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TherImmune R esearch C orporation smosso. 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. W olfe, 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: 1132-100 yj/y I 3/15 c N-EtFOSE, PFOS, PFOSA D TABLE OF CONTENTS TRC No. 1132-100 COMPLIANCE STATEMENT ........................................................................................................................................4 STUDY IDENTIFICATION .............................................................................................................................................5 STUDY PERSONNEL....................................................................................................................................................... 6 0 SUM M ARY..........................................................................................................................................................................7 G INTRODUCTION............................................................................................................................................................... 9 TEST AND CONTROL ARTICLES................................................................................................................................9 0 TEST ANIMALS AND H USBA N D R Y .........................................................................................................................10 D M E T H O D S........................................................................................................................................................................11 Group Assignment and Dose L ev els................................................................................................................. 11 Test Article Formulation and Adm inistration.............................................. 11 C Observations and R eco rd s.................................................................................................................................12 Clinical Chemistry and Compound Level A n a ly sis....................................................................................... 13 T erm ination........................................................................................................................................................ 13 Organ Weights ................................................................................................................................................... 14 Cell Proliferation Tissue Collection and Immunohistochemical Evaluation ............................................. 14 Palmitoyl-CoA Oxidase Tissue Collection and Analyses .............................................................................14 D Tissue Collection for Electron Microscopic E valuation............................................................................... 14 Remaining Liver Tissue ................................................................................................................................... 15 Histopathology ................................................................................................................................................... 15 n Record R etention................................................................................................................................................ 15 R E SU L T S.......................................................................................................................................................................... 16 Body Weights and Body Weight Gains ......................................................................................................... 16 D Feed C onsum ption............................................................................................................................................. 16 Test Material C onsum ption..............................................................................................................................16 G Clinical O bservations........................................................................................................................................ 17 Terminal Body Weights and Liver W eigh ts.................................................................................................... 17 D SIGNATURE PAGE ........................................................................................................................................................19 TABLES D 1- SUMMARY OF BODY WEIGHTS (G ram s)................................................................................. 20 D 1A -SUMMARY OF BODY WEIGHT GAINS (G ram s)..................................................................................22 2- SUMMARY OF FEED CONSUMPTION (Grams) .................................................................... 23 D 3- SUMMARY OF CLINICAL OBSERVATIONS ..........................................................................25 G 3M Corporate Toxicology G 2 C 3/6 N-EtFOSE, PFOS, PFOSA 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 T IO S........................................................................................................................... 30 APPENDIX TABLES 1 - MALES: INDIVIDUAL BODY WEIGHTS (G ram s)......................................................................32 1A - INDIVIDUAL BODY WEIGHT GAINS (G ram s)........................................................................... 