Document npGr6jRb7ORkQb2B6GawZOM32

T herIm m u n e Research Corporation Sponsor: 3M Corporate Toxicology Building 220-2E-02, 3M Center St. Paul, MN 55144-1000 FINAL REPORT Study Title: Cell Proliferation Study with N-Ethyl Perfluorooctanesulfonamido Ethanol (N-EtFOSE; 3M T-6316.11), Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; 3M T-6295.16), and N-Ethyl Perfluoroctanesulfonamide (PFOSA 3M T-7091.1) in Rats Test Articles: N-EtFOSE PFOS PFOSA Authors: Gary W. Wolfe, Ph.D., D.A.B.T. Kimberly A. Layton, B.S. Study Completion Date: May 2, 2000 Performing Laboratory: TherImmune Research Corporation 15 Firstfield Road Gaithersburg, MD 20878 TRC Study Number: N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 TABLE OF CONTENTS COMPLIANCE STATEMENT ..................................................................................................................................4 STUDY IDENTIFICATION .......................................................................................................................................5 STUDY PERSONNEL.................................................................................................................................................6 S U M M A R Y .................................................................................................................................................................. 7 INTRODUCTION........................................................................................................................................................ 9 TEST AND CONTROL ARTICLES.......................................................................................................................... 9 TEST ANIMALS AND HUSBANDRY....................................................................................................................10 METHODS ................................................................................................................................................................ 11 Group Assignment and Dose Levels............................................................................................................ 11 Test Article Formulation and Administration............................................................................................. 11 Observations and R eco rd s............................................................................................ 12 Clinical Chemistry and Compound Level A nalysis................................................................................... 13 Term ination................................................................................................................................................. 13 Organ Weights ............................................................................................................................................ 14 Cell Proliferation Tissue Collection and Immunohistochemical Evaluation 14 Palmitoyl-CoA Oxidase Tissue Collection and Analyses ......................................................................... 14 Tissue Collection for Electron Microscopic E valuation............................................................................14 Remaining Liver Tissue ............................................................................................................................. 15 Histopathology ............................................................................................................................................ 15 Record Retention..........................................................................................................................................15 R E SU L T S...................................................................................................................................................................16 Body Weights and Body Weight Gains .................................................................................................... 16 Feed Consumption....................................................................................................................................... 16 Test Material Consum ption........................................................................................................................ 16 Clinical Observations.................................................................................................................................. 17 Terminal Body Weights and Liver W eights............................................................................................... 17 SIGNATURE PAGE ................................................................................................................................................. 19 TABLES 1- SUMMARY OF BODY WEIGHTS (Grams)..............................................................................20 1A - SUMMARY OF BODY WEIGHT GAINS (Grains) ................................................................. 22 2 - SUMMARY OF FEED CONSUMPTION (Grams) ................................................................. 23 3 - SUMMARY OF CLINICAL OBSERVATIONS ...................................................................... 25 3M Corporate Toxicology 2 N-EtFOSE, PFOS, PFQSA TRC No. 1132-100 TABLES (Continued) TABLE OF CONTENTS (contd.) 4 - SUMMARY OF TEST MATERIAL CONSUMPTION (ppm) ................................................28 5 - SUMMARY OF ABSOLUTE LIVER WEIGHTS (Grams) AND ORGAN TO BODY WEIGHT R A TIO S......................................................................................................................30 APPENDIX TABLES 1 - MALES: INDIVIDUAL BODY WEIGHTS (G ram s)...................................................................32 1A 234- INDIVIDUAL BODY WEIGHT GAINS (G ram s)........................................................................35 INDIVIDUAL FEED CONSUMPTION (G ram s)........................................................................37 INDIVIDUAL CLINICAL OBSERVATIONS.............................................................................40 INDIVIDUAL TEST MATERIAL CONSUMPTION (p p m )...................................................... 55 5 - INDIVIDUAL ABSOLUTE LIVER WEIGHTS (Grams) AND ORGAN TO BODY WEIGHT R A TIO S......................................................................................................................58 3M Corporate Toxicology 3 N-EtFOSE, PFQS, PFOSA TRC No. 1132-100 COMPLIANCE STATEMENT Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats This study was conducted in the spirit of the Good Laboratory Practice Regulations as set forth in Title 21 of the U.S. Code of Federal Regulations Part 58, issued December 22, 1978 (effective June 20, 1979) and was not reviewed by Quality Assurance. There were no deviations from the aforementioned regulations which affected the quality or integrity of the study or the interpretation of the results in the report. Study Director: 1 / 0 ` I aJ ^zk bife, Ph.DJD.A.B.T./Date 3M Corporate Toxicology 4 D C N-EtFOSE, PFQS, PFOSA_________________________________ TRC No. 1132-100 C STUDY IDENTIFICATION Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats D TRC Study Number: 1132-100 0 Test Articles: D 0 Sponsor: D 0r-) Sponsor's Representative: in_1 D Study Director: 0 LnJ p Study Monitor/Principal Investigator: D Study Timetable Study Initiation: ri-- Initiation of Dosing: 48-Hour Post-Dose Sacrifice: Dr--. 7-Day Post-Dose Sacrifice: 14-Day Post-Dose Sacrifice: 1-Week Recovery D 4-Week Recovery Study Termination: C 3M Corporate Toxicology D C N-Ethyl Perfluorooctanesulfonamido Ethanol (N-EtFOSE) Perfluorooctane Sulfonic Acid Potassium Salt (PFOS) N-Ethyl Perfluoroctanesulfonamide (PFOSA) 3M Corporate Toxicology Building 220-2E-02, 3M Center St. Paul, MN 55144-1000 Marvin T. Case, D.V.M ., Ph.D. 3M Corporate Toxicology St. Paul, MN 55144-1000 Phone: 651-733-5180 Fax: 651-733-1773 Gary W. Wolfe, Ph.D., D.A.B.T. Therlmmune Research Corporation 15 Firstfield Road Gaithersburg, MD 20878 Phone: 301-330-3723 Sandra R. Eldridge, Ph.D. Pathology Associates International Phone: 301-663-2036 January 12, 1999 February 23, 1999 February 25, 1999 March 2, 1999 March 9, 1999 March 16, 1999 April 6, 1999 April 6, 1999 5 i ; N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 STUDY PERSONNEL Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats Study Director: Gary W. Wolfe, Ph.D., D.A.B.T. Study Pathologist: Carolyn Moyer, D.V.M., A.C.V.P. Veterinarian: Edward T. Greenstein, D.V .M ., A.C.L.A.M. Quality Assurance Director: E. Paige Lacy, B.S. Health and Safety Officer/ Facility Manager Robert K. Blackford, A.A., LATG Technical Supervisor: Patrick Benson, B.S., LATG Report Supervisor: Lori B. Kaiser, B.S. Technical Writer/Project Leader: Kimberly A. Layton, B.S. Laboratory Head Technician: Paula Davis, B.S./Sharron Stewart Technicians: Daniel A. Jack Kelly Musselman, B.S. Brett Chaney, B.S., LATG Felecia Bishop, A.A., LATG Francis Onwuemene Larissa Nehrebeckyj, B.S. JoAnn Murphy Paul Martin, B.S. 3M Corporate Toxicology 6 N-EtFOSE, PFOS, PFOSA SUMMARY TRC No. 1132-100 This study was designed to assess cell proliferation and peroxisome proliferation in rats administered N-Ethyl Perfluorooctanesulfonamido, Perfluorooctane Sulfonic Acid Potassium Salt, N-Ethyl Perfluoroctanesulfonamide and Wy-14,643 in the diet. Animals in Groups 1, 2, and 3 received the test articles in the feed for 48 hours, 7 days, and 14 days, respectively, and were necropsied immediately following completion of exposure. Animals in Groups 4 and 5 received the test articles in the feed for 14 days followed by a 1-week and 4- week recovery period, respectively, and were necropsied following the recovery period. All Groups were divided into Subgroups. Subgroups 1, 2, 3, 4, 5, 6, and 7 received 0, 300, 100, and 30 ppm of N-EtFOSE, 20 ppm of PFOS, 100 ppm of PFOSA, and 100 ppm Wy 14,643 respectively. In Group 1, each Subgroup contained 10 animals with the exception of Subgroup 7 with only 5 animals. In Groups 2, 3, 4, and 5, Subgroup 1 contained 10 animals and received the control diet. The remaining Subgroups contained 5 animals each. Criteria evaluated for test article effect included mean body weights and body weight gains, feed and test material consumption, clinical observations, clinical pathology, organ weights, gross pathology, histopathology, cell proliferation, immunohistochemistry, palmitoyl-CoA oxidase activity, and electron microscopy. There were no treatment related findings for feed consumption, test material consumption, and clinical observations. However, there were treatment-related effects found in the mean body weights and mean body weight gains of the recovery animals. There were decreases seen in mean body weights on Study Day (SD) 15 for the 1-week recovery animals in the 300 ppm N-EtFOSE, PFOSA, and Wy-14,643 groups. In addition, there were decreases seen in mean body weight gains on SD 8-15 for the 1-week recovery animals in the 300 and 100 ppm N-EtFOSE, PFOSA, and Wy-14,643 groups and for the 4-week recovery animals on SD 8-15 in the 300 ppm NEtFOSE group and on SD 22-29 in the 30 ppm N-EtFOSE group. Treatment related findings were also seen in absolute and relative (g liver weight/g body weight) liver weights. Increases were seen in the absolute liver weights of the 48-hour post dose sacrifice animals in the 100 ppm N-EtFOSE and 100 ppm Wy-14 , 643 groups and an increase in 3M Corporate Toxicology 7 N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 the relative liver weight in the 100 ppm Wy-14,643 group. For the 7-day post-dose sacrifice animals, absolute liver weights were increased in the 100 ppm PFOSA and 100 ppm Wy-14,643 groups and relative organ weights were increased in the 300 ppm N-EtFOSE, 100 ppm PFOSA, and 100 ppm Wy-14,643 groups. Absolute and relative liver weights o f the 14-Day post-dose sacrifice animals were increased in the 300 ppm N-EtFOSE (relative only), 100 ppm PFOSA, and 100 ppm Wy-14,643 groups. Terminal body weights of the one week recovery animals were decreased in the 300 ppm N-EtFOSE, 100 ppm PFOSA, and 100 ppm Wy-14,643 groups. Absolute liver weights were increased in the 300 ppm N-EtFOSE group of these animals. Also, relative liver weights were increased in the 300 ppm N-EtFOSE, 100 ppm PFOSA, and 100 ppm Wy-14,643 groups. In addition, absolute and relative liver weights of the four week recovery animals were increased in the 300 ppm N-EtFOSE and 100 ppm PFOSA (relative only) groups. Results of clinical pathology, histopathology, cell proliferation, immunohistochemistry, palmitoyl-CoA oxidase activity, and electron microscopy will be reported separately. 