5.0 5.3 3.1 10.2 2.52 6 4.6 1.14 6 Dose Level: 0 .03 12.2 8.1 6.8 7.6 8.6 3.0 3.6 4.6 8.7 2.41 4 5.0 2.52 4 Dose Level: 0 .15 7.6 12.0 7.1 14.4 11.3 8.0 2.6 7.4 2.6 9.4 5.4 3.3 10.1 2.94 6 5.1 2.81 6 Dosage Unit: mg/kg/day 3.3 4.9 2.6 6.0 5.8 4.3 .6 .7 .7 .8 1.2 .5 .2 .1 .1 .6 .7 .1 4.5 .8 .3 1.36 .24 .2 666 Dosage Unit: mg/kg/day 2.7 .6 .2 4.1 .9 .1 2.5 .6 .1 2.4 .5 .1 2.9 .6 .1 .79 .17 .0 444 Dosage Unit: mg/kg/day 3.6 1.2 3.7 .7 3.5 .9 4.2 .7 4.4 .8 3.4 .7 .2 .2 .2 .0 .7 .6 3.8 .8 .3 .40 .20 .2 666 0 45 45 0 51 42 1 59 31 1 39 48 0 40 44 0 38 54 82 61 81 75 96 62 0 0 1 1 0 0 0 45 44 7 3 0 05 8.3 7.6 1 . 2 2 . 1 .5 666666 0 70 2 2 5 1 36 50 1 1 0 53 36 9 0 60 32 6 0 55 35 05 14.3 11.6 444 8 2.8 4 2 1 2 1 2 .6 4 0 1 0 0 0 .5 4 0 35 48 15 0 62 31 6 0 36 49 12 0 65 29 5 0 48 39 7 1 41 42 9 2 2 2 0 6 8 0 0 0 0 0 1 0 48 40 9 3 0 04 13.0 8.4 3.8 3.0 .4 666666 519 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level : 0.75 Dosage Unit: mg/kg/day 10.0 4.1 5.1 .7 .0 .0 41 51 7 0 0 13.3 6.9 5.2 .7 .4 .0 52 39 6 3 0 9.6 4.4 3.5 1.3 .3 .1 46 36 14 3 1 8.9 5.4 2.4 .9 .1 .0 61 27 10 1 0 8.3 5.9 2 . 0 .4 .0 .0 71 24 4 0 0 3.8 2.0 1.2 .5 .0 .0 53 32 14 1 0 9.0 3.08 6 4.8 1.70 6 3.2 1.66 6 .8 .1 .0 54 35 91 0 .32 .18 04 10.7 9.7 4.2 1.4 .4 66666666 520 Appendix 4 Individual Clinical Hematology Data Females Day -27 26-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 105529 105530 105531 I05535 I05544 105549 - - - - Group: 2 Dose Level: 0.03 I05537 - - - I05541 - - - I05547 - - - 105550 - - - Group: 3 Dose Level: 0.15 I05532 - - - 105538 - - - 105539 - - - I05545 - - - I05548 - - - I05552 - - - Group: 4 Dose Level: 0.75 105533 - - - 105534 - - - I05536 - - - I05540 - - - I05542 - - - I05551 - - - Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 521 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.53 6.32 6.83 6.50 6.20 6.34 13.0 13.0 12.2 12.1 11.6 12.2 6.45 .221 6 12.4 .55 6 Dose Level: 0.03 7.32 6.51 6.35 7.26 13.0 12.5 12.2 12.2 6.86 .501 4 12.5 .38 4 Dose Level: 0.15 6.34 6.99 7.20 6.78 6.31 6.34 12.8 12.3 12.7 12.6 12.3 12.1 6.66 .385 6 12.5 .27 6 Dosage Unit: mg/kg/day 41.4 42.7 40.9 39.5 38.6 40.6 63.4 67.5 59.8 60.7 62.3 64.0 19.9 20.5 17.8 18.6 18.7 19.3 40.6 1.44 6 63.0 2.74 6 19.1 .97 6 Dosage Unit: mg/kg/day 47.9 42.5 39.0 40.3 65.5 65.2 61.4 55.6 17.8 19.2 19.2 16.8 42.4 3.93 4 61.9 4.61 4 18.2 1.17 4 Dosage Unit: mg/kg/day 41.3 41.5 42.1 41.3 41.4 39.8 65.1 59.3 58.5 60.9 65.6 62.7 20.3 17.6 17.7 18.5 19.5 19.1 41.2 .76 6 62.0 2.96 6 18.8 1.06 6 31.4 30.4 29.8 30.7 30.0 30.1 30.4 .58 6 27.2 29.4 31.2 30.1 29.5 1.69 4 31.1 29.7 30.2 30.5 29.7 30.4 30.3 .53 6 369 443 474 644 375 614 486 117. 8 6 492 629 344 665 532 146. 1 4 421 483 498 544 519 388 476 59. 6 6 .1 .2 .3 .1 .1 .5 .2 .16 6 .6 .8 .3 .0 .4 .35 4 .3 .4 .6 .4 .2 .3 .4 .14 6 7 13 20 6 6 32 14 10.4 6 44 52 19 0 29 23.8 4 19 28 43 27 13 19 25 10.5 6 522 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 7.03 6.57 6.84 5.80 6.60 6.32 12.3 11.4 12.1 10.9 12.1 12.3 6.53 .431 6 11.8 .57 6 Dosage Unit: mg/kg/day 41.0 39.6 41.9 37.1 40.3 41.5 58.3 60.2 61.3 63.9 61.0 65.6 17.4 17.3 17.6 18.8 18.3 19.4 40.2 1.74 6 61.7 2.63 6 18.1 .85 6 29.9 28.7 28.8 29.5 30.1 29.6 29.4 .57 6 459 69 PA 399 490 362 519 383 164.3 6 .3 .3 .3 .4 .5 .5 .4 .10 6 21 20 21 23 33 32 25 5.9 6 523 ANIMAL NUMBER Group: 1 I05508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 I05505 I05510 105518 105523 105524 105528 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 5.2 7.8 7.1 6.8 7.5 11.2 1.8 2.5 3.5 3.5 4.7 7.5 7.6 1.98 6 3.9 2.01 6 Dose Level: 0.03 11.9 8.0 12.1 11.0 10.8 1.89 4 5.9 3.1 8.2 8.1 6.3 2.40 4 Dose Level: 0.15 11.7 8.8 9.4 11.1 6.9 12.4 9.3 5.1 3.9 7.0 3.5 7.2 10.0 2.06 6 6.0 2.23 6 Dosage Unit: mg/kg/day 2.9 .4 .0 4.2 .9 .0 3.4 .2 .1 2.9 .4 .0 2 . 2 .3 .2 2 . 8 .9 .0 3.1 .5 .0 .67 .31 08 666 Dosage Unit: mg/kg/day 5.3 .5 .2 4.1 .6 .2 3.1 .7 .2 2.4 .3 .1 3.7 .5 .2 1.26 .17 05 444 Dosage Unit: mg/kg/day 2 . 0 .2 .3 2.9 .7 .0 4.6 .8 .0 3.6 .4 .1 2 . 6 .8 .0 3.6 .7 .8 3.2 .6 .2 .91 .24 32 666 0 34 57 91 0 2 32 53 12 02 0 49 48 31 0 0 52 43 5 0 0 0 63 30 4 3 0 0 67 25 8 0 0 0 50 43 08 14.4 12.8 666 7 3.4 6 1 1.2 6 0 .8 6 0 50 44 0 39 51 0 67 25 0 74 2 2 42 72 52 31 0 0 0 0 0 58 36 52 0 00 15.9 14.2 1.7 .5 .0 444444 0 79 17 2 0 58 32 8 0 42 49 8 0 63 32 4 1 50 37 12 1 58 30 5 2 1 0 1 0 6 0 0 0 0 1 0 0 58 33 6 2 0 05 12.5 10.4 3.6 2.3 .4 666666 524 ro i> cn (NLD Io O (N (rNo I Eh 0U)2ro d fd > o u Individual Clinical Hematology Data i--l i --l O i --I :--I I--I i--I in o\ Oui c CQ I o\ I 5' uoi H cn H o ro H O O H H C' en in O O h o u o o\ 1 O1 rH M 5O2 |iiii U in c uM 5O wX o\ f0f-1i 2 1 11 i Hsi1H(N^CNoeCiN roo oro oro c-eo EPn HX Pen O5 XP iii CO 2 W2 W o\ i 1 c o ^ c n in ro H (N o u o ^ l> i> i> in i> <HU! POP OOOX O2 fc[r>o fdX OPP 5XU XH0-1 5H Oi WW Pu 1' S1<L 1 i o rXH 1 1 Ocn i1 <CQ! P_ ii O H O H O H O OinI D Q fEhfi iOn M (N ^1 \1 S eo X Eh CO UI Uii--a) PEh - UI2fd >HEfOHn EHhH BUHH PEh o SM X^ 11 1 Oi WJ 1 i! O1 Hl \Tc5dx Xtj) tj) rH i--li--I ro i--l o o i--I :--i eo CO c-c--st<m i>cn eoh eo UIXOEh < O5O X ii1 jj H 2 HPp PHcnH cenu cn <! u E0oh-1 X wHP i> CN 2 ii PuB i Q-i O s>H Xr j P |1 i| 11 Pu ' 1 1Ww Ho 11 Pd a) tfCdnO 0 Q ii>n o ococo^^o (N ro (N CN CN ro ^ ro o in in c N ro ro co in ro eo rH (N cn in eo (N eo ceno eo eo ro x : P U UB a>) a) H c u o in io o i p l> l> H CO l> O ro iH>i o st1 C&Q<o aCO) rH rH rH rH rH o XQ 525 Xi i>i>cnrH (N(N Wi CQ 1 2i ft o o o rH rH (N d0 in in in in in in in in in in in in s Pi 5i H o oooooo MMMMHM H2 S N Appendix 4 Individual Clinical Hematology Data Males Day 37 26-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 I05508 I05517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 I05505 I05510 I05518 105523 105524 I05528 Group: 4 105506 105507 I05509 105511 105512 I05522 Dose Level: 0 ------------ Dose Level: 0.03 --------- Dose Level: 0.15 ------------- Dose Level: 0.75 ------------- Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 526 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.43 6.51 6.37 6.52 5.78 6.85 12.3 12.7 11.6 11.8 11.6 13.3 6.41 .351 6 12.2 .69 6 Dose Level: 0.03 6.60 5.70 6.79 7.29 10.9 11.7 11.6 13.2 6.60 .664 4 11.8 .97 4 Dose Level: 0.15 6.43 6.40 6.35 6.85 7.09 6.19 11.9 11.3 12.0 12.4 11.9 11.4 6.55 .343 6 11.8 .41 6 Dosage Unit: mg/kg/day 40.4 42.1 38.8 39.1 37.9 44.4 62.8 64.7 60.8 60.0 65.6 64.8 19.1 19.6 18.1 18.0 20.0 19.5 40.5 2.42 6 63.1 2.31 6 19.0 .83 6 Dosage Unit: mg/kg/day 38.1 40.5 39.0 44.7 57.8 70.9 57.4 61.3 16.6 20.6 17.0 18.1 40.6 2.92 4 61.8 6.28 4 18.1 1.80 4 Dosage Unit: mg/kg/day 39.5 38.4 40.6 41.2 39.8 38.8 61.3 60.1 63.8 60.1 56.1 62.7 18.5 17.7 18.9 18.1 16.8 18.5 39.7 1.06 6 60.7 2.68 6 18.1 .75 6 30.5 30.2 29.8 30.0 30.5 30.0 30.2 .29 6 28.7 29.0 29.7 29.6 29.2 .48 4 30.1 29.5 29.5 30.1 29.8 29.5 29.7 .29 6 647 629 439 538 499 475 538 84.2 6 448 391 417 411 417 23.6 4 451 398 406 300 553 478 431 85.3 6 .3 .5 .2 .1 .4 .5 .3 .16 6 .3 .7 .1 .1 .3 .28 4 .4 .4 .1 .3 .3 .2 .3 .12 6 19 33 13 7 23 34 22 10.8 6 20 40 7 7 18 15.6 4 26 26 6 21 21 12 19 8.0 6 527 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 6.04 5.91 6.43 6.09 6.66 6.12 11.6 11.3 11.7 11.4 12.2 11.1 6.21 .280 6 11.6 .38 6 Dosage Unit: mg/kg/day 38.0 38.4 41.3 37.1 41.8 37.9 62.8 65.0 64.2 60.9 62.8 62.0 19.1 19.2 18.3 18.7 18.3 18.2 39.1 1.96 6 63.0 1.48 6 18.6 .44 6 30.5 29.5 28.4 30.8 29.2 29.3 29.6 .89 6 345 532 531 501 555 351 469 95.4 6 .3 .7 .2 .1 .2 .5 .3 .23 6 18 41 13 6 13 31 20 13.1 6 528 ANIMAL NUMBER Group: 1 105529 105530 105531 I05535 105544 105549 MEAN S.D. N Group: 2 105537 I05541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 I05552 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 9.6 12.1 14.6 21.4 8.6 10.1 6.2 8.3 11.7 12.2 2.3 5.9 12.7 4.75 6 7.8 3.77 6 Dose Level: 0.03 7.7 11.5 7.3 11.7 3.5 6.5 5.0 7.9 9.6 2.37 4 5.7 1.90 4 Dose Level: 0.15 8.0 9.4 4.4 10.0 11.7 11.2 5.4 5.1 1.2 5.2 7.7 8.2 9.1 2.66 6 5.5 2.48 6 Dosage Unit: mg/kg/day 2.8 2.8 1.9 5.9 5.2 2.8 5. 1 10 .0 9. 1 24 . 7 7. 3 10 .4 3.6 1.59 6 11 67 6 .3 .26 6 Dosage Unit: mg/kg/day 2.8 3.7 1.7 2.8 8 11 5 8 .5 .2 .1 .2 2.8 .82 4 8 .2 24 .17 44 Dosage Unit: mg/kg/day 2.0 4. 1 3.4 6 .3 2.8 4. 1 3.9 7. 1 3.0 5. 4 2.2 4. 5 2.9 .72 6 5. 13 6 2 .18 6 .0 .0 .1 .2 .0 .0 .0 .08 6 .1 .0 .0 .0 .0 .05 4 .0 .0 .0 .0 .0 .0 .0 .00 6 65 68 80 57 26 58 59 18 6 46 56 68 68 60 10 4 68 54 26 52 66 73 56 17 6 30 23 13 28 61 28 30 16.2 6 36 32 24 24 29 6.0 4 25 36 63 39 26 19 35 15.7 6 5 8 6 11 8 10 8 2.3 6 10 10 7 6 8 2.1 4 5 6 8 7 4 4 6 1.6 6 1 0 1 3 4 4 2 1.7 6 6 2 1 2 3 2.2 4 2 3 2 1 4 4 3 1.2 6 0 0 0 1 1 0 0 .5 6 2 0 0 0 0 1.0 4 0 0 0 0 0 0 0 .0 6 529 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level 0.75 Dosage Unit: mg/kg/day 8 . 8 3.9 4.4 .4 .0 .0 45 50 5 0 0 8 . 8 4.6 3.0 .9 .2 .0 52 34 1 1 31 7.6 4.8 2 . 0 .6 .1 .0 63 27 8 2 0 9.7 5.0 3.9 .6 .1 .0 51 40 71 0 13.7 11.5 1.8 .4 .0 .0 84 13 3 0 0 5.0 2.2 2.3 .4 .1 .0 44 47 72 0 8.9 5.3 2.9 .6 .1 .0 56 35 71 0 2.85 3.19 1.06 .20 .08 .00 15.1 13.7 2.7 1.2 .4 66666666666 530 Appendix 4 Individual Clinical Hematology Data Females Day 37 26-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 105529 105530 105531 I05535 I05544 105549 - - - - Group: 2 Dose Level: 0.03 I05537 - - - I05541 - - - I05547 - - - 105550 - - - Group: 3 Dose Level: 0.15 I05532 - - - 105538 - - - 105539 - - - I05545 - - - I05548 - - - I05552 - - - Group: 4 Dose Level: 0.75 105533 - - - 105534 - - - I05536 - - - I05540 - - - I05542 - - - I05551 - - - Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 531 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.68 6.29 6.93 6.53 6.10 6.43 13.2 12.9 12.2 12.4 11.7 12.5 6.49 .292 6 12.5 .53 6 Dose Level: 0.03 6.86 6.61 6.44 7.44 12.2 12.6 12.0 12.7 6.84 .437 4 12.4 .33 4 Dose Level: 0.15 6.47 6.82 7.10 6.51 6.54 6.19 13.0 12.4 12.7 12.7 12.6 11.5 6.60 .315 6 12.5 .52 6 Dosage Unit: mg/kg/day 42.0 42.8 41.6 39.9 38.1 42.3 62.8 68.0 59.9 61.1 62.4 65.8 19.8 20.4 17.6 18.9 19.1 19.4 41.1 1.78 6 63.3 3.03 6 19.2 .95 6 Dosage Unit: mg/kg/day 41.7 42.3 39.4 42.2 60.9 63.9 61.1 56.8 17.7 19.1 18.7 17.1 41.4 1.36 4 60.7 2.92 4 18.2 .91 4 Dosage Unit: mg/kg/day 41.6 40.1 41.5 40.9 42.1 38.2 64.2 58.8 58.5 62.8 64.3 61.8 20.1 18.2 17.8 19.5 19.3 18.6 40.7 1.42 6 61.7 2.56 6 18.9 .87 6 31.5 30.1 29.4 31.0 30.7 29.5 30.4 .84 6 29.1 29.9 30.6 30.0 29.9 .62 4 31.3 30.9 30.5 31.0 30.0 30.2 30.6 .50 6 463 423 524 699 377 644 522 126. 9 6 .1 .5 .3 .0 .1 .7 .3 .27 6 438 647 376 684 536 152. 1 4 .1 1.0 .4 .0 .4 .45 4 450 499 578 625 520 349 504 97. 3 6 .5 .5 .6 .1 .0 .2 .3 .25 6 7 31 21 0 6 45 18 17.3 6 7 66 26 0 25 29.6 4 32 34 43 7 0 12 21 17.3 6 532 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 7.46 6.81 6.69 5.86 6.90 6.65 13.1 12.1 11.9 11.1 12.8 12.8 6.73 .516 6 12.3 .75 6 Dosage Unit: mg/kg/day 43.4 40.5 40.0 37.6 41.6 43.8 58.2 59.4 59.8 64.1 60.3 65.9 17.6 17.7 17.7 18.9 18.5 19.3 41.2 2.31 6 61.3 3.02 6 18.3 .72 6 30.2 29.8 29.6 29.5 30.7 29.3 29.8 .52 6 534 36 480 629 359 586 437 217.8 6 .3 .1 .5 .4 .0 .4 .3 .19 6 22 7 33 23 0 27 19 12.6 6 533 ANIMAL NUMBER WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 7.4 3.7 8.0 6.7 2.1 3.1 8 . 0 3.8 6 . 0 3.2 7.8 2.4 7.3 .81 6 3.0 .68 6 Dose Level: 0 .03 8.1 10.3 12.1 11.6 10.5 1.79 4 5.0 4.6 7.3 7.5 6.1 1.51 4 Dose Level: 0 .15 10.8 13.3 9.9 12.7 7.7 16.4 11.8 3.02 6 8.0 8.7 3.2 7.7 3.2 11.1 7.0 3.16 6 Dosage Unit: mg/kg/day 3.3 .4 4.7 1.0 3.2 .4 3.4 .6 2 . 2 .5 4.2 .9 0 1 0 1 1 2 3.5 .87 6 .6 .26 6 1 08 6 Dosage Unit: mg/kg/day 2.3 .5 4.3 1.2 3.5 1.1 3.4 .5 2 2 1 2 3.4 .82 4 .8 .38 4 2 05 4 Dosage Unit: mg/kg/day 2.3 .2 3.7 .7 5.8 .8 4.5 .4 3.4 1.0 3.6 1.3 3 1 1 1 1 4 3.9 1.18 6 .7 .40 6 2 13 6 .0 49 45 5 .1 27 59 12 .0 46 48 5 .1 48 43 7 .0 52 36 9 .0 31 54 12 .0 42 48 .05 10.5 8 . 2 666 8 3.2 6 .0 62 29 6 .0 44 42 12 .0 61 29 9 .0 65 29 4 .0 58 32 8 .00 9.5 6.5 3.5 4444 .0 73 2 1 2 .0 65 28 6 .0 32 59 8 .0 60 36 3 .1 41 44 13 .1 68 22 8 .0 56 35 7 .05 16.3 14.6 4.0 6666 1 1 1 1 2 3 2 .8 6 2 2 1 2 2 .5 4 3 1 1 1 1 2 2 .8 6 0 2 0 1 0 0 0 .8 6 0 0 0 0 0 .0 4 0 0 0 0 1 0 0 .4 6 534 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level 0.75 Dosage Unit: mg/kg/day 6.5 2.5 3.5 .4 14.6 9.6 3.6 1 . 0 10.6 6.4 2.8 .7 7.7 4.2 3.0 .4 7.7 3.6 3.5 .6 10.7 5.5 4.3 .7 .1 .2 .6 .1 .0 .2 .0 38 54 .2 6 6 24 .1 60 27 .0 54 39 .0 46 45 .0 51 40 61 72 76 51 80 62 0 1 1 0 0 0 9.6 5.3 3.4 .6 .2 .0 52 38 6 2 0 2.97 2.52 .52 .23 .21 .08 10.0 11.2 1.0 2.1 .5 66666666666 535 Appendix 4 Individual Clinical Hematology Data Males Day 62 26-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 I05508 I05517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 I05505 I05510 I05518 105523 105524 I05528 Group: 4 105506 105507 I05509 105511 105512 I05522 Dose Level: 0 ------------ Dose Level: 0.03 --------- Dose Level: 0.15 ------------- Dose Level: 0.75 ------------- Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 536 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.15 5.93 6.56 7.02 4.91 6.83 12.0 12.1 12.1 12.7 11.5 13.4 6.23 .766 6 12.3 .66 6 Dose Level: 0.03 6.44 5.67 6.82 7.01 10.9 12.2 11.9 12.9 6.48 .593 4 12.0 .83 4 Dose Level: 0.15 9.13 6.64 6.45 6.74 6.80 6.21 17.2 11.8 12.5 12.2 11.7 11.6 7.00 1.068 6 12.8 2.17 6 Dosage Unit: mg/kg/day 38.4 39.7 40.5 42.4 35.4 44.9 62.4 66.8 61.6 60.4 72.1 65.8 19.5 20.3 18.5 18.2 23.4 19.6 40.2 3.27 6 64.9 4.33 6 19.9 1.87 6 Dosage Unit: mg/kg/day 37.8 40.5 39.2 43.4 58.8 71.3 57.4 62.0 16.9 21.4 17.4 18.4 40.2 2.39 4 62.4 6.25 4 18.5 2.02 4 Dosage Unit: mg/kg/day 55.9 40.0 40.4 40.3 38.4 38.9 61.2 60.3 62.6 59.8 56.4 62.6 18.8 17.8 19.3 18.0 17.2 18.6 42.3 6.70 6 60.5 2.31 6 18.3 .76 6 31.3 30.4 30.0 30.0 32.4 29.8 30.6 1.01 6 28.8 30.1 30.3 29.7 29.7 .67 4 30.8 29.5 30.9 30.2 30.4 29.7 30.3 .57 6 668 515 644 600 506 501 572 74. 6 6 357 507 548 437 462 83. 8 4 306 456 374 326 667 486 436 133. 5 6 .5 .6 .1 .3 .7 .5 .4 .22 6 .3 .7 .8 .0 .4 .37 4 .1 .6 .0 .7 .3 .5 .4 .28 6 31 36 7 21 34 34 27 11.2 6 19 40 55 0 28 24.1 4 9 40 0 47 20 31 24 18.2 6 537 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 6.04 5.74 6.72 6.13 6.75 6.32 11.7 11.4 12.2 11.9 12.1 11.7 6.28 .397 6 11.8 .29 6 Dosage Unit: mg/kg/day 39.0 37.9 42.6 39.5 42.6 39.5 64.6 66.0 63.5 64.5 63.0 62.5 19.3 19.8 18.2 19.4 18.0 18.6 40.2 1.96 6 64.0 1.27 6 18.9 .72 6 29.9 30.0 28.7 30.1 28.5 29.7 29.5 .70 6 355 620 622 432 665 333 504 148.3 6 .4 .5 .1 .6 .0 .1 .3 .25 6 24 29 7 37 0 6 17 14.9 6 538 ANIMAL NUMBER Group: 1 105529 105530 105531 I05535 105544 105549 MEAN S.D. N Group: 2 105537 I05541 105547 105550 MEAN S.D. N Group: 3 105532 105538 105539 105545 105548 I05552 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 5.8 13.0 14.1 10.9 10.5 12.4 2.9 7.8 9.9 3.5 2.9 7.9 11.1 2.93 6 5.8 3.08 6 Dose Level: 0 .03 10.6 8.3 7.2 8.8 5.7 2.4 3.7 5.6 8.7 1.42 4 4.4 1.59 4 Dose Level: 0 .15 8.9 10.6 6.1 9.7 7.1 10.1 5.7 5.7 2.2 4.0 2.3 6.0 8.8 1.78 6 4.3 1.75 6 Dosage Unit: mg/kg/day 2 . 2 .5 4.5 .5 3.0 .9 5.4 1 .4 7.0 .0 3.7 .4 .1 .1 .2 .5 .5 .3 4.3 .6 .3 1.73 .48 .18 666 Dosage Unit: mg/kg/day 3.4 .8 .5 5.0 .6 .2 2.7 .5 .2 2.4 .7 .1 3.4 .6 .2 1.16 .13 .17 444 Dosage Unit: mg/kg/day 2.3 .7 .1 4.1 .4 .4 3.1 .5 .2 5.0 .5 .2 3.7 .7 .3 3.2 .3 .5 3.6 .5 .3 .93 .16 .15 666 0 50 38 9 0 60 35 4 1 70 2 2 6 2 32 49 13 0 27 67 0 0 64 30 3 1 1 1 5 5 2 0 50 40 6 2 08 17.6 15.9 4.6 2.0 66666 1 0 1 1 0 0 0 .5 6 1 54 33 8 5 1 1 29 61 8 2 1 0 52 38 72 0 0 63 27 8 1 0 0 50 40 8 2 0 06 14.5 14.9 .5 1.7 .6 444444 0 64 26 8 0 54 39 4 1 37 51 9 0 41 51 5 1 32 52 10 0 60 32 3 1 4 3 2 5 5 0 48 42 05 13.1 11.2 666 6 2.9 6 3 1.6 6 0 0 1 0 1 0 0 .5 6 539 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level 8.4 18.0 6.7 8.1 10.0 4.8 9.3 4.59 6 0.75 3.2 12.8 3.9 4.5 6.9 2.1 5.6 3.89 6 Dosage Unit: mg/kg/day 4.8 .4 3.6 1.4 1 . 8 .7 2.9 .6 2 . 6 .4 2.3 .3 .0 .2 .2 .1 .1 .1 3.0 .6 .1 1.07 .40 .08 666 .0 38 57 4 .1 71 2 0 8 .1 58 27 1 1 .0 55 36 7 .0 69 27 4 .0 44 48 6 0 1 3 1 1 1 .0 56 36 7 1 .05 13.2 14.2 2.7 1.0 66666 0 0 1 0 0 0 0 .4 6 540 Appendix 4 Individual Clinical Hematology Data Females Day 62 26-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 105529 105530 105531 I05535 I05544 105549 - - - - Group: 2 Dose Level: 0.03 I05537 - - - I05541 - - - I05547 - - - 105550 - - - Group: 3 Dose Level: 0.15 I05532 - - - 105538 - - - 105539 - - - I05545 - - - I05548 - - - I05552 - - - Group: 4 Dose Level: 0.75 105533 - - - 105534 - - - I05536 - - - I05540 - - - I05542 - - - I05551 - - - Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 541 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL % Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.39 6.21 6.92 6.45 6.01 6.59 12.8 12.8 12.2 12.1 11.5 12.8 6.43 .314 6 12.4 .53 6 Dose Level: 0.03 6.96 6.71 6.43 7.88 12.3 12.8 12.2 13.4 7.00 .628 4 12.7 .55 4 Dose Level: 0.15 6.07 6.64 6.95 6.33 6.48 6.51 12.1 12.2 12.5 12.5 12.4 12.3 6.50 .295 6 12.3 .16 6 Dosage Unit: mg/kg/day 39.6 41.3 40.7 39.2 37.4 43.8 62.0 66.6 58.8 60.8 62.3 66.4 20.0 20.7 17.6 18.8 19.2 19.4 40.3 2.17 6 62.8 3.11 6 19.3 1.06 6 Dosage Unit: mg/kg/day 42.2 42.9 40.4 44.7 60.6 63.9 62.8 56.8 17.7 19.1 19.0 17.0 42.5 1.78 4 61.0 3.13 4 18.2 1.02 4 Dosage Unit: mg/kg/day 39.4 39.6 40.9 40.0 41.9 40.3 64.8 59.6 58.8 63.2 64.6 61.8 19.9 18.3 18.0 19.7 19.2 18.8 40.4 .93 6 62.1 2.53 6 19.0 .76 6 32.2 31.1 29.9 30.8 30.8 29.3 30.7 1.00 6 29.2 29.8 30.2 30.0 29.8 .43 4 30.7 30.7 30.5 31.2 29.7 30.5 30.6 .49 6 387 406 475 671 384 614 490 124.3 6 389 630 290 741 512 208.8 4 505 487 501 585 555 346 496 82.6 6 .3 .7 .1 .1 .2 .6 .3 .26 6 .3 1.0 1.3 .2 .7 .54 4 1.6 .4 .2 .4 .2 .3 .5 .54 6 19 43 7 6 12 40 21 16.4 6 21 67 84 16 47 33.7 4 97 27 14 25 13 20 33 32.0 6 542 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 7.22 6.81 6.37 5.94 7.13 6.48 13.0 11.9 11.3 11.2 12.9 12.7 6.66 .488 6 12.2 .81 6 Dosage Unit: mg/kg/day 42.6 41.5 38.3 38.0 43.0 42.3 59.0 61.0 60.2 64.0 60.2 65.3 18.0 17.4 17.7 18.8 18.1 19.5 41.0 2.23 6 61.6 2.47 6 18.2 .77 6 30.5 28.6 29.4 29.4 30.0 29.9 29.6 .65 6 522 50 475 552 396 592 431 198.6 6 .3 .4 .6 .4 .1 .6 .4 .19 6 22 27 38 24 7 39 26 11.8 6 543 ANIMAL NUMBER WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 6.1 7.8 5.8 5.1 5.1 10.2 2.3 2.9 2.5 1.7 1.7 3.3 6.7 1.99 6 2.4 .64 6 Dose Level: 0 .03 6.9 7.7 10.6 8.7 3.5 2.4 6.4 5.3 8.5 1.60 4 4.4 1.79 4 Dose Level: 0 .15 8.9 10.7 15.8 8.6 6.4 11.4 6.2 6.4 7.9 4.3 2.8 6.8 10.3 3.21 6 5.7 1.85 6 Dosage Unit: mg/kg/day 3.2 .3 .2 4.2 .6 .1 3.0 .2 .0 2.9 .4 .1 2 . 8 .4 .1 6 . 0 .6 .2 3.7 .4 .1 1.24 .16 .08 666 Dosage Unit: mg/kg/day 2 . 6 .6 .3 4.5 .6 .2 3.4 .6 .1 2.7 .6 .1 3.3 .6 .2 .8 8 . 0 0 .1 0 444 Dosage Unit: mg/kg/day 2.2 3.2 6.8 3.7 2.8 3.4 .3 .9 1.0 .4 .7 .6 .1 .1 .1 .1 .0 .5 3.7 .6 .2 1.61 .27 .18 666 .0 38 .1 37 .0 44 .0 34 .0 34 .0 33 .0 37 .04 4 66 .0 50 .0 31 .0 60 .0 61 .0 50 .00 13 44 .0 70 .1 60 .1 50 .0 50 .1 44 .0 59 .0 56 .05 9 66 52 54 52 57 56 59 55 2.8 6 38 58 32 31 40 12.6 4 25 30 43 43 44 30 36 8.4 6 5 8 3 8 8 6 6 2.1 6 8 8 6 7 7 1.0 4 4 9 6 5 11 6 7 2.6 6 4 1 1 1 3 2 2 1.3 6 4 2 1 1 2 1.4 4 1 1 1 1 0 5 2 1.8 6 1 1 0 1 0 0 0 .5 6 0 0 0 0 0 .0 4 0 1 1 0 1 0 0 .5 6 544 u)e-I u0)c2o drti > O u H H OOH O o\ O w c CQ H (N LT) H H CO o\ e o W Individual Clinical Hematology Data O O U)^ O (N oo\ eo MUc ii ) Ic--n rti 1--2C<rtODi uM EOfPPuti fE<EUOOfOPPfhttt! fwXXEO2tl OWPO2EXUPO tffttl ME HfEShfi L(fUNTt)) MXPEU>EU1XOEHPPup<u--hhhH-!i1il --EEWWOoUf<PEf2wPi--hhh-tt1 ftXw P-I E C4 off2XP\tt iiiiiii oOfWE\ti 0POiX--uB1 OUcCQl P iii 111 1 iiiiii ^1 \' OH OOH O o EHwof t x . ~i ; ii 1 e; \Tr5txi Xtj) OEO2 XOH PUB illll1ll ff2XPtt HO dX || iii1 tBn U) H LT) *s^ LT) CO 4PdHP Q0trC0dnO) LD CT>CO^ O U) CO CO (N CO (N ^ Pu ' OfWEt \oHX 1 |11 I[P> O lo o c o in o o CO LP LP [> (N l> H ou) IP (N p u O CO H LP CO CO O O O H LP (N CQ &O 545 ftPS 1 ftfCQt ii 2i uPE ii d0 o o LLoMDD [O> LLOMDD O LLOMDD iiLLOM----DD11CiLLOM--DD41CCLLOMDD44 s<! w2 S N Appendix 4 Individual Clinical Hematology Data Males Day 91 26-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 I05508 I05517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 I05505 I05510 I05518 105523 105524 I05528 Group: 4 105506 105507 I05509 105511 105512 I05522 Dose Level: 0 ------------ Dose Level: 0.03 --------- Dose Level: 0.15 ------------- Dose Level: 0.75 ------------- Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 546 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.13 6.50 6.44 6.71 5.26 6.81 11.9 13.0 12.0 12.1 11.3 13.4 6.31 .565 6 12.3 .77 6 Dose Level: 0.03 6.22 5.52 6.49 6.55 6.20 .472 4 10.6 12.8 11.3 12.2 11.7 .97 4 Dose Level: 0.15 6.49 6.70 6.16 6.89 6.59 6.14 12.2 12.0 12.1 12.7 11.5 11.7 6.50 .298 6 12.0 .42 6 Dosage Unit: mg/kg/day 38.3 43.2 39.2 40.1 37.0 44.1 62.5 66.5 60.9 59.9 70.4 64.7 19.4 20.0 18.6 18.0 21.5 19.7 40.3 2.79 6 64.1 3.90 6 19.5 1.21 6 Dosage Unit: mg/kg/day 37.1 40.8 37.5 41.3 59.7 73.9 57.8 63.0 17.0 23.1 17.5 18.6 39.2 2.18 4 63.6 7.19 4 19.0 2.78 4 Dosage Unit: mg/kg/day 40.0 40.8 39.3 40.9 37.6 37.8 61.6 61.0 63.8 59.3 56.9 61.6 18.8 18.0 19.7 18.4 17.5 19.0 39.4 1.44 6 60.7 2.35 6 18.6 .78 6 31.0 30.1 30.5 30.1 30.5 30.4 30.4 .33 6 28.4 31.3 30.2 29.6 29.9 1.21 4 30.6 29.5 30.8 31.1 30.7 30.9 30.6 .57 6 682 556 629 515 446 544 562 83.6 6 492 462 493 422 467 33.4 4 423 432 394 355 585 461 442 78.9 6 .2 .3 .4 .4 .3 .3 .3 .08 6 .5 .5 .6 .3 .5 .13 4 .2 .1 .3 .3 .3 .1 .2 .10 6 12 20 26 27 16 20 20 5.7 6 31 28 39 20 30 7.9 4 13 7 18 21 20 6 14 6.6 6 547 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 6.39 6.06 6.35 6.47 6.57 6.07 11.9 11.8 11.7 12.5 11.9 11.4 6.32 .210 6 11.9 .36 6 Dosage Unit: mg/kg/day 40.1 39.8 40.4 42.2 41.6 37.8 62.7 65.7 63.6 65.2 63.3 62.3 18.7 19.5 18.4 19.3 18.2 18.7 40.3 1.54 6 63.8 1.37 6 18.8 .51 6 29.8 29.7 28.9 29.5 28.7 30.1 29.4 .54 6 328 520 568 597 635 378 504 124.1 6 .1 .4 .1 .3 .0 .3 .2 .15 6 6 24 6 19 0 18 12 9.4 6 548 ANIMAL NUMBER WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 I05530 I05531 I05535 I05544 I05549 6.4 3.2 2 . 6 1 1 . 1 6 . 2 4.1 9.1 4.7 3.5 11.7 3.0 7.1 9.1 2.8 5.1 8.7 4.4 3.5 .5 .6 .6 .8 .6 .6 1 .0 50 41 2 .0 56 37 3 .0 51 38 7 .1 26 61 7 .0 30 56 2 .0 50 40 81 52 73 76 67 72 1 0 0 1 0 0 MEAN S.D. N 9.4 1.89 6 4.0 1.31 6 4.3 1.59 6 .6 .10 6 4 .0 44 46 7 4 0 27 .04 12.5 10.3 1.0 2.4 .5 6666666 Group: 2 Dose Level: 0 .03 Dosage Unit: mg/kg/day I05537 I05541 I05547 I05550 8.3 3.5 3.0 1.3 10.4 4.4 4.9 .8 4.1 1.7 2 . 0 .3 1 2 . 0 8 . 2 2.9 .8 3 .2 42 37 15 2 .0 42 47 8 1 .0 41 48 8 1 .0 6 8 24 6 32 20 30 10 MEAN S.D. N 8.7 3.42 4 4.4 2.74 4 3.2 1.22 4 .8 .41 4 2 .0 48 39 92 0 10 .10 13.2 11.2 3.9 1.0 1.0 4444444 Group: 3 Dose Level: 0 .15 Dosage Unit: mg/kg/day I05532 I05538 I05539 I05545 I05548 I05552 6.5 3.6 2.4 9.5 5.2 3.2 8.5 3.3 4.4 8 . 8 4.4 3.5 10.2 5.2 3.9 8.9 4.9 3.1 .3 .8 .5 .7 .7 .5 1 .0 56 37 2 .0 55 34 2 .0 39 52 1 .0 50 40 3 .0 51 38 4 .0 55 35 52 92 62 81 73 64 0 0 1 0 0 0 MEAN S.D. N 8.7 1.25 6 4.4 .82 6 3.4 .69 6 .6 .18 6 2 .0 51 39 72 0 12 .00 6.4 6.6 1.5 1.0 .4 6666666 549 Individual Clinical Hematology Data 550 ro i> 0(N1 LD Io O(rNo (UNI) U) E-< 0U)2ro dfd > o u LD HHOOOO O o\ O w c CQ I o\ I 5' wo H PI r l r o r o H O r l (N H U) LD o\ 1 c oHc NHO ^ r o u ) o ro U) O1 5| Oi 2i Qi Hi u C u H 5w OX f t ftl o\ ffi ft 2 X 1 1 1 i i rLPo ir>o croo Lron r(No i(>N uro) oH u) P PS P i i WO ft 2 2W o\ i 1 rH oeroc-soF oLPoU') [>' U) 'LDX'rHo'X' <! P O i Eh O UP WP ' CO u 1 OO OO 2 ft 1 1 S<L i O5 o PX H H O Pft U Xi l H H O O O O O OLDU ) ft S O 1 ftftl H fd CO 1 <! _ i CQ P 1 P in Eh o B 1 i H (N \ 2 U) M i H C N C N H O H H OCOU ) CO X Eh s d 1 <D H ^ 1 x 1-- P - CO 1 cd Ba)fd Eh CO O i T5 CO O W j ' \ ft fc >H f t n 1 tj) |i Eh \ H U Eh c-t'" ' O1 Btj) 'X'CN'X' Hp X< O CO Eh H OX 5 O l 1 i i 4P H H 2 HP PH 2i i Pi d P BP CO co co p-i u 0) tj) fd ro H (N CO (N 1> O O01U ) <! Eh uo f t i1 CO 0 s^ fO C N ro C N H (N H P-I X wft s rj i >H X | P1 1 Q P P' CN u 1 H H C O i n o H '>[L>D'> 1 Wo 1 LD 1> ro ^ (N U) I> ^ *sF H wH 1 o x : <D UB C2QfOOH 1 11 1il > P<D <COD 0 (N LP O I> LP (N C O C O lfHlO P fO Xl H Hf t CO H ft l fCQt lI 2i PI 5i ft d 0u o ro L>O PIH rororo LD LD LD LD LD LD LD LoHDLoHDLoHDLOHD LD OH LoHD s <! w 2 CO Appendix 4 Individual Clinical Hematology Data Females Day 91 26-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 105529 105530 105531 I05535 I05544 105549 - - - - Group: 2 Dose Level: 0.03 I05537 - - - I05541 - - - I05547 - - - 105550 - - - Group: 3 Dose Level: 0.15 I05532 - - - 105538 - - - 105539 - - - I05545 - - - I05548 - - - I05552 - - - Group: 4 Dose Level: 0.75 105533 - - - 105534 - - - I05536 - - - I05540 - - - I05542 - - - I05551 - - - Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 551 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.44 6.54 7.40 6.44 6.28 6.95 12.3 13.1 12.8 12.1 11.7 12.9 6.68 .421 6 12.5 .54 6 Dose Level: 0.03 6.80 7.26 6.55 7.71 12.0 13.0 12.4 12.9 7.08 .513 4 12.6 .46 4 Dose Level: 0.15 6.35 7.19 7.53 6.39 6.74 6.50 12.6 12.6 13.2 12.2 12.8 12.2 6.78 .479 6 12.6 .38 6 Dosage Unit: mg/kg/day 39.3 43.3 42.9 38.7 38.6 42.8 61.0 66.3 58.0 60.1 61.3 61.6 19.1 20.0 17.3 18.8 18.7 18.5 40.9 2.28 6 61.4 2.74 6 18.7 .88 6 Dosage Unit: mg/kg/day 40.8 44.0 39.6 42.4 59.9 60.7 60.5 55.0 17.7 17.9 18.9 16.7 41.7 1.91 4 59.0 2.70 4 17.8 .90 4 Dosage Unit: mg/kg/day 40.5 41.3 43.4 39.8 42.8 40.2 63.7 57.5 57.6 62.3 63.5 61.9 19.9 17.5 17.6 19.2 19.1 18.8 41.3 1.47 6 61.1 2.82 6 18.7 .95 6 31.4 30.2 29.9 31.2 30.5 30.1 30.6 .62 6 29.5 29.5 31.2 30.4 30.2 .82 4 31.2 30.5 30.5 30.8 30.0 30.4 30.6 .40 6 351 379 447 643 354 613 464 131.6 6 389 618 296 630 483 167.0 4 406 496 546 783 515 366 519 146.4 6 .1 .2 .4 .0 .1 .7 .2 .26 6 .2 .2 .4 .0 .2 .16 4 .5 .2 .4 .4 .6 .6 .4 .15 6 6 13 30 0 6 49 17 18.7 6 14 15 26 0 14 10.7 4 32 14 30 26 40 39 30 9.6 6 552 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 7.78 6.93 6.08 6.10 6.61 6.38 13.4 11.7 10.3 11.1 12.0 12.1 6.65 .641 6 11.8 1.04 6 Dosage Unit: mg/kg/day 45.8 39.3 36.1 37.7 40.4 40.5 59.0 56.7 59.4 61.8 61.2 63.6 17.3 16.8 16.9 18.2 18.2 19.0 40.0 3.32 6 60.3 2.43 6 17.7 .87 6 29.3 29.7 28.5 29.5 29.7 29.9 29.4 .50 6 486 21 373 553 405 552 398 199.1 6 .4 .1 .7 1.1 1.2 .1 .6 .48 6 31 7 43 67 79 6 39 30.3 6 553 ANIMAL NUMBER WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 5.3 6.7 6.7 7.8 5.2 12.3 1.8 1.7 2.9 2.3 1.6 5.9 7.3 2.62 6 2.7 1.64 6 Dose Level: 0 .03 10.0 8.8 11.3 9.6 9.9 1.04 4 6.2 3.1 6.4 6.8 5.6 1.70 4 Dose Level: 0 .15 11.8 9.3 9.7 13.8 6.7 9.2 8.6 5.5 2.9 8.3 1.9 3.8 10.1 2.44 6 5.2 2.81 6 Dosage Unit: mg/kg/day 2.9 .3 4.5 .4 3.5 .2 4.3 .7 2.9 .6 5.1 1.0 .4 .0 .1 .3 .1 .1 3.9 .5 .2 .91 .29 .15 666 Dosage Unit: mg/kg/day 3.0 .4 .3 4.8 .6 .2 3.8 .9 .2 2.3 .5 .1 3.5 .6 .2 1.08 .22 08 444 Dosage Unit: mg/kg/day 2.5 .5 .3 3.1 .6 .1 5.9 .8 .1 4.4 .6 .4 4.1 .7 .1 3.9 .8 .6 4.0 .7 .3 1.17 .12 21 666 .0 34 .0 25 .0 43 .2 30 .0 32 .0 48 .0 35 .08 8 66 .0 62 .0 35 .0 56 .0 70 .0 56 .00 15 44 .0 73 .0 59 .1 30 .0 60 .1 28 .1 42 .0 49 .05 18 66 54 68 52 55 56 42 54 8.3 6 30 55 34 24 36 13.5 4 21 33 61 32 61 43 42 16.4 6 5 6 3 9 11 8 7 2.9 6 4 7 8 5 6 1.8 4 4 7 9 4 10 8 7 2.5 6 7 0 1 4 1 1 2 2.7 6 3 3 2 1 2 1.0 4 2 1 1 3 1 6 2 2.0 6 0 0 0 2 0 0 0 .8 6 0 0 0 0 0 .0 4 0 0 1 0 1 1 0 .5 6 554 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level 0.75 Dosage Unit: mg/kg/day 6.7 2.5 3.6 .5 .1 .0 38 54 71 0 8.9 3.9 4.4 .5 .1 .0 44 50 51 0 13.2 10.0 1.8 1.4 .0 .0 76 13 1 1 0 0 5.9 2.2 3.2 .3 .2 .0 37 55 6 3 0 7.6 2.2 4.0 1.2 .1 .0 29 53 15 2 0 11.6 5.2 4.9 .9 .5 .1 45 42 8 4 1 9.0 4.3 3.6 .8 .2 .0 45 44 92 0 2.87 3.02 1.08 .44 .18 .04 16.3 16.1 3.7 1.5 .4 66666666666 555 Appendix 4 Individual Clinical Hematology Data Males Day 153 26-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 I05508 I05517 105519 105520 105526 105527 Group: 2 105514 105515 105516 105521 Group: 3 I05505 I05510 I05518 105523 105524 I05528 Group: 4 105506 105507 I05509 105511 105512 I05522 Dose Level: 0 ------------ Dose Level: 0.03 --------- Dose Level: 0.15 ------------- Dose Level: 0.75 ------------- Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 556 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 5.82 6.31 6.88 7.30 6.25 7.02 11.3 12.5 12.6 12.9 11.6 13.6 6.60 .559 6 12.4 .85 6 Dose Level: 0.03 6.74 5.74 6.96 7.20 10.9 12.2 11.7 13.1 6.66 .641 4 12.0 .92 4 Dose Level: 0.15 6.80 6.37 6.59 7.00 6.84 6.39 12.5 11.7 12.3 12.7 11.6 11.9 6.66 .257 6 12.1 .45 6 Dosage Unit: mg/kg/day 36.1 41.0 40.7 42.9 38.7 44.4 61.9 65.1 59.1 58.7 62.0 63.3 19.3 19.8 18.3 17.7 18.6 19.3 40.6 2.96 6 61.7 2.45 6 18.8 .77 6 Dosage Unit: mg/kg/day 38.5 40.3 39.0 43.9 57.0 70.3 56.0 61.0 16.2 21.2 16.8 18.2 40.4 2.44 4 61.1 6.52 4 18.1 2.23 4 Dosage Unit: mg/kg/day 40.8 38.5 40.6 41.5 38.3 39.4 60.0 60.5 61.6 59.3 55.9 61.6 18.4 18.4 18.7 18.1 17.0 18.7 39.9 1.31 6 59.8 2.12 6 18.2 .64 6 31.2 30.4 31.0 30.2 30.0 30.5 30.6 .46 6 28.4 30.2 30.0 29.8 29.6 .82 4 30.7 30.4 30.3 30.6 30.3 30.3 30.4 .18 6 609 544 586 469 498 416 520 73. 1 6 .2 .5 .1 .0 .7 .7 .4 .31 6 322 385 450 391 387 52. 3 4 .4 1.5 .1 .5 .6 .61 4 424 425 506 326 545 532 460 83. 7 6 .7 .4 .3 .0 .2 .2 .3 .24 6 12 32 7 0 44 49 24 20.5 6 27 86 7 36 39 33.6 4 48 25 20 0 14 13 20 16.1 6 557 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 6.67 6.20 6.07 5.97 6.56 6.51 12.2 12.1 11.0 11.5 11.6 11.9 6.33 .288 6 11.7 .44 6 Dosage Unit: mg/kg/day 41.2 41.4 36.8 37.3 40.0 40.3 61.7 66.7 60.7 62.4 60.9 61.9 18.4 19.5 18.2 19.2 17.6 18.3 39.5 1.98 6 62.4 2.21 6 18.5 .70 6 29.8 29.3 30.0 30.8 28.9 29.6 29.7 .65 6 320 582 563 491 671 322 492 144.0 6 .3 .3 .1 .0 .1 .2 .2 .12 6 20 19 6 0 7 13 11 7.9 6 558 ANIMAL NUMBER WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 8.4 8.3 14.5 8.3 8.7 10.0 5.1 1.8 9.9 2.4 2.9 5.3 9.7 2.44 6 4.6 2.98 6 Dose Level: 0 .03 8.5 6.5 15.9 6.4 4.2 2.2 10.2 3.5 9.3 4.49 4 5.0 3.55 4 Dose Level: 0 .15 5.6 10.6 6.3 11.0 7.6 7.5 2.5 6.6 1.1 5.3 3.2 3.4 8.1 2.23 6 3.7 1.98 6 Dosage Unit: mg/kg/day 2.6 .6 5.9 .5 3.8 .7 4.4 1.0 3.9 1.3 3.8 .7 .1 .1 .1 .5 .4 .1 4.1 .8 .2 1.08 .30 .18 666 Dosage Unit: mg/kg/day 3.0 3.6 2.8 2.1 .9 .5 2.6 .5 .4 .1 .1 .2 2.9 .62 4 1.1 1.00 4 .2 .14 4 Dosage Unit: mg/kg/day 2.4 .6 .1 2.9 .8 .3 4.5 .5 .2 4.8 .6 .2 3.1 .8 .4 3.0 .5 .5 3.4 .6 .3 .96 .14 15 666 0 60 31 71 0 0 22 70 6 2 0 0 6 8 26 51 0 1 28 52 1 2 6 1 1 34 45 15 5 1 1 53 38 71 1 0 44 44 9 3 0 05 18.7 15.9 3.9 2.3 .5 666666 2 49 35 10 42 1 34 56 8 1 1 1 64 18 16 1 0 0 55 34 92 0 1 50 36 1 1 2 1 08 12.6 15.6 3.6 1.4 1.0 444444 0 45 43 1 0 1 1 0 63 27 7 3 0 0 18 71 8 3 0 0 48 44 52 0 0 42 41 1 1 50 0 45 40 76 1 0 44 44 8 3 0 00 14.5 14.4 2.2 1.9 .5 666666 559 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level 0.75 8.2 13.2 10.1 11.7 9.0 4.6 2.1 3.8 6.6 7.4 5.0 1.7 9.5 2.99 6 4.4 2.33 6 Dosage Unit: mg/kg/day 4.9 .9 7.9 1.0 1.9 1.3 3.5 .6 3.6 .3 2.2 .6 .2 .4 .2 .1 .2 .0 4.0 .8 .2 2.19 .35 .13 666 .1 26 60 1 1 .1 29 60 7 .1 65 19 13 .0 64 30 5 .0 55 39 3 .0 38 48 13 .0 46 43 9 .05 17.4 16.5 4.3 6666 3 3 2 1 2 1 2 .9 6 1 1 1 0 0 1 1 .5 6 560 Appendix 4 Individual Clinical Hematology Data Females Day 153 26-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 105529 105530 105531 I05535 I05544 105549 - - - - Group: 2 Dose Level: 0.03 I05537 - - - I05541 - - - I05547 - - - 105550 - - - Group: 3 Dose Level: 0.15 I05532 - - - 105538 - - - 105539 - - - I05545 - - - I05548 - - - I05552 - - - Group: 4 Dose Level: 0.75 105533 - - - 105534 - - - I05536 - - - I05540 - - - I05542 - - - I05551 - - - Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 561 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.43 6.72 7.22 6.17 6.48 6.57 12.8 13.1 12.7 11.7 12.2 12.3 6.60 .354 6 12.5 .50 6 Dose Level: 0.03 6.88 6.47 6.61 7.86 12.1 12.2 12.5 13.1 6.96 .627 4 12.5 .45 4 Dose Level: 0.15 6.43 6.98 7.21 6.50 6.57 6.21 6.65 .372 6 12.5 12.4 12.8 12.6 12.6 11.9 12.5 .31 6 Dosage Unit: mg/kg/day 40.3 44.2 42.0 38.0 40.4 41.7 62.7 65.8 58.1 61.6 62.3 63.5 19.9 19.5 17.6 18.9 18.8 18.8 41.1 2.07 6 62.3 2.53 6 18.9 .78 6 Dosage Unit: mg/kg/day 42.5 40.7 40.8 44.5 61.7 62.9 61.7 56.6 17.6 18.8 18.9 16.7 42.1 1.79 4 60.7 2.81 4 18.0 1.05 4 Dosage Unit: mg/kg/day 41.8 40.8 42.1 40.7 41.8 39.0 65.0 58.4 58.4 62.6 63.5 62.9 19.5 17.8 17.7 19.3 19.2 19.1 41.0 1.15 6 61.8 2.76 6 18.8 .80 6 31.7 29.6 30.2 30.7 30.2 29.6 30.3 .79 6 28.5 29.9 30.6 29.5 29.6 .88 4 30.0 30.4 30.4 30.9 30.2 30.4 30.4 .30 6 404 399 445 591 392 571 467 90.4 6 398 559 246 663 466 183.0 4 411 464 514 526 527 380 470 63.1 6 .1 .2 .2 .1 .1 .3 .2 .08 6 .4 .2 .0 .1 .2 .17 4 .3 .3 .3 .3 .2 .3 .3 .04 6 6 13 14 6 6 20 11 5.8 6 28 13 0 8 12 11.8 4 19 21 22 20 13 19 19 3.2 6 562 ANIMAL NUMBER Group: 4 I05506 a I05507 I05511 I05512 I05522 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 7.69 6.64 5.76 6.46 6.44 13.3 11.0 10.4 11.7 12.3 6.32 .387 4 11.4 .83 4 Dosage Unit: mg/kg/day 44.3 38.4 35.7 39.8 41.5 57.7 57.9 62.0 61.6 64.5 17.2 16.5 18.1 18.1 19.1 38.8 2.45 4 61.5 2.72 4 17.9 1.08 4 29.9 28.5 29.2 29.4 29.6 29.2 .48 4 560 78 PA 486 429 610 401 228. 0 4 .2 .3 .5 .0 .0 .2 .24 4 15 20 29 0 0 12 14.6 4 a Unscheduled sacrifice on Day 179. 563 ANIMAL NUMBER Group: 1 I05508 105517 105519 105520 105526 105527 MEAN S.D. N Group: 2 105514 105515 105516 105521 MEAN S.D. N Group: 3 I05505 I05510 105518 105523 105524 105528 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 9.5 9.0 6.8 12.0 10.0 10.8 3.6 2.6 4.0 5.8 6.7 2.8 9.7 1.76 6 4.2 1.66 6 Dose Level: 0 .03 8.9 5.7 7.5 2.7 8 . 1 5.8 9.1 5.2 8.4 .74 4 4.8 1.46 4 Dose Level: 0 .15 10.3 9.1 13.6 10.8 6.1 10.0 7.5 4.6 6.6 6.3 1.6 4.6 10.0 2.44 6 5.2 2.10 6 Dosage Unit: mg/kg/day 4.8 5.6 2.5 5.0 2.8 6.0 .6 .6 .3 .7 .4 1 .6 .5 .1 .1 .4 .1 .3 4.4 .7 .2 1.46 .46 .18 666 Dosage Unit: mg/kg/day 2 . 6 .4 .2 3.6 .9 .2 1.9 .3 .1 3.2 .6 .1 2 . 8 .6 .2 .74 .26 .06 444 Dosage Unit: mg/kg/day 2.3 .4 .2 3.9 .4 .1 6 . 6 .3 .1 3.8 .5 .1 3.8 .5 .1 4.1 .7 .6 4.1 .5 .2 1.39 .14 .2 0 666 0 38 50 6 1 30 62 7 0 58 37 4 1 49 42 6 0 67 28 4 1 26 55 15 6 1 1 3 1 3 0 45 46 7 2 05 16.1 12.4 4.1 2.0 66666 0 64 30 4 0 36 48 12 0 71 23 4 0 58 35 6 2 3 1 1 0 57 34 6 2 00 15.1 10.6 3.8 1.0 44444 0 72 2 2 42 0 51 43 5 1 0 48 48 2 0 0 59 35 5 1 0 26 63 9 1 0 46 41 7 6 0 50 42 5 2 00 15.2 13.6 2.4 2.1 66666 0 1 0 1 0 1 0 .5 6 0 1 0 0 0 .5 4 0 0 0 0 0 0 0 .0 6 564 ANIMAL NUMBER Group: 4 I05506 a I05507 I05511 I05512 I05522 MEAN S.D. N WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level 19.7 9.4 5.1 6.6 9.2 7.6 2.09 4 0.75 14.7 3.9 2.0 1.9 3.9 2.9 1.13 4 Dosage Unit: mg/kg/day 4.0 1.0 4.9 .4 2.3 .6 4.3 .4 4.5 .6 .0 .1 .2 .0 .2 4.0 .5 .1 1.16 .12 .10 444 .0 74 2 0 50 0 .0 42 52 51 0 .1 39 45 1 1 41 .0 28 6 6 50 0 .1 43 49 6 2 1 .0 38 53 72 0 .06 6 .9 9.1 2 .9 1.7 .6 444444 a Unscheduled sacrifice on Day 179. 565 Appendix 4 Individual Clinical Hematology Data Males Day 182 26-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 I05508 I05517 I05519 I05520 I05526 I05527 Group: 2 I05514 I05515 I05516 b I05521 Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 Group: 4 I05506 a I05507 I05511 I05512 I05522 Dose Level: 0 -_ --_ -_ -_ -_ Dose Level: 0.03 -_ -_ -_ -_ Dose Level: 0.15 -_ -_ -_ -_ -_ -_ Dose Level: 0.75 -_ -_ -_ -_ -_ Dosage Unit: mg/kg/day ------------- Dosage Unit: mg/kg/day --------- Dosage Unit: mg/kg/day ------------- Dosage Unit: mg/kg/day ----------- a Unscheduled sacrifice on Day 179. b Plasmodium was observed. 566 Covance 6329-223 3M T-6295.7 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 5.66 6.38 6.63 7.04 6.20 6.52 11.0 12.6 12.0 12.7 11.9 12.5 6.40 .461 6 12.1 .64 6 Dose Level: 0.03 6.69 5.80 5.20 6.92 10.8 12.2 9.0 12.7 6.15 .798 4 11.2 1.66 4 Dose Level: 0.15 6.65 6.14 6.67 6.81 6.75 6.38 12.3 11.0 12.5 12.4 11.3 11.9 6.57 .256 6 11.9 .62 6 Dosage Unit: mg/kg/day 35.7 42.6 40.5 42.8 40.9 42.3 63.0 66.8 61.2 60.8 65.9 64.9 19.5 19.7 18.1 18.1 19.2 19.2 40.8 2.67 6 63.8 2.49 6 19.0 .70 6 Dosage Unit: mg/kg/day 38.9 41.4 30.1 42.7 58.2 71.3 58.0 61.8 16.2 21.1 17.4 18.3 38.3 5.67 4 62.3 6.23 4 18.2 2.09 4 Dosage Unit: mg/kg/day 40.8 37.6 41.9 41.0 37.8 40.2 61.3 61.2 62.7 60.3 56.1 63.0 18.4 17.9 18.8 18.3 16.8 18.7 39.9 1.78 6 60.8 2.50 6 18.2 .73 6 31.0 29.6 29.5 29.7 29.1 29.6 29.7 .65 6 27.9 29.5 30.0 29.7 29.3 .94 4 30.1 29.3 29.9 30.3 30.0 29.7 29.9 .35 6 595 583 534 369 439 383 484 100.1 6 442 380 501 394 429 54.7 4 373 381 400 318 484 517 412 74.4 6 .2 .4 .3 .2 .8 .6 .4 .24 6 .2 .2 .4 .1 .2 .13 4 .3 .3 .2 .0 .2 .1 .2 .12 6 11 26 20 14 50 39 27 15.1 6 13 12 21 7 13 5.8 4 20 18 13 0 14 6 12 7.5 6 567 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Appendix 4 Individual Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0.75 6.00 5.65 6.08 5.99 6.75 6.09 11.3 11.0 10.9 11.6 11.9 11.3 6.09 .360 6 11.3 .37 6 Dosage Unit: mg/kg/day 37.6 37.7 39.3 38.6 43.4 38.4 62.6 66.8 64.6 64.5 64.3 63.1 18.9 19.4 17.9 19.3 17.7 18.6 39.2 2.17 6 64.3 1.46 6 18.6 .71 6 30.1 29.1 27.8 29.9 27.5 29.5 29.0 1.09 6 288 587 559 454 725 328 490 166.0 6 .2 .5 .0 .0 .4 .1 .2 .21 6 12 28 0 0 27 6 12 12.7 6 568 ANIMAL NUMBER WBC X103/mcL Appendix 4 Individual Clinical Hematology Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 14.6 7.3 10.5 13.9 10.4 5.4 11.4 2.6 5.2 5.5 2.9 2.4 10.4 3.59 6 5.0 3.41 6 Dose Level: 0.03 10.1 6.6 6.8 10.4 5.4 2.4 4.0 5.5 8.5 2.05 4 4.3 1.45 4 Dose Level: 0.15 8.2 9.2 7.5 11.0 11.3 8.0 3.9 4.5 1.6 6.3 6.2 4.3 9.2 1.61 6 4.5 1.73 6 Dosage Unit: mg/kg/day 2.5 3.9 4.3 7.0 6.2 2.1 .6 .6 .7 1.0 .6 .7 .1 .2 .2 .3 .6 .1 4.3 .7 .2 1.96 .15 .19 666 Dosage Unit: mg/kg/day 3.1 1.1 3.5 .5 2.4 .4 3.7 .8 .4 .2 .1 .4 3.2 .7 .3 .57 .32 .15 444 Dosage Unit: mg/kg/day 3.8 .4 .1 3.8 .6 .3 4.9 .8 .1 3.9 .6 .1 3.7 .6 .7 3.0 .3 .4 3.8 .6 .3 .61 .18 .24 666 1 78 17 4 0 35 54 8 1 50 41 7 1 39 50 7 0 28 60 6 0 44 40 14 1 3 2 2 6 2 0 46 44 8 3 05 17.5 15.1 3.4 1.8 66666 1 0 1 1 0 0 0 .5 6 2 54 30 1 1 42 0 37 53 7 3 0 0 58 35 6 1 0 0 53 35 7 4 0 0 50 38 8 3 0 10 9.3 10.1 2.2 1.4 1.0 444444 0 48 46 51 0 0 49 41 6 4 0 1 22 65 10 2 2 0 57 36 6 1 0 0 55 33 56 0 0 54 37 4 4 0 0 48 43 6 3 0 04 13.0 11.7 2.1 2.0 .8 666666 569 ro i> 0(N1 LX) Io O(rNo)(UNI) U) E-< d) 2 U ro d fd > o u Individual Clinical Hematology Data LD HHHOOO O LX> o\ O co cCQ CO H H C N H r O H (N >X o\ o H oo\ O 2 C ACID M co o\ fftt OX 2 ftftl X PX P PcoO 2 ft co o\ O Eh O UP WCO Pu OO Oft2O 1 \B XI O PX ftCO P U rH o rH X Oi O ftlM CO cd ft ,-s fEfhiLfXt) c_ CQ PU e M (N S'X o CO d) >h Eh 3M x^ 1--1 Bfd d) En PEh C-O Ul O ft >Hft Eh CO O Wj U P HH U Eh o HHP rH X< OX OEh CO O 22 WP P h-I p co coco p-irij <!H 2U O p-i O-i>2"1 x iX wp H o' W( IX) CO IX) LX> CO CO ro U) rH Hcn^ocnco LX) -si1 ro ro U) (N CO (N H O) CO (N ro -st1 -st1 LX) (N 'X X U) -si1 *st1 H i--l i --l i --l O i --I O LX) i--I O CO H C N C N H rO H CO (N O lx> rd T5 O) X si1O (N LX) CO IX) rH rH [> Orol'X d P d) O) o fd CO O CO CO O CO C O h C O CO o r o ' X > ( N r o O ) H si1(N ( N O H C n o o OlrKO LX) ..................................................... I> ro LX) -st1 LX) ro -st1 H o p u CQ O <D > ro (1) L X iH - s P r o - s F - s t1 l > l > ' X 0P ..................................................... h o ic o o ro c o )(N d) rH rH rH CO O 570 ft i ft i CQ i 2i Pi i ft d 0 H o ro o XI rH ro ro ro LX) LX) LX) LX) LX) LX) LX) LX) LX) LX) LX) LX) LX) o o o OOO MMMMMM s <! w 2 CO Appendix 4 Individual Clinical Hematology Data Females Day 182 26-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 105529 105530 105531 I05535 I05544 105549 - - - - Group: 2 Dose Level: 0.03 I05537 - - - I05541 - - - I05547 - - - 105550 - - - Group: 3 Dose Level: 0.15 I05532 - - - 105538 - - - 105539 - - - I05545 - - - I05548 - - - I05552 - - - Group: 4 Dose Level: 0.75 105533 - - - 105534 - - - I05536 - - - I05540 - - - I05542 - - - I05551 - - - Dosage Unit: mg/kg/day - - Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ------- Dosage Unit: mg/kg/day ------- Covance 6329-223 3M T-6295.7 571 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.27 6.26 12.1 11.8 6.26 .007 2 12.0 .21 2 Dose Level: 0.15 6.53 6.45 13.0 12.4 6.49 .057 2 12.7 .42 2 Dose Level: 0.75 5.93 5.87 11.6 11.5 5.90 .042 2 11.6 .07 2 Dosage Unit: mg/kg/day 38.3 37.9 61.0 60.5 19.3 18.9 38.1 .28 2 60.8 .35 2 19.1 .28 2 Dosage Unit: mg/kg/day 41.6 39.8 63.7 61.8 19.9 19.3 40.7 1.27 2 62.8 1.34 2 19.6 .42 2 Dosage Unit: mg/kg/day 38.2 37.3 64.5 63.5 19.5 19.6 37.8 .64 2 64.0 .71 2 19.5 .07 2 31.7 31.2 31.5 .35 2 31.3 31.2 31.2 .07 2 30.3 30.9 30.6 .42 2 620 346 483 193.7 2 404 572 488 118.8 2 485 453 469 22.6 2 .3 .4 .4 .07 2 .4 .2 .3 .14 2 .3 .6 .4 .21 2 19 25 22 4.2 2 26 13 20 9.2 2 18 35 26 12.0 2 572 ANIMAL NUMBER WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 I05526 8.5 2.5 5.2 .5 3 .0 30 61 6 3 1 6 . 1 2.3 2.9 .7 2 .0 37 47 1 2 31 MEAN S.D. N 7.3 1.70 2 2.4 .14 2 4.0 1.63 2 .6 .14 2 2 .0 34 54 93 1 07 .00 4.9 9.9 4.2 .0 .0 2222222 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 8 . 8 4.7 3.0 .7 4 .0 53 34 8 5 0 I05523 14.2 7.6 6 . 0 .4 2 .0 53 42 31 0 MEAN S.D. N 11.5 3.82 2 6.2 2.05 2 4.5 2.12 2 .6 .21 2 3 .0 53 38 6 3 0 14 .00 .0 5.7 3.5 2 . 8 .0 2222222 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 I05522 8.9 4.1 3.9 .5 14.7 7.9 5.0 1.3 4 .0 46 44 5 .0 54 34 54 94 0 0 MEAN S.D. N 11.8 4.10 2 6.0 2.69 2 4.4 .78 2 .9 .57 2 4 .0 50 39 7 4 0 07 .00 5.7 7.1 2 . 8 .0 .0 2222222 573 APPENDIX 4 Individual Clinical Hematology Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 ---- Dose Level: 0.15 Dose Level: 0.75 ----- - Dosage Unit: mg/kg/day -- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day --- Covance 6329-223 3M T-6295.7 574 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 5.44 6.45 10.9 12.6 5.94 .714 2 11.8 1.20 2 Dose Level: 0.15 6.07 6.20 11.8 12.0 6.14 .092 2 11.9 .14 2 Dose Level: 0.75 6.13 6.72 11.8 12.2 6.42 .417 2 12.0 .28 2 Dosage Unit: mg/kg/day 33.5 40.3 61.5 62.4 20.1 19.6 36.9 4.81 2 62.0 .64 2 19.8 .35 2 Dosage Unit: mg/kg/day 37.2 38.0 61.4 61.3 19.5 19.4 37.6 .57 2 61.4 .07 2 19.5 .07 2 Dosage Unit: mg/kg/day 38.2 42.3 62.2 63.0 19.2 18.2 40.2 2.90 2 62.6 .57 2 18.7 .71 2 32.7 31.3 32.0 .99 2 31.8 31.6 31.7 .14 2 30.8 28.9 29.8 1.34 2 547 390 468 111.0 2 382 435 408 37.5 2 330 557 444 160.5 2 .1 .5 .3 .28 2 .2 .5 .4 .21 2 .3 .7 .5 .28 2 5 32 18 19.1 2 12 31 22 13.4 2 18 47 32 20.5 2 575 ANIMAL NUMBER WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 10.1 6.2 6.1 3.1 8.2 2.76 2 4.6 2.12 2 Dose Level: 0.15 6.9 1.8 8.4 3.5 7.6 1.06 2 2.6 1.20 2 Dose Level: 0.75 7.7 10.9 2.1 3.0 9.3 2.26 2 2.6 .64 2 Dosage Unit: mg/kg/day 3.0 .8 2.5 .4 1 1 2.8 .35 2 .6 .28 2 1 00 2 Dosage Unit: mg/kg/day 4.3 .7 3.8 .5 2 5 4.0 .35 2 .6 .14 2 4 21 2 Dosage Unit: mg/kg/day 5.0 .3 6.7 .8 3 2 5.8 1.20 2 .6 .35 2 2 07 2 .0 60 30 .0 50 41 81 72 0 0 .0 55 36 8 2 0 .00 7.1 7.8 .7 .7 .0 222222 .1 26 61 10 31 .0 41 45 6 6 1 .0 34 53 8 4 1 .07 10.6 11.3 2.8 2.1 .0 222222 .0 27 65 4 4 0 .1 28 62 8 2 1 .0 28 64 6 3 0 .07 .7 2 . 1 2 . 8 1.4 .7 222222 576 APPENDIX 4 Individual Clinical Hematology Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 ---- Dose Level: 0.15 Dose Level: 0.75 ----- - Dosage Unit: mg/kg/day -- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day --- Covance 6329-223 3M T-6295.7 577 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.75 6.28 13.0 12.2 6.52 .332 2 12.6 .57 2 Dose Level: 0.15 6.75 6.82 13.3 13.3 6.78 .049 2 13.3 .00 2 Dose Level: 0.75 6.06 6.33 11.4 12.4 6.20 .191 2 11.9 .71 2 Dosage Unit: mg/kg/day 40.6 37.9 60.2 60.3 19.3 19.4 39.2 1.91 2 60.2 .07 2 19.4 .07 2 Dosage Unit: mg/kg/day 42.5 41.8 62.9 61.3 19.8 19.4 42.2 .49 2 62.1 1.13 2 19.6 .28 2 Dosage Unit: mg/kg/day 39.0 39.9 64.4 63.0 18.8 19.5 39.5 .64 2 63.7 .99 2 19.2 .49 2 32.1 32.1 32.1 .00 2 31.4 31.7 31.6 .21 2 29.2 31.0 30.1 1.27 2 685 428 556 181.7 2 467 519 493 36.8 2 501 562 532 43.1 2 .1 .3 .2 .14 2 .1 .2 .2 .07 2 .8 .4 .6 .28 2 7 19 13 8.5 2 7 14 10 4.9 2 48 25 36 16.3 2 578 ANIMAL NUMBER WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 I05526 12.1 8.0 3.8 7.6 2.7 4.6 .5 .4 3 .0 31 63 3 .0 33 58 42 54 0 0 MEAN S.D. N 10.0 2.90 2 3.2 .78 2 6.1 2.12 2 .4 .07 2 3 .0 32 60 4 3 0 00 .00 1.4 3.5 .7 1.4 .0 2222222 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 I05523 10.6 12.2 5.2 4.1 5.8 5.6 .8 .4 4 .0 49 39 3 .0 48 46 84 32 0 0 MEAN S.D. N 11.4 1.13 2 5.5 .42 2 4.8 1.06 2 .6 .28 2 4 .0 48 42 6 3 0 07 .00 .7 4.9 3.5 1.4 .0 2222222 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 I05522 9.5 3.6 4.9 .6 17.3 7.6 7.4 1.5 4 .1 38 51 6 .1 44 43 64 94 1 1 MEAN S.D. N 13.4 5.52 2 5.6 2.83 2 6.2 1.77 2 1.0 .64 2 5 .1 41 47 8 4 1 14 .00 4.2 5.7 2 . 1 .0 .0 2222222 579 APPENDIX 4 Individual Clinical Hematology Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 ---- Dose Level: 0.15 Dose Level: 0.75 ----- - Dosage Unit: mg/kg/day -- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day --- Covance 6329-223 3M T-6295.7 580 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 5.70 6.74 11.3 13.3 6.22 .735 2 12.3 1.41 2 Dose Level: 0.15 6.88 6.61 12.9 12.5 6.74 .191 2 12.7 .28 2 Dose Level: 0.75 6.38 7.02 12.2 12.8 6.70 .453 2 12.5 .42 2 Dosage Unit: mg/kg/day 34.9 41.9 61.1 62.1 19.8 19.7 38.4 4.95 2 61.6 .71 2 19.8 .07 2 Dosage Unit: mg/kg/day 40.9 40.4 59.4 61.2 18.7 18.9 40.7 .35 2 60.3 1.27 2 18.8 .14 2 Dosage Unit: mg/kg/day 39.9 44.1 62.5 62.8 19.2 18.2 42.0 2.97 2 62.7 .21 2 18.7 .71 2 32.4 31.7 32.1 .49 2 31.4 31.0 31.2 .28 2 30.7 29.0 29.8 1.20 2 577 461 519 82.0 2 391 459 425 48.1 2 335 546 440 149.2 2 .2 .3 .2 .07 2 .1 .2 .2 .07 2 .1 .4 .2 .21 2 11 20 16 6.4 2 7 13 10 4.2 2 6 28 17 15.6 2 581 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL. X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 Dosage Unit: mg/kg/day 12.5 9.1 2 . 8 .5 .1 .0 73 2 2 41 0 10.3 5.1 4.0 .9 .3 .0 50 39 8 3 0 11.4 7.1 3.4 .7 .2 .0 62 30 6 2 0 1.56 2.83 .85 .28 .14 .00 16.3 12.0 2.8 1.4 0 22222222222 Dose Level: 0 .15 Dosage Unit: mg/kg/day 7.5 .9 5.3 1 . 0 .2 .1 12 71 13 3 1 11.4 5.1 4.6 1 . 0 .6 .0 45 40 9 5 0 9.4 3.0 5.0 1 . 0 .4 .0 28 56 1 1 4 0 2.76 2.97 .49 .00 .28 .07 23.3 21.9 2.8 1.4 7 22222222222 Dose Level: 0 .75 Dosage Unit: mg/kg/day 10.8 4.5 5.0 1.1 .2 .1 41 46 10 1 1 11.1 2.6 7.5 .7 .3 .1 23 67 6 3 1 11.0 3.6 6.2 .9 .2 .1 32 56 8 2 1 .2 1 1.34 1.77 .28 .07 .00 12.7 14.8 2.8 1.4 0 22222222222 582 APPENDIX 4 Individual Clinical Hematology Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05529 I05549 a Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 -_ -- Dose Level: 0.15 -_ -_ Dose Level: 0.75 -_ -_ Dosage Unit: mg/kg/day --- Dosage Unit: mg/kg/day --- Dosage Unit: mg/kg/day --- a Plasmodium was observed. Covance 6329-223 3M T-6295.7 583 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.86 6.58 13.0 12.3 6.72 .198 2 12.6 .49 2 Dose Level: 0.15 6.86 6.71 13.4 12.8 6.78 .106 2 13.1 .42 2 Dose Level: 0.75 6.10 6.80 11.5 13.1 6.45 .495 2 12.3 1.13 2 Dosage Unit: mg/kg/day 41.6 38.6 60.6 58.7 19.0 18.7 40.1 2.12 2 59.6 1.34 2 18.8 .21 2 Dosage Unit: mg/kg/day 43.2 40.3 62.9 60.1 19.5 19.1 41.8 2.05 2 61.5 1.98 2 19.3 .28 2 Dosage Unit: mg/kg/day 39.3 42.7 64.4 62.8 18.9 19.2 41.0 2.40 2 63.6 1.13 2 19.1 .21 2 31.3 31.9 31.6 .42 2 31.0 31.7 31.4 .49 2 29.3 30.6 29.9 .92 2 666 343 504 228.4 2 421 570 496 105.4 2 476 562 519 60.8 2 .2 .3 .2 .07 2 .6 .2 .4 .28 2 .4 .2 .3 .14 2 14 20 17 4.2 2 41 13 27 19.8 2 24 14 19 7.1 2 584 ANIMAL NUMBER WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 7.6 2.4 7.0 2.8 7.3 .42 2 2.6 .28 2 Dose Level: 0.15 13.1 9.9 8.1 5.2 11.5 2.26 2 6.6 2.05 2 Dose Level: 0.75 7.2 16.0 2.5 7.5 11.6 6.22 2 5.0 3.54 2 Dosage Unit: mg/kg/day 4.0 1.0 3.4 .5 1 1 3.7 .42 2 .8 .35 2 1 00 2 Dosage Unit: mg/kg/day 4.0 .6 4.2 .3 3 1 4.1 .14 2 .4 .21 2 2 14 2 Dosage Unit: mg/kg/day 4.0 .5 6.7 1.2 2 5 5.4 1.91 2 .8 .49 2 4 21 2 .0 32 53 13 .1 41 49 7 .0 36 51 10 .07 6.4 2.8 4.2 2222 .0 62 30 .0 53 42 5 3 .0 58 36 4 .00 6.4 8.5 1.4 2222 .0 34 56 .1 47 42 7 7 .0 40 49 7 .07 9.2 9.9 .0 2222 2 2 2 .0 2 3 1 2 1.4 2 2 3 2 .7 2 1 1 1 .0 2 0 0 0 .0 2 1 1 1 .0 2 585 APPENDIX 4 Individual Clinical Hematology Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 ---- Dose Level: 0.15 Dose Level: 0.75 ----- - Dosage Unit: mg/kg/day -- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day --- Covance 6329-223 3M T-6295.7 586 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 5.55 7.08 11.1 13.5 6.32 1.082 2 12.3 1.70 2 Dose Level: 0.15 6.59 6.69 12.6 12.5 6.64 .071 2 12.6 .07 2 Dose Level: 0.75 6.49 7.07 12.2 12.7 6.78 .410 2 12.5 .35 2 Dosage Unit: mg/kg/day 33.7 44.4 60.7 62.7 20.0 19.0 39.0 7.57 2 61.7 1.41 2 19.5 .71 2 Dosage Unit: mg/kg/day 39.7 40.5 60.2 60.5 19.1 18.6 40.1 .57 2 60.3 .21 2 18.8 .35 2 Dosage Unit: mg/kg/day 39.7 41.9 61.2 59.3 18.8 17.9 40.8 1.56 2 60.2 1.34 2 18.4 .64 2 33.0 30.3 31.6 1.91 2 31.7 30.8 31.2 .64 2 30.7 30.2 30.5 .35 2 606 414 510 135.8 2 419 427 423 5.7 2 343 538 440 137.9 2 .4 .4 .4 .00 2 .5 .2 .4 .21 2 .7 .2 .4 .35 2 22 28 25 4.2 2 33 13 23 14.1 2 45 14 30 21.9 2 587 ANIMAL NUMBER WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 9.6 8.0 8.8 1.13 2 7.1 3.7 5.4 2.40 2 Dose Level: 0.15 6.2 9.4 1.1 4.7 7.8 2.26 2 2.9 2.55 2 Dose Level: 0.75 10.8 7.6 5.0 3.7 9.2 2.26 2 4.4 .92 2 Dosage Unit: mg/kg/day 2.1 3.5 .4 .6 0 1 2.8 .99 2 .5 .14 2 0 07 2 Dosage Unit: mg/kg/day 4.3 .5 3.4 .6 2 6 3.8 .64 2 .6 .07 2 4 28 2 Dosage Unit: mg/kg/day 4.7 1.0 3.5 .3 1 1 4.1 .85 2 .6 .49 2 1 00 2 .0 73 2 2 .0 46 44 .0 60 33 .00 19.1 15.6 222 .0 18 69 .1 50 37 .0 .07 2 34 22.6 2 53 22.6 2 .1 46 43 .0 49 46 .0 .07 2 48 2.1 2 44 2.1 2 4 8 6 2.8 2 8 7 8 .7 2 9 4 6 3.5 2 0 2 1 1.4 2 4 6 5 1.4 2 0 1 0 .7 2 0 1 0 .7 2 1 1 1 .0 2 1 0 0 .7 2 588 APPENDIX 4 Individual Clinical Hematology Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 ---- Dose Level: 0.15 Dose Level: 0.75 ----- - Dosage Unit: mg/kg/day -- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day --- Covance 6329-223 3M T-6295.7 589 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.78 6.67 12.9 12.4 6.72 .078 2 12.6 .35 2 Dose Level: 0.15 6.89 6.71 13.6 12.8 6.80 .127 2 13.2 .57 2 Dose Level: 0.75 6.08 6.36 11.5 12.1 6.22 .198 2 11.8 .42 2 Dosage Unit: mg/kg/day 40.6 39.8 59.8 59.7 19.0 18.6 40.2 .57 2 59.8 .07 2 18.8 .28 2 Dosage Unit: mg/kg/day 43.2 40.6 62.6 60.5 19.8 19.1 41.9 1.84 2 61.5 1.48 2 19.4 .49 2 Dosage Unit: mg/kg/day 37.8 38.3 62.1 60.2 18.9 19.0 38.1 .35 2 61.1 1.34 2 19.0 .07 2 31.8 31.2 31.5 .42 2 31.6 31.5 31.5 .07 2 30.5 31.5 31.0 .71 2 692 396 544 209.3 2 434 548 491 80.6 2 542 603 572 43.1 2 .5 .1 .3 .28 2 .2 .1 .2 .07 2 .8 .3 .6 .35 2 34 7 20 19.1 2 14 7 10 4.9 2 49 19 34 21.2 2 590 ANIMAL NUMBER WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 I05526 9.5 4.3 4.5 7.8 4.0 3.0 .6 .7 1 .0 45 47 1 .0 52 38 71 91 0 0 MEAN S.D. N 8.6 1.20 2 4.2 .21 2 3.8 1.06 2 .6 .07 2 1 .0 48 42 8 1 0 00 .00 4.9 6.4 1.4 .0 .0 2222222 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 I05523 13.7 9.6 3.0 11.8 6.7 4.4 .9 .6 2 .0 70 2 2 1 .0 57 37 71 51 0 0 MEAN S.D. N 12.8 1.34 2 8.2 2.05 2 3.7 .99 2 .8 .21 2 2 .0 64 30 6 1 0 07 .00 9.2 10.6 1.4 .0 .0 2222222 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 I05522 6.3 2.2 3.1 11.6 5.8 4.7 .8 .9 2 .1 36 49 1 2 1 .0 50 40 8 31 10 MEAN S.D. N 9.0 3.75 2 4.0 2.55 2 3.9 1.13 2 .8 .07 2 2 .0 43 44 1 0 2 0 07 .07 9.9 6.4 2 . 8 1.4 .7 2222222 591 APPENDIX 4 Individual Clinical Hematology Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 ---- Dose Level: 0.15 Dose Level: 0.75 ----- - Dosage Unit: mg/kg/day -- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day --- Covance 6329-223 3M T-6295.7 592 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC X103/mcL Dose Level: 0 6.04 6.61 6.32 .403 2 11.9 12.8 12.3 .64 2 Dose Level: 0.15 6.81 6.71 12.5 12.5 6.76 .071 2 12.5 .00 2 Dose Level: 0.75 6.20 6.81 11.6 12.2 6.50 .431 2 11.9 .42 2 Dosage Unit: mg/kg/day 36.9 39.9 61.1 60.4 19.7 19.4 38.4 2.12 2 60.8 .49 2 19.6 .21 2 Dosage Unit: mg/kg/day 39.6 40.7 58.2 60.7 18.3 18.6 40.1 .78 2 59.4 1.77 2 18.4 .21 2 Dosage Unit: mg/kg/day 37.9 41.0 61.2 60.3 18.8 17.9 39.5 2.19 2 60.8 .64 2 18.4 .64 2 32.2 32.1 32.1 .07 2 31.5 30.6 31.0 .64 2 30.7 29.7 30.2 .71 2 645 447 546 140.0 2 399 546 472 103.9 2 314 534 424 155.6 2 .1 .3 .2 .14 2 .4 .3 .4 .07 2 .1 .5 .3 .28 2 6 20 13 9.9 2 27 20 24 4.9 2 6 34 20 19.8 2 593 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SEG LYMPH MONO EOSIN BASO N-SEG% X103/mcL X103/mcL. X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 Dosage Unit: mg/kg/day 14.9 10.0 3.2 1.4 .2 .0 67 2 2 10 1 0 8.7 4.4 3.3 .6 .3 .0 51 38 7 3 0 11.8 7.2 3.2 1 . 0 .2 .0 59 30 8 2 0 4.38 3.96 .07 .57 .07 .00 11.3 11.3 2.1 1.4 0 22222222222 Dose Level: 0.15 Dosage Unit: mg/kg/day 7.4 2.0 4.5 .7 .2 .0 27 61 10 30 11.4 6.5 3.9 .4 .6 .0 57 34 4 5 0 9.4 4.2 4.2 .6 .4 .0 42 48 7 4 0 2.83 3.18 .42 .21 .28 .00 21.2 19.1 4.2 1.4 0 22222222222 Dose Level: 0.75 Dosage Unit: mg/kg/day 7.8 10.0 2.3 3.1 5.0 6.1 .5 .1 .6 .2 .0 29 63 .0 31 61 71 62 0 0 8.9 2.7 5.6 .6 .2 .0 30 62 6 2 0 1.56 .57 .78 .07 .07 .00 1.4 1.4 .7 .7 0 22222222222 594 APPENDIX 4 Individual Clinical Hematology Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 ---- Dose Level: 0.15 Dose Level: 0.75 ----- - Dosage Unit: mg/kg/day -- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day --- Covance 6329-223 3M T-6295.7 595 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL 0Dose Level: 6.50 6.56 12.5 12.4 6.53 .0422 12.4 .207 Dose Level: 0.15 6.92 6.52 1132..65 6.72 .2823 13.0 .264 Dose Level: 6.09 6.37 6.23 .1928 0.75 12.0 12.3 12..2221 Dosage Unit: mg/kg/day 39.5 39.4 60.8 60.1 19.3 19.0 39.5 .207 60.5 .249 19..2221 Dosage Unit: mg/kg/day 43.3 39.1 62.7 60.0 19.6 19.2 41.2 2.927 61.3 1.921 19.4 .228 Dosage Unit: mg/kg/day 39.1 38.7 64.2 60.8 19.7 19.3 38.9 .228 62.5 2.420 19.5 .228 31.7 31.6 31.6 .207 31.3 32.1 31.7 .257 30.6 31.8 31.2 .285 641 387 514 1792.6 399 496 446828.6 520 495 508 172.7 ..20 .1 .214 ..20 .1 .214 1..05 .8 1.026 Covance 6329-223 3M T-6295.7 RETIC3 X103/mcL 130 6 29.2 140 7 29.9 910 46 642.3 596 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SE3G LYMPH MONO EOSIN 3 BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0Dose Level: Dosage Unit: mg/kg/day 10.7 10.9 5.9 7.3 42..81 ..68 ..01 ..10 55 67 38 25 6 7 10 10 10.8 6.6 3.4 .7 .0 .0 61 32 600 .214 .299 .292 .214 .207 207 28.5 29.2 2.7 2 7 2 7 Dose Level: 0.15 Dosage Unit: mg/kg/day 1131..28 69..86 3.0 4.0 1.1 .4 ..20 ..00 69 60 21 36 8 4 10 00 12.5 1.824 8.2 1.928 3.5 .271 .8 .249 .1 .214 .2000 64 26.4 21820.6 226.8 0 27 0 2 0 Dose Level: 0.75 Dosage Unit: mg/kg/day .8 09.4 4.5 3.7 .3 . 115.0 8.3 4.8 1.4 .4 . 