35 2 - INDIVIDUAL FEED CONSUMPTION (G ram s)........................................................................... 37 3 - INDIVIDUAL CLINICAL OBSERVATIONS................................................................................ 40 4 - INDIVIDUAL TEST MATERIAL CONSUMPTION (p p m ).........................................................55 5 - INDIVIDUAL ABSOLUTE LIVER WEIGHTS (Grams) AND ORGAN TO BODY WEIGHT R A T IO S........................................................................................................................... 58 3M Corporate Toxicology 3 0 N-EtFOSE, p r o s , PFOSA TRC No. 1132-100 D COMPLIANCE STATEMENT Cell Proliferation Study w ith N-EtFOSE, PFOS, and PFOSA in Rats 0 This study was conducted in the spirit of the Good Laboratory Practice Regulations as 0 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 D deviations from the aforementioned regulations which affected the quality or integrity of the C study or the interpretation of the results in the report. 0 0 Study Director: 0 D D D D D __________________________________________ 3M Corporate Toxicology D 4 0 3/8 o N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 D STUDY IDENTIFICATION Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats 0 TRC Study Number: D Test Articles: D Sponsor: D D Sponsor's Representative: 0 D Study Director: D D p Study Monitor/Principal Investigator: Lj D Study Timetable P Study Initiation: Initiation of Dosing: 48-Hour Post-Dose Sacrifice: Gr-> 7-Day Post-Dose Sacrifice: 14-Day Post-Dose Sacrifice: 1-Week Recovery pt--y 4-Week Recovery Study Termination: G 3M Corporate Toxicology c 1132-100 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 | ji1 5 G 3 /J c N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 0 STUDY PERSONNEL Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats D Study Director: p Study Pathologist: l_i D Veterinarian: Gary W. Wolfe, Ph.D ., D.A.B.T. Carolyn Moyer, D.V.M., A.C.V.P. Edward T. Greenstein, D.V .M ., A.C.L.A.M. 0 Quality Assurance Director: E. Paige Lacy, B.S. G Health and Safety Officer/ p Facility Manager L-- D Technical Supervisor: Report Supervisor: Robert K. Blackford, A.A., LATG Patrick Benson, B.S., LATG Lori B. Kaiser, B.S. D Technical Writer/Project Leader: 0 Laboratory Head Technician: D Technicians: D D C D c 3M Corporate Toxicology Kimberly A. Layton, B.S. Paula Davis, B.S./Sharron Stewart Daniel A. Jack Kelly Musselman, B.S. Brett Chaney, B.S., LATG FeleciaBishop, A.A., LATG Francis Onwuemene Larissa Nehrebeckyj, B.S. JoAnn Murphy Paul Martin, B.S. 6 c 33 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 c N-EtFOSE, PFOS, PFOSA TRC N o. 1132-100 D 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 D 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 of the 14-Day post-dose C 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. G 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 D 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. C Results of clinical pathology, histopathology, cell proliferation, immunohistochemistry, 0 palmitoyl-CoA oxidase activity, and electron microscopy will be reported separately. 0 D 0 D 0 D C D 3M Corporate Toxicology 8 -M e? N-EtFOSE, PEPS. PFOSA TRC N o. 1132-10 INTRODUCTION D D This study was designed fo assess cell proliferation and peroxisome proliferation in rats administered N-EtFOSE, PFOS, PFOSA and Wy-14,643. The design of this study included 5 0 groups of animals. Each Group contained 7 Subgroups. Subgroups 1, 2, 3, 4, 5, 6, and 7 D 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 D 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, 0 1999, respectively. In Group 1, the test diets were administered to 10 animals/Subgroup with the G 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 D control diet. D TEST AND CONTROL ARTICLES One 34.88 g sample of N-EtFOSE T-6316 (Lot No. 30035,30037, and 30039 combined), 0 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 D 5 years. One 81.97 g sample of Fxl2 Fluorad T-7091 (PFOSA) (Lot No. not provided), an C 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 0 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 D powder, was received from Cayman Chemical, Ann Arbor, MI, on February 22,1999 and stored 0 at ambient temperature. The purity was greater than 98 % and was stable for at least two years. 