3M Corporate Toxicology 8 N-EtFOSE, PFOS, PFOSA________________________ INTRODUCTION TRC No. 1132-100 This study was designed to assess cell proliferation and peroxisome proliferation in rats administered N-EtFOSE, PFOS, PFOSA and Wy-14,643. The design of this study included 5 groups of animals. Each Group contained 7 Subgroups. Subgroups 1, 2, 3, 4, 5, 6, and 7 received the following: Control (0 ppm), N-EtFOSE (300 ppm, 100 ppm, 30 ppm), PFOS (20 ppm), PFOSA (100 ppm) and Wy-14,643 (1000 ppm), respectively. Dosing was initiated on February 23, 1999 for all groups. Groups 1, 2, and 3 each received the test diets for 48 hours, 7 days, and 14 days, respectively and interim necropsies occurred on February 25, March 1, and March 8, 1999, respectively. Groups 4 and 5 received the same test diets for 14 days and terminal necropsies occurred after a 1 and 4-week recovery period on March 16 and April 6, 1999, respectively. In Group 1, the test diets were administered to 10 animals/Subgroup with the exception of Subgroup 7 with 5 animals. In Groups 2, 3 ,4 , and 5, the test diets were administered to 5 animals/Subgroup, with the exception of Subgroup 1 with 10 animals which received the control diet. TEST AND CONTROL ARTICLES One 34.88 g sample of N-EtFOSE T-6316 (Lot No. 30035, 30037, and 30039 combined), a waxy solid, was received from Covance Laboratories, Inc., Madison, WI, on December 31, 1998 and stored at ambient temperature. The purity was 98.1% and was stable for greater than 5 years. One 81.97 g sample of Fxl2 Fluorad T-7091 (PFOSA) (Lot No. not provided), an amber waxy solid, and one 97.13 g sample of FC-95 Fluorad T6295 (PFOS) (Lot No. Not provided), a white powder, were received from 3M, St. Paul, MN, on December 31, 1998 and stored at ambient temperature. Both test articles had a purity assumed to be 100 % and were both stable for greater than 5 years. A 1 gram sample of Wy-14,643 (Lot No. 11990d), a white powder, was received from Cayman Chemical, Ann Arbor, MI, on February 22, 1999 and stored at ambient temperature. The purity was greater than 98% and was stable for at least two years. 3M Corporate Toxicology 9 N-EtFOSE, PFQS, PFOSA TRC No. 1132-100 A reserve sample of each lot was taken and stored at ambient temperature. These samples were transferred to the Sponsor after the completion of the in-life phase. Any remaining test material will be returned to the Sponsor's representative. TEST ANIMALS AND HUSBANDRY Rats were used because of the extensive historical data base, and FDA requirements for a rodent species. Two hundred forty-eight male approximately five weeks old Crl:CD(SD) IGS BR rats were received from Charles River Laboratories, Raleigh, North Carolina on February 9, 1999. The animals were assigned temporary animal numbers upon receipt. The rats were acclimated to laboratory conditions for thirteen days prior to initiation of treatment. Each rat was identified by an ear tag and cage card bearing a unique animal number. Animals were housed one per cage from receipt to termination. During the study, all animals were housed in stainless steel suspended wire cages on stainless-steel racks equipped with plastic backed polyliners. Animals were provided with filtered tap water ad libitum via an Edstrom automatic watering system or water bottle. TekladTM 7012 Certified Rodent diet was available ad libitum in glass jars with stainless steel lids and followers. Fresh food was provided weekly. The water is analyzed at least two times per year for contaminants and specific microbes. The feed is analyzed by the manufacturer for concentrations of specified heavy metals, aflatoxin, chlorinated hydrocarbons, organophosphates, and specified nutrients. The results of the feed and water analyses are on file at Therlmmune Research Corporation. No contaminants were known to be present in the diet or water at levels which might interfere with achieving the objectives of the study. During the study period, the temperature and relative humidity of the study room were recorded twice daily. In addition, the animal room temperature and humidity were continuously monitored by a ReesTM Scientific Monitoring System. The animal room was set to maintain temperatures at 64 and 79F and relative humidity between 30% and 70%. A 12-hour light/12hour dark cycle was maintained through the acclimation and study periods. 3M Corporate Toxicology 10 N-EtFOSE, PFOS, PFOSA METHODS TRC No. 1132-100 j ! Group Assignment and Dose Levels Following examination by a staff veterinarian for physical condition, the rats were assigned to the study: Number of Male Rats Group Number Control | (Time Point) (0 ppm) . Subgroup...... (48 Hours) (7 Days) ell 10 10 3 (14 Days) 10 N-EtFOSE 300 ppm III 10 100 ppm ;3* 10 30 ppm !: 1 ! 10 5 55 5 55 PFOS (20 ppm) 5 10 5 5 PFOSA Wy-14,643 Total No. 1 (100 ppm) (1000 ppm) of Animals 6........ ill | 10 5 65 5 5 40 5 5 40 4 (1 wk recovery) 5 j ( 4 wk recovery) I Total No. Of 10 10 50 5 5 30 55 55 30 30 5 5 30 5 5 30 5 40 5 40 I25 225 Computer-generated random numbers were used for assignment to groups. At the time of randomization, the weight variation of the animals used did not exceed 2 S.D. of the mean weight, and the mean body weights for each group and sex were not statistically different. The body weights at initiation of treatment ranged from 175.2 g to 271.1 g. Extra animals were removed and discarded without necropsy. Test Article Formulation and Administration Dietary formulations of the test articles and Teklad 7012C Feed were prepared using the following procedure: For Group 1, the appropriate amount of feed was weighed into a plastic container and stored at ambient temperature and protected from light. For each dose level, the appropriate 3M Corporate Toxicology 11 N-EtFOSE, PFQS. PFOSA TRC No. 1132-100 quantity of Teklad 7012C feed was accurately weighed into plastic containers. The proper amount of the test article was weighed, using a stainless steel spatula, into a glass beaker. The appropriate amount of acetone was added to allow the test material to go into solution. A dietary premix was prepared for each dose level of each test article by adding the appropriate amount of feed with the test article with a stainless steel spatula until no feed/chemical agglomerates remained. Additional feed was added in increments that approximately doubled the amount of premix until an adequate premix was achieved. Following each addition, the formulation was mixed throughly with a stainless steel spatula. When the test article/feed mix was transferred from one container to other, the container was rinsed at least three times with premix feed. All feed used for rinsing and preparing the premix was taken from the preweighed feed in the plastic containers for each dose level. From the preweighed feed, 10 kilograms was layered evenly into the Patterson-Kelly Blender. The premix was then poured in equal amounts into the right and left blender ports and spread evenly. The premix container was then rinsed three times with the vehicle, from the preweighed feed. Each rinse was poured evenly into the blender. The remaining preweighed feed was evenly poured into the blender. The blender was sealed and the dietary formulation was blended for approximately 30 minutes. Dietary formulations were stored in sealed plastic containers and were stable for 21 days at room temperature. The formulations were dispensed into glass jars with stainless steel followers and lids. Diets were prepared for the entire study in one Mix. Two 100 g samples of each batch (per mix) of each dose level of the test article formulation and stored were stored in heat sealable foil bags protected from light at room temperature. At the request of the Sponsor, samples will be returned for analysis. Unless used for analysis, samples will be discarded at least one month after the completion of the in-life phase. Observations and Records Each animal was observed twice daily (a.m. and p.m.) for mortality and moribundity. Findings were recorded as they were observed. 3M Corporate Toxicology 12 N-EtFOSE, PFQS, PFOSA TRC No. 1132-100 Individual body weights and physical examinations were recorded prior to treatment (at randomization (physical examinations not reported) and weekly for Week 1 through 4 weeks of recovery, starting on Study Day (SD) 1. Body weights and physical examinations were also recorded prior to SD 1 and not used or reported because of a delay in the start of the study. Food consumption was measured weekly for Week 1 through 4 weeks of recovery, starting on SD 1. Clinical Chemistry and Compound Level Analysis Samples were taken for clinical chemistry evaluation and compound level analysis from all animals immediately prior to scheduled sacrifices. Blood was collected from the jugular vein into a serum-separator tube. Serum enzyme levels of alanine aminotransferase (ALT), alkaline phosphatase, asparatate aminotransferase (AST), cholesterol and triglycerides were determined. Serum samples for clinical chemistry were sent to PAI in Chevy Chase, MD for analysis. Serum sample for compound level analysis are being stored in a freezer at approximately -80 C until shipped to Dr. Kris J. Hansen, 3M E.T. & S., St. Paul, MN. The results will be reported separately. Termination Interim sacrifices were conducted after 48 hours, 7 days, and 14 days o f exposure to the test diets, following blood collection. The animals scheduled for interim sacrifices were anesthetized with C 02, weighed, and exsanguinated. The abdominal cavity o f each animal was opened, the liver removed, weighed and liver samples collected. The animals were discarded after liver collection. Terminal necropsies were conducted, following blood collection, on animals scheduled for 1 and 4 week recovery after 14 days of exposure to the test diets. The animals were anesthetized with C 02, weighed, exsanguinated, and necropsied. Necropsies included examination of the external features of the carcass, all external body orifices, and the cranial, thoracic, and abdominal cavities, organs and tissues. In addition, the liver was removed, weighed and liver samples collected. 3M Corporate Toxicology 13 N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 Organ Weights The liver was weighed for all surviving scheduled necropsy animals. Cell Proliferation Tissue Collection and Immunohistochemical Evaluation Representative samples of the left lateral lobe of the liver and any microscopic lesions of the liver were collected and preserved in formalin. After fixation, the samples were delivered to Dr. Sandra Eldridge at Pathology Associates International, Frederick, MD. Proliferation cell nuclear antigen (PNCA) evaluation was performed on the samples. In addition, liver sections prepared from the same tissue block were stained with hematoxylin and eosin and examined microscopically. The results will be reported separately. Palmitovl-CoA Oxidase Tissue Collection and Analyses A sample (approximately 500 mg) of the right lateral lobe of the liver was also collected from select animals and flash-frozen in liquid nitrogen. The liver tissue was stored frozen at approximately -80 C until they were shipped on dry ice to Dr. Ron Markevitch, Covance Laboratories, Madison, WI for palmitoyl-CoA Oxidase activity. The liver samples analyzed included all study animals, with the exception of the Wy-14,643 animals and the 4-week recovery Group. The results will be reported separately. Tissue Collection for Electron Microscopic Evaluation Sections of the left lateral lobe of the liver from all animals were collected, minced to approximately one millimeter cubes and placed in a fixative appropriate for electron microscopy. The containers and fixative were provided by PAI, Frederick, MD. Samples were shipped to Sharon Ambrose, Pathology Associates International, Durham, NC. Electron microscopy was performed on one animal per treatment group exhibiting the highest cell proliferative response as well as one control animal at the discretion of the Sponsor, from one time point as well as the 4week recovery. Thus, EM will be performed on one animal from the control, N-EtFOSE (one dose only to be determined), PFOS, PFOSA, and the Wy-14,643 Subgroups at one of the time 3M Corporate Toxicology 14 N-EtFOSE, PFQS, PFOSA TRC No. 1132-100 points, as well as the 4-week recovery, for a total of ten animals. The results will be reported separately. Remaining Liver Tissue The remaining liver tissue was frozen and stored at approximately -80C at Pathology Associates International, Frederick, MD in the long-term archive for possible future analysis. Histopathology Livers from each animal that was examined for cell proliferation were stained with hematoxylin and eosin, and examined microscopically for histopathological changes. The results will be reported separately. Record Retention All raw data, documentation, records, protocol, specimens, and final report generated as a result of this study will be archived in the storage facilities of PAI for a period of one 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. All raw data stored on magnetic media will remain at PAI. 3M Corporate Toxicology 15 N-EtFOSE, PFOS, PFOSA____________________ TRC No. 1132-100 RESULTS Body Weights and Body Weight Gains Mean body weights are summarized in Table 1 and presented individually in Appendix Table 1. Mean body weight gains are summarized in Table 1A and presented individually in Appendix 1A. Mean body weights and body weight gains were comparable in all groups throughout the study with the exception of the 1-Week recovery animals on SD 15. There was a 14, 8, and 12% decrease in mean body weights in the 300 ppm N-EtFOSE, PFOSA, and Wy-14,643 groups, respectively. Mean body weight gains were decreased by 62, 32, 36, and 35 % in the 300 and 100 ppm N-EtFOSE, PFOSA, and Wy-14,643 groups, respectively on SD 8-15. In addition, mean body weight gains were decreased in the 4-Week recovery animals by 40% in the 300 ppm N-EtFOSE group on SD 8-15 and by 38% in the 30 ppm N-EtFOSE group on SD 22-29. Feed Consumption Mean feed consumption is summarized in Table 2 and presented individually in Appendix Table 2. Mean feed consumption was comparable in all groups with the exception of decreases of 16 % in the 14-Day PFOSA group animals on SD 14 and 20 % and 14 % in the 1-Week recovery 30 ppm N-EtFOSE and PFOSA groups, respectively on SD 15. Test Material Consumption Mean test material consumption is summarized in Table 4 and presented individually in Appendix Table 4. Test article consumption averaged 31.6 mg/kg for 300 ppm N-EtFOSE, 11.1 mg/kg for 100 ppm N-EtFOSE, 3.3 ppm for 30 ppm N-EtFOSE, 2.2 mg/kg for PFOS, 10.8 mg/kg for PFOSA, and 10.9 mg/kg for Wy-14,643. 