48 40 55 32 9 9 3 3 10 12.2 3.926 6.4 2.629 4.2 .278 1.1 .242 .4 .207 .0 207 52 42.9 36 25.7 29 .0 3 2 0 0 27 597 APPENDIX 4 Individual Clinical Hematology Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 --- Dose Level: 0 --- Dose Level: 0 --- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 598 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL 0Dose Level: 5.96 6.60 11.9 13.0 6.28 .4523 12.4 .278 Dose Level: 0.15 6.69 6.85 6.77 .1123 12.5 12.7 12.6 .214 Dose Level: 6.56 6.52 6.54 .0228 0.75 1122..21 12.2 .207 Dosage Unit: mg/kg/day 36.1 40.2 60.5 61.0 19.9 19.7 38.1 2.920 60.8 .235 19.8 .214 Dosage Unit: mg/kg/day 39.8 41.7 59.5 60.8 18.7 18.6 40.8 1.324 60.2 .292 18.6 .207 Dosage Unit: mg/kg/day 39.7 40.5 60.5 62.1 18.7 18.5 40.1 .257 61.3 1.123 18.6 .214 32.9 32.3 32.6 .242 31.4 30.5 31.0 .264 30.9 29.8 30.4 .278 635 433 534 1422.8 408 504 456 672.9 320 577 448 1812.7 ..21 .2 .207 ..21 .2 .207 ..21 .2 .207 Covance 6329-223 3M T-6295.7 RETIC3 X103/mcL 6 13 10 42.9 13 7 10 42.2 7 13 10 42.2 599 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SE3G LYMPH MONO EOSIN 3 BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0Dose Level: Dosage Unit: mg/kg/day 8.5 6.4 42..62 3.1 2.5 1..28 ..13 ..00 50 41 36 38 10 19 42 00 7.4 3.4 2.8 1.0 1.428 1.123 .242 .228 .2 .214 ..0020 46 26.4 37 21.4 14 26.4 3 21.4 0 2 0 Dose Level: 0.15 Dosage Unit: mg/kg/day 8.5 7.7 2.5 3.5 4.4 3.0 1..26 .3 .5 ..01 30 45 52 39 148 3 7 10 8.1 .257 3.0 .271 3.7 .299 .9 .242 .4 .214 .0 .207 31820.6 46 29.2 11 42.2 225.8 0 27 Dose Level: 0.75 Dosage Unit: mg/kg/day 11.4 5.1 5.1 1.1 10.3 4.3 5.4 .5 ..02 ..00 44 42 45 52 10 5 20 00 10.8 .278 4.7 .257 5..2221 .8 .242 .1 .214 ..0020 43 21.4 48 42.9 8 32.5 1 21.4 0 2 0 600 APPENDIX 4 Individual Clinical Hematology Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 --- Dose Level: 0 --- Dose Level: 0 --- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 601 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL 0Dose Level: 6.82 6.44 13.3 12.5 6.63 .2629 12.9 .257 Dose Level: 0.15 7.19 7.12 14.1 13.8 7.16 .0429 14..2021 Dose Level: 0.75 56..6983 6.30 .5320 11.9 13.2 12.6 .292 Dosage Unit: mg/kg/day 41.2 39.3 60.4 61.0 19.4 19.4 40.2 1.324 60.7 .242 19..0420 Dosage Unit: mg/kg/day 46.3 44.9 64.3 63.0 19.6 19.4 45.6 .299 63.7 .292 19.5 .214 Dosage Unit: mg/kg/day 38.7 42.5 65.3 63.7 20.1 19.8 40.6 2.629 64.5 1.123 19..2921 32.2 31.8 32.0 .228 30.5 30.8 30..2621 30.9 31.1 31.0 .214 584 337 460 1742.7 415 566 490 1062.8 445 576 510 922.6 ..24 .3 .214 ..15 .3 .228 1..04 .7 .299 Covance 6329-223 3M T-6295.7 RETIC3 X103/mcL 27 13 20 29.9 36 7 22 202.5 830 42 582.7 602 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SE3G LYMPH MONO EOSIN 3 BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% 0Dose Level: Dosage Unit: mg/kg/day 1112..20 5.4 7.5 4.9 3.8 ..67 ..11 ..01 48 62 44 32 6 5 11 10 11.6 .257 6.4 1.428 4.4 .278 .6 .207 ..0120 .0 .207 55 29.9 38 28.5 6 2.7 21.0 0 27 Dose Level: 0.15 Dosage Unit: mg/kg/day 10.7 12.5 4.1 5.7 56..26 .8 .5 ..22 ..00 38 45 52 49 7 4 21 00 11.6 1.227 4.9 1.123 5.9 .242 ..6221 ..2020 ..0020 42 42.9 5022.1 226.1 2 2.7 0 20 Dose Level: 0.75 Dosage Unit: mg/kg/day 2112..20 7.5 13.1 36..05 1..67 .2 .5 ..11 63 62 29 28 6 7 1 3 10 16.6 6.521 10.3 3.926 4.8 1.727 1.2 .264 ..2421 ..0120 62 2.7 28 2.7 6 2.7 2 21.4 0 2 603 APPENDIX 4 Individual Clinical Hematology Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 --- Dose Level: 0 --- Dose Level: 0 --- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 604 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL 0Dose Level: 56..8683 11.3 13.5 6.26 .8824 12.4 1.526 Dose Level: 0.15 6.61 6.70 6.66 .0624 12.7 12.7 12..0720 Dose Level: 0.75 6.62 7.51 12.7 13.5 7.06 .6229 13.1 .257 Dosage Unit: mg/kg/day 34.8 42.2 61.8 61.3 20.1 19.6 38.5 5.223 61.6 .235 19.8 .235 Dosage Unit: mg/kg/day 40.2 41.4 60.9 61.9 19.3 19.0 40.8 .285 61.4 .271 19..2221 Dosage Unit: mg/kg/day 40.7 45.2 61.4 60.1 19.1 18.0 42.9 3.128 60.8 .292 18.5 .278 32.6 31.9 32.2 .249 31.7 30.6 31.2 .278 31.2 29.9 30.6 .292 580 407 494 1222.3 441 461 451 142.1 293 598 446 2152.7 .6 .4 .5 .214 ..24 .3 .214 .0 .3 ..2221 Covance 6329-223 3M T-6295.7 RETIC3 X103/mcL 34 28 31 42.2 26 13 20 29.2 0 23 12 162.3 605 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SE3G LYMPH MONO EOSIN 3 BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level: 8.2 9.3 8.8 .278 0 4.5 4.3 4.4 .214 Dose Level: 0.15 11.1 8.7 25..60 9.9 1.720 3.8 1.720 Dose Level: 0.75 191..29 10.6 .292 3.5 2.5 3.0 .271 Dosage Unit: mg/kg/day 2.9 3.8 ..68 .2 .4 3.4 .7 .3 .264 .214 .214 Dosage Unit: mg/kg/day 4.7 4.6 1..08 ..84 4.6 .9 .6 .207 .214 .228 Dosage Unit: mg/kg/day 5.1 1.0 7.3 .9 .2 .4 6.2 1.0 1.526 .207 .3 .214 ..00 55 46 36 41 78 2 4 ..0020 50 26.4 38 32.5 8 2.7 3 21.4 ..00 45 29 43 52 9 9 3 9 ..0020 31721.3 48 26.4 29 .0 6 42.2 ..21 3262 51 65 108 2 4 .2 29 58 9 3 .207 29.9 29.9 21.4 21.4 00 0 20 00 0 20 21 2 2 606 APPENDIX 4 Individual Clinical Hematology Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 --- Dose Level: 0 --- Dose Level: 0 --- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 607 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL 0Dose Level: 6.54 6.59 1122..66 6.56 .0325 12..6020 Dose Level: 0.15 6.80 7.00 13.5 13.8 6.90 .1421 13..2621 Dose Level: 0.75 6.42 6.42 6..040220 12.7 12.5 12.6 .214 Dosage Unit: mg/kg/day 39.9 41.4 61.0 62.8 19.2 19.1 40.7 1.026 61.9 1.227 19.2 .207 Dosage Unit: mg/kg/day 43.6 44.2 64.1 63.1 19.8 19.8 43.9 .242 63.6 .271 19..0820 Dosage Unit: mg/kg/day 43.5 41.3 42.4 1.526 67.6 64.3 66.0 2.323 19.7 19.5 19.6 .214 31.5 30.5 31.0 .271 30.9 31.3 31.1 .228 29.2 30.3 29.8 .278 503 366 434 962.9 377 369 373 25.7 478 562 520 592.4 .7 .3 .5 .228 .7 .7 ..0720 .9 .3 .6 .242 Covance 6329-223 3M T-6295.7 RETIC3 X103/mc 4206 33 182.4 48 49 48 2.7 58 19 38 272.6 608 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SE3G LYMPH MONO EOSIN 3 BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 7.1 2.0 9.6 4.2 8.4 1.77 2 3.1 1.56 2 Dose Level: 0.15 8.1 13.7 3.8 6.2 10.9 3.96 2 5.0 1.70 2 Dose Level: 0.75 15.7 16.2 10.9 8.8 16.0 .35 2 9.8 1.48 2 Dosage Unit: mg/kg/day 4.3 .5 4.1 1.1 .1 .1 4.2 .8 .1 .14 .42 .00 222 Dosage Unit: mg/kg/day 3.2 .9 .2 6 . 2 .7 .5 4.7 2.12 2 .8 .4 .14 . 2 1 22 Dosage Unit: mg/kg/day 3.4 1.2 5.4 1.3 .1 .4 4.4 1.41 2 1.2 .07 2 .2 .21 2 .3 28 60 7 1 4 .0 44 43 1 1 1 1 .2 36 52 .21 11.3 12.0 222 9 2.8 2 1 0 2 2 2.1 2 .1 47 39 1 1 2 1 .1 45 45 5 3 1 .1 46 42 8 2 1 .00 1.4 4.2 4.2 7 .0 222222 .1 70 2 2 .3 54 33 71 82 1 2 .2 62 28 8 2 2 .14 1 1 . 3 7.8 .7 7 .7 222222 609 APPENDIX 4 Individual Clinical Hematology Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 --- Dose Level: 0 --- Dose Level: 0 --- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 610 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N APPENDIX 4 Individual Clinical Hematology Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC X106/mcL HGB G/DL HCT MCV FL MCH PG MCHC PLT RETIC X103/mcL Covance 6329-223 3M T-6295.7 RETIC3 X103/mc Dose Level: 0 5.52 6.51 11.1 12.6 6.02 .700 2 11.8 1.06 2 Dose Level: 0.15 6.60 6.33 12.6 12.0 6.46 .191 2 12.3 .42 2 Dose Level: 0.75 6.62 6.81 12.5 12.3 6.72 .134 2 12.4 .14 2 Dosage Unit: mg/kg/day 34.6 40.5 62.6 62.3 20.1 19.4 37.5 4.17 2 62.5 .21 2 19.8 .49 2 Dosage Unit: mg/kg/day 41.2 39.3 62.4 62.1 19.1 18.9 40.2 1.34 2 62.2 .21 2 19.0 .14 2 Dosage Unit: mg/kg/day 41.0 40.6 61.9 59.7 18.9 18.1 40.8 .28 2 60.8 1.56 2 18.5 .57 2 32.1 31.1 31.6 .71 2 30.7 30.5 30.6 .14 2 30.5 30.3 30.4 .14 2 533 483 508 35.4 2 405 408 406 2.1 2 293 500 396 146.4 2 .6 .3 .4 .21 2 .3 .6 .4 .21 2 .2 .4 .3 .14 2 33 20 26 9.2 2 20 38 29 12.7 2 13 27 20 9.9 2 611 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N WBC X103/mcL APPENDIX 4 Individual Clinical Hematology Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS N-SE3G LYMPH MONO EOSIN 3 BASO N-SEG% X103/mcL X103/mcL X103/mcL X103/mcL X103/mcL LYMPH% MONO% EOSIN% Covance 6329-223 3M T-6295.7 BASO% Dose Level: 0 6.9 15.6 3.5 10.5 11.2 6.15 2 7.0 4.95 2 Dose Level: 0.15 13.8 9.2 7.1 3.8 11.5 3.25 2 5.4 2.33 2 Dose Level: 0.75 9.8 11.0 3.2 3.0 10.4 .85 2 3.1 .14 2 Dosage Unit: mg/kg/day 2.5 .7 3.2 1.3 .2 .4 2.8 .49 2 1.0 .42 2 .3 .14 2 Dosage Unit: mg/kg/day 5.1 3.4 1.0 1.1 .4 .7 4.2 1.20 2 1.0 .07 2 .6 .21 2 Dosage Unit: mg/kg/day 5.7 .5 .1 7.0 .5 .3 6.4 .5 .2 .92 .00 .14 222 .1 .2 .2 .07 2 .2 .2 .2 .00 2 .2 .1 .2 .07 2 50 67 58 12.0 2 51 41 46 7.1 2 33 28 30 3.5 2 36 20 28 11.3 2 37 37 37 .0 2 58 64 61 4.2 2 10 9 10 .7 2 8 12 10 2.8 2 5 5 5 .0 2 2 3 2 .7 2 3 7 5 2.8 2 1 2 2 .7 2 1 1 1 0 2 2 2 2 0 2 2 1 2 7 2 612 APPENDIX 4 Individual Clinical Hematology Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER ANISO POLY POIK HYPO TOXNEUT Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 --- Dose Level: 0 --- Dose Level: 0 --- Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 613 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0 62 2 2 76 2 1 74 27 69 17 75 19 99 17 76 12.5 6 20 3. 8 6 Dose Level : 0 .03 76 17 69 17 58 29 75 16 70 8.3 4 20 6 .2 4 Dose Level : 0 .15 59 2 0 138 16 95 2 2 76 2 0 69 25 58 24 82 30.4 6 21 3. 3 6 Dosage Unit: mg/kg/day 1 . 0 8.7 4.6 1.3 9.2 4.7 1 . 2 9.3 5.0 1 . 1 8.7 4.9 1 . 1 9.4 5.2 1 . 2 8 . 8 4.9 1.2 .10 6 9.0 .32 6 4.9 .21 6 Dosage Unit: mg/kg/day 1.2 1.0 1.1 1.4 9.7 9.5 8.8 10.2 5.5 4.6 5.0 5.6 1.2 .17 4 9.6 .58 4 5.2 .46 4 Dosage Unit: mg/kg/day 1.2 .9 1.5 1.1 1.4 1.3 9.3 8.8 10.1 9.3 9.6 9.7 5.2 4.4 5.3 5.2 5.2 5.2 1.2 .22 6 9.5 .44 6 5.1 .34 6 4.1 4.5 4.3 3.8 4.2 3.9 4.1 .26 6 4.2 4.9 3.8 4.6 4.4 .48 4 4.1 4.4 4.8 4.1 4.4 4.5 4.4 .26 6 1.3 1.0 .3 .7 .3 .2 .6 .45 6 .5 .2 .6 .3 .4 .18 4 1.3 .3 .5 .3 .7 .7 .6 .37 6 5 11 10 9 9 9 9 2 .0 6 88 137 174 111 150 170 138 33. 7 6 71 92 58 78 63 58 70 13 6 9 8 11 8 9 1 .4 4 138 111 98 93 110 2 0 .1 4 41 48 113 41 61 35 4 14 10 9 8 10 8 10 2 .2 6 186 157 124 124 141 175 151 26. 1 6 48 59 55 53 62 57 56 4 6 614 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0.75 67 102 71 58 75 64 18 22 22 21 22 18 73 15.4 6 20 2 .0 6 Dosage Unit: mg/kg/day 1.3 9.6 5.1 1.4 9.9 5.0 1.4 9.5 5.3 1 . 1 8 . 8 4.7 1.3 9.2 5.3 1.3 9.5 5.5 1.3 .11 6 9.4 .38 6 5.2 .28 6 4.5 4.9 4.2 4.1 3.9 4.0 4.3 .37 6 .4 .4 .8 1.0 .3 .3 .5 .29 6 10 7 10 8 10 9 9 1.3 6 129 121 117 115 188 159 138 29.3 6 68 58 62 55 77 83 67 11.0 6 615 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 58 24 84 51 58 33 36 26 58 31 43 29 56 16. 5 6 32 9. 7 6 Dose Level: 0.03 53 27 38 43 43 48 43 26 44 6.3 4 36 1 1 .2 4 Dose Level: 0.15 66 99 39 29 54 34 99 78 84 118 93 56 72 23.5 6 69 35. 7 6 Dosage Unit: mg/kg/day 546 628 514 866 1156 556 152 125 117 88 211 113 8 9 9 4 7 6 711 252.6 6 134 42.8 6 7 1.9 6 Dosage Unit: mg/kg/day 642 787 1002 369 155 125 182 103 4 4 2 3 700 265. 6 4 141 34.5 4 3 1 .0 4 Dosage Unit: mg/kg/day 720 814 579 716 1165 624 194 130 124 82 154 278 12 4 2 16 10 5 770 2 1 0 .3 6 160 68.4 6 8 5. 4 6 1086 1908 783 660 1671 692 1133 535.3 6 1955 348 848 595 936 709. 0 4 670 1109 1047 1549 820 1329 1087 322. 3 6 451 508 448 336 250 376 395 93.4 6 413 715 435 340 476 164. 6 4 367 450 326 471 469 236 386 94. 5 6 12 226 12 17 25 37 55 84.4 6 19 43 60 17 35 2 0 .6 4 133 15 33 29 56 39 51 42. 4 6 284 325 249 220 168 235 247 54 6 243 441 326 196 302 107. 4 4 190 301 218 291 296 156 242 62. 4 6 616 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level: 0.75 54 49 54 94 80 181 71 32 69 48 80 78 68 1 1 .7 6 80 54. 2 6 Dosage Unit: mg/kg/day 1443 447 585 927 646 992 167 138 156 199 105 259 6 9 6 6 5 5 840 360.9 6 171 53.3 6 6 1.5 6 1602 575 1265 540 907 1676 1094 497.4 6 653 515 704 543 396 362 529 135.6 6 52 19 39 99 15 21 41 31.8 6 359 326 435 325 274 224 324 72.2 6 617 Appendix 4 Individual Clinical Chemistry Data Males Day -27 26-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 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level : 0 10.2 10.3 11.1 10.5 11.8 10.7 6.5 5.8 6.6 6.1 7.5 5.0 10.8 .60 6 6.2 .84 6 Dose Level : 0 .03 12.2 11.3 11.1 12.0 6.5 6.9 7.1 6.1 11.6 .53 4 6.6 .44 4 Dose Level : 0 .15 11.9 10.7 12.2 11.2 11.9 10.9 5.9 7.5 6.9 6.6 8.8 6.7 11.5 .62 6 7.1 .99 6 Dosage Unit: mg/kg/day 154 4.9 106 154 4.8 106 161 5.9 113 158 5.7 1 1 1 166 6 . 1 1 1 1 160 4.9 109 159 4.6 6 5.4 .58 6 109 2 6 Dosage Unit: mg/kg/day 171 6 . 2 114 159 5.8 1 1 0 159 5.5 109 167 6 . 1 1 1 2 164 6.0 4 5.9 .32 4 111 2 4 Dosage Unit: mg/kg/day 161 5.8 1 1 2 156 5.8 1 1 1 169 7.2 113 164 6 . 1 116 168 7.0 1 1 0 158 6.3 108 163 5.3 6 6.4 .60 6 112 2 6 Covance 6329-223 3M T-6295.7 618 Appendix 4 Individual Clinical Chemistry Data Males Day -27 26-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: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 11.8 11.3 10.9 10.5 11.8 11.7 8.0 6.0 5.9 6.1 7.0 8.3 11.3 .54 6 6.9 1.06 6 Dosage Unit: mg/kg/day 165 6 . 1 1 1 2 157 6.5 108 158 5.5 104 156 4.8 106 162 5.8 109 168 6.3 1 1 0 161 4.8 6 5.8 .62 6 108 2 6 Covance 6329-223 3M T-6295.7 619 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0 54 23 108 23 70 23 51 19 82 2 2 92 2 1 76 22.2 6 22 1 .6 6 Dose Level : 0 .03 71 2 1 66 23 89 2 2 67 24 73 10.7 4 22 1 .3 4 Dose Level : 0 .15 86 20 87 2 1 82 29 72 2 0 55 2 1 74 27 76 12.0 6 23 3. 9 6 Dosage Unit: mg/kg/day 1 . 2 9.4 1.3 9.9 1.3 8.6 1.3 9.9 1.2 1.1 10.8 9.0 5.1 5.5 4.6 4.6 4.7 4.9 1.2 .08 6 9.6 .78 6 4.9 .35 6 Dosage Unit: mg/kg/day 1.3 1.2 1.2 1.1 10.0 9.2 8.9 9.0 4.9 4.5 4.6 4.8 1.2 .08 4 9.3 .50 4 4.7 .18 4 Dosage Unit: mg/kg/day 1 . 2 10.7 1 . 1 9.8 1.3 9.2 1 . 1 9.1 1 . 0 9.1 1 . 1 9.8 5.5 5.2 3.9 4.7 4.4 4.6 1.1 .10 6 9.6 .62 6 4.7 .57 6 4.3 4.4 4.0 5.3 6.1 4.1 4.7 .83 6 5.1 4.7 4.3 4.2 4.6 .41 4 5.2 4.6 5.3 4.4 4.7 5.2 4.9 .38 6 1.2 .3 .5 .5 .4 .3 .5 .34 6 .5 .7 .3 .6 .5 .17 4 .8 .3 .6 .9 .5 .6 .6 .21 6 7 10 7 4 7 7 7 1 .9 6 93 168 137 203 133 159 149 37. 2 6 56 91 54 131 56 48 73 32 6 5 6 9 6 6 1 .7 4 120 133 146 120 130 1 2 .4 4 68 69 55 56 62 7 4 7 7 7 37 11 6 12 1 2 .1 6 162 142 141 156 122 140 144 14. 0 6 50 42 66 74 63 53 58 11 6 620 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level: 0.75 106 27 71 2 1 88 17 74 26 71 25 60 26 78 16.3 6 24 3. 9 6 Dosage Unit: mg/kg/day 1.3 1.4 1.2 1.1 1.3 .9 9.4 10.1 10.5 8.6 8.8 8.8 4.9 5.5 4.6 4.4 4.6 4.5 1.2 .18 6 9.4 .78 6 4.8 .40 6 4.5 4.6 5.9 4.2 4.2 4.3 4.6 .65 6 .4 .4 .3 .4 .5 1.3 .6 .37 6 11 8 9 8 9 7 9 1.4 6 163 149 137 164 152 158 154 10.1 6 69 65 53 37 86 56 61 16.6 6 621 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 1MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 66 202 65 2 1 1 75 215 61 48 61 82 55 83 64 6.7 6 140 76. 9 6 Dose Level: 0 .03 68 89 54 146 44 80 50 98 54 10.2 4 103 29. 4 4 Dose Level: 0 .15 77 76 68 135 39 65 140 160 74 143 48 78 74 35.5 6 110 41. 0 6 Dosage Unit: mg/kg/day 195 101 274 121 217 98 550 163 256 204 254 50 3 5 7 5 3 3 291 130.1 6 123 54.0 6 4 1 .6 6 Dosage Unit: mg/kg/day 200 184 210 211 166 72 62 75 2 3 3 4 201 12.5 4 94 48.5 4 3 8 4 Dosage Unit: mg/kg/day 2 0 1 127 454 120 1 2 2 64 198 41 334 80 232 91 2 4 2 8 6 3 257 118.5 6 87 32.9 6 4 2 .4 6 484 1588 792 872 896 1242 979 384 .3 6 706 395 477 356 484 156 .7 4 1192 1003 362 663 1073 769 844 306 .4 6 425 281 360 314 595 272 374 1 2 1 .9 6 219 293 433 566 378 153 .7 4 366 411 269 484 352 617 416 1 2 1 .0 6 27 39 46 12 27 19 28 1 2 .5 6 265 135 211 184 342 185 220 73 6 25 12 17 48 26 15. 9 4 152 189 286 322 237 79 4 35 46 44 25 0 62 35 2 1 .2 6 177 230 179 272 210 393 244 81 6 622 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level: 0.75 1 0 1 216 63 88 68 148 57 126 74 99 67 63 72 15..4 6 123 54. 2 6 Dosage Unit: mg/kg/day 301 121 329 64 575 63 182 52 204 79 269 70 5 3 7 4 3 1 310 141.4 6 75 24.3 6 4 2.0 6 3858 902 2229 417 1377 964 1624 1251. 5 6 411 545 336 380 294 337 384 88.6 6 25 0 15 39 31 4 19 15.4 6 269 343 205 223 196 246 247 54.1 6 623 Appendix 4 Individual Clinical Chemistry Data Females Day -27 26-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 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level : 0 10.9 13.0 10.4 12.4 11.5 10.3 5.8 6.5 5.6 7.1 6.8 5.7 11.4 1.10 6 6.2 .63 6 Dose Level : 0 .03 10.9 11.7 10.3 10.8 4.4 3.8 4.4 6.1 10.9 .58 4 4.7 .99 4 Dose Level : 0 .15 11.5 11.5 10.5 10.3 10.6 11.6 6.2 5.6 6.1 4.9 5.3 7.1 11.0 .59 6 5.9 .78 6 Dosage Unit: mg/kg/day 155 5.6 106 173 8 . 0 119 159 5.4 1 1 0 166 6.4 116 167 6 . 0 118 156 5.7 1 1 2 163 7.1 6 6.2 .96 6 114 5 6 Dosage Unit: mg/kg/day 165 5.2 113 164 6.5 117 158 5.4 1 1 2 165 6.5 119 163 3.4 4 5.9 .70 4 115 3 4 Dosage Unit: mg/kg/day 167 6.4 113 164 6.3 116 164 6.3 118 156 5.3 1 1 1 152 5.5 1 1 2 166 7.0 118 162 6.1 6 6.1 .63 6 115 3 6 Covance 6329-223 3M T-6295.7 624 Appendix 4 Individual Clinical Chemistry Data Females Day -27 26-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: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 10.9 11.6 12.1 10.7 11.7 10.7 5.1 5.7 5.7 6.1 4.7 5.6 11.3 .59 6 5.5 .50 6 Dosage Unit: mg/kg/day 163 5.1 114 164 6.3 1 1 2 168 6 . 0 115 159 6 . 8 116 167 7.1 115 155 5.3 113 163 4.9 6 6.1 .80 6 114 1 6 Covance 6329-223 3M T-6295.7 625 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0 54 2 0 68 19 57 26 62 19 54 19 65 16 60 5.9 6 20 3. 3 6 Dose Level : 0 .03 65 2 2 72 14 58 2 1 53 16 62 8.3 4 18 3. 9 4 Dose Level : 0 .15 52 17 62 17 71 19 68 18 68 26 47 28 61 9.8 6 21 4. 9 6 Dosage Unit: mg/kg/day 1 . 1 9.2 4.8 1 . 2 9.9 4.8 1 . 1 8.5 4.5 1 . 0 8.7 4.8 .9 8.4 4.6 1 . 2 8 . 8 4.8 1.1 .12 6 8.9 .56 6 4.7 .13 6 Dosage Unit: mg/kg/day 1.4 10.0 1 . 1 9.9 1 . 0 7.8 1.3 9.5 5.7 4.8 4.7 4.9 1.2 .18 4 9.3 1.02 4 5.0 .46 4 Dosage Unit: mg/kg/day 1 . 1 9.0 5.0 .8 9.0 4.7 1.4 9.7 4.9 1 . 1 9.3 5.2 1.4 8 . 8 4.5 1 . 1 9.4 4.7 1.2 .23 6 9.2 .33 6 4.8 .25 6 4.4 5.1 4.0 3.9 3.8 4.0 4.2 .49 6 4.3 5.1 3.1 4.6 4.3 .85 4 4.0 4.3 4.8 4.1 4.3 4.7 4.4 .32 6 1.4 1.1 .4 .9 .4 .4 .8 .43 6 .6 .2 .4 .4 .4 .16 4 1.0 .3 .4 .3 .6 .7 .6 .27 6 8 11 9 7 10 8 9 1 .5 6 118 171 161 117 134 139 140 2 2 .1 6 9 7 8 6 8 1 .3 4 148 132 108 83 118 28. 4 4 7 176 7 159 8 135 8 116 7 134 9 155 8 8 6 146 2 1 .5 6 70 85 45 90 48 74 69 18 6 51 45 50 41 47 4 4 50 54 61 65 59 56 58 5 6 626 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level: 0.75 58 2 0 75 24 66 19 54 2 1 64 23 71 18 65 7.8 6 21 2.3 6 Dosage Unit: mg/kg/day 1.4 9.1 4.9 1.4 9.4 5.0 1.3 9.9 5.4 1 . 1 9.3 4.5 1 . 2 8 . 8 5.1 1.3 9.4 5.5 1.3 .12 6 9.3 .37 6 5.1 .36 6 4.2 4.4 4.5 4.8 3.7 3.9 4.2 .40 6 .5 .3 .4 .7 .2 .4 .4 .17 6 8 1 1 2 109 6 109 72 6 127 68 5 130 62 8 156 108 9 143 128 7 130 1.5 18. 0 66 91 27 6 627 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 37 30 53 59 46 28 26 23 35 27 71 69 45 15.9 6 39 19. 5 6 Dose Level: 0.03 30 23 38 53 35 36 45 46 37 6.3 4 40 13. 0 4 Dose Level:: 0.15 55 58 25 2 0 46 38 35 45 54 91 70 45 48 15.9 6 50 23. 8 6 Dosage Unit: mg/kg/day 776 605 690 876 1552 830 159 130 112 77 203 126 4 7 11 5 9 7 888 339.5 6 134 42.9 6 7 2 .6 6 Dosage Unit: mg/kg/day 855 999 1284 365 144 104 153 77 2 4 2 5 876 384.3 4 120 35.4 4 3 1 .5 4 Dosage Unit: mg/kg/day 721 1042 733 878 1359 643 154 127 117 73 103 239 10 1 3 6 6 3 896 267.3 6 136 57.3 6 5 3. 2 6 173 170 231 99 160 1291 354 461. 0 6 169 137 186 273 191 58. 2 4 176 138 140 143 222 287 184 59. 7 6 482 268 451 349 235 462 374 106. 3 6 440 666 421 310 459 149. 3 4 339 451 339 436 407 240 369 78. 9 6 21 23 12 11 17 45 22 1 2 .5 6 288 155 235 223 152 278 222 58 6 14 44 18 20 24 13. 6 4 252 391 314 171 282 93 4 29 6 61 39 42 65 40 2 1 .7 6 163 295 212 264 238 155 221 55 6 628 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level: 0.75 29 2 0 33 35 54 87 46 36 50 43 48 54 43 1 0 ..0 6 46 23. 0 6 Dosage Unit: mg/kg/day 1772 564 967 798 808 1069 149 112 169 138 85 197 3 2 2 2 2 2 996 417.0 6 142 39.9 6 2 .4 6 154 164 436 143 329 473 283 149.7 6 675 536 626 539 348 409 522 124.7 6 38 9 21 35 20 30 26 10.9 6 341 329 380 311 236 247 307 55 6 629 Appendix 4 Individual Clinical Chemistry Data Males Day 37 26-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 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level : 0 10.3 11.0 10.6 10.5 10.4 10.7 7.0 6.7 7.0 6.8 7.4 5.1 10.6 .25 6 6.7 .80 6 Dose Level : 0 .03 12.9 10.8 10.5 10.7 9.0 6.8 6.5 5.2 11.2 1.12 4 6.9 1.58 4 Dose Level : 0 .15 11.2 11.2 11.4 10.9 10.4 10.6 5.4 7.4 6.4 6.9 8.3 6.3 11.0 .39 6 6.8 1.00 6 Dosage Unit: mg/kg/day 161 5.4 114 163 5.8 115 155 5.3 1 1 2 158 5.2 115 159 5.2 114 165 5.8 1 2 2 160 3.6 6 5.4 .28 6 115 3 6 Dosage Unit: mg/kg/day 180 6 . 6 1 2 1 162 6 . 2 114 160 5.1 116 158 5.2 1 1 1 165 10.1 4 5.8 .74 4 116 4 4 Dosage Unit: mg/kg/day 159 5.1 114 161 5.3 116 162 5.6 114 163 6 . 1 116 163 5.8 115 155 5.9 115 160 3.1 6 5.6 .38 6 115 6 Covance 6329-223 3M T-6295.7 630 Appendix 4 Individual Clinical Chemistry Data Males Day 37 26-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: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 10.6 10.6 10.9 10.6 11.3 11.6 7.8 5.1 6.1 5.2 7.8 7.6 10.9 .43 6 6.6 1.29 6 Dosage Unit: mg/kg/day 164 5.1 119 158 5.1 1 1 1 162 5.4 115 157 5.8 114 162 5.5 114 166 5.7 113 162 3.4 6 5.4 .29 6 114 2 6 Covance 6329-223 3M T-6295.7 631 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0 50 2 1 86 25 57 25 43 16 59 27 55 18 58 14.7 6 22 4. 4 6 Dose Level : 0 .03 87 2 0 65 2 2 65 18 50 25 67 15.2 4 21 3. 0 4 Dose Level : 0 .15 53 2 2 60 2 1 72 15 64 17 48 2 0 60 25 60 8.4 6 20 3. 6 6 Dosage Unit: mg/kg/day .9 1.3 1.2 1.1 1.1 .9 9.2 9.0 8.5 9.6 10.6 9.1 4.5 4.8 4.4 4.0 4.5 4.5 1.1 .16 6 9.3 .71 6 4.4 .26 6 Dosage Unit: mg/kg/day 1 . 1 9.1 4.4 1 . 1 9.3 4.4 1 . 0 8.4 4.4 1 . 1 9.2 4.7 1.1 .05 4 9.0 .41 4 4.5 .15 4 Dosage Unit: mg/kg/day 1 . 0 9.4 4.4 1 . 0 9.0 4.7 1 . 1 9.0 3.9 1 . 0 9.4 4.7 1 . 0 8.9 4.0 1 . 0 9.5 4.0 1.0 .04 6 9.2 .26 6 4.3 .37 6 4.7 4.2 4.1 5.6 6.1 4.6 4.9 .80 6 4.7 4.9 4.0 4.5 4.5 .39 4 5.0 4.3 5.1 4.7 4.9 5.5 4.9 .40 6 1.1 .4 .8 .3 .6 .2 .6 .34 6 .4 .8 .2 .5 .5 .25 4 .7 .4 .7 .6 .4 .5 .6 .14 6 8 8 7 7 8 8 8 5 6 106 154 160 183 127 151 147 26. 9 6 64 56 65 123 63 56 71 25. 7 6 5 10 10 10 9 2 .5 4 114 130 137 116 124 1 1 .1 4 60 78 50 69 64 1 2 .0 4 8 7 7 15 7 7 8 3. 2 6 146 105 149 162 114 123 133 2 2 .4 6 60 36 65 66 54 63 57 1 1 .3 6 632 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0.75 86 27 70 19 77 15 58 2 1 74 30 56 2 2 70 11.5 6 22 5.4 6 Dosage Unit: mg/kg/day 1 . 1 9.2 4.3 1.3 9.1 4.3 1 . 1 9.6 4.3 1 . 0 9.0 4.5 1 . 2 8.7 4.5 .9 8.9 4.4 1.1 .14 6 9.1 .31 6 4.4 .10 6 4.9 4.8 5.3 4.5 4.2 4.5 4.7 .38 6 .3 .3 .3 .4 .4 .7 .4 .15 6 9 136 6 130 7 102 6 121 7 138 6 113 68 59 51 61 110 46 7 123 1 . 2 14. 1 66 66 23 6 633 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 1MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 28 36 54 108 33 51 44 38 44 38 60 85 44 12.1 6 59 30. 2 6 Dose Level: 0.03 49 73 68 81 29 51 49 76 49 15.9 4 70 13. 3 4 Dose Level:: 0.15 33 35 41 69 26 49 45 125 35 70 38 60 36 6.6 6 68 30. 9 6 Dosage Unit: mg/kg/day 209 88 400 98 330 80 583 138 351 164 298 44 3 9 4 7 3 5 362 125.6 6 102 42.9 6 5 2 .4 6 Dosage Unit: mg/kg/day 2 1 0 170 257 65 193 54 301 64 3 2 3 5 240 48.7 4 88 54.7 4 3 1 .3 4 Dosage Unit: mg/kg/day 286 103 459 90 130 73 219 43 423 70 396 76 1 4 2 2 5 4 319 129.0 6 76 20.3 6 3 1 .5 6 109 205 156 180 274 518 240 146 .6 6 287 761 165 301 378 262 .2 4 206 121 110 267 123 363 198 1 0 1 .3 6 376 244 326 332 494 263 339 89 .9 6 254 344 423 514 384 1 1 0 .9 4 364 387 305 533 317 580 414 115 .1 6 14 27 38 11 18 0 18 13. 2 6 232 107 188 186 279 169 194 58 6 24 15 23 50 28 15. 2 4 168 218 273 290 237 55 4 41 50 36 41 0 36 34 17. 4 6 172 200 198 282 179 350 230 70 6 634 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level: 0.75 34 56 37 35 42 49 37 50 2 2 40 45 46 36 8 .0 6 46 7. 5 6 Dosage Unit: mg/kg/day 305 95 543 37 743 52 269 46 296 61 332 60 1 2 2 3 3 1 415 188.9 6 58 20.0 6 2 .9 6 153 766 352 413 130 174 331 242..1 6 404 485 341 394 233 383 373 83.3 6 32 15 20 27 24 21 23 5.9 6 261 298 203 215 119 284 230 66.0 6 635 Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-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 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level : 0 10.5 10.8 9.7 10.6 10.6 10.2 6.8 5.6 5.0 5.6 6.4 5.0 10.4 .39 6 5.7 .73 6 Dose Level : 0 .03 9.9 10.7 9.8 10.4 4.7 4.3 3.8 4.2 10.2 .42 4 4.2 .37 4 Dose Level : 0 .15 9.2 10.0 8.5 10.5 9.7 10.2 5.5 4.9 5.2 4.0 4.9 5.9 9.7 .73 6 5.1 .65 6 Dosage Unit: mg/kg/day 151 5.3 108 163 6 . 0 1 1 1 165 6 . 2 1 2 0 161 5.9 117 162 5.4 115 162 5.4 117 161 4.9 6 5.7 .38 6 115 4 6 Dosage Unit: mg/kg/day 154 4.0 1 1 0 166 6 . 2 118 159 5.1 117 164 5.5 1 2 0 161 5.4 4 5.2 .92 4 116 4 4 Dosage Unit: mg/kg/day 159 5.0 113 154 5.3 114 156 5.3 114 160 5.0 116 155 4.8 113 159 5.9 114 157 2.5 6 5.2 .39 6 114 1 6 Covance 6329-223 3M T-6295.7 636 Appendix 4 Individual Clinical Chemistry Data Females Day 37 26-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: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 10.0 10.5 10.6 10.5 10.7 10.3 5.4 4.1 4.9 5.1 5.4 4.9 10.4 .25 6 5.0 .48 6 Dosage Unit: mg/kg/day 152 5.6 114 162 5.9 117 161 5.9 117 158 6.3 115 168 6.3 1 2 2 158 5.2 114 160 5.3 6 5.9 .42 6 116 3 6 Covance 6329-223 3M T-6295.7 637 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0 51 2 1 71 17 54 26 56 16 52 2 2 70 17 59 9.1 6 20 3. 9 6 Dose Level : 0 .03 56 18 62 17 61 25 57 18 59 2.9 4 20 3. 7 4 Dose Level : 0 .15 58 16 59 14 83 16 84 19 62 2 2 54 24 67 13.3 6 18 3. 9 6 Dosage Unit: mg/kg/day 1 . 1 9.1 4.7 1 . 2 9.3 4.8 1 . 1 8.4 4.7 1 . 0 8.3 4.4 1 . 0 8 . 1 4.7 1 . 1 8 . 2 4.4 1.1 .08 6 8.6 .50 6 4.6 .17 6 Dosage Unit: mg/kg/day 1 . 2 8 . 6 4.9 1.3 9.9 4.8 1 . 0 8.4 4.2 1.3 9.3 5.0 1.2 .14 4 9.0 .69 4 4.7 .36 4 Dosage Unit: mg/kg/day 1 . 1 8 . 8 4.9 .8 8 . 1 4.1 1.3 9.0 4.8 1 . 2 9.0 5.4 1.3 8.4 4.4 1 . 2 9.2 4.3 1.2 .19 6 8.8 .42 6 4.6 .48 6 4.4 4.5 3.7 3.9 3.4 3.8 4.0 .42 6 3.7 5.1 4.2 4.3 4.3 .58 4 3.9 4.0 4.2 3.6 4.0 4.9 4.1 .44 6 1.3 1.0 .4 .8 .3 .3 .7 .42 6 .5 .4 .3 .3 .4 .10 4 .9 .3 .3 .3 .5 .5 .5 .23 6 8 11 11 8 8 10 9 1 .5 6 132 179 178 124 147 158 153 23. 0 6 13 8 10 9 10 2 .2 4 142 129 98 89 114 25. 1 4 9 8 10 13 10 9 10 1 .7 6 183 145 142 130 135 132 144 19. 7 6 67 97 44 63 48 56 62 19. 0 6 57 73 71 41 60 14. 8 4 53 57 48 55 46 83 57 13. 4 6 638 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0.75 Dosage Unit: mg/kg/day 68 18 1.3 8 . 2 4.4 3.8 95 23 1.4 9.1 4.5 4.6 71 18 1 . 2 9.3 5.1 4.2 67 17 1 . 1 8 . 8 4.3 4.5 71 2 2 1.4 8.4 4.9 3.5 70 17 1 . 2 8 . 8 5.7 3.1 .3 10 106 .3 8 104 .3 14 117 .4 6 125 .2 1 1 144 .3 9 155 70 81 62 56 96 94 74 19 1.3 8 . 8 4.8 4.0 .3 10 125 76 10.6 2.6 .12 .41 .53 .59 .06 2 .7 20.6 16.6 6666666666 639 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N 0Dose Level: 34 24 44 47 45 24 2271 33 27 33 59 36 76.9 34 156. 2 Dose Level: 0.03 26 16 43 57 38 40 34 28 35 7.2 4 35 17. 5 4 Dose Level:: 0.15 44 23 4201 38 31 41 40 49 55 47 33 40 69.4 31761.7 Dosage Unit: mg/kg/day 709 512 742 848 1455 767 110524 125 77 209 114 48 9 5 9 5 839 3216.9 130 466.2 276.3 Dosage Unit: mg/kg/day 634 955 1125 287 121 109 147 87 5 25 5 750 369.9 4 116 25.0 4 41.5 4 Dosage Unit: mg/kg/day 643 980 698 798 1181 535 143 134 109 80 106 194 101 36 29 806 2376.8 128 396.4 5 36. 8 116 144 148 82 143 156 132 276. 8 93 210731 129 149 47. 7 4 127 157 133 175 152 173 153 196. 9 510 280 448 365 197 428 371 1156. 8 359 641 383 331 428 143. 3 4 305 442 327 436 354 203 344 896. 3 18 47 21019 27 22 136. 9 11 38 9 27 21 13. 8 4 312 168 235 241 133 256 224 646 214 390 295 182 270 92 4 140 32 24 23 26 21061.3 155 294 216 221628 135 213 616 640 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level: 0.75 26 28 27 31 36 64 43 38 34 34 35 63 34 6 .3 6 43 16. 2 6 Dosage Unit: mg/kg/day 1502 462 626 683 725 941 139 96 127 127 89 171 4 2 2 2 3 3 823 367.0 6 125 29.9 6 3 .8 6 155 163 300 169 189 244 203 57.2 6 657 496 593 516 340 390 499 119.4 6 38 14 15 20 8 40 22 13.4 6 349 312 367 299 237 243 301 53 6 641 Appendix 4 Individual Clinical Chemistry Data Males Day 62 26-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 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level : 0 10.0 10.8 10.6 10.0 10.9 10.3 6.8 6.9 7.6 6.4 8.2 6.8 10.4 .39 6 7.1 .66 6 Dose Level : 0 .03 10.0 11.0 10.3 10.7 6.8 7.2 7.5 5.5 10.5 .44 4 6.8 .88 4 Dose Level : 0 .15 10.6 10.1 10.7 10.4 10.2 10.1 5.3 7.4 6.6 7.2 7.8 5.3 10.4 .26 6 6.6 1.08 6 Dosage Unit: mg/kg/day 159 4.7 116 161 5.7 118 157 5.7 1 2 1 158 5.4 1 2 0 159 5.0 1 2 1 165 5.8 123 160 2.9 6 5.4 .44 6 120 2 6 Dosage Unit: mg/kg/day 160 5.1 117 185 7.0 136 159 5.2 116 161 5.2 1 2 0 166 12.5 4 5.6 .92 4 122 9 4 Dosage Unit: mg/kg/day 158 4.9 1 2 1 154 4.9 115 161 6 . 1 1 2 0 162 5.1 1 2 1 161 5.8 1 2 0 164 5.3 126 160 3.5 6 5.4 .50 6 120 3 6 Covance 6329-223 3M T-6295.7 642 Appendix 4 Individual Clinical Chemistry Data Males Day 62 26-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: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 10.0 10.3 10.1 10.1 11.1 11.4 7.6 6.2 5.9 5.1 8.7 7.3 10.5 .60 6 6.8 1.31 6 Dosage Unit: mg/kg/day 159 5.3 1 2 1 153 5.6 118 158 5.3 1 2 1 152 4.7 115 163 6.5 123 169 6 . 0 1 2 0 159 6.4 6 5.6 .63 6 120 2 6 Covance 6329-223 3M T-6295.7 643 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 51 18 .9 8.5 4.4 4.1 69 2 2 1 . 2 8 . 6 4.5 4.1 61 25 1 . 2 8.5 4.5 4.0 47 16 1 . 2 9.5 4.2 5.3 67 24 1 . 2 9.8 4.0 5.8 46 2 2 1 . 0 9.3 4.5 4.8 .9 8 93 59 .3 9 152 59 .7 8 176 61 .4 9 227 185 .6 9 126 79 .3 10 156 70 57 10.2 6 21 3. 5 6 1.1 .13 6 9.0 .57 6 4.4 .21 6 4.7 .75 6 .5 .24 6 9 155 8 45 4 66 86 49 4 6 Dose Level : 0 .03 Dosage Unit: mg/kg/day 92 19 1 . 1 9.2 4.4 4.8 62 23 1 . 1 9.2 4.2 5.0 58 19 1 . 0 8.3 4.3 4.0 54 26 1 . 1 8.7 4.4 4.3 .4 7 126 .8 8 130 .3 15 140 .8 1 2 113 87 99 50 68 66 17.3 4 22 3. 4 4 1.1 .05 4 8.8 .44 4 4.3 .10 4 4.5 .46 4 .6 10 127 76 .26 3. 7 11 2 21 5 4444 Dose Level : 0 .15 Dosage Unit: mg/kg/day 53 2 0 1 . 2 9.2 4.7 4.5 60 2 0 1 . 0 9.1 4.6 4.5 76 18 1 . 1 8.9 4.0 4.9 79 16 .9 9.0 4.4 4.6 48 2 0 1 . 0 8 . 8 4.0 4.8 57 24 1 . 0 9.1 4.0 5.1 .8 1 0 148 .4 9 113 .8 6 153 .4 15 153 .5 13 1 1 2 .6 9 145 58 33 86 62 75 68 62 12.6 6 20 2 .7 6 1.0 .10 6 9.0 .15 6 4.3 .33 6 4.7 .24 6 .6 10 137 64 .18 3. 2 19 5 18 0 6666 644 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level: 0.75 Dosage Unit: mg/kg/day 88 19 1 . 2 8 . 8 4.4 4.4 73 2 0 1.4 9.5 4.7 4.8 75 14 1 . 2 9.6 4.3 5.3 68 18 1 . 1 9.0 4.5 4.5 74 19 1 . 2 8.5 4.2 4.3 69 29 1 . 0 8.7 4.4 4.3 .3 9 139 .5 9 142 .2 9 1 0 1 .4 12 148 .3 6 1 2 0 .4 8 1 1 1 53 63 56 78 68 50 74 7.2 6 20 5.0 6 1.2 .13 6 9.0 .44 6 4.4 .17 6 4.6 .39 6 .4 .10 6 9 127 1.9 18.9 66 61 10.5 6 645 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 35 49 38 49 32 45 39 39 41 49 40 86 38 3.4 6 53 16. 7 6 Dose Level: 0 .03 55 77 41 98 33 60 51 73 45 9.9 4 77 15. 8 4 Dose Level: 0.15 35 31 46 87 29 43 48 105 33 41 33 54 37 7.8 6 60 29.3 6 Dosage Unit: mg/kg/day 245 86 331 92 321 83 665 170 290 159 308 48 2 6 5 6 2 4 360 152.5 6 106 47.7 6 4 1 .8 6 Dosage Unit: mg/kg/day 241 150 239 67 186 53 297 66 3 2 4 7 241 45.3 4 84 44.5 4 4 2 .2 4 Dosage Unit: mg/kg/day 233 99 451 89 129 72 2 0 2 39 428 68 386 81 2 5 3 4 4 4 305 134.0 6 75 20.8 6 4 1.0 6 182 226 490 294 245 138 262 123. 6 6 352 272 346 330 498 251 342 8 6 .9 6 316 334 182 270 276 67. 9 4 244 296 410 483 358 108. 3 4 302 124 121 253 142 224 194 76.1 6 365 381 271 528 310 605 410 129.7 6 11 5 38 5 26 0 14 14.7 6 219 118 201 191 286 170 198 55 6 27 0 12 38 19 16.7 4 166 196 270 280 228 55 4 41 35 30 11 0 53 28 19.6 6 172 208 180 283 182 380 234 82 6 646 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level: 0.75 29 39 35 41 31 44 31 52 19 33 43 42 31 7. 8 6 42 6 ..2 6 Dosage Unit: mg/kg/day 285 96 506 39 755 52 240 48 250 52 351 62 2 2 1 2 2 2 398 200.5 6 58 20.0 6 2 .4 6 172 285 204 483 113 200 243 130..1 6 414 503 340 434 241 377 385 89.4 6 30 41 23 34 18 15 27 9.9 6 271 317 204 240 161 283 246 56 6 647 Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-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 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level : 0 9.7 9.6 10.4 10.3 9.9 10.3 5.9 6.2 5.9 6.5 5.7 5.5 10.0 .34 6 6.0 .36 6 Dose Level : 0 .03 9.7 10.2 10.0 9.8 4.8 4.2 4.4 4.8 9.9 .22 4 4.6 .30 4 Dose Level : 0 .15 9.7 10.0 8.8 10.1 9.9 9.4 5.2 4.8 5.3 4.3 5.2 5.8 9.6 .48 6 5.1 .51 6 Dosage Unit: mg/kg/day 151 4.7 114 159 6.3 114 166 6 . 0 123 167 6 . 1 125 160 5.5 119 168 6 . 0 125 162 6.5 6 5.8 .59 6 120 5 6 Dosage Unit: mg/kg/day 159 4.9 1 2 0 163 5.6 119 156 4.8 118 160 5.6 123 160 2.9 4 5.2 .43 4 120 2 4 Dosage Unit: mg/kg/day 166 6.5 127 156 5.4 1 2 1 160 5.6 127 158 5.5 1 2 1 158 4.7 1 2 2 162 5.1 1 2 1 160 3.6 6 5.5 .60 6 123 3 6 Covance 6329-223 3M T-6295.7 648 Appendix 4 Individual Clinical Chemistry Data Females Day 62 26-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: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 9.9 10.8 11.0 9.4 10.4 10.0 5.0 4.6 5.1 5.2 4.7 5.4 10.2 .60 6 5.0 .30 6 Dosage Unit: mg/kg/day 157 5.4 118 163 6.9 1 2 1 160 6 . 2 119 157 5.8 1 2 1 164 5.1 119 165 5.3 123 161 3.5 6 5.8 .67 6 120 1 6 Covance 6329-223 3M T-6295.7 649 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0 53 19 64 19 57 29 54 19 56 17 74 2 0 60 8.0 6 20 4. 3 6 Dose Level : 0 .03 57 19 74 14 64 26 59 19 64 7.6 4 20 4. 9 4 Dose Level : 0 .15 65 15 70 14 108 19 78 16 75 26 53 2 2 75 18.5 6 19 4. 6 6 Dosage Unit: mg/kg/day 1 . 0 8.7 4.7 1.3 9.1 4.8 1 . 1 8.3 4.7 1 . 0 8.4 4.7 1 . 1 8.3 4.8 1.3 9.2 5.0 1.1 .14 6 8.7 .40 6 4.8 .12 6 Dosage Unit: mg/kg/day 1 . 2 9.0 1 . 2 10.3 1 . 1 8.5 1 . 6 10.5 5.1 5.2 5.1 5.9 1.3 .22 4 9.6 .98 4 5.3 .39 4 Dosage Unit: mg/kg/day 1 . 2 8.7 5.1 1 . 0 9.0 4.9 1.3 9.0 5.0 1 . 0 9.1 5.2 1.4 8 . 8 4.8 1 . 2 9.2 5.0 1.2 .16 6 9.0 .19 6 5.0 .14 6 4.0 4.3 3.6 3.7 3.5 4.2 3.9 .33 6 3.9 5.1 3.4 4.6 4.2 .75 4 3.6 4.1 4.0 3.9 4.0 4.2 4.0 .21 6 1.2 1.1 .5 .8 .3 .4 .7 .38 6 .6 .3 .4 .4 .4 .13 4 .8 .3 .2 .3 .5 .5 .4 .22 6 6 119 61 8 177 1 0 1 9 170 56 8 132 81 7 151 43 9 177 66 8 154 1 .2 24. 6 66 68 20 6 7 143 8 132 7 109 8 119 8 126 6 14. 9 44 51 60 64 42 54 9 4 8 6 8 9 14 8 9 2 .7 6 173 163 125 139 136 161 150 18. 8 6 49 56 38 48 68 44 50 10 6 650 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0.75 Dosage Unit: mg/kg/day 63 2 0 1 . 6 9.5 5.5 4.0 1 1 1 2 1 1 . 6 9.8 5.1 4.7 75 18 1.3 9.8 5.4 4.4 62 18 1 . 1 9.0 4.7 4.3 63 2 0 1.4 9.0 5.3 3.7 65 18 1.3 9.5 5.5 4.0 .3 9 107 88 .2 8 80 57 .3 17 90 59 .3 9 105 56 .2 1 0 147 6 8 .3 7 141 108 73 19 1.4 9.4 5.2 4.2 .3 1 0 1 1 2 73 19.1 1.3 .19 .36 .31 .35 .05 3.6 27. 0 2 1 6666666666 651 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 41 25 48 45 46 31 27 24 36 24 36 63 39 7.7 6 35 15..8 6 Dose Level: 0 .03 26 16 35 38 37 46 43 142 35 7.0 4 60 55..8 4 Dose Level: 0.15 46 39 25 2 1 41 37 34 38 45 87 61 49 42 12.2 6 45 22.4 6 Dosage Unit: mg/kg/day 706 533 782 901 1408 863 152 102 130 82 226 126 4 6 11 7 9 5 866 296.2 6 136 50.1 6 7 2.6 6 Dosage Unit: mg/kg/day 692 824 1306 335 127 113 181 104 5 4 2 5 789 401.7 4 131 34.5 4 4 1.4 4 Dosage Unit: mg/kg/day 710 1097 645 724 1271 660 143 160 111 76 108 244 11 1 4 11 4 3 851 265.3 6 140 58.6 6 6 4.3 6 222 164 166 120 167 168 168 32.4 6 130 153 189 227 175 42.5 4 164 137 140 129 194 220 164 36.2 6 525 275 437 377 251 487 392 111.8 6 386 741 396 338 465 185.6 4 356 501 324 454 394 235 377 94.9 6 18 23 0 20 53 84 33 30.3 6 10 134 30 18 48 57.9 4 38 5 25 25 12 56 27 18.3 6 359 184 261 275 186 325 265 71.2 6 254 492 322 205 318 125.4 4 200 365 240 306 266 174 258 70 6 652 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level: 0.75 29 2 1 30 34 40 75 43 35 31 34 41 65 36 6 .3 6 44 21. 0 6 Dosage Unit: mg/kg/day 1624 463 563 566 726 900 154 108 122 118 95 166 3 2 2 1 2 2 807 428.6 6 127 27.4 6 2 .6 6 133 174 305 204 157 308 214 75. 7 6 730 556 409 345 353 414 468 149.1 6 63 18 26 35 15 38 32 17.5 6 433 381 417 320 263 287 350 70 6 653 Appendix 4 Individual Clinical Chemistry Data Males Day 91 26-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 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level : 0 9.7 11.0 9.8 10.2 9.5 11.4 6.9 6.3 6.6 6.7 6.9 7.4 10.3 .77 6 6.8 .37 6 Dose Level : 0 .03 9.8 10.1 10.6 11.6 10.5 .79 4 6.9 6.7 7.5 5.8 6.7 .70 4 Dose Level : 0 .15 11.0 11.4 10.0 10.7 10.4 10.3 5.8 8.2 6.6 6.5 8.0 5.8 10.6 .51 6 6.8 1.05 6 Dosage Unit: mg/kg/day 158 4.7 115 160 5.1 117 154 4.7 1 1 2 156 5.2 114 159 4.9 119 174 6 . 2 127 160 7.1 6 5.1 .56 6 117 5 6 Dosage Unit: mg/kg/day 163 4.6 117 173 6 . 8 125 163 5.1 117 169 6.4 123 167 4.9 4 5.7 1.04 4 120 4 4 Dosage Unit: mg/kg/day 160 4.8 117 169 5.6 129 159 5.3 115 160 5.7 1 2 2 162 5.7 1 1 0 155 5.3 1 1 2 161 4.6 6 5.4 .35 6 118 7 6 Covance 6329-223 3M T-6295.7 654 Appendix 4 Individual Clinical Chemistry Data Males Day 91 26-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: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 10.7 11.2 10.4 10.3 11.2 11.1 7.1 6.7 5.6 5.0 6.6 7.5 10.8 .41 6 6.4 .94 6 Dosage Unit: mg/kg/day 170 5.1 125 160 5.8 114 158 5.1 117 158 5.0 116 163 5.2 115 167 6 . 1 114 163 5.0 6 5.4 .45 6 117 4 6 Covance 6329-223 3M T-6295.7 655 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level : 0 48 2 0 78 2 2 95 2 1 58 15 78 2 2 42 18 66 20.5 6 20 2 .7 6 Dose Level : 0 .03 81 18 51 2 2 61 2 2 80 26 68 14.7 4 22 3. 3 4 Dose Level : 0 .15 62 15 55 2 0 74 18 49 24 45 17 74 26 60 12.4 6 20 4. 2 6 Dosage Unit: mg/kg/day 1 . 0 8 . 8 4.7 1.3 9.8 5.4 1 . 2 8.5 4.5 1 . 2 9.4 4.4 1 . 1 9.7 4.4 1 . 1 9.3 4.7 1.2 .10 6 9.2 .51 6 4.7 .38 6 Dosage Unit: mg/kg/day 1 . 1 9.0 4.7 1 . 2 9.8 4.7 1 . 0 8 . 1 4.3 1 . 1 9.0 4.6 1.1 .08 4 9.0 .69 4 4.6 .19 4 Dosage Unit: mg/kg/day 1 . 1 9.2 4.8 1 . 1 9.3 4.9 1 . 0 8.7 3.8 1 . 0 8.9 4.6 1 . 0 9.0 4.3 1 . 0 9.3 4.2 1.0 .05 6 9.1 .24 6 4.4 .41 6 4.1 4.4 4.0 5.0 5.3 4.6 4.6 .51 6 4.3 5.1 3.8 4.4 4.4 .54 4 4.4 4.4 4.9 4.3 4.7 5.1 4.6 .32 6 .7 8 99 65 .3 6 189 65 .4 10 182 61 .3 7 217 88 .5 9 136 57 .3 9 171 65 .4 8 166 67 .16 1 .5 42. 0 1 0 .9 6666 .3 7 114 53 .9 7 143 81 .4 8 149 50 .4 10 129 60 .5 8 134 61 .27 1 .4 15. 6 14. 0 4444 .6 7 153 42 .3 7 122 35 .4 8 143 77 .5 2 2 151 67 .4 10 125 43 .4 8 143 72 .4 10 140 56 .10 5. 8 13. 1 18. 0 6666 656 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 TRIG MG/DL Dose Level: 0.75 84 2 2 89 18 89 14 63 2 0 93 32 56 26 79 15.5 6 22 6.3 6 Dosage Unit: mg/kg/day 1.2 1.4 1.2 1.4 1.3 .9 9.8 9.5 9.6 10.0 9.1 8.8 4.8 5.0 4.5 5.2 4.5 4.6 1.2 .19 6 9.5 .45 6 4.8 .29 6 5.0 4.5 5.1 4.8 4.6 4.2 4.7 .33 6 .3 9 142 62 .3 6 131 76 .3 6 65 51 .3 13 105 53 .3 7 115 78 .5 24 109 42 .3 1 1 1 1 1 60 .08 7.0 26.6 14 6666 657 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 36 55 57 78 35 43 53 38 40 38 44 74 44 9.1 6 54 17. 9 6 Dose Level: 0.03 39 72 39 80 30 50 64 114 43 14.6 4 79 26. 6 4 Dose Level:: 0.15 30 34 37 57 23 52 56 153 38 54 40 54 37 11.1 6 67 42. 8 6 Dosage Unit: mg/kg/day 2 2 0 81 322 123 292 84 583 161 274 164 284 50 3 9 6 7 5 4 329 128.7 6 110 46.5 6 6 2 .2 6 Dosage Unit: mg/kg/day 219 220 238 73 168 53 307 67 2 2 3 11 233 57.5 4 103 78.3 4 4 4. 4 4 Dosage Unit: mg/kg/day 235 98 531 85 157 69 229 42 404 68 390 82 1 4 3 2 7 7 324 140.3 6 74 19.2 6 4 2 .5 6 188 1481 128 2407 146 368 786 947. 2 6 247 250 165 217 220 39. 4 4 196 149 107 345 230 227 209 81. 8 6 387 292 410 350 510 269 370 87. 4 6 269 348 454 487 390 99. 8 4 447 426 290 520 329 640 442 127. 6 6 8 0 45 10 25 0 15 17. 5 6 23 2 23 25 18 1 0 .9 4 130 41 26 25 0 18 40 46. 1 6 264 144 259 224 327 198 236 62 6 190 249 330 306 269 62 4 245 261 213 319 214 443 282 87 6 658 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level: 0.75 35 43 38 34 33 42 31 41 2 0 40 50 71 34 9. 8 6 45 13. 0 6 Dosage Unit: mg/kg/day 296 106 447 43 6 6 8 54 294 52 280 58 346 63 1 1 2 2 2 2 388 150.1 6 63 22.3 6 2 .5 6 1132 476 367 141 105 276 416 377. 0 6 389 482 343 480 225 353 379 96.5 6 35 0 18 35 16 12 19 13.6 6 281 338 221 292 169 279 263 59.4 6 659 Appendix 4 Individual Clinical Chemistry Data Females Day 91 26-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 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level : 0 10.2 11.1 10.3 11.0 8.1 10.7 5.5 6.0 4.8 6.8 5.6 5.5 10.2 1.11 6 5.7 .66 6 Dose Level : 0 .03 9.7 11.5 8.8 10.9 4.5 3.6 4.5 4.0 10.2 1.21 4 4.2 .44 4 Dose Level : 0 .15 9.7 10.7 9.2 10.1 10.4 9.9 5.4 5.0 5.4 4.1 5.2 6.0 10.0 .53 6 5.2 .63 6 Dosage Unit: mg/kg/day 151 5.0 109 168 6.7 125 160 5.1 116 166 5.7 125 160 4.8 118 162 6 . 1 117 161 5.9 6 5.6 .74 6 118 6 6 Dosage Unit: mg/kg/day 156 4.6 1 1 0 170 6.5 1 2 2 154 4.5 113 165 5.4 124 161 7.5 4 5.2 .93 4 117 6 4 Dosage Unit: mg/kg/day 160 5.2 116 161 6 . 2 1 2 1 156 5.3 116 156 5.6 118 160 5.7 125 165 6.3 125 160 3.4 6 5.7 .45 6 120 4 6 Covance 6329-223 3M T-6295.7 660 Appendix 4 Individual Clinical Chemistry Data Females Day 91 26-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: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level: 0.75 10.4 10.5 10.7 11.5 10.6 9.7 4.9 4.2 5.0 5.8 5.3 5.2 10.6 .58 6 5.1 .53 6 Dosage Unit: mg/kg/day 159 5.4 1 2 2 165 6 . 2 124 160 5.9 114 170 6 . 6 117 163 5.8 118 157 5.1 115 162 4.7 6 5.8 .54 6 118 3 6 Covance 6329-223 3M T-6295.7 661 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level: 0 57 2 2 74 16 52 25 55 19 60 2 0 65 2 0 60 8.0 6 20 3.0 6 Dose Level: 0.03 56 18 63 19 60 2 2 66 17 61 4.3 4 19 2.2 4 Dose Level: 0.15 58 2 1 62 16 71 24 74 17 65 27 48 25 63 9.4 6 22 4.5 6 Dosage Unit: mg/kg/day 1.0 1.2 1.1 1.0 1.2 1.3 7.7 8.9 7.9 8.2 8.1 8.6 4.6 5.0 4.7 4.6 5.0 4.9 1.1 .12 6 8.2 .45 6 4.8 .19 6 Dosage Unit: mg/kg/day 1 . 1 8.3 5.0 1.3 9.6 5.2 1 . 1 7.9 5.0 1.5 9.4 5.5 1.2 .19 4 8.8 .83 4 5.2 .24 4 Dosage Unit: mg/kg/day 1 . 1 8.4 5.3 .9 8 . 2 4.7 1.3 9.3 5.4 1 . 1 9.6 4.7 1.4 8.5 5.0 1 . 1 8 . 6 4.8 1.2 .18 6 8.8 .55 6 5.0 .3 6 3.1 3.9 3.2 3.6 3.1 3.7 3.4 .34 6 3.3 4.4 2.9 3.9 3.6 .66 4 3.1 3.5 3.9 4.9 3.5 3.8 3.8 .61 6 1.2 1.2 .4 .6 .4 .3 .7 .41 6 .5 .3 .4 .4 .4 .08 4 .7 .3 .4 .2 .6 .6 .5 .20 6 8 11 12 11 9 10 10 1.5 6 7 8 8 6 7 1.0 4 11 7 10 9 11 14 10 2.3 6 115 178 183 124 147 178 154 29.9 6 136 127 117 98 120 16.3 4 191 135 145 129 136 157 149 22.8 6 68 82 39 78 42 54 60 18.3 6 49 97 49 44 60 24.9 4 49 69 73 74 64 59 65 9.5 6 58 77 84 57 70 67 69 10.6 6 52 45 42 43 46 4.5 4 74 60 56 49 53 36 55 12.5 6 662 ANIMAL NUMBER Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0.75 Dosage Unit: mg/kg/day 80 2 2 1 . 6 9.4 5.4 4.0 98 23 1.4 9.0 4.8 4.2 60 2 1 1 . 2 9.0 4.2 4.8 55 17 1 . 0 9.0 4.6 4.4 91 19 1 . 2 8.7 5.1 3.6 72 19 1.3 9.2 5.4 3.8 .2 1 1 57 51 16 .2 14 29 29 9 .3 17 65 89 18 .3 8 75 41 25 .2 24 76 58 27 .2 13 87 95 2 0 76 2 0 1.3 9.0 4.9 4.1 .2 14 65 60 19 17.0 2.2 .20 .23 .48 .43 .05 5. 5 20.3 26.3 6 66666666666 663 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 29 31 34 51 37 29 23 2 2 30 30 33 95 31 4.9 6 43 27. 3 6 Dose Level: 0.03 2 2 13 35 59 35 43 28 28 30 6.3 4 36 19. 8 4 Dose Level:: 0.15 43 72 28 43 33 40 2 0 36 50 75 63 63 40 15.7 6 55 17. 2 6 Dosage Unit: mg/kg/day 723 490 666 842 1370 659 156 125 128 79 238 126 2 2 8 3 1 1 792 305.3 6 142 53.1 6 3 2 .6 6 Dosage Unit: mg/kg/day 606 778 1093 258 132 109 163 88 4 3 1 1 684 348.2 4 123 32.2 4 2 1 .5 4 Dosage Unit: mg/kg/day 740 848 720 897 1241 673 160 143 129 70 121 262 4 1 2 1 7 8 853 207.5 6 148 63.8 6 4 3. 1 6 157 130 194 135 184 191 165 28. 5 6 92 144 188 108 133 42. 6 4 218 178 201 122 213 225 193 38. 4 6 527 290 457 408 226 446 392 1 1 2 .8 6 403 713 420 344 470 165. 2 4 348 514 356 479 402 475 429 69. 9 6 28 27 12 20 12 39 23 1 0 .5 6 14 100 19 31 41 40. 0 4 30 9 36 28 36 860 166 339. 9 6 377 203 285 307 174 309 276 74 6 273 502 360 220 339 123 4 211 392 274 346 282 365 312 67 6 664 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level: 0.75 28 24 31 39 52 85 44 33 40 46 37 85 39 8 .8 6 52 26. 6 6 Dosage Unit: mg/kg/day 1262 239 902 415 377 683 168 109 88 98 70 141 2 2 5 2 2 2 646 384.1 6 112 36.1 6 2 1.2 6 180 219 954 207 267 285 352 297..5 6 758 499 504 494 439 406 517 124.5 6 61 9 25 33 25 36 32 17.2 6 475 359 371 340 346 296 364 59 6 665 Appendix 4 Individual Clinical Chemistry Data Males Day 153 26-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 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level : 0 9.0 11.0 10.3 9.8 9.9 10.8 6.6 6.2 6.8 6.9 6.9 6.3 10.1 .73 6 6.6 .31 6 Dose Level : 0 .03 10.2 11.3 10.4 11.2 10.8 .56 4 6.6 6.6 7.2 4.7 6.3 1.09 4 Dose Level : 0 .15 9.6 10.1 11.3 10.9 9.9 10.3 5.7 7.2 6.9 6.2 8.6 6.5 10.4 .64 6 6.8 1.01 6 Dosage Unit: mg/kg/day 154 4.7 116 160 5.4 116 150 5.3 1 1 0 151 5.3 1 1 2 163 5.8 1 2 1 164 6 . 1 119 157 6.1 6 5.4 .48 6 116 4 6 Dosage Unit: mg/kg/day 154 5.0 113 163 6 . 1 114 159 4.9 118 161 6 . 1 1 2 2 159 3.9 4 5.5 .67 4 117 4 4 Dosage Unit: mg/kg/day 161 5.7 1 2 0 154 4.8 119 159 6 . 0 114 158 5.3 116 161 5.6 109 154 5.8 1 1 2 158 3.2 6 5.5 .43 6 115 4 6 Covance 6329-223 3M T-6295.7 666 Appendix 4 Individual Clinical Chemistry Data Males Day 153 26-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: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 11.4 10.4 9.5 10.5 11.4 11.3 7.9 6.7 4.3 5.9 9.1 7.2 10.8 .76 6 6.8 1.66 6 Dosage Unit: mg/kg/day 171 6 . 6 128 150 6.4 1 1 1 153 4.8 107 153 5.8 108 160 5.1 109 163 6 . 2 114 158 7.9 6 5.8 .73 6 113 7 6 Covance 6329-223 3M T-6295.7 667 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 48 2 1 74 2 2 62 25 57 16 57 23 47 15 58 9.9 6 20 4. 0 6 Dose Level : 0 .03 46 18 70 25 72 12 68 24 64 12.1 4 20 6 .0 4 Dose Level : 0 .15 49 2 0 53 23 62 18 59 24 58 23 60 27 57 4.9 6 22 3. 1 6 Dosage Unit: mg/kg/day .9 7.6 4.3 1.3 9.6 5.6 1 . 2 8 . 2 4.6 1 . 2 9.2 4.4 1 . 1 9.4 4.6 1 . 1 9.3 4.8 1.1 .14 6 8.9 .80 6 4.7 .47 6 Dosage Unit: mg/kg/day 1 . 0 8 . 6 4.4 1.3 8.9 4.6 .9 8.3 3.8 1 . 1 8.5 4.7 1.1 .17 4 8.6 .25 4 4.4 .40 4 Dosage Unit: mg/kg/day 1 . 1 9.2 5.1 1 . 0 8.5 4.6 1 . 2 8 . 8 4.2 1 . 0 8.3 4.7 1 . 1 8.7 4.3 1 . 0 9.0 4.1 1.1 .08 6 8.8 .33 6 4.5 .37 6 3.3 4.0 3.6 4.8 4.8 4.5 4.2 .63 6 4.2 4.3 4.5 3.8 4.2 .29 4 4.1 3.9 4.6 3.6 4.4 4.9 4.2 .48 6 1.0 .3 .6 .4 .6 .3 .5 .27 6 .4 1.0 .2 .5 .5 .34 4 .6 .3 .4 .5 .4 .6 .5 .12 6 7 9 9 9 9 11 9 1 .3 6 80 175 177 226 143 175 163 48. 5 6 53 65 70 175 59 56 80 47. 1 6 6 9 10 9 8 1 .7 4 102 128 82 127 110 2 2 .1 4 61 123 65 77 82 28. 5 4 8 7 9 12 15 8 10 3. 1 6 133 100 144 136 107 162 130 23. 2 6 54 57 72 83 86 60 69 13. 7 6 39 73 64 56 42 81 59 16 8 6 43 61 41 42 47 95 4 33 37 56 37 48 34 41 9 6 668 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level: 0.75 Dosage Unit: mg/kg/day 81 2 1 1 . 2 9.6 5.1 4.5 .3 15 1 0 0 62 25 74 12 1.4 9.1 4.6 4.5 .3 9 128 69 23 70 13 1 . 1 9.0 3.9 5.1 .2 8 62 44 2 0 62 15 1 . 1 8.7 4.6 4.1 .3 8 80 67 16 87 18 1 . 1 8.4 4.2 4.2 .4 9 77 84 25 46 26 1 . 0 8 . 6 4.6 4.0 .4 43 99 55 28 70 18 1 . 2 8.9 4.5 4.4 .3 15 91 64 23 14.6 5.3 .14 .43 .41 .40 .08 13.8 23.1 13.5 4 66666666666 669 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05530 QS I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 52 159 33 82 30 51 31 48 37 44 33 79 36 8.2 6 77 43. 3 6 Dose Level: 0.03 54 88 33 70 17 18 46 146 38 16.2 4 80 52. 8 4 Dose Level:: 0.15 36 47 31 53 24 38 61 131 26 75 38 52 36 13.4 6 66 34. 1 6 Dosage Unit: mg/kg/day 175 78 305 115 277 82 593 171 266 176 272 53 3 1 2 2 1 2 315 143.3 6 112 51.2 6 2 8 6 Dosage Unit: mg/kg/day 2 2 1 254 233 70 280 42 312 68 3 2 2 1 262 42.2 4 108 97.8 4 2 8 4 Dosage Unit: mg/kg/day 259 100 498 78 169 68 228 38 401 67 292 78 2 3 3 2 1 8 308 120.9 6 72 20.3 6 3 2 .5 6 192 377 156 362 155 169 235 105. 0 6 395 293 79 253 255 131. 7 4 268 118 201 330 126 412 242 116. 5 6 395 296 383 361 499 302 373 74. 3 6 249 358 394 513 378 108. 8 4 371 405 280 494 310 733 432 165. 5 6 11 45 8 25 0 18 17. 7 5 285 175 255 244 342 232 256 55. 7 6 25 3 11 33 18 13. 5 4 182 276 302 341 275 67. 7 4 23 45 34 28 0 19 25 15. 2 6 212 264 211 322 208 541 293 129. 4 6 670 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level: 0.75 33 45 73 42 34 41 30 40 2 2 62 46 60 40 18..1 6 48 1 0 ..0 6 Dosage Unit: mg/kg/day 285 107 359 44 616 47 230 44 216 57 310 66 1 2 7 2 1 1 336 146.9 6 61 24.2 6 2 2.3 6 297 3173 99 139 154 306 695 1217.1 6 374 554 344 404 232 373 380 104.1 6 33 6 23 36 31 30 26 10.9 6 284 406 238 270 178 308 281 76.1 6 671 Appendix 4 Individual Clinical Chemistry Data Females Day 153 26-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 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level :0 9.4 1110..17 1100..17 9.4 10.2 .687 56..02 5.8 5.8 5.2 5.8 5.6 .634 Dose Level : 0. 03 8.4 111000...009 4.0 4.9 3.0 4.6 9.8 1.04 4 4.1 .84 4 Dose Level : 0. 15 9.5 9.3 9.7 9.9 1100..24 5.0 3.8 5.7 4.0 5.1 6.3 9.8 .642 5.0 .696 Dosage Unit: mg/kg/day 144 169 155 163 159 161 158 86.5 46..67 5.8 6.9 5.6 6.5 6.0 .681 107 124 116 125 125 116 119 76 Dosage Unit: mg/kg/day 148 163 56..11 108 118 151 5.3 113 159 5.8 124 155 6.9 4 5.6 .46 4 1166 4 Dosage Unit: mg/kg/day 153 4.7 110 152 5.3 118 154 5.8 115 152 158 5.7 4.8 112104 154 5.9 118 15426.2 5.4 .652 116 36 Covance 6329-223 3M T-6295.7 672 Appendix 4 Individual Clinical Chemistry Data Females Day 153 26-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: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 10.6 11.7 10.5 10.1 10.6 9.7 5.0 6.0 5.0 4.0 4.3 5.3 10.5 .67 6 4.9 .71 6 Dosage Unit: mg/kg/day 158 5.3 116 166 7.1 114 153 7.1 116 153 5.9 1 1 1 161 6.5 124 156 5.7 114 158 5.0 6 6.3 .75 6 116 4 6 Covance 6329-223 3M T-6295.7 673 ANIMAL NUMBER Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level: 0 64 18 68 14 51 25 59 16 57 2 1 64 17 60 6.1 6 18 3.9 6 Dose Level: 0.03 62 18 77 12 59 27 57 16 64 9.1 4 18 6.3 4 Dose Level: 0.15 70 15 71 13 83 18 68 16 72 19 57 2 0 70 8.3 6 17 2.6 6 Dosage Unit: mg/kg/day 1 . 1 8.5 4.9 1 . 2 9.1 4.9 1 . 0 7.7 4.6 .8 7.7 4.5 1 . 2 8.4 5.1 1 . 2 8 . 1 4.6 1.1 .16 6 8.2 .54 6 4.8 .23 6 Dosage Unit: mg/kg/day 1.2 1.2 1.0 1.4 8.6 9.1 8.0 9.5 4.9 4.8 4.8 5.5 1.2 .16 4 8.8 .65 4 5.0 .34 4 Dosage Unit: mg/kg/day 1.1 .8 1.2 1.1 1.3 1.1 8.6 8.2 8.5 9.0 8.4 8.2 5.2 4.4 5.0 5.2 4.8 4.7 1.1 .17 6 8.5 .30 6 4.9 .3 6 3.6 4.2 3.1 3.2 3.3 3.5 3.5 .40 6 3.7 4.3 3.2 4.0 3.8 .47 4 3.4 3.8 3.5 3.8 3.6 3.5 3.6 .17 6 .9 .8 .5 .5 .3 .4 .6 .23 6 .3 .2 .4 .3 .3 .08 4 .5 .2 .3 .3 .4 .4 .4 .10 6 5 127 7 166 5 186 6 112 6 165 6 158 6 152 .8 27.5 66 5 4 5 5 5 .5 4 135 104 98 102 110 17.0 4 8 190 5 136 7 119 5 137 5 151 5 149 6 147 1.3 24.0 66 45 55 37 35 41 55 45 8.7 6 28 35 41 27 33 6.6 4 22 51 31 45 32 35 36 10.4 6 56 66 82 53 67 54 63 11.1 6 47 42 38 41 42 3.7 4 73 53 48 39 42 32 48 14.3 6 674 ANIMAL NUMBER Group: 4 I05506 a I05507 I05511 I05512 I05522 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0.75 Dosage Unit: mg/kg/day 107 28 1 . 8 9.2 4.4 4.8 .2 58 67 75 1 1 93 2 2 1.4 9.3 4.8 4.5 .2 28 28 2 2 8 66 23 .9 8 . 0 4.2 3.8 .2 18 59 36 2 0 78 27 1.3 8 . 8 5.2 3.6 .2 7 38 19 10 67 16 1.4 9.8 5.4 4.4 .3 19 69 44 15 76 2 2 1 . 2 9.0 4.9 4.1 .2 18 48 30 13 1 2 . 6 4. 5 .24 .77 .53 .44 .05 8 . 6 18.8 1 1 . 8 5 44444444444 a Unscheduled sacrifice on Day 179. 675 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 182 26 -WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T- 6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 28 32 35 52 41 27 23 26 30 26 33 69 32 6.2 6 39 17. 9 6 Dose Level: 0.03 19 16 34 35 29 34 27 31 27 6.2 4 29 8 .8 4 Dose Level: 0.15 30 39 21 20 39 51 2 2 58 50 69 51 43 36 13.3 6 47 16. 9 6 Dosage Unit: mg/kg/day 756 420 628 776 1322 510 169 126 149 72 266 118 2 5 10 3 7 11 735 318.7 6 150 65.6 6 6 3. 7 6 Dosage Unit: mg/kg/day 548 552 1085 233 136 100 182 87 2 6 2 4 604 353.5 4 126 42.6 4 4 1 .9 4 Dosage Unit: mg/kg/day 650 634 558 697 1035 557 171 133 115 95 125 250 4 3 7 3 13 5 688 178.3 6 148 55.8 6 6 3. 8 6 122 106 526 207 159 140 210 158. 7 6 93 219 143 96 138 58. 8 4 118 102 116 101 296 314 174 1 0 1 .5 6 524 308 440 388 243 454 393 1 0 2 .8 6 379 646 391 354 442 136. 5 4 412 431 336 472 397 240 381 82. 3 6 15 37 19 30 22 51 29 13.4 6 15 37 15 27 24 10.6 4 36 7 36 36 37 27 30 11.8 6 373 210 281 298 194 327 280 6 8 .5 6 260 443 329 224 314 96. 4 4 234 333 256 337 277 184 270 59. 0 6 676 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05506 a I05507 I05511 I05512 I05522 MEAN S.D. N Dose Level: 0.75 73 29 30 46 41 25 36 44 30 73 34 5. 3 4 47 19. 7 4 Dosage Unit: mg/kg/day 876 134 208 110 344 101 422 71 581 132 10 2 4 3 2 389 155.7 4 104 25.3 4 3 1.0 4 4040 192 101 175 258 182 64..5 4 738 474 524 379 408 446 65.3 4 67 17 27 32 68 36 22.2 4 432 344 339 297 299 320 25.2 4 a Unscheduled sacrifice on Day 179. 677 Appendix 4 Individual Clinical Chemistry Data Males Day 182 26-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 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level : 0 10.1 10.9 10.2 9.7 10.5 9.9 6.8 5.5 6.5 6.2 7.7 5.6 10.2 .43 6 6.4 .82 6 Dose Level : 0 .03 9.9 9.9 9.9 10.3 5.7 5.3 7.1 4.9 10.0 .20 4 5.8 .96 4 Dose Level : 0 .15 10.8 9.7 10.2 10.2 10.1 9.7 5.0 6.5 6.1 6.3 7.5 5.8 10.1 .41 6 6.2 .82 6 Dosage Unit: mg/kg/day 156 4.7 1 1 1 160 5.3 113 149 5.2 1 1 2 151 5.2 109 159 5.2 1 1 2 150 4.9 1 1 0 154 4.8 6 5.1 .23 6 111 1 6 Dosage Unit: mg/kg/day 157 5.1 1 1 2 155 4.8 107 154 4.7 109 157 5.4 108 156 1.5 4 5.0 .32 4 109 2 4 Dosage Unit: mg/kg/day 157 4.8 1 1 2 152 4.9 113 147 5.4 107 158 5.2 1 1 2 158 5.2 1 1 0 150 4.8 106 154 4.7 6 5.0 .25 6 110 2 6 Covance 6329-223 3M T-6295.7 678 Appendix 4 Individual Clinical Chemistry Data Males Day 182 26-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: 4 I05506 a I05507 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 10.6 10.1 9.6 10.3 11.1 6.9 7.2 4.4 6.1 6.7 10.3 .62 4 6.1 1.22 4 Dosage Unit: mg/kg/day 157 7.5 1 1 1 144 5.5 99 152 5.2 1 1 1 157 5.6 109 158 5.4 106 153 6.4 4 5.4 .17 4 106 5 4 a Unscheduled sacrifice on Day 179. Covance 6329-223 3M T-6295.7 679 ANIMAL NUMBER Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 35 23 .8 8 . 0 4.4 3.6 .9 58 2 1 1.3 9.6 5.5 4.1 .3 68 2 2 1 . 2 8.4 4.5 3.9 .4 44 16 1 . 2 9.4 4.7 4.7 .3 75 2 2 1 . 2 9.5 4.4 5.1 .4 65 14 1 . 0 8.7 4.6 4.1 .2 5 87 46 32 6 181 48 71 6 176 74 59 6 226 72 60 7 143 55 43 6 149 44 73 58 15.2 6 20 3. 7 6 1.1 .18 6 8.9 .66 6 4.7 .42 6 4.2 .55 6 .4 .25 6 6 160 6 46. 5 66 56 13. 3 6 56 16 0 6 Dose Level : 0 .03 Dosage Unit: mg/kg/day 62 18 1 . 1 9.1 4.6 4.5 .5 58 18 1 . 2 9.3 4.7 4.6 .8 53 19 .8 7.6 3.7 3.9 .2 44 25 1 . 0 8.5 4.6 3.9 .5 4 99 53 33 6 143 66 54 4 109 31 42 7 138 45 37 54 7.8 4 20 3. 4 4 1.0 .17 4 8.6 .76 4 4.4 .47 4 4.2 .38 4 .5 .24 4 5 1 .5 4 122 2 1 .6 4 49 14. 7 4 42 91 4 Dose Level : 0 .15 Dosage Unit: mg/kg/day 80 17 1 . 1 9.2 5.0 4.2 .4 10 130 44 25 63 17 .9 8 . 6 4.6 4.0 .3 7 98 26 34 66 18 1 . 1 9.0 4.3 4.7 .4 6 154 68 58 56 2 1 1 . 0 8.4 4.7 3.7 .5 1 1 137 56 38 55 16 .9 8.5 4.3 4.2 .3 7 108 37 38 66 24 1 . 0 9.6 4.0 5.6 .3 7 149 61 25 64 9.0 6 19 3. 1 6 1.0 .09 6 8.9 .47 6 4.5 .35 6 4.4 .67 6 .4 .08 6 8 2 .0 6 129 2 2 .3 6 49 15. 8 6 36 12 6 680 ANIMAL NUMBER Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N GLU MG/DL Appendix 4 Individual Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level: 0.75 Dosage Unit: mg/kg/day 78 23 1 . 2 9.1 4.8 4.3 74 2 2 1.4 9.4 4.8 4.6 86 12 1 . 2 9.9 4.0 5.9 67 18 1 . 1 9.1 4.7 4.4 80 2 2 1 . 1 9.2 4.4 4.8 55 25 .9 8 . 8 4.6 4.2 .2 5 8 8 46 2 2 .2 6 93 77 15 .2 5 67 34 2 1 .3 12 76 45 1 1 .2 4 66 67 26 .4 1 1 1 0 2 50 31 73 11.0 6 20 4.7 6 1.2 .16 6 9.2 .37 6 4.6 .31 6 4.7 .63 6 .2 .08 6 7 82 53 2 1 3.4 14.7 15.8 7 6666 681 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 91 262 30 55 25 42 37 56 39 61 26 47 41 25.0 6 87 85. 9 6 Dose Level: 0 .03 58 61 34 60 26 55 50 1 1 1 42 14.6 4 72 26. 3 4 Dose Level: 0.15 34 38 29 32 2 1 43 59 126 42 35 35 43 37 13.0 6 53 36.1 6 Dosage Unit: mg/kg/day 169 86 274 113 243 81 554 172 237 182 2 2 2 48 10 2 4 5 7 2 283 137.1 6 114 53.3 6 5 3.1 6 Dosage Unit: mg/kg/day 207 260 218 70 296 50 236 65 3 2 5 15 239 39.7 4 111 99.5 4 6 6.0 4 Dosage Unit: mg/kg/day 228 102 363 69 118 74 219 41 303 65 295 76 5 5 2 3 14 13 254 85.3 6 71 19.7 6 7 5.2 6 151 197 84 287 134 422 212 123.4 6 2745 209 147 190 823 1281.8 4 167 95 238 321 109 164 182 84.7 6 350 282 407 351 530 345 378 84.6 6 254 337 347 496 358 100.7 4 372 430 302 514 335 683 439 140.9 6 19 16 103 14 41 0 32 37.1 6 14 12 8 41 19 15.0 4 56 52 42 29 0 17 33 21.6 6 252 158 274 234 355 275 258 64 6 184 252 265 341 260 64 4 204 272 232 323 226 505 294 111.7 6 682 ANIMAL NUMBER Appendix 4 Individual Clinical Chemistry Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level: 0.75 33 43 33 34 31 38 25 37 32 59 44 53 33 6 .2 6 44 9. 9 6 Dosage Unit: mg/kg/day 243 107 245 43 659 58 217 48 2 1 2 63 320 65 4 1 4 2 5 4 316 172.4 6 64 22.7 6 3 1.5 6 253 203 189 296 515 251 284 119.3 6 337 467 408 399 279 358 375 64.9 6 29 9 19 68 42 20 31 21.2 6 256 338 277 252 213 300 273 43.1 6 683 Appendix 4 Individual Clinical Chemistry Data Females Day 182 26-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 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level : 0 9.1 11.1 9.8 10.6 10.2 10.1 4.5 6.1 5.2 6.1 5.7 4.1 10.2 .68 6 5.3 .84 6 Dose Level : 0 .03 9.2 10.9 9.1 9.4 4.2 4.2 5.0 4.3 9.6 .84 4 4.4 .39 4 Dose Level : 0 .15 9.7 9.6 9.8 9.9 9.6 10.0 5.4 3.3 5.8 3.7 4.6 5.9 9.8 .16 6 4.8 1.10 6 Dosage Unit: mg/kg/day 142 4.5 1 0 2 159 6 . 1 1 1 2 155 5.1 108 159 5.0 1 1 2 160 5.4 115 158 5.7 115 156 6.8 6 5.3 .56 6 111 5 6 Dosage Unit: mg/kg/day 148 3.9 106 163 6 . 1 114 149 4.5 1 1 0 149 4.5 107 152 7.2 4 4.8 .94 4 109 3 4 Dosage Unit: mg/kg/day 155 4.8 1 1 0 149 4.4 108 155 5.1 1 1 0 156 5.1 1 1 2 151 5.0 113 158 5.5 1 1 0 154 3.3 6 5.0 .37 6 110 1 6 Covance 6329-223 3M T-6295.7 684 Appendix 4 Individual Clinical Chemistry Data Females Day 182 26-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: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 9.3 10.8 10.9 9.9 11.0 10.0 4.7 5.3 5.3 4.4 6.6 5.0 10.3 .69 6 5.2 .76 6 Dosage Unit: mg/kg/day 148 4.3 109 160 6 . 6 113 162 5.9 1 1 2 155 5.0 106 158 5.7 107 155 4.9 113 156 4.9 6 5.4 .82 6 110 3 6 Covance 6329-223 3M T-6295.7 685 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 59 12 1 . 1 7.9 4.6 3.3 .6 1 1 1 1 2 43 49 55 19 1 . 0 8 . 2 4.7 3.5 .4 13 152 44 67 57 16 1 . 0 8 . 0 4.6 3.4 .5 12 132 44 58 2 . 8 4.9 .07 .21 .07 .14 .14 1.4 28.3 .7 12.7 22222222222 Dose Level : 0 .15 Dosage Unit: mg/kg/day 61 17 .8 8.7 5.1 3.6 78 17 1 . 0 9.3 5.1 4.2 .8 16 184 .5 16 131 37 75 41 47 70 17 .9 9.0 5.1 3.9 .6 16 158 39 61 12.0 .0 .14 .42 .00 .42 .21 .0 37.5 2 . 8 19.8 22222222222 Dose Level : 0 .75 Dosage Unit: mg/kg/day 70 13 1 . 0 8.7 4.3 4.4 .6 12 140 46 33 76 16 1 . 1 8.7 4.8 3.9 .6 17 134 92 2 2 73 14 1 . 0 8.7 4.6 4.2 .6 14 137 69 28 4.2 2 . 