0 3M Corporate Toxicology 9 D J 3 i N-EtFOSE, PFOS, 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 79 F 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 c D N-EtFOSE, PFOS, PFOSA 0 METHODS TRC No. 1132-100 D flroun Assipnment. and Dose Levels Following examination by a staff veterinarian for physical condition, the rats were assigned to the study: Number of Male Rats D I Group Number (Time Point) C !eg s 1 0 (48 Hours) 2 (7 Days) 3 D (14 Days) 11 (1 wk r4ecovery) D 5 (4 wk recovery) D Total No. Of Control (0 ppm) 1 10 N-EtFOSE 300 ppm 2 10 100 ppm 3 10 30 ppm 4 10 10 5 5 5 10 5 5 5 10 5 5 5 10 5 55 50 30 30 30 PFOS (20 ppm) 5 10 5 5 5 5 30 PFOSA (100 ppm) 6 10 5 5 5 5 30 Wy-14,643 (1000 ppm) 7 5 5 5 5 5 25 Total No. 1 of Animals I 65 40 40 40 40 225 C 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 E 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 G removed and discarded without necropsy. D Test Article Formulation and Administration Dietary formulations of the test articles and Teklad 7012C Feed were prepared using the D following procedure: For Group 1, the appropriate amount of feed was weighed into a plastic container and C stored at ambient temperature and protected from light. For each dose level, the appropriate 0 3M Corporate Toxicology D 11 3S D N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 quantity of Teklad 7012C feed was accurately weighed into plastic containers. The proper amount D of the test article was weighed, using a stainless steel spatula, into a glass beaker. The 0 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 0 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 0 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 D used for rinsing and preparing the premix was taken from the preweighed feed in the plastic D containers for each dose level. From the preweighed feed, 10 kilograms was layered evenly into the Patterson-Kelly D 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 D preweighed feed. Each rinse was poured evenly into the blender. The remaining preweighed feed D was evenly poured into the blender. The blender was sealed and the dietary formulation was blended for approximately 30 minutes. D 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 0 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 C formulation and stored were stored in heat sealable foil bags protected from light at room D 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. D Observations and Records 0 Each animal was observed twice daily (a.m. and p.m.) for mortality and moribundity. 0 Findings were recorded as they were observed. 3M Corporate Toxicology 12 3< 2 N-EtFOSE, PFOS, PFQSA 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 o f 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 of exposure to the test diets, following blood collection. The animals scheduled for interim sacrifices were anesthetized with C 0 2, weighed, and exsanguinated. The abdominal cavity of 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 0 2, weighed, exsanguinated, andnecropsied. 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, PFQS, PFOSA TRC N o. 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 c N-EtFOSE, PFOS, PFOSA TOC No. 1132-100 points, as well as the 4-week recovery, for a total o f ten animals. The results will be reported separately. Remaining Liver Tissue The remaining liver tissue was frozen and stored at approximately -80 C at Pathology Associates International, Frederick, MD in the long-term archive for possible future analysis. Histooathology Livers from each animal that was examined for cell proliferation were stained with D hematoxylin and eosin, and examined microscopically for histopathological changes. The results C will be reported separately. c Record Retention All raw data, documentation, records, protocol, specimens, and final report generated as D 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 D charged. All raw data stored on magnetic media will remain at PAI. 0 C D 0 c C D 3M Corporate Toxicology G 15 3A9 D N-EtFOSE, PFOS, PFOSA____________________ TOC No. 1132-100 RESULTS 0 Body Weights and Body Weight Gains C 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 D Appendix 1A. Mean body weights and body weight gains were comparable in all groups throughout the C study with the exception of the 1-Week recovery animals on SD 15. There was a 14, 8, and 12% C 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 n u 100 ppm N-EtFOSE, PFOSA, and Wy-14,643 groups, respectively on SD 8-15. In addition, D 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. P Feed Consumption D Mean feed consumption is summarized in Table 2 and presented individually in Appendix D Table 2. Mean feed consumption was comparable in all groups with the exception o f decreases of n u 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. D Test Material Consumption C Mean test material consumption is summarized in Table 4 and presented individually in D Appendix Table 4. Test article consumption averaged 31.6 mg/kg for 300 ppm N-EtFOSE, 11.1 mg/kg for C 100 ppm N-EtFOSE, 3.3 ppm for 30 ppm N-EtFOSE, 2.2 mg/kg for PFOS, 10.8 mg/kg for 0 PFOSA, and 10.9 mg/kg for Wy-14,643. 0 D 3M Corporate Toxicology 16 D 330 I N-EtFOSE, PFO S, PFOSA TRC N o. 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 onSD21. 