3M Corporate Toxicology 16 N-EtFOSE, FFQS, PFOSA TRC No. 1132-100 Clinical Observations Clinical observations are summarized in Table 3, and presented individually in Appendix Table 3. No treatment-related clinical observations were noted, however the following clinical observations were seen during SD 2-15 in most of the Groups: thinness, abrasions, alopecia, rough haircoat, lacrimation, soft feces, and diarrhea. One 48-Hour PFOSA animal had paraphimosis on SD 3. One 1-Week recovery control animal was moribund killed due to a dislocated nasal bone on SD 21. Terminal Body Weights and Liver Weights Terminal body weights and absolute and relative liver weights are summarized in Table 5, and presented individually in Appendix Table 5. Terminal body weights of the 48-hour, 7-day, and 14-day post dose sacrifice and 4-week recovery animals were comparable to the controls. Decreases were seen in the terminal body weights in the 300 ppm N-EtFOSE (14%), 100 ppm PFOSA (9%), and 100 ppm Wy-14,643 (15%) groups of the 1-Week recovery animals. For the 48-hour post-dose animals, absolute liver weights were increased by 13 %and 27 % in the 100 ppm N-EtFOSE and 100 ppm Wy-14,643 groups, respectively. Relative liver weights were also increased by 22% in the 100 ppm Wy-14,643 group. The 100 ppm PFOSA and 100 ppm Wy-14,643 groups of the 7-day post dose animals had absolute liver weight increases of 20 % and 90%, respectively. Relative liver weights for these animals were increased in the 300 ppm N-EtFOSE (20%), 100 ppm PFOSA (16%), and 100 ppm Wy-14,643 (86%) groups. Increases were seen in the absolute liver weights in the 300 ppm N-EtFOSE (44%) and 100 ppm Wy-14,643 (104%) groups of the 14-day post dose sacrifice animals. Relative liver weights were increased 12-49% in the 30, 100, and 300 ppm N-EtFOSE groups, 22% in the 100 ppm PFOSA group and 114% in the 100 ppm Wy-14,643 group. Increases of 25% and 4 4 %were seen in the absolute and relative liver weights of the 1-Week recovery animals in the 300 ppm N-EtFOSE group. Relative liver weight increases of 23-25% were seen in the 100 ppm PFOSA and 100 ppm Wy-14,643 3M Corporate Toxicology 17 N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 groups. For the 4-Week recovery animals in the 300 ppm N-EtFOSE group, increases were seen in the absolute and relative liver weights of 34% and 29%, respectively. Relative liver weights were increased in the 100 ppm PFOSA group by 27%. Gross Observations No treatment-related'gross findings were seen. The following incidental findings were noted: an enlarged spleen in the 100 ppm WY-14,643 group of 1-week recovery animals, a mottled liver in the 20 ppm PFOS group, and a small right testis and focus on the left cauda epididymis in the 100 ppm Wy-14,643 group of the 4-week recovery animals. 3M Corporate Toxicology 18 N-EtFOSE, PFQS, PFOSA Study Director: SIGNATURE PAGE TRC No. 1132-100 Technical Writer: Report Supervisor: Lori B. Kaiser, B.S./Date 3M Corporate Toxicology 19 N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 TABLE 1 SUMMARY OF BODY WEIGHTS (Grams) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP: 1 (48-Hour Post Dose Sacrifice) DOSE: (1) (2) (3) (4) PERIOD SUBGROUP;: 1-M 2-M 3-M 4-M (5) 5-M DAY 1 MEAN S.D. N 231.4 15.84 10 229.1 16.30 10 243.0 9.08 10 230.0 10.76 10 233.0 15.13 10 (6) 6-M 235.1 21.52 10 STUDY: 1132-100 SEX: MALE PERIOD DOSE: SUBGROUP;: <1> 1-M DAY 1 MEAN S.D. 229.2 10.06 N 10 GROUP: 2 (7-Day Post Dose Sacrifice) (2) (3) (4) 2-M 3-M 4-M 228.4 13.74 5 244.8 12.06 5 227.1 10.09 5 (5) 5-M 229.9 5.75 5 (6) 6-M 242.6 15.37 5 STUDY: 1132-100 SEX: MALE DOSE: <1) PERIOD SUBGROUP : 1-M DAY 1 MEAN 229.0 S.D. 18.70 N 10 GROUP: 3 (14-Day Post Dose Sacrifice) (2) (3) (4) 2-M 3-M 4-M 241.0 26.37 5 224.9 15.78 5 230.5 14.12 5 (5) 5-M 227.8 12.98 5 (6) 6-M 222.0 12.44 5 DAY 8 MEAN S.D. N 273.7 13.71 10 286.3 27.35 5 276.2 15.55 5 286.3 10.79 5 276.9 12.31 5 261.6 10.43 5 STUDY: 1132-100 SEX: MALE PERIOD DOSE: SUBGROUP : 0) 1-M DAY 1 MEAN S.D. 234.8 11.72 N 10 GROUP: 4 <1 -Week Recovery) (2) (3) 2-M 3-M 223.5 15.66 5 230.7 13.49 5 (4) 4-M 237.0 12.19 5 (5) 5-M 227.6 9.90 5 (6) 6-M 232.8 11.18 5 DAY 8 MEAN S.D. N 281.9 23.79 10 261.0 9.12 5 279.2 14.93 5 279.5 10.22 5 279.1 11.95 5 277.8 8.68 5 DAY 15 MEAN S.D. N 344.7 23.28 10 *295.9 16.07 5 321.6 19.72 5 327.4 12.47 5 330.2 15.28 5 *317.8 10.88 5 * = P less than .05 Analysis of Variance using DUNNETT'S Procedure NOTE: Terminal body weights for all Groups were food-fasted weights and will be reported separately. (1> = Control 0 ppm (2) = N-EtFOSE 300 ppm (3> = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm <7) = Wy-14,643 100 ppm (7) 7-M 240.2 6.04 5 (7) 7-M 237.3 17.24 5 (7) 7-M 233.3 14.48 5 276.5 19.55 5 (7) 7-M 216.5 15.95 5 261.4 19.20 5 *302.4 19.57 5 3M Corporate Toxicology 20 0 c D C 0 0 D G D D D C D N-EtFOSE, PFOS, PFOSA STUDY : 1132-100 DOSE: PERIOD SUBGROUP: DAY 1 MEAN S.D. N TABLE 1(Continued) SUMMARY OF BODY WEIGHTS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats SEX: MALE (1) 1-M GROUP: 5 (4-Week Recovery) (2) (3) 2-M 3-M (4) 4-M (5) 5-M 232.4 16.93 10 239.7 7.52 5 229.7 7.60 5 234.0 8.87 5 230.7 14.41 5 DAY 8 MEAN S.D. N 278.0 24.62 10 273.1 10.13 5 270.5 5.10 5 284.0 14.47 5 283.1 17.94 5 DAY 15 MEAN S.D. N 332.9 27.44 10 305.9 9.64 5 312.8 11.07 5 331.0 30.35 5 333.5 20.67 5 TRC No. 1132-100 (6) 6-M 216.4 24.23 5 264.6 12.93 5 307.1 8.32 5 (7) 7-M 224.1 16.63 5 274.0 18.07 5 319.1 22.02 5 DAY 22 MEAN S.D. N 364.8 28.98 9 340.2 7.04 5 340.6 15.55 5 362.4 38.96 5 366.2 24.02 5 334.0 15.52 5 DAY 29 MEAN S.D. N 395.7 30.90 9 376.0 11.36 5 372.1 21.27 5 381.6 36.41 5 396.3 27.87 5 366.9 15.72 5 DAY 36 MEAN S.D. N 417.4 34.65 9 402.0 13.87 5 390.1 23.25 5 401.1 33.87 5 414.3 35.80 5 391.6 16.31 5 * P less than .05 Analysis of Variance using DUNNETT'S Procedure NOTE: Terminal body weights for all Groups were food-fasted weights and will be reported separately. (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Wy-14,643 100 ppm 342.2 25.79 5 377.2 31.93 5 404.1 35.66 5 D C 0 3M Corporate Toxicology D G 21 0 D D C D 0 C 0 D D G D C D D G D D N - E t F O S E , P F O S , PFOSA_________________________________________________ TABLE 1A SUMMARY OF BODY WEIGHT GAINS (Grams) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP: 3 (14-Day Post Dose Sacrifice) DOSE: (1) (2) (3) (4) PERIOD SUBGROUP 1-M 2-M 3-M 4-M (5) 5-M DAY 8 MEAN 44.7 45.2 51.3 * 55.8 49.1 S.D. N 8.03 10 1.58 5 5.44 5 9.23 5 8.29 5 TRC No. 1132-100 (6) 6-M 39.6 4.84 5 (7) 7-M 43.2 8.01 5 STUDY: 1132-100 SEX: MALE DOSE: CD PERIOD SUBGROUP 1-M DAY 8 MEAN 47.1 S.D. 13.98 N 10 GROUP: 4 <1- Week Recovery) (2) (3) 2-M 3-M 37.5 8.65 5 48.6 6.12 5 (4) 4-M 42.4 2.92 5 DAY 15 MEAN S.D. N STUDY: 1132-100 DOSE: PERIOD SUBGROUP: DAY 8 MEAN S.D. N 62.8 13.62 10 SEX: MALE (1) 1-M * 34.9 15.25 * 42.4 9.50 55 GROUP: 5 (4-Week Recovery) (2) (3) 2-M 3-M 45.5 13.67 10 33.4 5.79 5 40.7 6.19 5 47.9 3.43 5 (4) 4-M 50.0 8.34 5 DAY 15 MEAN S.D. N 54.9 7.26 10 * 32.8 3.60 5 42.3 11.83 5 47.1 16.86 5 (5) 5-M 51.5 4.78 5 51.1 7.96 5 (5) 5-M 52.3 4.26 5 50.4 8.13 5 (6) 6-M 45.0 9.06 5 * 39.9 4.39 5 (6) 6-M 48.2 14.43 5 42.6 6.70 5 (7) 7-M 44.9 3.99 5 * 41.0 8.06 5 (7) 7-M 49.9 6.54 5 45.1 6.88 5 DAY 22 DAY 29 DAY 36 MEAN S.D. N MEAN S.D. N MEAN S.D. N 29.1 5.40 9 30.9 5.27 9 21.7 5.45 9 34.3 5.44 5 35.8 5.45 5 26.1 5.80 5 27.9 6.01 5 31.5 6.49 5 18.0 11.13 5 31.4 9.52 5 * 19.1 8.87 5 19.5 2.62 5 32.7 4.63 5 30.1 5.03 5 18.0 8.93 5 26.8 11.61 5 32.9 6.00 5 24.8 5.17 5 23.1 8.45 5 35.0 7.87 5 26.9 7.06 5 * P less than .05 Analysis of Variance using DUNNETT'S Procedure Note: Animals in Groups 1(48 -Hour Post Dose Sacrifice) and 2(7-Day Post Dose Sacrifice) were not reported due to only one body weight taken and the terminal body weights being excluded due to food fasting. C D = Control 0 ppm <25 = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Uy-14,643 100 ppm 3M Corporate Toxicology 22 i N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 TABLE 2 SUMMARY OF FEED CONSUMPTION (Grams) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP: 1 (48-Hour Post Dose Sacrifice) DOSE: (1) (2) (3) (4) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M (5) 5-M DAY 2 MEAN S.D, N 22.9 2.86 10 26.1 2.00 10 26.7 3.64 10 25.0 2.18 10 23.9 3.81 10 STUDY: 1132-100 SEX: MALE PERIOD DOSE: (mg/kg) SUBGROUP: (1) 1-M DAY 7 MEAN 163.4 S.D. 12.65 N 10 GROUP: 2 (7-Day Post Dose Sacrifice) (2) (3) (4) 2-M 3-M 4-M 155.6 8.77 5 171.8 17.12 5 159.0 7.97 5 (5) 5-M 156.0 5.38 5 STUDY: 1132-100 SEX: MALE DOSE: (1) PERIOD SUBGROUP: 1-M DAY 8 MEAN 181.4 S.D. 10.78 N 10 GROUP: 3 C14-Day Post Dose Sacrifice) (2) (3) (4) 2-M 3-M 4-M 190.0 14.43 5 189.9 4.50 5 196.4 9.75 5 (5) 5-M 188.5 11.11 5 DAY 14 MEAN S.D. N 178.7 20.78 10 163.0 14.68 5 163.8 5.42 5 178.9 13.77 5 166.9 9.60 5 STUDY: 1132-100 SEX: MALE PERIOD DOSE: SUBGROUP: (1) 1-M DAY 8 MEAN S.D. 195.2 17.45 N 10 GROUP: 4 (1- Week Recovery) (2) (3) 2-M 3-M 174.5 12.37 5 194.6 10.37 5 (4) 4-M 190.4 11.29 5 (5) 5-M 191.0 6.19 5 DAY 15 MEAN S.D. N 212.8 21.73 10 *170.6 18.96 5 190.7 15.24 5 193.8 12.15 5 193.4 9.63 5 DAY 21 MEAN S.D. N * P less than .05 185.4 160.6 173.0 176.1 167.6 15.82 17.74 15.01 7.34 9.91 10 5 5 5 5 Analysis of Variance using DUNNETT'S Procedure Note = Feed consumption measured for 6 days on SD 7, 14, 21. Note = Control feed given to all Groups during the recovery period (SD 21-SD 42). (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Wy 14,643 100 ppm (6) 6-M 26.9 4.29 10 (6) 6-M 165.9 14.06 5 (6) 6-M 171.9 11.91 5 *150.4 11.64 5 (6) 6-M 187.6 5.85 5 *183.7 6.65 5 171.8 8.45 5 (7) 7-M 25.2 1.99 5 (7) 7-M 157.1 13.61 5 (7) 7-M 189.3 19.22 5 166.9 13.65 5 (7) 7-M 180.1 18.58 5 189.4 17.61 5 169.8 16.25 5 3M Corporate Toxicology 23 N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 TABLE 2 (Continued) SUMMARY OF FEED CONSUMPTION (Grains) __________________________ Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats___________________ STUDY: 1132-100 SEX: MALE GROUP: 5 (4-Week Recovery) DOSE: (1) (2) (3) (4) (5) (6) (7) ________ SUBGROUP:________1-M__________ 2-M__________ 3-M__________ 4-M__________ 5-M 6-M 7-M DAY 8 MEAN S.D. N 189.4 19.09 10 182.7 17.16 5 190.1 8.55 5 197.6 6.65 5 192.7 12.11 5 185.3 15.74 5 186.1 12.03 5 DAY 15 MEAN S.D. N 199.0 20.01 10 176.5 14.22 5 192.4 14.71 5 197.4 18.74 5 192.6 14.90 5 180.4 9.32 5 192.0 10.39 5 DAY 22 MEAN S.D. N 196.7 14.88 9 189.7 6.21 5 197.4 12.00 5 203.2 18.27 5 204.9 14.75 5 188.7 14.03 5 198.0 13.81 5 DAY 29 MEAN S.D. N 196.5 14.41 9 191.8 14.17 5 194.0 17.53 5 180.1 12.70 5 193.0 17.90 5 189.7 14.67 5 207.7 17.83 5 DAY 36 MEAN S.D. N 198.0 18.25 9 201.6 9.36 5 196.6 17.68 5 181.8 17.07 5 191.8 21.42 5 198.9 12.70 5 209.8 21.30 5 DAY 42 MEAN S.D. N 163.6 19.66 9 166.0 8.50 5 161.2 13.10 5 158.9 8.91 5 163.2 20.71 5 162.9 16.13 5 166.6 18.64 5 * P less than .05 Analysis of Variance using DUNNETT'S Procedure Note = Feed consumption measured for 6 days on SD 42. Note = Control feed given to alt Groups during the recovery period (SD 21 -SD 42). (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Wy-14,643 100 ppm 3M Corporate Toxicology 24 N-EtFOSE, PFOS, PFOSA TABLE 3 SUMMARY OF CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP: 1 (48- Hour IPost Dose Sacrifice) DOSE: <1) (2) (3) (4) (5) (6) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M DAY 1 No. Observed Normal Di scharge 10 10 100% 0 10 10 100% 0 10 9 90% 1 10% 10 10 100% 0 10 10 100% 0 10 10 100% 0 TRC No. 1132-100 (7) 7-M 5 5 100% 0 DAY 3 No. Observed Terminal Kill Normal Thin Alopecia Rough Haircoat Lacrimat ion Paraphimosis Soft Feces 10 10 100% 3 30% 7 70% 0 0 1 10% 0 1 10% 10 10 100% 6 60% 4 40% 0 0 0 0 0 10 10 100% 8 80% 2 20% 0 0 0 0 0 10 10 100% 6 60% 4 40% 0 1 10% 0 0 0 10 10 100% 4 40% 4 40% 0 0 0 1 10% 0 10 10 100% 8 80% 2 20% 0 0 0 0 0 5 5 100% 2 40% 2 40% 1 20% 0 0 0 1 20% STUDY: 1132-100 SEX: MALE PERIOD DOSE: SUBGROUP : (1) 1-M DAY 1 No. Observed Normal Lacrimation 10 10 100% 0 GROUP: 2 I[7-Day Post Dose Sacrifice) (2) (3) (4) (5) 2-M 3-M 4-M 5-M 5 5 100% 0 5 5 100% 0 5 5 100% 0 5 5 100% 0 (6) 6-M 5 4 80% 1 20% (7) 7-M 5 5 100% 0 DAY 8 No. Observed Terminal Kill Normal Thin 10 10 100% 9 90% 1 10% 5 5 100% 4 80% 1 20% 5 5 100% 5 100% 0 5 5 100% 4 80% 1 20% 5 5 100% 5 100% 0 5 5 100% 5 100% 0 5 5 100% 5 100% 0 STUDY: 1132-100 SEX: MALE PERIOD DOSE: SUBGROUP : CD 1-M DAY 1 No. Observed 10 Normal 10 100% GROUP: 3 (14-Day Post Dose Sacrifice) (2) (3) (4) (5) 2-M 3-M 4-M 5-M 5 5 100% 5 5 100% 5 5 100% 5 5 100% (6) 6-M 5 5 100% (7) 7-M 5 5 100% DAY 8 No. Observed Normal Soft Feces 10 9 90% 1 10% 5 5 100% 0 5 5 100% 0 5 5 100% 0 5 5 100% 0 5 5 100% 0 5 5 100% 0 DAY 15 No. Observed Terminal Kill Normal Thin Soft Feces 10 10 100% 9 90% 1 10% 0 5 5 100% 5 100% 0 0 5 5 100% 4 80% 1 20% 0 5 5 100% 5 100% 0 0 5 5 100% 4 80% 1 20% 1 20% 5 5 100% 3 60% 2 40% 0 5 5 100% 5 100% 0 0 (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Wy-14,643 100 ppm 3M Corporate Toxicology 25 N-EtFOSE. PFOS, PFOSA TRC No. 1132-100 TABLE 3 (continued) SUMMARY OF CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP : 4 (1-Week Recovery) PERIOD DOSE: SUBGROUP: (1) (2) (3) (4) (5) (6) 1-M 2-M 3-M 4-M 5-M 6-M DAY 1 No. Observed Normal 10 10 100% 5 5 100% 5 5 100% 5 5 100% 5 5 100% 5 5 100% DAY 8 No. Observed Normal Abrasion Lacrimation 10 10 100% 0 0 5 5 100% 0 0 5 5 100% 0 0 5 5 100% 0 0 5 4 80% 0 1 20% 5 4 80% 1 20% 0 DAY 15 No. Observed Normal Thin Abrasion Diarrhea 10 10 100% 0 0 0 5 3 60% 1 20% 0 1 20% 5 5 100% 0 0 0 5 5 100% 0 0 0 5 5 100% 0 0 0 5 4 80% 0 1 20% 0 DAY 22 No. Observed Terminal Kill