1 .07 .00 .35 .35 .00 3.5 4.2 32.5 7.8 22222222222 686 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 19 23 24 28 22 3.5 2 26 3.5 2 Dose Level: 0.15 43 45 31 42 37 8.5 2 44 2.1 2 Dose Level: 0.75 36 28 29 68 32 4.9 2 48 28.3 2 Dosage Unit: mg/kg/day 709 1156 62 237 3 4 932 316.1 2 150 123.7 2 4 .7 2 Dosage Unit: mg/kg/day 917 186 669 89 11 13 793 175.4 2 138 68.6 2 12 1.4 2 Dosage Unit: mg/kg/day 538 127 499 159 1 2 518 27.6 2 143 22.6 2 2 .7 2 84 194 139 77.8 2 177 146 162 21.9 2 177 223 200 32.5 2 400 276 338 87.7 2 424 484 454 42.4 2 543 467 505 53.7 2 30 41 36 7.8 2 48 45 46 2.1 2 23 53 38 21.2 2 292 209 250 58 2 244 332 288 62 2 362 329 346 23 2 687 APPENDIX 4 Individual Clinical Chemistry Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level : 0 9.6 10.4 5.5 7.1 10.0 .57 2 6.3 1.13 2 Dose Level : 0 .15 11.5 10.4 6.6 6.6 11.0 .78 2 6.6 .00 2 Dose Level : 0 .75 10.6 10.9 5.4 7.0 10.8 .21 2 6.2 1.13 2 Dosage Unit: mg/kg/day 150 4.6 1 1 2 154 5.3 1 1 0 152 2.8 2 5.0 .49 2 111 1 2 Dosage Unit: mg/kg/day 156 5.5 1 1 0 154 5.1 106 155 1.4 2 5.3 .28 2 108 2 2 Dosage Unit: mg/kg/day 157 5.4 1 1 2 161 5.5 1 1 0 159 2.8 2 5.4 .07 2 111 1 2 Covance 6329-223 3M T-6295.7 688 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 51 19 .7 8.3 4.4 3.9 .7 13 86 108 33 67 12 .9 8.9 4.7 4.2 .1 15 152 37 74 59 11.3 2 16 4.9 2 .8 8 . 6 4.6 .14 .42 .21 222 4.0 .21 2 .4 14 119 72 54 .42 1.4 46.7 50.2 29.0 22222 Dose Level : 0.15 Dosage Unit: mg/kg/day 76 19 1 . 0 8 . 6 4.1 4.5 .6 14 142 59 61 77 16 1 . 0 8 . 8 4.0 4.8 .6 13 148 52 26 76 18 1 . 0 8.7 4.0 4.6 .6 14 145 56 44 .7 2.1 .00 .14 .07 .21 .00 .7 4.2 4.9 24.7 22222222222 Dose Level : 0.75 Dosage Unit: mg/kg/day 82 2 1 1 . 1 9.6 5.0 4.6 68 25 .8 9.0 4.2 4.8 .6 14 135 .5 24 131 62 25 93 42 75 23 1 . 0 9.3 4.6 4.7 .6 19 133 78 34 9.9 2.8 .21 .42 .57 .14 .07 7.1 2 . 8 21.9 1 2 . 0 22222222222 689 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 35 1 2 0 34 86 34 .7 2 103 24..0 2 Dose Level: 0 .15 19 43 33 54 26 9.9 2 48 7..8 2 Dose Level: 0 .75 23 38 23 61 23 .0 2 50 16. 3 2 Dosage Unit: mg/kg/day 161 81 208 41 4 5 184 33.2 2 61 28.3 2 4 .7 2 Dosage Unit: mg/kg/day 113 69 251 72 1 7 182 97.6 2 70 2.1 2 4 4.2 2 Dosage Unit: mg/kg/day 241 200 121 68 2 5 220 29.0 2 94 37.5 2 4 2.1 2 157 117 137 28.3 2 117 1197 657 763.7 2 144 186 165 29.7 2 377 309 343 48.1 2 313 658 486 244.0 2 394 296 345 69.3 2 26 0 13 18.4 2 48 17 32 21.9 2 35 41 38 4.2 2 257 232 244 17 2 235 466 350 163 2 289 222 256 47 2 690 APPENDIX 4 Individual Clinical Chemistry Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level : 0 9.7 5.9 9.9 3.7 9.8 .14 2 4.8 1.56 2 Dose Level : 0.15 9.9 5.7 9.7 5.3 9.8 .14 2 5.5 .28 2 Dose Level : 0.75 10.4 10.2 5.4 6.3 10.3 .14 2 5.8 .64 2 Dosage Unit: mg/kg/day 145 5.0 103 152 5.9 1 1 2 148 4.9 2 5.4 .64 2 108 6 2 Dosage Unit: mg/kg/day 155 5.5 1 1 2 150 5.5 109 152 3.5 2 5.5 .00 2 110 2 2 Dosage Unit: mg/kg/day 152 5.2 1 1 1 152 4.9 108 152 .0 2 5.0 .21 2 110 2 2 Covance 6329-223 3M T-6295.7 691 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 116 15 1 . 2 8 . 8 4.9 3.9 .5 86 17 1 . 0 8 . 6 4.8 3.8 .4 8 114 28 73 9 155 38 81 101 21.2 2 16 1.4 2 1.1 .14 2 8.7 .14 2 4.8 .07 2 3.8 .07 2 .4 .07 2 8 .7 2 134 29.0 2 33 7.1 2 77 57 2 Dose Level : 0 .15 Dosage Unit: mg/kg/day 79 17 1 . 2 9.1 5.3 3.8 .8 5 193 44 103 83 17 1 . 0 8.9 5.2 3.7 .4 1 1 128 52 65 81 2.8 2 17 .0 2 1.1 .14 2 9.0 .14 2 5.2 .07 2 3.8 .07 2 .6 .28 2 8 160 4.2 46.0 22 48 5.7 2 84 26 9 2 Dose Level : 0 .75 Dosage Unit: mg/kg/day 61 16 1 . 0 8 . 6 4.4 4.2 84 18 1 . 0 9.1 4.9 4.2 .4 7 132 .4 15 139 56 54 71 51 72 17 1 . 0 8 . 8 4.6 4.2 .4 1 1 136 64 52 16.3 1.4 .00 .35 .35 .00 .00 5.7 4.9 10.6 2 22222222222 692 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 24 27 30 28 27 4.2 2 28 7 2 Dose Level: 0.15 49 40 19 40 34 21.2 2 40 0 2 Dose Level: 0.75 42 33 49 73 46 4.9 2 53 28. 3 2 Dosage Unit: mg/kg/day 664 1137 68 220 2 6 900 334.5 2 144 107.5 2 4 2.8 2 Dosage Unit: mg/kg/day 882 186 793 98 6 1 838 62.9 2 142 62.2 2 4 3.5 2 Dosage Unit: mg/kg/day 736 156 625 176 1 6 680 78.5 2 166 14.1 2 4 3.5 2 145 209 177 45.3 2 189 124 156 46.0 2 178 336 257 111.7 2 409 307 358 72.1 2 422 503 462 57.3 2 628 460 544 118.8 2 33 52 42 13.4 2 22 52 37 21.2 2 17 48 32 21.9 2 306 234 270 50 2 241 353 297 79 2 410 333 372 54 2 693 APPENDIX 4 Individual Clinical Chemistry Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level : 0 9.9 10.4 6.2 7.1 10.2 .35 2 6.6 .64 2 Dose Level : 0.15 11.3 10.5 10.9 .57 2 6.5 6.8 6.6 .21 2 Dose Level : 0.75 10.4 11.3 6.2 7.8 10.8 .64 2 7.0 1.13 2 Dosage Unit: mg/kg/day 152 5.0 117 157 5.0 117 154 3.5 2 5.0 .00 2 117 2 Dosage Unit: mg/kg/day 160 5.2 118 159 5.1 116 160 .7 2 5.2 .07 2 117 1 2 Dosage Unit: mg/kg/day 159 5.0 118 164 5.4 114 162 3.5 2 5.2 .28 2 116 2 2 Covance 6329-223 3M T-6295.7 694 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 48 2 0 .7 8.5 4.5 4.0 .8 8 94 61 52 68 15 1 . 2 9.4 4.7 4.7 .3 10 168 53 88 58 14.1 2 18 3.5 2 1.0 .35 2 9.0 .64 2 4.6 .14 2 4.4 .49 2 .6 .35 2 9 131 1.4 52.3 22 57 5.7 2 70 25.5 2 Dose Level : 0.15 Dosage Unit: mg/kg/day 83 19 1 . 1 8 . 8 4.0 4.8 .5 12 163 72 91 91 2 1 .9 9.2 4.2 5.0 .3 10 138 70 52 87 2 0 1 . 0 9.0 4.1 4.9 .4 1 1 150 71 72 5.7 1.4 .14 .28 .14 .14 .14 1.4 17.7 1.4 27.6 22222222222 Dose Level : 0.75 Dosage Unit: mg/kg/day 92 2 2 1.3 9.8 5.0 4.8 91 2 2 1 . 2 9.0 4.4 4.6 .2 19 151 61 54 .3 1 1 147 129 73 92 2 2 1 . 2 9.4 4.7 4.7 .2 15 149 95 64 .7 .0 .07 .57 .42 .14 .07 5.7 2 . 8 48.1 13.4 22222222222 695 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 42 158 29 74 36 9.2 2 116 59.4 2 Dose Level: 0 .15 24 61 37 71 30 9.2 2 66 7.1 2 Dose Level: 0 .75 28 41 2 2 39 25 4.2 2 40 1.4 2 Dosage Unit: mg/kg/day 160 73 203 44 2 3 182 30.4 2 58 20.5 2 2 .7 2 Dosage Unit: mg/kg/day 113 77 262 83 1 5 188 105.4 2 80 4.2 2 3 2.8 2 Dosage Unit: mg/kg/day 249 121 224 74 2 1 236 17.7 2 98 33.2 2 2 .7 2 204 132 168 50.9 2 120 663 392 384.0 2 168 129 148 27.6 2 363 295 329 48.1 2 311 654 482 242.5 2 385 277 331 76.4 2 21 0 10 14.8 2 46 21 34 17.7 2 113 19 66 66.5 2 261 222 242 27 2 235 458 346 157 2 289 212 250 54 2 696 APPENDIX 4 Individual Clinical Chemistry Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level : 0 9.6 4.8 9.8 4.4 9.7 .14 2 4.6 .28 2 Dose Level : 0.15 9.5 10.2 5.6 5.2 9.8 .49 2 5.4 .28 2 Dose Level : 0.75 10.2 11.0 4.9 5.9 10.6 .57 2 5.4 .71 2 Dosage Unit: mg/kg/day 147 4.5 1 1 1 153 4.8 118 150 4.2 2 4.6 .21 2 114 4 2 Dosage Unit: mg/kg/day 148 4.9 117 155 5.9 1 2 0 152 4.9 2 5.4 .71 2 118 2 2 Dosage Unit: mg/kg/day 155 4.8 116 166 6 . 2 125 160 7.8 2 5.5 .99 2 120 6 2 Covance 6329-223 3M T-6295.7 697 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 80 13 1.3 8 . 8 4.8 4.0 54 18 1 . 1 8 . 2 4.6 3.6 .7 .1 3 112 25 54 2 149 47 75 67 18.4 2 16 3.5 2 1.2 .14 2 8.5 .42 2 4.7 .14 2 3.8 .28 2 .4 .42 2 2 .7 2 130 26.2 2 36 15.6 2 64 14.8 2 Dose Level : 0 .15 Dosage Unit: mg/kg/day 76 18 .9 9.0 5.2 3.8 72 2 0 1 . 1 8.7 4.9 3.8 .5 1 1 203 .3 7 132 38 94 57 57 74 2.8 2 19 1.4 2 1.0 .14 2 8.8 .21 2 5.0 .21 2 3.8 .00 2 .4 .14 2 9 168 2 . 8 50.2 22 48 13.4 2 76 26.2 2 Dose Level : 0 .75 Dosage Unit: mg/kg/day 63 2 0 1 . 0 8 . 8 4.5 4.3 76 15 1.3 8.9 5.1 3.8 .4 5 135 .2 1 0 143 58 45 91 35 70 9.2 2 18 3.5 2 1.2 .21 2 8.8 .07 2 4.8 .42 2 4.0 .35 2 .3 .14 2 8 139 3.5 5.7 22 74 23.3 2 40 7.1 2 698 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 19 31 37 39 28 12.7 2 35 5.7 2 Dose Level: 0 .15 31 42 2 2 36 26 6.4 2 39 4.2 2 Dose Level: 0 .75 41 39 36 69 38 3.5 2 54 21.2 2 Dosage Unit: mg/kg/day 552 1131 60 188 4 10 842 409.4 2 124 90.5 2 7 4.2 2 Dosage Unit: mg/kg/day 925 195 776 96 2 6 850 105.4 2 146 70.0 2 4 2.8 2 Dosage Unit: mg/kg/day 821 158 557 169 3 4 689 186.7 2 164 7.8 2 4 .7 2 151 201 176 35.4 2 157 125 141 22.6 2 167 294 230 89.8 2 368 267 318 71.4 2 414 475 444 43.1 2 572 453 512 84.1 2 31 41 36 7.1 2 41 37 39 2.8 2 18 52 35 24.0 2 277 201 239 53 2 232 338 285 75 2 377 331 354 32 2 699 APPENDIX 4 Individual Clinical Chemistry Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level : 0 10.3 10.0 5.2 6.8 10.2 .21 2 6.0 1.13 2 Dose Level : 0.15 12.0 10.3 6.2 6.5 11.2 1.20 2 6.4 .21 2 Dose Level : 0.75 10.8 11.6 5.7 7.0 11.2 .57 2 6.4 .92 2 Dosage Unit: mg/kg/day 157 5.9 116 150 5.6 115 154 4.9 2 5.8 .21 2 116 2 Dosage Unit: mg/kg/day 164 5.9 123 154 5.4 114 159 7.1 2 5.6 .35 2 118 6 2 Dosage Unit: mg/kg/day 158 5.4 115 163 5.9 1 1 2 160 3.5 2 5.6 .35 2 114 2 2 Covance 6329-223 3M T-6295.7 700 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 45 23 67 16 56 15.6 2 20 4.9 2 Dose Level : 0.15 78 19 71 23 74 4.9 2 21 2.8 2 Dose Level : 0.75 95 2 0 90 26 92 3.5 2 23 4.2 2 Dosage Unit: mg/kg/day .8 8 . 1 4.2 .8 9.3 4.6 .8 8.7 4.4 .00 .85 .28 222 Dosage Unit: mg/kg/day .8 8.7 4.0 1 . 0 9.1 4.0 .9 8.9 4.0 .14 .28 .00 222 Dosage Unit: mg/kg/day .9 9.2 4.7 1 . 1 8.7 4.1 1.0 .14 2 9.0 .35 2 4.4 .42 2 3.9 4.7 4.3 .57 2 4.7 5.1 4.9 .28 2 4.5 4.6 4.6 .07 2 1.0 .2 .6 .57 2 .5 .2 .4 .21 2 .1 .1 .1 .00 2 7 10 8 2.1 2 5 5 5 .0 2 4 7 6 2.1 2 88 170 129 58.0 2 148 139 144 6.4 2 145 144 144 .7 2 42 53 48 7.8 2 67 51 59 11.3 2 47 92 70 31.8 2 43 80 62 26.2 2 68 36 52 22.6 2 53 59 56 4.2 2 701 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 47 128 33 79 40 9.9 2 104 34.6 2 Dose Level: 0 .15 27 60 47 57 37 14.1 2 58 2.1 2 Dose Level: 0 .75 42 51 16 36 29 18.4 2 44 10.6 2 Dosage Unit: mg/kg/day 138 70 188 45 2 4 163 35.4 2 58 17.7 2 3 1.4 2 Dosage Unit: mg/kg/day 105 77 4 238 76 14 172 94.0 2 76 .7 2 9 7.1 2 Dosage Unit: mg/kg/day 244 108 208 66 6 4 226 25.5 2 87 29.7 2 5 1.4 2 167 435 301 189.5 2 113 2316 1214 1557.8 2 165 120 142 31.8 2 328 290 309 26.9 2 287 649 468 256.0 2 396 235 316 113.8 2 18 0 9 12.7 2 50 98 74 33.9 2 34 31 32 2.1 2 232 218 225 9 2 214 465 340 177 2 295 177 236 83 2 702 APPENDIX 4 Individual Clinical Chemistry Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level : 0 9.3 10.4 4.6 4.2 9.8 .78 2 4.4 .28 2 Dose Level : 0.15 9.5 5.3 9.5 5.2 9.5 .00 2 5.2 .07 2 Dose Level : 0.75 10.4 10.4 5.8 4.6 10.4 .00 2 5.2 .85 2 Dosage Unit: mg/kg/day 144 4.3 107 155 5.6 114 150 7.8 2 5.0 .92 2 110 4 2 Dosage Unit: mg/kg/day 152 5.4 115 148 4.1 107 150 2.8 2 4.8 .92 2 111 5 2 Dosage Unit: mg/kg/day 154 6 . 1 1 2 1 157 6 . 0 117 156 2.1 2 6.0 .07 2 119 2 2 Covance 6329-223 3M T-6295.7 703 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level :0 7684 19 16 71 42.2 1822.1 Dose Level : 0. 15 45 26 78 30 62 232.3 2822.8 Dose Level : 0. 75 55 76 66 142.8 18 19 18 2.7 Dosage Unit: mg/kg/day 11..23 1.2 .207 88..65 8.6 .207 4.7 4.9 4.8 .214 Dosage Unit: mg/kg/day 11..63 9.0 8.4 5.2 5.0 1..2421 8.7 .242 5.1 .214 Dosage Unit: mg/kg/day 1.2 8.2 4.4 1.7 8.9 5.0 1.4 .235 8.6 .249 4.7 .242 3.8 3.7 3.8 .207 3.8 3.4 3.6 .228 3.8 3.9 3.8 .207 ..80 .4 .257 1..22 .7 .271 ..62 .4 .228 56 109 158 6 134 2.7 342.6 67 36 52 212.9 86 209 117 7 163 21.4 652.1 48 74 61 182.4 6 137 9 136 54 127 228.1 136 2.7 90 512.6 57 81 69 172.0 91 54 72 262.2 44 34 39 27.1 704 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT .ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 34 34 42 43 38 5.7 2 38 6.4 2 Dose Level: 0.15 60 63 46 73 53 9.9 2 68 7.1 2 Dose Level: 0.75 76 59 46 92 61 21.2 2 76 23.3 2 Dosage Unit: mg/kg/day 499 1046 50 199 3 5 772 386.8 2 124 105.4 2 4 1.4 2 Dosage Unit: mg/kg/day 995 189 770 92 6 6 882 159.1 2 140 68.6 2 6 .0 2 Dosage Unit: mg/kg/day 844 156 573 158 3 1 708 191.6 2 157 1.4 2 2 1.4 2 860 1071 966 149.2 2 515 624 570 77.1 2 787 1308 1048 368.4 2 512 462 487 35.4 2 1618 976 1297 454.0 2 727 523 625 144.2 2 90 98 94 5.7 2 380 352 366 19 2 871 549 710 227.7 2 1193 731 962 326 2 36 25 30 7.8 2 503 382 442 85 2 705 APPENDIX 4 Individual Clinical Chemistry Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level : 0 10.1 10.8 5.0 5.8 10.4 .49 2 5.4 .57 2 Dose Level : 0.15 11.6 10.3 6.3 5.4 11.0 .92 2 5.8 .64 2 Dose Level : 0.75 9.9 11.2 5.0 6.6 10.6 .92 2 5.8 1.13 2 Dosage Unit: mg/kg/day 148 4.9 107 153 5.1 106 150 3.5 2 5.0 .14 2 106 .7 2 Dosage Unit: mg/kg/day 154 5.1 104 154 5.0 108 154 .0 2 5.0 .07 2 106 2 2 Dosage Unit: mg/kg/day 151 5.1 108 158 5.6 108 154 4.9 2 5.4 .35 2 108 .0 2 Covance 6329-223 3M T-6295.7 706 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 44 16 1.4 8.4 4.4 4.0 64 14 1 . 1 8.5 4.3 4.2 .9 6 89 48 .1 13 148 36 41 74 54 15 1 . 2 8.4 4.4 4.1 .5 10 118 42 58 14.1 1.4 .21 .07 .07 .14 .57 4.9 41.7 8.5 23.3 22222222222 Dose Level : 0.15 Dosage Unit: mg/kg/day 69 27 1.4 8 . 2 3.8 4.4 58 28 1 . 2 9.3 4.0 5.3 .5 1 1 141 1 0 2 74 .5 6 154 69 46 64 7.8 2 28 .7 2 1.3 .14 2 8.8 .78 2 3.9 .14 2 4.8 .64 2 .5 .00 2 8 148 3.5 9.2 22 86 23.3 2 60 19.8 2 Dose Level : 0.75 Dosage Unit: mg/kg/day 86 25 1 . 6 9.1 4.6 4.5 84 12 1.4 8 . 2 4.0 4.2 .1 .0 8 139 68 60 5 119 81 60 85 1.4 2 18 9.2 2 1.5 .14 2 8.7 .64 2 4.3 .42 2 4.4 .21 2 .0 .07 2 6 129 2 . 1 14.1 22 74 9.2 2 60 .0 2 707 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 66 97 46 77 56 14.1 2 87 14.1 2 Dose Level: 0 .15 36 71 60 85 48 17.0 2 78 9.9 2 Dose Level: 0 .75 43 70 46 155 44 2.1 2 112 60.1 2 Dosage Unit: mg/kg/day 143 82 169 39 2 5 156 18.4 2 60 30.4 2 4 2.1 2 Dosage Unit: mg/kg/day 114 67 205 79 4 9 160 64.3 2 73 8.5 2 6 3.5 2 Dosage Unit: mg/kg/day 250 105 2 2 0 55 2 1 235 21.2 2 80 35.4 2 2 .7 2 1212 1024 1118 132.9 2 602 1513 1058 644.2 2 1471 659 1065 574.2 2 390 342 366 33.9 2 386 722 554 237.6 2 448 450 449 1.4 2 0 0 0 .0 2 63 83 73 14.1 2 33 94 64 43.1 2 277 260 268 12 2 288 524 406 166 2 337 339 338 1 2 708 APPENDIX 4 Individual Clinical Chemistry Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level : 0 9.8 5.0 9.6 4.4 9.7 .14 2 4.7 .42 2 Dose Level : 0.15 9.4 10.2 4.8 5.5 9.8 .57 2 5.2 .49 2 Dose Level : 0.75 10.3 10.3 4.4 4.1 10.3 .00 2 4.2 .21 2 Dosage Unit: mg/kg/day 146 5.1 1 0 0 148 4.8 107 147 1.4 2 5.0 .21 2 104 4 2 Dosage Unit: mg/kg/day 148 5.2 107 154 5.1 109 151 4.2 2 5.2 .07 2 108 1 2 Dosage Unit: mg/kg/day 154 5.2 109 158 5.8 1 1 1 156 2.8 2 5.5 .42 2 110 1 2 Covance 6329-223 3M T-6295.7 709 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 74 17 71 24 72 2.1 2 20 4.9 2 Dose Level : 0.15 73 23 76 28 74 2.1 2 26 3.5 2 Dose Level : 0.75 63 19 76 17 70 9.2 2 18 1.4 2 Dosage Unit: mg/kg/day 1.3 8.9 5.0 1.3 8.9 5.3 1.3 .00 2 8.9 .00 2 5.2 .21 2 Dosage Unit: mg/kg/day 1 . 2 9.0 5.4 1 . 1 8 . 1 4.9 1.2 .07 2 8.6 .64 2 5.2 .35 2 Dosage Unit: mg/kg/day 1 . 1 8.3 4.5 1.3 8.5 5.0 1.2 .14 2 8.4 .14 2 4.8 .35 2 3.9 3.6 3.8 .21 2 3.6 3.2 3.4 .28 2 3.8 3.5 3.6 .21 2 .7 .3 .5 .28 2 1.1 .5 .8 .42 2 .6 .3 .4 .21 2 5 6 6 .7 2 7 6 6 .7 2 6 3 4 2.1 2 105 148 126 30.4 2 206 127 166 55.9 2 116 122 119 4.2 2 35 46 40 7.8 2 33 64 48 21.9 2 36 66 51 21.2 2 51 71 61 14.1 2 93 54 74 27.6 2 41 34 38 4.9 2 710 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 46 45 53 38 50 4.9 2 42 4.9 2 Dose Level: 0.15 64 63 55 70 60 6.4 2 66 4.9 2 Dose Level: 0.75 62 48 58 84 60 2.8 2 66 25.5 2 Dosage Unit: mg/kg/day 387 1040 53 222 3 8 714 461.7 2 138 119.5 2 6 3.5 2 Dosage Unit: mg/kg/day 915 188 725 98 9 8 820 134.4 2 143 63.6 2 8 .7 2 Dosage Unit: mg/kg/day 765 154 479 156 6 2 622 202.2 2 155 1.4 2 4 2.8 2 2123 2151 2137 19.8 2 1243 1747 1495 356.4 2 617 2004 1310 980.8 2 388 363 376 17.7 2 1640 948 1294 489.3 2 616 415 516 142.1 2 38 37 38 .7 2 298 246 272 36.8 2 793 365 579 302.6 2 1207 710 958 351.4 2 35 31 33 2.8 2 414 302 358 79.2 2 711 APPENDIX 4 Individual Clinical Chemistry Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 10.3 11.0 4.2 5.2 10.6 .49 2 4.7 .71 2 Dose Level: 0.15 11.9 9.9 5.7 5.5 10.9 1.41 2 5.6 .14 2 Dose Level: 0.75 10.2 10.9 5.2 4.6 10.6 .49 2 4.9 .42 2 Dosage Unit: mg/kg/day 154 5.3 1 1 1 157 5.5 1 1 1 156 2.1 2 5.4 .14 2 111 2 Dosage Unit: mg/kg/day 160 5.8 113 150 5.1 109 155 7.1 2 5.4 .49 2 111 2 2 Dosage Unit: mg/kg/day 153 5.9 113 156 5.0 108 154 2.1 2 5.4 .64 2 110 3 2 Covance 6329-223 3M T-6295.7 712 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 54 56 21 18 55 1.4 2 20 2.1 2 Dose Level : 0.15 66 22 80 26 73 9.9 2 24 2.8 2 Dose Level : 0.75 91 2 1 85 25 88 4.2 2 23 2.8 2 Dosage Unit: mg/kg/day .9 8.9 4.7 1 . 1 9.0 4.7 1.0 .14 2 9.0 .07 2 4.7 .00 2 Dosage Unit: mg/kg/day 1 . 1 8.3 3.8 1 . 0 9.1 4.0 1.0 .07 2 8.7 .57 2 3.9 .14 2 Dosage Unit: mg/kg/day 1 . 2 9.2 4.9 1 . 1 8 . 1 4.0 1.2 .07 2 8.7 .78 2 4.4 .64 2 4.2 4.3 4.2 .07 2 4.5 5.1 4.8 .42 2 4.3 4.1 4.2 .14 2 1.1 .4 .8 .49 2 .8 .7 .8 .07 2 .3 .4 .4 .07 2 5 6 6 .7 2 6 6 6 .0 2 13 5 9 5.7 2 112 162 137 35.4 2 136 138 137 1.4 2 152 131 142 14.8 2 56 42 49 9.9 2 66 43 54 16.3 2 55 95 75 28.3 2 40 79 60 27.6 2 71 36 54 24.7 2 55 66 60 7.8 2 713 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 1 1 0 297 61 106 86 34.6 2 202 135.1 2 Dose Level: 0.15 37 61 62 95 50 17.7 2 78 24.0 2 Dose Level: 0.75 67 78 45 83 56 15.6 2 80 3.5 2 Dosage Unit: mg/kg/day 157 109 167 45 7 5 162 7.1 2 77 45.3 2 6 1.4 2 Dosage Unit: mg/kg/day 109 78 8 188 80 15 148 55.9 2 79 1.4 2 12 4.9 2 Dosage Unit: mg/kg/day 243 117 213 56 5 3 228 21.2 2 86 43.1 2 4 1.4 2 2978 1838 2408 806.1 2 733 1009 871 195.2 2 2353 1241 1797 786.3 2 459 338 398 85.6 2 304 630 467 230.5 2 527 431 479 67.9 2 33 0 16 23.3 2 42 52 47 7.1 2 47 47 47 .0 2 336 265 300 50 2 231 459 345 161 2 412 329 370 58 2 714 APPENDIX 4 Individual Clinical Chemistry Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 9.7 10.1 5.6 4.2 9.9 .28 2 4.9 .99 2 Dose Level: 0.15 9.0 4.8 9.9 4.7 9.4 .64 2 4.8 .07 2 Dose Level: 0.75 10.5 10.0 4.6 4.3 10.2 .35 2 4.4 .21 2 Dosage Unit: mg/kg/day 144 4.3 103 151 5.6 109 148 4.9 2 5.0 .92 2 106 4 2 Dosage Unit: mg/kg/day 146 4.9 108 151 5.9 1 1 1 148 3.5 2 5.4 .71 2 110 2 2 Dosage Unit: mg/kg/day 153 5.3 1 1 1 157 5.6 113 155 2.8 2 5.4 .21 2 112 1 2 Covance 6329-223 3M T-6295.7 715 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 80 12 68 16 74 8.5 2 14 2.8 2 Dose Level : 0 .15 88 15 94 17 91 4.2 2 16 1.4 2 Dose Level : 0 .75 64 13 75 14 70 7.8 2 14 .7 2 Dosage Unit: mg/kg/day 1 . 2 8.9 5.2 1 . 2 8.5 4.9 1.2 .00 2 8.7 .28 2 5.0 .21 2 Dosage Unit: mg/kg/day 1 . 2 9.3 5.4 1 . 1 8.9 5.5 1.2 .07 2 9.1 .28 2 5.4 .07 2 Dosage Unit: mg/kg/day 1 . 0 8.5 4.5 1.3 9.3 5.4 1.2 .21 2 8.9 .57 2 5.0 .64 2 3.7 3.6 3.6 .07 2 3.9 3.4 3.6 .35 2 4.0 3.9 4.0 .07 2 .8 .3 .6 .35 2 .6 .3 .4 .21 2 .8 .3 .6 .35 2 3 3 3 0 2 5 6 6 7 2 4 3 4 7 2 122 142 132 14.1 2 216 139 178 54.4 2 122 114 118 5.7 2 31 32 32 .7 2 39 43 41 2.8 2 37 81 59 31.1 2 56 61 58 3.5 2 106 55 80 36.1 2 44 26 35 12.7 2 716 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 19 2 1 29 26 24 7.1 2 24 3.5 2 Dose Level: 0.15 29 46 2 1 45 25 5.7 2 46 .7 2 Dose Level: 0.75 37 32 30 50 34 4.9 2 41 12.7 2 Dosage Unit: mg/kg/day 394 59 847 189 2 10 620 320.3 2 124 91.9 2 6 5.7 2 Dosage Unit: mg/kg/day 971 198 771 101 2 1 871 141.4 2 150 68.6 2 2 .7 2 Dosage Unit: mg/kg/day 458 129 379 148 1 0 418 55.9 2 138 13.4 2 0 .7 2 77 126 102 34.6 2 163 119 141 31.1 2 179 225 202 32.5 2 319 276 298 30.4 2 413 487 450 52.3 2 480 364 422 82.0 2 11 21 16 7.1 2 14 17 16 2.1 2 20 13 16 4.9 2 246 220 233 18.4 2 235 353 294 83.4 2 326 263 294 44.5 2 717 APPENDIX 4 Individual Clinical Chemistry Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 10.4 10.1 5.7 6.4 10.2 .21 2 6.0 .49 2 Dose Level: 0 .15 12.6 10.9 6.6 7.2 11.8 1.20 2 6.9 .42 2 Dose Level: 0 .75 10.0 11.1 3.9 6.7 10.6 .78 2 5.3 1.98 2 Dosage Unit: mg/kg/day 156 5.7 113 150 5.1 109 153 4.2 2 5.4 .42 2 111 2 2 Dosage Unit: mg/kg/day 167 6.3 118 161 5.6 113 164 4.2 2 6.0 .49 2 116 3 2 Dosage Unit: mg/kg/day 152 4.6 113 158 5.4 109 155 4.2 2 5.0 .57 2 111 2 2 Covance 6329-223 3M T-6295.7 718 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 48 17 79 17 64 21.9 2 17 .0 2 Dose Level : 0 .15 79 16 78 18 78 .7 2 17 1.4 2 Dose Level : 0 .75 98 101 17 21 100 2.1 2 19 2.8 2 Dosage Unit: mg/kg/day .9 8.3 4.6 1 . 0 8.7 4.6 1.0 .07 2 8.5 .28 2 4.6 .00 2 Dosage Unit: mg/kg/day 1 . 0 8.4 4.1 .9 9.0 4.1 1.0 .07 2 8.7 .42 2 4.1 .00 2 Dosage Unit: mg/kg/day 1 . 1 9.1 4.9 1 . 0 8 . 2 4.1 1.0 .07 2 8.7 .64 2 4.5 .57 2 3.7 4.1 3.9 .28 2 4.3 4.9 4.6 .42 2 4.2 4.1 4.2 .07 2 1.0 .3 .6 .49 2 .6 .5 .6 .07 2 .2 .3 .2 .07 2 7 99 4 142 6 2.1 2 120 30.4 2 60 52 56 5.7 2 4 144 6 144 5 144 1.4 .0 22 83 59 71 17.0 2 5 137 42 3 139 114 4 138 1.4 1.4 22 78 50.9 2 34 67 50 23.3 2 58 36 47 15.6 2 55 72 64 12.0 2 719 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 56 183 30 85 43 18.4 2 134 69.3 2 Dose Level: 0.15 25 34 40 66 32 10.6 2 50 22.6 2 Dose Level: 0.75 25 64 25 43 25 .0 2 54 14.8 2 Dosage Unit: mg/kg/day 139 96 174 49 6 3 156 24.7 2 72 33.2 2 4 2.1 2 Dosage Unit: mg/kg/day 94 76 4 186 81 10 140 65.1 2 78 3.5 2 7 4.2 2 Dosage Unit: mg/kg/day 248 124 216 63 0 3 232 22.6 2 94 43.1 2 2 2.1 2 200 244 222 31.1 2 112 254 183 100.4 2 134 114 124 14.1 2 293 244 268 34.6 2 242 436 339 137.2 2 360 233 296 89.8 2 9 12 10 2.1 2 15 11 13 2.8 2 13 23 18 7.1 2 216 192 204 17 2 189 312 250 87 2 277 183 230 66 2 720 APPENDIX 4 Individual Clinical Chemistry Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 9.6 10.2 4.9 5.4 9.9 .42 2 5.2 .35 2 Dose Level: 0.15 9.5 10.1 5.3 5.0 9.8 .42 2 5.2 .21 2 Dose Level: 0.75 10.3 10.5 5.1 5.6 10.4 .14 2 5.4 .35 2 Dosage Unit: mg/kg/day 144 4.9 105 152 5.1 1 1 0 148 5.7 2 5.0 .14 2 108 3 2 Dosage Unit: mg/kg/day 151 5.4 1 1 1 153 5.9 1 1 2 152 1.4 2 5.6 .35 2 112 2 Dosage Unit: mg/kg/day 155 5.6 114 154 6 . 8 118 154 .7 2 6.2 .85 2 116 2 2 Covance 6329-223 3M T-6295.7 721 ANIMAL NUMBER Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 Dosage Unit: mg/kg/day 79 14 1 . 2 8.7 4.6 4.1 .5 86 18 1.3 8.9 4.8 4.1 .2 6 119 30 63 5 150 32 77 82 4.9 2 16 2.8 2 1.2 .07 2 8.8 .14 2 4.7 .14 2 4.1 .00 2 .4 .21 2 6 .7 2 134 21.9 2 31 1.4 2 70 9.9 2 Dose Level : 0 .15 Dosage Unit: mg/kg/day 77 19 1 . 2 8 . 6 4.9 3.7 .6 81 19 1 . 1 9.0 5.3 3.7 .3 5 200 3 132 31 114 40 69 79 2.8 2 19 .0 2 1.2 .07 2 8.8 .28 2 5.1 .28 2 3.7 .00 2 .4 .21 2 4 166 1.4 48.1 22 36 6.4 2 92 31.8 2 Dose Level : 0 .75 Dosage Unit: mg/kg/day 75 16 1.4 9.5 5.0 4.5 .8 4 145 37 67 83 16 1.4 9.3 5.2 4.1 .3 10 132 52 47 79 5.7 2 16 .0 2 1.4 .00 2 9.4 .14 2 5.1 .14 2 4.3 .28 2 .6 .35 2 7 138 4.2 9.2 22 44 10.6 2 57 14.1 2 722 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 19 2 0 28 30 24 6.4 2 25 7.1 2 Dose Level: 0.15 31 36 30 33 30 .7 2 34 2.1 2 Dose Level: 0.75 45 37 27 42 36 12.7 2 40 3.5 2 Dosage Unit: mg/kg/day 309 49 701 183 1 19 505 277.2 2 116 94.8 2 10 12.7 2 Dosage Unit: mg/kg/day 846 178 662 93 1 5 754 130.1 2 136 60.1 2 3 2.8 2 Dosage Unit: mg/kg/day 467 149 342 147 0 0 404 88.4 2 148 1.4 2 0 .0 2 78 144 111 46.7 2 130 212 171 58.0 2 165 165 165 .0 2 265 259 262 4.2 2 357 446 402 62.9 2 519 362 440 111.0 2 10 17 14 4.9 2 12 13 12 .7 2 22 11 16 7.8 2 203 201 202 1.4 2 206 321 264 81.3 2 334 260 297 52.3 2 723 APPENDIX 4 Individual Clinical Chemistry Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 10.8 10.5 6.5 6.6 10.6 .21 2 6.6 .07 2 Dose Level: 0.15 11.4 11.0 6.3 7.6 11.2 .28 2 7.0 .92 2 Dose Level: 0.75 12.0 11.8 5.4 6.2 11.9 .14 2 5.8 .57 2 Dosage Unit: mg/kg/day 162 6.4 1 2 0 157 5.6 1 1 1 160 3.5 2 6.0 .57 2 116 6.4 2 Dosage Unit: mg/kg/day 164 5.8 117 169 6.9 1 2 2 166 3.5 2 6.4 .78 2 120 3.5 2 Dosage Unit: mg/kg/day 174 6 . 0 1 2 1 169 6 . 2 116 172 3.5 2 6.1 .14 2 118 3.5 2 Covance 6329-223 3M T-6295.7 724 ANIMAL NUMBER Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N GLU MG/DL APPENDIX 4 Individual Clinical Chemistry Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS 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 Covance 6329-223 3M T-6295.7 HDL MG/DL Dose Level : 0 67 17 53 16 60 9.9 2 16 .7 2 Dose Level : 0 .15 71 19 74 17 72 2.1 2 18 1.4 2 Dose Level : 0 .75 100 93 19 19 96 4.9 2 19 .0 2 Dosage Unit: mg/kg/day .9 1.0 8.2 8.8 4.4 4.4 1.0 .07 2 8.5 .42 2 4.4 .00 2 Dosage Unit: mg/kg/day 1 . 1 8.5 3.9 .8 8 . 2 3.6 1.0 .21 2 8.4 .21 2 3.8 .21 2 Dosage Unit: mg/kg/day 1 . 2 9.0 4.6 1 . 2 7.9 4.0 1.2 .00 2 8.4 .78 2 4.3 .42 2 3.8 4.4 4.1 .42 2 4.6 4.6 4.6 .00 2 4.4 3.9 4.2 .35 2 .8 .3 .6 .35 2 .5 .6 .6 .07 2 .3 .3 .3 .00 2 6 5 6 .7 2 5 5 5 .0 2 6 4 5 1.4 2 96 152 124 39.6 2 147 129 138 12.7 2 145 147 146 1.4 2 55 51 53 2.8 2 73 46 60 19.1 2 40 112 76 50.9 2 44 83 64 27.6 2 86 37 62 34.6 2 68 79 74 7.8 2 725 ANIMAL NUMBER APPENDIX 4 Individual Clinical Chemistry Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS AST/SGOT ALT/SGPT ALK PHOS IU/L IU/L IU/L GGT IU/L SDH IU/L CK IU/L AMYLASE LIPASE IU/L IU/L P AMYL U/L Covance 6329-223 3M T-6295.7 Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 53 191 30 49 42 16.3 2 120 100.4 2 Dose Level: 0 .15 27 31 26 37 26 .7 2 34 4.2 2 Dose Level: 0 .75 36 79 19 39 28 12.0 2 59 28.3 2 Dosage Unit: mg/kg/day 131 93 171 45 0 0 151 28.3 2 69 33.9 2 0 .0 2 Dosage Unit: mg/kg/day 96 76 195 82 2 1 146 70.0 2 79 4.2 2 2 .7 2 Dosage Unit: mg/kg/day 240 117 186 61 3 0 213 38.2 2 89 39.6 2 2 2.1 2 216 93 154 87.0 2 80 109 94 20.5 2 164 97 130 47.4 2 316 245 280 50.2 2 252 454 353 142.8 2 372 250 311 86.3 2 11 12 12 .7 2 14 8 11 4.2 2 12 18 15 4.2 2 232 192 212 28.3 2 195 327 261 93.3 2 286 195 240 64.3 2 726 APPENDIX 4 Individual Clinical Chemistry Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER CA MG/DL I PHOS MG/DL NA MMOL/L K MMOL/L CL MMOL/L Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 10.1 10.1 5.2 5.6 10.1 .00 2 5.4 .28 2 Dose Level: 0.15 9.8 10.2 5.4 4.9 10.0 .28 2 5.2 .35 2 Dose Level: 0.75 10.3 10.7 5.9 5.4 10.5 .28 2 5.6 .35 2 Dosage Unit: mg/kg/day 150 5.1 108 152 5.3 1 1 1 151 1.4 2 5.2 .14 2 110 2 2 Dosage Unit: mg/kg/day 155 5.4 1 1 2 157 6 . 1 117 156 1.4 2 5.8 .49 2 114 3 2 Dosage Unit: mg/kg/day 159 5.6 115 165 6.7 124 162 4.2 2 6.2 .78 2 120 6 2 Covance 6329-223 3M T-6295.7 727 Appendix 4 Individual Clinical Urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 37.0 28.0 47.0 75.0 32.0 30.0 1.025 1.032 1.025 1.018 1.030 1.023 41.5 17.76 6 1.026 .0050 6 Dose Level: 0.03 67.0 46.0 52.0 45.0 1.019 1.023 1.020 1.023 52.5 10.15 4 1.021 .0021 4 Dose Level: 0.15 228.0 52.0 93.0 43.0 46.0 125.0 1.007 1.025 1.020 1.026 1.025 1.013 97.8 71.41 6 1.019 .0078 6 Dosage Unit: mg/kg/day 8.0 7.0 8.0 7.5 7.5 6.0 7.3 .75 6 Dosage Unit: mg/kg/day 7.0 7.5 7.0 8.0 7.4 .48 4 Dosage Unit: mg/kg/day 7.0 7.0 7.0 7.0 7.5 7.0 7.1 .20 6 Covance 6329-223 3M T-6295.7 728 Appendix 4 Individual Clinical Urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 43.0 59.0 68.0 173.0 92.0 66.0 1.026 1.022 1.018 1.008 1.013 1.022 83.5 46.63 6 1.018 .0066 6 Dosage Unit: mg/kg/day 7.0 7.5 7.0 7.0 7.5 7.0 7.2 .26 6 Covance 6329-223 3M T-6295.7 729 Appendix 4 Individual Clinical Urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 Group: 2 I05514 I05515 I05516 I05521 Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 Dose Level: 0 010 00+ 10 + 0- Dose Level:: 0.03 0010 10 - Dose Level:: 0.15 010 30 + 10 10 0- Dose Level: 0.75 10 010 0010 - Dosage Unit: mg/kg/day +++ +++ -- +++ +- ++ - +++ -- -- -- Dosage Unit: mg/kg/day --++ - -- + - Dosage Unit: mg/kg/day -- ---++ - -- +++ -- - Dosage Unit: mg/kg/day ++ --- -+-- + ++ - - + - - - - - - - Covance 6329-223 3M T-6295.7 730 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Males Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05508 0 0 0 3 0 2B4D 0 DK - I05517 0 0 2 3 0 2B4D 0 DK PQ I05519 0 0 0 3 0 4B4E 0 CL - I05520 0 0 1 2 0 4B4D 0 BK - I05526 0 0 1 2 0 4B3D 0 CK - I05527 0 0 0 1 0 4B3E 0 BK - Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05514 0 0 1 3 0 4B2E 0 CK - I05515 0 0 0 3 0 4B4D 4E CL - I05516 0 0 0 3 0 4B2D 0 CK - I05521 0 0 0 3 0 4B4D 0 BL - Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 0 1 2 0 3B 0 BK - I05510 0 0 0 3 0 4B4D 4E BL - I05518 0 0 4 3 0 4B 0 DL - I05523 0 0 0 3 0 4B2D 0 BL - I05524 0 0 0 3 0 3B4D 0 CK - I05528 0 0 1 3 0 4B 0 BK - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05506 2 0 1 3 0 2B2D 0 CK - I05507 0 1 0 3 0 4B4D 0 CL Q I05509 0 1 4 3 0 4B1E 0 BK Q I05511 0 0 1 3 0 4B 0 BK Q I05512 0 0 1 3 0 2B 0 BK - I05522 0 1 1 2 0 2B 0 BJ - 731 Appendix 4 Individual Clinical Urinalysis Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 52.0 100.0 57.0 45.0 240.0 50.0 1.017 1.020 1.020 1.023 1.007 1.023 90.7 75.84 6 1.018 .0060 6 ro o o Dose Level: 225.0 48.0 45.0 52.0 1.007 1.023 1.024 1.023 92.5 88.38 4 1.019 .0082 4 Dose Level: 0.15 140.0 61.0 53.0 62.0 64.0 51.0 1.012 1.023 1.026 1.018 1.020 1.025 71.8 33.80 6 1.021 .0052 6 Dosage 7.0 7.0 7.5 7.0 7.5 8.0 7.3 .41 6 Dosage 7.5 7.0 7.0 7.0 7.1 .25 4 Dosage 8.0 7.5 8.0 7.0 8.0 8.0 7.8 .42 6 mg/kg/day mg/kg/day mg/kg/day Covance 6329-223 3M T-6295.7 732 Appendix 4 Individual Clinical Urinalysis Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 35.0 59.0 64.0 247.0 72.0 51.0 1.026 1.024 1.023 1.007 1.019 1.021 88.0 78.91 6 1.020 .0068 6 Dosage Unit: mg/kg/day 7.5 8.0 7.5 7.0 7.0 7.0 7.3 .41 6 Covance 6329-223 3M T-6295.7 733 Appendix 4 Individual Clinical Urinalysis Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS, T 6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 Group: 2 I05537 I05541 I05547 I05550 Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 Dose Level: 0 0_ 10 0_ 0_ 0_ 0_ Dose Level: 0 .03 0_ 0_ 10 _ 0_ Dose Level: 0 .15 0_ 0_ 10 _ 0_ 0_ 0_ Dose Level: 0 .75 10 _ 0_ 0_ 0_ 0_ 0_ Dosage Unit: mg/kg/day ++ --++ -- -- -+ - -+ - Dosage Unit: mg/kg/day - - +++ +-- - ++ --- Dosage Unit: mg/kg/day -- +-++ +- -- ++ -- - Dosage Unit: mg/kg/day +++ --- --- +- -- - - - - - - - - Covance 6329-223 3M T-6295.7 734 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Females Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 1 1 3 1H 3B4D 0 BK P I05530 0 0 0 3 0 4B 0 DL - I05531 0 0 1 3 0 4B4D 0 CK - I05535 0 0 0 3 0 2B2D 0 CL - I05544 0 0 2 3 0 4B 0 AK - I05549 0 0 0 1 0 4B1D 1E BK - Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05537 0 0 1 3 0 I05541 0 1 1 3 0 I05547 0 0 0 3 0 I05550 0 0 1 2 0 4B4D 4B2D 2B 4B1E 0 0 0 0 BK DL DL - CK - Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05532 0 0 2 2 0 1D4F 0 BJ - I05538 0 0 1 2 0 1B1E 1F CK - I05539 0 0 1 3 0 4B 0 CK - I05545 0 0 1 2 0 4B 0 CK P I05548 0 0 0 3 0 2B 0 CL - I05552 0 0 2 3 0 4B 0 CL - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 1 2 3 0 I05534 0 0 1 2 0 I05536 0 0 1 3 0 I05540 0 0 4 3 0 I05542 0 1 1 3 0 I05551 0 0 1 3 0 2B4D 4B4D 3B3D 0 4B1E 4B1D 0 0 0 0 0 0 DK CL CL AK CK CK - 735 Appendix 4 Individual Clinical Urinalysis Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N 0Dose Level: 56.0 47.0 4686..00 26.0 58.0 1.023 11..002215 1.013 1.006 1.017 50.2 13.765 1.018 .00761 ro o o Dose Level: 62.0 108.0 38.0 82.0 1.020 1.017 1.028 1.019 72.5 29.73 4 1.021 .0048 4 Dose Level: 0.15 307.0 34.0 70.0 54.0 37.0 64.0 1.002 1.023 1.017 1.019 1.028 1.025 94.3 105.166 1.019 .00962 Dosage 8.0 78..00 7.0 7.5 7.5 7.5 .645 Dosage 7.0 78..05 7.5 7.5 .41 4 Dosage 7.0 7.5 7.5 7.5 7.0 7.0 7.2 .627 mg/kg/day mg/kg/day mg/kg/day Covance 6329-223 3M T-6295.7 736 Appendix 4 Individual Clinical Urinalysis Data Males Day 37 K CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T -6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level: 0.75 50.0 52.0 36.0 110.0 146.0 80.0 1.023 1.026 1.023 1.008 1.007 1.018 79.0 42.12 6 1.018 .0082 6 Dosage Unit: mg/kg/day 8.0 8.0 8.0 6.5 7.0 6.5 7.3 .75 6 Covance 6329-223 3M T-6295.7 737 Appendix 4 Individual Clinical Urinalysis Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 Group: 2 I05514 I05515 I05516 I05521 Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 Dose Level: 0 0_ 00_ 0_ 0_ 0_ Dose Level: 0.03 0_ 0_ 0_ 0_ Dose Level: 0.15 0_ 0_ 0_ 0_ 0_ 0_ Dose Level: 0.75 0_ 0_ 0_ 0_ 0_ 0_ Dosage Unit: mg/kg/day +++ -+++ +- -- - --- - Dosage Unit: mg/kg/day ------- --- Dosage Unit: mg/kg/day -- -+-++ - -- -- - Dosage Unit: mg/kg/day ++ -- -- +++++ - -- - -- - - - - - - - Covance 6329-223 3M T-6295.7 738 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Males Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 Dose Level: 0 00 00 00 00 00 00 Dosage Unit: mg/kg/day 12 12 02 11 01 01 0 0 0 0 0 0 4D 1D 3E3F 0 1B1D 4D 0 0 0 0 0 0 BK CK BK - BJ P BJ - BJ P Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05514 1 0 1 2 0 2E 0 BK PQ I05515 0 0 0 3 0 4B4D 0 BK P I05516 0 0 1 2 0 4B1D 0 CK - I05521 0 0 0 2 0 4B2D 1E BL - Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 0 0 0 0 1B 0 AJ Q I05510 0 0 0 3 0 4D 0 BK - I05518 0 0 0 1 0 3D 0 BK PQ I05523 0 0 1 2 0 2D3E 0 BK Q I05524 0 1 1 1 0 0 0 CK - I05528 0 0 02 0 4B1E 0 BK - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05506 0 0 1 2 0 0 0 BK P I05507 0 0 0 1 0 3B4D 0 BK Q I05509 0 0 1 1 0 0 0 BK Q I05511 0 0 0 3 0 1B 0 BJ Q I05512 0 0 0 3 0 2B 0 BJ - I05522 0 0 02 0 0 0 BK PQ 739 Appendix 4 Individual Clinical Urinalysis Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 14.0 20.0 31.0 564.0 38.0 44.0 1.010 1.003 1.026 1.001 1.020 1.021 118.5 218.53 6 1.014 .0103 6 ro o o Dose Level: 170.0 46.0 76.0 55.0 1.011 1.020 1.016 1.024 86.8 56.91 4 1.018 .0056 4 Dose Level: 0.15 78.0 186.0 66.0 85.0 47.0 40.0 1.014 1.006 1.019 1.012 1.024 1.026 83.7 53.05 6 1.017 .0076 6 Dosage 8.5 8.0 8.0 7.5 8.0 8.0 8.0 .32 6 Dosage 7.5 8.0 8.0 7.5 7.8 .29 4 Dosage 7.5 7.5 7.0 7.5 8.0 7.5 7.5 .32 6 mg/kg/day mg/kg/day mg/kg/day Covance 6329-223 3M T-6295.7 740 Appendix 4 Individual Clinical Urinalysis Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLG ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 38.0 32.0 44.0 417.0 34.0 36.0 1.024 1.026 1.028 1.003 1.025 1.026 100.2 155.27 6 1.022 .0094 6 Dosage 8.0 8.5 8.0 8.0 7.0 7.0 7.8 .61 6 Covance 6329-223 3M T-6295.7 741 Appendix 4 Individual Clinical Urinalysis Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 Group: 2 I05537 I05541 I05547 I05550 Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 Dose Level: 0 0_ 10 0_ 0_ 0_ 0_ Dose Level: 0.03 0_ 0_ 0_ 0_ Dose Level: 0.15 0_ 0_ 0_ 0_ 0_ 0_ Dose Level: 0.75 0_ 10 _ 0_ 0_ 0_ 0_ Dosage Unit: mg/kg/day --- - - ++ --- - +++ +-- --- Dosage Unit: mg/kg/day --+---- --- Dosage Unit: mg/kg/day --- ------+-- --- Dosage Unit: mg/kg/day +--- -+++ -- + - - -- - - - - - Covance 6329-223 3M T-6295.7 742 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Females Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 0 2 1 0 I05530 0 0 0 3 0 I05531 0 1 02 0 I05535 0 0 1 1 0 I05544 0 0 02 0 I05549 0 1 0 30 Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05537 0 0 1 2 0 I05541 0 0 1 2 0 I05547 0 0 0 1 0 I05550 0 0 0 1 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05532 0 1 1 2 0 I05538 0 0 2 1 0 I05539 0 0 0 3 0 I05545 0 0 1 3 0 I05548 0 0 0 3 0 I05552 0 0 1 1 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 1 1 3 0 I05534 0 0 1 1 0 I05536 0 0 0 1 0 I05540 0 0 1 2 0 I05542 0 1 1 1 0 I05551 0 1 1 2 0 1E2F 4B 3B4D 0 3B3D 1E1F 4B 4B4D 2D 1B 4B2E 3B 4B3E 4B4D 3B1D 3B1D 3B3D 2B4D 4B1D 0 3D 4B1D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1E 1E 0 3E 0 0 0 BJ P BLM CL AK BK BK - BK BK BK P BK - BK BK BK BL BK BL - BK BK P BL AK BK P BK - 743 Appendix 4 Individual Clinical Urinalysis Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 40.0 67.0 54.0 65.0 179.0 60.0 1.025 1.017 1.017 1.014 1.010 1.022 77.5 50.66 6 1.018 .0054 6 ro o o Dose Level: 44.0 69.0 28.0 108.0 1.010 1.020 1.028 1.016 62.2 34.86 4 1.018 .0076 4 Dose Level: 0.15 192.0 53.0 82.0 131.0 25.0 84.0 1.006 1.021 1.014 1.006 1.031 1.014 94.5 59.43 6 1.015 .0095 6 Dosage 8.0 8.0 8.0 7.5 8.0 8.5 8.0 .32 6 Dosage 8.5 8.0 7.5 8.0 8.0 .41 4 Dosage 8.0 8.0 8.0 7.5 8.0 7.0 7.8 .42 6 mg/kg/day mg/kg/day mg/kg/day Covance 6329-223 3M T-6295.7 744 Appendix 4 Individual Clinical Urinalysis Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 50.0 66.0 34.0 107.0 89.0 62.0 1.020 1.018 1.023 1.009 1.013 1.019 68.0 26.39 6 1.017 .0051 6 Dosage Unit: mg/kg/day 7.5 8.0 8.0 8.0 7.5 8.5 7.9 .38 6 Covance 6329-223 3M T-6295.7 745 Appendix 4 Individual Clinical Urinalysis Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS, T 6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 Group: 2 I05514 I05515 I05516 I05521 Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 Dose Level: 0 10 _ 10 0_ 0_ 0_ 10 _ Dose Level: 0 .03 0_ 10 _ 10 _ 0_ Dose Level: 0 .15 0_ 0_ 0_ 0_ 10 _ 0_ Dose Level: 0 .75 10 _ 10 _ 10 _ 0_ 0_ 10 _ Dosage Unit: mg/kg/day ++ +-+++ +- -- -- -- - Dosage Unit: mg/kg/day -- ++ ++ - -- - --- Dosage Unit: mg/kg/day -- --++++ +- +++ -- - Dosage Unit: mg/kg/day +++ --- -+++ -- -- -+++ - - - - - Covance 6329-223 3M T-6295.7 746 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Males Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05508 0 0 0 3 0 2B3D 0 CK Q I05517 0 1 1 2 0 2B2D 0 CK - I05519 0 0 1 1 0 2E 0 CK - I05520 0 0 1 2 0 2B3D 0 BK - I05526 0 0 1 2 0 2B 0 BJ - I05527 0 0 1 3 0 2B4D 0 CK - Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05514 0 0 1 2 0 2B1E 0 AJ Q I05515 0 0 1 3 0 2B4D 0 CK - I05516 0 0 1 2 0 4D 0 CK P I05521 0 0 0 3 0 3B1D 0 BK - Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 1 0 3 0 4B1D 0 AK Q I05510 0 0 0 1 0 3B4D 1E CK - I05518 0 0 1 3 0 4B3D 0 BK - I05523 0 1 1 2 0 2B 0 AK - I05524 0 0 1 2 0 2B4D 0 CK P I05528 0 0 1 2 0 3B1E 0 BK P Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05506 0 0 1 1 0 4D 0 CK Q I05507 0 0 1 2 0 4D 0 CK P I05509 0 1 1 1 0 0 0 CK P I05511 0 0 1 1 0 2B1D 0 BK Q I05512 0 0 1 2 0 1D 0 BJ - I05522 0 1 0 3 0 1B3D 0 BK - 747 Appendix 4 Individual Clinical Urinalysis Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T -6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 62.0 68.0 31.0 195.0 60.0 30.0 1.020 1.022 1.024 1.005 1.016 1.026 74.3 61.32 6 1.019 .0076 6 Dose Level: 0.03 97.0 18.0 50.0 49.0 1.015 1.028 1.018 1.021 53.5 32.58 4 1.020 .0056 4 Dose Level: 0.15 98.0 56.0 47.0 98.0 30.0 45.0 1.010 1.022 1.022 1.016 1.028 1.020 62.3 28.86 6 1.020 .0061 6 Dosage Unit: mg/kg/day 8.0 8.5 8.0 8.0 8.0 8.5 8.2 .26 6 Dosage Unit: mg/kg/day 8.0 8.0 7.5 7.0 7.6 .48 4 Dosage Unit: mg/kg/day 7.5 8.0 8.0 8.0 7.5 8.0 7.8 .26 6 Covance 6329-223 3M T-6295.7 748 Appendix 4 Individual Clinical Urinalysis Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLG ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 45.0 115.0 42.0 158.0 99.0 27.0 1.020 1.011 1.024 1.010 1.007 1.030 81.0 51.27 6 1.017 .0091 6 Dosage 7.5 8.0 7.5 8.0 7.5 7.0 7.6 .38 6 Covance 6329-223 3M T-6295.7 749 Appendix 4 Individual Clinical Urinalysis Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS,; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 Group: 2 I05537 I05541 I05547 I05550 Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 Dose Level: 0 10 10 00010 - Dose Level: 0 .03 10 10 10 10 - Dose Level: 0 .15 10 10 10 010 10 - Dose Level: 0 .75 10 010 0010 - Dosage Unit: mg/kg/day ++++ - + - ++ - - - -+++ -- - Dosage Unit: mg/kg/day - ++++ ++++ - - - --- Dosage Unit: mg/kg/day + - +++ - ++++ +++ - - - -- --- Dosage Unit: mg/kg/day +-+--- +++ - - -- - - - - Covance 6329-223 3M T-6295.7 750 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Females Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 0 1 2 0 I05530 1 0 1 3 0 I05531 0 1 1 2 0 I05535 0 0 1 2 0 I05544 0 0 1 1 0 I05549 0 0 1 3 0 Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05537 0 0 1 2 0 I05541 0 1 1 3 0 I05547 0 1 1 1 0 I05550 0 1 2 1 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05532 0 42 1 0 I05538 0 0 1 2 0 I05539 0 1 2 1 0 I05545 0 0 1 1 0 I05548 0 1 1 3 0 I05552 0 1 02 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 1 1 1 2 0 I05534 0 0 2 3 0 I05536 0 1 1 1 0 I05540 0 1 1 3 0 I05542 0 1 1 3 0 I05551 0 1 1 3 0 4D 4B 2B3D 0 4D1E 2B1D 2B4D 4B4D 4B2D 2D 0 3B3D 4D 4B1D 4D 2B2D 4B2D 4D 3D1E 1B 2B3D 2B4D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 CK P CK CK BJ P BK CK - BK P CK P CK P CK P BJ P CK CK P BK CK P CK - CK BK P CK P BK AJ P CK P 751 Appendix 4 Individual Clinical Urinalysis Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGU ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 a MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 46.0 40.0 60.0 43.0 52.0 44.0 1.023 1.026 1.017 1.023 1.026 1.031 47.5 7.31 6 1.024 .0046 6 Dose Level: 0.03 29.0 66.0 46.0 122.0 1.010 1.017 1.025 1.019 65.8 40.43 4 1.018 .0062 4 Dose Level: 0.15 241.0 48.0 106.0 72.0 42.0 98.0 1.005 1.010 1.017 1.010 1.021 1.018 101.2 73.16 6 1.014 .0061 6 Dosage 8.0 6.0 8.0 7.5 7.5 8.0 7.5 .77 6 Dosage 8.0 8.0 7.5 7.5 7.8 .29 4 Dosage 7.0 7.0 8.0 7.0 7.5 8.0 7.4 .49 6 a Sample collected on Day 92. 752 Covance 6329-223 3M T-6295.7 Appendix 4 Individual Clinical Urinalysis Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 42.0 28.0 48.0 70.0 82.0 54.0 1.021 1.030 1.021 1.017 1.010 1.023 54.0 19.47 6 1.020 .0066 6 Dosage Unit: mg/kg/day 6.5 8.0 8.0 8.0 6.0 7.0 7.2 .88 6 Covance 6329-223 3M T-6295.7 753 Appendix 4 Individual Clinical Urinalysis Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS,; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 Group: 2 I05514 I05515 I05516 I05521 a Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 Dose Level: 0 10 10 10 10 10 10 - Dose Level: 0 .03 010 10 0- Dose Level: 0 .15 000010 0- Dose Level: 0 .75 10 10 00010 - Dosage Unit: mg/kg/day - ++++ + ++++ + - - - - --- - Dosage Unit: mg/kg/day ------- --- Dosage Unit: mg/kg/day -- ---++ - -- -- - Dosage Unit: mg/kg/day ++++ - - ++ - - - -- - -- - - - - - a Sample collected on Day 92. Covance 6329-223 3M T-6295.7 754 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Males Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05508 0 0 0 3 0 3D2F 0 CK - I05517 0 0 2 3 0 4B 0 CK P I05519 0 0 0 3 0 3B1D 1F BK - I05520 0 0 0 3 0 4B4D 1E BK - I05526 0 0 02 0 1B4D 0 CK - I05527 0 0 0 2 0 4B4D 3E CL - Group: 2 Dose Level:: 0.03 Dosage Unit: mg/kg/day I05514 0 0 0 3 0 4B2E 0 BK Q I05515 0 0 0 3 0 4B1D 0 BK - I05516 0 0 1 3 0 1D 0 CK - I05521 a 0 0 0 1 0 4B2E 0 CK Q Group: 3 Dose Level:: 0.15 Dosage Unit: mg/kg/day I05505 0 0 1 2 0 0 0 AJ PQ I05510 0 1 0 3 0 3B 0 BK PQ I05518 0 0 0 3 0 2B1E 0 BL - I05523 0 1 0 3 0 4B 0 AK PQ I05524 0 0 1 2 0 0 0 CK P I05528 0 0 0 2 0 3B2E 1F BK Q Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05506 0 1 1 2 0 0 0 CK PQ I05507 0 0 0 1 0 4B4D 1E CL - I05509 0 0 0 3 0 1B 0 BJ - I05511 0 0 02 0 3B1E 0 BL Q I05512 0 0 1 2 0 0 0 BJ P I05522 0 0 1 1 0 4D 0 BJ Q a Sample collected on Day 92. 755 Appendix 4 Individual Clinical Urinalysis Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 45.0 67.0 62.0 229.0 65.0 92.0 1.016 1.020 1.019 1.006 1.018 1.012 93.3 68.15 6 1.015 .0053 6 Dose Level: ro o o 104.0 31.0 60.0 64.0 1.017 1.021 1.014 1.021 64.8 30.02 4 1.018 .0034 4 Dose Level: 0.15 102.0 74.0 56.0 48.0 61.0 38.0 63.2 22.56 6 1.011 1.012 1.026 1.014 1.020 1.028 1.018 .0073 6 Dosage 8.0 8.0 8.0 8.0 8.0 8.0 8.0 .00 6 Dosage 7.0 7.5 7.0 8.0 7.4 .48 4 Dosage 8.0 7.0 7.5 6.5 8.0 8.0 7.5 .63 6 mg/kg/day mg/kg/day mg/kg/day Covance 6329-223 3M T-6295.7 756 Appendix 4 Individual Clinical Urinalysis Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLG ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 30.0 46.0 268.0 295.0 38.0 46.0 1.025 1.023 1.005 1.005 1.022 1.024 120.5 125.14 6 1.017 .0096 6 Dosage 8.0 8.0 8.0 8.0 7.0 7.5 7.8 .42 6 Covance 6329-223 3M T-6295.7 757 Appendix 4 Individual Clinical Urinalysis Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 Group: 2 I05537 I05541 I05547 I05550 Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 Dose Level: 0 10 _ 10 10 _ 10 _ 10 _ 0_ Dose Level: 0.03 0_ 10 _ 0_ 30 _ Dose Level: 0.15 10 _ 0_ 10 _ 0_ 10 _ 10 _ Dose Level: 0.75 10 _ 10 _ 0_ 0_ 10 _ 10 _ Dosage Unit: mg/kg/day --- - +++ ------- --- Dosage Unit: mg/kg/day --- +---- - - +++ Dosage Unit: mg/kg/day --- +-+ --+-+-- --- Dosage Unit: mg/kg/day +--- -++ -- - - -- - - - - - Covance 6329-223 3M T-6295.7 758 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Females Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 0 0 3 0 I05530 4 0 0 3 0 I05531 0 0 0 3 0 I05535 0 0 1 3 0 I05544 0 0 0 3 0 I05549 0 0 1 3 0 Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05537 0 0 1 2 0 I05541 0 0 1 3 0 I05547 0 0 0 3 0 I05550 4 0 1 3 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05532 0 1 4 3 0 I05538 0 0 2 3 0 I05539 0 0 02 0 I05545 0 0 1 1 0 I05548 0 0 1 1 0 I05552 0 0 1 1 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 3 1 3 0 I05534 0 0 02 0 I05536 0 0 1 2 0 I05540 0 0 2 3 0 I05542 0 2 1 30 I05551 0 0 1 3 0 3B4D 3B4D 4B2E 2B1F 2B 2B1D 3B1D 4B4D 3B1D 3B 1B4D 3D 4B2E 0 4B4D 4B1D 4D 4B4D 3D 0 2B2D 3B1D 0 0 0 0 0 1E 1E 1E1F 0 0 0 0 0 0 0 1E 0 0 0 0 0 0 BK BL BL BJ BL BK BK BL BL CL BK BK BL BK BL CL CK BL AJ AK BK BL - P - P - P P - 759 Appendix 4 Individual Clinical Urinalysis Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T -6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N Dose Level: 0 68.0 76.0 210.0 34.0 320.0 80.0 1.017 1.013 1.004 1.019 1.005 1.021 131.3 110.42 6 1.013 .0072 6 Dose Level: 0.03 56.0 46.0 34.0 84.0 1.017 1.020 1.028 1.017 55.0 21.32 4 1.020 .0052 4 Dose Level: 0.15 360.0 92.0 66.0 140.0 44.0 125.0 1.004 1.009 1.014 1.008 1.022 1.011 137.8 114.54 6 1.011 .0062 6 Dosage Unit: mg/kg/day 7.5 7.0 7.5 6.5 6.5 7.5 7.1 .49 6 Dosage Unit: mg/kg/day 7.5 7.0 7.0 8.0 7.4 .48 4 Dosage Unit: mg/kg/day 7.5 7.0 7.0 7.0 7.0 7.0 7.1 .20 6 Covance 6329-223 3M T-6295.7 760 Appendix 4 Individual Clinical Urinalysis Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLG ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 MEAN S.D. N Dose Level : 0.75 80.0 200.0 32.0 390.0 280.0 98.0 1.012 1.008 1.026 1.003 1.005 1.013 180.0 136.48 6 1.011 .0082 6 Dosage 7.0 7.5 6.0 7.0 7.5 7.5 7.1 .58 6 Covance 6329-223 3M T-6295.7 761 Appendix 4 Individual Clinical Urinalysis Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS, T 6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 Group: 2 I05514 I05515 I05516 I05521 Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 Group: 4 I05506 I05507 I05509 I05511 I05512 I05522 Dose Level: 0 0_ 00_ 0_ 0_ 0_ Dose Level: 0 .03 0_ 0_ 0_ 0_ Dose Level: 0 .15 0_ 0_ 0_ 0_ 0_ 0_ Dose Level: 0 .75 0_ 0_ 10 _ 0_ 0_ 0_ Dosage Unit: mg/kg/day - ++ ++++ + - - - - --- - Dosage Unit: mg/kg/day ++ ++ -- -- + -- - Dosage Unit: mg/kg/day -- -+-++ - -- -- - Dosage Unit: mg/kg/day +++ -++ --- -- -- -- - - - - - Covance 6329-223 3M T-6295.7 762 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Males Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05508 0 0 1 3 0 4B 0 BK Q I05517 0 0 1 2 0 0 0 BK P I05519 0 0 02 0 0 0 AJ - I05520 0 0 1 3 0 0 0 BK - I05526 0 0 1 3 0 0 0 AK - I05527 0 0 0 3 0 4B4D 0 BL Q Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05514 0 0 0 3 0 3B1D 1E BK PQ I05515 0 0 1 3 0 1B1D 1E BK PQ I05516 0 0 1 3 0 4B1D 0 BK PQ I05521 0 0 1 3 0 4B4D 0 BL - Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 0 1 3 0 I05510 0 0 1 3 0 I05518 0 0 0 3 0 I05523 0 1 1 3 0 I05524 0 0 1 2 0 I05528 0 1 1 3 0 0 0 4B 0 0 0 0 0 0 0 0 0 AK BK BK - BK Q BK - BK Q Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05506 0 0 1 3 0 2B 0 BK Q I05507 0 0 02 0 0 0 AK - I05509 0 1 1 3 0 0 0 BK P I05511 0 0 02 0 0 0 AK - I05512 0 0 1 2 0 0 0 AK - I05522 0 0 1 3 0 0 0 BK - 763 Appendix 4 Individual Clinical Urinalysis Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 0 44.0 36.0 36.0 145.0 100.0 150.0 1.022 1.024 1.023 1.006 1.011 1.007 85.2 53.91 6 1.016 .0084 6 ro o o Dose Level: 110.0 40.0 26.0 66.0 1.013 1.020 1.017 1.016 60.5 36.93 4 1.016 .0029 4 Dose Level: 0.15 44.0 46.0 54.0 46.0 28.0 26.0 1.023 1.027 1.018 1.018 1.022 1.027 40.7 11.15 6 1.022 .0040 6 Dosage 7.5 8.0 7.5 7.0 7.5 7.5 7.5 .32 6 Dosage 7.0 7.0 6.5 7.5 7.0 .41 4 Dosage 7.0 7.0 7.0 7.0 7.5 7.0 7.1 .20 6 mg/kg/day mg/kg/day mg/kg/day Covance 6329-223 3M T-6295.7 764 Appendix 4 Individual Clinical Urinalysis Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLG ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 30.0 52.0 110.0 270.0 36.0 36.0 1.025 1.011 1.012 1.005 1.021 1.026 89.0 93.46 6 1.017 .0085 6 Dosage 7.0 8.0 7.5 6.0 7.0 7.0 7.1 .66 6 Covance 6329-223 3M T-6295.7 765 Appendix 4 Individual Clinical Urinalysis Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 Group: 2 I05537 I05541 I05547 I05550 Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 Dose Level: 0 10 _ 10 0_ 0_ 0_ 0_ Dose Level: 0.03 0_ 30 _ 10 _ 0_ Dose Level: 0.15 0_ 0_ 0_ 0_ 10 _ 0_ Dose Level: 0.75 0_ 0_ 0_ 0_ 0_ 0_ Dosage Unit: mg/kg/day + - +++ --+-+---- --- Dosage Unit: mg/kg/day + ++ +++ + - - - +++ - - Dosage Unit: mg/kg/day ++++ +++ +++ - +++ - - - Dosage Unit: mg/kg/day +++ -- -- +++ ++ - - - - - - - Covance 6329-223 3M T-6295.7 766 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Females Day 153 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 2 1 0 30 I05530 0 1 0 30 I05531 0 0 02 0 I05535 0 0 1 2 0 I05544 0 0 1 3 0 I05549 0 0 2 3 0 Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05537 0 0 1 3 0 I05541 4 1 1 3 0 I05547 0 1 1 3 0 I05550 0 0 2 3 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05532 0 4 2 2 0 I05538 0 0 1 1 0 I05539 0 1 3 3 0 I05545 0 0 2 3 0 I05548 0 1 1 3 0 I05552 0 0 1 3 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 1 1 3 0 I05534 0 0 1 3 0 I05536 0 1 1 2 0 I05540 0 1 2 1 0 I05542 0 2 1 30 I05551 0 1 1 3 0 3B1D 4B4D 4B4D 0 4B 0 2B4D 0 3B2E 0 0 1D 1D 4D 4B4D 4D 2B2D 2B4D 4B3D 0 2B4D 3B4D 0 0 2E4F 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1E 0 0 0 BL BL BL BK BL BK BK CK BL BK BK CK BK BK BL CK BK BK BL AK BK CK P - P P - P P P P - 767 Appendix 4 Individual Clinical Urinalysis Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N 0Dose Level: 184.0 49.0 16022..00 242.0 58.0 111...000120216 1.013 1.006 1.023 116.2 79.363 1.014 .00762 ro o o Dose Level: 94.0 52.0 15042..00 1.014 1.019 1.018 1.016 75.5 26.20 4 1..0001272 4 Dose Level: 0.15 316282..00 2781..00 49.0 96.0 11..001023 1.016 1.017 1.015 1.016 122.3 125.463 1.013 .00563 Dosage 8.0 78888.....00005 7..2960 Dosage 8.0 788...005 7.9 .25 4 Dosage 88..00 86..05 68..05 71..0560 mg/kg/day mg/kg/day mg/kg/day Covance 6329-223 3M T-6295.7 768 Appendix 4 Individual Clinical Urinalysis Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05507 I05511 I05512 I05522 MEAN S.D. N Dose Level: 0.75 280.0 96.0 36.0 72.0 1.005 1.017 1.018 1.012 121.0 108.83 4 1.013 .0059 4 Dosage Unit: mg/kg/day 7.5 8.0 6.5 7.0 7.2 .65 4 Covance 6329-223 3M T-6295.7 769 Appendix 4 Individual Clinical Urinalysis Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05508 I05517 I05519 I05520 I05526 I05527 Group: 2 I05514 I05515 I05516 I05521 Group: 3 I05505 I05510 I05518 I05523 I05524 I05528 Group: 4 I05507 I05511 I05512 I05522 Dose Level: 0 10 _ 10 10 _ 10 _ 10 _ 10 _ Dose Level: 0.03 10 _ 10 _ 10 _ 10 _ Dose Level: 0.15 10 _ 10 _ 10 _ 10 _ 10 _ 10 _ Dose Level: 0.75 10 _ 10 _ 10 _ 10 _ Dosage Unit: mg/kg/day --- --------- +-- Dosage Unit: mg/kg/day ------- --- Dosage Unit: mg/kg/day -- --++ -- -- -- - Dosage Unit: mg/kg/day --- ------- - - - - - Covance 6329-223 3M T-6295.7 770 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Males Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05508 0 0 0 3 0 I05517 0 0 02 0 I05519 0 0 0 3 0 I05520 0 0 0 3 0 I05526 0 1 0 30 I05527 0 0 0 3 0 Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05514 0 0 02 0 I05515 0 0 0 3 0 I05516 0 0 1 3 0 I05521 0 0 0 3 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 0 0 3 0 I05510 0 0 1 3 0 I05518 0 0 0 3 0 I05523 0 0 0 1 0 I05524 0 0 0 3 0 I05528 0 0 0 1 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05507 0 0 0 1 0 I05511 0 0 1 2 0 I05512 0 0 02 0 I05522 0 0 1 2 0 2B1E 3B3D 4B 3B1D 2B 4B4D 2B2E 4B1E 2B 4B 2B 2B1E 4B4D 1B 0 4B1E 0 4B 0 2D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 BK BL BK BL AK BL - BK Q BK BK BL - AK BK BK BJ P BK BL - AJ Q BK Q BJ P BK PQ 771 Appendix 4 Individual Clinical Urinalysis Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 MEAN S.D. N Dose Level: 50.0 62.0 57.0 159.0 86.0 100.0 0 1.020 1.015 1.023 1.009 1.017 1.013 85.7 40.59 6 1.016 .0050 6 ro o o Dose Level: 108.0 38.0 95.0 64.0 1.013 1.020 1.009 1.020 76.2 31.48 4 1.016 .0054 4 Dose Level: 0.15 118.0 61.0 70.0 66.0 82.0 43.0 1.010 1.021 1.022 1.013 1.014 1.023 73.3 25.33 6 1.017 .0055 6 Dosage 8.0 8.0 8.5 8.0 8.0 8.0 8.1 .20 6 Dosage 7.0 7.5 8.0 8.0 7.6 .48 4 Dosage 8.0 8.0 8.0 7.5 8.0 8.0 7.9 .20 6 mg/kg/day mg/kg/day mg/kg/day Covance 6329-223 3M T-6295.7 772 Appendix 4 Individual Clinical Urinalysis Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLG ANIMAL NUMBER U VOL ML SP GR U PH Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 MEAN S.D. N Dose Level : 0.75 47.0 82.0 72.0 450.0 84.0 56.0 1.016 1.015 1.017 1.003 1.018 1.018 131.8 156.54 6 1.014 .0058 6 Dosage 7.5 8.0 8.0 7.5 8.0 8.0 7.8 .26 6 Covance 6329-223 3M T-6295.7 773 Appendix 4 Individual Clinical Urinalysis Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05530 I05531 I05535 I05544 I05549 Group: 2 I05537 I05541 I05547 I05550 Group: 3 I05532 I05538 I05539 I05545 I05548 I05552 Group: 4 I05533 I05534 I05536 I05540 I05542 I05551 Dose Level: 0 10 _ 10 10 _ 10 _ 10 _ 10 _ Dose Level: 0.03 10 _ 10 _ 10 _ 10 _ Dose Level: 0.15 10 _ 10 _ 10 _ 10 _ 10 _ 10 _ Dose Level: 0.75 30 _ 10 _ 10 _ 10 _ 10 _ 10 _ Dosage Unit: mg/kg/day --- --------- --+ Dosage Unit: mg/kg/day ++ ++ -- -- --- - Dosage Unit: mg/kg/day ----------- --- Dosage Unit: mg/kg/day +++ --- --- -- +++ + - - - - - - - Covance 6329-223 3M T-6295.7 774 ANIMAL NUMBER Appendix 4 Individual Clinical Urinalysis Data Females Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER. HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 0 1 3 0 4B1D 0 BL - I05530 0 0 0 3 0 4B2D 0 BL - I05531 0 0 1 3 1G 4B1E 0 BK - I05535 0 0 1 3 0 4D 0 BK - I05544 0 0 1 3 0 4B 0 BL - I05549 0 1 1 3 0 2B1D 0 BK - Group: 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05537 0 1 1 3 0 3B2E 0 BK - I05541 0 1 1 3 0 3B1E 0 BL - I05547 0 0 1 3 0 4B 0 BK P I05550 0 0 1 3 0 4B1E 0 BL - Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05532 0 3 0 3 0 2B2E 0 BK - I05538 0 0 1 2 0 4B2E 1F BL - I05539 0 0 0 1 0 3B1E 0 BL - I05545 0 0 1 2 0 2B2D 0 BK - I05548 0 0 1 3 0 3B 0 BK - I05552 0 1 1 3 0 3B3D 0 BL - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 2 0 1 30 0 0 BK - I05534 0 1 1 3 0 3B 0 BL - I05536 0 0 2 2 0 4B3D 0 BL - I05540 0 0 1 2 0 1B 0 AK - I05542 0 0 0 3 0 4B 0 BK - I05551 0 1 1 3 0 3B3D 0 BL - 775 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 162.0 197.0 1.010 1.010 179.5 24.75 2 1.010 .0000 2 Dose Level: 0.15 296.0 183.0 1.005 1.009 239.5 79.90 2 1.007 .0028 2 Dose Level: 0.75 62.0 113.0 1.011 1.015 87.5 36.06 2 1.013 .0028 2 Dosage Unit: mg/kg/day 7.5 7.0 7.2 .35 2 Dosage Unit: mg/kg/day 7.5 7.5 7.5 .00 2 Dosage Unit: mg/kg/day 6.5 7.5 7.0 .71 2 Covance 6329-223 3M T-6295.7 776 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 00- Dose Level: 0.15 00- Dose Level: 0.75 00- Dosage Unit: mg/kg/day --- Dosage Unit: mg/kg/day --- Dosage Unit: mg/kg/day -+ -- - - - Covance 6329-223 3M T-6295.7 777 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Males Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 URINE APP1 COMMENTS Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 0 1 0 1 0 4B BK - I05526 0 0 1 2 0 4B BJ Q Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 0 0 2 0 2B AJ - I05523 0 0 0 2 0 2B AK Q Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 0 0 1 3 0 3B BK - I05522 0 0 0 3 0 3B BK - Covance 6329-223 3M T-6295.7 778 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 88.0 198.0 1.020 1.009 143.0 77.78 2 1.014 .0078 2 Dose Level: 0.15 178.0 64.0 1.015 1.015 121.0 80.61 2 1.015 .0000 2 Dose Level: 0.75 63.0 115.0 1.015 1.015 89.0 36.77 2 1.015 .0000 2 Dosage Unit: mg/kg/day 8.0 7.5 7.8 .35 2 Dosage Unit: mg/kg/day 7.5 7.0 7.2 .35 2 Dosage Unit: mg/kg/day 7.0 8.0 7.5 .71 2 Covance 6329-223 3M T-6295.7 779 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 00- Dose Level: 0.15 10 10 - Dose Level: 0.75 00- Dosage Unit: mg/kg/day ----+ Dosage Unit: mg/kg/day - - +++ +-- Dosage Unit: mg/kg/day +---- - - - Covance 6329-223 3M T-6295.7 780 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Females Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 URINE APP1 COMMENTS Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 0 1 3 0 I05549 0 0 0 3 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05539 4 0 1 3 0 I05552 0 0 1 3 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 0 1 3 0 I05542 0 0 0 3 0 4B 3B 4B3E 4B 4B 3B CK AK BK BK BK BK Covance 6329-223 3M T-6295.7 781 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 202.0 189.0 1.008 1.010 195.5 9.19 2 1.009 .0014 2 Dose Level: 0.15 290.0 102.0 1.005 1.014 196.0 132.94 2 1.010 .0064 2 Dose Level: 0.75 62.0 104.0 1.014 1.020 83.0 29.70 2 1.017 .0042 2 Dosage Unit: mg/kg/day 7.5 8.0 7.8 .35 2 Dosage Unit: mg/kg/day 7.5 7.5 7.5 .00 2 Dosage Unit: mg/kg/day 7.5 8.0 7.8 .35 2 Covance 6329-223 3M T-6295.7 782 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 00- Dose Level: 0.15 00- Dose Level: 0.75 