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% inthe 100 ppm Wy-14,643 group. Increases of25% and44%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-ElFOSE, 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 G 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. D C D 0 0 D C D C ______ __________________________________ __ 3M Corporate Toxicology 18 0 n 33A- N-EtFOSE, PFOS, PFOSA D SIGNATURE PAGE TRC No. 1132-100 D Study Director: Technical Writer: 0 D Report Supervisor: 0 0 Lori B. Kaiser, B.S./Date 0 0 D D D 0 D 3M Corporate Toxicology n 19 D 333 D D N-EtFOSE. PrOS. PFOSA TRC No. 1132-tQO TABLE 1 D SUMMARY OF BODY HEIGHTS (Grams) Ceil Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP: 1 (48-Hour Post Dose Sacrifice) PERIOD DOSE: SUBGROUP: (1) 1-M (2) 2-M (3) 3-M (4) 4-M (5) 5-M (6) 6-M (7) 7-M 0 DAY 1 MEAN 231.4 229.1 243.0 230.0 233.0 235.1 240.2 S.D. 15.84 16.30 9.08 10.76 15.13 21.52 6.04 DN 10 10 10 10 10 10 5 STUDY: 1132-100 SEX: MALE GROUP: 2 (7-Day Post Dose Sacrifice) C DOSE: <1) (2) (3) <4) (5) (6) (7) PERIOD SUBGROUP; 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 1 MEAN 229.2 228.4 244.8 227.1 229.9 242.6 237.3 S.D. 10.06 13.74 12.06 10.09 5.75 15.37 17.24 N 10 5 5 5 5 5 5 STUDY: 1132-100 SEX: MALE GROUP: 3 (14-Day Post Dose Sacrifice) D DOSE: (1) (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 1 MEAN 229.0 241.0 224.9 230.5 227.8 222.0 233.3 S.D. 18.70 26.37 15.78 14.12 12.98 12.44 14.48 N 10 5 5 5 5 5 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 5 276.5 19.55 5 D STUDY: 1132-100 SEX: MALE GROUP: 4 (1-Week Recovery) DOSE: (1) (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 1 0 MEAN S.D. N 234.8 11.72 10 223.5 15.66 5 230.7 13.49 5 237.0 12.19 5 227.6 9.90 5 232.8 511.18 216.5 15.95 5 DAY 8 DAY 15 C MEAN S.D. N MEAN S.D. N 281.9 23.79 10 261.0 9.12 5 344.7 23.28 10 *295.9 16.07 5 279.2 14.93 5 321.6 19.72 5 279.5 10.22 5 327.4 12.47 5 279.1 11.95 5 330.2 15.28 5 277.8 8.68 5 *317.8 10.88 5 261.4 19.20 5 *302.4 19.57 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 P (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (S) = PFOS 20 ppm n (7)(6) = PFOSA 100 ppm = Wy-14,643 100 ppm D _______ 3M Corporate Toxicology D ,-- i 0 D W-EtFOSE. pros. PFOSA TRC No. 1132-100 TABLE 1(Continued) D SUMMARY OF BODY UEIGHTS Cell Proliferation Study with M-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132-100 SEX: MALE GROUP: 5 (4-Week Recovery) DOSE: <1> (2) (3) (4) (5) (6) (7) D PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 1 MEAN 232.4 239.7 229.7 234.0 230.7 216.4 224.1 S.D. 16.93 7.52 7.60 8.87 14.41 24.23 16.63 N 10 5 5 5 5 5 5 DAY 8 MEAN 278.0 273.1 270.5 284.0 283.1 264.6 274.0 D S.D. N 24.62 10 10.13 5 5.10 5 14.47 5 17.94 5 12.93 5 18.07 5 DAY 15 0 MEAN S.D. 332.9 27.44 305.9 9.64 312.8 11.07 331.0 30.35 333.5 20.67 307.1 8.32 319.1 22.02 N 10 5 5 5 5 5 5 D DAY 22 MEAN 364.8 340.2 340.6 362.4 366.2 334.0 342.2 S.D. 28.98 7.04 15.55 38.96 24.02 15.52 25.79 N 9 5 5 5 5 5 5 0 DAY 29 MEAN 395.7 376.0 372.1 381.6 396.3 366.9 377.2 S.D. H 30.90 9 11.36 5 21.27 5 36.41 5 27.87 5 15.72 5 31.93 5 D DAY 36 MEAN S.D. 417.4 34.65 402.0 13.87 390.1 23.25 401.1 33.87 414.3 35.80 391.6 16.31 404.1 35.66 N 95555 5 5 D * 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. D (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm C (4) = N-EtFOSE 30 ppm (5) = PF0S 20 ppm (6) = PFOSA 100 ppm (7) = Wy-14,643 100 ppm C D 0 D D _______ 3M Corporate Toxicology D D 33S 0 c N-EtFOSE. PFOS, PFOSA TRC Wo. 1132-100 TABLE 1A D SUMMARY OF BODY WEIGHT GAINS (Grams) STUDY: 1132-100 SEX: MALE GROUP: 3 (14-Day Post Dose Sacrifice) DOSE: (1) (2) (3) (4) (5) (6) (7) 0 PERIOD SUBGROUP; 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 8 MEAN 44.7 45.2 51.3 * 55.8 49.1 39.6 43.2 S.D. 8.03 1.58 5.44 9.23 8.29 4.84 8.01 N 10 5 5 5 5 5 5 D STUDY: 1132-100 SEX: MALE GROUP: 4 (1-Week Recovery) DOSE: (1) (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP : 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 8 D MEAN S.D. N 47.1 13.98 10 37.5 8.65 5 48.6 6.12 5 42.4 2.92 5 51.5 4.78 5 45.0 9.06 5 44.9 3.99 5 DAY 15 MEAN S.D. N 62.8 13.62 10 * 34.9 15.25 5 * 42.4 9.50 5 47.9 3.43 5 51.1 7.96 5 * 39.9 4.39 5 * 41.0 8.06 5 D STUDY: 1132-100 SEX: MALE GROUP: 5 (4-Week Recovery) DOSE: (1) (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 8 0 MEAN S.D. N 45.5 13.67 10 33.4 5.79 5 40.7 6.19 5 50.0 8.34 5 52.3 4.26 5 48.2 14.43 5 49.9 6.54 5 D DAY 15 MEAN S.D. 54.9 7.26 * 32.8 3.60 42.3 11.83 47.1 16.86 50.4 8.13 42.6 6.70 45.1 6.88 N 10 5 5 55 5 5 D DAY 22 MEAN 29.1 34.3 27.9 31.4 32.7 26.8 23.1 S.D. N 5.40 9 5.44 5 6.01 5 9.52 5 4.63 5 11.61 5 8.45 5 DAY 29 MEAN 30.9 35.8 31.5 * 19.1 30.1 32.9 35.0 S.D. 5.27 5.45 6.49 8.87 5.03 6.00 7.87 N 95 5 5 5 5 5 DAY 36 MEAN 21.7 26.1 18.0 19.5 18.0 24.8 26.9 S.D. 5.45 5.80 11.13 2.62 8.93 5.17 7.06 D "N 95 5 5 5 5 5 * P less than .05 Analysis of Variance using DUNNETT'S Procedure D 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, D (1) = 'Control 0 ppm (2) = !N-EtFOSE 300 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm (7) = Wy-14,643 100 ppm (3) = IN-EtFOSE 100 ppm (6) = PFOSA 100 ppm G 3M Corporate Toxicology 22 D 336 0 N-EtFOSE. PFOS, PFOSA TRC Ho. 1132-100 TABLE 2 D STUDY: 1132-100 SUMMARY OF FEED CONSUMPTION (Grams) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats SEX: MALE GROUP: 1 (48-Hour Post Dose Sacrifice) DOSE: C D (2) (3) (4) (5) (6) (7) D PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 2 MEAN 22.9 26.1 26.7 25.0 23.9 26.9 25.2 S.D. 2.86 2.00 3.64 2.18 3.81 4.29 1.99 N 10 10 10 10 10 10 5 STUDY: 1132-100 SEX: MALE GROUP: 2 (7-Day Post Dose Sacrifice) D DOSE: (mg/kg) ( D (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 7 MEAN 163.4 155.6 171.8 159.0 156.0 165.9 157.1 S.D. 12.65 8.77 17.12 7.97 5.38 14.06 13.61 0 N 10 5 5 5 5 5 5 STUDY: 1132-100 SEX: MALE GROUP: 3 (14-Day Post Dose Sacrifice) D DOSE: (1) (2) (3) . (4) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M . 