Normal Thin Abrasion Lacrimation Diarrhea 10 10 100% 7 70% 1 10% 0 0 1 10% 5 5 100% 2 40% 3 60% 0 0 0 5 5 100% 4 80% 1 20% 0 0 0 5 5 100% 5 100% 0 0 0 0 5 5 100% 4 80% 0 0 1 20% 0 5 5 100% 4 80% 1 20% 0 0 0 STUDY : 1132-100 SEX: MALE GROUP : 5 (4-Week Recovery) DOSE: (1) (2) (3) (4) PERIOD SUBGROUP: 1 -M 2-M 3-M 4-M DAY 1 No. Observed 10 5 5 5 Normal 10 100% 5 100% 5 100% 5 100% (5) 5-M 5 5 100% (6) 6-M 5 5 100% DAY 8 No. Observed Normal Thin Abrasion Lacrimation 10 8 80% 0 1 10% 1 10% 5 5 100% 0 0 0 5 5 100% 0 0 0 5 5 100% 0 0 0 5 4 80% 1 20% 0 0 5 5 100% 0 0 0 DAY 15 No. Observed Normal Thin Abrasion Lacrimation (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (A) = N-EtFOSE 30 ppm (3) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Wy-14,643 100 ppm 10 9 90% 0 1 10% 0 5 5 100% 0 0 0 5 5 100% 0 0 0 5 4 80% 1 20% 0 0 5 2 40% 2 40% 0 1 20% 5 5 100% 0 0 0 (7) 7-M 5 5 100% 5 4 80% 1 20% 0 5 4 80% 0 1 20% 0 5 5 100% 2 40% 2 40% 1 20% 0 0 (7) 7-M 5 5 100% 5 4 80% 0 0 1 20% 5 5 100% 0 0 0 3M Corporate Toxicology 26 N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 TABLE 3 (continued) SUMMARY OF CLINICAL OBSERVATIONS STUDY: 1132-100 Celt Prolif--er--ation Stud.y1 with, N-E-t-F-OS-E,1 ,PFOS,' -an-d PFOSA in Rats SEX: MALE GROUP: 5 (4-Week Recovery) DOSE: (1) (2) (3) (4) (5) (6) SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M DAY 21 No. Observed 100 00 0 oo2 Moribund Kill 100 00 0 DAY 22 No. Observed Normal Thin Abrasion Alopecia Lacrimat ion 9 8 88% 0 1 11% 1 11% 0 5 5 100% 0 0 0 0 5 5 100% 0 0 0 0 5 5 100% 0 0 0 0 5 4 80% 0 0 0 1 20% 5 4 80% 1 20% 0 0 0 DAY 29 No. Observed Normal Thin Abrasion Alopecia Lacrimation 9 7 77% 0 2 22% 1 11% 0 5 5 100% 0 0 0 0 5 5 100% 0 0 0 0 5 2 40% 2 40% 0 0 1 20% 5 4 80% 0 0 0 1 20% 5 5 100% 0 0 0 0 DAY 36 No. Observed Normal Thin Reddened Abrasion Alopecia Lacrimai ion 9 6 66% 0 1 11% 2 22% 1 11% 0 5 5 100% 0 0 0 0 0 5 5 100% 0 0 0 0 0 5 3 60% 1 20% 0 0 0 1 20% 5 4 80% 0 0 0 1 20% 1 20% 5 5 100% 0 0 0 0 0 DAY 43 No. Observed Terminal Kill Normal Thin Abrasion Alopecia Lacrimai ion 9 9 100% 7 77% 0 1 11% 1 11% 0 5 5 100% 5 100% 0 0 0 0 5 5 100% 5 100% 0 0 0 0 5 5 100% 3 60% 1 20% 0 0 1 20% 5 5 100% 4 80% 0 0 1 20% 1 20% 5 5 100% 5 100% 0 0 0 0 (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Wy-14,643 100 ppm (7) 7-M 0 0 5 5 100% 0 0 0 0 5 5 100% 0 0 0 0 5 5 100% 0 0 0 0 0 5 5 100% 3 60% 2 40% 0 0 0 3M Corporate Toxicology 27 N-EtFOSE, PFOS, PFOSA TABLE 4 SUMMARY OF TEST MATERIAL CONSUMPTION (PPM) Cell Proliferation Study with N-EtFOSE. PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE DOSE: PERIOD SUBQROUP: GROUP: 1 (48-Hour Post Dose Sacrifice) (1) (2) (3) <4) 1-M 2-M 3-M 4-M (5) 5-M DAY 2 MEAN S.D. N 0.0 0.00 10 34.3 3.18 10 11.0 1.56 10 3.0 0.31 10 2.1 0.35 10 STUDY: 1132-100 SEX: MALE DOSE: PERIOD SUBGROUP: DAY 7 MEAN S.D. N GROUP: 2 (7-Day Post Dose Sacrifice) C D (2) (3) (4) 1-M 2-M 3-M 4-M 0.0 0.00 10 34.2 2.85 5 11.7 0.90 5 3.5 0.13 5 (5) 5-M 2.2 0.09 5 STUDY: 1132-100 SEX: MALE DOSE: PERIOD SUBGROUP: DAY 8 MEAN S.D. N GROUP: 3 (14-Day Post Dose Sacrifice) 0 ) (2) (3) (4) 1-M 2-M 3-M 4-M 0.0 0.00 10 33.9 2.36 5 12.1 0.79 5 3.7 0.28 5 (5) 5-M 2.3 0.04 5 DAY 14 MEAN S.D. N 0.0 0.00 10 28.5 0.85 5 9.9 0.65 5 3.1 0.27 5 2.0 0.08 5 STUDY: 1132-100 SEX: MALE DOSE: PERIOD SUBGROUP: DAY 8 MEAN S.D. N GROUP: 4 (1-Week Recovery) (1) (2) (3) 1-M 2-M 3-M 0.0 0.00 10 33.6 3.60 5 12.1 0.68 5 (4) 4-M 3.4 0.09 5 (5) 5-M 2.4 0.16 5 DAY 15 MEAN S.D. N 0.0 0.00 10 28.0 3.28 5 9.8 0.53 5 3.0 0.09 5 2.0 0.11 5 (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Uy 14,643 100 ppm TRC Wo. 1152-100 (6) 6-M 11.4 1.69 10 (6) 6-M 11.4 0.55 5 (6) 6-M 11.1 0.58 5 9.6 0.55 5 (6) 6-M 11.5 0.65 5 9.4 0.22 5 (7) 7-M 10.5 1.01 5 (7) 7-M 11.1 0.08 5 (7) 7-M 11.6 0.55 5 10.0 0.19 5 (7) 7-M 11.9 0.55 5 10.3 0.38 5 3K Corporate Toxicology 28 N-EtFOSE, PFOS, PFOSA TABLE 4 (Continued) SUMMARY OF TEST MATERIAL CONSUMPTION (PPM) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP: 5 (4 Week Recovery Animals) DOSE: (1) (2) (3) (4) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M (5) 5-M DAY 8 DAY 15 MEAN S.D. N MEAN S.D. N 0.0 0.00 10 0.0 0.00 10 32.7 3.22 5 27.7 1.79 5 11.8 0.88 5 10.2 0.88 5 3.6 0.15 5 3.0 0.15 5 2.3 0.05 5 2.0 0.11 5 (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (6) = PFOSA 100 ppm (7) = Wy 14,643 100 ppm TRC No. 1132-100 (6) 6-M 12.4 1.96 5 9.8 0.55 5 (7) 7-M 11.8 0.35 5 10.0 0.48 5 3M Corporate Toxicology 29 LJ D D n L p L nu p L_ P l_ n._. D D r~ r-- u P L 0 G p u n LJ PL - cc N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 STUDY: 1132-100 DOSE: SUBGROUP: TABLE 5 SUMMARY OF ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO BODY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats SEX: MALE GROUP: 1 (48-Hour Post Dose Sacrifice) (1) C2) (3) (4) (5) (6) 1-M 2-M 3-M 4-M 5-M 6-M (7) 7-M BODY WEIGHT (G) MEAN S.D. N 207.6 13.59 10 208.7 16.57 10 221.1 8.72 10 207.9 9.22 10 208.9 13.37 10 213.7 20.61 10 217.2 6.30 5 Liver (GKABSOLUTE) MEAN S.D. N 7.514 0.6364 10 7.878 0.8943 10 * 8.515 0.5893 10 7.788 0.5117 10 7.748 0.7929 10 7.982 0.9430 10 * 9.555 0.4102 5 Liver (% BODY WEIGHT) MEAN S.D. N 3.620 0.1979 10 3.769 0.2273 10 3.850 0.1845 10 3.749 0.2424 10 3.703 0.2152 10 3.731 0.1968 10 * 4.400 0.1559 5 STUDY: 1132-100 DOSE: SUBGROUP: SEX: MALE GROUP: 2 (7-Day Post Dose Sacrifice) (1) (2) (3) (4) 1-M 2-M 3-M 4-M BOOY WEIGHT (G) MEAN S.D. N 248.1 14.52 10 235.1 12.65 5 258.6 17.66 5 244.2 12.86 5 Liver (GKABSOLUTE) MEAN S.D. N 8.475 0.9646 10 9.642 0.7004 5 9.665 0.8252 5 8.541 0.7364 5 Liver <% BODY WEIGHT) MEAN S.D. N 3.409 0.2353 10 * 4.105 0.2972 5 3.740 0.2463 5 3.496 0.2157 5 (5) (6) (7) 5-M 6-M 7-M 243.4 9.94 5 257.5 18.54 5 253.6 17.88 5 8.830 0.3776 5 * 10.193 1.2284 5 * 16.087 1.2524 5 3.630 0.1349 5 * 3.949 0.2018 5 * 6.349 0.3791 5 STUDY: 1132-100 SEX: MALE GROUP: 3 (14-Day Post Dose Sacrifice) DOSE: (1) (2) (3) (4) (5) <6) (7) SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M BODY WEIGHT (G) MEAN S.D. N Liver (G)(ABSOLUTE) MEAN S.D. N 297.4 25.14 10 287.7 26.80 5 284.4 12.60 5 9.795 1.0821 10 * 14.148 1.9481 5 11.272 0.8740 5 300.0 12.82 5 285.8 14.93 5 11.053 1.0243 5 10.002 0.8465 5 268.1 10.83 5 283.1 15.81 5 10.766 0.9285 5 * 19.975 1.3302 5 Liver (% BODY WEIGHT) MEAN S.D. N 3.290 0.1816 10 * 4.903 0.3177 5 * 3.967 0.3149 5 * 3.684 0.3060 5 3.495 0.1243 5 * 4.013 0.2723 5 * 7.058 0.3263 5 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm Subgroup 4 = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm 3M Corporate Toxicology 30 I N-EtFOSE. PFOS, PFOSA TRC No. 1132-100 STUDY: 1132-100 DOSE: SUBGROUP: TABLE 5 (Continued) SUMMARY OF ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO BODY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE,, PFOS, and PFOSA in Rats SEX: MALE GROUP:: 4 (1-Week Recovery) (1) (2) (3) 1-M 2-M 3-M (4) 4-M (5) 5-M (6) 6-M (7) 7-M BODY WEIGHT (G) MEAN S.D. N 339.3 23.50 10 * 293.3 15.15 5 318.0 22.33 5 321.9 12.76 5 320.5 16.88 5 * 309.8 12.25 5 * 289.2 24.15 5 Liver (G)(ABSOLUTE) MEAN S.D. N 11.321 1.8076 10 * 14.118 2.3810 5 11.966 1.2780 5 10.549 0.7992 5 11.095 0.9263 5 12.681 0.7755 5 11.991 1.7505 5 Liver (% BODY WEIGHT) MEAN S.D. N 3.320 0.3244 10 * 4.794 0.5861 5 3.764 0.3017 5 3.278 0.2359 5 3.460 0.1768 5 * 4.094 0.1785 5 * 4.142 0.4693 5 STUDY: 1132-100 SEX: MALE GROUP : 5 (4-Week Recovery) DOSE: (1) (2) (3) (4) (5) (6) (7) SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M BODY WEIGHT (G) MEAN S.D. N 407.3 37.62 9 395.5 12.11 5 385.0 22.75 5 393.6 34.06 5 401.9 33.28 5 382.7 19.84 5 392.7 37.67 5 Liver (GHABSOLUTE) MEAN S.D. N 12.800 3.1700 9 * 17.146 1.9137 5 12.785 1.3292 5 13.103 0.5906 5 13.457 1.1267 5 15.152 1.6710 5 13.480 2.2220 5 Liver (% BODY WEIGHT) MEAN S.D. N 3.115 0.5079 9 * 4.333 0.4281 5 3.316 0.1849 5 3.346 0.2701 5 3.351 0.1470 5 * 3.956 0.3258 5 3.417 0.2545 5 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 Subgroup 5 Subgroup 6 Subgroup 7 0 ppm (Control) N-EtFOSE 300 ppm N-EtFOSE 100 ppm N-EtFOSE 30 ppm PFOS 20 ppm PFOSA 100 ppm Wy-14,643 100 ppm 3M Corporate Toxicology 31 nnnnrnnnrnnnrnnnnrDrnnnnnn N-EtFOSE, 1PFOS. PFOSA 1KL NO. 1I3-IUU APPENDIX TABLE 1 INDIVIDUAL BODY WEIGHTS (Grams) Cell Proliferation Study with N-EtFOSE , PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP : 1 (48-Hour Post Dose Sacrifice) SUBGROUP 1 SUBGROUP 2 SUBGROUP 3 SUBGROUP 4 ANIMAL # DAY 1 Animal # DAY 1 Animal # DAY 1 Animal # DAY 1 R 10381 226.0 R10391 215.5 R 10401 245.0 R10411 217.9 R 10382 258.4 R10392 244.9 R 10402 242.7 R10412 242.4 R 10383 229.9 R10393 221.6 R 10403 254.8 R 10413 215.7 R10384 241.5 R10394 193.7 R 10404 253.8 R10414 234.2 R 10385 221.0 R10395 246.0 R 10405 236.9 R10415 223.6 R 10386 207.7 R 10396 229.4 R10406 247.6 R 10416 230.7 R 10387 222.6 R 10397 238.9 R 10407 232.3 R10417 225.4 R 10388 216.9 R 10398 243.3 R 10408 228.5 R 10418 222.3 R 10389 238.7 R 10399 223.1 R 10409 251.1 R10419 242.7 R 10390 251.0 R 10400 234.4 R10410 237.2 R10420 245.4 SUBGROUP 5 Animal # R 10421 R10422 R10423 R10424 R10425 R10426 R 10427 R10428 R10429 R10430 DAY 1 241.6 237.2 240.1 229.9 243.1 239.8 196.9 243.1 216.4 242.0 SUBGROUP 6 Animal # R 10431 R 10432 R 10433 R 10434 R 10435 R 10436 R10437 R10438 R10439 R10440 DAY 1 241.3 185.7 221.8 265.5 233.7 249.1 250.5 232.8 244.0 226.8 SUBGROUP 7 Animal # R10441 R10442 R 10443 R 10444 R 10445 DAY 1 237.2 247.8 245.3 233.5 237.3 STUDY: 1132-100 SEX: MALE GROUP: 2 <7-Day Post Dose Sacrifice) SUBGROUP 1 ANIMAL # DAY 1 SUBGROUP 2 Animal # DAY 1 SUBGROUP 3 Animal # DAY 1 SUBGROUP 4 Animal # DAY 1 R 10446 R 10447 221.6 219.5 R 10456 R 10457 229.3 215.7 R10461 R 10462 250.3 243.1 R10466 R10467 212.5 236.3 R 10448 244.4 R 10458 214.2 R 10463 258.4 R 10468 226.2 R10449 231.8 R 10459 246.5 R 10464 246.4 R 10469 236.9 R 10450 218.4 R10460 236.4 R 10465 225.8 R 10470 223.5 R10451 217.1 R10452 232.0 R 10453 226.6 R 10454 238.5 R 10455 241.7 STUDY: 1132-100 SEX: MALE GROUP : 3 (14-Day Post Dose Sacrifice) SUBGROUP 1 ANIMAL # 1DAY 1 DAY 8 SUBGROUP 2 ANIMAL # DAY 1 DAY 8 SUBGROUP 3 Animal # DAY 1 DAY 8 R 10486 223.5 277.4 R 10496 271.1 315.8 R10501 227.3 269.0 R 10487 214.9 260.3 R 10497 198.8 241.5 R10502 237.8 291.2 R10488 230.4 282.7 R 10498 244.0 290.0 R 10503 223.7 276.5 R 10489 247.1 292.0 R 10499 241.0 287.7 R10504 237.0 290.4 R 10490 199.9 254.5 R 10500 250.3 296.3 R10505 198.9 254.1 R10491 239.6 274.5 R 10492 212.1 258.5 R 10493 248.7 285.3 R 10494 257.3 288.9 R 10495 216.6 262.9 SUBGROUP 5 Animal # R10471 R 10472 R 10473 R10474 R 10475 DAY 1 232.7 221.0 229.7 229.4 236.6 SUBGROUP 6 Animal # R10476 R10477 R10478 R10479 R 10480 DAY 1 256.5 240.0 258.4 236.8 221.1 SUBGROUP 7 Animal # R10481 R 10482 R 10483 R 10484 R 10485 DAY 1 233.4 229.9 247.8 215.2 260.1 SUBGROUP 4 Animal # R10506 R10507 R10508 R10509 R10510 DAY 1 242.1 239.0 210.3 221.0 240.1 DAY 8 296.7 295.7 270.7 287.0 281.3 SUBGROUP 5 Animal # R10511 R10512 R10513 R10514 R10515 DAY 1 211.0 219.9 240.0 226.7 241.2 DAY 8 273.7 260.2 288.2 272.4 289.9 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA , 100 ppm Subgroup 7 = Wy 14 ,643, 100 ppm 3M Corporate Toxicology 32 nnnnnnnnnnnnnncn N-EtFOSE, PFOS, PFOSA STUDY: 1132-100 SUBGROUP 6 ANIMAL # DAY 1 R 10516 R 10517 211.7 206.4 R 10518 228.0 R10519 228.1 R10520 236.0 SEX: MALE DAY 8 255.4 247.6 272.1 261.9 271.1 APPENDIX TABLE 1 (Continued) INDIVIDUAL BODY WEIGHTS (Grams) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP : 3 (14-Day Post Dose Sacrifice) SUBGROUP 7 ANIMAL # DAY 1 DAY 8 R10521 R10522 R10523 R10524 R10525 218.7 234.4 246.4 218.4 248.5 260.5 268.9 302.7 258.9 291.3 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 1 R10526 238.9 R10527 245.9 R 10528 242.2 R 10529 213.4 R 10530 224.3 R10531 228.9 R10532 239.3 R 10533 240.6 R 10534 223.6 R 10535 250.9 SEX: MALE DAY 8 269.0 314.0 301.7 244.8 273.4 264.3 297.0 286.2 256.9 311.5 DAY 15 335.3 385.7 371.7 336.3 321.8 321.0 354.6 330.2 323.6 366.4 GROUP : 4 (1-Week Recovery) SUBGROUP 2 ANIMAL # DAY 1 DAY 8 R10536 219.3 254.5 R 10537 246.9 276.1 R 10538 229.6 262.9 R10539 216.4 254.3 R1054O 205.4 257.3 AY 15 284.5 303.7 293.7 278.6 319.1 SUBGROUP 3 Animal # DAY 1 R10541 236.3 R10542 250.5 R10543 225.6 R 10544 226.3 R10545 214.6 DAY 8 290.4 299.9 267.2 269.3 269.4 DAY 15 338.0 342.5 294.3 311.4 321.8 STUDY: 1132-100 SUBGROUP 5 ANIMAL # DAY 1 R10551 234.2 R10552 223.0 R10553 213.5 R10554 238.9 R10555 228.4 SEX: MALE DAY 8 279.6 272.8 263.2 294.5 285.5 DAY 15 319.2 319.3 318.9 349.0 344.8 GROUP : 4 (1-Week Recovery) SUBGROUP 6 ANIMAL # DAY 1 DAY 8 R10556 232.5 280.0 R10557 220.9 263.1 R10558 250.4 283.9 R10559 226.0 284.4 R 10560 234.4 277.8 DAY 15 324.7 299.3 318.3 326.7 319.8 SUBGROUP 7 Animal # DAY 1 R10561 223.9 R10562 223.5 R 10563 191.7 R 10564 210.5 R10565 232.7 DAY 8 268.2 272.0 233.6 250.9 282.2 0AY 15 309.4 312.0 268.2 305.3 317.0 nnnn i-- i TRC No. 1132-100 SUBGROUP 4 Animal # DAY 1 R10546 R10547 R10548 R10549 R10550 242.1 219.8 232.1 252.7 238.5 DAY 8 DAY 15 282.0 326.6 265.5 311.3 273.7 320.1 292.3 342.3 283.8 336.7 Note: Animals in Groups 1(48-Hour Post Dose Sacrifice) and 2C7-Day Post Dose Sacrifice) were not reported due to only one body weight taken and the terminal body weights being excluded due to food fasting. Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 Subgroup 5 Subgroup 6 Subgroup 7 0 ppm (Control) N-EtFOSE, 300 ppm N-EtFOSE, 100 ppm N-EtFOSE, 30 ppm PFOS, 20 ppm PFOSA, 100 ppm Wy-14,643, 100 ppm 3M Corporate Toxicology 33 n n c io n n n D o n o a a n a n n c in n n c ] H-EtFOSE, PFOS. P F O S A ________________________________________________________________________________________________________________ _________ __________TRC No. 1132-100 APPENDIX TABLE 1 (Continued) INDIVIDUAL BODY WEIGHTS (Grams) _______________________________________ Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 1 R 10566 R 10567 233.8 240.1 R10568 R 10569 240.6 266.6 R10570 R10571 R10572 201.7 217.8 230.6 R10573 222.3 R 10574 234.4 R10575 236.4 SEX: MALE DAY 8 290.1 266.5 294.0 334.8 247.7 262.7 257.0 278.5 268.1 280.2 DAY 15 346.7 332.3 347.6 393.8 294.2 307.6 311.7 337.7 331.1 326.2 GROUP: 5 (4-Week Recovery) DAY 22 369.0 363.0 384.6 421.1 319.0 a 337.2 375.9 360.6 353.1 IDAY 29 408.0 401.6 411.9 450.9 341.7 a 367.2 408.4 391.2 380.5 DAY 36 435.5 417.4 437.8 480.5 360.9 a 385.3 433.0 405.1 401.2 SUBGROUP 2 ANIMAL # DAY 1 R10576 R10577 231.8 241.7 R10578 231.9 R10579 244.7 R10580 248.3 DAY 8 257.5 278.1 269.1 283.6 277.1 DAY 15 290.3 307.3 304.4 313.0 314.5 DAY 22 331.9 337.9 339.3 340.6 351.3 DAY 29 368.4 369.8 374.4 371.4 395.9 DAY 36 399.7 398.5 392.3 393.5 426.2 STUDY: 1132-100 SUBGROUP 3 ANIMAL # DAY 1 R10581 228.9 R 10582 232.4 R 10583 218.1 R10584 230.1 R10585 239.1 SEX : MALE DAY 8 272.0 275.7 262.5 273.3 268.8 DAY 15 321.4 312.2 317.9 318.5 293.9 GROUP : 5 (4- Week Recovery) DAY 22 350.9 337.5 355.3 343.9 315.6 DAY 29 384.0 362.6 395.4 378.1 340.5 DAY 36 412.4 365.4 405.1 403.3 364.5 SUBGROUP 4 ANIMAL # DAY 1 R10586 243.5 R10587 232.8 R10588 239.7 R10589 220.2 R 10590 233.9 DAY 8 287.0 289.3 295.9 258.8 288.9 DAY 15 322.8 343.2 346.7 278.5 354.0 DAY 22 359.6 376.4 380.3 297.3 398.6 DAY 29 385.4 402.3 399.7 317.7 402.8 DAY 36 403.7 420.5 418.7 341.8 420.6 STUDY: 1132-100 SUBGROUP 5 ANIMAL # DAY 1 R10591 214.4 R10592 220.5 R 10593 235.5 R10594 251.6 R10595 231.6 SEX : MALE DAY 8 260.6 271.7 287.0 307.8 288.2 DAY 15 312.0 324.2 323.4 364.5 343.4 GROUP : 5 (4- Week Recovery) DAY 22 338.1 353.9 359.1 399.6 380.4 DAY 29 360.2 386.7 387.5 432.1 415.1 DAY 36 367.1 399.1 405.6 454.9 445.0 SUBGROUP 6 ANIMAL # DAY 1 R 10596 217.6 R 10597 228.0 R10598 238.0 R10599 175.2 R10600 223.3 DAY 8 263.6 265.6 284.2 248.1 261.4 DAY 15 307.9 304.1 321.2 301.6 300.9 DAY 22 339.2 332.9 349.4 340.1 308.3 DAY 29 379.9 360.7 375.5 376.2 342.0 DAY 36 397.0 390.3 404.2 402.5 364.1 STUDY: 1132-100 SUBGROUP 7 ANIMAL # DAY 1 R10601 241.1 R10602 231.7 R 10603 R10604 210.6 234.6 R 10605 202.5 SEX : MALE DAY 8 290.7 286.8 250.5 283.1 258.9 DAY 15 343.0 338.5 292.7 319.2 301.9 GROUP : 5 (4- Week Recovery) DAY 22 365.4 374.0 317.9 331.4 322.1 DAY 29 398.9 422.5 352.1 360.6 351.7 DAY 36 419.7 459.7 374.2 383.8 383.0 a - Animal was moribund killed on Day 21. Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm Subgroup 4 = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm 3M Corporate Toxicology 34 nncinnaaanarnanaam m nnna N-EtFOSE. PFOS, PFOSA___________________________________________________________________________________________________________________________________________ TRC Wo. 1132-100 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 8 R 10486 53.9 R 10487 45.4 R 10488 52.3 R 10489 44.9 R 10490 54.6 R10491 34.9 R10492 46.4 R 10493 36.6 R 10494 31.6 R 10495 46.3 APPENDIX TABLE 1A INDIVIDUAL BODY WEIGHT GAINS (Grams) Cell Proliferation Study with N -EtFOSE, PFOS, and PFOSA in Rats SEX: MALE GROUP : 3 (14-Day Post Dose Sacrifice) SUBGROUP 2 ANIMAL # DAY 8 SUBGROUP 3 ANIMAL H DAY 8 SUBGROUP 4 ANIMAL # DAY 8 SUBGROUP 5 ANIMAL # DAY 8 SUBGROUP 6 ANIMAL # R 10496 44.7 R10501 41.7 R10506 54.6 R10511 62.7 R 10516 R10497 42.7 R 10502 53.4 R10507 56.7 R 10512 40.3 R 10517 R 10498 46.0 R 10503 52.8 R10508 60.4 R10513 48.2 R10518 R10499 46.7 R 10504 53.4 R10509 66.0 R10514 45.7 R 10519 ' R10500 46.0 R10505 55.2 R10510 41.2 R 10515 48.7 R10520 DAY 8 43.7 41.2 44.1 33.8 35.1 SUBGROUP 7 ANIMAL # R10521 R10522 R10523 R10524 R10525 DAY 8 41.8 34.5 56.3 40.5 42.8 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 8 R10526 30.1 R 10527 68.1 R 10528 59.5 R10529 31.4 R10530 49.1 R10531 35.4 R10532 57.7 R10533 45.6 R10534 33.3 R10535 60.6 SEX: HALE GROUP: 4 (1-Week Recovery) SUBGROUP 2 SUBGROUP 3 DAY 15 ANIMAL # DAY 8 DAY 15 Animal # DAY 8 66.3 R10536 35.2 30.0 R10541 54.1 71.7 R 10537 29.2 27.6 R 10542 49.4 70.0 R 10538 33.3 30.8 R10543 41.6 91.5 R10539 37.9 24.3 R 10544 43.0 48.4 R10540 51.9 61.8 R 10545 54.8 56.7 57.6 44.0 66.7 54.9 DAY 15 47.6 42.6 27.1 42.1 52.4 SUBGROUP 4 Animal # R10546 R10547 R10548 R 10549 R10550 DAY 8 39.9 45.7 41.6 39.6 45.3 DAY 15 44.6 45.8 46.4 50.0 52.9 SUBGROUP 5 Animal # R10551 R10552 R10553 R10554 R10555 DAY 8 45.4 49.8 49.7 55.6 57.1 DAY 15 39.6 46.5 55.7 54.5 59.3 STUDY: 1132-100 SUBGROUP 6 ANIMAL # DAY 8 R10556 47.5 R10557 R10558 42.2 33.5 R10559 58.4 R 10560 43.4 SEX: MALE GROUP: 4 (1-Week Recovery) SUBGROUP 7 DAY 15 ANIMAL # DAY 8 DAY 15 44.7 R 10561 44.3 41.2 36.2 34.4 R 10562 R10563 48.5 41.9 40.0 34.6 42.3 42.0 R10564 R 10565 40.4 49.5 54.4 34.8 Note: Animals in Groups 1(48-Hour Post Dose Sacrifice) and 2(7-Day Post Dose Sacrifice) were not reported due to only one body weight taken and the terminal body weights being excluded due to food fasting. Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm 3M Corporate Toxicology 35 n n n n n n n n ci n ri n n tri tri o m n o n in N-EtFOSE, PFOS, PFOSA_____________________________________________________________________________________________________________________ _________________ TRC No. 1132-100 STUDY: 1132-100 SEX : MALE SUBGROUP 1 ANIMAL # DAY 8 DAY 15 DAY 22 R10566 56.3 56.6 22.3 R10567 26.4 65.8 30.7 R 10568 53.4 53.6 37.0 R 10569 68.2 59.0 27.3 R10570 46.0 46.5 24.8 R10571 44.9 44.9 a R10572 26.4 54.7 25.5 R10573 56.2 59.2 38.2 R10574 33.7 63.0 29.5 R 10575 43.8 46.0 26.9 APPENDIX TABLE 1A (Continued) INDIVIDUAL BODY WEIGHT GAINS (Grams) Cell Proliferation Study with M-EtFOSE, PFOS, and PFOSA in Rats GROUP : 5 (4-Week Recovery) DAY 29 DAY 36 SUBGROUP 2 ANIMAL # DAY 8 DAY 15 DAY 22 DAY 291 DAY 36 39.0 38.6 27.3 29.8 22.7 a 30.0 32.5 30.6 27.4 27.5 15.8 25.9 29.6 19.2 a 18.1 24.6 13.9 20.7 R10576 R10577 R10578 R10579 R1O580 25.7 36.4 37.2 38.9 28.8 32.8 29.2 35.3 29.4 37.4 41.6 30.6 34.9 27.6 36.8 36.5 31.9 35.1 30.8 44.6 31.3 28.7 17.9 22.1 30.3 STUDY : 1132-100 SEX : MALE SUBGROUP 1 ANIMAL # DAY 8 DAY 15 DAY 22 R10581 43.1 49.4 29.5 R10582 43.3 36.5 25.3 R10583 44.4 55.4 37.4 R 10584 43.2 45.2 25.4 R10585 29.7 25.1 21.7 GROUP : 5 (4-Week Recovery) DAY 29 33.1 25.1 40.1 34.2 24.9 DAY 36 28.4 2.8 9.7 25.2 24.0 SUBGROUP 4 ANIMAL # DAY 8 R10586 43.5 R 10587 R 10588 56.5 56.2 R 10589 38.6 R 10590 55.0 DAY 15 45.8 53.9 50.8 19.7 65.1 DAY 22 26.8 33.2 33.6 18.8 44.6 DAY 29 25.8 25.9 19.4 20.4 4.2 DAY 36 18.3 18.2 19.0 24.1 17.8 STUDY: 1132-100 SEX : MALE SUBGROUP 5 ANIMAL # DAY 8 DAY 15 DAY 22 R10591 46.2 51.4 26.1 R10592 51.2 52.5 29.7 R10593 51.5 36.4 35.7 R10594 56.2 56.7 35.1 R10595 56.6 55.2 37.0 GROUP : 5 (4-Week Recovery) DAY 29 22.1 32.8 28.4 32.5 34.7 DAY 36 6.9 12.4 18.1 22.8 29.9 SUBGROUP 6 ANIMAL # DAY 8 R 10596 46.0 R 10597 37.6 R 10598 46.2 R10599 72.9 R10600 38.1 DAY 15 44.3 38.5 37.0 53.5 39.5 DAY 22 DAY 29 DAY 36 31.3 40.7 17.1 28.8 27.8 29.6 28.2 26.1 28.7 38.5 36.1 26.3 7.4 33.7 22.1 STUDY: 1132-100 SEX : MALE SUBGROUP 7 ANIMAL # DAY 8 DAY 15 DAY 22 R10601 49.6 52.3 22.4 R 10602 55.1 51.7 35.5 R 10603 39.9 42.2 25.2 R 10604 48.5 36.1 12.2 R 10605 56.4 43.0 20.2 GROUP : 5 (4-Week Recovery) DAY 29 33.5 48.5 34.2 29.2 29.6 DAY 36 20.8 37.2 22.1 23.2 31.3 a - Animal was moribund killed on Day 21 Note: Animals in Groups 1(48-Hour Post Dose Sacrifice) and 2(7-Day Post Dose Sacrifice) were not reported due to only one body weight taken and the terminal body weights being excluded due to food fasting. Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm Subgroup 4 = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm 3M Corporate Toxicology 36 n n n n n n n n n n n n n o n n n n n n rn N-EtFOSE.,1 P'F--O-S,1 'P'FOSA_____________ ______________________________________________________________________________________________________________________________ TRC No. 1132-100 STUDY: 1132-100 SEX: MALE SUBGROUP 1 SUBGROUP 2 ANIMAL # DAY 2 Animal # DAY 2 R10381 27.4 R 10391 24.5 R10382 26.1 R 10392 24.2 R10383 23.1 R 10393 23.5 R10384 22.0 R 10394 26.4 R10385 22.3 R 10395 26.4 R10386 23.6 R10396 25.7 R10387 R10388 22.6 22.9 R10397 R10398 30.1 28.6 R 10389 16.5 R 10399 25.3 R 10390 22.4 R 10400 26.2 APPENDIX TABLE 2 INDIVIDUAL FEED CONSUMPTION (Grams) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP 3 SUBGROUP 4 Animal # DAY 2 Animal # DAY 2 SUBGROUP 5 Animal # DAY 2 SUBGROUP 6 Animal # R10401 R 10402 R 10403 R 10404 R 10405 R 10406 R 10407 R 10408 R 10409 R 10410 28.1 29.8 27.6 28.2 29.6 17.1 27.3 26.0 28.1 25.6 R10411 R10412 R10413 R10414 R 10415 R10416 R 10417 R 10418 R 10419 R10420 26.1 26.1 25.5 23.5 26.5 24.8 25.3 19.6 27.5 25.5 R10421 R10422 R 10423 R 10424 R 10425 R 10426 R10427 R 10428 R 10429 R 10430 27.5 27.3 27.5 27.3 23.8 22.0 22.7 16.5 25.1 19.4 R10431 R10432 R 10433 R10434 R10435 R10436 R10437 R10438 R 10439 R10440 DAY 2 28.5 20.0 26.3 29.6 25.9 20.5 26.9 34.8 27.3 28.8 SUBGROUP 7 Animal # R 10441 R 10442 R 10443 R 10444 R 10445 DAY 2 26.1 24.2 22.2 26.0 27.3 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 7 R 10446 149.8 R 10447 R 10448 156.1 184.2 R 10449 R 10450 173.3 152.7 R10451 R 10452 R10453 154.5 164.8 149.9 R10454 R10455 168.9 179.6 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 1 R 10486 R10487 R 10488 R 10489 R 10490 196.2 173.2 199.3 179.0 170.5 R 10491 R10492 179.8 171.2 R10493 R 10494 178.7 192.9 R 10495 173.1 SEX: MALE GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP 2 SUBGROUP 3 SUBGROUP i Animal # DAY 7 Animal # DAY 7 Animal # DAY 7 R10456 142.7 R 10461 176.6 R 10466 146.5 R10457 155.3 R 10462 181.4 R 10467 168.3 R10458 163.3 R 10463 192.2 R 10468 162.3 R10459 164.1 R 10464 150.2 R 10469 159.3 R 10460 152.5 R 10465 158.6 R 10470 158.4 SEX: MALE DAY 8 190.2 169.6 209.5 160.6 161.6 203.1 150.8 181.0 199.1 161.2 GROUP: 3 (14 Day Post Dose Sacrifice) SUBGROUP 2 ANIMAL # DAY 1 DAY 8 SUBGROUP 3 Animal # DAY 1 R 10496 R 10497 R 10498 189.1 166.2 192.9 171.7 138.1 167.7 R10501 R10502 R10503 186. 7 188. 5 189. 9 R 10499 198.0 162.6 R10504 197.6 R10500 203.9 175.0 R10505 186.8 DAY 8 155.2 162.5 164.9 169.2 167.2 SUBGROUP 5 Animal # R10471 R 10472 R 10473 R10474 R10475 DAY 7 155.4 154.7 160.8 147.9 161.0 SUBGROUP 6 Animal # R 10476 R 10477 R10478 R 10479 R 10480 DAY 7 166.5 163.4 189.3 155.7 154.4 SUBGROUP 7 Animal # R 10481 R 10482 R 10483 R 10484 R 10485 DAY 7 142.5 148.6 162.4 154.5 177.6 SUBGROUP 4 Animal # R10506 R 10507 R 10508 R 10509 R 10510 DAY 1 199.6 198.1 186.1 210.2 188.0 DAY 8 181.8 165.4 176.0 201.0 170.5 SUBGROUP 5 Animal # DAY 1 R 10511 R 10512 203.4 173.0 R 10513 R10514 191.2 184.1 R10515 190.7 DAY 8 171.3 150.0 170.5 169.1 173.7 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppen Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA , 100 ppm Subgroup 7 = Wy-14 ,643, TOO ppm 3M Corporate Toxicology 37 n n n rn n n rn c in rzin n m c T n n n c irn n rn N-EtFOSE, PFOS. PFOSA TRC No. 1132-100 APPENDIX TABLE 2 (Continued) INDIVIDUAL FEED CONSUMPTION CGrams) ______________ _________________________________________ Cell Proliferation Study with N-EtFOSE. PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP 6 ANIMAL # DAY 1 DAY 8 SUBGROUP 7 ANIMAL U DAY 1 DAY 8 R10516 R10517 R 10518 R10519 170.1 158.8 186.9 162.7 154.0 137.8 156.9 138.9 R 10521 R 10522 R 10523 R 10524 178.6 180.6 208.7 167.9 159.8 163.6 184.0 150.0 R 10520 181.0 164.4 R10525 210.6 177.2 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 1 R10526 175.5 R10527 222.6 R10528 212.5 R10529 182.0 R10530 185.7 R10531 181.0 R 10532 209.2 R 10533 191.1 R10534 178.3 R 10535 213.2 SEX: MALE DAY 8 200.9 239.8 248.9 233.3 188.8 190.4 215.4 191.2 203.2 16.56 DAY 15 169.2 206.7 209.2 193.5 165.1 178.2 183.0 172.8 176.9 199.7 GROUP: 4 (1-Week Recovery) SUBGROUP 2 ANIMAL # DAY 1 DAY 8 R10536 164.6 150.4 R 10537 179.4 164.3 R 10538 177.3 176.6 R 10539 160.0 161.4 R10540 191.0 200.1 DAY 15 148.4 144.0 167.4 154.9 188.1 SUBGROUP 3 Animal # DAY 1 R10541 204.9 R10542 203.9 R10543 182.0 R 10544 185.9 R10545 196.3 DAY 8 208.1 199.1 168.0 185.0 193.5 DAY 15 192.5 176.1 150.4 173.4 172.8 STUDY: 1132-100 SUBGROUP 5 ANIMAL # DAY 1 R 10551 180.7 R10552 192.0 R10553 190.9 R10554 194.4 R10555 196.9 SEX: MALE DAY 8 179.1 190.6 192.9 200.5 203.8 DAY 15 165.0 158.9 158.4 174.6 180.9 GROUP: 4 (1-Week Recovery) SUBGROUP 6 ANIMAL # DAY 1 DAY 8 R10556 R10557 R10558 R10559 R10560 193.9 183.4 187.2 193.0 180.5 189.7 173.9 181.2 189.9 183.7 DAY 15 180.1 168.5 164.6 181.7 164.3 SUBGROUP 7 Animal it DAY 1 R10561 176.6 R10562 197.3 R10563 156.5 R10564 169.7 R10565 200.3 DAY 8 189.3 192.2 162.8 190.4 212.3 DAY 15 164.3 171.2 145.7 179.1 188.7 SUBGROUP 4 Animal # DAY 1 R10546 187.1 R 10547 179.0 R10548 183.3 R10549 207.6 R10550 195.2 DAY 8 190.5 178.6 188.2 209.7 201.8 DAY 15 175.8 169.0 168.6 182.9 184.0 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm 3M Corporate Toxicology 38 nnm nnnnnnnnnnnnnnnaan N-EtFOSE. PFOS, P F O S A ___________________ __ ___________________________________________________________________________________________________________________ TRC No. 1132-100 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 1 R 10566 206.1 R10567 171.1 R 10568 201.1 R 10569 229.2 R10570 171.3 R 10571 170.0 R10572 182.1 R10573 198.7 R10574 182.8 R10575 181.9 STUDY: 1132-100 SUBGROUP 3 ANIMAL # DAY 1 R10581 191.0 R 10582 187.4 R 10583 199.0 R 10584 195.9 R 10585 177.0 SEX : MALE DAY 8 DAY 15 214.4 198.2 204.3 192.7 199.6 212.4 236.2 216.4 179.6 176.1 168.9 a 188.8 185.7 214.3 215.1 202.4 191.3 191.1 182.4 SEX : MALE DAY 8 196.1 182.2 207.2 204.1 172.6 DAY 15 204.0 188.3 214.7 194.5 185.5 APPENDIX TABLE 2 (Continued) INDIVIDUAL FEED CONSUMPTION (Grams) Cell