010 - Dosage Unit: mg/kg/day --- Dosage Unit: mg/kg/day --- Dosage Unit: mg/kg/day --- - - - Covance 6329-223 3M T-6295.7 783 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Males Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 0 0 1 3 0 I05526 0 0 0 3 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 0 0 3 0 I05523 0 1 1 2 1H Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 0 0 1 2 0 I05522 0 0 0 3 0 0 1D 0 2B2F 3D 4B 0 0 0 0 0 0 AJ Q AJ - AJ AJ PQ BJ BL - 784 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 46.0 188.0 1.026 1.010 117.0 100.41 2 1.018 .0113 2 Dose Level: 0.15 176.0 87.0 1.015 1.018 131.5 62.93 2 1.016 .0021 2 Dose Level: 0.75 57.0 126.0 1.014 1.019 91.5 48.79 2 1.016 .0035 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 7.0 7.5 7.2 .35 2 Dosage Unit: mg/kg/day 7.5 8.0 7.8 .35 2 Covance 6329-223 3M T-6295.7 785 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;? T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 10 0- Dose Level: 0.15 00- Dose Level: 0.75 10 0- Dosage Unit:: mg/kg/day --- Dosage Unit:: mg/kg/day --- Dosage Unit:: mg/kg/day +-- - - - Covance 6329-223 3M T-6295.7 786 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Females Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 0 0 3 0 I05549 0 0 1 3 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05539 0 0 1 3 0 I05552 0 0 1 1 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 1 1 3 0 I05542 0 0 1 2 0 3B1D 2B 1B 4B1E 2B1D 3B2E 1E 0 0 0 0 2F BK BJ BJ BL BK BL 787 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 248.0 320.0 1.004 1.003 284.0 50.91 2 1.004 .0007 2 Dose Level: 0.15 354.0 114.0 1.004 1.010 234.0 169.71 2 1.007 .0042 2 Dose Level: 0.75 32.0 103.0 1.026 1.011 67.5 50.20 2 1.018 .0106 2 Dosage Unit: mg/kg/day 6.5 7.0 6.8 .35 2 Dosage Unit: mg/kg/day 7.5 7.0 7.2 .35 2 Dosage Unit: mg/kg/day 6.5 7.5 7.0 .71 2 Covance 6329-223 3M T-6295.7 788 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;? T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 00- Dose Level: 0.15 010 - Dose Level: 0.75 10 0- Dosage Unit:: mg/kg/day --- Dosage Unit:: mg/kg/day -- +++ Dosage Unit:: mg/kg/day +-- - - - Covance 6329-223 3M T-6295.7 789 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Males Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 URINE APP1 COMMENTS Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 0 0 0 3 0 I05526 0 0 1 2 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 0 0 3 0 I05523 0 0 0 3 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 0 0 0 2 0 I05522 0 0 0 3 0 0 0 0 0 1B4E 1B AJ AJ AJ BJ BJ BJ - PQ - Covance 6329-223 3M T-6295.7 790 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 118.0 165.0 1.007 1.005 141.5 33.23 2 1.006 .0014 2 Dose Level: 0.15 90.0 37.0 1.016 1.023 63.5 37.48 2 1.020 .0050 2 Dose Level: 0.75 23.0 106.0 1.011 1.010 64.5 58.69 2 1.010 .0007 2 Dosage Unit: mg/kg/day 7.5 8.0 7.8 .35 2 Dosage Unit: mg/kg/day 7.5 7.5 7.5 .00 2 Dosage Unit: mg/kg/day 8.0 6.5 7.2 1.06 2 Covance 6329-223 3M T-6295.7 791 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;? T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 00- Dose Level: 0.15 10 10 - Dose Level: 0.75 10 0- Dosage Unit:: mg/kg/day --- Dosage Unit:: mg/kg/day -++ - - Dosage Unit:: mg/kg/day -++ - - - - Covance 6329-223 3M T-6295.7 792 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Females Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 URINE APP1 COMMENTS Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 0 1 3 0 I05549 0 0 1 3 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05539 0 1 1 3 0 I05552 0 0 1 3 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 0 0 3 0 I05542 0 0 1 3 0 0 1D 1B2E 4B 4B 1B AJ AJ BJ BL BL BJ P - - P Covance 6329-223 3M T-6295.7 793 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 116.0 476.0 1.015 1.002 296.0 254.56 2 1.008 .0092 2 Dose Level: 0.15 166.0 33.0 1.009 1.023 99.5 94.05 2 1.016 .0099 2 Dose Level: 0.75 51.0 44.0 1.013 1.026 47.5 4.95 2 1.020 .0092 2 Dosage Unit: mg/kg/day 6.5 7.0 6.8 .35 2 Dosage Unit: mg/kg/day 7.0 6.0 6.5 .71 2 Dosage Unit: mg/kg/day 6.0 6.0 6.0 .00 2 Covance 6329-223 3M T-6295.7 794 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 00- Dose Level: 0.15 00- Dose Level: 0.75 00- Dosage Unit: mg/kg/day +++ - -- Dosage Unit: mg/kg/day -+++ - - Dosage Unit: mg/kg/day ++++ ++++ --- - Covance 6329-223 3M T-6295.7 795 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Males Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 URINE APP1 COMMENTS Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 0 0 1 1 0 1B BJ - I05526 0 0 1 1 0 0 AJ Q Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 0 1 1 3 0 3B BJ - I05523 0 0 1 3 0 2B BJ - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 0 1 1 2 0 2B BJ Q I05522 0 0 0 2 0 0 BJ Q Covance 6329-223 3M T-6295.7 796 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 87.0 354.0 1.010 1.003 220.5 188.80 2 1.006 .0050 2 Dose Level: 0.15 76.0 42.0 1.015 1.021 59.0 24.04 2 1.018 .0042 2 Dose Level: 0.75 71.0 113.0 1.017 1.012 92.0 29.70 2 1.014 .0035 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 7.0 6.0 6.5 .71 2 Dosage Unit: mg/kg/day 6.5 7.0 6.8 .35 2 Covance 6329-223 3M T-6295.7 797 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 010 - Dose Level: 0.15 00- Dose Level: 0.75 10 0- Dosage Unit: mg/kg/day -- ++ Dosage Unit: mg/kg/day ++ +++++ --- Dosage Unit: mg/kg/day +++ ++ -- - - Covance 6329-223 3M T-6295.7 798 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Females Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 URINE APP1 COMMENTS Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 1 1 2 0 I05549 0 0 1 3 0 Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05539 0 1 1 3 0 I05552 0 0 1 3 0 Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 1 1 2 0 I05542 0 1 1 1 0 2B 0 1D 1B 0 0 BJ AJ BK CJ BJ BJ Covance 6329-223 3M T-6295.7 799 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N 0Dose Level: 149.0 264.0 1.019 1.015 206.5 81.322 1.017 .00228 Dose Level: 0.15 82.0 67.0 1.018 1.018 74.5 10.621 1..00010820 Dose Level: 0.75 100.0 80.0 11..002125 90.0 14.124 1.018 .00520 Dosage Unit: mg/kg/day 8.0 7.5 7.8 .235 Dosage Unit: mg/kg/day 8.0 7.0 7.5 .271 Dosage Unit: mg/kg/day 76..05 6.8 1.026 Covance 6329-223 3M T-6295.7 800 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;r T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 10 ++++ 10 + Dose Level: 0.15 0+ 10 - Dose Level: 0.75 10 10 + Dosage Unit:: mg/kg/day -+ -+ Dosage Unit:: mg/kg/day -+ ++ +++ Dosage Unit:: mg/kg/day - ++ - +++ - - - Covance 6329-223 3M T-6295.7 801 ANIMAL NUMBER Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 Dose Level: 0 Dosage Unit: mg/kg/day 0 1 1 30 0 0 1 30 Dose Level: 0.15 Dosage Unit: mg/kg/day 0012 0 0 1 1 30 Dose Level: 0.75 Dosage Unit: mg/kg/day 0 0 0 30 0 0 1 30 3B1E 3B1K 3B3D 3B3D 4B3D 3B 1K 0 0 0 0 0 BL BL BL CK BK BL COMMENTS Q - - Covance 6329-223 3M T-6295.7 802 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 166.0 150.0 1.011 1.011 158.0 11.31 2 1.011 .0000 2 Dose Level: 0.15 78.0 59.0 1.020 1.022 68.5 13.44 2 1.021 .0014 2 Dose Level: 0.75 43.0 109.0 1.018 1.019 76.0 46.67 2 1.018 .0007 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 7.0 7.0 7.0 .00 2 Dosage Unit: mg/kg/day 6.5 7.5 7.0 .71 2 Covance 6329-223 3M T-6295.7 803 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 0+ 0+ Dose Level:: 0.15 10 10 + Dose Level:: 0.75 10 10 + Dosage Unit: mg/kg/day -+ -+ Dosage Unit: mg/kg/day + +++ ++ ++ Dosage Unit: mg/kg/day ++ ++ ++ - - - Covance 6329-223 3M T-6295.7 804 ANIMAL NUMBER APPENDIX 4 Individual Clinical Urinalysis Data Females Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 COMMENTS Covance 6329-223 3M T-6295.7 Group: 1 Dose Level: 0 Dosage Unit: mg/kg/day I05529 0 0 0 3 0 4B2D 3K BL - I05549 0 0 1 3 0 4B1D 0 BL - Group: 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05539 0 0 1 3 0 4K 0 BK - I05552 0 0 1 3 0 3B1D 0 BL - Group: 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05533 0 1 1 3 0 2B 0 BK - I05542 0 0 0 3 0 3B3K 0 BL - 805 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 100.0 270.0 1.012 1.008 185.0 120.21 2 1.010 .0028 2 Dose Level: 0.15 286.0 78.0 1.004 1.011 182.0 147.08 2 1.008 .0050 2 Dose Level: 0.75 90.0 78.0 1.008 1.015 84.0 8.49 2 1.012 .0050 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Covance 6329-223 3M T-6295.7 806 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 00- Dose Level: 0.15 010 - Dose Level: 0.75 00- Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ----- - - - Covance 6329-223 3M T-6295.7 807 ANIMAL NUMBER Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 Dose Level: 0 Dosage Unit: mg/kg/day 0 0 0 30 0 0 1 30 Dose Level: 0.15 Dosage Unit: mg/kg/day 0002 0 0 0 0 30 Dose Level: 0.75 Dosage Unit: mg/kg/day 0 0 1 30 0 0 0 30 1B1D 0 0 4B1D 0 2B4D 0 0 0 0 0 0 BK AJ AJ BK BJ BJ COMMENTS Q Q Covance 6329-223 3M T-6295.7 808 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 98.0 330.0 1.013 1.005 214.0 164.05 2 1.009 .0057 2 Dose Level: 0.15 198.0 92.0 1.008 1.014 145.0 74.95 2 1.011 .0042 2 Dose Level: 0.75 60.0 176.0 1.002 1.008 118.0 82.02 2 1.005 .0042 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 7.5 8.0 7.8 .35 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Covance 6329-223 3M T-6295.7 809 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 010 - Dose Level: 0.15 00- Dose Level: 0.75 00- Dosage Unit: mg/kg/day --- - +++ Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ----+ - - - Covance 6329-223 3M T-6295.7 810 ANIMAL NUMBER Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 Dose Level: 0 Dosage Unit: mg/kg/day 0 0 1 30 0 1 1 30 Dose Level: 0.15 Dosage Unit: mg/kg/day 0 1 1 30 0 0 1 30 Dose Level: 0.75 Dosage Unit: mg/kg/day 0 0 1 30 0 0 0 30 2B4D 0 0 3B 2B 4B 0 0 0 0 0 0 BK AJ AJ BK AK AL COMMENTS Covance 6329-223 3M T-6295.7 811 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05520 I05526 MEAN S.D. N Group: 3 I05505 I05523 MEAN S.D. N Group: 4 I05511 I05522 MEAN S.D. N Dose Level: 0 480.0 380.0 1.005 1.005 430.0 70.71 2 1.005 .0000 2 Dose Level: 0.15 405.0 195.0 1.004 1.008 300.0 148.49 2 1.006 .0028 2 Dose Level: 0.75 345.0 100.0 1.005 1.015 222.5 173.24 2 1.010 .0071 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 7.5 8.0 7.8 .35 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Covance 6329-223 3M T-6295.7 812 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 Dose Level: 0 00- Dose Level: 0.15 00- Dose Level: 0.75 00- Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day ----- - - - Covance 6329-223 3M T-6295.7 813 ANIMAL NUMBER Group: 1 I05520 I05526 Group: 3 I05505 I05523 Group: 4 I05511 I05522 APPENDIX 4 Individual Clinical Urinalysis Data Males Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 Dose Level: 0 Dosage Unit: mg/kg/day 0011 0 0 0 0 30 Dose Level: 0.15 Dosage Unit: mg/kg/day 0002 0 0001 0 Dose Level: 0.75 Dosage Unit: mg/kg/day 0001 0 0001 0 1B 1B 0 2B 1B 2B1D 0 0 0 0 0 2E AJ AJ AJ AJ AJ BK COMMENTS Q Q Q Covance 6329-223 3M T-6295.7 814 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U VOL ML SP GR U PH Group: 1 I05529 I05549 MEAN S.D. N Group: 3 I05539 I05552 MEAN S.D. N Group: 4 I05533 I05542 MEAN S.D. N Dose Level: 0 105.0 160.0 1.015 1.007 132.5 38.89 2 1.011 .0057 2 Dose Level: 0.15 85.0 50.0 1.017 1.019 67.5 24.75 2 1.018 .0014 2 Dose Level: 0.75 42.0 156.0 1.017 1.010 99.0 80.61 2 1.014 .0050 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Dosage Unit: mg/kg/day 8.0 8.0 8.0 .00 2 Covance 6329-223 3M T-6295.7 815 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS ANIMAL NUMBER U PRO MG/DL U GLU U KET U BILI U BLOOD UROBILI Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 Dose Level: 0 0 0 Dose Level: 0.15 10 _ 10 - Dose Level: 0.75 0 0_ Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day ----- Dosage Unit: mg/kg/day - - +++ - - Covance 6329-223 3M T-6295.7 816 ANIMAL NUMBER Group: 1 I05529 I05549 Group: 3 I05539 I05552 Group: 4 I05533 I05542 APPENDIX 4 Individual Clinical Urinalysis Data Females Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS RBC WBC EPITH BACT CASTS CRYSTALS CRYSTALS PER HPF PER HPF PER HPF PER HPF PER LPF PER LPF1 PER LPF2 URINE APP1 Dose Level: 0 Dosage Unit: mg/kg/day 01 00 02 02 0 0 Dose Level: 0.15 Dosage Unit: mg/kg/day 0002 0 0002 0 Dose Level: 0.75 Dosage Unit: mg/kg/day 0002 0 01 1 1 0 2B2D 2B 3B1E 2B2E 3B3D 3B 1F 0 0 0 0 0 BJ BJ BK BL BL AL COMMENTS Covance 6329-223 3M T-6295.7 817 APPENDIX 5 Covance 6329-223 3M T-6295.7 Individual Palmitoyl CoA Oxidase Determinations Individual Anatomic Pathology Data 818 Appendix 5 Individual Palmitoyl CoA Oxidase Determinations Terminal Sacrifice Males 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; 1 ANIMAL NUMBER PCOAO IU/G Group: 1 I05508 I05517 I05519 I05527 MEAN S.D. N Group: 2 I05514 I05515 I05516 I05521 MEAN S.D. N Group: 3 I05510 I05518 I05524 I05528 MEAN S.D. N Dose Level 4 4 6 7 0 5 1.5 4 Dose Level 4 5 4 6 5 1.0 4 Dose Level 6 6 5 5 6 .6 4 Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 819 Appendix 5 Individual Palmitoyl CoA Oxidase Determinations Terminal Sacrifice Males 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER PCOAO IU/G Group: 4 I05507 I05512 MEAN S.D. N Dose Level: 0.75 8 6 7 1.4 2 Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 820 Appendix 5 Individual Palmitoyl CoA Oxidase Determinations Terminal Sacrifice Females 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; 1 ANIMAL NUMBER PCOAO IU/G Group: 1 I05530 I05531 I05535 I05544 MEAN S.D. N Group: 2 I05537 I05541 I05547 I05550 MEAN S.D. N Group: 3 I05532 I05538 I05545 I05548 MEAN S.D. N Dose Level 3 4 4 5 0 4 .8 4 Dose Level 4 4 2 5 4 1.3 4 Dose Level 5 5 6 7 6 1.0 4 Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 821 Appendix 5 Individual Palmitoyl CoA Oxidase Determinations Terminal Sacrifice Females 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS ANIMAL NUMBER PCOAO IU/G Group: 4 I05534 I05536 I05540 I05551 MEAN S.D. N Dose Level: 0.75 6 7 6 5 6 .8 4 Dosage Unit: mg/kg/day Covance 6329-223 3M T-6295.7 822 APPENDIX 5 Individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 ANIMAL NUMBER: I05506 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (M) DATE OF DEATH: 02/20/99 STUDY DAY OF DEATH: 179 STUDY WEEK OF DEATH: 26 TERMINAL BODY WEIGHT: 3625.0 GRAMS DATE AND TIME OF NECROPSY: 02/20/99 12:40 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIEDRICH POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: NANCY DIEDRICH ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) GALLBLADDER (GB) BILE(VOLUME) (BI) ABSOLUTE ORGAN WEIGHT (GRAMS) .4730 .3840 65.9350 1.2760 1.2520 6.1230 5.9240 88.6340 7.0730 7.0020 6.7010 .1980 .2070 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0130 % .0106 % 1.8189 % .0352 % .0345 % .1689 % .1634 % 2.4451 % .1951 % .1932 % .1849 % .0055 % .0057 % ORGAN TO BRAIN WEIGHT RATIO .0072 .0058 1.0000 .0194 .0190 .0929 .0898 1.3443 .1073 .1062 .1016 .0030 .0031 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NOT SCHEDULED NOT SCHEDULED NECROPSY OBSERVATIONS HISTOPATHOLOGY BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MODERATELY SEVERE BRAIN (BR) : -INFILTRATE, LYMPHOHISTIOCYTIC, PERIVASCULAR,-MINIMAL -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-MINIMAL -INFILTRATE, LYMPHOHISTIOCYTIC, MENINGEAL,-SLIGHT KIDNEY (KD) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL -CAST, PROTEINACEOUS,-SLIGHT 823 APPENDIX 5 Individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 ANIMAL NUMBER: I05506 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (M) DATE OF DEATH: 02/20/99 STUDY DAY OF DEATH:: 179 STUDY WEEK OF DEATH: 26 TERMINAL BODY WEIGHT: 3625.0 GRAMS DATE AND TIME OF NECROPSY: 02/20/99 12:40 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIEDRICH POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: NANCY DIEDRICH NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -HYPERTROPHY, HEPATOCELLULAR,-MODERATE, DIFFUSE -STASIS, BILE,-SLIGHT, MULTI-FOCAL THYMUS (TH) : -CYST,-PRESENT -ATROPHY,-MODERATELY SEVERE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL ESOPHAGUS (ES) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT THYROID (TY) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT -CYST, ULTIMOBRANCHIAL,-PRESENT ADRENAL, CORTEX (AC) : -MINERALIZATION, VASCULAR,-MINIMAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT SPINAL CORD (SC) : -INFILTRATION, LYMPHOHISTIOCYTIC MENINGEAL/PERIVASCULAR,SLIGHT DUODENUM (DU) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT URINARY BLADDER (UB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT 824 APPENDIX 5 Individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 ANIMAL NUMBER: I05506 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (M) DATE OF DEATH: 02/20/99 STUDY DAY OF DEATH: 179 STUDY WEEK OF DEATH: 26 TERMINAL BODY WEIGHT: 3625.0 GRAMS DATE AND TIME OF NECROPSY: 02/20/99 12:40 PROSECTOR: DAVID SCHUETTE RECORDER: NANCY DIEDRICH POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: NANCY DIEDRICH NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS CAUSE OF DEATH (CD) : -UNDETERMINED,-PRESENT THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), LN, MESENTERIC (MS), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), PANCREAS (PA), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE) 825 APPENDIX 5 Individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 ANIMAL NUMBER: I05509 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (D) DATE OF DEATH: 01/27/99 STUDY DAY OF DEATH: 155 STUDY WEEK OF DEATH: 23 TERMINAL BODY WEIGHT: NOT ENTERED DATE AND TIME OF NECROPSY: 01/27/99 10:21 PROSECTOR: NANCY DIEDRICH RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: NOT AVAILABLE *** ORGAN WEIGHTS WERE NOT RECORDED *** NECROPSY OBSERVATIONS HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); ALL LOBES TO EACH OTHER AND PLEURA: MULTIPLE INDISTINCT ADHESIONS; CANNOT DISTINGUISH LOBES FROM ONE ANOTHER; COLLECTED -MOTTLED; ALL RIGHT LOBES: RED, DARK RED, AND TAN; LOBES APPEAR FIRM -EROSION(S)/ULCERATION(S); APPEARS TO BE RIGHT CAUDAL LOBE: SINGLE ULCERATED AREA, 2.5 X 1.5 CM; ULCERATED AREA EXTENDS DEEP INTO LUNG TISSUE; WALLS OF ULCERATION APPEAR GREEN, TAN, GRAY AND MOIST; COLLECTED INTACT LIVER (LI) : -MOTTLED; ALL LOBES: DARK BROWN AND TAN -LARGE; ALL LOBES: THICKENED BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MODERATELY SEVERE MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT KIDNEY (KD) : -MINERALIZATION, PAPILLARY,-MODERATE LUNG (LU) : -FIBROSIS, PLEURAL/SUBPLEURAL,-MODERATE -INFILTRATE, MACROPHAGE, ALVEOLAR,-MODERATE -NECROSIS,-SEVERE -INFLAMMATION, ACUTE,-SEVERE -FIBRIN, PLEURAL,-MODERATELY SEVERE LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR,-SLIGHT, DIFFUSE -VACUOLATION, HEPATOCELLULAR, CENTRILOBULAR,-MODERATE THYMUS (TH) : -ATROPHY,-MODERATE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL 826 APPENDIX 5 Individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 5 ANIMAL NUMBER: I05509 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (D) DATE OF DEATH: 01/27/99 STUDY DAY OF DEATH: 155 STUDY WEEK OF DEATH: 23 TERMINAL BODY WEIGHT: NOT ENTERED DATE AND TIME OF NECROPSY: 01/27/99 10:21 PROSECTOR: NANCY DIEDRICH RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: NOT AVAILABLE NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY COLON (CO) : -DARK FOCUS(I)/AREA(S); WITHIN MUCOSA: SINGLE DARK BROWN AREA, 0.3 X 0.2 CM; COLLECTED ON ROUTINE SECTION LN, TRACHEOBRON (TB) : -LARGE; UP TO 1.0 X 0.9 X 0.5 CM (CAP 29) JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, ILEUM (IL) : -INFILTRATE, MACROPHAGE, COLON (CO) : >UNREMARKABLE PIGMENTED,-MODERATE PIGMENTED,-SLIGHT CAUSE OF DEATH (CD) : -NECROSIS, PULMONARY,-PRESENT LN, TRACHEOBRON (TB) : -INFLAMMATION, ACUTE,-MODERATE 827 APPENDIX 5 Individual Anatomic Pathology Data Unscheduled Deaths 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 6 ANIMAL NUMBER: I05509 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: UNSCHEDULED (D) DATE OF DEATH: 01/27/99 STUDY DAY OF DEATH: 155 STUDY WEEK OF DEATH: 23 TERMINAL BODY WEIGHT: NOT ENTERED DATE AND TIME OF NECROPSY: 01/27/99 10:21 PROSECTOR: NANCY DIEDRICH RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: NOT AVAILABLE THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), GENERAL COMMENT (GC), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), LN, MESENTERIC (MS), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), CECUM (CE), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE) (MA), 828 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 ANIMAL NUMBER: I05508 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3285.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 10:24 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .2650 .2010 62.3670 .8310 1.0370 5.8660 5.4930 59.3880 5.5360 5.1190 4.3000 .1520 .1390 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0081 % .0061 % 1.8985 % .0253 % .0316 % .1786 % .1672 % 1.8079 % .1685 % .1558 % .1309 % .0046 % .0042 % ORGAN TO BRAIN WEIGHT RATIO .0042 .0032 1.0000 .0133 .0166 .0941 .0881 .9522 .0888 .0821 .0689 .0024 .0022 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY LUNG (LU) : -RED FOCUS(I)/AREA(S); ALL LOBES: MULTIPLE DARK RED PINPOINT FOCI SPLEEN (SP) : -LARGE; 7 . 0 X 4 . 0 X 3 . 0 C M BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MODERATELY SEVERE KIDNEY (KD) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT -GLOMERULOSCLEROSIS,-MINIMAL LUNG (LU) : -HYPERPLASIA, LYMPHOCYTIC, PERIBRONCHIOLAR/PERIVASCULAR,SLIGHT LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL SPLEEN (SP) : >UNREMARKABLE 829 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 ANIMAL NUMBER: I05508 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3285.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 10:24 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.4890 GRAMS BILE VOLUME IS 1.6000 ML LN, MESENTERIC (MS) : -HEMORRHAGE,-SLIGHT TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT COLON (CO) : -INFILTRATE, EOSINOPHILIC,-SLIGHT MAMMARY, MALE (MM) : >SECTION EXAMINED; TISSUE NOT PRESENT PROSTATE (PR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-MINIMAL 830 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 ANIMAL NUMBER: I05508 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3285.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 10:24 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), HEART (HT), GALLBLADDER THYMUS (TH), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), RECTUM (RE), SKIN (SK), URINARY BLADDER SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE) (GB), (UB), 831 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 ANIMAL NUMBER: I05517 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3055.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .2840 .1430 62.4920 1.0930 1.2250 5.9980 5.7530 44.2710 8.0310 8.1690 5.8790 .1490 .1400 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0093 % .0047 % 2.0456 % .0358 % .0401 % .1963 % .1883 % 1.4491 % .2629 % .2674 % .1924 % .0049 % .0046 % ORGAN TO BRAIN WEIGHT RATIO .0045 1..00000203 .0175 .0196 .0960 .0921 .7084 .1285 .1307 .0941 ..00002224 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MODERATE MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT LUNG (LU) : -HYPERPLASIA, LYMPHOCYTIC, PERIBRONCHIOLAR/PERIVASCULAR,MINIMAL LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL LN, MESENTERIC (MS) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE 832 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 5 ANIMAL NUMBER: I05517 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3055.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.6330 GRAMS BILE VOLUME IS 1.6000 ML TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT ADRENAL, CORTEX (AC) : -HYPERTROPHY, CORTICAL CELL,-MINIMAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL PANCREAS (PA) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL COLON (CO) : -PARASITISM, INTRAMUSCULAR,-PRESENT 833 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 6 ANIMAL NUMBER: I05517 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3055.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), JEJUNUM (JE), ILEUM (IL), CECUM (CE), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE) 834 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 7 ANIMAL NUMBER: I05519 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3140.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 6:57 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .2820 .2330 62.8980 .7730 .8270 5.5490 5.3860 53.1740 2.7780 2.9990 5.5570 .1310 .1220 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0090 % .0074 % 2.0031 % .0246 % .0263 % .1767 % .1715 % 1.6934 % .0885 % .0955 % .1770 % .0042 % .0039 % ORGAN TO BRAIN WEIGHT RATIO .0045 .0037 1.0000 .0123 .0131 .0882 .0856 .8454 .0442 .0477 .0883 .0021 .0019 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MODERATELY SEVERE MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-MINIMAL KIDNEY (KD) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL LUNG (LU) : -HYPERPLASIA, LYMPHOCYTIC, PERIBRONCHIOLAR/PERIVASCULAR,SLIGHT 835 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 8 ANIMAL NUMBER: I05519 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3140.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 6:57 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL GALLBLADDER (GB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT PARATHYROID (PT) : -CYST,-PRESENT ADRENAL, CORTEX (AC) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE CECUM (CE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE MAMMARY, MALE (MM) : >SECTION EXAMINED; TISSUE NOT PRESENT PROSTATE (PR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-MINIMAL EPIDIDYMIDES (EP) : -HYPOSPERMIA,-MODERATE TESTIS (TE) : -IMMATURE,-PRESENT 836 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 9 ANIMAL NUMBER: I05519 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3140.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 6:57 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.7260 GRAMS BILE VOLUME IS 1.2000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), HEART (HT), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), ESOPHAGUS (ES), THYROID (TY), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), COLON (CO), RECTUM (RE), SKIN (SK), URINARY BLADDER (UB), SEMINAL VESICLES (SV) 837 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 10 ANIMAL NUMBER: I05527 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 4680.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 11:00 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .3120 .2600 64.8130 1.8660 1.7750 7.5090 7.3890 62.8470 11.5730 10.6940 6.0920 .2380 .2750 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0067 % .0056 % 1.3849 % .0399 % .0379 % .1604 % .1579 % 1.3429 % .2473 % .2285 % .1302 % .0051 % .0059 % ORGAN TO BRAIN WEIGHT RATIO .0048 .0040 1.0000 .0288 .0274 .1159 .1140 .9697 .1786 .1650 .0940 .0037 .0042 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-SLIGHT MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-MINIMAL LUNG (LU) : -HYPERPLASIA, LYMPHOCYTIC, PERIBRONCHIOLAR/PERIVASCULAR,SLIGHT LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -GRANULOMA,-MINIMAL, FOCAL 838 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 11 ANIMAL NUMBER: I05527 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 4680.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 11:00 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY SKIN (SK) : -ABRASION(S)/ULCERATION(S); 2.0 CM FROM TIP OF TAIL: SINGLE RED, MOIST ABRADED AREA, 0.8 CM IN DIAMETER; COLLECTED GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.6430 GRAMS BILE VOLUME IS 2.4000 ML THYMUS (TH) : -ATROPHY,-SEVERE SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL MUSCLE, SKELETAL (SM) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL DUODENUM (DU) -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE SKIN (SK) : -HYPERPLASIA, EPIDERMAL (ACANTHOSIS),-MODERATE -INFLAMMATION, CHRONIC-ACTIVE,-SLIGHT -ULCERATION,-MODERATELY SEVERE URINARY BLADDER (UB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL 839 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 12 ANIMAL NUMBER: I05527 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 4680.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 11:00 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), PANCREAS (PA), JEJUNUM (JE), CECUM (CE), COLON (CO), RECTUM (RE), MAMMARY, MALE (MM), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE) 840 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 13 ANIMAL NUMBER: I05514 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3495.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:21 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .3620 .2420 62.4280 1.1580 1.0010 6.0230 6.1700 64.2170 6.7090 5.1600 4.7970 .3130 .3200 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0104 % .0069 % 1.7862 % .0331 % .0286 % .1723 % .1765 % 1.8374 % .1920 % .1476 % .1373 % .0090 % .0092 % ORGAN TO BRAIN WEIGHT RATIO .0058 .0039 1.0000 .0185 .0160 .0965 .0988 1.0287 .1075 .0827 .0768 .0050 .0051 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); ALL LOBES TO EACH OTHER, PLEURA, PERICARDIAL SAC, AND CAUDAL LOBES TO DIAPHRAGM: MULTIPLE RED, TAN, FIBROUS ADHESIONS; COLLECTED INTACT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL THYMUS (TH) : -ATROPHY,-MODERATE 841 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 14 ANIMAL NUMBER: I05514 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3495.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:21 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.7220 GRAMS BILE VOLUME IS 1.4000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 842 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 15 ANIMAL NUMBER: I05515 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3475.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 6:45 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .2770 .1900 63.7670 .7590 .8690 6.4220 6.2010 55.8260 2.7190 3.3300 5.0260 .1340 .1240 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0080 % .0055 % 1.8350 % .0218 % .0250 % .1848 % .1784 % 1.6065 % .0782 % .0958 % .1446 % .0039 % .0036 % ORGAN TO BRAIN WEIGHT RATIO .0043 .0030 1.0000 .0119 .0136 .1007 .0972 .8755 .0426 .0522 .0788 .0021 .0019 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.4620 GRAMS BILE VOLUME IS 1.2000 ML LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL 843 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 16 ANIMAL NUMBER: I05515 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3475.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 6:45 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: THYMUS (TH) 844 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 17 ANIMAL NUMBER: I05516 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3170.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:15 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN S T A rr U S LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .2940 .2410 67.0240 .8820 .7570 6.8380 7.0240 68.1040 3.3570 5.1290 3.0500 .2040 .1430 .0093 % .0076 % 2.1143 % .0278 % .0239 % .2157 % .2216 % 2.1484 % .1059 % .1618 % .0962 % .0064 % .0045 % .0044 .0036 1.0000 .0132 .0113 .1020 .1048 1.0161 .0501 .0765 .0455 .0030 .0021 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY SPLEEN (SP) : -LARGE; 7.0 X 5.0 X 3.0 CM TESTIS (TE) : -LARGE; RIGHT: 2.5 X 1.5 X 1.4 CM (FOR COMPARISON, LEFT IS 2.0 X 1.5 X 1.0 CM) GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS SPLEEN (SP) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL THYMUS (TH) : -CYST',-PRESENT TESTIS (TE) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL 845 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 18 ANIMAL NUMBER: I05516 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3170.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:15 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.6300 GRAMS BILE VOLUME IS 1.4000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER (LI) 846 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 19 ANIMAL NUMBER: I05521 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 4385.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 10:48 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .3090 .2230 53.9580 2.8840 2.7980 7.1230 7.6030 60.2000 18.7540 18.8730 6.3800 .4490 .4660 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0070 % .0051 % 1.2305 % .0658 % .0638 % .1624 % .1734 % 1.3729 % .4277 % .4304 % .1455 % .0102 % .0106 % ORGAN TO BRAIN WEIGHT RATIO .0057 .0041 1.0000 .0534 .0519 .1320 .1409 1.1157 .3476 .3498 .1182 .0083 .0086 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -VACUOLATION, HEPATOCELLULAR,-MINIMAL, MULTI-FOCAL -STASIS, BILE,-MODERATE, MULTI-FOCAL THYMUS (TH) : -ATROPHY,-MODERATELY SEVERE 847 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 20 ANIMAL NUMBER: I05521 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 4385.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 10:48 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.4810 GRAMS BILE VOLUME IS 1.4000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 848 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 21 ANIMAL NUMBER: I05510 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3180.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 9:48 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .2490 .1600 56.7600 1.0910 1.0750 6.4950 6.1190 54.2060 6.0950 5.8860 3.8800 .1660 .1960 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0078 % .0050 % 1.7849 % .0343 % .0338 % .2042 % .1924 % 1.7046 % .1917 % .1851 % .1220 % .0052 % .0062 % ORGAN TO BRAIN WEIGHT RATIO .0044 .0028 1.0000 .0192 .0189 .1144 .1078 .9550 .1074 .1037 .0684 .0029 .0035 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); BILATERAL CAUDAL LOBES TO PLEURA AND DIAPHRAGM: MULTIPLE TAN, FIBROUS ADHESIONS; COLLECTED INTACT ADIPOSE TISSUE (AT) : -RAISED FOCUS(I)/AREA(S); DIFFUSE, THROUGHOUT MESENTERY AND THORACIC CAVITY: MULTIPLE, TAN, FIRM NODULES, UP TO 0.6 CM IN DIAMETER WITHIN MESENTERY (CAP 29), UP TO 0.3 CM IN DIAMETER WITHIN THORACIC CAVITY (CAP 30) AND COLLECTED INTACT WITH LUNG ADHESIONS GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL ADIPOSE TISSUE (AT) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL 849 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 22 ANIMAL NUMBER: I05510 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3180.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 9:48 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.6690 GRAMS BILE VOLUME IS 2.4000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER (LI), THYMUS (TH) 850 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 23 ANIMAL NUMBER: I05518 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3070.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 9:20 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .2790 .2460 62.8420 .8790 1.0970 5.6790 5.6110 57.5930 4.5720 4.6220 3.1580 .2450 .3110 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0091 % .0080 % 2.0470 % .0286 % .0357 % .1850 % .1828 % 1.8760 % .1489 % .1506 % .1029 % .0080 % .0101 % ORGAN TO BRAIN WEIGHT RATIO .0044 .0039 1.0000 .0140 .0175 .0904 .0893 .9165 .0728 .0735 .0503 .0039 .0049 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5320 GRAMS BILE VOLUME IS 1.3000 ML THYMUS (TH) : -ATROPHY,-MINIMAL 851 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 24 ANIMAL NUMBER: I05518 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3070.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 9:20 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER (LI) 852 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 25 ANIMAL NUMBER: I05524 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3035.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:42 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .2420 .1860 63.9330 .9350 .9840 5.0370 4.8440 52.5550 4.6940 4.2750 4.6550 .1210 .1330 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0080 % .0061 % 2.1065 % .0308 % .0324 % .1660 % .1596 % 1.7316 % .1547 % .1409 % .1534 % .0040 % .0044 % ORGAN TO BRAIN WEIGHT RATIO .0038 .0029 1.0000 .0146 .0154 .0788 .0758 .8220 .0734 .0669 .0728 .0019 .0021 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.9610 GRAMS BILE VOLUME IS 0.8000 ML THYMUS (TH) : -ATROPHY,-MINIMAL 853 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 26 ANIMAL NUMBER: I05524 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3035.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:42 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER (LI) 854 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 27 ANIMAL NUMBER: I05528 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3475.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 10:19 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .3070 .2620 69.8730 .9990 .9290 6.3390 6.3690 64.9760 5.0300 5.2350 5.8230 .2980 .3900 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0088 % .0075 % 2.0107 % .0287 % .0267 % .1824 % .1833 % 1.8698 % .1447 % .1506 % .1676 % .0086 % .0112 % ORGAN TO BRAIN WEIGHT RATIO .0044 .0037 1.0000 .0143 .0133 .0907 .0912 .9299 .0720 .0749 .0833 .0043 .0056 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5220 GRAMS BILE VOLUME IS 1.8000 ML LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -HYPERTROPHY, HEPATOCELLULAR,-SLIGHT, DIFFUSE THYMUS (TH) : -ATROPHY,-SLIGHT 855 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 28 ANIMAL NUMBER: I05528 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3475.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 10:19 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 856 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 29 ANIMAL NUMBER: I05507 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3870.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .4540 .3210 71.7900 2.0740 2.3260 6.5150 6.2950 112.4190 12.6370 12.5000 5.2280 .2850 .3460 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0117 % .0083 % 1.8550 % .0536 % .0601 % .1683 % .1627 % 2.9049 % .3265 % .3230 % .1351 % .0074 % .0089 % ORGAN TO BRAIN WEIGHT RATIO .0063 .0045 1.0000 .0289 .0324 .0908 .0877 1.5659 .1760 .1741 .0728 .0040 .0048 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY LIVER (LI) : -MOTTLED; ALL LOBES: BROWN AND TAN BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-SLIGHT MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, LYMPHOHISTIOCYTIC, PERIVASCULAR,-MINIMAL -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-SLIGHT KIDNEY (KD) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL -MINERALIZATION, CORTEX,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR,-MODERATE, DIFFUSE 857 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 30 ANIMAL NUMBER: I05507 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3870.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY LN, MESENTERIC (MS) : -DIFFUSELY RED; DARK RED ADRENAL, CORTEX (AC) : -DIFFUSELY DARK; BILATERAL: DARK BROWN GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5330 GRAMS BILE VOLUME IS 2.0000 ML LIVER (LI) : -VACUOLATION, HEPATOCELLULAR, CENTRILOBULAR,-MODERATELY SEVERE THYMUS (TH) : -CYST,-PRESENT -ATROPHY,-MODERATELY SEVERE LN, MESENTERIC (MS) : >UNREMARKABLE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT ADRENAL, CORTEX (AC) : >UNREMARKABLE JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE PROSTATE (PR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-MINIMAL 858 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 31 ANIMAL NUMBER: I05507 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3870.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 8:11 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE) 859 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 32 ANIMAL NUMBER: I05512 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2285.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:21 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ORGAN NAME LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF EPIDIDYMIS (EP0) RT EPIDIDYMIS (EP1) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF TESTIS (TE0) RT TESTIS (TE1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) ABSOLUTE ORGAN WEIGHT (GRAMS) .2790 .2240 60.7370 .5450 .4350 4.5470 4.5140 58.1440 1.4310 1.3310 3.0430 .1190 .1260 ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) .0122 % .0098 % 2.6581 % .0239 % .0190 % .1990 % .1975 % 2.5446 % .0626 % .0582 % .1332 % .0052 % .0055 % ORGAN TO BRAIN WEIGHT RATIO .0046 .0037 1.0000 .0090 .0072 .0749 .0743 .9573 .0236 .0219 .0501 .0020 .0021 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN NECROPSY OBSERVATIONS HISTOPATHOLOGY LIVER (LI) : -MOTTLED; ALL LOBES: BROWN AND TAN BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MODERATE MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-MINIMAL LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SLIGHT GALLBLADDER (GB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT THYMUS (TH) : -ATROPHY,-MODERATELY SEVERE 860 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 33 ANIMAL NUMBER: I05512 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2285.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:21 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY ADRENAL, CORTEX (AC) : -DIFFUSELY DARK; BILATERAL: BROWN GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.3100 GRAMS BILE VOLUME IS 1.2000 ML LN, MESENTERIC (MS) : -HEMORRHAGE,-MINIMAL TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT -INFLAMMATION, ACUTE,-MINIMAL ADRENAL, CORTEX (AC) : >UNREMARKABLE SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT MAMMARY, MALE (MM) : >SECTION EXAMINED; TISSUE NOT PRESENT PROSTATE (PR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-MINIMAL EPIDIDYMIDES (EP) : -HYPOSPERMIA,-SEVERE TESTIS (TE) : -IMMATURE,-PRESENT 861 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 34 ANIMAL NUMBER: I05512 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2285.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:21 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), KIDNEY (KD), LUNG (LU), HEART (HT), SPLEEN (SP), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), URINARY BLADDER (UB), SEMINAL VESICLES (SV) (PA), 862 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 35 ANIMAL NUMBER: I05530 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2755.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 11:29 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) ORGAN TO BRAIN WEIGHT RATIO ORGAN S T A rr U S LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) NECROPSY .2480 .1640 60.5500 5.6520 5.4770 49..11282000 .1280 4..22140700 .2150 .0090 % .0060 % 2.1978 % .2052 % .1988 % 1.7851 % .0044 % .0046 % .1542 % .0076 % .0078 % OBSERVATIONS .0041 1..00000207 .0933 .0905 ...008001222012 .0701 .0035 .0036 WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); ALL LOBES TO EACH OTHER, PLEURA, PERICARDIAL SAC, AND CAUDAL LOBES TO DIAPHRAGM: MULTIPLE RED, TAN, FIBROUS ADHESIONS; COLLECTED INTACT BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MINIMAL BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-MODERATE KIDNEY (KD) : -GLOMERULOSCLEROSIS,-MINIMAL LUNG (LU) : -HYPERPLASIA, LYMPHOCYTIC, PERIBRONCHIOLAR/PERIVASCULAR,MINIMAL -FIBROSIS, PLEURAL/SUBPLEURAL,-SLIGHT LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL 863 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 36 ANIMAL NUMBER: I05530 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2755.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 11:29 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5970 GRAMS BILE VOLUME IS 1.2000 ML THYROID (TY) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL MUSCLE, SKELETAL (SM) : -DEGENERATION,-SLIGHT -INFLAMMATION, GRANULOMATOUS,-MODERATE -REGENERATION, MYOFIBER,-MODERATELY SEVERE URINARY BLADDER (UB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL 864 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 37 ANIMAL NUMBER: I05530 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2755.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 11:29 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS(UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), ESOPHAGUS (ES), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV) 865 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 38 ANIMAL NUMBER: I05531 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2625.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:15 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .2360 .1480 54.3050 4.3520 4.2910 42.1310 .0990 .0930 3.9080 .1970 .1740 .0090 % .0056 % 2.0688 % .1658 % .1635 % 1.6050 % .0038 % .0035 % .1489 % .0075 % .0066 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0043 .0027 1.0000 .0801 .0790 .7758 .0018 .0017 .0720 .0036 .0032 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-SLIGHT KIDNEY (KD) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL ADRENAL, CORTEX (AC) : -HYPERTROPHY, CORTICAL CELL,-MINIMAL SPINAL CORD (SC) : -PIGMENT, NEURONAL,-SLIGHT JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE 866 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 39 ANIMAL NUMBER: I05531 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2625.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:15 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.7250 GRAMS BILE VOLUME IS 1.8000 ML ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MINIMAL UTERUS (UT) : -AMYLOID,-SLIGHT 867 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 40 ANIMAL NUMBER: I05531 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2625.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:15 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY(OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: BONE, FEMUR (FE), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), OVARY (OV), VAGINA (VA), CERVIX (CV) 868 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 41 ANIMAL NUMBER: I05535 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3270.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 8:13 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3770 .3150 51.9670 6.6940 6.1830 64.3990 .2280 .2100 5.0450 .4660 .4370 .0115 % .0096 % 1.5892 % .2047 % .1891 % 1.9694 % .0070 % .0064 % .1543 % .0143 % .0134 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0073 .0061 1.0000 .1288 .1190 1.2392 .0044 .0040 .0971 .0090 .0084 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); ALL LOBES TO EACH OTHER, PLEURA, AND PERICARDIAL SAC: MULTIPLE RED, TAN, FIBROUS ADHESIONS; COLLECTED INTACT STOMACH, GL (ST) : -RED FOCUS(I)/AREA(S); MUCOSA, FUNDIC: SINGLE RED FOCUS, 0.3 MM IN DIAMETER; FOCUS HAS A STELLATE PATTERN MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT LUNG (LU) : -FIBROSIS, PLEURAL/SUBPLEURAL,-SEVERE -FIBROSIS, INTERSTITIAL,-MODERATELY SEVERE LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -VACUOLATION, HEPATOCELLULAR,-MINIMAL, MULTI-FOCAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT STOMACH, GL (ST) : >UNREMARKABLE 869 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 42 ANIMAL NUMBER: I05535 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3270.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 8:13 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY STOMACH, GL (ST) : >NOTE:>FUNDIC MUCOSA, ALONG GREATER CURVATURE: SINGLE APPARENT HOOK WORM EMBEDDED INTO MUCOSA, 3.0 X 0.1 X 0.1 CM GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>ANIMAL APPEARS TO BE IN ESTROUS GALLBLADDER WEIGHT IS 0.6970 GRAMS BILE VOLUME IS 2.6000 ML DUODENUM (DU) -INFILTRATE, MACROPHAGE, PIGMENTED, -MODERATE JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED, -MODERATE ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED, -MODERATE CECUM (CE) : -INFILTRATE, MACROPHAGE, PIGMENTED, -SLIGHT MAMMARY, FEMALE (MF) : -INFLAMMATION, ACUTE,-MINIMAL URINARY BLADDER (UB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL UTERUS (UT) : -AMYLOID,-SLIGHT 870 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 43 ANIMAL NUMBER: I05535 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3270.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 8:13 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: BONE, FEMUR (FE), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), PANCREAS (PA), COLON (CO), RECTUM (RE), SKIN (SK), OVARY (OV), VAGINA (VA), CERVIX (CV) 871 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 44 ANIMAL NUMBER: I05544 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2635.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:55 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3120 .2440 59.7410 5.3110 5.2470 48.6600 .2260 .1380 4.5080 .1540 .1560 .0118 % .0093 % 2.2672 % .2016 % .1991 % 1.8467 % .0086 % .0052 % .1711 % .0058 % .0059 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0052 .0041 1.0000 .0889 .0878 .8145 .0038 .0023 .0755 .0026 .0026 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LIVER (LI) : -LIGHT FOCUS(I)/AREA(S); TRIM COMMENT: DIAPHRAGMATIC SURFACE OF LEFT LATERAL LOBE: SINGLE TAN AREA, 1.0 CM IN DIAMETER; SUBMITTED ON ROUTINE SECTION MARROW, STERNUM (SE) : -HYPOCELLULAR, MARROW,-SLIGHT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-MODERATE LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL GALLBLADDER (GB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL LN, MESENTERIC (MS) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT 872 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 45 ANIMAL NUMBER: I05544 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2635.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:55 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.3810 GRAMS BILE VOLUME IS 2.2000 ML ESOPHAGUS (ES) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL PARATHYROID (PT) : >SECTION EXAMINED; TISSUE NOT PRESENT MUSCLE, SKELETAL (SM) : -PARASITES, CYST,-PRESENT >NOTE:>HEAVY BURDEN, SARCOCYST-LIKE. DUODENUM (DU) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT MAMMARY, FEMALE (MF) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT URINARY BLADDER (UB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT OVARY (OV) : -MINERALIZATION,-MODERATE 873 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 46 ANIMAL NUMBER: I05544 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2635.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:55 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: BONE, FEMUR (FE), MARROW, FEMUR (FM), BONE, STERNUM (SB), EYE (EY), KIDNEY (KD), LUNG (LU), HEART (HT), SPLEEN (SP), THYMUS (TH), THYROID (TY), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY SALIV GL, MANDIB (SG), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), PANCREAS (PA), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), UTERUS (UT), VAGINA (VA), CERVIX (CV) (PI), 874 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 47 ANIMAL NUMBER: I05537 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 4055.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 7:31 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3730 .3030 61.3750 7.0240 6.6650 75.2140 .2790 .2280 6.1370 .3200 .3400 .0092 % .0075 % 1.5136 % .1732 % .1644 % 1.8548 % .0069 % .0056 % .1513 % .0079 % .0084 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0061 .0049 1.0000 .1144 .1086 1.2255 .0045 .0037 .1000 .0052 .0055 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -ANIMAL OBESE GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5100 GRAMS BILE VOLUME IS 3.0000 ML LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, THYMUS (TH) : -ATROPHY,-MINIMAL SPINAL CORD (SC) : -PIGMENT, NEURONAL,-SLIGHT MULTI-FOCAL 875 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 48 ANIMAL NUMBER: I05537 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 4055.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 7:31 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 876 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 49 ANIMAL NUMBER: I05541 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2510.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 9:47 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .4170 .3060 63.2760 4.9450 4.6880 47.6610 .1240 .1570 5.0750 .2130 .2300 .0166 .0122 2.5210 .1970 .1868 1.8988 .0049 .0063 .2022 .0085 .0092 % % % % % % % % % % % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0066 .0048 1.0000 .0781 .0741 .7532 .0020 .0025 .0802 .0034 .0036 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); RIGHT AND LEFT CAUDAL LOBES AND LEFT INTERMEDIATE LOBE TO DIAPHRAGM: MULTIPLE TAN, FIBROUS ADHESIONS; COLLECTED INTACT -DARK FOCUS(I)/AREA(S); ALL LOBES: MULTIPLE DARK BROWN AREAS, PINPOINT AND UP TO 0.7 X 0.4 CM LIVER (LI) : -ADHESION(S); DIAPHRAGMATIC SURFACE OF RIGHT LATERAL LOBE TO SURROUNDING MESENTERY, ALONG MARGIN: MULTIPLE TAN, FIBROUS ADHESIONS (CAP 29) LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL THYMUS (TH) : -ATROPHY,-MODERATE SPINAL CORD (SC) : -PIGMENT, NEURONAL,-MODERATE 877 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 50 ANIMAL NUMBER: I05541 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2510.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 9:47 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5260 GRAMS BILE VOLUME IS 1.0000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 878 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 51 ANIMAL NUMBER: I05547 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2570.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 9:20 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3130 .2300 60.8690 5.4180 5.5840 49.9520 .1590 .2030 5.1480 .1550 .1410 .0122 % .0089 % 2.3684 % .2108 % .2173 % 1.9437 % .0062 % .0079 % .2003 % .0060 % .0055 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0051 .0038 1.0000 .0890 .0917 .8206 .0026 .0033 .0846 .0025 .0023 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); LEFT CAUDAL LOBE TO DIAPHRAGM: MULTIPLE TAN FIBROUS ADHESIONS; COLLECTED INTACT -DARK FOCUS(I)/AREA(S); ALL LOBES: MULTIPLE DARK BROWN AREAS, PINPOINT AND UP TO 0.5 X 0.3 CM GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, THYMUS (TH) : -CYST,-PRESENT -ATROPHY,-SLIGHT MULTI-FOCAL 879 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 52 ANIMAL NUMBER: I05547 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2570.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 9:20 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5380 GRAMS BILE VOLUME IS 1.2000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: SPINAL CORD (SC) 880 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 53 ANIMAL NUMBER: I05550 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2820.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 6:43 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .4230 .2680 56.9130 6.0900 6.1500 54.4840 .1270 .1270 7.2830 .1670 .2290 .0150 % .0095 % 2.0182 % .2160 % .2181 % 1.9321 % .0045 % .0045 % .2583 % .0059 % .0081 % NECROPSY O B S E R V A T I <O N S ORGAN TO BRAIN WEIGHT RATIO .0074 .0047 1.0000 .1070 .1081 .9573 .0022 .0022 .1280 .0029 .0040 ORGAN S T A T1 U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); ALL LOBES TO EACH OTHER, PLEURA, PERICARDIAL SAC, CAUDAL LOBES TO DIAPHRAGM: MULTIPLE RED, TAN, FIBROUS ADHESIONS; COLLECTED INTACT GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL,r MULTI- FOCAL -VACUOLATION, HEPATOCELLULAR,-SLIGHT, MULTI-FOCAL THYMUS (TH) : -ATROPHY,-MINIMAL SPINAL CORD (SC) : -PIGMENT, NEURONAL,-SLIGHT 881 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 54 ANIMAL NUMBER: I05550 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2820.