4-M 5-M 6-M 7-M DAY 8 MEAN 181.4 190.0 189.9 196.4 188.5 171.9 189.3 D S.D. N 10.78 10 14.43 5 4.50 5 9.75 5 11.11 5 11.91 5 19.22 5 DAY 14 C 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 *150.4 11.64 5 166.9 13.65 5 D STUDY: 1132-100 SEX: MALE GROUP: 4 (1-Week Recovery) DOSE: (1) (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 8 D MEAN S.D. N 195-2 17.45 10 174.5 12.37 5 194.6 10.37 :5 190.4 11.29 5 191.0 6.19 5 187.6 5.85 5 180.1 18.58 5 DAY 15 0 MEAN 212.8 *170.6 190.7 193.8 193.4 *183.7 189.4 S.D. 21.73 18.96 15.24 12.15 9.63 6.65 17.61 N 10 5 5 5 5 5 5 0 DAY 21 MEAN 185.4 160.6 173.0 176.1 167.6 171.8 169.8 S.D. 15.82 17.74 15.01 7.34 9.91 8.45 16.25 N 10 5 5 5 5 5 5 * P less than .05 Analysis of Variance using DUNNETT'S Procedure C 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 D (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm D (S) = PFOSA 100 ppm (7) = Wy 14,643 100 ppm G 3M Corporate Toxicology D 23 337 G D N-EtFOSE, PFOS. PFOSA TRC No. 1132-100 TABLE 2 (Continued) G SUMMARY OF FEED CONSUMPTION (Grams) cell Proliferation Study with N-EtFOSE. PFOS. and PFOSA in Rats STUDY: 1132-100 SEX:: MALE GROUP: 5 14-Week Recovery) DOSE: C D C2) (3) (4) (5 ) C6) (7) n SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY S MEAN 189.4 182.7 190.1 197.6 192.7 185.3 186.1 S.D. N 19.09 10 17.16 5 8.55 5 6.65 5 12.11 5 15.74 5 12.03 5 DAY 15 n 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 n DAY 22 MEAN 196.7 189.7 197.4 203.2 204.9 188.7 198.0 U S.D. 14.88 6.21 12.00 18.27 14.75 14.03 13.81 N 95555 55 0 DAY 29 MEAN 196.5 191.8 194.0 180.1 193.0 189.7 207.7 S.D. 14.41 14.17 17.53 12.70 17.90 14.67 17.83 DN DAY 36 955555 5 MEAN 198.0 201.6 196.6 181.8 191.8 198.9 209.8 n S.D. N 18.25 9 9.36 5 17.68 5 17.07 5 21.42 5 12.70 5 21.30 5 DAY 42 n MEAN 163.6 166.0 161.2 158.9 163.2 162.9 166.6 S.D. 19.66 8.50 13.10 8.91 20.71 16.13 18.64 Lw N 9 5 5 5 5 5 5 D * 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 all Groups during the recovery period CSD 21-SD 42). nL J C D s Control 0 ppm (2) = N-EtFOSE 300 ppm (3) s N-EtFOSE 100 ppm D (4) = N-EtFOSE 30 ppm (5) * PFOS 20 ppm (6) = PFOSA 100 ppm (7) Wy-14,643 100 ppm D G D c 0 3M Corporate Toxicology c D 24 33? D N-EtFOSE, PFOS, PFOSA TRC Wo. 1132-100 TABLE 3 D SUMMARY OF CLINICAL OBSERVATIONS 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) (5) (6) (7) D PERIOD DAY 1 SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M No. Observed 10 10 10 10 10 10 5 Normal 0 Discharge 10 100% 0 10 100% 0 9 90% 1 10% 10 100% 0 10 100% 0 10 100% 0 5 100% 0 DAY 3 No. Observed 0 Terminal Kill Normal Thin Alopecia 0 Rough Haircoat Lacrimation D 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 GROUP: 2 (7-Day Post Dose Sacrifice) E PERIOD DAY 1 DOSE: C D (2) (3) (4) (5) (6) SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M (7) 7-M No. Observed 10 5 5 5 5 5 5 D Normal Lacrimation 10 100% 0 5 100% 0 5 100% 0 5 100% 0 5 100% 0 4 80% 1 20% 5 100% 0 DAY 8 D 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 DOSE: SEX: MALE (1) GROUP: 3 (14-Day Post Dose Sacrifice) (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 1 n No. Observed Normal 10 10 100% 5 5 100% 5 5 100% 5 5 100% 5 5 100% 5 5 100% 5 5 100% 0 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 D 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 D (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) a N-EtFOSE 30 ppm D (5) = PFOS 20 ppm (6) = PFOSA 100 ppm <7) = Wy-14,643 100 ppm D D 3M Corporate Toxicology 25 D 331 0 bp nL.^ brn D br~i bn o D bP p Li D niwi c p D Ln j D c c 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) 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 10 5 10 100% 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% O O 0 5 5 100% 0 0 0 oCO 5 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 O 1 20% 0 5 5 100% 4 80% 1 20% 0 0 0 STUDY: 1132-100 SEX: MALE DOSE: (1) PERIOD SUBGROUP 1-M GROUP: 5 (4-Week Recovery) (2) (3) (4) 2-M 3-M 4-M DAY 1 No. Observed Normal 10 10 100% 5 5 100% 5 5 100% 5 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 (4) = N-EtFOSE 30 ppm (5) = 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 0 0 1 20% 5 5 100% 0 0 0 4N 0XO9 3M Corporate Toxicology 26 34 nu Li 0 0 Un D un u nL i 0 nL i nLj D D D D D D 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: 5 (4-Week Recovery) DOSE: SUBGROUP: (1) (2) (3) (4) (5) (6) 1-M 2-M 3-M 4-M 5-M 6-M DAY 21 No. Observed Moribund Kill 10 0 0 0 0 1 100% 0 0 0 0 0 DAY 22 No. Observed Normal Thin Abrasion Alopecia Lacrimation DAY 29 No. Observed Normal Thin Abrasion Alopecia Lacrimation 9 8 88% 0 1 11% 1 11% 0 9 7 77% 0 2 22% 1 11% 0 5 5 100% 0 0 0 0 05 5 100% 0 0 0 5 5 100% 0 0 0 0 5 5 100% 0 0 0 0 5 5 100% 0 0 00 225 40% 40% 0 0 1 20% 5 4 80% 0 0 0 1 20% 5 4 80% 0 0 0 1 20% 5 4 80% 1 20% 0 0 0 5 5 100% 0 0 0 0 DAY 36 No. Observed Normal Thin Reddened Abrasion Alopecia Lacrimation 69 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 Lacrimation 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 O 0 (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) a N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) a PFOS 20 ppm <6> = PFOSA 100 ppm (7) = Wy-14,643 100 ppm (7) 7-M 0 0 5 5 100% 0 0 00 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 