Prol.iteration Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 5 (4-Week Recovery) SUBGROUP ;1 DAY 22 DAY 29 DAY 36 ANIMAL # DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 206.8 209.7 175.0 R10576 157.5 153.3 183.3 185.4 193.7 168.4 195.0 193.8 154.4 R 10577 193.8 174.8 191.0 175.8 198.0 157.5 204.2 204.4 167.3 R 10578 199.5 191.0 199.5 206.3 207.9 167.5 213.3 231.3 201.3 R 10579 189.4 182.4 185.8 184.3 193.8 158.4 173.5 175.1 139.0 R10580 173.1 181.2 189.0 207.3 214.8 178.3 a aa 185.4 190.2 149.6 213.9 212.3 182.6 196.0 188.9 153.1 180.5 175.9 150.5 GROUP: 5 (4-Ueek Recovery) SUBGROUP 1 DAY 22 DAY 29 DAY 36 ANIMAL # DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 202.4 206.7 172.6 R10586 191.4 199.5 200.1 193.7 199.3 170.8 176.0 170.7 144.1 R10587 205.3 205.5 212.2 183.6 185.7 163.4 217.5 211.8 174.4 R10588 201.9 205.1 207.3 189.5 193.7 151.6 196.5 208.1 163.0 R 10589 190.0 164.9 173.9 164.5 173.9 148.8 177.4 185.9 151.9 R10590 199.3 212.2 222.4 169.3 156.5 159.7 STUDY: 1132-100 SUBGROUP 5 SEX : MALE GROUP: 5 (4-Week Recovery) ANIMAL # DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 R10591 181.8 180.8 188.6 168.0 161.5 146.8 R10592 R 10593 R10594 R 10595 177.3 201.8 201.1 201.5 184.3 180.2 210.3 207.2 189.9 209.9 216.4 219.8 182.5 197.5 204.2 213.0 178.8 197.2 210.5 211.0 147.6 149.9 186.5 185.2 STUDY: 1132-100 SEX : MALE GROUP: 5 SUBGROUP 7 ANIMAL # DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 R10601 196.4 202.5 196.6 205.0 198.9 152.1 R 10602 193.4 189.4 214.6 234.7 246.9 197.1 R 10603 170.2 187.3 209.4 214.5 208.7 169.9 R 10604 R10605 194.4 202.5 183.7 176.2 178.5 185.7 194.6 189.9 199.3 195.4 161.9 151.9 a - Animal was moribund killed on Day 21. SUBGROUP 6 ANIMAL # DAY 1 R 10596 186.8 R10597 161.8 R10598 205.4 R 10599 R10600 190.1 182.3 DAY 8 187.1 168.8 191.0 181.8 173.4 DAY 15 201.3 179.3 199.5 194.3 168.9 DAY 22 203.5 182.0 201.2 193.8 168.2 DAY 29 209.2 186.2 210.7 203.9 184.3 DAY 36 180.1 148.0 172.5 170.3 143.5 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, '100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm .- 3M Corporate Toxicology 39 N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 INDIVIDUAL CLINICAL OBSERVATIONS ________________________ Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 1 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10381 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R 10382 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R 10383 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R 10384 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R 10385 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R 10386 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10387 Normal Soft Feces Thin Terminal Kill DAY 1 DAY 3 DAY 3 DAY 3 R 10388 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10389 Normal Lacrimation Thin Terminal Kill R7, L7 DAY 1 DAY 3 DAY 3 DAY 3 R10390 Normal DAY 1 Thin DAY 3 Terminal Kill DAY 3 STUDY: 1132-100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP 2 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10391 Normal DAY 1 Thin DAY 3 Terminal Kill DAY 3 R 10392 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10393 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R 10394 Normal Thin Terminal Kill Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm DAY 1 DAY 3 DAY 3 R7 = Right Eye L7 = Left Eye TRC No. 1132-100 3M Corporate Toxicology 40 N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132 -100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 2 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10395 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R 10396 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R 10397 R 10398 Normal Terminal Kill Normal Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 R 10399 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10400 Normal Terminal Kill STUDY: 1132 -100 GROUP: 1 (48-Hour Post Dose Sacrifice) ANIMAL # OBSERVATIONS SEVERITY LOC R10401 Discharge, Red Normal M7 Terminal Kill DAY 1-DAY 3 DAY 3 SUBGROUP: 3 TIME OCCURRED DAY 1 DAY 3 DAY 3 R10402 R 10403 Normal Terminal Kill Normal Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 R 10404 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R 10405 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10406 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10407 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10408 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R 10409 R10410 Normal Terminal Kill Normal Thin Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm M7 = Nose TRC No. 1132-100 3M Corporate Toxicology 41 N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS ________________________ Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 4 ANIMAL # OBSERVATIONS _____ SEVERITY LOC TIME OCCURRED ____ R10411 Normal DAY 1 Thin Terminal Kill DAY 3 DAY 3 R10412 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10413 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10414 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10415 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R1Q416 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10417 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10418 R1Q419 Normal Thin Terminal Kill Normal Rough Haircoat Thin Terminal Kill DAY 1 DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 DAY 3 R10420 Normal DAY 1-DAY 3 Terminal Kill DAY 3 STUDY: 1132-100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 5 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10421 Normal DAY 1-DAY 3 Terminal Kill DAY 3 R10422 R10423 Normal Paraphimosis Terminal Kill Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 R10424 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10425 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R 10426 Normal Terminal Kill DAY 1-DAY 3 DAY 3 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtfOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm TRC No. 1132-100 3M Corporate Toxicology 42 c D G D G G G G D G G G C D G G G G G N-EtFOSE, PFOS. PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE. PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 5 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED ______ R10427 Normal DAY 1 Thin DAY 3 Terminal Kill DAY 3 R 10428 R 10429 Normal Thin Terminal Kill Normal Terminal Kill DAY 1 DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 R 10430 Normal DAY 1-DAY 3 Terminal Kill DAY 3 STUDY: 1132-100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 6 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10431 Normal DAY 1-DAY 3 Terminal Kill DAY 3 R10432 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10433 Normal Terminal Kilt DAY 1-DAY 3 DAY 3 R 10434 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R 10435 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10436 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10437 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10438 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10439 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R 10440 Normal Terminal Kill DAY 1-DAY 3 DAY 3 Subgroup 1 = 0 ppm (Control) Subg roup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subg roup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm TRC No. 1132-100 3M Corporate Toxicology 43 n L f-- D n u n U G n L p L: nL_i 0 P U P U P Li p L 0 0 D 0 N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE , PFOS, and PFOSA in Rats STUDY: 1132--100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 7 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10441 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10442 Alopecia Normal Terminal Kill V1 DAY 3 DAY 1 DAY 3 R 10443 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10444 Normal Soft Feces Thin Terminal Kill DAY 1 DAY 3 DAY 3 DAY 3 R 10445 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 STUDY: 1132 -100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 1 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10446 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10447 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10448 Normal Thin Terminal Kill DAY 1 DAY 8 DAY 8 R 10449 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10450 R10451 R10452 R10453 R10454 R 10455 Normal Terminal Kill Normal Terminal Kill Normal Terminal Kill Normal Terminal Kill Normal Terminal Kill Normal Terminal Kill DAY 1-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm V1 = Ventral Front Right Area TRC No. 1132-100 3M Corporate Toxicology 44 I !. p <-- L p u D 0 u Ln_. Ln-! c p Li nLI ni-- < n' L p L P Lj D 0 D D N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 2 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10456 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10457 R10458 Normal Terminal Kill Normal Thin Terminal Kill DAY 1-DAY 8 DAY 8 DAY 1 DAY 8 DAY 8 R10459 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10460 Normal DAY 1-DAY 8 Terminal Kill DAY 8 STUDY: 1132-100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 3 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10461 Normal DAY 1-DAY 8 Terminal Kill DAY 8 R10462 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10463 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10464 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10465 Normal DAY 1-DAY 8 Terminal Kill DAY 8 STUDY: 1132-100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 4 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10466 Normal DAY 1 Thin DAY 8 Terminal Kill DAY 8 R10467 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10468 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10469 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10470 Normal Terminal Kill DAY 1-DAY 8 DAY 8 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm TRC No. 1132-100 _________________ 3M Corporate Toxicology 45 I I i j i 1! pL D Ll U 1-t r-, D p ^ rIni U pLi n fI-- ! l-- i '-- C 0 G 0 N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE , PFOS, and PFOSA in Rats #STUDY: 1132--100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 5 ANIMAL OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10471 Normal DAY 1-DAY 8 Terminal Kill DAY 8 R 10472 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10473 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10474 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10475 Normal DAY 1-DAY 8 Terminal Kill DAY 8 #STUDY: 1132 -100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 6 ANIMAL OBSERVATIONS SEVERITY LOC TIME OCCURRED R10476 Lacrimation M7 DAY 1 Normal DAY 8 Terminal Kill DAY 8 R10477 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10478 Normal Terminal Kilt DAY 1-DAY 8 DAY 8 R 10479 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10480 Normal DAY 1-DAY 8 Terminal Kill DAY 8 #STUDY: 1132 -100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 7 ANIMAL OBSERVATIONS SEVERITY LOC TIME OCCURRED R10481 Normal DAY 1-DAY 8 Terminal Kill DAY 8 R 10482 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10483 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10484 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R104S5 Normal Terminal Kill =Subgroup 1 =Subgroup 2 =Subgroup 3 =Subgroup 4 =Subgroup 5 =Subgroup 6 =Subgroup 7 0 ppm (Control) N-EtFOSE, 300 ppm N-EtFOSE, 100 ppm N-EtFOSE, 30 ppm PFOS, 20 ppm PFOSA, 100 ppm Wy-14,643, 100 ppm =M7 Both Eyes DAY 1-DAY 8 DAY 8 TRC No. 1132-100 3M -Corporate Toxicology 46 ! I Ii N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS ________________________ Cell Proliferation Study with N-EtFOSE. PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 1 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10486 Normal DAY 1-DAY 15 Terminal Kill DAY 15 R 10487 Normal Soft Feces Normal Terminal Kill DAY 1 DAY 8 DAY 15 DAY 15 R 10488 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10489 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R 10490 R10491 Normal Terminal Kill Normal Terminal Kill DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 R 10492 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10493 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R 10494 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R 10495 Normal DAY 1-DAY 8 Thin DAY 15 Terminal Kill DAY 15 STUDY: 1132-100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 2 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10496 Normal DAY 1-DAY 15 Terminal Kill DAY 15 R 10497 R10498 Normal Terminal Kill Normal Terminal Kill DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 R10499 R 10500 Normal Terminal Kill Normal Terminal Kill DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 Subgroup 5 Subgroup 6 Subgroup 7 0 ppm (Control) N-EtFOSE 300 ppm N-EtFOSE 100 ppm N-EtFOSE 30 ppm PFOS 20 ppm PFOSA 100 ppm Wy-14,643 100 ppm TRC No. 1132-100 3M Corporate Toxicology 47 D D D D D D 0 0 D 0 D D 0 D 0 D D D D N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 3 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10S01 Normal Thin Terminal Kill DAY 1-DAY 8 DAY 15 DAY 15 R 10502 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10503 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10504 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10505 Normal DAY 1-DAY 15 Terminal Kill DAY 15 STUDY: 1132-100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 4 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10506 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R1507 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10508 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10509 