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 6:43 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.6200 GRAMS BILE VOLUME IS 1.2000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 882 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 55 ANIMAL NUMBER: I05532 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2550.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 6:47 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3230 .2160 60.2360 5.0310 4.9920 58.3190 .0630 .0870 4.5080 .1150 .1020 .0127 % .0085 % 2.3622 % .1973 % .1958 % 2.2870 % .0025 % .0034 % .1768 % .0045 % .0040 % NECROPSY O B S E R VATI'O N S ORGAN TO BRAIN WEIGHT RATIO .0054 .0036 1.0000 .0835 .0829 .9682 .0010 .0014 .0748 .0019 .0017 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -RED FOCUS(I)/AREA(S); ALL LOBES: MULTIPLE DARK RED PINPOINT FOCI GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.4650 GRAMS BILE VOLUME IS 1.2000 ML LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL THYMUS (TH) : -ATROPHY,-SEVERE SPINAL CORD (SC) : -PIGMENT, NEURONAL,-MODERATE 883 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 56 ANIMAL NUMBER: I05532 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2550.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 6:47 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER (LI) 884 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 57 ANIMAL NUMBER: I05538 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3200.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 10:25 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3850 .2630 55.6900 5.8390 5.3480 59.5780 .2420 .1690 4.8070 .1350 .1480 .0120 % .0082 % 1.7403 % .1825 % .1671 % 1.8618 % .0076 % .0053 % .1502 % .0042 % .0046 % NECROPSY O B S E R V A T I <O N S ORGAN TO BRAIN WEIGHT RATIO .0069 .0047 1.0000 .1048 .0960 1.0698 .0043 .0030 .0863 .0024 .0027 ORGAN S T A T1 U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -DARK FOCUS(I)/AREA(S); ALL LOBES, DIFFUSE: MULTIPLE BLACK PINPOINT FOCI SPLEEN (SP) : -LIGHT FOCUS(I)/AREA(S); DIFFUSE: MULTIPLE GRAY AREAS , UP TO 1.2 X 0.7 CM LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL LIVER (LI) : -INFILTRATE, :LYMPHOHISTIOCYTIC,-]MINIMAL r MULTI- FOCAL SPLEEN (SP) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL THYMUS (TH) : -ATROPHY,-SLIGHT SPINAL CORD (SC) : -PIGMENT, NEURONAL,-MINIMAL CECUM (CE) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL 885 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 58 ANIMAL NUMBER: I05538 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3200.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 10:25 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY CECUM (CE) : -RED FOCUS(I)/AREA(S); SEROSAL SURFACE: MULTIPLE DARK RED FOCI, UP TO 0.5 CM IN DIAMETER; COLLECTED ON ROUTINE SECTION GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5060 GRAMS BILE VOLUME IS 1.6000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 886 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 59 ANIMAL NUMBER: I05545 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2460.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 7:31 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .2640 .2060 55.6590 5.4870 5.2040 52.4930 .2040 .1400 4.1150 .2030 .1190 .0107 % .0084 % 2.2626 % .2230 % .2115 % 2.1339 % .0083 % .0057 % .1673 % .0083 % .0048 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0047 .0037 1.0000 .0986 .0935 .9431 .0037 .0025 .0739 .0036 .0021 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS -NO MACROSCOPIC LESIONS LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -DEGENERATION/NECROSIS, HEPATOCELLULAR,-MINIMAL, MULTI-FOCAL THYMUS (TH) : -CYST,-PRESENT -ATROPHY,-MINIMAL SPINAL CORD (SC) : -PIGMENT, NEURONAL,-MINIMAL 887 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 60 ANIMAL NUMBER: I05545 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2460.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 7:31 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.7210 GRAMS BILE VOLUME IS 1.4000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY(OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 888 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 61 ANIMAL NUMBER: I05548 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2865.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 11:00 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3880 .2850 61.9790 6.0250 6.0670 57.7670 .2400 .1510 5.0690 .1640 .1640 .0135 % .0099 % 2.1633 % .2103 % .2118 % 2.0163 % .0084 % .0053 % .1769 % .0057 % .0057 % NECROPSY O B S E R VATI'O N S ORGAN TO BRAIN WEIGHT RATIO .0063 .0046 1.0000 .0972 .0979 .9320 .0039 .0024 .0818 .0026 .0026 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); ADHERED TO PLEURA, DIAPHRAGM, PERICARDIUM, AND EACH OTHER: MULTIPLE GRAY, FIBROUS ADHESIONS; COLLECTED INTACT CECUM (CE) : -RED FOCUS(I)/AREA(S); DIFFUSE: MULTIPLE DARK RED FOCI, UP TO 0.5 CM IN DIAMETER; COLLECTED ON ROUTINE SECTION LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MODERATE, THYMUS (TH) : -ATROPHY,-MODERATELY SEVERE SPINAL CORD (SC) : -PIGMENT, NEURONAL,-SLIGHT CECUM (CE) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL FOCAL 889 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 62 ANIMAL NUMBER: I05548 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2865.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 11:00 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.7810 GRAMS BILE VOLUME IS 2.6000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) 890 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 63 ANIMAL NUMBER: I05534 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2500.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 8:14 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3290 .2270 54.3510 4.8280 4.9920 75.5500 .1600 .1480 4.4740 .1370 .1210 .0132 % .0091 % 2.1740 % .1931 % .1997 % 3.0220 % .0064 % .0059 % .1790 % .0055 % .0048 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0061 .0042 1.0000 .0888 .0918 1.3900 .0029 .0027 .0823 .0025 .0022 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -DARK FOCUS(I)/AREA(S); ALL LOBES: MULTIPLE DARK BROWN PINPOINT FOCI -LIGHT FOCUS(I)/AREA(S); RIGHT AND LEFT CAUDAL LOBES: MULTIPLE TAN AREAS, UP TO 0.2 X 0.1 CM BONE, FEMUR (FE) : -GROWTH PLATE OPEN,-MODERATE KIDNEY (KD) : -MINERALIZATION, MEDULLA,-MINIMAL LUNG (LU) : -HYPERPLASIA, LYMPHOCYTIC, PERIBRONCHIOLAR/PERIVASCULAR,MINIMAL -INFILTRATE, MACROPHAGE, ALVEOLAR,-MINIMAL LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -HYPERTROPHY HEPATOCELLULAR,-SLIGHT, DIFFUSE -VACUOLATION HEPATOCELLULAR,-SLIGHT, DIFFUSE 891 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 64 ANIMAL NUMBER: I05534 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2500.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 8:14 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY ADRENAL, CORTEX (AC) : -DIFFUSELY DARK; BILATERAL: BROWN CECUM (CE) : -DARK FOCUS(I)/AREA(S); SEROSAL SURFACE AND LUMEN, DIFFUSE: MULTIPLE DARK BROWN, SLIGHTLY RAISED AREAS, UP TO 0.5 X 0.2 CM; COLLECTED ON ROUTINE SECTION COLON (CO) : -DARK FOCUS(I)/AREA(S); SEROSAL SURFACE AND LUMEN, DIFFUSE: MULTIPLE DARK BROWN, SLIGHTLY RAISED FOCI, UP TO 0.3 CM IN DIAMETER; COLLECTED ON ROUTINE SECTION ADIPOSE TISSUE (AT) : -RAISED FOCUS(I)/AREA(S); MESENTERY, DIFFUSE: FOCI, UP TO 0.3 CM IN DIAMETER (CAP 29) GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN MULTIPLE TAN THYMUS (TH) : -ATROPHY,-MODERATE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT ADRENAL, CORTEX (AC) : >UNREMARKABLE DUODENUM (DU) : -INFILTRATE, MACROPHAGE, PIGMENTED,-MODERATE JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT CECUM (CE) : -PARASITISM,-PRESENT COLON (CO) : -PARASITISM, INTRAMUSCULAR,-PRESENT URINARY BLADDER (UB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL OVARY (OV) : -MINERALIZATION,-MINIMAL ADIPOSE TISSUE (AT) : -LYMPHOID TISSUE,-PRESENT 892 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 65 ANIMAL NUMBER: I05534 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2500.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 8:14 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5260 GRAMS BILE VOLUME IS 2.0000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), LN, MESENTERIC (MS), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), PANCREAS (PA), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), UTERUS (UT), VAGINA (VA), CERVIX (CV) 893 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 66 ANIMAL NUMBER: I05536 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3185.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:56 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3290 .2360 58.3990 6.9900 7.4110 93.8600 .1010 .1360 4.7900 .1910 .2400 .0103 % .0074 % 1.8336 % .2195 % .2327 % 2.9469 % .0032 % .0043 % .1504 % .0060 % .0075 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0056 .0040 1.0000 .1197 .1269 1.6072 .0017 .0023 .0820 .0033 .0041 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -DARK FOCUS(I)/AREA(S); ALL LOBES, PINPOINT BLACK FOCI LIVER (LI) : -MOTTLED; ALL LOBES: BROWN AND TAN DIFFUSE: MULTIPLE MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-MINIMAL LUNG (LU) : ^UNREMARKABLE LIVER (LI) : -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-MODERATE -VACUOLATION, HEPATOCELLULAR, CENTRILOBULAR,-MODERATELY SEVERE GALLBLADDER (GB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL 894 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 67 ANIMAL NUMBER: I05536 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3185.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:56 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY ADRENAL, CORTEX (AC) : -DIFFUSELY DARK; BILATERAL: BROWN GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN THYMUS (TH) : -CYST,-PRESENT -ATROPHY,-MODERATELY SEVERE TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT THYROID (TY) : -CYST, ULTIMOBRANCHIAL,-PRESENT ADRENAL, CORTEX (AC) : -HYPERTROPHY, CORTICAL CELL,-MINIMAL -PIGMENT,-SLIGHT SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL SPINAL CORD (SC) : -PIGMENT, NEURONAL,-MODERATE DUODENUM (DU) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT ILEUM (IL) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT CECUM (CE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT UTERUS (UT) : -AMYLOID,-MODERATE OVARY (OV) : -AMYLOID,-MODERATE -ONE EXAMINED,-PRESENT 895 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 68 ANIMAL NUMBER: I05536 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/25/99 STUDY DAY OF DEATH: 184 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 3185.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/99 9:56 PROSECTOR: STEVE VAN ADESTINE RECORDER: TODD ACKER POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: TODD ACKER NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY GENERAL COMMENT (GC) : -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.6650 GRAMS BILE VOLUME IS 2.6000 ML THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: BONE, FEMUR (FE), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), KIDNEY (KD), HEART (HT), SPLEEN (SP), LN, MESENTERIC (MS), ESOPHAGUS (ES), PARATHYROID (PT), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), MUSCLE, SKELETAL (SM), NERVE, SCIATIC (SN), STOMACH, GL (ST), PANCREAS (PA), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), VAGINA (VA), CERVIX (CV) 896 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 69 ANIMAL NUMBER: I05540 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2700.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 10:20 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3440 .2550 56.3190 5.2090 4.8440 63.0760 .1400 .1410 4.4510 .2480 .2540 .0127 % .0094 % 2.0859 % .1929 % .1794 % 2.3361 % .0052 % .0052 % .1649 % .0092 % .0094 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0061 .0045 1.0000 .0925 .0860 1.1200 .0025 .0025 .0790 .0044 .0045 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -RED FOCUS(I)/AREA(S); RIGHT CAUDAL AND APICAL LOBES: MULTIPLE DARK RED INDISTINCT AREAS MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFILTRATE, MACROPHAGES, PIGMENTED, PERIVASCULAR,-SLIGHT LUNG (LU) : -HEMORRHAGE,-MODERATE LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SLIGHT THYMUS (TH) : -CYST,-PRESENT -ATROPHY,-SLIGHT 897 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 70 ANIMAL NUMBER: I05540 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2700.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 10:20 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY SKIN (SK) : -ALOPECIA-FOCAL; RIGHT DORSAL THORACIC REGION: 0.3 X 2.5 CM (CAP 29) GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>GALLBLADDER WEIGHT IS 0.5650 GRAMS BILE VOLUME IS 1.6000 ML TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL THYROID (TY) : -CYST, ULTIMOBRANCHIAL,-PRESENT AORTA (AO) : -PROLIFERATION, INTIMAL,-MODERATE MUSCLE, SKELETAL (SM) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL DUODENUM (DU) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT SKIN (SK) : -HAIR FOLLICLES, DECREASED,-MODERATE 898 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 71 ANIMAL NUMBER: I05540 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2700.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 10:20 PROSECTOR: STEVE VAN ADESTINE RECORDER: JOHN S. HALFORD POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: JOHN S. HALFORD THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: BONE, FEMUR (FE), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), LN, MESENTERIC (MS), ESOPHAGUS (ES), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), PITUITARY (PI), SALIV GL, MANDIB (SG), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV) 899 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 72 ANIMAL NUMBER: I05551 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2230.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:43 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA ORGAN NAME ABSOLUTE ORGAN WEIGHT (GRAMS) ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) LEFT ADRENAL (AD0) RIGHT ADRENAL (AD1) BRAIN (BR) LF KIDNEY (KD0) RT KIDNEY (KD1) LIVER (LI) LF OVARY (OV0) RT OVARY (OV1) PANCREAS (PA) LF THYROID/PARA (TT0) RT THYROID/PARA (TT1) .3850 .2960 59.3140 6.0280 5.9040 68.7130 .2350 .1740 3.7750 .1730 .1630 .0173 % .0133 % 2.6598 % .2703 % .2648 % 3.0813 % .0105 % .0078 % .1693 % .0078 % .0073 % NECROPSY OBSERVATIONS ORGAN TO BRAIN WEIGHT RATIO .0065 .0050 1.0000 .1016 .0995 1.1585 .0040 .0029 .0636 .0029 .0027 ORGAN S T A rr U S WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN WEIGHT TAKEN HISTOPATHOLOGY LUNG (LU) : -RED FOCUS(I)/AREA(S); ALL LOBES: MULTIPLE DARK RED FOCI, PINPOINT AND UP TO 1 MM IN DIAMETER MARROW, FEMUR (FM) : >SECTION EXAMINED; TISSUE NOT PRESENT BRAIN (BR) : -INFLAMMATION, LYMPHOHISTIOCYTIC,-MINIMAL KIDNEY (KD) : -MINERALIZATION, MEDULLA,-MINIMAL LUNG (LU) : ^UNREMARKABLE LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL, MULTI-FOCAL -HYPERTROPHY, HEPATOCELLULAR, CENTRILOBULAR,-SLIGHT GALLBLADDER (GB) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL 900 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 73 ANIMAL NUMBER: I05551 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2230.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:43 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA NECROPSY O B S E R V A T I O N S (CONTINUED) HISTOPATHOLOGY SKIN (SK) : -ALOPECIA-DIFFUSE; ALL FOUR LIMBS: HAIRCOAT THIN; COLLECTED GENERAL COMMENT (GC) : -BONE MARROW SMEAR TAKEN -EYES - DAVIDSONS GENERAL INFORMATION (XX) : >NOTE:>ANIMAL APPEARS TO BE IN ESTROUS GALLBLADDER WEIGHT IS 0.6040 GRAMS BILE VOLUME IS 1.8000 ML TRACHEA (TR) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL THYROID (TY) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL SALIV GL, MANDIB (SG) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL MUSCLE, SKELETAL (SM) : -PARASITES, CYST,-PRESENT SPINAL CORD (SC) : -PIGMENT, NEURONAL,-MODERATE JEJUNUM (JE) : -INFILTRATE, MACROPHAGE, PIGMENTED,-SLIGHT SKIN (SK) : -HAIR FOLLICLES, DECREASED,-SLIGHT 901 APPENDIX 5 Individual Anatomic Pathology Data Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 74 ANIMAL NUMBER: I05551 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 02/26/99 STUDY DAY OF DEATH: 185 STUDY WEEK OF DEATH: 27 TERMINAL BODY WEIGHT: 2230.0 GRAMS DATE AND TIME OF NECROPSY: 02/26/99 7:43 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: ROBERT LEEDLE WEIGHER: MICHELE ZIMA THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), LIVER (LI), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), ADIPOSE TISSUE (AT), LN, TRACHEOBRON (TB), LN, ANT MES/PANC (AP) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: BONE, FEMUR (FE), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), HEART (HT), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), ESOPHAGUS (ES), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV) 902 APPENDIX 5 Individual Anatomic Pathology Data Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 1 ANIMAL NUMBER: I05511 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC DATE OF DEATH: 02/25/00 STUDY DAY OF DEATH: 549 STUDY WEEK OF DEATH: 79 TERMINAL BODY WEIGHT: 4240.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/00 7:56 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: AS ASSIGNED WEIGHER: MICHELE ZIMA *** ORGAN WEIGHTS WERE NOT RECORDED *** NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-SLIGHT THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: LIVER (LI), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), CAVITY, THORACIC (TA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER, BIOPSY (LI0) 903 APPENDIX 5 Individual Anatomic Pathology Data Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 2 ANIMAL NUMBER: I05522 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC DATE OF DEATH: 02/25/00 STUDY DAY OF DEATH: 549 STUDY WEEK OF DEATH: 79 TERMINAL BODY WEIGHT: 4350.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/00 8:35 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: AS ASSIGNED WEIGHER: MICHELE ZIMA *** ORGAN WEIGHTS WERE NOT RECORDED *** NECROPSY OBSERVATIONS HISTOPATHOLOGY LUNG (LU) : -ADHESION(S); ALL LOBES TO EACH OTHER, PLEURA, PERICARDIAL SAC AND CAUDAL LOBES TO DIAPHRAGM: MULTIPLE TAN FIBROUS ADHESIONS CAVITY, THORACIC (TA) : -NODULE(S); WITHIN ADHESIONS: MULTIPLE TAN AND FIRM NODULES UP TO 0.3 CM IN DIAMETER LIVER, BIOPSY (LI0) : -PIGMENT, HEPATOCELLULAR,-SLIGHT LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MODERATE -PIGMENT, HEPATOCELLULAR,-SLIGHT -HYPERPLASIA, BILE DUCT,-MODERATE -INFLAMMATION, EOSINOPHILIC, PERI-BILE DUCT,-MODERATE LUNG (LU) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: LIVER (LI), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, MALE (MM), URINARY BLADDER (UB), PROSTATE (PR), SEMINAL VESICLES (SV), EPIDIDYMIDES (EP), TESTIS (TE), GENERAL COMMENT (GC) 904 APPENDIX 5 Individual Anatomic Pathology Data Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 3 ANIMAL NUMBER: I05533 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC DATE OF DEATH: 02/25/00 STUDY DAY OF DEATH: 549 STUDY WEEK OF DEATH: 79 TERMINAL BODY WEIGHT: 2535.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/00 8:58 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: AS ASSIGNED WEIGHER: MICHELE ZIMA *** ORGAN WEIGHTS WERE NOT RECORDED *** NECROPSY OBSERVATIONS HISTOPATHOLOGY LIVER (LI) : -ADHESION(S); DIAPHRAGMATIC SURFACE OF RIGHT MEDIAN LOBE TO DIAPHRAGM: SINGLE TAN, FIBROUS LINEAR AREA, 2.0 CM IN LENGTH GALLBLADDER (GB) : >NOTE:>NO BILE AVAILABLE FOR SPECIAL PROCEDURE LIVER (LI) : -FIBROSIS, CAPSULAR,-SLIGHT GALLBLADDER (GB) : >NOT REQUIRED TO BE EXAMINED FOR ANIMAL THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), GENERAL COMMENT (GC), CAVITY, THORACIC (TA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER, BIOPSY (LI0) 905 APPENDIX 5 Individual Anatomic Pathology Data Recovery Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-223 3M T-6295.7 PAGE: 4 ANIMAL NUMBER: I05542 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC DATE OF DEATH: 02/25/00 STUDY DAY OF DEATH: 549 STUDY WEEK OF DEATH: 79 TERMINAL BODY WEIGHT: 3705.0 GRAMS DATE AND TIME OF NECROPSY: 02/25/00 9:23 PROSECTOR: KEVIN BILLINGS RECORDER: MICHELE ZIMA POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: AS ASSIGNED WEIGHER: MICHELE ZIMA *** ORGAN WEIGHTS WERE NOT RECORDED *** NECROPSY OBSERVATIONS HISTOPATHOLOGY GENERAL COMMENT (GC) : -NO MACROSCOPIC LESIONS LIVER (LI) : -INFILTRATE, LYMPHOHISTIOCYTIC,-MINIMAL THE FOLLOWING ORGANS WERE UNREMARKABLE AT NECROPSY: LIVER (LI), BONE, FEMUR (FE), MARROW, FEMUR (FM), MARROW, STERNUM (SE), BONE, STERNUM (SB), EYE (EY), BRAIN (BR), KIDNEY (KD), LUNG (LU), HEART (HT), GALLBLADDER (GB), SPLEEN (SP), THYMUS (TH), LN, MESENTERIC (MS), TRACHEA (TR), ESOPHAGUS (ES), THYROID (TY), PARATHYROID (PT), ADRENAL, CORTEX (AC), ADRENAL, MEDULLA (MA), AORTA (AO), PITUITARY (PI), SALIV GL, MANDIB (SG), MUSCLE, SKELETAL (SM), SPINAL CORD (SC), NERVE, SCIATIC (SN), STOMACH, GL (ST), DUODENUM (DU), PANCREAS (PA), JEJUNUM (JE), ILEUM (IL), CECUM (CE), COLON (CO), RECTUM (RE), SKIN (SK), MAMMARY, FEMALE (MF), URINARY BLADDER (UB), UTERUS (UT), OVARY (OV), VAGINA (VA), CERVIX (CV), CAVITY, THORACIC (TA) THE FOLLOWING TISSUES WERE UNREMARKABLE AT MICROSCOPIC EXAMINATION: LIVER, BIOPSY (LI0) 906 Covance 6329-223 3M T-6295.7 APPENDIX 6 AniLytics Inc. Quality Assurance Statements Summary and Individual Blood Hormone Determination Note: This appendix contains information supplied and audited by AniLytics Inc. 907 Covance 6329-223 3M T-6295.7 MV i J_ JL INCORPORATED 230001-G92ir1a-r0d1S6t8reet, S8u0it0e-223070-,2G8a1i5thersburg, MD 20877 The reports listed below was reviewed for compliance with the FDA Good Laboratory Practices and with the EPA Good Laboratory Practices. The final report and all associated raw data were reviewed for accuracy and consistency and the findings were reported to management. The methods used were the methods described and the report accurately reflects the data. Therefore, these studies were done in compliance with the FDA and EPA Good Laboratory Practices. sponsor : CoZ5fZc A/f65 QA Auditor STUDY: REPORT TYPE: AUDIT DATE: REPORT TO MGMT: AUDIT #: T&vfi,ry,rv % L-n MANAGEMENT 908 Covance 6329-223 3M T-6295.7 909 Covance 6329-223 3M T-6295.7 910 Covance 6329-223 3M T-6295.7 911 Covance 6329-223 3M T-6295.7 #Vi 1 / V 200 Girard Street, Suite 200, Gaithersburg, MD 20877 I NC OR P OR AT E D .301-921-0168 800-237-2815 The reports listed below was reviewed for compliance with the FDA Good Laboratory Practices and with the EPA Good Laboratory Practices. The final report and all associated raw data were reviewed for accuracy and consistency and the findings were reported to management. The methods used were the methods described and the report accurately reflects the data. Therefore, these studies were done in compliance with the FDA and EPA Good Laboratory Practices. __ Franklin B. Newman QA Auditor SPONSOR: C0\/Qfl/& A/j-05 STUDY: REPORT TYPE: 2c,tTjj3,'fT&?r,ot, f} AUDIT DATE: REPORT TO MGMT: AUDIT #: /-Te-?? <71-1% MANAGEMENT 9/H/'Vl 912 Covance 6329-223 3M T-6295.7 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 800-237-2815 The reports listed below was reviewed for compliance with the FDA Good Laboratory Practices and with EPA Good Laboratory Practices. The final report and all associated raw data were reviewed for accuracy and consistency and the findings were reported to management. The methods used were the methods described and the report accurately reflects the data. Therefore, these studies were done in compliance with the FDA and EPA Good Laboratory Practices. 913 Covance 6329-223 3M T-6295.7 914 Covance 6329-223 3M T-6295.7 915 Covance 6329-223 3M T-6295.7 916 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -50 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05508 I05517 I05519 I05520 I05526 I05527 54.69 49.55 64.74 47.30 60.37 50.69 14.54 36..1024 10.74 0.09 6.48 MEAN S.D. N 54.56 66.785 6.84 56.199 Group: Male 2 Dose Level: 0.03 I05514 I05515 I05516 I05521 71.04 38.63 58.36 58.05 1.18 9.81 0.34 14.26 MEAN S.D. N 56.52 13.374 4 6.40 6.767 4 Group: Male 3 Dose Level: 0.15 I05505 I05510 I05518 I05523 I05524 I05528 48.00 38.05 50.92 56.98 62.46 63.18 3.04 0.41 3.77 41..0328 0.97 MEAN S.D. N 53.27 69.606 2.27 16.674 Dosage Unit: mg/kg/day 29.48 51.76 31.21 30.92 31.69 43.40 20.01 54.86 17.51 39.76 27.63 24.47 000000......000000000000 36.41 69.077 30.71 146.158 600..00000 Dosage Unit: mg/kg/day 38.90 27.91 32.30 59.78 51.37 17.75 29.41 62.35 0000....00000000 39.72 14.114 4 40.22 20.296 4 00..00000 4 Dosage Unit: mg/kg/day 43.24 23.74 53.56 43.26 30.26 26.50 30.43 26.96 28.80 39.35 26.55 18.67 000000......000000000000 36.76 116.692 28.46 66.698 600..00000 0.44 0.98 200...189612 3.34 1.44 16.084 1.44 1.04 1.13 1.45 10..22171 4 1.20 0.60 10..0607 0.62 1.04 0.86 60.578 89.59 125.67 82.21 122.59 132.25 102.72 109.17 206.673 133.26 83.16 138.37 130.08 121.22 25.600 4 122.64 115.95 124.80 162.12 117.52 113.68 126.12 186.122 4.96 3.25 5.11 3.13 3.80 3.52 3.96 60.864 6.14 3.32 8.91 4.56 5.73 2.412 4 5.60 3.48 4.29 6.48 4.28 4.49 4.77 16.079 917 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -50 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 4 Dose Level: 0.75 I05506 I05507 I05509 I05511 I05512 I05522 46.92 41.20 65.60 48.27 49.15 44.81 3.31 212..2415 18.86 0.29 12.56 MEAN S.D. N 49.33 86.464 9.78 69.117 Group: Female 1 Dose Level: 0 I05529 I05530 I05531 I05535 I05544 I05549 68.63 64.90 55.89 51.86 55.61 52.20 0.49 0.03 0.36 0.38 0.38 0.04 MEAN S.D. N 58.18 66.956 0.28 60.195 Group: Female 2 Dose Level: 0.03 I05537 I05541 I05547 I05550 MEAN S.D. N 73.24 82.66 71.82 46.90 68.66 15.280 4 00..6169 0.16 0.29 0.33 0.230 4 Dosage Unit: mg/kg/day 26.45 49.83 30.80 32.75 38.12 49.93 29.18 33.79 24.47 46.01 22.90 48.77 000000......000000000000 37.98 69.951 34.19 106.950 600..00000 Dosage Unit: mg/kg/day 48.75 48.53 53.05 50.13 37.23 50.33 38.12 32.43 61.53 31.55 26.87 27.55 000000......000000000000 48.0 56.519 36.34 126.984 600..00000 Dosage Unit: mg/kg/day 91.05 60.36 55.87 50.49 129.22 42.73 39.96 46.09 0000....00000000 64.44 18.191 4 64.50 43.219 4 00..00000 4 0.08 1.45 1.81 0.42 10..6660 1.00 60.726 0.75 0.74 0.30 1.14 2.67 0.69 1.05 60.838 0.00 0.65 00..8789 0.58 0.398 4 148.18 111132..1617 152.20 162.79 151.90 140.14 216.669 91.26 153.02 45.26 128.93 96.13 87.95 100.43 376.095 158.33 140.97 115.35 107.01 130.42 23.561 4 4.90 4.66 5.14 4.13 4.63 3.36 4.47 60.639 5.25 8.79 16.59 3.80 4.13 4.43 7.17 46.963 6.80 6.99 4.66 4.27 5.68 1.414 4 918 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -50 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 3 Dose Level: 0.15 I05532 I05538 I05539 I05545 I05548 I05552 56.59 51.32 66.59 63.69 65.26 49.09 0.13 0.23 0.34 0.25 0.45 0.33 MEAN S.D. N 58.76 76.502 600..12190 Group: Female 4 Dose Level: 0.75 I05533 I05534 I05536 I05540 I05542 I05551 58.99 59.49 51.68 46.17 87.39 67.04 0.35 0.05 0.29 0.15 0.63 0.38 MEAN S.D. N 61.79 146.438 600..23011 Dosage Unit: mg/kg/day 51.67 52.69 129.12 176.45 63.53 23.32 35.53 35.81 82.62 132.50 47.80 15.96 000000......000000000000 82.80 576.794 58.37 426.484 600..00000 Dosage Unit: mg/kg/day 96.99 42.90 47.76 54.58 3896..8067 64.39 34.98 46.31 88.38 31.81 107.99 000000......000000000000 61.36 246.447 62.31 306.672 600..00000 40..0406 1.48 00..0607 1.52 1.36 16.663 2.10 0.98 0.17 1.51 00..2312 0.88 60.795 64.50 137.04 117.92 135.57 104.23 71.94 105.20 31.6182 101.63 97.38 124.27 126.16 109.29 95.16 108.98 13.6480 5.49 3.21 5.68 5.05 4.24 6.35 5.00 16.123 4.25 4.94 5.78 5.23 6.44 5.78 5.40 60.766 919 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -40 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05508 I05517 I05519 I05520 I05526 I05527 57.43 43.65 71.52 52.42 84.79 79.36 3.30 2.35 1100...123017 5.72 MEAN S.D. N 64.86 166.197 3.84 46.098 Group: Male 2 Dose Level: 0.03 I05514 I05515 I05516 I05521 79.55 67.38 87.16 62.83 1.10 5.86 0.19 9.82 MEAN S.D. N 74.23 11.141 4 4.24 4.473 4 Group: Male 3 Dose Level: 0.15 I05505 I05510 I05518 I05523 I05524 I05528 50.93 77.83 67.52 61.48 63.60 72.30 4.07 0.53 0.93 10..6881 6.04 MEAN S.D. N 65.61 69.320 2.34 26.235 Dosage Unit: mg/kg/day 23.93 42.46 32.19 46.29 26.36 33.96 11.61 29.34 19.63 35.48 20.87 34.93 000000......000000000000 34.20 86.780 25.31 69.507 600..00000 Dosage Unit: mg/kg/day 2351..0500 23.13 63.80 4.64 28.82 23.58 49.29 0000....00000000 35.86 19.695 4 26.58 18.359 4 00..00000 4 Dosage Unit: mg/kg/day 45.97 31.51 45.46 34.64 31.45 28.17 18.34 17.29 25.93 27.49 16.37 13.10 000000......000000000000 36.20 76.651 19.75 56.688 600..00000 0.26 0.50 0.56 0.34 1.13 0.95 0.62 60.345 10..2116 10..1924 0.86 0.442 4 0.85 0.69 10..0807 00..0705 0.69 60.689 113.08 104.32 122.61 137.32 154.19 99.03 121.76 206.932 140.65 97.32 127.13 120.13 121.31 18.118 4 130.66 104.25 145.93 136.56 107.44 111.71 122.76 176.258 4.24 2.99 5.26 3.54 3.86 4.72 4.10 60.819 6.28 4.57 5.92 6.34 5.78 0.826 4 6.01 3.94 4.76 5.13 4.14 3.63 4.60 60.881 920 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -40 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 4 Dose Level: 0.75 I05506 I05507 I05509 I05511 I05512 I05522 49.42 44.53 82.95 75.12 81.05 58.08 1.27 7.01 1.03 16.78 100..1114 MEAN S.D. N 65.19 166.683 6.06 66.565 Group: Female 1 Dose Level: 0 I05529 I05530 I05531 I05535 I05544 I05549 81.80 70.50 85.44 85.08 89.58 66.75 00..0411 0.25 0.37 0.44 0.15 MEAN S.D. N 79.86 69.123 0.27 60.168 Group: Female 2 Dose Level: 0.03 I05537 I05541 I05547 I05550 79.24 108.45 67.50 89.13 0.17 0.77 0.19 0.23 MEAN S.D. N 86.08 17.337 4 0.34 0.288 4 Dosage Unit: mg/kg/day 28.98 32.46 27.21 37.12 37.24 52.20 21.20 30.79 14.40 42.06 21.98 49.26 000000......000000000000 35.87 86.991 29.95 136.432 600..00000 Dosage Unit: mg/kg/day 42.94 90.55 52.80 79.48 72.70 50.29 31.46 65.47 91.87 52.46 46.44 34.57 000000......000000000000 64.79 186.833 53.71 226.407 600..00000 Dosage Unit: mg/kg/day 59.21 116.25 40.43 62.40 48.11 90.73 67.42 61.31 0000....00000000 69.57 32.593 4 66.89 17.818 4 00..00000 4 0.82 1.92 0.57 0.59 0.25 1.54 0.95 60.643 000...001001 0.73 2.16 0.69 0.62 60.827 0.01 0.26 1.14 0.93 0.59 0.536 4 157.93 88.90 116.45 188.61 169.66 158.85 146.73 366.914 75.62 128.68 73.71 125.42 106.71 76.27 97.74 256.813 131.29 132.70 86.87 88.98 109.96 25.465 4 5.12 6.69 4.44 4.90 3.80 3.42 4.73 16.157 4.60 5.65 4.93 4.02 3.73 4.49 4.57 60.680 6.03 6.63 4.59 2.99 5.06 1.624 4 921 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -40 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 3 Dose Level: 0.15 I05532 I05538 I05539 I05545 I05548 I05552 63.15 70.84 68.60 64.50 67.75 53.55 0.06 0.08 0.35 00..6163 0.40 MEAN S.D. N 64.73 66.148 0.28 60.234 Group: Female 4 Dose Level: 0.75 I05533 I05534 I05536 I05540 I05542 I05551 69.41 60.42 66.67 65.40 92.90 64.20 0.73 0.28 0.15 0.08 0.32 0.42 MEAN S.D. N 69.83 116.681 0.33 60.230 Dosage Unit: mg/kg/day 33.18 53.04 492.12 114.49 75.11 45.64 29.09 40.85 272.75 81.43 55.06 48.94 000000......000000000000 135.60 1766.980 88.02 926.174 600..00000 Dosage Unit: mg/kg/day 90.70 60.87 66.36 35.46 59.88 76.86 76.17 66.05 59.95 33.64 43.92 82.48 000000......000000000000 65.02 186.541 60.37 186.740 600..00000 10..0308 1.33 00..0107 2.13 0.84 60.901 0.00 0.13 0.04 11..0329 0.24 0.47 60.587 95.64 114.53 114.65 106.43 116.19 82.66 105.02 13.6401 108.13 81.98 114.01 119.54 151.57 108.31 113.92 22.6513 4.36 3.19 6.09 4.61 4.02 4.69 4.49 60.953 4.03 4.39 5.41 4.36 7.00 5.21 5.07 16.087 922 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N 59.85 50.40 74.30 55.75 72.92 67.71 63.49 69.676 2.60 2.25 0.40 3.11 0.48 2.43 1.88 16.151 Group: Male 2 Dose Level: 0.03 I05514 I05515 I05516 I05521 81.35 77.44 50.15 61.80 1.41 1.40 0.31 3.03 MEAN S.D. N 67.69 14.422 4 11..15241 4 Group: Male 3 Dose Level: 0.15 I05505 I05510 I05518 I05523 I05524 I05528 58.10 68.33 54.45 66.60 91.70 69.75 5.40 0.38 1.06 21..1316 0.74 MEAN S.D. N 68.16 136.025 1.84 16.867 Dosage Unit: mg/kg/day 18.82 35.11 25.09 29.31 22.23 29.56 27.46 41.06 31.24 51.38 21.97 26.74 000000......000000000000 26.69 56.838 33.31 106.926 600..00000 Dosage Unit: mg/kg/day 31.71 26.17 29.91 40.47 43.75 32.63 35.52 57.63 0000....00000000 32.07 6.060 4 42.38 11.204 4 00..00000 4 Dosage Unit: mg/kg/day 30.42 25.88 26.53 25.62 23.61 22.60 27.04 22.77 39.19 37.12 2321..6262 000000......000000000000 25.78 26.718 30.00 76.358 600..00000 000000......000000000000 600..00000 0000....00000000 00..00000 4 00..0000 0000....00030002 0.05 60.131 101.15 112.05 112.26 115.75 127.37 92.95 110.26 116.939 120.88 126.21 97.87 105.02 112.50 13.269 4 117.98 114.00 149.51 140.05 86.43 100.82 118.13 236.608 3.82 3.11 4.39 2.89 2.83 3.90 3.49 60.637 5.30 2.51 5.85 4.16 4.46 1.475 4 5.76 3.90 4.50 6.33 3.74 3.55 4.63 16.155 923 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 4 Dose Level: 0.75 I05506 I05507 I05509 I05511 I05512 I05522 47.35 48.45 71.85 71.00 65.67 61.00 0.85 1.81 1.13 2.40 0.17 3.96 MEAN S.D. N 60.89 106.801 1.72 16.341 Group: Female 1 Dose Level: 0 I05529 I05530 I05531 I05535 I05544 I05549 72.55 76.75 48.35 68.60 52.84 55.44 0.28 0.07 0.50 0.35 0.42 0.07 MEAN S.D. N 62.42 116.701 0.28 60.179 Group: Female 2 Dose Level: 0.03 I05537 I05541 I05547 I05550 80.90 66.41 83.87 47.16 0.16 0.17 0.46 0.31 MEAN S.D. N 69.59 16.783 4 0.28 0.141 4 Dosage Unit: mg/kg/day 26.15 32.25 24.92 24.62 33.79 36.25 31.68 32.53 22.42 48.45 36.30 41.15 000000......000000000000 29.66 56.047 35.42 86.885 600..00000 Dosage Unit: mg/kg/day 35.08 122.95 75.71 61.83 208.06 45.31 49.80 102.72 92.55 59.99 101.29 59.93 000000......000000000000 91.49 646.841 77.71 236.710 600..00000 Dosage Unit: mg/kg/day 63.92 70.21 65.82 44.95 82.77 78.87 70.18 119.41 0000....00000000 61.23 11.165 4 87.81 21.716 4 00..00000 4 000000......000000000000 600..00000 0000....00000001 10..0206 0.21 60.514 0000....00000000 00..00000 4 149.78 117.94 130.15 137.80 128.50 133.19 132.89 106.581 82.65 184.14 90.39 109.23 145.88 99.05 118.56 386.982 167.85 119.83 284.36 110.60 170.66 79.847 4 5.35 6.72 5.49 4.61 3.49 3.60 4.88 16.235 4.40 8.76 8.31 5.76 5.54 5.97 6.46 16.705 9.01 7.95 6.35 4.93 7.06 1.792 4 924 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day -27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ng/mL ESTRADIOL pg/mL ESTRONE pg/mL ESTRIOL pg/mL THYROID STIMULATING ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 3 Dose Level: 0.15 I05532 I05538 I05539 I05545 I05548 I05552 57.80 87.05 50.45 57.66 56.95 62.72 0.18 0.09 0.08 0.03 0.59 0.54 MEAN S.D. N 62.11 126.832 0.25 60.248 Group: Female 4 Dose Level: 0.75 I05533 I05534 I05536 I05540 I05542 I05551 80.05 71.00 48.50 68.05 82.95 63.39 0.55 0.19 0.16 0.05 0.37 0.18 MEAN S.D. N 68.99 126.436 0.25 60.179 Dosage Unit: mg/kg/day 73.31 34.86 45.40 97.36 80.60 35.64 64.68 46.45 87.24 92.73 76.53 71.52 000000......000000000000 61.20 266.181 73.19 166.617 600..00000 Dosage Unit: mg/kg/day 197.69 75.81 51.69 27.69 53.10 133.61 243.31 98.79 75.52 27.51 54.14 259.85 000000......000000000000 89.93 636.894 126.52 996.828 600..00000 10000.....0000900008 0.08 0.34 60.802 000000......000000000004 0.01 60.016 221.66 133.62 122.82 126.61 125.43 99.82 138.33 42.6411 298.47 161.23 130.92 94.60 124.93 119.61 154.96 73.6494 8.42 6.15 8.69 7.04 5.95 6.53 7.13 16.168 7.38 6.76 6.89 48..8986 7.73 7.10 16.295 925 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05508 I05517 I05519 I05520 I05526 I05527 MEAN S.D. N 59.57 58.12 56.30 51.45 54.80 56.59 56.14 26.818 0.56 1.38 20..1316 0.89 10.76 2.68 46.010 Group: Male 2 Dose Level: 0.03 I05514 I05515 I05516 I05521 72.96 56.42 53.39 60.98 2.64 1000...129024 MEAN S.D. N 60.94 8.601 4 3.48 4.532 4 Group: Male 3 Dose Level: 0.15 I05505 I05510 I05518 I05523 I05524 I05528 MEAN S.D. N 6616..1305 52.23 61.98 64.07 73.61 63.22 66.968 0.76 0.60 200...168813 1.04 1.00 60.563 Dosage Unit: mg/kg/day 14.21 30.66 19.61 31.75 17.02 31.22 21.01 42.28 34.97 65.45 32.02 47.15 000000......000000000000 24.08 86.004 40.48 156.181 600..00000 Dosage Unit: mg/kg/day 32.81 23.69 14.32 37.38 84.41 39.25 48.23 98.72 0000....00000000 27.05 10.218 4 67.65 28.460 4 00..00000 4 Dosage Unit: mg/kg/day 23.37 24.13 26.75 27.07 15.77 10.40 36.78 29.76 38.59 44.88 33.62 23.33 000000......000000000000 21.25 66.703 34.49 76.452 600..00000 0000....08002600 0.47 0.70 0.34 60.387 0.70 0.43 0.13 0.14 0.35 0.272 4 00..6087 00..0902 00..0312 0.33 60.387 252.81 298.92 279.29 241.26 316.62 250.74 273.27 306.081 306.12 283.59 272.54 229.90 273.04 31.973 4 265.64 255.41 272.85 228241..2001 228.32 254.57 256.007 3.21 4.67 4.18 4.63 3.30 4.37 4.06 60.649 6.21 3.96 4.83 5.43 5.11 0.951 4 4.21 4.29 3.46 5.45 3.41 3.17 4.00 60.844 926 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 4 Dose Level: 0.75 I05506 I05507 I05509 I05511 I05512 I05522 60.57 69.37 86.47 75.68 64.22 53.06 1.13 14.80 1.24 1.50 0.25 37.59 MEAN S.D. N 68.23 116.785 9.42 146.866 Group: Female 1 Dose Level: 0 I05529 I05530 I05531 I05535 I05544 I05549 58.61 77.09 60.99 61.72 62.18 56.68 0.31 00..2008 0.25 0.46 0.18 MEAN S.D. N 62.88 76.266 0.25 60.130 Group: Female 2 Dose Level: 0.03 I05537 I05541 I05547 I05550 76.40 81.53 63.15 64.55 0.23 0.31 0.39 0.27 MEAN S.D. N 71.41 8.993 4 0.30 0.068 4 Dosage Unit: mg/kg/day 24.16 51.78 17.49 261..1305 69.66 182.56 91.86 35.79 35.89 39.97 162.36 000000......000000000000 31.76 236.908 91.41 666.580 600..00000 Dosage Unit: mg/kg/day 42.85 39.24 88.53 40.91 75.30 65.95 72.21 74.66 208.96 63.01 65.02 56.58 000000......000000000000 58.80 206.805 90.07 586.605 600..00000 Dosage Unit: mg/kg/day 64.21 61.86 45.86 55.39 177.41 127.77 76.97 143.29 0000....00000000 56.83 8.209 4 131.36 41.770 4 00..00000 4 0.00 00..6366 0.14 0.04 0.03 0.21 60.259 0.18 0.69 0.27 0.40 20..2611 0.73 60.941 000...060081 0.27 0.24 0.319 4 229.83 199.81 259.19 230.58 246.92 270.21 239.42 256.037 256.85 189.21 211.24 267.83 216.47 236.08 229.61 296.621 279.90 240.82 223.65 232.10 244.12 24.864 4 3.61 3.33 4.31 4.22 2.99 3.18 3.61 60.549 58..0514 6.09 5.64 4.38 5.23 5.82 16.217 6.02 6.09 4.37 3.75 5.06 1.180 4 927 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 37 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM ,SALT (PFOS;:T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXU ^g/dL Group: Female 3 Dose Level: 0.15 I05532 I05538 I05539 I05545 I05548 I05552 66.39 54.30 50.23 46.45 46.73 56.82 0.20 0.07 0.08 0.09 0.30 0.48 MEAN S.D. N 53.49 76.537 0.20 60.162 Group: Female 4 Dose Level: 0.75 I05533 I05534 I05536 I05540 I05542 I05551 63.27 53.74 55.56 54.54 54.14 68.07 0.29 0.15 0.19 0.07 00..1029 MEAN S.D. N 58.22 56.998 0.15 60.080 Dosage Unit: mg/kg/day 383.80 27.95 38.80 119.09 34.02 27.36 351.81 58.49 86.17 227.52 52.35 51.92 000000......000000000000 105.17 1406.935 138.04 1246.485 600..00000 Dosage Unit: mg/kg/day 70.06 49.92 42.44 31.28 67.52 104.58 150.87 123.86 63.03 47.69 67.27 271.41 000000......000000000000 60.97 256.978 120.69 836.839 600..00000 11000.....2000500016 0.91 0.61 60.703 1.07 10..0509 0.26 00..1502 0.59 60.622 192.15 225.80 221.63 237.82 184.62 220.15 213.70 20.6701 190.90 203.76 204.79 191.80 196.18 190.95 196.40 6.6414 4.53 3.21 3.49 4.18 2.78 3.89 3.68 60.646 3.51 5.03 3.62 3.16 4.84 5.21 4.23 60.895 928 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05508 I05517 I05519 I05520 I05526 I05527 64.62 57.71 60.20 50.13 63.25 43.13 0.50 1.30 0.39 2.28 0.65 1.40 MEAN S.D. N 56.51 8.318 6 1.09 0.719 6 Group: Male 2 Dose Level: 0.03 I05514 I05515 I05516 I05521 86.10 59.33 49.45 62.77 2.10 0.67 0.27 3.13 MEAN S.D. N 64.41 15.522 4 1.54 1.318 4 Group: Male 3 Dose Level: 0.15 I05505 I05510 I05518 I05523 I05524 I05528 70.82 58.68 60.80 76.60 62.76 63.38 1.07 0.51 0.77 2.83 0.94 0.77 MEAN S.D. N 65.51 6.813 6 1.15 0.845 6 Dosage Unit: mg/kg/day 17.70 35.89 27.43 27.41 15.13 38.03 28.21 51.07 24.22 69.97 34.66 42.05 0.00 0.00 0.00 0.00 0.00 0.00 26.93 9.256 6 41.70 16.877 6 0.00 0.000 6 Dosage Unit: mg/kg/day 29.19 27.02 17.22 44.97 71.76 53.19 77.85 95.20 0.00 0.00 0.00 0.00 29.60 11.494 4 74.50 * 17.333 4 0.00 0.000 4 Dosage Unit: mg/kg/day 34.40 25.73 31.30 35.79 21.61 14.54 36.91 26.22 30.11 62.53 31.79 33.29 0.00 0.00 0.00 0.00 0.00 0.00 27.23 8.199 6 36.81 13.086 6 0.00 0.000 6 0.25 1.72 0.00 0.00 0.00 1.42 0.57 0.790 6 0.54 0.11 0.47 0.57 0.42 0.213 4 1.22 1.53 2.85 0.00 0.00 0.29 0.98 1.118 6 119.34 163.61 145.97 164.61 139.41 135.30 144.71 17.407 6 147.03 143.03 118.77 148.62 139.36 13.928 4 131.32 117.68 167.15 166.99 135.36 131.96 141.74 20.528 6 2.89 2.79 2.77 3.81 1.73 2.55 2.76 0.667 6 4.36 3.15 4.47 3.64 3.91 * 0.624 4 3.22 2.56 2.73 4.44 2.60 2.90 3.08 0.711 6 929 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 4 Dose Level: 0.75 I05506 I05507 I05509 I05511 I05512 I05522 70.92 69.36 80.21 83.50 69.38 65.14 0.61 2.05 1.10 1.52 0.19 1.87 MEAN S.D. N 73.09 * 7.137 6 1.22 0.728 6 Group: Female 1 Dose Level: 0 I05529 I05530 I05531 I05535 I05544 I05549 73.17 80.23 63.57 77.78 72.02 67.18 0.25 0.03 0.23 0.29 0.24 0.11 MEAN S.D. N 72.33 6.264 6 0.19 0.100 6 Group: Female 2 Dose Level: 0.03 I05537 I05541 I05547 I05550 75.87 88.44 67.51 72.45 0.24 0.30 0.41 0.42 MEAN S.D. N 76.07 8.934 4 0.34 0.087 4 Dosage Unit: mg/kg/day 6.89 14.27 8.28 4.43 20.03 30.27 84.83 50.89 33.16 43.47 35.68 56.44 0.00 0.00 0.00 0.00 0.00 0.00 14.03 9.757 6 50.75 18.886 6 0.00 0.000 6 Dosage Unit: mg/kg/day 42.49 40.60 87.01 135.19 110.97 88.68 95.52 73.45 154.45 166.44 116.03 104.97 0.00 0.00 0.00 0.00 0.00 0.00 84.16 37.377 6 118.48 35.602 6 0.00 0.000 6 Dosage Unit: mg/kg/day 97.35 95.89 71.56 63.70 171.29 128.24 149.12 160.38 0.00 0.00 0.00 0.00 82.13 17.053 4 152.26 18.393 4 0.00 0.000 4 0.00 0.33 0.97 0.00 0.00 0.00 0.22 0.392 6 2.88 0.32 0.00 0.00 3.86 0.10 1.19 1.718 6 0.00 0.09 1.74 0.00 0.46 0.856 4 110.61 96.11 120.78 133.14 121.31 142.07 120.67 16.237 6 86.34 157.85 105.00 104.25 94.26 141.85 114.93 28.369 6 178.52 124.69 122.85 116.15 135.55 28.879 4 2.24 2.24 3.01 3.42 1.84 2.79 2.59 0.585 6 2.55 5.01 3.16 3.14 3.32 3.98 3.53 0.859 6 4.64 5.27 3.51 2.87 4.07 1.083 4 930 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 62 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 3 Dose Level: 0.15 I05532 I05538 I05539 I05545 I05548 I05552 63.46 62.14 65.91 60.86 48.14 61.25 0.05 0.06 0.00 0.05 0.36 0.44 MEAN S.D. N 60.29 6.228 6 0.16 0.189 6 Group: Female 4 Dose Level: 0.75 I05533 I05534 I05536 I05540 I05542 I05551 68.36 67.55 73.98 73.87 66.81 113.15 1.04 0.05 0.12 0.09 0.40 0.10 MEAN S.D. N 77.29 17.850 6 0.30 0.384 6 Dosage Unit: mg/kg/day 196.89 40.91 50.54 142.62 60.76 60.28 162.41 57.31 122.72 226.73 96.83 85.06 0.00 0.00 0.00 0.00 0.00 0.00 92.00 63.048 6 125.18 61.195 6 0.00 0.000 6 Dosage Unit: mg/kg/day 539.64 21.16 53.49 47.69 414.10 98.43 637.44 92.30 103.29 87.57 248.93 208.43 0.00 0.00 0.00 0.00 0.00 0.00 195.75 222.733 6 229.66 210.776 6 0.00 0.000 6 3.00 0.00 1.30 0.00 0.48 0.13 0.82 1.176 6 1.64 1.91 0.17 0.00 0.69 0.00 0.74 0.849 6 100.87 122.69 109.98 147.17 99.01 102.13 113.64 18.596 6 92.49 104.34 101.67 102.37 84.83 85.64 95.22 8.753 6 4.30 1.97 3.15 2.68 1.94 2.55 2.77 0.880 6 2.41 3.70 2.53 1.65 3.75 4.45 3.08 1.049 6 931 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05508 I05517 I05519 I05520 I05526 I05527 63.12 72.02 68.04 50.11 60.09 48.19 0.65 1.78 0.44 2.53 0.96 1.57 MEAN S.D. N 60.26 9.547 6 1.32 0.786 6 Group: Male 2 Dose Level: 0.03 I05514 I05515 I05516 I05521 70.30 48.85 58.29 64.30 1.86 0.96 0.34 10.76 MEAN S.D. N 60.44 9.148 4 3.48 4.893 4 Group: Male 3 Dose Level: 0.15 I05505 I05510 I05518 I05523 I05524 I05528 63.97 58.44 52.27 64.33 73.62 72.47 1.54 1.05 0.90 2.03 0.82 0.73 MEAN S.D. N 64.18 8.157 6 1.18 0.506 6 Dosage Unit: mg/kg/day 3.16 22.72 14.07 19.55 16.52 35.93 20.61 53.30 30.76 65.61 29.74 51.35 0.00 0.00 0.00 0.00 0.00 0.00 18.66 10.784 6 41.90 17.359 6 0.00 0.000 6 Dosage Unit: mg/kg/day 29.08 29.88 28.37 41.20 82.17 40.06 40.27 107.46 0.00 0.00 0.00 0.00 32.13 * 6.076 4 67.49 33.199 4 0.00 0.000 4 Dosage Unit: mg/kg/day 17.57 20.81 20.88 20.84 13.64 21.33 37.08 34.69 26.72 47.88 34.88 23.84 0.00 0.00 0.00 0.00 0.00 0.00 19.18 3.040 6 34.18 8.478 6 0.00 0.000 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 0.00 0.00 0.00 0.00 0.00 0.000 4 0.00 0.00 0.17 0.00 0.00 0.00 0.03 0.069 6 141.51 162.07 144.10 148.94 161.62 162.45 153.45 9.720 6 166.24 148.07 151.67 146.06 153.01 9.120 4 143.76 141.60 156.52 174.10 119.61 143.77 146.56 18.023 6 3.96 4.25 3.67 4.53 2.93 4.02 3.89 0.553 6 5.41 4.38 5.22 6.17 5.30 * 0.735 4 4.56 4.37 4.49 6.03 3.93 3.45 4.47 0.870 6 932 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 4 Dose Level: 0.75 I05506 I05507 I05509 I05511 I05512 I05522 73.97 49.60 86.62 60.08 64.66 67.73 0.48 2.71 1.73 1.70 0.26 1.87 MEAN S.D. N 67.11 12.571 6 1.46 0.923 6 Group: Female 1 Dose Level: 0 I05529 I05530 I05531 I05535 I05544 I05549 74.49 69.78 50.36 62.89 70.71 65.26 0.55 0.06 0.30 0.29 1.05 0.32 MEAN S.D. N 65.58 8.513 6 0.43 0.342 6 Group: Female 2 Dose Level: 0.03 I05537 I05541 I05547 I05550 75.93 89.16 68.87 61.58 0.30 0.37 0.38 0.28 MEAN S.D. N 73.89 11.748 4 0.33 0.050 4 Dosage Unit: mg/kg/day 2.29 22.58 4.65 3.05 13.32 19.66 48.87 40.22 34.03 38.67 33.13 57.55 0.00 0.00 0.00 0.00 0.00 0.00 10.93 8.875 6 42.08 9.438 6 0.00 0.000 6 Dosage Unit: mg/kg/day 59.28 30.39 76.52 126.05 218.24 85.32 96.58 37.67 104.81 94.80 115.65 88.15 0.00 0.00 0.00 0.00 0.00 0.00 99.30 66.222 6 89.61 27.146 6 0.00 0.000 6 Dosage Unit: mg/kg/day 276.11 88.60 48.03 34.29 579.38 143.46 87.11 106.94 0.00 0.00 0.00 0.00 111.76 111.968 4 229.22 234.602 4 0.00 0.000 4 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 0.00 0.00 0.00 0.00 0.00 0.000 4 107.40 89.57 127.61 144.57 102.29 136.40 117.97 * 21.468 6 95.65 200.64 117.41 144.43 160.65 139.16 142.99 36.187 6 161.68 144.58 121.55 160.17 147.00 18.641 4 4.98 4.45 4.61 5.46 3.78 4.38 4.61 0.570 6 3.94 6.12 4.52 4.54 4.46 5.01 4.77 0.746 6 5.86 6.55 5.03 6.54 6.00 0.720 4 933 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 91 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 3 Dose Level: 0.15 I05532 I05538 I05539 I05545 I05548 I05552 53.44 54.36 56.38 50.87 46.19 55.40 0.07 0.09 0.01 0.00 0.30 0.38 MEAN S.D. N 52.77 3.737 6 0.14 0.159 6 Group: Female 4 Dose Level: 0.75 I05533 I05534 I05536 I05540 I05542 I05551 63.67 57.80 71.04 85.09 58.02 91.43 0.51 0.04 0.14 0.26 0.23 0.42 MEAN S.D. N 71.18 14.228 6 0.27 0.174 6 Dosage Unit: mg/kg/day 208.42 55.31 48.35 64.59 29.92 74.01 161.28 71.47 96.47 142.80 64.58 74.24 0.00 0.00 0.00 0.00 0.00 0.00 80.10 64.629 6 101.81 40.773 6 0.00 0.000 6 Dosage Unit: mg/kg/day 162.24 34.90 29.06 42.06 95.90 394.36 186.20 67.09 60.95 65.39 72.08 503.53 0.00 0.00 0.00 0.00 0.00 0.00 126.42 140.697 6 159.21 175.397 6 0.00 0.000 6 0.09 0.00 0.00 0.00 0.00 0.00 0.02 0.037 6 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.000 6 120.33 113.79 114.24 113.45 109.64 92.26 110.62 * 9.628 6 95.87 81.56 92.51 90.84 81.86 83.67 87.72 * 6.128 6 4.88 3.27 3.49 4.38 3.13 3.47 3.77 0.697 6 4.18 5.45 4.94 3.81 5.99 5.15 4.92 0.807 6 934 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05508 I05517 I05519 I05520 I05526 I05527 49.36 44.88 54.72 37.96 60.22 39.62 0.80 0.89 0.41 3.20 0.91 2.05 MEAN S.D. N 47.79 8.681 6 1.38 1.049 6 Group: Male 2 Dose Level: 0.03 I05514 I05515 I05516 I05521 57.72 41.90 43.62 53.31 1.43 0.44 0.31 8.03 MEAN S.D. N 49.14 7.613 4 2.55 3.686 4 Group: Male 3 Dose Level: 0.15 I05505 I05510 I05518 I05523 I05524 I05528 42.54 39.10 46.25 57.87 51.67 52.89 0.25 2.63 0.70 2.06 0.73 0.42 MEAN S.D. N 48.39 7.014 6 1.13 0.973 6 Dosage Unit: mg/kg/day 11.03 26.64 21.40 19.07 15.79 43.81 16.55 34.19 24.00 35.67 22.56 46.79 0.00 0.00 0.00 0.00 0.00 0.00 22.96 11.485 6 29.96 10.990 6 0.00 0.000 6 Dosage Unit: mg/kg/day 29.26 9.14 16.57 41.46 65.16 29.60 29.96 70.45 0.00 0.00 0.00 0.00 24.11 14.242 4 48.79 22.060 4 0.00 0.000 4 Dosage Unit: mg/kg/day 28.98 25.43 28.63 26.43 20.26 9.63 21.56 19.76 25.41 39.59 20.89 13.61 0.00 0.00 0.00 0.00 0.00 0.00 23.23 7.363 6 23.47 8.774 6 0.00 0.000 6 0.01 1.43 0.48 0.35 0.30 0.02 0.43 0.524 6 0.76 0.32 0.11 0.15 0.34 0.298 4 1.10 0.51 2.09 0.18 0.09 0.46 0.74 0.751 6 153.39 155.85 152.78 168.82 162.99 164.16 159.67 6.579 6 148.24 133.97 77.19 117.72 119.28 * 30.705 4 134.08 110.87 136.26 144.20 114.48 107.88 124.63 * 15.365 6 4.94 4.14 4.19 4.97 3.38 4.68 4.38 0.608 6 5.02 3.70 5.04 5.13 4.72 0.683 4 4.41 3.40 4.42 4.67 3.94 3.12 3.99 0.621 6 935 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM ,SALT (PFOS;:T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXII ^g/dL Group: Male 4 Dose Level: 0.75 I05507 I05511 I05512 I05522 59.90 43.70 70.20 59.49 2.10 0.69 0.04 1.80 MEAN S.D. N 58.32 10.935 4 1.16 0.961 4 Group: Female 1 Dose Level: 0 I05529 I05530 I05531 I05535 I05544 I05549 65.21 74.89 35.19 74.58 61.62 41.85 0.17 0.01 0.03 0.52 0.34 0.02 MEAN S.D. N 58.89 16.743 6 0.18 0.209 6 Group: Female 2 Dose Level: 0.03 I05537 I05541 I05547 I05550 76.03 61.45 39.39 59.31 0.29 0.13 0.26 0.14 MEAN S.D. N 59.05 15.063 4 0.21 0.082 4 Dosage Unit: mg/kg/day 0.00 1.01 0.00 2.00 33.59 27.68 22.69 36.89 0.00 0.00 0.00 0.00 0.75 * 0.958 4 30.21 6.298 4 0.00 0.000 4 Dosage Unit: mg/kg/day 232.49 47.22 51.65 318.47 162.44 78.63 351.64 68.58 77.36 239.29 153.92 61.78 0.00 0.00 0.00 0.00 0.00 0.00 148.48 110.143 6 158.76 116.512 6 0.00 0.000 6 Dosage Unit: mg/kg/day 254.69 47.66 41.73 156.72 492.79 101.86 164.10 364.55 0.00 0.00 0.00 0.00 125.20 101.227 4 280.83 180.363 4 0.00 0.000 4 1.59 0.34 0.59 1.18 0.93 0.566 4 1.33 0.00 0.00 0.06 2.75 0.22 0.73 1.115 6 0.00 0.08 0.85 1.77 0.68 0.824 4 58.09 97.68 34.06 75.57 66.35 * 26.941 4 95.65 183.66 115.47 139.41 152.04 125.36 135.27 30.659 6 148.10 131.20 98.77 102.12 120.05 23.703 4 5.27 7.00 3.25 5.85 5.34 1.569 4 4.83 7.22 5.01 5.84 5.08 5.95 5.66 0.894 6 5.29 5.85 3.35 2.84 4.33 1.462 4 936 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 182 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 3 Dose Level: 0.15 I05532 I05538 I05539 I05545 I05548 I05552 47.71 36.38 42.82 48.24 32.13 48.26 0.01 0.04 0.00 0.04 0.03 0.16 MEAN S.D. N 42.59 6.904 6 0.05 0.058 6 Group: Female 4 Dose Level: 0.75 I05533 I05534 I05536 I05540 I05542 I05551 63.42 66.38 51.73 60.27 56.03 96.30 0.17 0.05 0.09 0.15 0.19 0.07 MEAN S.D. N 65.69 15.876 6 0.12 0.058 6 Dosage Unit: mg/kg/day 197.86 45.10 52.30 52.62 39.61 36.02 141.98 64.69 100.79 74.46 51.74 60.51 0.00 0.00 0.00 0.00 0.00 0.65 70.59 62.705 6 82.36 33.716 6 0.11 0.265 6 Dosage Unit: mg/kg/day 36.11 9.45 0.00 47.41 93.61 52.80 55.31 37.27 53.37 60.05 115.82 99.85 0.00 0.00 0.00 0.00 0.00 0.00 39.90 33.589 6 70.28 30.505 6 0.00 0.000 6 4.33 0.25 0.89 0.62 0.98 0.57 1.27 1.520 6 2.31 1.10 0.62 0.21 0.55 0.22 0.84 0.793 6 90.44 100.45 106.11 86.22 103.15 93.10 96.58 * 7.824 6 83.76 81.38 76.41 71.65 92.22 104.92 85.06 * 11.963 6 4.36 2.83 3.63 4.00 4.03 4.59 3.91 * 0.622 6 5.31 6.31 5.96 3.74 5.83 6.49 5.61 1.002 6 937 ANIMAL NUMBER Appendix 6 Summary and Individual Blood Hormone Determination Additional Collection - Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TOTAL FREE TOTAL FREE TRIIODOTHYRONINE 'TRIIODOTHYRONINE THYROXINf THYROXIN ng/dL pg/mL ^g/dL ng/dL Group: Male 1 Dose Level : 0 I05508 I05519 I05527 126.89 110.98 107.16 5.18 3.61 3.83 MEAN S.D. N 115.01 10.464 3 4.21 0.850 3 Group: Male 2 Dose Level : 0.03 I05514 I05515 I05516 I05521 111.98 103.61 120.14 106.40 5.14 4.58 5.44 5.36 MEAN S.D. N 110.53 7.289 4 5.13 0.388 4 Group: Male 3 Dose Level : 0.15 I05510 I05518 I05524 I05528 95.90 93.03 86.79 100.26 4.19 4.41 3.88 4.85 MEAN S.D. N 94.00 * 5.649 4 4.33 0.408 4 Dosage Unit: mg/kg/day 3.46 2.73 3.56 1.02 0.86 1.15 3.25 0.453 3 1.01 0.145 3 Dosage Unit: mg/kg/day 3.97 3.01 4.11 4.31 1.07 1.10 1.16 1.50 3.85 0.577 4 1.21 0.199 4 Dosage Unit: mg/kg/day 2.88 2.49 2.38 3.07 1.02 0.93 0.79 1.01 2.71 0.324 4 0.94 0.106 4 Covance 6329-223 3M T-6295.7 938 ANIMAL NUMBER Appendix 6 Summary and Individual Blood Hormone Determination Additional Collection - Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TOTAL FREE TOTAL FREE TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROXIN ng/dL pg/mL ^g/dL ng/dL Group: Male 4 Dose Level: 0.75 I05506 I05507 I05512 59.28 55.46 13.96 2.74 3.07 1.55 MEAN S.D. N 42.90 * 25.135 3 2.45 * 0.800 3 Group: Female 1 Dose Level : 0 I05530 I05531 I05535 I05544 131.98 87.43 98.87 104.98 5.33 3.10 3.48 4.28 MEAN S.D. N 105.82 18.899 4 4.05 0.986 4 Group: Female 2 Dose Level : 0.03 I05541 I05547 I05550 109.59 81.34 86.09 4.13 3.14 3.49 MEAN S.D. N 92.34 15.127 3 3.59 0.502 3 Dosage Unit: mg/kg/day 4.90 3.16 1.83 1.36 1.15 0.86 3.30 1.540 3 1.12 0.251 3 Dosage Unit : mg/kg/day 5.50 2.62 4.93 3.52 1.43 0.78 1.17 0.86 4.14 1.313 4 1.06 0.299 4 Dosage Unit : mg/kg/day 4.24 3.41 2.80 1.32 0.86 0.85 3.48 0.723 3 1.01 0.269 3 Covance 6329-223 3M T-6295.7 939 ANIMAL NUMBER Appendix 6 Summary and Individual Blood Hormone Determination Additional Collection - Terminal Sacrifice 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TOTAL FREE TOTAL FREE TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROXIN ng/dL pg/mL ^g/dL ng/dL Group: Female 3 Dose Level: 0.15 I05532 I05538 I05545 I05548 74.72 77.02 72.24 94.86 3.27 2.98 2.96 3.87 MEAN S.D. N 79.71 * 10.287 4 3.27 0.424 4 Group: Female 4 Dose Level: 0.75 I05534 I05536 I05540 I05551 51.14 59.03 60.77 64.05 2.88 2.43 3.13 2.83 MEAN S.D. N 58.75 * 5.482 4 2.82 0.290 4 Dosage Unit: mg/kg/day 3.03 1.89 2.71 3.88 1.04 0.59 0.90 1.06 2.88 0.823 4 0.90 0.217 4 Dosage Unit: mg/kg/day 4.52 3.87 2.04 3.30 1.49 1.00 0.79 1.03 3.43 1.054 4 1.08 0.295 4 Covance 6329-223 3M T-6295.7 940 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05520 I05526 38.18 44.16 2.66 2.51 MEAN S.D. N 41.17 4.228 2 2.59 0.106 2 Group: Male 3 Dose Level: 0.15 I05505 I05523 27.26 52.61 0.99 3.84 MEAN S.D. N 39.94 17.925 2 2.42 2.015 2 Group: Male 4 Dose Level: 0.75 I05511 I05522 51.54 44.31 4.72 5.36 MEAN S.D. N 47.93 5.112 2 5.04 0.453 2 Dosage Unit: mg/kg/day 17.90 10.98 64.49 25.43 0.00 0.00 14.44 4.893 2 44.96 27.620 2 0.00 0.000 2 Dosage Unit: mg/kg/day 17.56 21.73 32.66 59.98 0.00 0.00 19.65 2.949 2 46.32 19.318 2 0.00 0.000 2 Dosage Unit: mg/kg/day 0.00 27.09 37.83 70.81 0.00 0.00 13.55 19.156 2 54.32 23.320 2 0.00 0.000 2 1.61 2.12 1.87 0.361 2 1.21 0.97 1.09 0.170 2 1.67 1.05 1.36 0.438 2 159.60 183.22 171.41 16.702 2 154.43 164.81 159.62 7.340 2 165.18 129.72 147.45 25.074 2 3.75 2.87 3.31 0.622 2 3.28 4.20 3.74 0.651 2 4.74 2.51 3.625 1.577 2 941 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 217 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 1 Dose Level: 0 I05529 I05549 54.69 40.39 0.86 0.12 MEAN S.D. N 47.54 10.112 2 0.49 0.523 2 Group: Female 3 Dose Level: 0.15 I05539 I05552 57.55 59.07 0.10 0.82 MEAN S.D. N 58.31 1.075 2 0.46 0.509 2 Group: Female 4 Dose Level: 0.75 I05533 I05542 55.91 66.34 0.61 0.37 MEAN S.D. N 61.13 7.375 2 0.49 0.170 2 Dosage Unit: mg/kg/day 53.08 43.63 83.74 64.84 0.00 0.00 48.36 6.682 2 74.29 13.364 2 0.00 0.000 2 Dosage Unit: mg/kg/day 44.84 68.85 71.13 88.81 0.00 0.00 56.85 16.978 2 79.97 12.502 2 0.00 0.000 2 Dosage Unit: mg/kg/day 133.46 88.23 289.99 154.68 0.00 0.00 110.85 31.982 2 222.34 95.679 2 0.00 0.000 2 1.78 1.66 1.72 0.85 2 1.88 0.59 1.24 0.912 2 1.76 1.56 1.66 0.141 2 116.20 133.52 124.86 12.247 2 114.34 121.25 117.80 4.886 2 99.29 101.57 100.43 1.612 2 4.89 6.58 5.74 1.195 2 3.37 3.91 3.64 0.382 2 3.93 3.51 3.72 0.297 2 942 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05520 I05526 52.17 44.90 2.83 1.40 MEAN S.D. N 48.54 5.141 2 2.12 1.011 2 Group: Male 3 Dose Level: 0.15 I05505 I05523 46.88 54.44 0.50 7.18 MEAN S.D. N 50.66 5.346 2 3.84 4.723 2 Group: Male 4 Dose Level: 0.75 I05511 I05522 37.08 25.17 1.55 2.99 MEAN S.D. N 31.13 8.422 2 2.27 1.018 2 Dosage Unit: mg/kg/day 40.85 16.61 79.85 31.48 0.00 0.00 28.73 17.140 2 55.67 34.203 2 0.00 0.000 2 Dosage Unit: mg/kg/day 23.84 25.40 43.65 59.41 0.00 0.00 24.62 1.103 2 51.53 11.144 2 0.00 0.000 2 Dosage Unit: mg/kg/day 17.87 26.57 53.06 77.43 0.00 0.00 22.22 6.152 2 65.25 17.232 2 0.00 0.000 2 0.25 0.00 0.13 0.177 2 0.10 0.00 0.05 0.071 2 0.67 0.33 0.50 0.240 2 171.00 133.39 152.20 26.594 