3/ D N-EtFDSE, PFOS. PFOSA__________________________________________________________ __ TRC NO. 1132-100 TABLE 4 D SUMMARY OF TEST MATERIAL CONSUMPTION (PPM) 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) (5) (6) (7) D PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 2 MEAN 0.0 34.3 11.0 3.0 2.1 11.4 10.5 S.D. 0.00 3.18 1.56 0.31 0.35 1.69 1.01 DH 10 10 10 10 10 10 5 STUDY: 1132-100 SEX: MALE GROUP: 2 (7-Day Post Dose Sacrifice) D DOSE: (1) (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 7 MEAN 0.0 34.2 11.7 3.5 2.2 11.4 11.1 G S.D. N 0.00 10 2.85 5 0.90 5 0.13 5 0.09 5 0.55 5 0.08 5 STUDY: 1132-100 SEX: MALE GROUP: 3 (14-Day Post Dose Sacrifice) DOSE: (1) (2) (3) (4) (5) (6) (7) 0 PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 8 MEAN 0.0 33.9 12.1 3.7 2.3 11.1 11.6 S.D. 0.00 2.36 0.79 0.28 0.04 0.58 0.55 D N 10 5 5 5 5 5 5 DAY 14 0 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 9.6 0.55 5 10.0 0.19 5 D STUDY: 1132-100 SEX: MALE GROUP: 4 (1-Week Recovery) DOSE: (1) (2) (3) (4) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M DAY 8 D MEAN S.D. 0.0 0.00 33.6 3.60 12.1 0.68 3.4 0.09 2.4 0.16 11.5 0.65 11.9 0.55 N 10 5 5 5 5 5 5 0 DAY 15 D 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 9.4 0.22 5 10.3 o.3a 5 (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm 0 (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm G (6) = PFOSA 100 ppm (7) = Wy 14,643 100 ppm D 0 D 3M Corporate Toxicology 0 28 c D N-EtFOSE. PFOS. PFOSft TRC No. 1132-100 TABLE 4 (Continued) G 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) (5) (6) (7) PERIOD SUBGROUP: 1-M 2-M 3-M 4-M 5-M 6-M 7-M 0 DAY 8 n DAY 15 G 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 12.4 1.96 5 9.8 0.55 5 11.8 0.35 5 10.0 0.48 5 (1) = Control 0 ppm (2) = N-EtFOSE 300 ppm (3) = N-EtFOSE 100 ppm (4) = N-EtFOSE 30 ppm (5) = PFOS 20 ppm D (6) = PFOSA 100 ppm (7) = Wy 14,643 100 ppm D D C D 0 D 0 D G _______ c 3M Corporate Toxicology 0 3<X3 0 p Lj nU nU nb D ip_i D D D PU--1 D 0 P bp D C D 0 G 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) (2) (3) (4) 1-M 2-M 3-M 4-M (5) 5-M (6) 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 Liver (GXABSOLUTE) MEAN S.D. N 7.514 0.6364 10 7.878 0.8943 10 * 8.515 0.5893 10 7.788 0.5117 10 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 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 BODY 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 (GXABSOLUTE) 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 STUDY: 1132-100 DOSE: SUBGROUP: SEX: MALE GROUP: 3 (14-Day Post Dose Sacrifice) (1) (2) (3) (4) 1-M 2-M 3-M 4-M BODY WEIGHT (G) MEAN S.D. N 297.4 25.14 10 287.7 26.80 5 284.4 12.60 5 300.0 12.82 5 Liver (GXABSOLUTE) MEAN S.D. N 9.795 1.0821 10 * 14.148 1.9481 5 11.272 0.8740 5 11.053 1.0243 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 Subgroup 1 = 0 ppm (Control) Subgroup 2 = H-EtFOSE 300 ppm Subgroup 3 = H-EtFOSE 100 ppm Subgroup 4 = N-EtFOSE 30 ppm Sitogroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm 208.9 13.37 10 7.748 0.7929 10 3.703 0.2152 10 (5) 5-M 243.4 9.94 5 8.830 0.3776 5 3.630 0.1349 5 (5) 5-M 285.8 14.93 5 10.002 0.8465 5 3.495 0.1243 5 213.7 20.61 10 7.982 0.9430 10 3.731 0.1968 10 (6) 6-M 257.5 18.54 5 * 10.193 1.2284 5 * 3.949 0.2018 5 (6) 6-M 268.1 10.83 5 10.766 0.9285 5 * 4.013 0.2723 5 217.2 6.30 5 * 9.555 0.4102 5 * 4.400 0.1559 5 (7) 7-M 253.6 17.88 5 * 16.087 1.2524 5 * 6.349 0.3791 5 (7) 7-M 283.1 15.81 5 * 19.975 1.3302 5 * 7.058 0.3263 5 3M Corporate Toxicology 30 N-EtFOSE. PFOS, PFOSA______________________________________________________________________________ TRC No. 1132-100 TABLE 5 (Continued) D SUMMARY OF ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO BODY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE,r PF0Sr and PFOSA in Rats STUDY:.1132-100 SEX: MALE GROUP : 4 (1-Week Recovery) DCISE: (1) (2) (3) (4) (5) (6) (7) D SUBGROUP: 1-K 2-M 3-M 4-M 5-M 6-M 7-M BODY WEIGHT (G) MEAN D 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) D 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 D Liver (% BODY WEIGHT) MEAN 3.320 * 4.794 3.764 3.278 3.460 * 4.094 * 4.142 S.D. 0.3244 0.5861 0.3017 0.2359 0.1768 0.1785 0.4693 N 10 5 5 ' ;5 5 5 5 0 STUDY: 1132-100 SEX: MALE GROUP : 5 (4-Week Recovery) ' DOSE: (1) (2) (3) (4) (5) (6) (7) D SUBGROUP: BODY WEIGHT (G) 1-M 2-M 3-M 4-M 5-M 6-M 7-M MEAN 407.3 395.5 385.0 393.6 401.9 382.7 392.7 S.D. 37.62 12.11 22.75 34.06 33.28 19.84 37.67 N 9 55 55 5 5 Liver (GKABSOLUTE) MEAN 12.800 * 17.146 12.785 13.103 13.457 15.152 13.480 D S.D. N 3.1700 9 1.9137 5 1.3292 5 0.5906 5 1.1267 5 1.6710 5 2.2220 5 D Liver (% BODY WEIGHT) MEAN 3.115 * 4.333 3.316 3.346 3.351 * 3.956 3.417 S.D. 0.5079 0.4281 0.1849 0.2701 0.1470 0.3258 0.2545 0N 9 55 55 5 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 D Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm D D D C 3M Corporate Toxicology c 3S nncinatnci.aaapaonacinannn N-EtFOSE. P'F'O-S,f 'P'FOSA_______________________________ _________________________ ________________ ____________________________________________ ________ TRC No. 1132-100 APPENDIX TABLE 1 INDIVIDUAL BODY WEIGHTS (Grams) tell 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 SUBGROUP 5 SUBGROUP 6 ANIMAL # DAY 1 Animal # DAY 