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R1051Q Normal DAY 1-DAY 15 Terminal Kill DAY 15 STUDY: 1132-100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 5 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10511 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10512 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10513 Normal Soft Feces Thin Terminal Kill DAY 1-DAY 8 DAY 15 DAY 15 DAY 15 R10514 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10515 Normal Terminal Kill DAY 1-DAY 15 DAY 15 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 Subgroup 5 Subgroup 6 Subgroup 7 0 ppm (Control) N-EtFOSE, 300 ppm N-EtFOSE, 100 ppm N-EtFOSE, 30 ppm PFOS, 20 ppm PFOSA, 100 ppm Wy-14,643, 100 ppm TRC No. 1132-100 3M Corporate Toxicology 48 D C C D D D D D 0 0 D 0 D D 0 D D D D C N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE , PFOS. and PFOSA in Rats STUDY: 1132- 100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 6 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R1051 Normal DAY 1-DAY 15 Terminal Kill DAY 15 R10517 Normal Thin Terminal Kill DAY 1-DAY 8 DAY 15 DAY 15 R10518 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10519 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10520 Normal DAY 1-DAY 8 Thin DAY 15 Terminal Kill DAY 15 STUDY: 1132-100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 7 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10521 Normal DAY 1-DAY 15 Terminal Kill DAY 15 R10522 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10523 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10524 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10525 Normal Terminal Kill STUDY: 1132 -100 GROUP: 4 (1-Week Recovery) ANIMAL # OBSERVATIONS SEVERITY R10526 Normal Terminal Kill DAY 1-DAY 15 DAY 15 SUBGROUP: 1 LOC TIME OCCURRED DAY 1-DAY 22 DAY 22 R10527 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10528 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10529 Normal Diarrhea Terminal Kill DAY 1-DAY 15 DAY 22 DAY 22 R10530 Normal Terminal Kill DAY 1-DAY 22 DAY 22 RI0531 R10532 Normal Terminal Kill Normal Terminal Kill DAY 1-DAY 22 D!A.Y 22 DAY 1-DAY 22 DAY 22 R 10533 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R 10534 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10535 Normal Terminal Kill Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm DAY 1-DAY 22 DAY 22 Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 7 - Wy-14,643, 100 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm 3M Corporate Toxicology 49 N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS ________________________ Cell Proliferation Study with N-EtFOSE. PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 4 (1-Week Recovery) SUBGROUP: 2 ANIMAL # OBSERVATIONS _______ SEVERITY LOC TIME OCCURRED__________________ R 10536 Normal Thin Thin Terminal Kill DAY 1-DAY 8 DAY 15 DAY 22 DAY 22 R 10537 Normal Diarrhea Normal Terminal Kill DAY 1-DAY 8 DAY 15 DAY 22 DAY 22 R10538 Normal Thin Termi na l Kill DAY 1-DAY 15 DAY 22 DAY 22 R10539 Normal Thin Terminal Kill DAY 1-DAY 15 DAY 22 DAY 22 R10540 Normal Terminal Kill STUDY: 1132-100 GROUP: 4 (1-Week Recovery) ANIMAL # OBSERVATIONS SEVERITY R10541 Normal Terminal Kill DAY 1-DAY 22 DAY 22 SUBGROUP: 3 LOC TIME OCCURRED DAY 1-DAY 22 DAY 22 R10542 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10543 Normal Thin Terminal Kill DAY 1-DAY 15 DAY 22 DAY 22 R 10544 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10545 Normal Terminal Kill DAY 1-DAY 22 DAY 22 STUDY: 1132-100 GROUP: 4 <1-Week Recovery) SUBGROUP: 4 ANIMAL # OBSERVATIONS SEVERITY_____ LOC TIME OCCURRED R 10546 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R 10547 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10548 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10549 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10550 Normal Terminal Kill DAY 1-DAY 22 DAY 22 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 Subgroup 5 Subgroup 6 Subgroup 7 0 ppm (Control) N-EtFOSE, 300 ppm N-EtFOSE, 100 ppm N-EtFOSE, 30 ppm PFOS, 20 ppm PFOSA, 100 ppm Wy-14,643, 100 ppm TRC No. 1132-100 3M Corporate Toxicology 50 N-E-tF-O-SE., -P-F-OS,, PFOSA______________________________________________________________________________________________________ T.R.WC N-Wo.. 1,132-1I0V0V APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132 -100 GROUP: 4 (1-Week Recovery) SUBGROUP: 5 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10551 Normal DAY 1 Lacrimat ion Normal Terminal Kill R7 DAY 8 DAY 15-DAY 22 DAY 22 R10552 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10553 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10554 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10555 Normal Terminal Kill STUDY: 1132 -100 GROUP: 4 (1-Week Recovery) ANIMAL # OBSERVATIONS SEVERITY R10556 Normal Terminal Kill DAY 1-DAY 22 DAY 22 SUBGROUP: 6 LOC TIME OCCURRED DAY 1-DAY 15 DAY 22 R10557 Normal Abrasion Thin Terminal Kill DAY 1 M1 DAY 8-DAY 15 DAY 22 DAY 22 R10558 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10559 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R1Q560 Normal Terminal Kill STUDY: 1132 -100 GROUP: 4 (1-Week Recovery) ANIMAL # OBSERVATIONS SEVERITY R10561 Normal Abrasion Terminal Kill DAY 1-DAY 22 DAY 22 SUBGROUP: 7 LOC TIME OCCURRED DAY 1 M1 DAY 8-DAY 22 DAY 22 R10562 R10563 Normal Thin Terminal Kill Normal Thin Terminal Kill DAY 1-DAY 15 DAY 22 DAY 22 DAY 1-DAY 15 DAY 22 DAY 22 R10564 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R 10565 Normal Terminal Kill DAY 1-DAY 22 DAY 22 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm R7 = Right Eye M1 = Ventral side of Neck 3M Corporate Toxicology 51 N-EtFOSE. PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132- 100 GROUP: 5 (4-Week Recovery) SUBGROUP: 1 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10566 Normal DAY 1-DAY 43 Terminal Kill DAY 43 R10567 Normal Abrasion Alopecia Alopecia Terminal Kill DAY 1 M1 DAY 8-DAY 36 R7 DAY 22-DAY 36 M7 DAY 43 DAY 43 R10568 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10569 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R 10570 Normal Lacrimaiion Normal Terminal Kill R7,L7 DAY 1 DAY 8 DAY 15- DAY 43 DAY 43 R10571 Normal Moribund Kill DAY 1-DAY 15 DAY 21 R10572 Normal Reddened Normal Terminal Kill DAY 1-DAY 29 M6 DAY 36 DAY 43 DAY 43 R10573 Normal Abrasi on Terminal Kill DAY 1-DAY 22 M1 DAY 29-DAY 43 DAY 43 R10574 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10575 Normal Terminal Kill STUDY: 1132-100 GROUP: 5 (4-Week Recovery) ANIMAL # OBSERVATIONS SEVERITY R10576 Normal Terminal Kill DAY 1-DAY 43 DAY 43 SUBGROUP: 2 LOC TIME OCCURRED DAY 1-DAY 43 DAY 43 R 10577 R10578 R 10579 R1058Q Normal Terminal Kill Normal Terminal Kill Normal Terminal Kill Normal Terminal Kill DAY 1-DAY 43 DAY 43 DAY 1-DAY 43 DAY 43 DAY 1-DAY 43 DAY 43 DAY 1-DAY 43 DAY 43 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm M1 = Ventral Side of Neck M6 = Inguinal Ventral side M7 = Dorsal Side of Neck R7 = Right Eye, Right Front Leg L7 = Left Eye 3M Corporate Toxicology 52 TRC No. 1152-100 N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS ________________________ Cell Proliferation Study with N-EtFOSE. PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 5 (4-Week Recovery) SUBGROUP: 3 ANIMAL # OBSERVATIONS_________________SEVERITY LOC TIME OCCURRED R10581 Normal DAY 1-DAY 43 Terminal Kill DAY 43 R10582 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10583 Normal Termi na 1 Kill DAY 1-DAY 43 DAY 43 R10584 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10585 Normal Terminal Kill STUDY: 1132-100 GROUP: 5 (4-Week Recovery) ANIMAL # OBSERVATIONS_________________ SEVERITY R10586 Normal Terminal Kill DAY 1-DAY 43 DAY 43 SUBGROUP: 4 LOC TIME OCCURRED DAY 1-DAY 43 DAY 43 R10587 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10588 Normal Thin Normal Terminal Kill DAY 1-DAY 22 DAY 29 DAY 36-DAY 43 DAY 43 R10589 Normal Thin Normal Thin Terminal Kill DAY 1-DAY 8 DAY 15 DAY 22 DAY 29-DAY 43 DAY 43 R10590 Normal Lacrimation Lacrimation Lacrimation Terminal Kill STUDY: 1132-100 GROUP: 5 (4-Week Recovery) ANIMAL # OBSERVATIONS SEVERITY R10591 Normal Thin Normal Terminal Kill DAY 1-DAY 22 L7 DAY 29 R7 DAY 29-DAY 36 R7 DAY 43 DAY 43 SUBGROUP: 5 LOC TIME OCCURRED DAY 1 DAY 8-DAY 15 DAY 22-DAY 43 DAY 43 R10592 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10593 Normal Lacrimation Lacrimation Lacrimation Lacrimation Alopecia Alopecia Terminal Kill R7 R7 L7 L7 R7,L7 R7,L7 DAY 1-DAY 8 DAY 15 DAY 22 DAY 22-DAY 36 DAY 43 DAY 36 DAY 43 DAY 43 R10594 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10595 Normal Thin Normal Terminal Kill Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm R7 = Right Eye, Right Front Leg L7 = Left Eye, Left Front Leg DAY 1-DAY 8 DAY 15 DAY 22-DAY 43 DAY 43 Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 7 = Wy-14,643, 100 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm 3M Corporate Toxicology 53 N-EtFOSE, PFOS, PFOSA APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE. PFOS, and PFOSA in Rats STUDY: 1132-100 GROUP: 5 (4-Week Recovery) SUBGROUP: 6 ANIMAL # O B S E R V A T I O N S ______________ SEVERITY LOC TIME OCCURRED R10596 Normal DAY 1-DAY 43 Terminal Kill DAY 43 R10597 Normal Thin Normal Terminal Kill DAY 1-DAY 15 DAY 22 DAY 29-DAY 43 DAY 43 R10598 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10599 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R 10600 Normal Terminal Kill STUDY: 1132 -100 GROUP: 5 (4-Week Recovery) ANIMAL # OBSERVATIONS SEVERITY R10601 Normal Lacrimation Normal Terminal Kill DAY 1-DAY 43 DAY 43 SUBGROUP: 7 LOC TIME OCCURRED DAY 1 R7 DAY 8 DAY 15-DAY 43 DAY 43 R10602 R 10603 R10604 R10605 Normal Terminal Kill Normal Thin Terminal Kill Normal Thin Terminal Kill Normal Terminal Kill DAY 1-DAY 43 DAY 43 DAY 1-DAY 36 DAY 43 DAY 43 DAY 1-DAY 36 DAY 43 DAY 43 DAY 1-DAY 43 DAY 43 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm Subgroup 4 = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm ' :- R7 = Right Eye TRC No. 1132-100 3M Corporate Toxicology 54 cincincnnonnaannancincinna N-EtFOSE. PFOS, PFOSA_____________ ______________________________________________________________________________________________________________________________ TRC Wo. 1132-100 STUDY: 1132 -100 SUBGROUP 1 ANIMAL # DAY 2 R 10381 0.0 R 10382 0.0 R 10383 0.0 R 10384 0.0 R 10385 0.0 R 10386 0.0 R 10387 0.0 R 10388 0.0 R10389 0.0 R 10390 0.0 SEX: MALE GROUP: SUBGROUP 2 Animal # DAY 2 R10391 34.1 R10392 29.6 R10393 31.8 R 10394 40.9 R 10395 32.2 R 10396 33.6 R10397 37.8 R10398 35.3 R10399 R10400 34.0 33.5 APPENDIX TABLE 4 INDIVIDUAL TEST MATERIAL CONSUMPTION (PPM) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats 1 (48-Hour Post Dose Sacri fice) SUBGROUP 3 Animal ft DAY 2 SUBGROUP 4 Animal # IDAY 2 SUBGROUP 5 Animal # DAY 2 R 10401 R 10402 R 10403 R 10404 R10405 R 10406 R 10407 R 10408 R10409 R10410 11.5 12.3 10.8 11.1 12.5 6.9 11.8 11.4 11.2 10.8 R10411 R10412 R10413 R10414 R10415 R 10416 R10417 R10418 R 10419 R1042O 3.6 3.2 3.5 3.0 3.6 3.2 3.4 2.6 3.4 3.1 R10421 R 10422 R10423 R10424 R10425 R10426 R10427 R 1 0428 R10429 R10430 2.3 2.3 2.3 2.4 2.0 1.8 2.3 1.4 2.3 1.6 SUBGROUP 6 Animal # R10431 R10432 R10433 R 10434 R10435 R10436 R 10437 R 10438 R 10439 R 10440 DAY 2 11.8 10.8 11.9 11.1 11.1 8.2 10.7 14.9 11.2 12.7 SUBGROUP 7 Animal # R 10441 R 10442 R 10443 R10444 R 10445 DAY 2 11.0 9.8 9.1 11.1 11.5 STUDY: 1132 -100 SUBGROUP 1 ANIMAL # DAY 7 R 10446 0.0 R 10447 0.0 R 10448 R 10449 0.0 0.0 R10450 0.0 R10451 0.0 R10452 R10453 R10454 0.0 0.0 0.0 R10455 0.0 SEX: MALE GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP 2 SUBGROUP 3 SUBGROUP 4 Animal # DAY 7 Animal # DAY 7 Animal # DAY 7 R10456 31.1 R10461 11.8 R 10466 3.4 R10457 36.0 R10462 12.4 R 10467 3.6 R10458 38.1 R 10463 12.4 R 10468 3.6 R10459 33.3 R 10464 10.2 R 10469 3.3 R10460 32.3 R 10465 11.7 R 10470 3.5 SUBGROUP 5 Animal # R 10471 R10472 R10473 R10474 R10475 DAY 7 2.2 2.3 2.3 2.1 2.3 SUBGROUP 6 Animal tt R 10476 R 10477 R 10478 R 10479 R10480 DAY 7 10.8 11.3 12.2 11.0 11.6 SUBGROUP 7 Animal # R 10481 R10482 R10483 R10484 R10485 DAY 7 10.2 10.8 10.9 12.0 11.4 STUDY: 1132 -100 SUBGROUP 1 ANIMAL # DAY 8 R 10486 0.0 R 10487 0.0 R 10488 0.0 R 10489 0.0 R 10490 0.0 R10491 0.0 R 10492 0.0 R 10493 0.0 R 10494 0.0 R 10495 0.0 SEX: MALE DAY 14 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 GROUP : 3 (14-Day Post Dose Sacrifice) SUBGROUP 2 SUBGROUP 3 ANIMAL # DAY 8 DAY 14 Animal # R 10496 29.9 27.2 R10501 R 10497 35.8 28.6 R 10502 R 10498 33.9 28.9 R10503 R 10499 35.2 28.3 R 10504 R 10500 34.9 29.5 R10505 DAY 13 11.7 11.3 12.1 11.9 13.4 DAY 14 9.6 9.3 9.9 9.7 11.0 SUBGROUP 4 Animal # R10506 R 10507 R10508 R10509 R10510 DAY 8 3.5 3.6 3.8 4.1 3.4 DAY 14 3.1 2.8 3.3 3.5 3.0 SUBGROUP 5 Animal # R105 11 R10512 R 10513 R10514 R10515 DAY 8 2.3 2.2 2.3 2.3 2.3 DAY 14 2.1 1.9 2.0 2.1 2.0 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm Subgroup 4 = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm 3 Corporate Toxicology 55 onaaaanacnacnoara-n N-EtFOSE. PFOS, PFOSA STUDY: 1132-100 SUBGROUP 6 ANIMAL # DAY 8 R 10516 11 .5 R 10517 11 .0 R10518 11.7 R 10519 10.2 R10520 11.0 SEX: MALE DAY 14 10.1 9.3 9.6 8.8 10.1 APPENDIX TABLE 4 (Continued) INDIVIDUAL TEST MATERIAL CONSUMPTION (PPM) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP 7 ANIMAL # DAY 8 DAY 14 R10521 R10522 R10523 R 10524 R10525 11.7 11.0 12.1 11.0 12.1 10.2 10.1 10.1 9.7 10.1 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 8 R10526 0.0 R10527 0.0 R10528 0.0 R10529 0.0 R10530 0.0 R10531 0.0 R10532 0.0 R10533 0.0 R10534 0.0 R 10535 