2 154.84 151.74 153.29 2.192 2 170.42 137.27 153.85 23.441 2 4.18 1.74 2.96 1.725 2 3.79 3.37 3.58 0.297 2 4.18 2.45 3.32 1.223 2 943 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 245 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 1 Dose Level: 0 I05529 I05549 56.47 43.54 0.12 0.07 MEAN S.D. N 50.01 9.143 2 0.10 0.035 2 Group: Female 3 Dose Level: 0.15 I05539 I05552 63.10 60.29 0.07 0.28 MEAN S.D. N 61.70 1.987 2 0.18 0.148 2 Group: Female 4 Dose Level: 0.75 I05533 I05542 62.75 81.69 0.66 0.06 MEAN S.D. N 72.22 13.393 2 0.36 0.424 2 Dosage Unit: mg/kg/day 38.61 112.14 95.66 115.58 0.00 0.00 75.38 51.994 2 105.62 14.086 2 0.00 0.000 2 Dosage Unit: mg/kg/day 61.24 88.08 137.78 94.05 0.00 0.00 74.66 18.979 2 115.92 30.922 2 0.00 0.000 2 Dosage Unit: mg/kg/day 257.61 114.63 255.84 120.11 0.00 0.00 186.12 101.102 2 187.98 95.976 2 0.00 0.000 2 0.68 0.98 0.83 0.212 2 0.81 0.00 0.41 0.573 2 1.04 0.82 0.93 0.156 2 130.32 136.09 133.21 4.080 2 127.17 142.77 134.97 11.031 2 118.99 121.98 120.49 2.114 2 4.93 5.81 5.37 0.622 2 3.56 3.76 3.66 0.141 2 3.84 3.38 3.61 0.325 2 944 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Male 1 Dose Level: 0 I05520 I05526 34.89 45.23 1.76 1.40 MEAN S.D. N 40.06 7.311 2 1.58 0.255 2 Group: Male 3 Dose Level: 0.15 I05505 I05523 42.85 61.34 3.64 2.55 MEAN S.D. N 52.10 13.074 2 3.10 0.771 2 Group: Male 4 Dose Level: 0.75 I05511 I05522 59.62 26.17 2.36 4.12 MEAN S.D. N 42.90 23.653 2 3.24 1.245 2 Dosage Unit: mg/kg/day 17.17 14.11 62.84 34.27 0.00 0.00 15.64 2.164 2 48.56 20.202 2 0.00 0.000 2 Dosage Unit: mg/kg/day 25.06 25.26 39.86 63.44 0.00 0.00 25.16 0.141 2 51.65 16.674 2 0.00 0.000 2 Dosage Unit: mg/kg/day 6.94 30.46 51.42 83.94 0.00 0.00 18.70 16.631 2 67.68 22.995 2 0.00 0.000 2 0.00 0.02 0.01 0.014 2 0.25 0.00 0.13 0.177 2 0.24 0.09 0.17 0.106 2 134.97 167.54 151.26 23.030 2 146.70 161.73 154.22 10.628 2 163.13 163.73 163.43 0.424 2 5.56 2.40 3.98 2.234 2 2.43 3.31 2.87 0.622 2 4.19 2.36 3.28 1.294 2 945 ANIMAL NUMBER CORTISOL ^g/dL Appendix 6 Summary and Individual Blood Hormone Determination Day 274 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL THYROID STIMULATING ng/mL pg/mL pg/mL pg/mL ^U/mL TOTAL TRIIODOTHYRONINE ng/dL Covance 6329-223 3M T-6295.7 TOTAL THYROXIN ^g/dL Group: Female 1 Dose Level: 0 I05529 I05549 64.71 47.01 0.44 0.02 MEAN S.D. N 55.86 12.516 2 0.23 0.297 2 Group: Female 3 Dose Level: 0.15 I05539 I05552 45.77 44.48 0.04 0.18 MEAN S.D. N 45.13 0.912 2 0.11 0.099 2 Group: Female 4 Dose Level: 0.75 I05533 I05542 49.13 63.28 0.49 0.40 MEAN S.D. N 56.21 10.006 2 0.45 0.064 2 Dosage Unit: mg/kg/day 43.91 42.07 115.88 57.38 0.00 0.00 42.99 1.301 2 86.63 41.366 2 0.00 0.000 2 Dosage Unit: mg/kg/day 48.03 114.70 127.24 124.21 0.00 0.00 81.37 47.143 2 125.73 2.143 2 0.00 0.000 2 Dosage Unit: mg/kg/day 109.08 108.09 153.99 128.04 0.00 0.00 108.59 0.700 2 141.02 18.349 2 0.00 0.000 2 0.00 0.68 0.34 0.481 2 0.29 0.00 0.15 0.205 2 0.64 0.01 0.33 0.445 2 91.10 130.21 110.66 27.655 2 114.25 103.46 108.86 7.630 2 115.88 85.17 100.53 21.715 2 4.88 4.88 4.88 0.000 2 3.00 2.98 2.99 0.014 2 2.59 3.22 2.91 0.445 2 946 ANIMAL NUMBER Appendix 6 Covance 6329-223 3M T-6295.7 Summary and Individual Blood Hormone Determination Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS THYROID TOTAL FREE TOTAL FREE CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROX ^g/dL ng/mL pg/mL pg/mL pg/mL ^U/mL ng/dL pg/mL ^g/dL ng/dL Group: Male 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 I05526 48.93 54.85 1.68 1.47 22.29 12.73 66.72 34.79 0.00 0.00 0.00 0.08 MEAN S.D. N 51.89 4.186 2 1.58 0.148 2 17.51 6.760 2 50.76 22.578 2 0.00 0.000 2 0.04 0.057 2 Group: Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 I05523 35.82 56.14 0.16 2.50 21.68 21.64 35.93 55.20 0.00 0.00 0.15 0.00 MEAN S.D. N 45.98 14.368 2 1.33 1.655 2 21.66 0.028 2 45.57 13.626 2 0.00 0.000 2 0.08 0.106 2 Group: Male 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 I05522 52.62 27.46 1.59 1.66 0.00 14.90 43.71 66.78 0.00 0.00 0.01 0.05 MEAN S.D. N 40.04 17.791 2 1.63 0.049 2 7.45 10.536 2 55.25 16.313 2 0.00 0.000 2 0.03 0.028 2 113.68 167.98 140.83 38.396 2 141.49 150.29 145.89 6.223 2 145.00 116.61 130.81 20.075 2 4.34 6.23 5.29 1.336 2 4.68 5.39 5.04 0.502 2 4.78 4.24 4.51 0.382 2 3.20 3.35 3.28 0.106 2 3.96 4.09 4.03 0.092 2 4.61 2.84 3.73 1.252 2 1.27 1.26 1.27 0.007 2 1.44 1.51 1.48 0.049 2 1.17 0.95 1.06 0.156 2 947 ANIMAL NUMBER Appendix 6 Covance 6329-223 3M T-6295.7 Summary and Individual Blood Hormone Determination Day 322 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS THYROID TOTAL FREE TOTAL FREE CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROX ^g/dL ng/mL pg/mL pg/mL pg/mL ^U/mL ng/dL pg/mL ^g/dL ng/dL Group: Female 1 I05529 I05549 60.74 55.31 MEAN S.D. N 58.03 3.840 2 Group: Female 3 I05539 I05552 54.81 61.78 MEAN S.D. N 58.30 4.929 2 Group: Female 4 I05533 I05542 40.44 66.14 MEAN S.D. N 53.29 18.173 2 Dose Level: 0 Dosage Unit : mg/kg/day 0.66 0.04 93.93 67.50 136.07 78.68 0.00 0.00 0.14 0.22 0.35 0.438 2 80.72 18.689 2 107.38 40.581 2 0.00 0.000 2 0.18 0.057 2 Dose Level: 0.15 Dosage Unit : mg/kg/day 0.00 0.15 46.03 78.67 127.28 179.51 0.00 0.00 0.00 0.33 0.08 0.106 2 62.35 23.080 2 153.40 36.932 2 0.00 0.000 2 0.17 0.233 2 Dose Level: 0.75 Dosage Unit : mg/kg/day 0.02 0.03 95.89 95.19 182.57 116.98 0.00 0.00 0.85 0.00 0.03 0.007 2 95.54 0.495 2 149.78 46.379 2 0.00 0.000 2 0.43 0.601 2 95.57 102.40 98.99 4.830 2 102.53 86.79 94.66 11.130 2 127.50 94.51 111.01 23.327 2 3.84 3.31 3.58 0.375 2 2.30 2.66 2.48 0.255 2 4.40 2.64 3.52 1.245 2 3.87 4.09 3.98 0.156 2 3.24 3.34 3.29 0.071 2 4.41 4.04 4.23 0.262 2 1.16 1.37 1.27 0.148 2 0.99 1.04 1.02 0.035 2 1.38 1.08 1.23 0.212 2 948 ANIMAL NUMBER Appendix 6 Covance 6329-223 3M T-6295.7 Summary and Individual Blood Hormone Determination Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS THYROID TOTAL FREE TOTAL FREE CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROX ^g/dL ng/mL pg/mL pg/mL pg/mL ^U/mL ng/dL pg/mL ^g/dL ng/dL Group: Male 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 I05526 56.87 50.92 2.87 2.98 31.48 22.18 71.33 39.48 0.00 0.00 0.00 0.01 MEAN S.D. N 53.90 4.207 2 2.93 0.078 2 26.83 6.576 2 55.41 22.521 2 0.00 0.000 2 0.01 0.007 2 Group: Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 I05523 35.11 69.91 5.86 3.19 27.97 21.80 33.61 59.64 0.00 0.00 0.15 0.00 MEAN S.D. N 52.51 24.607 2 4.53 1.888 2 24.89 4.363 2 46.63 18.406 2 0.00 0.000 2 0.08 0.106 2 Group: Male 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 I05522 53.56 42.27 2.07 1.98 12.59 22.13 50.72 61.86 0.00 0.00 0.00 0.00 MEAN S.D. N 47.92 7.983 2 2.03 0.064 2 17.36 6.746 2 56.29 7.877 2 0.00 0.000 2 0.00 0.000 2 142.33 173.51 157.92 22.048 2 141.33 136.42 138.88 3.472 2 189.73 142.92 166.33 33.100 2 4.92 5.87 5.40 0.672 2 4.17 4.73 4.45 0.396 2 6.84 6.13 6.49 0.502 2 3.54 3.31 3.43 0.163 2 3.71 3.76 3.74 0.035 2 3.92 3.06 3.49 0.608 2 1.36 1.43 1.40 0.049 2 1.35 1.21 1.28 0.099 2 1.07 1.07 1.07 0.000 2 949 ANIMAL NUMBER Appendix 6 Covance 6329-223 3M T-6295.7 Summary and Individual Blood Hormone Determination Day 364 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS THYROID TOTAL FREE TOTAL FREE CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROX ^g/dL ng/mL pg/mL pg/mL pg/mL ^U/mL ng/dL pg/mL ^g/dL ng/dL Group: Female 1 I05529 I05549 56.92 54.02 MEAN S.D. N 55.47 2.051 2 Group: Female 3 I05539 I05552 48.00 74.04 MEAN S.D. N 61.02 18.413 2 Group: Female 4 I05533 I05542 61.92 89.59 MEAN S.D. N 75.76 19.566 2 Dose Level: 0 Dosage Unit : mg/kg/day 0.36 0.01 46.66 72.28 106.07 120.53 0.00 0.00 0.38 0.00 0.19 0.247 2 59.47 18.116 2 113.30 10.225 2 0.00 0.000 2 0.19 0.269 2 Dose Level: 0.15 Dosage Unit : mg/kg/day 0.01 0.13 53.88 25.95 120.92 71.07 0.00 0.00 0.12 0.39 0.07 0.085 2 39.92 19.749 2 96.00 35.249 2 0.00 0.000 2 0.26 0.191 2 Dose Level: 0.75 Dosage Unit : mg/kg/day 0.13 0.07 166.75 164.57 352.52 175.61 0.00 0.00 0.28 0.00 0.10 0.042 2 165.66 1.541 2 264.07 125.094 2 0.00 0.000 2 0.14 0.198 2 114.22 94.96 104.59 13.619 2 113.58 89.22 101.40 17.225 2 108.62 105.87 107.25 1.945 2 3.48 2.75 3.12 0.516 2 2.73 3.99 3.36 0.891 2 3.84 3.34 3.59 0.354 2 3.48 3.89 3.69 0.290 2 3.40 3.06 3.23 0.240 2 3.20 3.31 3.26 0.078 2 1.17 1.40 1.29 0.163 2 1.10 1.03 1.07 0.049 2 1.15 1.07 1.11 0.057 2 950 ANIMAL NUMBER Appendix 6 Covance 6329-223 3M T-6295.7 Summary and Individual Blood Hormone Determination Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS THYROID TOTAL FREE TOTAL FREE CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROX ^g/dL ng/mL pg/mL pg/mL pg/mL ^U/mL ng/dL pg/mL ^g/dL ng/dL Group: Male 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 I05526 45.28 42.55 3.12 2.03 24.62 20.60 33.29 17.89 0.00 0.00 4.00 3.18 MEAN S.D. N 43.92 1.930 2 2.58 0.771 2 22.61 2.843 2 25.59 10.889 2 0.00 0.000 2 3.59 0.580 2 Group: Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05505 I05523 35.05 58.45 5.77 4.15 33.45 34.94 15.52 31.76 0.00 0.00 3.02 2.40 MEAN S.D. N 46.75 16.546 2 4.96 1.146 2 34.20 1.054 2 23.64 11.483 2 0.00 0.000 2 2.71 0.438 2 Group: Male 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 I05522 34.37 18.72 2.19 5.27 15.15 32.89 34.29 47.87 0.00 0.00 2.70 2.67 MEAN S.D. N 26.55 11.066 2 3.73 2.178 2 24.02 12.544 2 41.08 9.603 2 0.00 0.000 2 2.69 0.021 2 160.85 158.81 159.83 1.442 2 156.75 189.99 173.37 23.504 2 200.22 142.75 171.49 40.637 2 7.90 7.34 7.62 0.396 2 5.12 8.58 6.85 2.447 2 8.55 6.89 7.72 1.174 2 5.07 3.03 4.05 1.442 2 4.10 4.63 4.37 0.375 2 3.56 4.05 3.81 0.346 2 2.53 1.83 2.18 0.495 2 1.85 2.07 1.96 0.156 2 1.51 1.83 1.67 0.226 2 951 ANIMAL NUMBER Appendix 6 Covance 6329-223 3M T-6295.7 Summary and Individual Blood Hormone Determination Day 456 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS THYROID TOTAL FREE TOTAL FREE CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROX ^g/dL ng/mL pg/mL pg/mL pg/mL ^U/mL ng/dL pg/mL ^g/dL ng/dL Group: Female 1 I05529 I05549 61.24 45.43 MEAN S.D. N 53.34 11.179 2 Group: Female 3 I05539 I05552 59.18 40.35 MEAN S.D. N 49.77 13.315 2 Group: Female 4 I05533 I05542 52.84 88.82 MEAN S.D. N 70.83 25.442 2 Dose Level: 0 Dosage Unit : mg/kg/day 0.75 0.16 60.82 58.64 62.11 17.39 0.00 0.00 3.41 2.27 0.46 0.417 2 59.73 1.541 2 39.75 31.622 2 0.00 0.000 2 2.84 0.806 2 Dose Level: 0.15 Dosage Unit : mg/kg/day 0.06 0.15 111.82 63.26 73.29 56.27 0.00 0.00 5.31 5.26 0.11 0.064 2 87.54 34.337 2 64.78 12.035 2 0.00 0.000 2 5.29 0.035 2 Dose Level: 0.75 Dosage Unit : mg/kg/day 0.73 0.30 101.24 180.10 86.37 115.95 0.00 0.00 5.20 4.19 0.52 0.304 2 140.67 55.762 2 101.16 20.916 2 0.00 0.000 2 4.70 0.714 2 131.39 127.08 129.24 3.048 2 127.44 104.90 116.17 15.938 2 140.68 147.41 144.05 4.759 2 6.12 5.03 5.58 0.771 2 4.32 5.02 4.67 0.495 2 4.86 4.23 4.55 0.445 2 4.81 4.72 4.77 0.064 2 3.48 3.31 3.40 0.120 2 3.55 3.15 3.35 0.283 2 2.15 2.27 2.21 0.085 2 1.46 1.10 1.28 0.255 2 1.56 1.11 1.34 0.318 2 952 ANIMAL NUMBER Appendix 6 Covance 6329-223 3M T-6295.7 Summary and Individual Blood Hormone Determination Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS THYROID TOTAL FREE TOTAL FREE CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROX ^g/dL ng/mL pg/mL pg/mL pg/mL ^U/mL ng/dL pg/mL ^g/dL ng/dL Group: Male 1 Dose Level: 0 Dosage Unit: mg/kg/day I05520 I05526 41.44 48.80 3.51 2.29 19.03 21.13 35.81 22.20 0.00 0.00 3.01 3.34 MEAN 45.12 2.90 20.08 29.01 0.00 S.D. 5.204 0.863 1.485 9.624 0 . 0 0 0 N 2 2 2 22 Group: Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day 3.18 0.233 2 I05505 I05523 43.54 55.25 2.03 4.77 22.13 33.60 11.11 27.76 0.00 0.00 3.11 3.17 MEAN S.D. N 49.40 8.280 2 3.40 1.937 2 27.87 8.111 2 19.44 11.773 2 0.00 0.000 2 3.14 0.042 2 Group: Male 4 Dose Level: 0.75 Dosage Unit: mg/kg/day I05511 I05522 31.74 17.51 6.17 6.28 27.18 30.18 34.39 40.74 0.00 0.00 1.92 3.36 MEAN S.D. N 24.63 10.062 2 6.23 0.078 2 28.68 2.121 2 37.57 4.490 2 0.00 0.000 2 2.64 1.018 2 141.17 144.88 143.03 2.623 2 127.36 164.68 146.02 26.389 2 211.71 133.42 172.57 55.359 2 5.57 5.51 5.54 0.042 2 4.68 7.26 5.97 1.824 2 7.91 6.19 7.05 1.216 2 4.31 4.10 4.21 0.148 2 3.06 3.91 3.49 0.601 2 5.89 3.90 4.90 1.407 2 1.98 1.97 1.98 0.007 2 1.51 1.83 1.67 0.226 2 1.92 1.80 1.86 0.085 2 953 ANIMAL NUMBER Appendix 6 Covance 6329-223 3M T-6295.7 Summary and Individual Blood Hormone Determination Day 546 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS THYROID TOTAL FREE TOTAL FREE CORTISOL TESTOSTERONE ESTRADIOL ESTRONE ESTRIOL STIMULATING TRIIODOTHYRONINE TRIIODOTHYRONINE THYROXIN THYROX ^g/dL ng/mL pg/mL pg/mL pg/mL ^U/mL ng/dL pg/mL ^g/dL ng/dL Group: Female 1 I05529 I05549 61.95 50.10 MEAN S.D. N 56.03 8.379 2 Group: Female 3 I05539 I05552 58.68 26.08 MEAN S.D. N 42.38 23.052 2 Group: Female 4 I05533 I05542 49.05 82.98 MEAN S.D. N 66.02 23.992 2 Dose Level: 0 0.32 0.15 88.86 55.18 0.24 0.120 2 72.02 23.815 2 Dose Level: 0.15 0.22 0.18 249.40 228.31 0.20 0.028 2 238.86 14.913 2 Dose Level: 0.75 0.73 0.40 89.07 94.97 0.57 0.233 2 92.02 4.172 2 Dosage Unit : mg/kg/day 60.95 29.70 0.00 0.00 2.28 2.86 45.33 22.097 2 0.00 0.000 2 2.57 0.410 2 Dosage Unit : mg/kg/day 112.37 104.83 0.00 0.00 4.32 2.22 108.60 5.332 2 0.00 0.000 2 3.27 1.485 2 Dosage Unit : mg/kg/day 85.47 46.34 0.00 0.00 3.89 4.50 65.91 27.669 2 0.00 0.000 2 4.20 0.431 2 113.93 122.28 118.11 5.904 2 133.88 194.67 164.28 42.985 2 122.53 131.85 127.19 6.590 2 4.61 4.59 4.60 0.014 2 QNS 7.69 7.69 - 1 4.63 4.36 4.50 0.191 2 4.23 4.96 4.60 0.516 2 3.65 6.48 5.07 2.001 2 3.41 3.46 3.44 0.035 2 1.65 1.91 1.78 0.184 2 1.63 1.81 1.72 0.127 2 1.41 1.31 1.36 0.071 2 954 ANIMAL NUMBER E2 pg/mL FSH ng/mL Appendix 6 Summary and Individual E2, FSH, and LH Additional Serum Analysis at Anilytics 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS LH ng/mL Group: Male 1 Dose Level: 0 Dosage Unit: mg/kg/day I05508 I05527 0.00 9.89 MEAN S.D. N 4.95 6.993 2 Group: Male 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05514 I05515 I05516 I05521 17.02 0.49 1.53 47.01 MEAN S.D. N 16.51 21.691 4 Group: Male 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05510 I05518 I05524 I05528 6.62 3.35 0.76 3.24 MEAN S.D. N 3.49 2.404 4 Covance 6329-223 3M T-6295.7 955 ANIMAL NUMBER E2 pg/mL FSH ng/mL Appendix 6 Summary and Individual E2, FSH, and LH Additional Serum Analysis at Anilytics 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS LH ng/mL Group: Male 4 Dose Level: 0.75 Dosage Unit: mg/kg/day 105506 105507 I05512 I05522a I05511a 0.00 0.00 0.00 18.68 12.85 MEAN S.D. N 6.31 8.877 5 a Recovery animal. Covance 6329-223 3M T-6295.7 956 ANIMAL NUMBER E2 pg/mL FSH ng/mL Appendix 6 Summary and Individual E2, FSH, and LH Additional Serum Analysis at Anilytics 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS LH ng/mL Group: Female 1 Dose Level: 0 Dosage Unit: mg/kg/day I05530 I05531 I05535 I05544 27.79 132.76 27.20 85.52 3.46 1.61 1.21 0.36 0.75 0.81 2.93 1.95 MEAN S.D. N 68.32 50.931 4 1.66 1.308 4 1.61 1.039 4 Group: Female 2 Dose Level: 0.03 Dosage Unit: mg/kg/day I05541 I05547 I05550 76.34 88.20 33.55 2.24 2.83 0.51 2.25 0.83 1.85 MEAN S.D. N 66.03 28.747 3 1.86 1.206 3 1.64 0.732 3 Group: Female 3 Dose Level: 0.15 Dosage Unit: mg/kg/day I05532 I05538 I05545 I05548 40.88 87.24 42.82 33.03 2.03 1.80 0.38 0.42 2.79 2.19 2.17 1.86 MEAN S.D. N 50.99 24.533 4 1.16 0.88 4 2.25 0.389 4 Covance 6329-223 3M T-6295.7 957 ANIMAL NUMBER E2 pg/mL FSH ng/mL Appendix 6 Summary and Individual E2, FSH, and LH Additional Serum Analysis at Anilytics 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS LH ng/mL Group: Female 4 I05534 I05536 I05540 I05551 I05542a I05533a 0.00 0.00 4.45 19.30 159.41 122.77 MEAN S.D. N 50.99 71.102 6 Dose Level: 0.75 Dosage Unit: mg/kg/day 0.38 0.76 0.88 0.32 1.37 1.50 2.20 2.03 2.06 1.73 2.55 1.58 0.87 0.490 6 2.03 0.344 6 a Recovery animal. Covance 6329-223 3M T-6295.7 958 Appendix 6 Summary and Individual T3, T4, Free T4, TSH, and Estradiol Additional Serum Analysis at Mayo Clinic - Week 27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS T3 T4 Free T4 TSH Estradiol nq/dL uq/dL nq/dL mIU/L pq/mL Group: Male 1 Dose Level: 0 Dosage Unit: mq/kq/day I05508 160 3 1.4 0.24 <35 I05527 132 3.5 1.5 0.86 <35 Mean 146.0 3.3 SD 19.80 0.35 N 22 Group: Male 2 Dose Level: 0. 03 I05514 154 3.6 I05515 135 3 I05516 166 4 I05521 126 4.1 1.5 0.6 NA 0.07 0.44 NA 2 2 NA Dosaqe Unit:: mq/kq/day 1.5 0.48 <35 1.4 0.49 <35 1 . 8 0.7 <35 1.4 0.55 <35 Mean 151.7 3.5 SD 15.63 0.50 N 33 Group: Male 3 Dose Level: 0. 15 I05510 123 3.2 I05524 128 2.9 I05528 133 2.8 1.6 0.6 NA 0.21 0.12 NA 3 3 NA Dosaqe Unit:: mq/kq/day 1.3 1.5 <35 1 . 6 0.55 <35 NS NS <35 Mean SD N 128.0 5.00 3 3.0 0.21 3 1.5 0.21 2 1.0 0.67 2 NA NA NA NS Test cancelled. Quantity not sufficient. 959 Covance 6329-223 3M T-6295.7 Appendix 6 Summary and Individual T3, T4, Free T4, TSH, and Estradiol Additional Serum Analysis at Mayo Clinic - Week 27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS T3 T4 ng/dL ug/dL Group: Male 4 Dose Level: 0.75 I05506 94 5.6 I05507 81 3.3 I05512 53 2.4 Free T4 TSH Estradiol ng/dL mIU/L pg/mL Dosage Unit : mg/kg/day 1.6 1.7 <35 1.5 1.4 <35 1.4 1.2 <35 Mean 76.0 3.8 SD 20.95 1.65 N 33 Group: Female 1 Dose Level: 0 I05530 176 4.7 I05531 128 2.9 I05535 I05544 134 4.7 154 2.8 1.5 0.10 1.4 0.25 33 Dosage Unit: mg/kg/day 1.8 0.69 1.4 0.27 1.7 NS 1.2 2.1 NA NA NA <35 146 <35 83 Mean 148.0 3.8 SD 27.73 1.07 N 44 Group: Female 2 Dose Level: 0. 03 I05541 140 4.4 I05547 150 4.4 I05550 124 3.3 1.5 1.0 114.5 0.28 4 0.96 3 44.55 2 Dosage Unit: mg/kg/day 2 0.52 73 1.6 0.7 48 1.5 1.1 <35 Mean SD N 138.0 13.11 3 4.0 0.64 3 1.7 0.26 3 0.8 0.30 3 60.5 17.68 2 NS Test cancelled. Quantity not sufficient. 960 Covance 6329-223 3M T-6295.7 Appendix 6 Summary and Individual T3, T4, Free T4, TSH, and Estradiol Additional Serum Analysis at Mayo Clinic - Week 27 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS T3 T4 Free T4 TSH Estradiol nq/dL uq/dL nq/dL mIU/L pq/mL Group: Female 3 Dose Level: 0..15 Dosage Unit: mq/kq/day I05532 1 0 0 3.5 1.4 3 <35 I05538 1 2 1 2.5 1 . 1 0.63 78 I05545 105 3.3 1.3 0.68 <35 I05548 137 3.6 1 . 6 0.99 <35 I05538 1 2 1 2.5 1 . 1 0.63 78 Mean 116.8 3.1 SD 14.70 0.54 N 55 Group: Female 4 Dose Level: 0. 75 I05534 79 4.2 I05540 101 2.8 I05551 120 4 1.3 1 . 2 78.0 0.21 1.03 0.00 552 Dosaqe Unit: mq/kq/day 1.9 3.3 <35 1.3 1.5 <35 1 . 6 0 . 8 8 <35 Mean SD N 100.0 20.52 3 3.7 0.76 3 1.6 0.30 3 1.9 1.26 3 NA NA NA Covance 6329-223 3M T-6295.7 961 Appendix 6 Summary and Individual T3, T4, Free T4, TSH, and Estradiol Additional Serum Analysis at Mayo Clinic - Week 79 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T -6295) IN CYNOMOLGUS MONKEYS T3 T4 nq/dL uq/dL Group: Male 4 Dose Level: 0.75 I05522 132 3 I05511 240 5.3 Free T4 TSH Estradiol nq/dL mIU/L pg/mL Dosage Unit: mg/kg/day 1.2 0.49 <35 1.3 0.035 <35 Mean 186.0 4.2 SD 76.37 1.63 N 22 Group: Female 4 Dose Level: 0. 75 I05542 134 3.3 I05533 134 3.5 1.3 0.3 NA 0.07 2 0.32 2 NA NA Dosaqe Unit: mg/kg/day 1.4 0.79 152 1.4 1.4 53 Mean SD N 134.0 3.4 1.4 1.1 102.5 0.00 0.14 0.00 0.43 70.00 2 2222 Covance 6329-223 3M T-6295.7 962 APPENDIX 7 Cell Proliferation Report Covance 6329-223 3M T-6295.7 Note: This appendix contains information supplied and audited by Pathology Associates International (PAI). 963 Covance 6329-223 3M T-6295.7 964 TABLE OF CONTENTS Contents Narrative Table Signature Page Quality Assurance Statement Appendix Covance 6329-223 3M T-6295.7 Section I II III IV V 965 Covance 6329-223 3M T-6295.7 Final Cell Proliferation Report Covance Study Number 6329-223 Page I-1 I. CELL PROLIFERATION REPORT 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS; T-6295) IN CYNOMOLGUS MONKEYS COVANCE STUDY NUMBER 6329-223 PURPOSE The purpose of the study was to assess the effect of the test material on critical enzyme levels, hormones, and other selected biochemical parameters when administered daily by capsule to cynomolgus monkeys for at least 26 weeks. This report, submitted by Pathology Associates - A Charles River Company (PAI) to the study Sponsor, 3M, represents the cell proliferation findings and interpretation for Covance Study Number 6329-223 entitled "26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys". All aspects of the tasks associated with PAI's portion of this study were conducted in compliance with the Environmental Protection Agency Good Laboratory Practice (GLP) Regulations as set forth in Title 40 of the US Code of Federal Regulations, Part 792, issued November 29, 1983 (effective December 29, 1983), and with any applicable amendments. MATERIALS AND METHODS Tissue Collection for Cell Proliferation Four animals per sex in groups 1 - 4 were sacrificed after 26 weeks on study. A representative sample of the liver, testes (males only) and pancreas from each animal was fixed in formalin, processed and embedded to paraffin block by Covance per protocol specifications. Tissue blocks were then shipped to PAI for sectioning and staining. From each block, a slide was prepared for H&E evaluation and immunohistochemical detection of proliferating cell nuclear antigen (PCNA), a marker of cell proliferation. Immunohistochemistry for Cell Proliferation Sections of paraffin-embedded tissues were cut at 5 xm and placed on positively charged slides (Superfrost Plus, Fisher Scientific, Pittsburgh, PA) to ensure adhesion during processing for PCNA. Standard immunohistochemical methods were used to stain tissues for PCNA (PAI's Standard Operating Procedure for Immunohistochemical Staining (SOP #707). Briefly, tissue sections were incubated with a monoclonal antibody to PCNA and reagents required for the avidin-biotin peroxidase method for the detection of the antigen-antibody complex. PCNA expression in cells was localized by the chromagen 3,3'-diaminobenzidine (DAB). Tissue sections were counterstained with hematoxylin. 966 Covance 6329-223 3M T-6295.7 Cell Proliferation Measurements Final Cell Proliferation Report Covance Study Number 6329-223 Page 1-2 The percentage of hepatocytes in S-phase (labeling index, LI) was determined by scoring at least 3000 hepatocytes in 10 fields of liver. The LI in the testes (males only) was determined by scoring the number of PCNA-positive Leydig cells among at least 100 Leydig cells. The labeling index in the pancreas was scored subjectively with 4 being both acinar and islets stained heavily and 3 being predominant staining in the acinar region. A negative control slide was included in the staining run and consisted of study tissue that was not incubated with the primary antibody. For cell proliferation evaluations, slides were first perused at low magnification (100X) to judge quality of staining, processing and sectioning, potential patterns of cellular proliferation, and histomorphologic changes. Cell proliferation was then quantified at higher magnification (200X for liver and pancreas, and 400X for testes) as described above. Histomorphology was further assessed by evaluating the H&E slide prepared from the same tissue block for each animal evaluated for cell proliferation. Statistical Analysis The Student's f-test (two-sided, unequal variance) was used to test for statistical significance in LI between control and treatment groups using Microsoft Excel version 5.0. A P value of 0.05 or less was judged to be statistically significant. RESULTS Cell Proliferation Individual animal cell proliferation data are presented in Section II (Table II-1). Cell proliferation in the liver, testes and pancreas of control and test material-treated animals was similar. Histopathology Sections from the same tissue blocks used for preparation of PCNA-stained slides were stained with hematoxylin and eosin (H&E) for histopathologic evaluation to facilitate the interpretation of the immunostained slides. Individual animal findings are presented in Appendix I. Single sections of liver, pancreas, and testes from 16 adult male monkeys and single sections of liver and pancreas from 16 adult female monkeys representing control, low-dose (0.03 mg/kg/day), mid-dose (0.15 mg/kg/day) and high-dose (0.75 mg/kg/day) treatment groups were evaluated histologically. Each tissue section was stained with hematoxylin and eosin. The purpose of this evaluation was to determine whether or not morphologic changes were occurring in these tissues which may alter or confound the specificity of the PCNA staining observed in these animals. 967 Covance 6329-223 3M T-6295.7 Final Cell Proliferation Report Covance Study Number 6329-223 Page 1-3 The results showed that no significant changes were observed in either the liver, pancreas, or testicular tissues from male monkeys or the liver and pancreas tissues from female monkeys, which would alter the interpretation of the PCNA staining in this study. DISCUSSION In the present study, cell proliferation was measured within the liver, testes and pancreas of male monkeys, and the liver and pancreas of female monkeys from control (0 mg/kg/day), low dose (0.03 mg/kg/day), mid-dose (0.15 mg/kg/day) and high dose (0.75 mg/kg/day) groups after 26 weeks on study to assess the effect of the test material on critical enzyme levels, hormones, and other selected biological parameters, including cell proliferation. There did not appear to be a cell proliferative response to the test material in the liver, testes or pancreas, as determined by labeling indices, which were similar in all animals. SUMMARY In the present study, cell proliferation, as determined by measuring the labeling index, was not increased in the liver, testes or pancreas of monkeys. 968 Covance 6329-223 3M T-6295.7 II. TABLE Legend ND, not determined due to suboptimal staining NP, slide not present Liver labeling index: Percentage of hepatocytes in S-phase Pancreas labeling index: Scored subjectively with 4 = islets and acinar staining heavily; 3 staining more abundant in acinar cells than islets Testes labeling index: Percentage of PCNA-positive Leydig cells 969 Covance 6329-223 3M T-6295.7 TABLE II-1.CELL PROLIFERATION INMONKEYS COVANCE STUDY NO. 6329-223 Page 11-1 A nim al Labeling Index Labeling Index Labeling Index Dose Group 0 mg/kg/day (Control) 0 mg/kg/day (Control) 0 mg/kg/day (Control) 0 mg/kg/day (Control) 0.03mg/kg/day (Low dose) S ex/G ro up F/l F/l F/l F/l F/2 Num ber 105530 105531 105535 105544 M ean SEM 105537 Liver 0.000% 0.027% 0.000% 0.199% 0.057% 0 .0 4 8 % 0.113% P a n c re a s 4 3 3 4 3.5 0.3 3 Testes NP NP NP NP - - NP 0.03 mg/kg/day (Low dose) F/2 105541 0.125% 4 NP 0,03 mg/kg/day (Low dose) 0.03mg/kg/day (Low dose) 0.15mg/kg/day (Mid dose) 0.15mg/kg/day (Mid dose) F/2 105547 F/2 105550 M ean SEM F/3 105532 F/3 105538 0.000% 0,212% 0.112% 0.044% 0.000% 0.086% 3 NP 3 NP 3.3 0.3 3 NP 3 NP 0.15mg/kg/day (Mid dose) F/3 105545 0.029% 3 NP 0.15mg/kg/day (Mid dose) F/3 105548 0.120% 4 NP 0,75mg/kg/day (High dose) 0.75mg/kg/day (High dose) M ean SEM F/4 105534 F/4 105536 0.059% 0.027% 0.000% 0.313% 3.3 0.3 - 3 NP 3 NP 0.75mg/kg/day (High dose) F/4 105540 0.000% 3 NP 0.75mg/kg/day (High dose) F/4 105551 M ean SEM 0.000% 3 NP 0.078% 3.0 - 0.078% 0.0 - 0 mg/kg/day (Control) M/l 105508 0.100% 4 9.52% 0 mg/kg/day (Control) M/l 105517 0.062% 3 9.00% 0 mg/kg/day (Control) M/l 105519 0.108% 3 20.75% 0 mg/kg/day (Control) M/l 105527 0.464% 4 19.23% M ean 0.184% 3.5 14.63% 0,03mg/kg/day (Low dose) SEM M/2 105514 0.094% 0.095% 0.3 3.12% 3 16.36% 0.03mg/kg/day (Low dose) M/2 105515 0.000% 3 18,52% 0.03mg/kg/day (Low dose) M/2 105516 0.000% 3 22,95% 0,03mg/kg/day (Low dose) M/2 105521 0.000% 4 12.38% M ean 0.024% 3.3 17.55% 0.15mg/kg/day (Mid dose) SEM M/3 105510 0 .0 2 4 % 0.053% 0.3 2.20% 3 9.17% 0,15mg/kg/day (Mid dose) 0,15mg/kg/day (Mid dose) 0.15mg/kg/day (Mid dose) M/3 105518 M/3 105524 M/3 105528 0.029% 0.155% 0.000% 4 17.14% 3 14.42% 4 10.71% M ean 0 .0 5 9 % 3.5 12.86% 0.75mg/kg/day (High dose) 0.75mg/kg/day (High dose) 0.75mg/kg/day (High dose) 0.75mg/kg/day (High dose) SEM M/4 105506 M/4 105507 M/4 105509 M/4 105512 0 .0 3 4 % 0.030% 0.027% NP 0.000% 0.3 1.80% 3 7.69% 3 19,61% NP NP 3 ND M ean SEM 0 .0 1 9 % 0 .0 0 9 % 3.0 13.65% 0.0 5.96% ND, notdetermined due tosuboptimal staining NP, slidenotpresent Liver:Percentage ofhepatocytes InS-phase Pancreas: Scored subjectivelywith4=lsletsand acinarstained heavily(>50% labeled); 3=aclnarislets Testes:Percentage ofproliferating Leydig cells 970 Covance 6329-223 3M T-6295.7 971 Covance 6329-223 3M T-6295.7 IV. QUALITY ASSURANCE STATEMENT 972 Covance 6329-223 3M T-6295.7 973 Covance 6329-223 3M T-6295.7 APPENDIX I 974 Covance 6329-223 3M T-6295.7 Individual A nim al Findings 3MP #6329-223 26-W EEK CAPSULE TOX ICITY STUDY W ITH PERFLUOROOCTANE SULFONIC ACID PO TASSIUM SALT (PFO S; T6295) IN CYNOM OLGUS M ONKEYS * ANIM AL NUMBER SEX DOSE GROUP H ISTO LO G IC FINDINGS 105530 105531 105535 105544 105537 105541 105547 105550 105532 105538 105545 105548 105534 105536 105540 105551 105508 105517 105519 105527 105514 105515 105516 105521 105510 F F F F F F F F F F F F F F F F M M M M M M M M M 1 Liver - NSF Pancreas - NSF 1 Liver - NSF Pancreas - NSF 1 Liver - chronic inflammation, minimal Pancreas - NSF 1 Liver - NSF Pancreas - NSF 2 Liver - NSF Pancreas - NSF 2 Liver - chronic inflammation, minimal Pancreas - NSF 2 Liver - NSF Pancreas - NSF 2 Liver - NSF Pancreas - NSF 3 Liver - NSF Pancreas - NSF 3 Liver - chronic inflammation, minimal Pancreas - NSF 3 Liver - chronic inflammation, minimal Pancreas - NSF 3 Liver - chronic inflammation, minimal Pancreas - NSF 4 Liver - NSF Pancreas - NSF 4 Liver - fat infiltration, centrilobular, moderate Pancreas - NSF 4 Liver - NSF Pancreas - NSF 4 Liver - NSF Pancreas - NSF__________________________ 1 Liver - chronic inflammation, minimal Pancreas - chronic inflammation, minimal Testes - NSF 1 Liver - NSF Pancreas - NSF Testes - crush artifact, focal 1 Liver - NSF Pancreas - NSF Testes - NSF 1 Liver - NSF Pancreas - NSF Testes - NSF 2 Liver - chronic inflammation, minimal Pancreas - chronic inflammation, minimal Testes - NSF 2 Liver - chronic inflammation, minimal Pancreas - NSF Testes - NSF 2 Liver - NSF Pancreas - NSF Testes - NSF 2 Liver - NSF Pancreas - NSF Testes - NSF 3 Liver - chronic inflammation, minimal Pancreas - NSF Testes - NSF Legend: NSF = no significant findings 975 Covance 6329-223 3M T-6295.7 L egend: NSF = no significant findings 976 Covance 6329-223 3M T-6295.7 APPENDIX 8 Electron Microscopic Evaluation of Liver in Cynomolgus Monkeys Note: This appendix contains information supplied and audited by Pathology Associates International (PAI). 977 Covance 6329-223 3M T-6295.7 Pathology Associates International A Company of Science Applications International Corporation An Employee-Owned Company PATHOLOGY REPORT (ANCILLARY STUDY) ELECTRON MICROSCOPIC EVALUATION OF LIVER IN CYNOMOLGUS MONKEYS (RECOVERY ANIMALS) 26-WEEK CAPSULE TOXICITY STUDY W ITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS CLIENT STUDY NUMBER 6329-223 PAI STUDY NUMBER EM 99.76 Prepared by: Jam es B. Nold, D.V.M., Ph.D., Diplomate, A.C.V.P. Pathology Associates International 4915-D Prospectus Drive Durham, NC 27713 Septem ber 1, 2000 PREPARED FOR 3M CORPORATE TOXICOLOGY, 3M CENTER, ST. PAUL, MN 55144-1000 4915 D Prospectus Drive Durham, North Carolina 27713 (919) 544-5257 (919) 544-3218 FAX 978 Pathology Narrative Light Microscopy and Transmission Electron Micrograph Interpretation Forms Transmission Electron Micrographs Quality Assurance Statement Covance 6329-223 3M T-6295.7 Section I n HI IV 979 Covance 6329-223 3M T-6295.7 I. Pathology Narrative 980 Covance 6329-223 3M T-6295.7 Electron Microscopy Report Covance Study No. 6329-223 Recovery Sacrifice Animals PATHOLOGY REPORT (ANCILLARY STUDY) ELECTRON MICROSCOPIC EVALUATION OF LIVER IN CYNOMOLGUS MONKEYS (RECOVERY ANIMALS) 26-WEEK CAPSULE TOXICITY STUDY W ITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS CLIENT STUDY NUMBER 6329-223 PAI STUDY NUMBER EM 99.76 SUMMMARY Two male and two female cvnomolgus monkeys treated for 26 weeks with 0.75 mg/kg PFOS were removed from treatment for up to 53 weeks. Liver samples obtained by biopsy at Week 57 and necropsy at Week 79 were examined for reversibility, persistence, or delayed occurrence of toxic effects. Light and electron microscopic evaluation of livers identified no pathological changes. The treatment-related changes of hepatocellular hypertrophy and vacuolation, noted at 26 weeks and characterized ultrastructurally by increased numbers of lipid droplets within hepatocytes, had completely disappeared during the recovery period. PROCEDURES The objective of this study was to examine by electron microscopy the livers from selected animals in a 26-week capsule toxicity study with PFOS in cynomolgus monkeys. In addition to a general qualitative evaluation for differences between control and treated animals, the ultrastructural endpoints included quantitation of peroxisomes within hepatocytes and membrane and mitochondrial changes in hepatocytes. Light microscopy ot paraffin-embedded liver sections was also performed. This report details the light and electron microscopy findings in the four high-dose male and female monkeys designated as recovery animals. A previous report (dated 6-24 1999) indicated that treatment of cynomolgus monkeys with 0.75 mg PFOS/kg/day for 26 weeks resulted in hepatocellular vacuolation and hypertrophy by light microscopy. Hepatocellular vacuolation and hypertrophy were primarily centrilobular m distribution and did vary in incidence and severity between individual animals. Ultrastructurally, there were increased lipid droplets within hepatocytes. Increased lipid droplets were 1-1 981 Covance 6329-223 3M T-6295.7 Electron Microscopy Report Covance Study No. 6329-223 Recovery Sacrifice Animals present in both the high-dose males examined and in two of four high-dose females examined. Increased hepatocellular glycogen was present in the remaining two high-dose females. These ultrastructural changes correlated with hepatocellular hypertrophy and vacuolation noted by light microscopy and with increased liver weight parameters in the high-dose animals. The no-effect level for hepatocellular vacuolation (lipid droplet accumulation) was 0.15 mg/kg/day of PFOS (mid-dose group). Quantitation of peroxisomes within hepatocytes by electron microscopy indicated no remarkable differences between control livers and livers treated with 0.03, 0.15, or 0.75 mg PFOS/kg/day. Ultrastructural differences in cellular membranes or mitochondria were not discernible between control and treated animals in the samples examined. The recovery' animals were examined to assess for reversibility or persistence of these hepatocellular changes, or for the delayed occurrence of additional PFOS-induced effects. For the toxicity study, 22 male and 22 female cynomolgus monkeys were given the test article or the vehicle once daily for at least 26 weeks according to Text Table 1. Text T able 1. G roup D esignations and D osage Levels Dosage Group I II III IV Dose Level img/kg/day)a (T 0.03 0.15 0.75 Total Material Dose Level (mg/kg/day)b 30a 15b 6C 30c Number of Males 6d 4 6d 6d Number of Females 6d 4 6d 6d J Dose levels were provided. The control group (Group 1) received an equivalent amount of lactose in gelatin capsules as the total material administered to Group 4. ` The low-dose group (Group 2; received the test material diluted with lactose (1:499. w:w). ' The mid-dose (Group 3) and high-dose (Group 4) groups received the test material diluted with lactose i 1:39. w:wi. " " Two animals in Groups 1. 3. and 4, designated as recovery animals, were treated for at least 26 weeks, then treatment was discontinued and the animals were observed for reversibility, persistence, or delayed occurrence of toxic effects for at least 52 weeks posttreatment. During W eek 57 (approximately 31 weeks into the recovery period), the 2 high-dose recovery males and 2 high-dose recovery females were anesthetized and liver biopsies were surgically obtained from each animal and chemically preserved and processed as described below. During Week 79, the 4 high-dose recovery animals were necropsied and liver samples obtained as described below. The two control recovery animals were returned to the Covance stock animal colony, and the two Group HI animals were transferred to a subsequent study (Covance 6329-268). Liver samples were not obtained and examined in the control recovery or Group HI recovery animals. Animals to be sacrificed at recovery sacrifice times were anesthetized with ketamine and xylazine. weighed, exsanguinated, and necropsied. Multiple tissues were collected and preserved in 10% neutral-buffered formalin according to the protocol. Additionally, 1-2 982 Covance 6329-223 3M T-6295.7 Electron Microscopy Report Covance Study No. 6329-223 Recovery Sacrifice Animals pieces of liver from each animal were thin-sliced and placed in `/z strength Karnovsky's fixative (2.0% paraformaldehyde/2.5% glutaraldehyde in 0.1M phosphate buffer) for subsequent ultrastructural examination. These livers were processed into Epon blocks and submitted to this laboratory for subsequent electron microscopy processing and evaluation. Hematoxylin and eosin (H&E)-stained slide sections of formalin-fixed, paraffin-embedded livers were submitted for light microscopic examination. The four high-dose recovery animals are listed in Text Table 2. For each animal, there was a 57-Week liver biopsy sample and a 79-Week terminal necropsy liver sample. Text Table 2. R ecovery Anim als Exam ined by Light and Electron M icroscopy 0.75 mg/kg/day PFOS (Group 4 High-Dose) Males Females 105511 105533 105522 105542 Thin sections (approximately 90 nm) from the Epon-embedded livers were cut, mounted on 200-mesh copper grids, stained with 5% methanolic uranyl acetate and Reynold's lead citrate, and examined on a Zeiss 900 transmission electron microscope. Centrilobular hepatocytes, where clearly identifiable in liver sections, were preferentially examined. Representative electron photomicrographs of liver were taken and significant ultrastructural features were summarized for each photograph and animal on a designated transmission electron micrograph interpretation form. The number of peroxisomes in hepatocytes was manually counted for each center photographed hepatocyte and recorded. For light microscopy, the H&E slides from the same animals selected for electron microscopy were evaluated and significant features were summarized on a light microscopic evaluation form. RESULTS AND DISCUSSION Individual interpretations of light microscopy slides and electron micrographs for each animal are shown in Section . Representative electron photomicrographs were selected as report figures, labeled, and are shown in Section HI. All remaining electron micrographs are separately attached to this report. Light Microscopy A summary of the incidence and severity of light microscopic findings in the control and high-dose livers is shown in Text Table 3. There were no microscopic findings that appeared to be associated with test material administration. Hepatocellular hypertrophy and vacuolation. noted after 26 weeks of treatment in some high-dose animals, were not identified in recovery' samples at either the 57-Week biopsy or 79-Week terminal necropsy samples, indicating complete reversal of the light microscopic liver changes. 1-3 983 Covance 6329-223 3M T-6295.7 Electron Microscopy Report Covance Study No. 6329-223 Recovery Sacrifice Animals The liver findings noted in the recovery animals were considered normal background histopathology of cvnomolgus monkeys. Text Table 3. Incidence and Severity of Light Microscopic Liver Findings Recovery Animals 0.75 ma/ke/dav (Hiah-Dose) Males Females 57-Week Biopsy (number examined) (2) 12) Infiltrate, lymphohistiocytic, minimal Terminal Necropsy - Infiltrate, lymphohistiocytic, minimal Hyperplasia, bile duct, slight Inflammation, lymphohistiocytic, slight Inflammation, eosinophilic, slight Clearing, cytoplasmic, centnlobular, minimal Incidence of zero. 1 9 i i i - 2 2 _ _ _ 1 Electron Microscopy Electron microscopic evaluation of the 57.-week biopsy and 79-week necropsy liver samples identified no abnormal features, and all tissue samples were considered to be ultrastructurallv normal (Text Table 4). The hepatocellular hypertrophy and vacuolation seen after 26 weeks of treatment, and characterized ultrastructurallv by increased lipid droplets, were not seen in the recovery animal liver samples, indicating recovery of these test material related effects. The electron microscopic features described in these recovery7samples were considered normal ultrastructural findings in hepatocytes. Figures 1-4 are representative electron micrographs from these samples and illustrate normal liver and hepatocellular features. Text Table 4. Summary of Ultrastructural Findings - Recovery Animals Treatment Group (mg/kg/day)/Sex (0.75) Male, 57-week biopsy (0.75) Male, 79- week necropsy (0.75) Male, 57-week biopsy (0.75) Male, 79-week necropsy (0.75) Female, 57-week biopsy (0.75) Female, 79-week necropsy (0.75) Female, 57-week biopsy (0.75) Female, 79-week necropsy Animal No. 105511 105511 105522 105522 105533 105533 105542 105542 Comments Normal Normal Normal Normal Normal Normal Normal Normal 1-4 984 Covance 6329-223 3M T-6295.7 Electron Microscopy Report Covance Study No. 6329-223 Recovery Sacrifice Animals Peroxisomes were identified and quantitated in representative hepatocytes (Text Table 5). Mean peroxisome numbers per hepatocyte were considered normal. Text Table 5 Quantitation of Hepatocellular Peroxisomes 0.75 ms PFOS/kg/day (Hish-Dose) Recovery Animals Male Female 57-week biopsy Animal Number1of Number Peroxisomes 105511 18.5 105522 19.4 Mean = 18.95 79-week necropsy Animal Number of Number Peroxisomes 105511 19.2 105522 25.8 Mean = ' 22.5 57-week biopsv Animal Number of Number Peroxisomes 105533 29.8 105542 23.0 Mean = 26.4 79-week necropsy Animal Number of Number Peroxisomes 105533 20.8 105542 15.2 Mean = 18.0 1Average number of peroxisomes per hepatocyte for five hepatocytes counted per animal. For Animal No. 10551 1 (biopsy), peroxisomes were counted in only four hepatocytes CONCLUSION Light and electron microscopic evaluation of livers from cvnomolgus monkevs treated with 0.75 mg PFOS/kg/day for 26 weeks and allowed to "recover" untreated for 3 1 and d3 weeks identified no pathological changes. The treatment-related changes of hepatocellular hypertrophy and vacuolation. characterized ultrastructurally by increased numbers of lipid droplets within hepatocytes at 26 weeks, had completely resolved during the recovery period. SIGNATURE OF AUTHOR P\ James B. Nold, D.V.M., Ph.D Diplomate, A.C.V.P. Date 985 Covance 6329-223 3M T-6295.7 II. Light Microscopy and Transmission Electron Micrograph Interpretation Forms 1 Forms are exact copies of signed/dated raw data sheets maintained in archived study file. 986 Covance 6329-223 3M T-6295.7 LIGHT MICROSCOPIC EVALUATION Study No.: 63 29-223 (EM 99.76) Species/Strain: Cvnomolgus Monkeys A n im a l N o: see below Sex: see below interpreting Pathologist (signature and date): Tissue: ___Liver April 7. 2000 D ose/Group i 0.75 mg/kg : (High-dose 1 : Recovers : Males ' : 57 wk biopsy ; 0.75 mg/kg ; (High-dose i ' Recover) Females ; 57 wk biopsv i 0.75 mg/kg i (High-dose) i Recovery : Maies i 79 wk ^ necropS} ; 0.75 mg/kg (High-dose) Recover} Females 798 week necropsy i 1 : : ; ; Animal Number 105511 105522 105533 05542 1055 11 105522 105533 105542 :' M icroscopic Findings and Comments : 1. Infiltrate, lymphohistiocytic, multifocal, minimal ; Normal ; 1. Infiltrate, lymphohistiocytic, focal, minimal ; 1. Infiltrate, lymphohistiocytic, multifocal, minimal : 1. Infiltrate, lymphohistiocytic, multifocal, minimal : 1. Infiltrate, lymphohistiocytic, multifocal, minimal : 2. Hyperplasia, focal, slight, bile duct 1 3. Inflammation, lymphohistiocytic, multifocal, slight ; 4. Inflammation, eosinophilic, multifocal, slight : 1. Infiltrate, lymphohistiocytic, multifocal, minimal : 1. Infiltrate, lymphohistiocytic, multifocal, minimal i 2. Clearing, cytoplasmic, centrilobular, minimal 987 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Species/Strain: Cvnomolgus Monkey Animal No.: 1055 11____________ 57-week biopsy Treatment Group: .75 mg/kg (hi-dose) Sex: Male Tissue: Liver - centrilobular Block No(s).: 99.76-31-1A Z 18823 - Photo/Negative No(s).: Z18827 Significant Lesions (check one): Yes X No Interpreting Pathologist (signature and date): ( f? O .T y f May 26. 2000 Features: Z18823. Liver. Hepatocyte. 15,290X. This hepatocyte has a small round central nucleus. The surrounding cytoplasm contains numerous round to oval mitochondria and several small to large lipid droplets. The darker round organelles, mostly slightly smaller than the mitochondria, are peroxisomes. Twenty-four (24) peroxisomes counted. The intervening cytosol contains profiles of endoplasmic reticulum and some fine granules, which may be glycogen. Z18829. Liver. 10,320X. Portions of three cells are present. The dorsal two hepatocytes exhibit a mixture of normal appearing cytoplasmic elements, including mitochondria, endoplasmic reticulum and scattered peroxisomes. The larger ventral cell's' cytoplasm contains irregular clear spaces surrounded by membranous material. Only a couple of mitochondria are evident, and this cell is probably not a hepatocyte. Around the periphery are several large structures containing finely granular and reticular material. This may represent smooth endoplasmic reticulum intermixed with glycogen and/or ribosomes. It appears to be membrane bound, but this may be a pseudomembrane caused by compacting of the surrounding cytoplasm. Or, these structures may represent cytoplasmic invaginations of extracellular material such as plasma. The nuclear profiles in these cells appear normal. Peroxisomes were not counted in this electron micrograph because an individual hepatocyte showing most of its cytoplasm is not present. Z18825. Liver. Hepatocyte. 10,320X, This hepatocyte is polygonal with a round central nucleus. Its surrounding cytoplasm contains numerous mitochondria and a few small lipid droplets. The intervening cytoplasm contains profiles of endoplasmic reticulum, scattered fine glycogen granules, and some dark round peroxisomes. Twenty-two (22) peroxisomes counted. Three adjacent hepatocytes appear essentially normal. At the bottom right of the photograph is a finely granular structure, which is outside of the centered hepatocyte and appears similar to that described in Z 18224. Z18826. Liver. Hepatocyte. 10,320X. This hepatocyte is bordered by an extracellular space along its right margin. The cell has a small nuclear profile and abundant cytoplasm containing numerous mitochondria and slightly dilated endoplasmic reticulum. Several lipid droplets are present. Seventeen (17) peroxisomes counted._____________________ 988 Covance 6329-223 3M T-6295.7 989 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Species/Strain: Cvnomolgus Monkey Animal No.: 1055 11_____________ 79-week necropsy Treatment Group: .75 mg/kg (hi-dose) Sex: Male Tissue: Liver - centrilobular Block No(s).: 99.76-32-2A Z18828 - Photo/Negative No(s).: Z18832 Significant Lesions (check one): Yes X No Interpreting Pathologist (signature and date): Cl .$J( May 29. 2000 Features: Z18828. Liver. Hepatocyte. 10,320X. This hepatocyte is somewhat oval in shape with a small round nucleus. Approximately 8-9 small to medium sized lipid droplets are present in the cytoplasm. The majority of the cytoplasm contains numerous round to rod-shaped mitochondria, intervening areas of smooth endoplasmic reticulum (SER) and "more clear" patches of glycogen. Some profiles of rough endoplasmic reticulum (RER) and round dark peroxisomes are also evident. Twenty-eight (28) peroxisomes counted. Bile canaliculi can be seen between the hepatocytes situated on the right and left with the central hepatocyte. Z18829. Liver. Hepatocyte. 10,320X. The central vein and surrounding extracellular collagen are present at the top right margin of this electron micrograph. A sinusoid is also present at the lower left margin. The intervening hepatocyte has a round nucleus and surrounding cytoplasm containing numerous profiles of endoplasmic reticulum and dark mitochondria. There is mild dilatation of the endoplasmic reticulum and nuclear envelope, which is a fixation artifact. Several dark residual bodies and occasional small lipid droplets are also identified. Differentiation between peroxisomes and mitochondria is difficult. Eleven (11) peroxisomes counted. Z18830. Liver. Hepatocyte. 10,320X. The cytoplasm of this hepatocyte contains abundant SER, although some profiles of RER are also evident, especially around some mitochondria. A nuclear profile is not evident in this plane of section of the centered hepatocyte. Approximately 20 lipid droplets are present. Twenty (20) peroxisomes counted. This hepatocyte's microvillous border is evident both dorsally and ventrally along sinusoids. The nucleus of an endothelial cell is present at the lower right. Adjacent hepatocytes are present to the left and right of the centered hepatocyte. Z18831. Liver. Hepatocyte. 10,320X. The morphology of this hepatocyte is very similar to Z 18828. The cytoplasm contains numerous mitochondria, endoplasmic reticulum and "more clear" patches of glycogen. Several lipid droplets are present. Nineteen (19) peroxisomes counted. The surrounding hepatocytes appear ultrastructurallv similar. 990 Covance 6329-223 3M T-6295.7 991 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION StLld>' No.: 6329-223 (EM 99.76) Species/Strain: Cvnomolgus Monkey Animal No.: 105522___________ 57-week biopsy Treatment Group: .75 mg/kg (hi-dose) Sex: ________ Male_____________ T issue:_____ Liver - centnlobular Block No(s).: 99.76-33-1A Z 18833 - Photo/Negative No(s).: Z18837 Significant Lesions (check one): ____ fes X No Interpreting Pathologist (signature and date): W ^ ^ f]TM May 29, 2000 Features: Z18833. Liver. Hepatocyte. 10,320X. A sinusoid containing finely granular plasma is along the right microvillous margin of this hepatocyte. The hepatocyte has an oval nucleus. In the surrounding cytoplasm are several very' electron-dense residual bodies. There is mild dilatation of the nuclear envelope and endoplasmic reticulum, u hich is a fixation artifact. Eighteen (18) peroxisomes counted. Mitochondria are numerous and are variably shaped. Z18839. Liver. Hepatocyte. 10,320X. This hepatocyte appears ultrastructurally similar to Z 18833. There is mild dilatation of the endoplasmic reticulum and nuclear envelope. The hepatocyte lines a sinusoid, which contains two erythrocytes and a granulated eosinophil. Eight (8) peroxisomes counted. Z18835. Liver. Hepatocyte. 10,320X. Several small lipid droplets are present in the cytoplasm of this hepatocyte. It has a slightly oval nucleus and abundant cytoplasm which contains numerous mitochondria and profiles of endoplasmic reticulum. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. A distinct myelin figure is evident associated with a lipid droplet to the left of the nucleus. Twenty-two p22) peroxisomes counted. Z18836. Liver. Hepatocyte. 10,320X. The hepatocyte has a large polygonal nucleus. The cytoplasm contains abundant SER and RER, which exhibit slight dilatation. Several small to large lipid droplets are present. Numerous round dark peroxisomes are evident. Thirty-five (35) peroxisomes counted. Mitochondria are numerous and variably shaped, but appear ultrastructurally normal. Z18837. Liver. Hepatocyte. 10,320X. A sinusoid is present along the left and lower margins of this electron micrograph. The lighter-staining endothelial cell is present along the lower margin. The centered hepatocyte has an oval nucleus and numerous mitochondria and endoplasmic reticulum in its surrounding cytoplasm. There is mild dilatation of the endoplasmic reticulum and nuclear envelope. Several lipid droplets and residual bodies are also discernible. Fourteen (14) peroxisomes counted._______________ Conclusions: Normal hepatocytes. Peroxisomes average 19.9 per hepatocyte. 992 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (E M 99.76) Species/Strain: Cvnom olgus M onkey Anim al No.: 105522________________ 79-week necropsy Treatm ent G ro u p : .75 mg/kg (hi-dose) S e x: Male Tissue: L iv e r - centrilobular B lock N o($).: 99.76-39-2A Z18838 Photo/Negative No(s).: Z18892 Significant Lesions (check one) Yes X No Interpreting Pathologist (signature and date) f? A May 29. 2000 Features: Z18838. Liver. Hepatocyte. 10,320X. This hepatocyte has a large round nucleus. At the very top left margin of the electron micrograph is a segment of sinusoid along its microvillous border. A bile canaliculus is evident at the lower left margin of the photograph, where the centered hepatocyte meets an adjacent hepatocyte. The centered hepatocyte has abundant cytoplasm, which contains numerous profiles of RER and SER. There is slight dilatation of the endoplasmic reticulum. Mitochondria are numerous are round to oval in shape. Approximately twenty-three (23) peroxisomes counted. Z18839. Liver. Hepatocyte. 10,320X. Two hepatocytes are clearly evident in this electron micrograph. They appear ultrastructurally similar. They exhibit mild dilatation of their endoplasmic reticulum and nuclear envelopes. They have numerous mitochondria and occasional lipid droplets and residual bodies. Peroxisomes-are usually round and more electron-dense than the mitochondria. Seventeen (17) peroxisomes counted in the upper hepatocyte. Z18840. Liver. Hepatocyte. 10.320X. This hepatocyte has a large round central nucleus. The surrounding cytoplasm has numerous mitochondria and many slightly dilated profiles of endoplasmic reticulum. Both the SER and RER appear slightly dilated. Approximately 15-16 small to medium sized lipid droplets are present, as are a few very electron dense residual bodies. Twenty-one (21) peroxisomes counted. Z18841, Liver. Hepatocyte. 10,320X. This hepatocyte's nucleus is not evident in this plane of section. A sinusoid containing an erythrocyte is present along the very top margin of this electron micrograph. There is slight dilatation of the endoplasmic reticulum throughout the cytoplasm. Also, random small to medium sized lipid droplets are present. Numerous peroxisomes are evident. Forty (40) peroxisomes counted. Z18842. Liver. Hepatocyte. 10,320X. This hepatocyte appears similar to Z18838, and is ultrastructurally normal. It has an oval nucleus and abundant surrounding cytoplasm containing numerous mitochondria and slightly dilated profiles of endoplasmic reticulum. Twenty-eight (28) peroxisomes counted. Sinusoids are evident at the upper left and lower right margins of the photograph.__________________________ Conclusions: Normal hepatocytes. Peroxisomes average 25.8 per hepatocyte. 993 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Species/Strain: Cvnomoleus Monkey Animal No.: _ 105533 57-week biopsy Treatment Group: .75 mg/kg (hi-dose) Sex: Female T issue:_____ Liver - centnlobular Block No(s).: 99.76-35-1A Z 18843 - Photo/Negative No(s).: Z18897 Significant Lesions (check one): Yes No Interpreting Pathologist (signature and date): May 29. 2000 Features: Z18893. Liver. Hepatocyte. 10,320X. This hepatocyte has a small nuclear profile. A sinusoid lined by an endothelial cell is present along the upper right margin of the electron micrograph, and an adjacent hepatocyte is present at the lower left margin. A prominent bile canaliculus is present betw-een the two hepatocytes. The cytoplasm of the centered hepatocyte is voluminous and contains numerous mitochondria and endoplasmic reticulum. The endoplasmic reticulum, nuclear envelope, and mitochondria appear to be slightly dilated. This dilatation is a fixation artifact. A few small to medium sized lipid droplets are present. Forty (40) peroxisomes counted. Z18844. Liver. Hepatocyte. 10,320X. This somewhat triangular-shaped hepatocyte has a large oval nucleus. Its cytoplasm contains numerous mitochondria and slightly dilated profiles of RER. Some glycogen granules appear to be intermixed with the SER. Eighteen (18) peroxisomes counted. Z18845. Liver. Hepatocyte. 