1 Animal # DAY 1 Animal # DAY 1 Animal # DAY 1 Animal # R 10381 R10382 R10383 R10384 R 10385 R10386 R10387 R10388 R 10389 R 10390 226.0 258.4 229.9 241.5 221.0 207.7 222.6 216.9 238.7 251.0 R 10391 R10392 R10393 R10394 R10395 R10396 R10397 R10398 R10399 R10400 215.5 244.9 221.6 193.7 246.0 229.4 238.9 243.3 223.1 234.4 R10401 R10402 R10403 R10404 R10405 R10406 R10407 R10408 R10409 R10410 245.0 242.7 254.8 253.8 236.9 247.6 232.3 228.5 251.1 237.2 R10411 R10412 R10413 R10414 R10415 R10416 R10417 R10418 R10419 R10420 217.9 242.4 215.7 234.2 223.6 230.7 225.4 222.3 242.7 245.4 R 10421 R10422 R10423 R10424 R10425 R10426 R10427 R10428 R10429 R10430 241.6 237.2 240.1 229.9 243.1 239.8 196.9 243.1 216.4 242.0 R10431 R10432 R10433 R10434 R10435 R10436 R10437 R10438 R10439 R 10440 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 R10443 R10444 R10445 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 R10446 R10447 221.6 219.5 R10456 R10457 229.3 215.7 R10461 R10462 250.3 243.1 R10466 R10467 212.5 236.3 R10448 244.4 R10458 214.2 R10463 258.4 R10468 226.2 R10449 R10450 231,8 218.4 R10459 R10460 246.5 236.4 R10464 R10465 246.4 225.8 R10469 R10470 236.9 223.5 R10451 217.1 R10452 232.0 R10453 226.6 R10454 238.5 R10455 241.7 STUDY: 1132-100 SUBGROUP 1 ANIMAL # 1DAY 1 R10486 223.5 R10487 R10488 214.9 230.4 R10489 247.1 R10490 R 10491 R 10492 199.9 239.6 212.1 R10493 248.7 R10494 257.3 R10495 216.6 SEX: MALE DAY 8 277.4 260.3 282.7 292.0 254.5 274.5 258.5 285.3 288.9 262.9 GROUP : 3 (14-Day Post Dose Sacrifice) SUBGROUP 2 SUBGROUP 3 ANIMAL # DAY 1 DAY 8 Animal # DAY 1 R10496 271.1 315.8 R10501 227.3 R 10497 198.8 241.5 R10502 237.8 R10498 244.0 290.0 R10503 223.7 R10499 241.0 287.7 R10504 237.0 R10500 250.3 296.3 R10505 198.9 DAY 8 269.0 291.2 276.5 290.4 254.1 SUBGROUP 5 Animal # R10471 R10472 R10473 R10474 R10475 DAY 1 232.7 221.0 229.7 229.4 236.6 SUBGROUP 6 Animal # R10476 R10477 R10478 R10479 R10480 DAY 1 256.5 240.0 258.4 236.8 221.1 SUBGROUP 7 Animal # R10481 R10482 R 10483 R10484 R 10435 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 # R1Q511 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 n n n n n n n o n fn n n n n in n n n n n r"! Mr -E--t-FO-S-E,1 P--FOS,i PFOSA________________________________________________________________________________________________________________________________TRC Ho. 1132-100 STUDY: 1132-100 SUBGROUP 6 ANIMAL # DAY 1 R10516 R10517 R10518 211.7 206.4 228.0 R10519 R10520 228.1 236.0 SEX: HALE 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 218.7 260.5 234.4 268.9 R10523 R10524 R10525 246.4 218.4 248.5 302.7 258.9 291.3 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 1 R10526 238.9 R10527 245.9 R10528 242.2 R10529 213.4 R10530 224.3 R10531 228.9 R10532 239.3 R10533 240.6 R10534 223.6 R10535 250.9 SEX: HALE 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 R10537 246.9 276.1 R10538 229.6 262.9 R10539 216.4 254.3 R10540 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 R10544 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 SUBGROUP 4 Animal # DAY 1 R10546 242.1 R10547 219.8 R10548 232.1 R10549 252.7 R10550 238.5 DAY 8 282.0 265.5 273.7 292.3 283.8 DAY 15 326.6 311.3 320.1 342.3 336.7 STUDY: 1132-100 SUBGROUP 5 SEX: MALE ANIMAL # DAY 1 DAY 8 DAY 15 R10551 R10552 234.2 279.6 319.2 . 223.0 272.8 319.3 R10553 213.5 263.2 318.9 R10554 238.9 294.5 349.0 R10555 228.4 285.5 344.8 GROUP: 4 (1-Week Recovery) SUBGROUP 6 ANIMAL # DAY 1 DAY 8 DAY 15 R10556 232.5 280.0 324.7 R10557 220.9 263.1 299.3 R10558 250.4 283.9 318.3 R10559 226.0 284.4 326.7 R10560 234.4 277.8 319.8 SUBGROUP 7 Animal # DAY 1 R10561 223.9 R10562 223.5 R10563 R10564 191.7 210.5 R10565 232.7 DAY 8 268.2 272.0 233.6 250.9 282.2 DAY 15 309.4 312.0 268.2 305.3 317.0 Note: Animats in Groups 1(48-Hour Post Dose Sacrifice) and 2(7-Day Post Dose Sacrifice) Mere 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 Subgroiqj 7 = Wy-14,643, 100 ppm 3H Corporate Toxicology 33 nnonnnnnnnonnnnnnnnno N-EtFOSE. PFOVSf,, PFOSA ____________ _________________________________________________________ ;__________________________ ;__________________ TRC No. 1132-100 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 1 R10566 233.8 R10567 240.1 R10568 240.6 R10569 266.6 R10570 201.7 R10571 217.8 R10572 230.6 R10573 222.3 R10574 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 APPENDIX TABLE 1 (Continued) INDIVIDUAL BODY WEIGHTS (Grams) Celt Prol iteration Study with N--EtFOSE, PFOS, and PFOSA in Rats GROUP: 5 (4-Week Recovery) DAY 22 DAY 29 DAY 36 SUBGROUP ;) ANIMAL # DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 369.0 363.0 384.6 421.1 319.0 a 337.2 375.9 360.6 353.1 408.0 401.6 411.9 450.9 341.7 a 367.2 408.4 391.2 380.5 435.5 417.4 437.8 480.5 360.9 a 385.3 433.0 405.1 401.2 R10576 R10577 R10578 R10579 R10580 231.8 241.7 231.9 244.7 248.3 257.5 278.1 269.1 283.6 277.1 290.3 307.3 304.4 313.0 314.5 331.9 337.9 339.3 340.6 351.3 368.4 369.8 374.4 371.4 395.9 DAY 36 399.7 398.5 392.3 393.5 426.2 STUDY: 1132-100 SUBGROUP 3 ANIMAL # DAY 1 R10581 228.9 R10582 232.4 R10583 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 R10590 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 R10593 235.5 R10594 251.6 R10595 231.6 SEXI: 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-Ueek 