0.0 SEX: MALE DAY 15 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 GROUP: 4 (1-Week Recovery) SUBGROUP 2 SUBGROUP 3 ANIMAL # DAY 8 DAY 15 Animal # R 10536 R10537 R10538 32.2 31.1 33.1 25.3 25.5 28.8 R10541 R10542 R10543 R10539 31.7 27.2 R10544 R10540 39.9 33.3 R10545 DAY 8 12.4 11.6 11.5 11.7 13.1 DAY 15 10.2 9.5 9.0 9.8 10.3 SUBGROUP 4 Animal # R 10546 R 10547 R 10548 R10549 R10550 DAY 8 3.3 3.5 3.4 3.5 3.5 DAY 15 2.9 2.9 2.9 3.1 3.0 STUDY: 1132-100 SUBGROUP: 6 ANIMAL # DAY 8 R10556 11.9 R10557 11.9 R10558 10.7 R10559 12.2 R 10560 11.0 SEX: MALE DAY 15 9.7 9.4 9.1 9.5 9.4 GROUP: 4 SUBGROUP: 7 Animal # DAY 8 R10561 11.3 R10562 12.6 R10563 11.7 R10564 11.5 R10565 12.3 DAY 15 10.1 10.1 10.0 10.8 10.7 nnnnon TRC No. 1132-100 SUBGROUP 5 Animal # R10551 R10552 R10553 R10554 R10555 DAY 8 2.2 2.5 2.6 2.3 2.5 DAY 15 1.8 2.0 2.1 1.9 2.0 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 Subgroup 5 Subgroup 6 Subgroup 7 0 ppm (Control) N-EtFOSE 300 ppm N-EtFOSE 100 ppm N-EtFOSE 30 ppm PFOS 20 ppm PFOSA 100 ppm Wy-14,643 100 ppm 3M Corporate Toxicology 56 nnnnnnnncnaaonanannraon N-EtFOSE. PFOS. P F O S A __________________ ____________________________________________________________________ _____________________________ _____________________ TRC No. 1132-100 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 8 R 10566 0.0 R10567 0.0 R10568 0.0 R 10569 0.0 R10570 0.0 R10571 0.0 R 10572 0.0 R10573 0.0 R 10574 0.0 R 10575 0.0 SEX: MALE DAY 15 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 APPENDIX TABLE 4 (Continued) INDIVIDUAL TEST MATERIAL CONSUMPTION (PPM) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 5 (4-Week Recovery) SUBGROUP 2 SUBGROUP 3 ANIMAL # DAY 8 DAY 15 ANIMAL # DAY 8 R10576 29.1 25.5 R10581 11.9 R10577 34.4 26.9 R10582 11.5 R 10578 36.9 30.4 R 10583 13.0 R10579 33.2 27.6 R 10584 12.2 R1O580 29.9 28.0 R10585 10.6 DAY 15 10.3 9.4 11.3 10.7 9.2 SUBGROUP 4 ANIMAL 1* R10586 R10587 R10588 R 10589 R10590 DAY 8 3.4 3.8 3.6 3.7 3.7 DAY 15 3.0 3.0 3.0 2.7 3.1 STUDY: 1132-100 SUBGROUP 6 ANIMAL # DAY 8 R 10596 12.3 R10597 10.1 R 10598 12.3 R10599 15.5 R 10600 11.7 SEX: MALE DAY 15 10.1 9.1 9.6 10.5 9.5 GROUP: 5 (4-Week Recovery) SUBGROUP 7 ANIMAL # DAY 8 DAY 15_____ R 10601 11.6 10.0 R10602 11.9 9.4 R1O603 11.5 10.7 R 10603 11.8 10.2 R 10604 12.4 9.8 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm Subgroup 4 = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm SUBGROUP 5 ANIMAL # R10591 R10592 R10593 R10594 R10595 DAY 8 2.4 2.3 2.4 2.3 2.5 DAY 15 2.0 1.9 1.8 2.0 2.1 3M Corporate Toxicology 57 nnnnnnoaaaonarjoainocina N-EtFOSE. PFOS, PFOSft___________________________________________________________________________________________________________________________________________ TRC No. 1132-100 STUDY: 1132-100 Subgroup: 1 ANIMAL ID: SEX: MALE APPENDIX TABLE 5 INDIVIDUAL ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO BODY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE, PFQS, and PFOSA in Rats GROUP: 1 (48 Hour Post Dose) R10381 R 10382 R 10383 R 10384 R10385 R 10386 R 10387 R 10388 BODY WEIGHT (G) 211.4 232.2 200.8 214.9 197.1 190.1 199.1 196.5 Liver (G) % BODY WEIGHT 8.186 3.872 8.454 3.641 7.254 3.613 6.922 3.221 7.356 3.732 6.978 3.671 6.828 3.429 6.914 3.519 STUDY: 1132-100 SEX: MALE GROUP: 1 (48 Hour Post Dose) Subgroup: 2 ANIMAL ID: R10391 R 10392 R 10393 R 10394 R10395 R 10396 R 10397 R 10398 BODY WEIGHT (G) 195.8 219.3 195.7 176.1 226.2 206.3 224.8 226.9 Liver (G) % BODY WEIGHT 7.123 3.638 7.703 3.513 7.659 3.914 6.158 3.497 7.902 3.493 8.001 3.878 8.791 3.911 9.397 4.141 STUDY: 1132-100 SEX: MALE GROUP: 1 (48 Hour Post Dose) Subgroup: 3 ANIMAL ID: R10401 R104O2 R10403 R 10404 R 10405 R 10406 R10407 R10408 BODY WEIGHT (G) 224.6 Liver (G) X BODY WEIGHT 8.109 3.610 219.5 9.187 4.185 237.6 9.724 4.093 228.4 8.574 3.754 218.3 7.972 3.652 221.5 8.326 3.759 208.9 7.853 3.759 210.0 8.260 3.933 STUDY: 1132-100 SEX: MALE GROUP: 1 (48 Hour Post Dose) Subgroup: 4 ANIMAL ID: R10411 R10412 R10413 R10414 R10415 R10416 R10417 R10418 BODY WEIGHT (G) Liver (G) % BODY HEIGHT 196.6 7.739 3.936 215.9 8.269 3.830 199.4 7.061 3.541 215.5 7.843 3.639 202.2 7.953 3.933 204.5 8.746 4.277 203.8 7.224 3.545 200.0 7.268 3.634 STUDY: 1132-100 SEX: MALE GROUP: 1 (48 Hour Post Dose) Subgroup: 5 ANIMAL ID: R10421 R10422 R 10423 R10424 R10425 R 10426 R 10427 R 10428 BODY WEIGHT (G) 220.6 Liver (G) % BODY WEIGHT 8.297 3.761 215.0 8.427 3.920 217.1 8.171 3.764 210.0 8.104 3.859 219.0 8.128 3.711 211.4 7.975 3.772 175.3 6.174 3.522 210.0 8.364 3.983 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 =0 ppm (Control) =N-EtFOSE 300 ppm =N-EtFOSE 100 ppm =N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm R10389 207.9 8.067 3.880 R 10390 225.8 8.180 3.623 R 10399 202.7 7.581 3.740 R10400 213.3 8.466 3.969 R 10409 226.7 8.893 3.923 R10410 215.4 8.256 3.833 R10419 221.2 8.025 3.628 R10420 219.9 7.754 3.526 R 10429 198.1 6.633 3.348 R10430 212.4 7.206 3.393 3M Corporate Toxicology 58 nnnnn n n ci o a n n n n c n n n n n N-EtFOr.SrE.r.i :PFOS, PFOSA___________________________________________________________________________________________________________________________________________ TRC No. 1132-100 STUDY: 1132-100 Subgroup: 6 ANIMAL ID: SEX: MALE APPENDIX TABLE 5 (Continued) INDIVIDUAL ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGANI TO BODY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 1 (48 Hour Post Dose) R10431 R 10432 R 10433 R 10434 R10435 R10436 R 10437 R 10438 BODY WEIGHT (G) 216.6 167.5 205.0 246.6 209.7 222.6 232.2 210.2 Liver (G) % BODY WEIGHT 7.666 3.539 5.890 3.516 7.391 3.605 9.169 3.718 7.759 3.700 8.067 3.624 9.131 3.932 8.484 4.036 STUDY: 1132-100 SEX: MALE GROUP: 1 (48 Hour Post Dose) Subgroup: 7 ANIMAL ID: R10441 R 10442 R 10443 R 10444 R10445 BODY WEIGHT (G) Liver (G) % BODY WEIGHT 211.9 9.692 4.574 223.7 10.169 4.546 224.2 9.532 4.252 211.5 9.268 4.382 214.6 9.114 4.247 R 10439 219.2 7.910 3.609 R 10440 207.2 8.349 4.029 STUDY: 1132-100 SEX: MALE GROUP: 2 (7 Day Post Dose) Subgroup: 1 ANIMAL ID: R 10446 R 10447 R 10448 R 10449 BODY WEIGHT (G) 240.7 Liver (G) X BODY WEIGHT 7.397 3.073 230.0 8.437 3.668 270.8 10.213 3.771 253.3 8.259 3.261 STUDY: 1132-100 SEX: MALE GROUP: 2 (7 Day Post Dose) Subgroup: 2 ANIMAL ID: R 10456 R10457 R 10458 R10459 BODY WEIGHT (G) 232.3 Liver (G) % BODY WEIGHT 8.632 3.716 220.7 9.842 4.459 227.3 9.704 4.269 252.6 10.572 4.185 STUDY: 1132-100 SEX: MALE GROUP: 2 (7 Day Post Dose) Subgroup: 4 ANIMAL ID: R 10466 R 10467 R 10468 R10469 BODY WEIGHT (G) 225.5 256.5 253.4 248.8 Liver (G) X BODY WEIGHT 8.224 3.647 9.225 3.596 8.820 3.481 9.030 3.629 R10450 230.2 7.160 3.110 R 10460 242.7 9.459 3.897 R10470 236.8 7.408 3.128 R 10451 236.9 7.894 3.332 R 10452 256.6 8.914 3.474 Subgroup: 3 R 10461 275.0 9.288 3.377 Subgroup: 5 R10471 247.1 8.531 3.452 R10453 239.2 7.852 3.283 R 10462 264.0 9.923 3.759 R 10472 232.6 8.558 3.679 R10454 258.7 9.101 3.518 R10463 272.1 10.994 4.040 R 10473 237.0 8.575 3.618 R 10455 264.3 9.526 3.604 R10464 249.6 9.144 3.663 R 10474 241.9 9.240 3.820 R 10465 232.4 8.974 3.861 R 10475 258.3 9.247 3.580 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm Subgroup 4 = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm 3M Corporate Toxicology 59 n n n n n n n a n rp o n o n n n n a ri n n N-EtFOSE, PFOS, PFOSA____________________________________________________________________________________________________________________________________ _______ TRC No. 1132-100 STUDY: 1132-100 Subgroup: 6 ANIMAL ID: APPENDIX TABLE 5 (Continued) INDIVIDUAL ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO BODY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats SEX: MALE GROUP: 2 (7 Days Post Dose) R 10476 R10477 R 10478 R10479 R10480 Subgroup: 7 R10481 R 10482 BODY WEIGHT (G) 270.9 Liver (G) X BODY WEIGHT 10.791 3.983 247.9 9.282 3.744 283.1 12.088 4.270 244.9 9.361 3.822 240.5 9.441 3.926 240.9 14.415 5.984 249.3 15.569 6.245 STUDY: 1132-100 SEX: MALE GROUP: 3 (14 Days Post Dose) Subgroup: 1 ANIMAL ID: R 10486 R10487 R 10488 R10489 R 10490 R10491 R 10492 R 10493 BODY WEIGHT (G) 300.5 Liver (G) % BODY WEIGHT 10.763 3.582 279.5 8.629 3.087 322.4 11.274 3.497 297.5 9.459 3.179 270.8 8.485 3.133 326.6 11.300 3.460 259.6 8.723 3.360 311.4 10.192 3.273 STUDY: 1132-100 SEX: MALE GROUP: 3 (14 Days Post Dose) Subgroup: 2 ANIMAL ID: R 10496 R 10497 R 10498 R10499 R10500 Subgroup: 3 R10501 R10502 BODY WEIGHT (G) 319.3 Liver (G) X BODY WEIGHT 16.134 5.053 245.3 11.055 4.507 292.7 15.086 5.154 286.5 14.856 5.185 294.8 13.611 4.617 276.5 11.837 4.281 299.8 10.967 3.658 STUDY: 1132-100 SEX: MALE GROUP: 3 (14 Days Post Dose) Subgroup: 4 ANIMAL ID: R10506 R10507 R10508 R 105 09 R 10510 Subgroup: 5 R 10511 R10512 BODY WEIGHT (G) 314.6 Liver (G) X BODY WEIGHT 11.681 3.713 307.9 11.629 3.777 288.8 11.918 4.127 304.0 10.561 3.474 284.5 9.478 3.331 290.1 10.275 3.542 261.2 8.616 3.299 STUDY: 1132-100 SEX: MALE GROUP: 3 (14 Days Post Dose) Subgroup: 6 ANIMAL ID: R 10516 R10517 R10518 RI0519 R10520 Subgroup: 7 R 10521 R10522 BODY WEIGHT (G) 266.9 253.5 275.4 263.4 281.5 273.5 279.6 Liver (G) X BODY WEIGHT 11.929 4.469 9.689 3.822 10.807 3.924 10.022 3.805 11.383 4.044 19.233 7.032 21.012 7.515 R10483 269.9 16.419 6.083 R 10494 330.3 10.084 3.053 R105O3 282.3 10.191 3.610 R10513 295.5 10.735 3.633 R10523 308.4 21.778 7.062 R10484 233.6 16.185 6.929 R10495 275.8 9.040 3.278 R 10504 294.4 12.437 4.225 R 10514 283.5 9.832 3.468 R10524 267.5 18.962 7.089 R10485 274.4 17.845 6.503 R10505 269.2 10.929 4.060 R10515 298.8 10.554 3.532 R10525 286.5 18.891 6.594 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 =0 ppm (Control) =N-EtFOSE 300 ppm =N-EtFOSE 100 ppm =N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm 3M Corporate Toxicology 60 N-EtFOSE, PFOS, PFOSA STUDY: 1132-100 Subgroup: 1 ANIMAL ID: SEX: MALE APPENDIX TABLE 5 (Continued) INDIVIDUAL ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO BODY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 4 (1 Week Recovery) R 10526 R10527 R10528 R10529 R10530 R10531 R 10532 R10533 BODY WEIGHT (G) 320.7 Liver (G) % BODY WEIGHT 9.938 3.099 378.4 14.030 3.708 369.4 14.007 3.792 338.7 11.954 3.529 311.9 8.511 2.729 323.4 10.041 3.105 351.8 11.082 3.150 328.1 11.224 3.421 STUDY: 1132-100 SEX: MALE GROUP: 4 (1 Week Recovery) Subgroup: 2 ANIMAL ID: R10536 R 10537 R10538 R10539 R10540 Subgroup: 3 R10541 R10542 BODY WEIGHT (G) 277.2 Liver (G) % BODY WEIGHT 12.879 4.646 294.8 13.775 4.673 296.3 15.268 5.153 282.0 11.204 3.973 316.1 17.466 5.525 343.0 13.108 3.822 336.0 13.407 3.990 STUDY: 1132-100 SEX: MALE GROUP: 4 (1 Week Recovery) Subgroup: 4 ANIMAL ID: R10546 R10547 R10548 R 10549 R10550 Subgroup: 5 R10551 R10552 BODY WEIGHT (G) 326.1 Liver (G) % BODY WEIGHT 11.798 3.618 302.8 10.312 3.406 315.9 9.597 3.038 329.9 10.642 3.226 334.9 10.395 3.104 315.7. 10.057 3.186 304.8 10.876 3.568 STUDY: 1132-100 SEX: MALE GROUP: 4 (1 Week Recovery) Subgroup: 6 ANIMAL ID: R10556 R10557 R10558 R10559 R10560 Subgroup: 7 R 10561 R 10562 BODY WEIGHT (G) 324.3 Liver (G) % BODY WEIGHT 13.898 4.286 293.2 12.498 4.263 304.5 12.203 4.008 318.9 12.907 4.047 307.9 11.899 3.865 286.7 13.896 4.847 300.4 13.225 4.402 STUDY: 1132-100 SEX: MALE GROUP: 5 (4 Week Recovery) Subgroup: 1 ANIMAL ID: R10566 R 10567 R 10568 R 10569 R10570 R 10572 R10573 R10574 BODY WEIGHT (G) 419.6 410.4 430.1 478.5 349.9 369.6 425.4 391.0 Liver (G) % BODY WEIGHT 12.914 3.078 13.400 3.265 12.560 2.920 20.255 4.233 11.635 3.325 9.622 2.603 14.000 3.291 10.276 2.628 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 = 0 ppm (Control) = N-EtFOSE 300 ppm = N-EtFOSE 100 ppm = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 - Wy-14,643 100 ppm 3M Corporate Toxicology 61 R 10534 314.6 10.006 3.181 R 10543 287.0 11.587 4.037 R10553 305.3 10.466 3.428 R10563 248.2 9.352 3.768 R10575 391.1 10.538 2.694 TRC No. 1132-100 R 10535 356.4 12.421 3.485 R 10544 309.6 11.404 3.683 R 10554 339.9 11.776 3.465 R10564 306.0 11.826 3.865 R 10545 314.2 10.325 3.286 R10555 336.7 12.298 3.653 R10565 304.6 11.654 3.826 nnnnnnnnnnnnmnnn N-EtFOSE. PFOS, PFOSA STUDY: 1132-100 Subgroup: 2 ANIMAL ID: APPENDIX TABLE 5 (Continued) INDIVIDUAL ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO BODY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats SEX: MALE GROUP: A (1 Week Recovery) R10576 R10577 R10578 R10579 R10580 Subgroup: 3 R10581 R 10582 BODY WEIGHT (G) 394.9 Liver (G) % BODY WEIGHT 18.930 4.794 390.8 17.760 4.545 389.7 14.301 3.670 385.6 16.167 4.193 416.3 18.573 4.461 404.3 13.739 3.398 369.6 11.940 3.231 STUDY: 1132-100 Subgroup: 4 ANIMAL ID: SEX: MALE GROUP: 4 (1 Week Recovery) R10586 R 10587 R10588 R 10589 BODY WEIGHT (G) 400.3 419.5 403.5 334.1 Liver (G) % BODY WEIGHT 13.786 3.444 13.145 3.133 13.568 3.363 12.480 3.735 R10590 410.5 12.535 3.054 Subgroup: 5 R 10591 359.4 11.787 3.280 R 10592 392.8 14.189 3.612 STUDY: 1132-100 SEX: MALE GROUP: 4 (1 Week Recovery) Subgroup: 6 ANIMAL ID: R 10596 R 10597 R 10598 R10599 BODY WEIGHT (G) 391.6 378.1 397.6 396.2 Liver (G) % BODY WEIGHT 14.315 3.656 13.607 3.599 17.252 4.339 16.640 4.200 R 10600 350.0 13.945 3.984 Subgroup: 7 R 10601 409.6 14.885 3.634 R 10602 451.5 16.676 3.693 nn R10583 406.9 14.615 3.592 R10593 386.0 12.789 3.313 R10603 363.3 12.285 3.382 non TRC No. 1132-100 R10584 390.1 12.139 3.112 R 10594 432.7 14.176 3.276 R 10604 370.8 11.371 3.067 R10585 354.1 11.490 3.245 R10595 438.5 14.346 3.272 R 10605 368.4 12.182 3.307 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 0 ppm (Control) N-EtFOSE 300 ppm N-EtFOSE 100 ppm N-EtFOSE 30 ppm Subgroup 5 Subgroup 6 Subgroup 7 PFOS 20 ppm PFOSA 100 ppm Wy-14,643 100 ppm 3M Corporate Toxicology 62