10,320X. This electron micrograph appears similar to Z 18844, although tw;o nuclear profiles are present, which is probably a function of the plane of section although it may be binucleated. Thirty-four (34) peroxisomes counted. Z18846. Liver. Hepatocyte. 10,320X. The centered hepatocyte contains a small round nucleus. The surrounding cytoplasm contains numerous mitochondria and slightly dilated profiles of endoplasmic reticulum, both SER and RER. One myelin figure and several lipid droplets are present. Thirty-three (33) peroxisomes counted. Some extracellular collagen and a sinusoid are present along the lower right margin of the photograph. The hepatocyte at the top right is more lightly staining than the centered hepatocyte, and its cytoplasm contain abundant SER. Some mitochondria and peroxisomes are also evident. Z18847. Liver. Hepatocyte. 10,320X. This electron micrograph appears very similar to Z 18844. Although there is slight dilatation of the endoplasmic reticulum, this hepatocyte appears ultrastructurally normal. Twenty-four (24) peroxisomes counted. Conclusions: Normal hepatocytes. Peroxisomes average 29.8 per hepatocyte. 994 Covance 6329-223 3M T-6295.7 995 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76! Species/Strain: Cynomolgus Monkey Animal No.: 105592__________ 57-week biopsy Treatment Group: .75 mg/kg/ (hi-dose) Se x: Female T issue:_____ Liver - periportal Block No(s).: 99.76-3 /-IA Z 18853 - Photo/Negative No(s).: Z18857 Significant Lesions (check one): Yes X___ No Interpreting Pathologist (signature May 29. 2000 Features: Z18853. Liver. Hpatocyte. 10,320X. This hepatocyte appears surrounded by adjacent hepatocytes on all sides. It has a large polygonal nucleus and abundant surrounding cytoplasm. Just to the lower left of its nucleus is a small segment of extracellular space containing some microvilli and collagen, probably next to a sinusoid. Several small lipid droplets are present in the cytoplasm of the centered hepatocyte. The endoplasmic reticulum is slightly dilated, and several residual bodies are present. Nineteen (19) peroxisomes counted. Z18859. Liver. Hepatocyte. 10,320X. Similar to Z18853, the endoplasmic reticulum of this hepatocyte is slightly dilated, which along with the dilated nuclear envelope, is an artifact of fixation. The mitochondria appear to also exhibit some slight artifactual swelling. Multiple bile canaliculi are evident along the margins of this cell's contact with adjacent hepatocytes. Approximately thirteen (13) peroxisomes counted. Z18855. Liver. Hepatocyte. 10,320X. This hepatocyte has a large round nucleus. It's surrounding cytoplasm contains numerous profiles of SER, which are minimally dilated. Approximately 20 small to medium sized lipid droplets are present in the cytoplasm. Fifty-one (51) peroxisomes counted. Z18856. Liver. Hepatocyte. 10,320X. Extracellular space containing numerous collagen fibrils is present next to the centered hepatocyte. The hepatocyte has a large oval nucleus and abundant surrounding cytoplasm with numerous mitochondria and endoplasmic reticulum. A few small lipid droplets are present. Thirteen (13) peroxisomes counted. Z18837. Liver. Hepatocyte. 10,320X. Smooth endoplasmic reticulum and mitochondria are abundant in the cytoplasm of this hepatocyte. The hepatocyte has a large round nucleus and several small to medium sized lipid droplets are present. Nineteen (19) peroxisomes counted. Conclusions: Normal hepatocytes. Peroxisomes average 23.0 per hepatocyte. 996 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105592___________ 79-week necropsy Treatment Group: .75 mg/kg (hi-dose) S ex :______ Female_____________ Mgniricant Lesions (check one): ________ Yes Species/Strain: Cvnomolgus Monkey Tissue:_____ Liver - centrilobular Block No(s).: 99.76-38-2A______ Z18858 - Photo/Negative No(s).: Z18862 X No Interpreting Pathologist (signature and date): g, /~) May 29. 2000______ Features: Z 18858. Liver. Hepatocyte. 10,320X. This hepatocyte has a round central nucleus. To the left of and beneath the nucleus are several medium sized lipid droplets. The remaining cytoplasm contains abundant SER, patches of glycogen, mitochondria, and some profiles of RER. Six (6) peroxisomes counted. Z_l_8859. Liver. Hepatocyte. 10.320X. The cytoplasm of this hepatocyte contains multiple areas of glycogen granule accumulation. These are lightly stained areas with numerous small electron dense granules. A few lipid droplets are also present in the cytoplasm. The darker and irregular cytoplasmic material is SER intermixed with glycogen. Five (5) peroxisomes counted. Z 18860. Liver. Hepatocyte. 10,320X. Thirty-two (32) peroxisomes are counted in this hepatocyte's cytoplasm. The cell has a large round nucleus. Most of the cytoplasm is occupied by SER, mitochondria, and occasional lipid droplets. Some profiles of RER are evident around mitochondria. A microvillous border and adjacent sinusoid are present along the right margin of this hepatocyte. Z18861. Liver. Hepatocyte. 10,320X. For this hepatocyte, its nuclear profile is not present in this plane of section. A moderate number of medium sized lipid droplets are present. Several of these contain some membranous or myelin-like debris. Numerous profiles of SER and RER are present. There is slight dilatation of the endoplasmic reticulum. Numerous variably shaped mitochondria are present, but they appear ultrastructurallv normal. Eleven (11) peroxisomes counted. T 18862. Liver. Hepatocyte. 10,320X. This hepatocyte appears somewhat triangular shaped in this plane of section. It has a large round nucleus and abundant surrounding cytoplasm. Several small to medium sized lipid droplets are present. Abundant SER, some profiles of RER, mitochondria, and peroxisomes occupy the majority of the cytoplasm. Approximately twenty-two (22) peroxisomes counted. A sinusoid with an endothelial cell and erythrocyte is present at the lower left margin of the photograph._____ Conclusions: Normal hepatocytes. Peroxisomes average 15.2 per hepatocyte. 997 Covance 6329-223 3M T-6295.7 IH. Transmission Electron Micrographs 998 Covance 6329-223 3M T-6295.7 999 Covance 6329-223 3M T-6295.7 1000 Covance 6329-223 3M T-6295.7 1001 Covance 6329-223 3M T-6295.7 1002 Covance 6329-223 3M T-6295.7 Figure Legends Electron Microscopy Report Covance Study No. 6329-223 Recovery Sacrifice Animals M agnification. Print magnification is indicated on the back of each photograph. The measurement bar on each photomicrograph equals one micron (0.001mm). Figure 1. Liver. Hepatocyte showing normal cytoplasmic organelles. Some peroxisomes and other normal organelles are identified. There is slight artifactual dilatation of the nuclear envelope and endoplasmic reticulum. Animal No. 105522, 0.75 mg/kg/day (high-dose male), 57-week biopsy, 10,320X magnification. Figure 2. Liver. Hepatocyte. Glycogen accumulations are shown. Glycogen are the small granules within the clear areas. Animal No. 105511, 0.75 mg/kg/day (high-dose male), 79-week necropsy, 10,320X magnification. Figure 3. Liver. Hepatocyte showing normal cytoplasmic organelles. There is slight artifactual dilatation of the endoplasmic reticulum and nuclear envelope. Animal No. 105542, 0.75 mg/kg/day (high-dose female), 57-week biopsy, 10,320X magnification. Figure 4. Liver. Hepatocyte showing normal cytoplasmic organelles. Animal No. 105533, 0.75 mg/kg/day (high-dose female), 79-week necropsy, 10,320X magnification. 1003 Covance 6329-223 3M T-6295.7 1004 Covance 6329-223 3M T-6295.7 IV. Quality Assurance Statement 1005 Covance 6329-223 3M T-6295.7 QUALITY ASSURANCE STATEMENT This electron microscopy study has been inspected and audited by the Quality Assurance Unit as required by the Good Laboratory Practices Regulations promulgated by the U.S. Food and Drug Administration, PAI has a functioning and responsive Quality Assurance Unit which reports directly to management. The following is a record of inspections/audits and their resulting reports: Date of Inspection Phase Inspected Date Findings Reported to Management and Study Pathologist 4/1, 2/99 4/2/99 7/13/99 7/13/99 5/25, 30/00 9/1/00 Data Audit Draft Report Audit Audit of Data from Additional Groups Final Report Audit Data and Draft Report Audit Recovery Animals Final Report Audit 4/2/99 4/2/99 7/13/99 7/13/99 5/30/00 9/1/00 1/(/oo Date Sponsor: 3M Corporate Toxicology Test Article: PFOS Study Number: 6329-223, PAI Study EM-99.76 1006 Pathology Associates International A Company of Science Applications International Corporation Covance 6329-223 3M T-6295.7 An Employee-Owned Company PATHOLOGY REPORT (ANCILLARY STUDY) ELECTRON MICROSCOPIC EVALUATION OF LIVER IN CYNOMOLGUS MONKEYS 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS CLIENT STUDY NUMBER 6329-223 PAI STUDY NUMBER EM 99.76 Prepared by: James B. Nold, D.V.M., Ph.D., Diplomate, A.C.V.P. Pathology Associates International 4915-D Prospectus Drive Durham, NC 27713 July 13,1999 PREPARED FOR 3M CORPORATE TOXICOLOGY, 3M CENTER, ST. PAUL, MN 55144-1000 4915 D Prospectus Drive Durham, North Carolina 27713 (919) 544-5257 (919) 544-3218 FAX 1007 Pathology Narrative Light Microscopy and Transmission Electron Micrograph Interpretation Forms Transmission Electron Micrographs Quality Assurance Statement Covance 6329-223 3M T-6295.7 Section I n m IV 1008 Covance 6329-223 3M T-6295.7 I. Pathology Narrative 1009 Covance 6329-223 3M T-6295.7 PATHOLOGY REPORT (ANCILLARY STUDY) Ancillary Pathology Report Covance Study No. 6329-223 ELECTRON MICROSCOPIC EVALUATION OF LIVER IN CYNOMOLGUS MONKEYS 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS CLIENT STUDY NUMBER 6329-223 PAI STUDY NUMBER EM 99.76 SUMMMARY Treatment of cynomolgus monkeys with 0.75 mg PFOS/kg/day for 26 weeks resulted in hepatocellular vacuolation and hypertrophy by light microscopy. Hepatocellular vacuolation and hypertrophy were primarily centrilobular in distribution and did vary in incidence and severity between individual animals. Ultrastructurally, there were increased lipid droplets within hepatocytes. Increased lipid droplets were present in both the high-dose males examined and in two of four high-dose females examined. Increased hepatocellular glycogen was present in the remaining two high-dose females. These ultrastructural changes correlated with hepatocellular hypertrophy and vacuolation noted by light microscopy and with increased liver weight parameters in the high-dose animals. The no-effect level for hepatocellular vacuolation (lipid droplet accumulation) was 0.15 mgA:g/day of PFOS (mid-dose group). Quantitation of peroxisomes within hepatocytes by electron microscopy indicated no remarkable differences between control livers and livers treated with 0.03, 0.15, or 0.75 mg PFOS/kg/day. Ultrastructural differences in cellular membranes or mitochondria were not discernible between control and treated animals in the samples examined. PROCEDURES The objective of this study was to examine by electron microscopy the livers from selected animals in a 26-week capsule toxicity study with PFOS in cynomolgus monkeys. In addition to a general qualitative evaluation for differences between control and treated animals, the ultrastructural endpoints included quantitation of peroxisomes within hepatocytes and membrane and mitochondrial changes in hepatocytes. Light microscopy of paraffin-embedded liver sections was also performed. For the toxicity study, 22 male and 22 female cynomolgus monkeys were given the test article or the vehicle once daily for at least 26 weeks according to Text Table 1. 1-1 1010 Covance 6329-223 3M T-6295.7 Ancillary Pathology Report Covance Study No. 6329-223 Text Table 1. Group Designations and Dosage Levels Dosage Dose Level Total Material Dose Group________(mg/kg/day)'1_______ Level (mg/k,g/day)b_____ Number of Males_____ Number of Females I 0a 30a 6d 6d II 0.03 15b 4 4 HI 0.15 6C 6d 6d IV_____________ 0 7 5 __________________ 3 0 __________________ id____________________ 6^________ a Dose levels were provided. The control group (Group 1) received an equivalent amount of lactose in gelatin capsules as the total material administered to Group 4. b The low-dose group (Group 2) received the test material diluted with lactose (1:499, w:w). c The mid-dose (Group 3) and high-dose (Group 4) groups received the test material diluted with lactose (1:39, w:w). d Two animals in Groups 1, 3, and 4, designated as recovery animals, were treated for at least 26 weeks, then treatment was discontinued and the animals were observed for reversibility, persistence, or delayed occurrence of toxic effects for at least 13 weeks posttreatment. Animals to be sacrificed at scheduled terminal and recovery sacrifice times were anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. Multiple tissues were collected and preserved in 10% neutral-buffered formalin according to the protocol. Additionally, pieces of liver from each animal were thin-sliced and placed in Vi strength Kamovsky's fixative (2.0% paraformaldehyde/2.5% glutaraldehyde in 0.1 M phosphate buffer) for subsequent ultrastructural examination. These livers were processed into Epon blocks and submitted to this laboratory for subsequent electron microscopy processing and evaluation. Hematoxylin and eosin (H&E)-stained slide sections of formalin-fixed, paraffin-embedded livers were submitted for light microscopic examination. Per sponsor request, tissue samples from terminal sacrifice control and high-dose males and females were initially processed and evaluated ultrastructurally (Text Table 2). Two high-dose males, Animals Nos. 105506 and 105509, died or were sacrificed in a moribund condition prior to scheduled terminal sacrifice. Ultrastructural examination of livers from these two unscheduled death animals was not performed. Following evaluation of the electron micrographs from the control and high-dose livers, the sponsor requested that electron microscopy be performed on the low- and mid-dose livers to evaluate whether increased lipid droplet accumulation was evident in these dose groups. Thin sections (approximately 90 nm) from the Epon-embedded livers were cut, mounted on 200-mesh copper grids, stained with 5% methanolic uranyl acetate and Reynold's lead 1-2 1011 Covance 6329-223 3M T-6295.7 Ancillary Pathology Report Covance Study No. 6329-223 citrate, and examined on a Zeiss EM10C/CR, a Zeiss EM 10, or a JEOL 100S transmission electron microscope. Centrilobular hepatocytes, where clearly identifiable in liver sections, were preferentially examined. Representative electron photomicrographs of liver were taken and significant ultrastructural features were summarized for each photograph and animal on a designated transmission electron micrograph interpretation form. The number of peroxisomes in hepatocytes was manually counted for each center photographed hepatocyte and recorded. For light microscopy, the H&E slides from the same animals selected for electron microscopy were evaluated and significant features were summarized on a light microscopic evaluation form. RESULTS AND DISCUSSION Individual interpretations of light microscopy slides and electron micrographs for each animal are shown in Section II. Representative electron photomicrographs were selected as report figures, labeled, and are shown in Section IH. All remaining electron micrographs are maintained in the archived study file. Light Microscopy A summary of the incidence and severity of light microscopic findings in the control and high-dose livers is shown in Text Table 3. There was an increased incidence of vacuolation of the cytoplasm of hepatocytes in high-dose treated animals compared with control animals. The distribution of this vacuolation was predominantly centrilobular, but for one high-dose female, Animal No. 105534, there was diffuse slight hepatocellular vacuolation. Affected animals generally also had enlargement (hypertrophy) of centrilobular hepatocytes. This enlargement appeared to be related to the presence of the small to large vacuoles with the cytoplasm. Some sporadic vacuolation noted in low- and mid-dose animals did not appear to be treatment-related and was not clearly associated with hepatocellular hypertrophy. 1-3 1012 Covance 6329-223 3M T-6295.7 Ancillary Pathology Report Covance Study No. 6329-223 Text Table 3 Continued. Incidence and Severity of Light Microscopic Liver Findings Microscopic Finding (number examined) Hypertrophy, hepatocellular, centrilobular minimal slight moderate Clearing, cytoplasmic, centrilobular minimal slight Clearing, cytoplasmic, diffuse minimal slight Infiltrate, lymphohistiocytic minimal slight Inflammation, eosinophilicgranulomatous minimal slight Pigment, hepatocellular, centrilobular slight Ectasia, biliary minimal Angiectasis minimal 0 mg/kg/day (Control) Males Females (4) (4) -- 12 -44 -1 1- 0.03 mg/kg (Low-Dose) Males Females (4) (4) -2 31 -44 1- 1-1 -- 0.15 mg/kg (Mid-Dose) Males Females (4) (4) -- 112 1133 -1 -- 0.75 mg/kg/day (High-Dose) Males Female s (2) (4) 12 11 12 -13 -- _- Electron Microscopy Control (0 mg/kg/day). Ultrastructural features of control hepatocytes are demonstrated in Figures 1 - 3. Hepatocytes characteristically contain numerous mitochondria and abundant endoplasmic reticulum. Peroxisomes are common organelles composed of a fine granular matrix surrounded by a membrane and normally vary in size from 0.1 - 1.5 microns in diameter. Hepatocytes exhibit a microvillous border which protrudes into the perisinusoidal space. Tight junctions border bile canaliculi between hepatocytes. Glycogen is common in the cytoplasm and may be in the form of small granules or slightly larger rosettes. Residual bodies are secondary lysosomes (phagolysosomes) containing electron dense degenerative cytoplasmic material. Lipid metabolism is a normal liver function, and it's normal to see random lipid droplets within hepatocytes. There were no discernible differences between control males and females in this study, and all were considered normal. A summary of ultrastructural findings is shown in Text Table 4. One male, Animal No. 105527, appeared to have increased numbers of peroxisomes compared with the other control animals. However, because so few animals and individual hepatocytes were examined, this value may not be significantly increased. 1-4 1013 <1 UJ Covance 6329-22 3M T-6295. Pathology Associates International 4 Company of Science Applications International Corporator! lllapy Patholo8yi X ovance Study No. f-O w ne d Company Text Table 4. Summary of Ultrastructural Findings Treatment Group (mg/kg/day)/Sex Animal No. Comments (0) Male (0) Male (0) Male (0) Male (0.03) Male (0.03) Male (0.03) Male 105508 105517 105519 105527 105514 105515 105516 Normal Normal Normal Normal. Increased peroxisomes Mild increase in lipid droplets Slight increase in lipid droplets Normal (0.03) Male 105521 Normal (0.15) Male 105510 Normal (0.15) Male 105518 Normal (0.15) Male (0.15) Male 105524 105528 Normal, slight increase in peroxisomes Normal (0.75) Male 105507 Lipid droplet accumulation, hepatocellular, moderately severe. (0.75) Male 105512 Increased glycogen Lipid droplet accumulation, moderate, hepatocellular. Increased peroxisomes (0) Female 105530 Normal (0) Female 105531 Normal (0) Female 105535 Normal (0) Female 105544 Normal (0.03) Female 105537 Normal (0.03) Female 105541 Normal (0.03) Female 105547 Normal (0.03) Female 105550 Normal (0.15) Female 105532 Normal (0.15) Female (0.15) Female 105538 105545 Increased glycogen Normal (0.15) Female 105548 Normal (0.75) Female (0.75) Female (0.75) Female (0.75) Female 105534 105536 105540 105551 Increased glycogen Lipid droplet accumulation, moderately severe Lipid droplet accumulation, mild to moderate Increased glycogen " Peroxisomes were identified and quantitated in representative hepatocytes. For the control livers, the average number of peroxisomes counted per hepatocyte photographed was 11.50 for control males and 10.94 peroxisomes per cell for control females. (Text Table 5). Depending upon fixation and staining, peroxisomes may be difficult to differentiate in routine electron photomicrographs from primary lysosomes or marginal cuts through the ends of mitochondria. Cytochemical and immunocytochemical methods are available for specifically identifying peroxisomes by light and electron microscopy, and utilization of these methods would provide a more specific and accurate method of peroxisome quantitation (Beier K, 1992; Reddy UN, 1988). 4915 D Prospectus Drive Durham, North Carolina 27713 (919) 544-5257 (919) 544-3218 FAX 1014 Covance 6329-223 3M T-6295.7 High-Dose (0.75 mg/kg/day). Lipid droplets were increased in animals given 0.75 mg PFOS/kg/day (Text Table 4). This increase was present in both high-dose males examined (Animal Nos. 105507 and 105512) and in two high-dose females (Animal Nos. 105536 and 105540). These are illustrated in Figures 4 - 7 . Lipid droplets were randomly distributed in the cytosol and varied in size from less than .1 micron to greater than several microns in diameter. They generally were clear, but occasionally contained wispy lamellar material or faint smooth electron density. They were not membrane-bound, but appeared to form a defined margin with surrounding cytoplasm. These lipid droplets correlate with hepatocellular vacuolation described in these animals by light microscopy. Increased cytoplasmic glycogen was evident in two high-dose females (Animal Nos. 105534 and 105551), and often formed distinct "pockets" of glycogen, resembling vacuoles or clear droplets, but containing glycogen particles (Figure 8). The accumulation of glycogen apparently correlates with the hepatocellular vacuolation described by light microscopy in these two animals. Lipid droplets did not appear increased in these two animals. For high-dose animals, the average number of peroxisomes per hepatocyte was 17.12 for males and 7.81 for females (Text Table 5). One male (Animal No. 105512) averaged 23.25 peroxisomes per hepatocyte, however, this is not remarkably higher than that found in the control male Animal No. 105527. Animal No. 105507 averaged 11.0 peroxisomes per hepatocyte, similar to the average control value for males. Thus, administration of 0.75 mg/kg/day of PFOS to monkeys for 26 weeks did not appear to induce peroxisome proliferation in the liver. 1-6 1015 Covance 6329-223 3M T-6295.7 Ancillary Pathology Report Covance Study No. 6329-223 Differences in mitochondria and cellular membranes were not discernible between high dose and control livers. Mitochondria from control and high-dose livers did not exhibit remarkable differences ultrastructurally (Figures 3, 9, 10). Low-Dose (0.03 mg/kg/day). Electron microscopic examination of the livers from monkeys given 0.03 mg/kg/day of PFOS did not identify any atypical ultrastructural features compared with control sample. Lipid droplets were identified in some hepatocytes, and two low-dose males appeared to have slightly increased lipid droplet accumulation (Animal Nos. 105514 and 105515). Flowever, increased lipid droplet accumulation was not seen in the low-dose females or in the mid-dose males and females, and this observation in the two low-dose males was believed to represent normal biological variance and sampling. As noted earlier, lipid metabolism is a normal liver function, and it's normal to see random lipid droplets within hepatocytes. Figure 11 illustrates a hepatocyte from the low-dose group. For low-dose animals, the average number of peroxisomes per hepatocyte was 9.75 for males and 12.10 for females (Text Table 5). M id-Dose (0.15 mg/kg/day). There was no consistent ultrastructural evidence of increased lipid droplet accumulation in the livers of the mid-dose monkeys given 0.15 mg/kg/day of PFOS. This mid-dose level, 0.15 mg/kg/day, is the no-effect level for the PFOS-related effect of increased hepatocellular lipid accumulation (vacuolation) in monkeys given PFOS. One female, Animal No. 105538, had increased glycogen, but a marked increase in glycogen was not seen in any other mid-dose livers examined. For mid-dose animals, the average number of peroxisomes per hepatocyte was 16.70 for males and 9.35 for females (Text Table 5). Figure 12 illustrates a hepatocyte from the mid-dose group. CONCLUSION Ultrastructural evaluation of livers from cynomolgus monkeys treated with 0.75 mg PFOS /kg/day for 26 weeks identified increased lipid droplets within hepatocytes. Increased lipid droplets were present in both treated males examined and in two of four treated females examined. Increased hepatocellular glycogen was present in the . remaining two high-dose females. These ultrastructural changes correlated with hepatocellular hypertrophy and vacuolation noted by light microscopy and with increased liver weight parameters in the high-dose animals. The no-effect level for hepatocellular vacuolation (lipid droplet accumulation) was 0.15 mg/kg/day of PFOS (mid-dose group). Quantitation of peroxisomes within hepatocytes by electron microscopy indicated no remarkable differences between control livers and livers treated with 0.03, 0.15 or 0.75 mg/kg/day. Ultrastructural differences in cellular membranes or mitochondria were not discernible between control and treated animals in the samples examined. 1016 Covance 6329-223 1017 Covance 6329-223 3M T-6295.7 II. Light Microscopy and Transmission Electron Micrograph Interpretation Forms 1 1Forms are typographically corrected versions of signed/dated raw data sheets maintained in archived study file. 1018 Covance 6329-223 3M T-6295.7 LIGHT MICROSCOPIC EVALUATION Study No.: 6329-223 (EM 99.76) Species/Strain: Cvnomolgus Monkeys Animal No: see below_____ Sex: see below Interpreting Pathologist (signature and date): Tissue: Liver Dose/Group 0 mg/kg (Control) Males 0 mg/kg (Control) Females 0.75 mg/kg (High-dose) Males 0.75 mg/kg (High-dose) Females Animai Number 105508 105517 105519 105527 105530 105531 105535 105544 105507 105512 105534 105536 105540 105551 Microscopic Findings and Comments 1. Infiltrate, lymphohistiocytic, multifocal, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Angiectasis, focal, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Inflammation, eosinophilic-granulomatous, focal, slight 1. Infiltrate, lymphohistiocytic, focal, minimal 2. Vacuolation, hepatocellular, centrilobular, moderately-severe 3. Hypertrophy, hepatocellular, centrilobular, moderate 1. Clearing, cytoplasmic, centrilobular, slight 2. Hypertrophy, hepatocellular, centrilobular, minimal 1. Infiltrate, lymphohistiocytic, focal, minimal 2. Vacuolation, hepatocellular, diffuse, slight 3. Hypertrophy, hepatocellular, centrilobular, minimal 1. Vacuolation, hepatocellular, centrilobular, moderately-severe 2. Hypertrophy, hepatocellular, centrilobular, moderate 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Vacuolation, hepatocellular, centrilobular, minimal 3. Clearing, cytoplasmic, centrilobular, slight 4. Hypertrophy, hepatocellular, centrilobular, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Vacuolation, hepatocellular, centrilobular, minimal 3. Clearing, cytoplasmic, centrilobular, slight 1019 Covance 6329-223 3M T-6295.7 Dose/Group 0.03 mg/kg (Low-dose) Males 0.03 mg/kg (Low-dose) Females 0.15 mg/kg (Mid-dose) Males 0.15 mg/kg (Mid-dose) Females Animal Number 105514 105515 105516 105521 105537 105541 105547 105550 105510 105518 105524 105528 105532 105538 105545 105548 Microscopic Findings and Comments 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Inflammation, eosinophilic-granulomatous, focal, minimal 3. Pigment, hepatocellular, multifocal, centrilobular, minimal 4. Clearing, cytoplasmic, centrilobular, slight 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Vacuolation, hepatocellular, centrilobular, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, slight 1. Infiltrate, lymphohistiocytic, multifocal minimal 2. Pigment, hepatocellular, multifocal, centrilobular, slight 3. Vacuolation, hepatocellular, multifocal, minimal 4. Clearing, cytoplasmic, centrilobular, slight 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, slight 1, Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Ectasia, biliary, focal, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, minimal 3. Vacuolation, hepatocellular, multifocal, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, diffuse, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, minimal 1. Clearing, cytoplasmic, centrilobular, slight 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, diffuse, slight 1. Infiltrate, lymphohistiocytic, multifocal, minimal 1. Infiltrate, lymphohistiocytic, multifocal, minimal 2. Clearing, cytoplasmic, centrilobular, slight 1. Infiltrate, lymphohistiocytic, multifocal, minimal 1. Infiltrate, lymphohistiocytic, multifocal, slight 2. Clearing, cytoplasmic, centrilobular, slight Interpreting Pathologist (signature and date): f sf\ ls!U ___ 1020 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105508 Treatment Group: 0 mg/kg (Control) S ex :_______ Male___ Species/Strain: Cynomolgus Monkey Tissue:_____Liver Block No(s).: --99076-~ 43401 - Photo/Negative No(s).: 43405 Significant Lesions (check one): Yes Interpreting Pathologist (signature and date): X___ No ^f? A J ~ J 1QQQ Features: 4340^: Liver. Hepatocyte exhibiting large central nucleus. The cytoplasm contains many mitochondria and abundant endoplasmic reticulum. Bile canaliculi are evident at the lower right and left margins of this hepatocyte. A number (approximately 20-25) of small to medium-size clear lipid droplets are present, principally in the upper portion of the cell. Mitochondria appear normal; normal matrix granules are evident in most. Several lysosomes and peroxisomes are present. Five (5) peroxisomes counted. 43402: Liver. Hepatocyte is possibly bi-nucleate, but this may be function of cut through the nucleus. Some small to medium-sized clear lipid droplets present, similar to 4340&.1 Microvillous border in space of Disse evident at top margin of cell. Several lamellar mylein-like bodies present within lysosomes. Five (5) peroxisomes counted. 43403. Liver. Hepatocyte with bile canaliculus at lower right. Only a few small to medium-size clear lipid droplets are evident. Numerous mitochondria and abundant endoplasmic reticulum are evident. Clear structure at the bottom may be dilated Golgi, reticulum or artifact. Nine (9) peroxisomes counted. 43404: Liver. Hepatocyte with adjacent endothelial cell and sinusoid at the bottom of the photograph. Hepatocyte contains several small to medium-sized clear lipid droplets. One droplet contains some lamellar material. Eleven (11) peroxisomes counted. 43405: Liver. Hepatocyte with higher magnification of mitochondria. Seven mitochondria present with intervening rough endoplasmic reticulum and cytosol. Outer membrane, cristae, matrix and granules appear normal. 4'r-v Conclusions: Normal hepatocyte. Average 7.5 peroxisomes counted per hepatocyte. 1021 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.:____105517________ Treatment Group: 0 mg/kg (control) Sex:____Male_________________ Species/Strain: Cvnomolgus Monkey Tissue:____ Liver_____________ Block No(s).: 99.76-2_______ 43406 - Photo/Negative No(s).: 43410 Significant Lesions (check one): v es X No Interpreting Pathologist (signature and date): IS \A ~3 x Features: 43406: Liver. Hepatocyte surrounded by other hepatocytes with bile canaliculi in the lower right and upper left margins of the cell. There are numerous mitochondria and abundant endoplasmic reticulum. The ER and nuclear envelope appeal^slightly dilated. Only a couple small clear lipid droplets evident. Several small lysosomes or vacuoles with microvesicles in them are present. Five (5) peroxisomes counted. 43407: Liver. Hepatocyte with perisinusoidal microvillous border evident in lower right and upper left of photograph. A bile canaliculus is present on the right middle margin of the cell. Several small to medium-sized clear lipid droplets are evident. One larger one contains some lamellar profiles. Four (4) peroxisomes counted. 43408: Liver. Hepatocyte with sinusoid containing erythrocytes at the top. A lipidcontaining perisinusoidal cell (Ito cell) is present at the top left and a bile canaliculus is present at the bottom. Random small clear lipid droplets are present in the hepatocellular cytoplasm and some of the ER appears mildly dilated. Eleven (11) peroxisomes counted. 43409: Liver. Hepatocyte contains numerous dense lysosomes and/or peroxisomes intermixed with mitochondria and abundant ER. Several small clear lipid droplets are evident. Twenty-nine (29) peroxisomes counted. 43410: Liver. Enlarged photograph of mitochondria. Ten mitochondria are clustered together in this photograph. Although the image is a little out of focus, these organelles appear essentially normal. There may be mild dilatation of the ER in the cytoplasm. Conclusions: Normal hepatocyte. Average 12.25 peroxisomes per hepatocyte. 1022 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal N o.:_____ 105519________ Treatment Group: 0 mg/kg (control) S e x : _______Male______________ Species/Strain: Cynomolgus Monkey Tissue: Liver_____________ Block No(s).: 99.76-3_______ 43421 - 43425, Photo/Negative No(s).: 43431 Features: 43421: Liver. Hepatocyte. At lower left is a prominent perisinusoidal fat storing cell (Ito cell) containing numerous large clear lipid droplets. The centered hepatocyte contains one large clear lipid droplet and several smaller ones. The nuclear envelope and ER is mildly dilated. Moderate numbers of glycogen granules present. Scattered residual bodies noted. Four (4) peroxisomes counted. 43422: Liver. Mitochondria and surrounding cytosol and ER. Membranes of ER are not very distinct. Glycogen in cytosol. Mitochondria appear essentially normal. Lamina of membranes and cristae appear parallel. Several normal granules in the matrix of the mitochondria. 43423: Liver. Mitochondria. Same view as 43422 but slightly less magnification. Some dilatation of ER. Mitochondria appear normal. A peroxisome is present in the lower left of the photograph. 43224: Liver. Hepatocyte with several medium-sized and one large clear lipid droplets. Small granules within cytosol and around ER appear to be glycogen particles or ribosomes and polyribosomes. Four (4) peroxisomes counted. Slightly out of focus. 43425: Liver. Hepatocyte surrounded by other hepatocytes and a sinusoid at lower right. Several bile canaliculi evident between hepatocytes. A single medium-sized clear lipid droplet is present in the hepatocyte. Four (4) peroxisomes counted. A couple of larger dense lysosomes also identified. 43431; Liver. The centered hepatocyte is oblong diagonally in the photograph, and doesn't contain any distinct lipid droplets. A few lipid droplets are present in adjacent hepatocytes. There is mild dilation of the ER and nuclear envelope. Only a few lysosomal structures noted. Two (2) peroxisomes counted. _________________ _____ Conclusions: Normal hepatocyte. Average 3.5 peroxisomes per hepatocyte. 1023 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105527 _______ Treatment Group: 0 mg/kg (control) Sex:______Male_______________ Species/Strain: Cvnomolgus Monkey Tissue:_____Liver_____________ Block No(s).: 99.76-4________ 43426 - Photo/Negative No(s).: 43420_____ Significant Lesions (check one): X Yes Interpreting Pathologist (signature and date): No ?> ( \ JL/ MR 3 1 iooq Features: 43426: Liver. Hepatocyte with several small to medium-sized lipid droplets (approximately 20). The adjacent lower left hepatocyte shows significant dilatation of its ER. At top left and right margin, the extracellular interstitium has some collagen fibers. Some residual bodies noted. Twenty-one (21) peroxisomes counted. 43427: Liver. Mitochondria. Membrane, cristae and matrix appear normal. Several normal granules present matrix. Some rough ER present adjacent to mitochondria. Lysosome present at left of center mitochondrion. 43428: Liver. Hepatocyte. There is mild dilation of the ER and nuclear envelope. Scattered small to medium-size clear lipid droplets (approximately 18). Scattered residual bodies noted. Twenty-five (25) peroxisomes counted. 43429: Liver. Hepatocyte. Bile canaliculi are evident at the lower right and top of the cell. The ER is mildly dilated. Scattered clear lipid droplets are evident. Abundant numbers of dense bodies (peroxisomes)/lysosomes and residual bodies are present. Thirty (30) peroxisomes counted. 43430: Liver. Hepatocyte appears similar to above described cells. There are some scattered small to medium-size clear lipid droplets. Some residual bodies are present. Fifteen (15) peroxisomes counted. Conclusions: Normal hepatocyte. Appear to be increased numbers of peroxisomes compared with other control samples. Average 22.75 peroxisomes per hepatocyte. 1024 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105507_________ Treatment Group: 0.75 mg/kg (Tri-dose) Sex:______ Male_____________ Species/Strain: Cynomolgus Monkey Tissue:____ Liver____________ Block No(s).: 99.76-9_______ 43411 - Photo/Negative Nofs).: 43415 Significant Lesions (check one): X__ Yes No Interpreting Pathologist (signature and date): il /). u . Features: 4 3 4 1 Liver. Hepatocyte containing a single very large clear lipid droplet and many small to medium-size clear lipid droplets. There appears to be an increase in the amount of glycogen a-rosette granules. Several foci of ER appear irregularly dilated. A few scattered lysosomes and peroxisomes noted. Nine (9) peroxisomes counted. 43412: Liver. Hepatocyte contains a large number of small to medium-sized clear lipid droplets in the cytosol (approximately 125), most being very small. Abundant glycogen as a-rosettes is present in the cytoplasm. Twenty-six (26) peroxisomes counted. 43413: Liver. Hepatocyte containing several very large clear lipid droplets and many smaller droplets. Some interstitial tissue containing some collagen fibers is present at the lower left of the photograph. Some residual bodies present. Many glycogen rosettes present in cytoplasm. Three (3) peroxisomes counted. 43414: Liver. Several mitochondria are shown which appear essentially normal. Some normal dense granules are present in the matrix and the cristae and enveloping membrane appear normal. In the cytoplasm there are multiple small lipid droplets, usually surrounded by fine dense granules (glycogen or ribosomes). 43415: Liver. Hepatocyte with a bile canaliculus at the bottom margin and an interstitial fibroblastic cell^ at the upper right. The hepatocyte contains abundant small to medium sized clear lipid droplets (>170). Random residual bodies are present. Six (6) peroxisomes counted. Conclusions: Lipid accumulation, moderately-severe, hepatocellular. Increased glycogen. Average 11.0 peroxisomes per hepatocyte. 1025 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105512_______ Treatment Group: 0.75 mg/kg (hi-dose) S e x :_________ Male____________ Species/Strain: Cynomolgus Monkey Tissue: Liver_____________ Block No(s).: 99.76-10______ 43416- Photo/Negative No(s).: 43420_____ Significant Lesions (check one): X Yes ________ No Interpreting Pathologist (signature and date): Features: 43416: Liver. Photographed hepatocyte is binucleated and contains many small clear lipid droplets. Most appear around 100 nm in diameter, although a few are larger and one is about 1.75 microns in diameter. They are too numerous to count. The droplets appear to be free within the cytosol and are not membrane-bound. Nine (9) peroxisomes counted. 43417: Liver. Hepatocyte contains multiple medium-sized clear lipid droplets (approximately 90). There are abundant numbers of dense primary lysosomes or peroxisomes. Forty-five (45) peroxisomes counted. 43418: Liver. Hepatocyte containing numerous small to medium-sized clear lipid droplets within the cytosol. They are too numerous to count. Twelve (12) peroxisomes counted. 43419: Liver. Hepatocyte adjacent to a central vein. Microvillous border in the perisinusoidal space and endothelium and erythrocytes are evident. Cell contains small lipid droplets too numerous to count. A moderate number of primary lysosomes and/or peroxisomes are evident. Twenty-five (25) peroxisomes counted. 43420. Liver. Mitochondria. Mitochondria appear essentially normal. Numerous small lipid droplets are present in the surrounding cytosol. 1026 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 ('EM 99.76) Animal No.: 105530________ Treatment Group: 0 mg/kg (control) Sex:_________ Female__________ Species/Strain: Cvnomolgus Monkey Tissue:_____Liver_____________ Block No(s).: 99.76-5 L4756 - Photo/Negative Nofs).: L4760 Significant Lesions (check one): Yes X No Interpreting Pathologist (signature and date): (<, yi JM _______!__ . 1 ...:.Yi-- Features: L4756: Liver. Hepatocyte contains three small lipid droplets. There are bile canaliculi at the top right at top left, and a perisinusoidal microvillous border at the bottom. The nuclear envelope and ER shows some mild artifactual (fixation) dilation. Numerous mitochondria are present. Five (5) peroxisomes counted. L4757: Liver. Mitochondria. Higher magnification of five mitochondria. Matrix and dense granules appear normal. ER between mitochondria is slightly dilated. L4758: Liver. Hepatocyte. A sinusoid is present at the top of the photograph, lined by an endothelial cell. Four (4) medium-sized lipid droplets are present in this cell. The nuclear envelope and ER shows some mild artifactual (fixation) dilation. Numerous mitochondria are present. Four (4) peroxisomes counted. L4759: Liver: Hepatocyte containing scattered small to medium-sized lipid droplets (approximately 14). Scattered primary lysosomes and/or peroxisomes present. There is a perisinusoidal microvillous border at the top beneath an endothelial cell and sinusoid. Twenty-five (25) peroxisomes counted. L4760: Liver. Hepatocyte containing approximately nine (9) small to medium-sized lipid droplets. Seventeen (17) peroxisomes counted. Conclusions: Normal hepatocyte. Average 12.75 peroxisomes per hepatocyte. 1027 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105531________ Treatment Group: 0 mg/kg (control) Sex: Female____________ Species/Strain: Cynomolgus Monkey Tissue:____ Liver____________ Block No(s).: --99.76-5~ L4761 - Photo/Negative No(s).: L4765 'i Significant Lesions (check one): Yes Interpreting Pathologist (signature and date): u X No MAR 3 1 Features: L4761: Liver. Hepatocyte with large central nucleus. Two margins are straight-edged by the grid bar. A few small to medium-sized clear to slightly shaded lipid droplets are present (approximately 32). ER profiles and glycogen granules are scattered throughout the cytosol. A moderate number of primary lysosomes and/or peroxisomes noted. Nine (9) peroxisomes counted. L4762: Liver. Mitochondria. One oval and one club-shaped mitochondria present. Both appear normal with cristae, membranes, and matrix. The club-shaped one contains several normal dense granules and some slightly dilated cristae, probably fixation artifact. Some RER and smooth ER (SER) are evident in the cytosol. L4763: Liver. Hepatocyte surrounded by interstitium containing some collagen fibers. Cell|s has slightly dilated ER and nuclear envelope. A single small lipid droplet is present in this cell. Four (4) peroxisomes counted. L4764: Liver. This hepatocyte shows some dilation of ER and several lamellar residual bodies in the cytoplasm. Four (4) small lipid droplets are evident. Numerous scattered glycogen granules are present. Eight (8) peroxisomes counted. L4765: Liver. Hepatocyte containing 5 small to medium-sized clear lipid droplets. Bile canaliculi are evident at the lower left and top right of the cell margins. A cluster of RER is present in the lower left side of the nucleus. Some larger dark lysosomes/peroxisomes are present among some of the mitochondria. Thirty-four (34) peroxisomes counted. Conclusions: Normal hepatocyte. Average 13.75 peroxisomes per hepatocyte. 1028 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105535_________ Treatment Group: 0 mg/kg (control) Sex:_____ Female____________ Species/Strain: Cvnomolgus Monkey Tissue:____ Liver____________ Block No(s).: 99.76-7_______ L4766- Photo/Negative Nofsl.: L4770 Significant Lesions (check one): Yes X No Interpreting Pathologist (signature and date): &V-1.M - Features: L4766: Liver. Hepatocyte contains some mild dilatation of the nuclear envelope and ER (fixation artifact). On the left and right sides are bile canaliculi, and ventrally is the sinusoidal margin showing the perisinusoidal microvillous border. Several dense residual bodies are present in the cytoplasm. Three small lipid droplets, one containing a lamellar body, are evident. One (1) peroxisome counted. L4767: Liver. Mitochondria. Higher magnification of four mitochondria show normal morphology. Membranes, cristae and matrix appear normal. Scattered dense granules are present. The ER in the cytosol is mildly dilated. L4768: Liver. Hepatocyte. There is moderate dilatation of the ER and nuclear envelope. Several scattered small to medium-sized clear lipid droplets are evident, as are some scattered residual bodies. Sinusoids are present at the bottom right and upper left of the photograph, and a bile canaliculus is present on the right margin of this centered hepatocyte with its neighbor hepatocyte. Two (2) peroxisomes counted. L4769: Liver. Hepatocyte with sinusoid in upper right corner and canaliculi prominent alongj^bottom border. The cell exhibits dilated ER and nuclear envelope like the previously described cells for this animal - indicating suboptimal fixation. Multiple residual bodies are present. Nineteen (19) peroxisomes counted. L4770: Liver. Hepatocyte with similar overall morphology as L4769. Six (6) peroxisomes counted. Conclusions: Normal hepatocyte. Suboptimal fixation. Average 7.0 peroxisomes per hepatocyte. 1029 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105544_________ Treatment Group: 0 mg/kg (control) S e x :______Female____________ Species/Strain: Cynomolgus Monkey Tissue:____ Liver____________ Block No(s).: 99.76-8 L4771 - Photo/Negative Nofsl.: L4775 Significant Lesions (check one): _______ Yes Interpreting Pathologist (signature and date): _> ___________________________________________ ______________ 4 ------------- Features: L4771: Liver. Along left margin of hepatocyteiYsome interstitium and collagen fibers. Hepatocyte contains approximately 17 small to medium-sized clear lipid droplets. A few residual bodies are evident. There is some minimal to mild dilatation of ER. Eight (8) peroxisomes counted. L4772: Liver. Enlarged photograph of three mitochondria. No abnormalities noted. L4773: Liver. Hepatocyte with one large and several small to medium-sized lipid droplets in the cytoplasm. Eight (8) peroxisomes counted. L4774: Liver. Hepatocyte with prominent microvillous border along bottom sinusoid. An endothelial cell nucleus is evident along this border. In the hepatocyte are several medium-sized clear lipid droplets. The ER does show some mild dilatation and there are abundant glycogen granules in the cytoplasm. Several dark residual bodies are present. Eight (8) peroxisomes counted. L4775: Liver. Hepatocyte with sinusoid on the right and prominent canaliculus on top and left margins. No lipid droplets present in centered hepatocyte, although one medium sized lipid droplet is present in top adjacent hepatocyte. Cytoplasm contains some RER but not much SER, possibly a periportal hepatocyte. Random peroxisomes and/or primary lysosomes noted. Seventeen (17) peroxisomes counted. Conclusions: Normal hepatocyte. Average 10.25 peroxisomes per hepatocyte. 1030 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105534________ Treatment Group: .75 mg/kg (hi-dose) Sex: Female_____ _________ Species/Strain: Cvnomolgus Monkey Tissue:____ Liver____________ Block No(s).: 99.76-11 L4798 - Photo/Negative No(s).: L4802 Significant Lesions (check one): X__ Yes No Interpreting Pathologist (signature and date): R, v\ ,Af ^^ Features: L4798: Liver. Hepatocyte surrounded by adjacent hepatocytes. It contains abundant numbers of mitochondria and ER. There is mild dilatation of the nuclear envelope and of some ER. Scattered residual bodies are present. Just one distinct lipid droplet is evident. Four (4) peroxisomes counted. L4799: Liver. Enlarged view of five mitochondria. Mitochondria appear essentially normal. Several dense granules are present in the matrix. The cristae and limiting membranes appear normal. At the-ride side is the mildly dilated nuclear envelope and the nucleus. r'3v'* Cf-* L4800: Liver. Hepatocyte. A few small clear lipid droplets are present in the cytoplasm There are also abundant glycogen granules in the cytoplasm. A number of "clear areas" in the cytoplasm appear to contain glycogen granules without a distinct lipid droplet margin. Two (2) peroxisomes counted. L4801. Liver. Hepatocyte. There are numerous small to medium-sized rarefied "pockets" in the cytoplasm (approximately 57). Some contain some w^nspy lamellar material, and some glycogen granules appear to belthese spaces. The margins of these droplets are not as sharply defined as clear round lipid droplets usually are. Four (4) peroxisomes counted. L4802: Liver. Hepatocyte appears similar to L4801 with some small to medium-sized lipid droplets and other rarefied areas with glycogen in the cytoplasm (approximately 29). Some contain some w^is^lamellar material. There are also abundant glycogen granules throughout the cytoplasm. Twelve (12)peroxisomes counted. Conclusions: Increased glycogen in this animal. Increased number of glycogen granules. Average-4r7frperoxisomes per hepatocyte. 5~-r A 'C'\\ 1031 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105536_________ Treatment Group: .75 mg/kg (hi-dose) S e x : ______Female_____________ Species/Strain: Cvnomolgus Monkey Tissue:____ Liver_____________ Block No(s).: 99.76-12_______ L4804 - Photo/Negative No(s).: L4808 Significant Lesions (check one): X Yes Interpreting Pathologist (signature and date): No J A MAR 3 1 im Features: L4804. Liver. Hepatocyte. Only a small segment of the nucleus is evident. There are multiple large clear lipid droplets in the cytoplasm. Numerous smaller droplets appear as less distinct dilatations in the cytosol. There are abundant glycogen granules in the cytoplasm. Three (3) peroxisomes counted. L4805: Liver. Hepatocyte. Multiple small to large clear lipid droplets in cytoplasm. Four (4) peroxisomes counted. L4806: Liver. Enlarged magnification of a cluster of mitochondria. Cristae are not well defined in this photograph, but matrix, granules and outer limiting membrane appear normal. L4507: Liver. Hepatocyte. Multiple small to large clear lipid droplets in cytoplasm (approximately 123). There are abundant glycogen granules in the cytoplasm. Three (3) peroxisomes counted. L4808: Liver. Hepatocyte contains multiple small to large lipid droplets. Droplets are too numerous to count. Several dense residual bodies present. Five (5) peroxisomes counted. Conclusions: Moderately-severe lipid accumulation in hepatocytes. Membranes and mitochondria appear essentially similar to controls. Average 3.75 peroxisomes per hepatocyte. 1032 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105540________ Treatment Group: .75 mg/kg (hi-dose) Sex:______Female____________ Species/Strain: Cvnomolgus Monkey Tissue: Liver_____________ Block No(s).: 99.76-13______ L4809- Photo/Negative No(s).: L4813 Significant Lesions (check one): X Yes Interpreting Pathologist (signature and date) No rifiy j i m s s Features: L4809: Liver. Hepatocyte. Only a small segment of nucleus is present in this photograph. Abundant ER and glycogen granules are present. There are scattered small to large lipid droplets, but not too many in this hepatocyte (approximately 15). A few dark residual bodies are evident. Fifteen (15) peroxisomes counted. L4810: Liver. Enlarged photograph of several mitochondria. No abnormalities noted. Cytoplasm contains some ER and scattered glycogen granules. L4811: Liver. Hepatocyte contains multiple medium to large clear lipid droplets (approximately 41). There is abundant glycogen in the cytoplasm. Five (5) peroxisomes counted. L4812: Liver. Hepatocyte. Similar to L4811. Hepatocyte contains multiple small to large clear lipid droplets, too numerous to count. There is abundant glycogen in the cytoplasm. Twenty-eight (28) peroxisomes counted. L4813: Liver. Hepatocyte contains abundant mitochondria and ER. Only a few clear lipid droplets are present. An endothelial cell is present at the top of the photograph. There is minimal to mild dilatation of the ER and nuclear envelope. Scattered residual bodies are present. Two (2) peroxisomes clearly identified. Conclusions: Mild to moderate increase in cytoplasmic lipid droplets. Increased glycogen in most hepatocytes. Average 12.5 peroxisomes per hepatocyte. 1033 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105551_______ Treatment Group: .15 mg/kg (hi-dose) Sex:_______Female___________ Species/Strain: Cynomolgus Monkey Tissue:____ Liver____________ Block No(s).: 99.76-14 L4814- Photo/Negative Nois).: L4818 Significant Lesions (check one): X Yes No Interpreting Pathologist (signature and date) mar 1 i m B/|( Features: L4814. Liver. Hepatocyte. There is a dilated canaliculus at the top right of the hepatocyte. In the cytoplasm there are multiple rarefied areas that mostly appear to contain glycogen granules. However, a few have some lamellar material in them. There is slight dilatation of the nuclear envelope and ER. Some residual bodies are present. No distinct lipid droplets are present in this hepatocyte, however, there are several lipid droplets in the perisinusoidal fat-storing cell (Ito cell) at the top left. Nine (9) peroxisomes counted. L4815: Liver. Enlargement of a cluster of mitochondria. These organelles appear essentially normal. v#- L4816: Liver. Hepatocyte contains a single medium-sized clear lipid droplet/ The cytoplasm contains abundant glycogen granules. Several residual bodies present. Four (4) peroxisomes clearly identified. Several small dark bodies appear to be tips of mitochondria. L4817: Liver. Hepatocyte appears similar to L4814. There is abundant glycogen in the cytoplasm, often making clear areas containing just glycogen granules. Several clusters of RER present. One small lipid droplet present. Fourteen (14) peroxisomes counted. L4818: Liver. Hepatocyte contains multiple rarefied "pockets" of glycogen granules. No lipid droplets present. Eleven (11) peroxisomes counted. Conclusions: Increased glycogen. Average 9.5 peroxisomes per hepatocyte. 1034 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 iEM 99.761 Animal N o.:___ 105514 Treatment Group: .03 mg/kg flow-dose) Sex:________ Male Species/Strain: Cynomolgus Monkey Tissue:____ Liver____________ Block No(s).: 99.76-15_______ Z16232- Photo/Negative No(s).: Z16236 Significant Lesions (check one): X Yes No Interpreting Pathologist (signature and date): U *H __ MT 2 0 1S33 Features: Z16232. Liver. Hepatocyte. Hepatocyte contains multiple small to medium sized lipid droplets scattered throughout its cytoplasm. At the top margin is a microvillous border and some collagen fibers in the space of Disse. Smooth endoplasmic reticulum (SER) and rough endoplasmic reticulum (RER) are present throughout the cytoplasm with many mitochondria also throughout. Mitochondria are well-preserved and cristae, granules and matrix are clearly evident. Several irregular dark staining residual bodies are present. One (1) peroxisome counted. Z16233. Liver. Hepatocyte. A moderate number of small to medium-sized lipid droplets are present in the cytoplasm, as well as several prominent residual bodies. The upper left and lower left borders show microvilli and collagen fibers adjacent to a sinusoid or central vein. The RER forms a distinct palisade a the bottom of the cell. Nine (9) peroxisomes counted. Z 16234. Liver. Hepatocyte. Centered hepatocyte shows minimal fixation artifact with some slight dilatation of SER and the nuclear envelope. There are a few small to medium-sized lipid droplets present. Four (4) peroxisomes counted. Z16235. Liver. Hepatocyte. Cell appears similar to those described above. There are random lipid droplets and multiple residual bodies. Five (5) peroxisomes counted. Z16236. Liver. Hepatocyte. Multiple small to medium-sized lipid droplets present in the cytoplasm. Only a small nuclear profile is evident in this cell. Eleven (11) probable peroxisomes counted. Conclusions: Tissue appears well-fixed for ultrastructural examination. There appears to be a mild increase in numbers of lipid droplets. Average 6.0 peroxisomes per hepatocyte. 1035 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105515__________ Treatment Group: .03 mg/kg (low-dose) Sex:______Male_______________ Species/Strain: Cvnomolgus Monkey Tissue: Liver_____________ Block No(s).: 99.76-16_______ Z16237 Photo/Negative No(s).: Z16241 Significant Lesions (check one): X Yes Interpreting Pathologist (signature and date): _______ No 2^ &A A f HAY > 0 Features: Z16237. Liver. Hepatocyte. A central vein is present at the top margin and contains a large amount of collagen extracellularly. A bile canaliculus is present on the left between three hepatocytes. the endoplasmic reticulum and nuclear envelope are slightly dilated - this is a fixation artifact. Several lipid droplets are present. Prominent glycogen granules are present throughout the cytoplasm. Twenty-two (22) peroxisomes. Z16238. Liver. Hepatocyte. A bile canaliculus is present at the top border with another hepatocyte. One large and several smaller lipid droplets are present. Mitochondria appear normal and have fine cristae, matrix, and granules. Twenty-one (21) peroxisomes. Z16239. Liver. Hepatocyte. Large central nucleus is adjacent to a large lipid droplet. A few smaller lipid droplets are present. There is artifactual dilatation of the RER and the nuclear envelope. Several residual bodies are present. Fourteen (14) peroxisomes counted. Z 16240, Liver. Hepatocyte. The centered hepatocyte contains several medium-sized lipid droplets. There is marked dilatation of the RER and the nuclear envelope. A bile canaliculus is present on the left margin of this cell and extracellular collagen is evident in the upper right. Ten (10) peroxisomes counted. Z16241. Liver. Hepatocyte. Hepatocyte contains two larger lipid droplets and several smaller ones. The RER and nuclear envelope are dilated. The ventral margin shows a microvillous border next to an endothelial cell at the bottom. A prominent bile canaliculus is present on the left, surrounded by dark desmosomes. Eight (8) peroxisomes counted.______________________________________________________ Conclusions: Slight (equivocal) increase in lipid droplets. Average 15.0 peroxisomes per hepatocyte. 1036 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105516_________ Treatment Group: ,03 mg/kg (low-dose) Sex:_______Male____________ Species/Strain: Cvnomolgus Monkey Tissue:_____Liver____________ Block No(s).: 97.76-17_____ Z16242 - Photo/Negative No(s).: Z16246 Significant Lesions (check one): _______ Yes X No Features: Z 16242. Liver. Hepatocyte. Hepatocyte is adjacent to a cell containing a large lipid droplet, probably a perisinusoidal fat-storing cell (Ito cell). The hepatocyte contains numerous normal-appearing mitochondria and scattered dark irregular residual bodies. Smooth and RER are present throughout the cytoplasm. One (1) probable peroxisome counted. Z16243. Liver. Hepatocyte. Hepatocyte has a bile canaliculus present along its right margin with an adjacent hepatocyte. The cytosol contains abundant smooth and RER and numerous mitochondria. A few residual bodies are present. Two (2) peroxisomes seen. Z 16244. Liver. Hepatocyte. Hepatocyte exhibits very slight dilatation of the endoplasmic reticulum and nuclear envelope. Glycogen granules are present throughout the cytoplasm, and scattered residual bodies are present. Two (2) probable peroxisomes identified. Z16245. Liver. Hepatocyte. A clear vacuole with a central round density is present to the left of the nucleus of the hepatocyte. This appears to be a cytoplasmic invagination from the plasma membrane. Normal-appearing mitochondria are present throughout the cytoplasm. A few residual bodies are present. Fifteen (15) peroxisomes counted. Z 16246. Liver. Hepatocyte. The centered hepatocyte appears essentially similar to above-described cells. There are glycogen granules throughout the cytoplasm. Sixteen (16) peroxisomes counted. ___________________________________________ Conclusions: Essentially normal hepatocytes. Average 7.2 peroxisomes per hepatocyte. 1037 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: _6329-223 (EM 99.76) Animal No.: 105521_________ Treatment Group: 0,03 mg/kg flow-dose') Sex:_______Male______________ Species/Strain: Cvnomolgus Monkey Tissue: Liver____________ Block No(s).: 99.76-18_______ Z 16247 Photo/Negative NofsL: Z16251 Significant Lesions (check one): _______ Yes Interpreting Pathologist (signature and date): X No --HAY 2 0 99^____ Features: Z 16247. Liver. Hepatocyte. Several large irregular electron-dense residual bodies are present in the centered hepatocyte and the subjacent hepatocyte. The SER and nuclear envelope are slightly dilated. Also, the mitochondria appears slightly swollen, although this appears to be artifactual along with the dilated SER. A few small lipid droplets are present. Fourteen (14) peroxisomes counted. Z 16248. Liver. Hepatocyte. Clusters of fine granules, probably glycogen, are present in the cytoplasm. The mitochondria appears slightly dilated, as does the SER in an adjacent hepatocyte to the top left. The smooth ER is poorly defined. Several small lipid droplets are present. Two erythrocytes are present at the lower right of the photograph. Eleven (11) peroxisomes counted. Z 16249. Liver. Hepatocyte. The RER, nuclear envelope, and SER in the hepatocyte are slightly dilated, consistent with some fixation artifact. Several small lipid droplets and residual bodies are present. A small segment of a perisinusoidal fat-storing cell is present at the lower right, adjacent to an endothelial cell. Sixteen (16) peroxisomes identified. Z16250. Liver. Hepatocyte. Several small lipid droplets are present in the hepatocyte. Multiple dark and irregular residual bodies are also present. The ER is slightly dilated throughout. Three (3) probable peroxisomes counted. Z16251. Liver. Hepatocyte. There is mild dilatation of the nuclear envelope and the endoplasmic reticulum throughout. Mitochondria have a paler matrix and may be slightly enlarged. On the left is the hepatocyte's microvillous border, with an adjacent endothelial cell and erythrocyte in the sinusoid. A bile canaliculus is present in the lower right. Ten (10) peroxisomes counted.__________________________________________________ Conclusions: Essentially normal hepatocytes. Some minimal to slight fixation artifacts Average 10.8 peroxisomes per hepatocyte. 1038 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: _6329-223 (EM 99.76) Animal No.: 105537_________ Treatment Group: .03 mg/kg (low-dose) Sex:______Female____________ Species/Strain: Cvnomolgus Monkey Tissue: Liver_____________ Block No(s).: 99.76-19________ Z16252Photo/Negative No(s).: Z16256 Significant Lesions (check one): Yes Interpreting Pathologist (signature and date): X No ^ _____ MAY 2 0 13s3 Features: Z16252, Liver. Hepatocyte. Fixation appears good. Dorsal to the hepatocyte is a central vein or sinusoid area. Several medium-sized lipid droplets are present in the cytoplasm. Fine glycogen granules are scattered throughout the cytoplasm. A desmosome is present at the lower left margin with an adjacent hepatocyte. Ten (10) peroxisomes counted. Z16253. Liver. Hepatocyte. Hepatocyte shows very slight dilatation of endoplasmic reticulum. There is one large lipid droplet and several small droplets within the cytoplasm. A bile canaliculus is present at the top right margin of the cell. Five (5) peroxisomes counted. Z 16254. Liver. Hepatocyte. This cell appears essentially similar to Z16253, although there are lesser numbers of lipid droplets. Two irregular dark-staining residual bodies are present on the left and right side of the nucleus. The one on the right is somewhat vacuolated. Eleven (11) peroxisomes counted. Z16255. Liver. Hepatocyte. A medium-sized lipid droplet containing some lamellar material is present to the right of the nucleus. Just a few smaller lipid droplets are present elsewhere in the cytoplasm. The endoplasmic reticulum is slightly dilated. At the bottom is the microvillous border extending into the space of Disse. A few small residual bodies are present. Six (6) probable peroxisomes counted. Z16256. Liver. Hepatocyte. In this hepatocyte two mitochondria appear paler and somewhat swollen. The rest appear normal. Twelve (12) probable peroxisomes counted. Conclusions: Essentially normal hepatocytes. Quantity of lipid appears within normal expectations. Average 8.8 peroxisomes per hepatocyte. 1039 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.761 Animal No.: 105541 Treatment Group: .03 mg/kg (low-dosel Sex: Female Species/Strain: Cvnomolgus Monkey Tissue: Liver Block No(s).: 99.76-20_____ Z 16257- Photo/Negative No(s).: Z16261 Significant Lesions (check one): _______ Yes Interpreting Pathologist (signature and date): X No R , J j , HAY 2 0 1983 Features: Z16257. Liver. Hepatocyte. Microvillar borders are present along the lower left and upper right margins of this hepatocyte. A bile canaliculus is present at the lower right. Lamellar material within a lipid droplet is present to the lower right of the central nucleus. There is abundant SER throughout the cell, and the RER appears slightly dilated. Seven (7) probable peroxisomes counted. Z16258. Liver. Hepatocyte. Several medium-size lipid droplets are present, as well as approximately eight residual bodies, in the cytoplasm. The lower left margin is a microvillous border, and a bile canaliculus is present in the mid and upper right margins of this hepatocyte. Eight (8) peroxisomes counted. Z16259. Liver. Hepatocyte. This cell is surrounded by several other hepatocytes, and contains approximately ten medium-sized lipid droplets in its cytoplasm. Several very dark round to oval residual bodies are present at the top of the cell. Several dark mitochondria noted; these are often difficult to differentiate from lysosomes or peroxisomes. Fourteen (14) peroxisomes counted. Z16260. Liver. Hepatocyte. Hepatocyte appears essentially similar to those described above. Two lipid droplets noted. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. Twenty-three (23) peroxisomes counted. Z16261. Liver. Hepatocyte. Cell contains approximately 5 small to medium-sized lipid droplets. At the bottom is a sinusoid containing a platelet or segment of a granulocyte in the circulation. Another sinusoidal margin and microvillous border is present at the top. There is slight dilatation of the endoplasmic reticulum. Eight (8) peroxisomes counted. Conclusions: Essentially normal hepatocytes. Some lipid droplets noted, but within normal expectations for hepatocytes. Average 12.0 peroxisomes per hepatocyte. 1040 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105547_________ Treatment Group: 0.3 rng/kg (low-dose) Sex:________ Females__________ Species/Strain: Cynomolgus Monkey Tissue:_____Liver_____________ Block No(s).: 99.76-21_______ Z 16262 - Photo/Negative Nofs).: Z16266 Significant Lesions (check one): ________Yes Interpreting Pathologist (signature and date): X No P .J - J _____ HAY 2 0 1999 Features: Z16262. Liver. Hepatocyte. Photograph shows a hepatocyte with just a small nuclear profile. A microvillous border is present at the top right. Some artifactual knife marks are present. Several dark residual bodies are present, and only about six small lipid droplets are evident in the cytoplasm. Abundant SER and RER are throughout the cytoplasm intermixed with numerous mitochondria. Four (4) peroxisomes identified, Z16263. Liver. Hepatocyte. Numerous collagen fibers are present along the dorsal extracellular margin. At the lower left this hepatocyte's microvillous border extends in the space of Disse. There is slight dilatation of the nuclear envelope and endoplasmic reticulum. Several residual bodies and lipid droplets are present. Fine glycogen granules are randomly scattered throughout the cytoplasm. Six (6) peroxisomes clearly identified. Z 16264. Liver. Hepatocyte. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. A bile canaliculus is present at the dorsal right margin of the cell, and another hepatocyte is present along the ventral margin. The general morphology is similar to the above described cells. Only one lipid droplet is evident in this cell. Several residual bodies are evident. Fourteen (14) probable peroxisomes identified. Z16265. Liver. Hepatocyte. A central vein and sinusoid surround this hepatocyte on the lower and upper left margins. Erythrocytes are present in the vascular lumens. Within the hepatocyte there is slight dilatation of the endoplasmic reticulum and nuclear envelope. Two small lipid droplets are present. Nine (9) peroxisomes counted. Z16266. Liver. Hepatocyte. Hepatocyte appears essentially similar to cells described above. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. A large irregularly-shaped residual body is present to the lower left of the nucleus. Seventeen (17) probable peroxisomes counted.___________________________________ Conclusions: Essentially normal hepatocytes. Average 10.0 peroxisomes per hepatocyte.______________________________________________________ 1041 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: _6329-223 (EM 99.76) Animal No.: 105550_________ Treatment Group: .03 mg/kg (low-dose) S e x : ______Female_____________ Species/Strain: Cvnomolgus Monkey Tissue: Liver_____________ Block No(s).: 99.76-22______ Z 16267 Photo/Negative No(s).: Z16272 Significant Lesions (check one): _______ Yes X No Interpreting Pathologist (signature and date): .-Af Features: Z16267. Liver. Hepatocyte. Abundant numbers of glycogen granules are present throughout the cytoplasm of this hepatocyte. Bile canaliculi are evident on the right, left and lower left margins. A large dark residual body is present in an adjacent hepatocyte at the top left. Several smaller residual bodies are present in the cytoplasm of the centered hepatocyte. Mitochondria appear normal, having cristae, sporadic granules and a fine grainy matrix. Five (5) probable peroxisomes counted. Z16268. Liver. Hepatocyte. Cytoplasm has a somewhat light appearance due to slight dilatation of the endoplasmic reticulum. The nuclear envelope is also slightly dilated. These are artifactual fixation-related changes. Prominent bile canaliculi are present on the left and lower right cellular margins. No lipid droplets evident. Fifteen (15) peroxisomes counted. Z16269. Liver. Hepatocyte. Cell appears similar to Z16267 described above. There appears to be abundant glycogen granules in the cytosol. A microvillous border is present at the upper right extending in to the space of Disse, while bile canaliculi are evident along the lower left and upper left margins. There are many dark mitochondria which are difficult to differentiate from peroxisomes. Twenty-seven (27) probable peroxisomes counted. Z16270. Liver. Hepatocyte. This hepatocyte appears to be binucleate. An endothelial cell is present lining the sinusoid ventrally and two erythrocytes are present dorsal to this cell. The endoplasmic reticulum and nuclear envelope is slightly dilated. Twenty (20) peroxisomes seen. Z16272. Liver. Hepatocyte. Two large and multiple smaller lipid droplets are present in this hepatocyte. Dorsally, the microvillous border extends into the space of Disse and is adjacent to an endothelial cell. Ventrally are a small segment of a lipid-containing cell, probably a perisinusoidal fat-storing cell and an adjacent hepatocyte. Twenty-one (21) probable peroxisomes counted.________________________________________________________ Conclusions: Essentially normal hepatocytes. Although one cell (Z16272) had a lot of lipid droplets, the overall impression is that lipid content in this liver was within expected normal limits. Average 17.6 peroxisomes per hepatocyte. 1042 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105510_________ Treatment Group: .15 mg/kg (mid-dose) Sex:_______Male________ Species/Strain: Cynomolgus Monkey Tissue: Liver____________ Block No(s).: 99.76-23________ Z16273 - Photo/Negative Nofs).: Z16277 Interpreting Pathologist (signature and date): HAY 2 0 1999 Features: Z16273. Liver. Hepatocyte. Numerous glycogen granules are present randomly throughout the SER and cytosol. Fixation appears good. One swollen "barbell shaped" mitochondria is present, but all other mitochondria appear normal. Scattered dark residual bodies are present. Thirteen (13) peroxisomes counted. Z16274, Liver. Hepatocyte. Several small to medium-sized lipid droplets are present in the cytoplasm of the hepatocyte. Along its right margin its microvillous border faces another hepatocyte. A poorly-defined bile canaliculus is present at the lower left. The cytoplasm is filled with SER, RER, mitochondria and glycogen granules throughout. Some peroxisomes are noted. Scattered dark residual bodies are present. Ten (10) peroxisomes counted. Z16275. Liver. Hepatocyte. Centered hepatocyte has only a small nuclear profile. At the bottom is a central vein surrounded by an endothelial cell and a moderate number of extracellular collagen fibers. An endothelial cell is the lighter shaded cell at the top right. Three lipid droplets present in the cytoplasm. Thirteen (13) peroxisomes counted. Z16276. Liver. Hepatocyte. This cell appears similar to Z 16273. Approximately 10 small to medium-sized lipid droplets are present in the cytoplasm. Numerous glycogen granules are evident in the cytosol. A lamellar body is present at the bottom margin of the cell. Fourteen (14) peroxisomes counted. Z 16277. Liver. Hepatocyte. Approximately a dozen small to medium-sized lipid droplets are present in the cytoplasm. The cluster of 5 droplets at the far right are in another cell. The cytoplasm contains abundant fine glycogen granules. Several residual bodies are noted. Three (3) probable peroxisomes counted._________________________ 1043 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 ('EM 99.76) Animal No.: 105518_________ Treatment Group: .15 mg/kg (mid-dose S e x :_________ Male____________ Species/Strain: Cvnomolgus Monkey Tissue:_____Liver_____________ Block No(s).: 99.76-24________ Z16278 - Photo/Negative No(s).: Z16282 Features: Z 16278. Liver. Hepatocyte. At the top right this hepatocyte is bordered by a perisinusoidal fat-storing cell containing several prominent lipid droplets. Four small lipid droplets are present in the hepatocyte. A bile canaliculus, adjacent to a large residual body, is present on the left margin of the cell. There is slight dilatation of the nuclear envelope and endoplasmic reticulum. Multiple irregular residual bodies are evident. Thirteen (13) peroxisomes clearly identified. Z16279. Liver. Hepatocyte. The centered hepatocyte is bordered by a darker hepatocyte on the right. On its left is a band of interstitial collagen. The nuclear envelope and endoplasmic reticulum are slightly dilated. Several endocytotic vesicles are present along the right cellular membrane. Sixteen (16) probable peroxisomes counted. Z 16280. Liver. Hepatocyte. Hepatocyte has prominent bile canaliculi along its right and left margins with the adjacent hepatocytes. One small lipid droplet noted. Mitochondria stain somewhat more pale in this cell and contrast with darker peroxisomes. Multiple clusters of RER evident. Twelve (12) peroxisomes counted. Z16281. Liver. Hepatocyte. This hepatocyte appears to be binucleate. At the top left is an erythrocyte within the central vein or sinusoid. Several small lipid droplets are present in the cytoplasm. There is slight to moderate dilatation of the endoplasmic reticulum and nuclear envelope. Some shrunken mitochondria are difficult to differentiate from lysosomes or peroxisomes. Thirty-two (32) probable peroxisomes counted. Z16282. Liver. Hepatocyte. General cellular morphology is similar to cell described above. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. Nineteen (19) peroxisomes counted. Conclusions: Essentially normal hepatocytes. Only small numbers of lipid droplets seen. Average 18.4 peroxisomes per hepatocyte.______________________________ 1044 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 ('EM 99.76) Animal No.: 105524_________ Treatment Group: .15 mg/kg (mid-dose) S e x : ________ Male_____________ Species/Strain: Cvnomolgus Monkey Tissue:_____Liver_____________ Block No(s).: 99.76-25________ Z16283 - Photo/Negative Noisk: Z16287 Significant Lesions (check one): X Yes No Features: Z16283. Liver. Hepatocyte. Hepatocyte contains two medium-sized lipid droplets. The nuclear envelope and endoplasmic reticulum are slightly dilated. At the top right is a bile canaliculus between this cell and an adjacent hepatocyte. Desmosomes are present around the canaliculus. Thirty-one (31) peroxisomes counted. Z16284, Liver. Hepatocyte. This centered hepatocyte is surrounded by other hepatocytes on all margins in this photograph. Bile canaliculi are evident at the top left and bottom left margins. No lipid droplets are evident in this cell. Mitochondria, RER and SER appear normal. Twenty-nine (29) probable peroxisomes counted. Z16285. Liver. Hepatocyte. Two erythrocytes are present in the sinusoid adjacent to the left of this hepatocyte. Collagen fibers are present in the space of Disse. Along the right margin of this cell is a prominent bile canaliculus . A single medium-sized lipid droplet is present in this cell. Twenty-seven (27) peroxisomes counted. Z16286. Liver. Hepatocyte. Cell appears essentially similar to cells described above. At top left and bottom right are erythrocytes within sinusoids. No distinct lipid droplets are present in this cell. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. Several dark residual bodies are present. Twenty-one (21) peroxisomes counted. Z16287. Liver. Hepatocyte. Cell has two large and several smaller lipid droplets present in its cytoplasm. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. Several dark residual bodies are present. Glycogen granules are present throughout the cytoplasm. Eight (8) peroxisomes counted. Conclusions: Essentially normal hepatocytes. Slight increase in average number of peroxisomes. No increase in lipid noted. Average 23.2 peroxisomes per hepatocyte. 1045 Covance 6329-223 3M T-6295.7 Significant Lesions (check one): ________Yes X No Interpreting Pathologist (signature and date): Features: Z16288. Liver. Hepatocyte. This hepatocyte contains about five medium sized and approximately fifteen small lipid droplets in its cytoplasm. Microvillous border beneath endothelial cells are evident at the upper right and lower left margins. A bile canaliculus surrounded by desmosomes is present at the lower right margin. Scattered dark-staining residual bodies are present in the cytoplasm. There is slight dilatation of the endoplasmic reticulum and the nuclear envelope. Five (5) peroxisomes clearly identified. Z16289. Liver. Hepatocyte. This hepatocyte's microvillous border extends into the space of Disse at the upper left margin of the photograph. At the lower left is a perisinusoidal fat-storing cell (Ito cell). There is slight dilatation of the endoplasmic reticulum and the nuclear envelope. Two small lipid droplets are evident. Sixteen (16) peroxisomes counted. Z16290. Liver. Hepatocyte. This cell is a little darker staining than previous cells. At lower left a granulocyte is present in the sinusoid or central vein. At the top right a perisinusoidal fat-storing cell (Ito cell) is present. Several small lipid droplets are present in the hepatocyte and a few residual bodies are evident. There is slight dilatation of the endoplasmic reticulum and the nuclear envelope. Nineteen (19) peroxisomes counted. Z16291. Liver. Hepatocyte. Much of the cytoplasm has a dense granular appearance, composed of SER, glycogen granules, and probable cytoskeletal components. Approximately eighteen small to medium-sized lipid droplets are present. Nineteen (19) probable peroxisomes counted. Z16292. Liver. Hepatocyte. Hepatocyte appears similar to Z 16291. There are several lipid droplets present in the cytoplasm. Fourteen probable (14) peroxisomes counted. Conclusions: Essentially normal hepatocytes. Lipid droplet numbers within normal expectations. Average 14.6 peroxisomes per hepatocyte.__________________________ 1046 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105532 Treatment Group: .15 mg/kg (mid-dose) Sex: Female Species/Strain: Cvnomolgus Monkey Tissue: Liver Block No(s).: 99.76-27_____ Z16293 - Photo/Negative No(s).: Z16297 Significant Lesions (check one): ________Yes Interpreting Pathologist (signature and date): X No g .O rA f HAY 2 0 1999 Features: Z16293. Liver. Hepatocyte. This photograph has a centered hepatocyte. At the top are multiple lipid droplets which are in an adjacent perisinusoidal fat-storing cell (Ito cell), not in this hepatocyte. There are numerous glycogen granules in the cytosol intermixed with the endoplasmic reticulum. Two very small lipid droplets are present. Mitochondria appear normal. They show fine cristae, some granules and finely grainy matrix. Four (4) peroxisomes clearly identified. Z 16294. Liver. Hepatocyte. A single large lipid droplet is present in the cytoplasm beneath the nucleus. Similar to Z16293, there are many fine granules in the cytoplasm which appear to be glycogen granules. Three (3) peroxisomes identified in this hepatocyte. Z 16295. Liver. Hepatocyte. Several medium-sized lipid droplets are present in this hepatocyte. At the upper right is a "P"-shaped extracellular area containing collagen fibers. Moderate amounts of glycogen are present in the cytoplasm of the hepatocyte. Several residual bodies are also present. Five (5) probable peroxisomes counted. Z 16296. Liver. Hepatocyte. Centered hepatocyte appears similar to those described above. Three lipid droplets are evident in its cytoplasm. At the bottom is a longitudinal profile of a bile canaliculus and a cross-section of a canaliculus at the top margin. Fine glycogen granules are present throughout. Six (6) peroxisomes counted. Z16297. Liver. Hepatocyte. . Centered hepatocyte appears similar to those described above. Two medium-sized and several small lipid droplets present. To the right is an area of interstitium containing some collagen fibers. The nucleus probably belongs to an endothelial cell. Three (3) peroxisomes counted.________________________________ Conclusions: Essentially normal hepatocytes. Moderate amounts of glycogen present in most cells. Lipid droplet numbers appear normal. Average 4.2 peroxisomes per hepatocyte. ___________________________________________________________ 1047 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105538_______ Treatment Group: .15 mg/kg ('mid-dose) Sex:_________ Female__________ Species/Strain: Cynomolgus Monkey Tissue:_____Liver_____________ Block No(s).: 99.76-28_______ Z 16298 - Photo/Negative No(s).: Z16302 Significant Lesions (check one): X Yes Interpreting Pathologist (signature and date): No (S . C ) g A ? ( _ HAY 2 0 1999 Features: Z16298. Liver. Hepatocyte. Section has a prominent single knife mark transecting the cell beneath the nucleus. Numerous glycogen granules are present in the cytoplasm. A single small lipid droplet is present. Mitochondria and other organelles appear normal. Five (5) peroxisomes counted. Z16299. Liver. Hepatocyte. Hepatocyte has a single large and several small lipid droplets. A sinusoid is present at the upper left margin where the microvillous border extends into the space of Disse. There are abundant glycogen granules in the cytoplasm. Some mitochondria are lighter staining than the majority of darker one. These light mitochondria are somewhat difficult to differentiate from lysosomes or peroxisomes. Eighteen (18) probable peroxisomes counted. Z 16300. Liver. Hepatocyte. Cell contains abundant glycogen often in irregular clear spaces or pockets in the cytosol. A single lipid droplet is present. Three (3) peroxisomes identified. Z16301. Liver. Hepatocyte. This centered hepatocyte has adjacent hepatocyte dorsally and ventrally and a microvillous-sinusoidal border at the top right. Its cytoplasm contains multiple irregular pockets of glycogen granules. Other organelles appear somewhat clumped between the glycogen pockets. Nine (9) peroxisomes counted. Z16302. Liver. Hepatocyte. This cell appears similar to Z16301, although it has more pockets of glycogen granules and has an overall light appearance. Other organelles appear clumped between the glycogen granules. One (1) peroxisome clearly identified. Conclusions: Essentially normal hepatocytes. There is increased glycogen in some of these hepatocytes. Average 7.2 peroxisomes per hepatocyte. 1048 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.:____ 105545_____ Treatment Group: .15 mg/kg (mid-dose) Sex:_____ Female Species/Strain: Cynomolgus Monkey Tissue:____ Liver____________ Block No(s).: 99.76-29_______ Z16303 - Photo/Negative No(s).: Z16307 Significant Lesions (check one): Yes Interpreting Pathologist (signature and date) X No hay a fi m Features: Z16303. Liver. Hepatocyte. This cell is bordered by hepatocytes on the top right and bottom right and by an interstitial margin on the left. Prominent bile canaliculi are evident between adjacent hepatocytes. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. No lipid droplets are evident. Several dark irregular residual bodes are present. Six (6) probable peroxisomes counted. Z16304. Liver. Hepatocyte. Centered hepatocyte is surrounded by hepatocytes on all margins. Bile canaliculi are evident at the right and bottom margins. Its endoplasmic reticulum and nuclear envelope are slightly dilated. Several residual bodies are present. No lipid droplets are present. Fourteen (14) probable peroxisome counted. Z16305. Liver. Hepatocyte. Hepatocyte appears similar to Z16303 above. At top left is a central vein, lined by an endothelial cell and containing a segment of an erythrocyte. No lipid droplets are evident in this hepatocyte. Seven (7) peroxisomes clearly identified. Z16306. Liver. Hepatocyte. This cell is somewhat lighter staining than previous hepatocytes, although the mitochondria still are staining fairly darkly. Cell on the far right may be an endothelial cell. Twelve (12) probable peroxisomes counted. Z16307. Liver. Hepatocyte. All mitochondria in this cell are darkly staining. There is slight dilatation of the endoplasmic reticulum. Six (6) peroxisomes identified. Conclusions: Essentially normal hepatocytes. No evidence of increased lipid droplets. Average 9.0 peroxisomes per hepatocyte. 1049 Covance 6329-223 3M T-6295.7 TRANSMISSION ELECTRON MICROGRAPH INTERPRETATION Study No.: 6329-223 (EM 99.76) Animal No.: 105548__________ Treatment Group: ,15 mg/kg (mid-dose) Sex: ______ Female____________ Species/Strain: Cvnomolgus Monkey Tissue: Liver___________ Block No(s).: 99.76-30 Z16308 -Z16309 Photo/Negative No(s).: Z16311Z16313 Significant Lesions (check one): Yes Interpreting Pathologist (signature and date): X No /I _____HAY 2 0 1939 Features: Z16308. Liver. Hepatocyte. The centered hepatocyte is bordered by adjacent hepatocytes on its left and right margins. On the right is a prominent bile canaliculus. A microvillous border is evident at the top right. Fixation appears good and cytoplasmic organelles appear normal. No lipid droplets are present in the cytoplasm. Abundant SER is present in the cytoplasm. There are a number of shrunken dark, variably-sized mitochondria, which are difficult to clearly differentiate frompossible lysosomes or peroxisomes. One large lysosome is present at about "4:40 o'clock" from the nucleus, and contains some linear debris. Twenty-nine (29) peroxisomes identified. Z16309. Liver. Hepatocyte. This hepatocyte exhibits slight dilatation of the endoplasmic reticulum and nuclear envelope. Three small to medium-sized lipid droplets are present. An erythrocyte is evident in a sinusoid at the bottom left of the photograph. Random dark and irregular residual bodies are present. Seventeen (17) peroxisomes clearly identified. Z16310. Liver. Hepatocyte. Crystalloid inclusions in some mitochondria, an occasional finding in mitochondria. Peroxisomes not counted in this hepatocyte. Z16311. Liver. Hepatocyte. One large and several smaller lipid droplets are present in the cytoplasm. There is slight dilatation of the endoplasmic reticulum and nuclear envelope. Prominent bile canaliculi are present on the left and right margins with adjacent hepatocytes. Sixteen (16) probable peroxisome counted. Z16312. Liver. Hepatocyte. This hepatocyte is bordered by adjacent hepatocyte on all margins. Several small lipid droplets are present in the cytoplasm. There is slight dilatation of the nuclear envelope and endoplasmic reticulum. Nine (9) probable peroxisomes counted. Z16313. Liver. Hepatocyte. Two medium-sized and several smaller lipid droplets are evident in the cytoplasm. At the bottom left of the photograph are some interstitial collagen fibers. A bile canaliculus is present at the top right margin of the cell. There is slight dilatation of the endoplasmic reticulum, especially the RER, and the nuclear envelope. A large lysosome is present in close proximity to the noted bile canaliculus; it contains some electron-dense material. Fourteen (14) peroxisomes counted._____________ Conclusions: Essentially normal hepatocytes. No substantial increase in lipid droplets noted. Average 17.0 peroxisomes per hepatocyte. 1050 Covance 6329-223 3M T-6295.7 DI. Transmission Electron Micrographs 1051 Covance 6329-223 3M T-6295.7 Figure Legends Draft Ancillary Pathology Report Covance Study No. 6329-223 Magnification. Print magnification is indicated on the back of each photograph. The measurement bar on each photomicrograph equals one micron (0.001mm). Figure 1. Liver. Hepatocyte showing normal cytoplasmic organelles. Some peroxisomes are identified and other normal organelles. Ventraily the microvillous border extends into the perisinusoidal space. Animal No. 105517, 0 mg/kg/day (control male), 10,920X magnification. Figure 2. Liver. Hepatocyte. Several lipid droplets are present. There is slight artifactual dilatation o f some rough endoplasmic reticulum. Some extracellular collagen is present in the interstitium in the upper right comer. An endothelial cell nucleus is present lining the sinusoid in the lower right comer o f the photograph. Animal No. 105544, 0 mg/kg/day (control female), 11,200X magnification. Figure 3. Liver. Hepatocyte. Mitochondria showing outer membrane, cristae, matrix and granules. These granules within the mitochondrial matrix are normal and are sites of calcium accumulation. Animal No. 105519, 0 mg/kg/day (control male), 112,000X magnification. Figure 4. Liver. Hepatocyte showing increased lipid droplet accumulation. Lipid droplets vary from small to very large. Several residual bodies are present. Peroxisomes are scare. Animal No. 105507, 0.75 mg/kg/day (high-dose male), 10,920X magnification. Figure 5. Liver. Hepatocyte showing numerous lipid droplets and peroxisomes. Several peroxisomes are labeled. Animal No.105512, 0.75 mg/kg/day (high-dose male), 10.920X magnification. Figure 6. Liver. Hepatocyte with many small to large lipid droplets. Representative peroxisomes are labeled. Desmosomes and a bile canaliculus is evident at the right. Animal No.105536, 0.75 mg/kg/day (high-dose female), 11,200X magnification. Figure 7. Liver. Hepatocyte with multiple lipid droplets and abundant glycogen granules in the cytoplasm. Animal No. 105540, 0.75 mg/kg/day (high-dose female), 11,200X magnification. Figure 8. Liver. Hepatocyte containing numerous "pockets" of glycogen. Animal No. 105551, 0.75 mg/kg/day (high-dose female), 11,200X magnification. 1052 Covance 6329-223 3M T-6295.7 Draft Ancillary Pathology Report Covance Study No. 6329-223 Figure 9. Liver. Hepatocyte. Mitochondria showing outer membrane, cristae and matrix. Small lipid droplets are present in the surrounding cytosol. Animal No. 105512, 0.75 mg/kg/day (high-dose male), 112.000X magnification. Figure 10, Liver. Hepatocyte. Mitochondria showing outer membrane, cristae, matrix, and granules. The nucleus is present on the right. Animal No. 105534, 0.75 mg/kg/day (high-dose female), 95,200X magnification. Figure 11. Liver. Hepatocyte. There is moderate accumulation of small to medium sized lipid droplets in this hepatocyte. Only a small nuclear profile is evident in this cell. The endoplasmic reticulum is slightly dilated. Animal No. 105514, 0.03 mg/kg/day (lowdose male), 11,200X magnification. Figure 12. Liver. Hepatocyte. Mitochondria, endoplasmic reticulum and some residual bodies make up the majority of this hepatocyte's cytoplasm. A few small dark mitochondria are present, but no clearly identifiable peroxisomes are present. No lipid droplets are present in this cell, although a single lipid droplet is present in the subjacent cell at the bottom of the photograph. Animal No. 105545, 0.15 mg/kg/day (mid-dose female), 11,200X magnification 1053 Covance 6329-223 3M T-6295.7 1054 Covance 6329-223 3M T-6295.7 1055 Covance 6329-223 3M T-6295.7 1056 Covance 6329-223 3M T-6295.7 1057 Covance 6329-223 3M T-6295.7 1058 Covance 6329-223 3M T-6295.7 1059 Ka > Covance 6329-223 3M T-6295.7 1060 Covance 6329-223 3M T-6295.7 1061 Covance 6329-223 3M T-6295.7 1062 Covance 6329-223 3M T-6295.7 1063 'r vi. Covance 6329-223 3M T-6295.7 1064 Covance 6329-223 3M T-6295.7 1065 Covance 6329-223 3M T-6295.7 1066 Covance 6329-223 3M T-6295.7 IV. Quality Assurance Statement 1067 Covance 6329-223 1068 APPENDIX 9 Urobilinogen Analysis Report Covance 6329-223 3M T-6295.7 Note: The report in this appendix was supplied by the Sponsor, based on data supplied by the Mayo Clinic. The analysis at the Mayo Clinic was not done in compliance with Good Laboratory Practice Regulations and was not audited by a Quality Assurance Unit. 1069 Covance 6329-223 3M T-6295.7 Urobilinogen Analysis Report for Study title: 26-Week Capsule Toxicity Study with Perfluorooctanesulfonic Acid Potassium Salt (PFOS) in Cynomolgus Monkeys Covance 6329-223, (3M Medical Dept number: T- 6295.7). Author: Andrew M. Seacat Final Report Date: 3/1/01 Introduction In an effort to understand the lowering of bilirubin in the blood of the PFOS high dose (0.75 mg/kg/day) Cynomolgus monkeys, the potential excretion of urobilinogen was evaluated. The hypothesis being tested is that increased fecal urobilinogen excretion is responsible for the observed lowering of bilirubin in the blood in the high dose animals. The null hypothesis would state that the is no significant difference between the control and high dose fecal urobilinogen values. Method summary Six-hour fecal samples were collected from the cages of the control and high dose male and female monkeys and were sent to Dr. Joe McConnell at Mayo Clinic for fecal urobilinogen analysis (1). Results The urobilinogen values obtained from the six hour fecal samples collected were not significantly different between the control and high dose groups of male and female Cynomolgus monkeys (Table 1). Therefore the null hypothesis cannot be rejected. The urobilinogen values were within the assay detection limits, but were very low compared to the typical human range of urobilinogen values. This could be due to a true physiological species difference or possibly due to analytical difficulties encountered with a new matrix. Reference: 1. Urobilinogen (UB) Analysis Results from Dr Joseph P. McConnell., Porphyrins and nutritional Biochemistry lab, Dept of Laboratory Medicine and Pathology. Mayo Clinic, Rochester MN. 1070 Covance 6329-223 3M T-6295.7 1071 APPENDIX 10 Dose Confirmation Analysis Report Compound Stability Report Analytical Laboratory Report Certificate of Analysis Quality Assurance Statement Covance 6329-223 3M T-6295.7 Note: This appendix contains information supplied and audited by the Sponsor. 1072 Covance 6329-223 3M T-6295.7 Dose Confirmation Analysis Report for Study title: 26-Week Capsule Toxicity Study with Perfluorooctanesulfonic Acid Potassium Salt (PFOS) in Cynomolgus Monkeys Covance 6329-223, (3M Medical Dept number: T- 6295.7). Author: Andrew M. Seacat Final Report Date: 3/1/01 Introduction Dose confirmation analysis were performed on samples of perfluorooctanesulfonic acid potassium salt (KPFOS) triturated in lactose at dilutions of 1:499 and 1:39 w:w. The low dose group (0.03 mg/kg/day of PFOS) received 15 mg/kg/d of the 1:499 w:w dilution in gelatin capsules. The mid-dose (0.25 mg/kg/day PFOS) and the high-dose (0.75 mg/kg/day) groups received 6 and 30 mg/kg/day respectively of the T.39 w:w dilution in gelatin capsule. Samples from the top, middle and bottom of each mixture were collected on day -15 prior to the in-life phase of the study for homogeneity analysis and sent to 3M Environmental lab. Samples collected from the middle of the preparations were collected prestudy and at the end of the treatment phase for material content analysis to assess compound stability in the dosing vehicle. Method summary The dose confirmation data were collected according to a method described fully in the Analytical Laboratory Report (1). Briefly, dose confirmation was performed by diluting the lactose dose samples 1000-fold with Milli-Q water, which were then extracted using the ion-pair reagent tetrabutylammonium hydrogen sulfate according to the procedure (1). The extracts from the 1:499 and the 1:39 dilutions were then diluted 1:5 and 1:50, respectively, to bring the PFOS levels in the linear range of the instrument. For each sample, (top, middle and bottom), the average PFOS spiked matrix extract value was used as correction factor for calculating the percent recovery. In all cases, samples were analyzed versus an unextracted curve using HPLC-ESMS/MS. Results The results indicated that the 1:499 dilution used for the 0.03 mg/kg/day dose group was 86 4 % of the target concentration, and that the 1:39 dilution used for the 0.75 and 0.15 mg/kg/day dose groups were 113 31 % of the target concentration (Table 1) The stability samples were obtained from the middle of each mixture and were received on 5-07-99. The stability sample for the 1:499 was 100 4 % of the target concentration, and the stability sample for the 1:39 was 69 0 % of the target concentration (Table 2). 1073 Covance 6329-223 3M T-6295.7 Covance: 6329-223 3M T-6295.7 Dose Analysis Report Reference: 1. Hansen K. J. Analytical Laboratory Report from the 26-Week Capsule Toxicity Study with Perfluorooctanesulfonic Acid Potassium Salt (PFOS) in Cynomolgus Monkeys on the Determination of the Presence and Concentration of Perfluorooctanesulfonate (PFOS) in Liver and Serum Samples. Project Identification: Covance 6329-222, 6329-223, 3M Medical Dept number: T- 6295.7, Analytical study: FACT TOX030, 3M Laboratory request No. U2279. 214 pp, 2000. 1074 Covance: 6329-223 3M T-6295.7 Dose Analysis Report Table 1. Dose sample analysis 6329-223 Lactose Dose Verification Appendix 8 /2 1 /9 8 A n a ly s is 1:39 D o s e (25000 ppm P F O S ) E xpected Cone. nq/m L Top 580 M id d le 500 B ottom 500 Avg SD Actual C one. nq/m L 479 650 422 %R e c o v e r y for nq/m L 83 130 84 E x p e c te d Cone. u g /g 25000 25000 25000 A c tu a l C alculated C one. I % Recovery _____ m is_____ I f o r u g /g 20647 83 32537 130 21108 84 MS Average R ecovery Corrected C one. .......... u g /g 23619 37219 24145 28328 7705 C o rre c te d % Recovery for ug/g 94 149 97 113 31 1 :499 D o s e Top M id d le B o tto m Avg SD (2000 ppm P FO S ) E xpected Cone. nq /m L 410 404 400 Actual C one. nq/m L 305 287 272 %R e c o v e r y for nq/m L 74 71 68 E x p e c te d Cone. u g /g 2000 2000 2000 A c tu a l C alculated C one. _____ m is_____ 1490 1425 1361 I % Recovery forI .......... ug/g 74 71 68 MS Average R ecovery C orrected C one. _______ naia________________ 1795 1716 1639 1717 78 C o rre c te d %R e c o v e r y for ug/g 90 86 82 86 4 A c tu a l M a trix S p ik e (M S ) C o n e . - A c tu a l B a c k g ro u n d C o n e , d iv id e d b y E x p e c te d tim e s 1 0 0 S p ik e d to o lo w w h ic h a c c o u n ts fo r th e w id e d iffe r e n c e s in r e c o v e r y 1:39 D o s e (25000 ppm P F O S ) M atrix S pike (M S ) E xpected C one. Actual C one. % R ecovery ng/m L nq/m L for n q/m L Top 604 507 84 M iddle 524 485 92 B ottom 524 438 83 Avg E x p e c te d A c tu a l C alculated Cone. Cone. C alculated Cone. _____ naia_____u g / g .................... _____________ u g / g ........... 21858 10.8 12.1 24252 12.5 -82.8 21889 12.5 7 .8 2 % Recovery for ug/g 112 -664* 63 87 * a n o u tlie r , n o t u s e d in a n y c a lc u la tio n s A c tu a l M a trix S p ik e C o n e . - A c tu a l B a c k g ro u n d C o n e , d iv id e d by E x p e c te d tim e s 1 0 0 1 :499 D o s e Top M id d le B o tto m A vg (2000 ppm P F O S ) M S E xpected Cone. Actual C one. nq /m L nq/m L 606 475 600 596 447 440 % R ecovery for nq/m L 78 C alculated Cone. usa... ................ ____________ 2320 75 2217 74 2202 Expected Cone. ug/g 9.77 9.92 10.0 A ctual C alculated Cone. .................... u g / g 8.30 7.93 8 .4 1 % Recovery fo r ug/g 85 80 84 83 =P F O S P e r f l u o r o o c t a n e s u l f o n a t e 3 1075 Covance 6329-223 3M T-6295.7 Covance: 6329-223 3M T-6295.7 Dose Analysis Report Table 2 . Stability Sample analysis Group Dose Method Blk QC Dose Sample # Lact091800-WBlk-l Lact091800-WBlk-2 Lact091800-(l :39)-MSl Lact091800-( 1:39)-MSD 1 Lact091800-(T.499)-MS 1 Lact091800-( 1:499)-MSD 1 Lact091800-(1:39)-1 Lact091800-( 1:39)-2 Avg Lact091800-(1:499)-1 Lact091800-( 1:499)-2 Avg Expected Cone. PFOS ng/mL 0.00 0.00 25 25 200 200 515 515 414 414 PFOS-Bckgrnd Cone. ng/mL NA NA 6.21 -17.89 236.6 177.4 NA NA NA NA PFOS % Recovery Accuracy NA NA 25% -71% 118% 89% 69% 69% 69% 103% 98% 100% Covance 6329-223 3M T-6295.7 1076 Covance: 6329-223 3M T-6295.7 Example calculations Dose Analysis Report Calculating cone. (Top 1:39) ug/g: (479.02 nq/m Lx 100 m Lx 1 mL) (0.02 mL x 0.116 g x 1000 ng/ug) = 20647 ug/g Expected concentration (Top 1:39) ug/g: (50 uq/mL x 0.025 mL) 0.1160 g = 10.8 ug/g Actual Calculated Cone. (Top 1:39) ug/g: (507 nq/mL x 100 mL x 1 mL) - (479.02 nq/mL x 100 mL x 1 mL) (0,02 m L x 0.116 q x 1000 nq/ua) (0.02 mL x 0.116 q x 1000 nq/uq) 100 = 12.1 ug/g The number is divided by 100 since the sample was diluted 1:100, 1.0 mL of diluted sample removed, then spiked with standard. 1077 Covance 6329-223 3M T-6295.7 3M Corporate Health Physics Corporate Occupational Medicine Corporate Product Responsibility Corporate Toxicology 3M Medical Department September 6, 2000 3M Center, 220-2E-02 PO Box 33220 St. Paul, MN 55133-3220 651 733 1110 Covance 6329-223 3M T-6295.7 Peter J. Thomford, Ph.D. Study Director, Toxicology Covance Laboratories Inc. 3301 Kinsman Blvd. Madison WI 53704 Re. Covance 6329-222 (T-6295.6), 6329-223 (T-6295.7). Perfluorooctanesulfonate Compound Stability Report Peter: The perfluorooctanesulfonic acid potassium salt (PFOS, FC-95 Lot 217) used in Covance 6329-222, 6329-223, has remained stable for the entire duration of the study. A Certificate of Analysis (C of A) dated March 9, 2000 (1), identified the compound as being 90.49% C8F17S03-K+ by a combination of LC/MS, `H-NMR, 19F-NMR, and elemental analysis techniques. Previously, on December 1st 1997, 19F-NMR was used to characterize FC-95 lot 217 and showed that the isomer distribution was identical to the C of A sent to you earlier this year (2). Additionally, 19F-NMR and 1H NMR conducted on August 24th2000 (3) were compared to the 19F-NMR completed on December 1st 1997 and indicated that there was no significant differences in the composition of this lot of PFOS over intervening 3 and a half year time period. Thus, PFOS, FC-95 Lot 217 used was stable for greater the time period during which these studies were conducted. Sincerely, Andrew M. Seacat Ph.D. Toxicology Specialist 1078 Peter Thomford, Ph.D Page 2 September 6, 2000 Covance 6329-223 3M T-6295.7 References 1. Payfer R.M. Certificate Of Analysis FC-95, Lot 217. 3M Specialty Chemicals Division. March 9, 2000 2. Kestner T. Fluorochemical Isomer Distribution by 19F-NMR Spectroscopy. FC-95, lot 217 Analytical Request 53030 . SA&C Analytical Lab. December 1, 1997 3. Kestner T. Chemical Characterization of PFOS (FC-95, lot 217) by !H-NMR & 19F-NMR Spectroscopy. Comparison to FC-95/217 analysis from Req.#53030Request No. 61886. 3M SA&C Analytical Lab - 236-2B-11. August 24, 2000. 1079 3M Medical Department Study: T-6295.7 Covance 6329-223 3M T-6295.7 LaboratoRryeRpoerqtuNeos.t FNAuCmTbeTrO-UX2-023709 A n a l y t ic a l Laboratory R eport FROM THE 26-Week Capsule Toxicity Study with Perfluorooctanesulfonic Acid Potassium Salt (T-6295) in Cynomolgus Monkeys . ON THE Determination of the Presence and Concentration of Perfluorooctanesulfonate (PFOS) in Liver and Serum Samples Project Identification 3M Medical Department Study: T-6295.7 Covance In-Life'Study: #6329-223 . Analytical Study: FACT TOX-030 3M Laboratory Request No. U2279 Study Completion Date At signing Total Num ber o f Pages 233 3M Environmental Laboratory 1080 Page 1 3m Medical Department Study: T-6295.7 3 M M edical D epartm ent S tudy: T -6 2 9 5 .7 GLP Compliance Statement Covance 6329-223 3M T-6295.7 Report No. FACT T O X - 0 3 0 laboratory Request Number-U2279 R eport N o . F A C T T O X -Q 30 Laboratory R equest N um ber-112279 Study T itie; A nalytical L abo ratory Report from the 2 6 -W eek C ap su le Toxicity S tudy with P erfluorooctanesulfonic Acid Potassium S alt (T -6 2 9 5 ) in Cynom olgus M o nkeys on th e D eterm ination o f the Presence and C oncentration o f P erfiuo ro od anesulfon ate (P F O S ) in Liver an d S eru m Sam ples Study Identification N um ber. F A C T T O X -0 3 0 , T -6 2 9 5 .7 , C o van ce # 8 3 2 9 -2 2 3 This study w a s conducted in co m p lian ce with U nited States E nvironm ental Protection A gency G ood Labo ratory P ractice (G L P ) S tan d ard s 4 0 C F R P art 79 2, with the excep tion s in th e bulleted list below . A ll raw d a ta an d sam ples for this study a re retained in archives a t the 3 M L ab an d w be retained fo r a period o f a t le a s t ten years. T h e an alytical phase com pleted a t the 3 M L ab w as perform ed in accordance w ith 3 M E T& S S S tan d ard O perating Procedures. E xceptions to G L P com pliance: T h e re w e re tw o study directors in this study. This study w as designed as tw o s e p a ra te studies. T h e in-life phase study w as considered to end a t t ie g eneration an d shipm ent o f specim en s. T h e analytical study w a s considered to start a t th e receipt o f th e s e specim ens fo r an alysis. T h is resulted in havin g tw o separate study directors, one fo r each phase o f th e sam e study. H ow ever, since th e te ch n ical perform ance o f each phase w as en tirely separate, no e ffe c t is exp ected from this excep tio n . O n a fe w occasions, d a ta w e re not recorded o r corrected ex actly as required by th e G L P s. T h e 3 M T O X 0 3 0 protocol states in the R egulatory C om pliance section that "Th is study w ill be conducted in accordance w ith the U nited S tates Environm ental Protection A gency G ood Laboratory P ractices S tan dards, 4 0 C F R 7 9 2 , with the exception th at analysis o f th e te s t m aterial m ixture fo r concentration, solubility, hom ogeneity, and stability will not b e conducted, and is th e responsibility o f th e Sponsor." A nalyses w ere, ho w ever, com pleted on the concentration and hom o geneity of the test m aterial m ixture, according to non-G LP validated m ethods, and are in d u d e d in this rep o rt A s per the protocol, solubility and stability determ inations w e re no t conducted. 1081 Covance 6329-223 3M T-6295.7 1082 Covance 6329-223 3M T-6295.7 INTERIM CERTIFICATE OF ANALYSIS Revision 1(9/7/00) Centre Analytical Laboratories COA Reference #: 023-018A 3M Product: PFOS,Lot217 Reference#: SD-018 _________________ Purity: 86.9%_________________ Test Name Specifications P u rity 1 Result 86.9% Appearance Identification NMR Metals (ICP/MS) 1. Calcium 2. Magnesium 3. Sodium 4. Potassium2 5. Nickel 6. Iron 7. Manganese Total % Impurity (NMR) Total % Impurity (LC/MS) Total % Impurity (GC/MS) Related Compounds POAA Residual Solvents (TGA) Purity by DSC Inorganic Anions (IC) 1. Chloride 2. Fluoride 3. Bromide 4. Nitrate 5. Nitrite 6. Phosphate 7. Sulfate4 Organic Acids 5 (IC) 1. TFA 2. PFPA 3. FIFBA 4. NFPA Elemental Analysis6: 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine White Crystalline Powder 1. Theoretical Value = 17.8% 2. Theoretical Value = 0% 3. Theoretical Value = 0% 4. Theoretical Value = 5.95% 5. Theoretical Value = 60% Conforms Positive 1. 0.005 wt.Avt.% 2. 0.001 wt.Avt.% 3. 1.439 wt.Avt.% 4. 6.849 wt.Avt.% 5. <0.001 wt.Avt.% 6. 0.005 wt.Avt.% 7. <0.001 wt.Avt.% 1.93 wt.Avt.% 8.41 wt.Avt.% None Detected 0.33 wt.Avt.% None Detected Not Applicable3 1. <0.015 wt.Avt.% 2. 0.59 wt.Avt.% 3. <0.040 wt.Avt.% 4. <0.009 wt.Avt.% 5. <0.006 wt.Avt.% 6. <0.007 wt.Avt.% 7. 8.76 wt.Avt.% 1. <0.1 wt.Avt.% 2. <0.1 wt.Avt.% 3. 0.10 wt.Avt.% 4. 0.28 wt.Avt.% 1. 12.48 wt.Avt.% 2. 0.244 wt.Avt.% 3. 1.74 wt.Avt.% 4. 8.84 wt.Avt.% 5. 54.1 wt.Avt.% COA023-018A Page 1 of 3 1083 Covance 6329-223 3M T-6295.7 IN TER IM CERTIFICATE OF ANALYSIS Centre Analytical Laboratories COA Reference #: 023-018A Date of Last Analysis: 08/31/00 Expiration Date: 08/31/01 Storage Conditions: Frozen <-10C Re-assessment Date: 08/31/01 'Purity = 100% - (sum of metal impurities, 1.45% +LC/MS impurities, 8.41%+Inorganic Fluoride, 0.59%+NMR impurities, 1.93%+organic acid impurities, 0.38%+POAA, 0.33%) Total impurity from all tests = 13.09% Purity = 100% - 13.09% = 86.9% 2Potassium is expected in this salt form and is therefore not considered an impurity. 3Purity by DSC is generally not applicable to materials of low purity. No endotherm was observed for this sample. 4Sulfur in the sample appears to be converted to SO4 and hence detected using the inorganic anion method conditions. The anion result agrees well with the sulfur determination in the elemental analysis, lending confidence to this interpretation. Based on the results, the SO4 is not considered an impurity. 5TFA HFBA NFPA PFPA Trifluoroacetic acid Heptafluorobutyric acid Nonofluoropentanoic acid Pentafluoropropanoic acid 6Theoretical value calculations based on the empirical formula, CgFnSCVfG (MW=538) This work was conducted under EPA Good Laboratory Practice Standards (40 CFR 160). C O A 023-018A 1084 Page 2 of 3 Covance 6329-223 3M T-6295.7 1085 Covance 6329-223 3M T-6295.7 Sponsor Protocol No.: FACT-TCR001 Centre Study No.: 023-018 QUALITY ASSURANCE STATEMENT Centre Study Number 023-018, entitled, "Characterization Study of PFOS, Lot 217 and Lot 171" was reviewed by Centre Analytical Laboratories' Quality Assurance Unit. All reviewed phases were reviewed for conduct according to Centre Analytical Laboratories' Standard Operating Procedures, the Study Protocol, and all applicable Good Laboratory Practice Standards. All findings were reported to the Study Director and to management. Phase Date Inspected Date Reported to Study Director and Date Reported to Centre Management Sponsor Management 1. Protocol Review 5/19/00 5/19/00 7/14/00 2. Label Checks (solubility) 7/14/00 7/17/00 Pending 3. Standard Solution Preparation and analysis by instrumentation 6/20,21/00 6/22/00 6/22/00 6/22/00 7/14/00 7/14/00 4. Raw Data Review 7/11-13/00 (NMR) 7/15/00 Pending 5. Standard Solution Preparation (Solubility) 7/14/00 7/20/00 Pending 6. Standard Solution 6/29, 30/00 Preparation 7/26/00 6/30/00 7/27/00 7/14/00 Pending 7. Report Review (DSC/TGA) 8/8/00 8/8/00 Pending 8. Data Review and 8/8,9/00 Interim Report Review 8/9/00 Pending 1086