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 R10596 R10597 217.6 228.0 R10598 238.0 R10599 R10600 175.2 223.3 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 R10603 210.6 R10604 234.6 R10605 202.5 SEXI: 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 nnnnnnarnncioonnorTinnnna N-EtFOSE, PFOS. PFOSA_______________________________________________________________________________________________________________________________________ TRC No. 1132-100 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 8 R10486 53.9 R1487 45.4 R10488 52.3 R10489 44.9 R10490 54.6 R10491 34.9 R10492 46.4 R10493 36.6 R10494 31.6 R10495 46.3 APPENDIX TABLE IA INDIVIDUAL BODY WEIGHT GAINS (Grams) Cell Proliferation Study with M-EtFOSE, PFOS, and PFOSA in Rats SEX: HALE GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP 2 SUBGROUP 3 SUBGROUP 4 SUBGROUP 5 SUBGROUP 6 ANIMAL # DAY 8 ANIMAL # DAY 8 ANIMAL # DAY 8 ANIMAL # DAY 8 ANIMAL # R10496 44.7 R10501 41.7 R1050 54.6 R10511 62.7 R10516 R10497 42.7 R10502 53.4 R10507 56.7 R10512 40.3 R10517 R10498 R10499 46.0 46.7 R10503 R10504 52.8 53.4 R10508 R10509 60.4 66.0 R10513 R10514 48.2 45.7 R10518 R10519 ' R10500 46.0 R10505 55.2 R10510 41.2 R10515 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 R10527 68.1 R10528 59.5 R10529 31.4 R10530 49.1 R10531 35.4 R10532 57.7 R10533 45.6 R10534 33.3 R10535 ... 60.6 SEX: MALE 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 R10537 29.2 27.6 R10542 49.4 70.0 R10538 33.3 30.8 R10543 41.6 91.5 R10539.. 37.9 24.3 R10544 43.0 48.4 R10540 51.9 61.8 R10545 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 R10549 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 # PAY 8 R10556 R10557 R10558 47.5 42.2 33.5 R10559 R10560 58.4 43.4 SEX: HALE GROUP: 4 (1-Week Recovery) SUBGROUP 7 DAY 15 ANIMAL # DAY 8 DAY 15 44.7 36.2 34.4 42.3 42.0 R10561 R10562 R10563 R10564 R10565 44.3 48.5 41.9 40.4 49.5 41.2 40.0 34.6 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 n n n a n n a n rn n n n a N-EtFOSE.* P`F--O-S.* "P'F-O-S-A___________ _________________________ ;__________________________________ ;__________________________ _____________________________ 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 R10568 53.4 53.6 37.0 R10569 68.2 59.0 27.3 R10570 46.0 46.5 24.8 R10571 44.9 44.9 a R10572 R10573 R10574 26.4 56.2 33.7 54.7 59.2 63.0 25.5 38.2 29.5 R10575 43.8 46.0 26.9 APPENDIX TABLE 1A (Continued) INDIVIDUAL BODY WEIGHT GAINS (Grams) Cell Proliferation Study with N-EtFOSE, PFOS. and PFOSA in Rats GROUP : 5 (4-Week Recovery) SUBGROUP 2 DAY 29 iDAY 36 ANIMAL # DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 39.0 27.5 R10576 25.7 32.8 41.6 36.5 31.3 38.6 15.8 R10577 36.4 29.2 30.6 31.9 28.7 27.3 25.9 R10578 37.2 35.3 34.9 35.1 17.9 29.8 29.6 R10579 38.9 29.4 27.6 30.8 22.1 22.7 19.2 R10580 28.8 37.4 36.8 44.6 30.3 aa 30.0 18.1 32.5 24.6 30.6 13.9 27.4 20.7 STUDY: 1132-100 SUBGROUP 1 SEX : MALE 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 R10584 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 R10587 56.5 R10588 56.2 R10589 38.6 R10590 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 R10596 46.0 R10597 R10598 37.6 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 28.2 27.8 26.1 29.6 28.7 38.5 36.1 26.3 7.4 33.7 22.1 STUDY: 1132-100 SEX: HALE SUBGROUP 7 ANIMAL # DAY 8 DAY 15 DAY 22 R10601 49.6 52.3 22.4 R10602 55.1 51.7 35.5 R10603 39.9 42.2 25.2 R10604 48.5 36.1 12.2 R10605 56.4 43.0 20.2 GROUP : 5 (4-Ueek 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 ose 3M Corporate Toxicology 36 n a o n n n n c iin a a n o c in in c in a n a ::..r-.-- r ""L ^ i -- IKL NO. II3- IUU STUDY: 1132-100 SEX: MALE SUBGROUP 1 SUBGROUP ;l ANIMAL # DAY 2 Animal # DAY 2 R10381 27.4 R10391 24.5 R10382 26.1 R10392 24.2 R10383 23.1 R10393 23.5 R10384 22.0 R10394 26.4 R10385 22.3 R10395 26.4 R10386 23.6 R10396 25.7 R10387 22.6 R10397 30.1 R10388 22.9 R10398 28.6 R10389 16.6 R10399 25.3 R 10390 22.4 R10400 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 Animal # DAY 2 R10401 28.1 R10402 29.8 R10403 27.6 R10404 28.2 R10405 29.6 R10406 17.1 R10407 27.3 R10408 26.0 R10409 28.1 R10410 25.6 SUBGROUP 4 Animal # DAY 2 R10411 26.1 R10412 26.1 R10413 R10414 R10415 R10416 R10417 R10418 R10419 R10420 25.5 23.5 26.5 24.8 25.3 19.6 27.5 25.5 SUBGROUP 5 Animal # R10421 R10422 R10423 R10424 R10425 R10426 R10427 R10428 R10429 R10430 DAY 2 27.5 27.3 27.5 27.3 23.8 22.0 22.7 16.5 25.1 19.4 SUBGROUP 6 Animal # R10431 R10432 R10433 R10434 R10435 R10436 R10437 R10438 R10439 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 # R10441 R10442 R10443 R10444 R10445 DAY 2 26.1 24.2 22.2 26.0 27.3 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 7 R10446 149.8 R10447 156.1 R10448 184.2 R 10449 173.3 R10450 152.7 R10451 154.5 R10452 164.8 R10453 149.9 R10454 168.9 R10455 179.6 STUDY: 1132-100 SUBGROUP 1 AN I M A L # DAY 1 R10486 196.2 R10487 1/i. R10488 199.3 R10489 179.0 R10490 170.5 R10491 179.8 R10492 171.2 R10493 178.7 R10494 192.9 R10495 173.1 SEX: MALE GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP ;1 SUBGROUP 3 SUBGROUP 4 Animal # DAY 7 Animal # DAY 7 Animal # DAY 7 R10456 142.7 R10461 176.6 R10466 146.5 R10457 155.3 R10462 181.4 R10467 168.3 R10458 163.3 R10463 192.2 R10468 162.3 R10459 164.1 R10464 150.2 R10469 159.3 R10460 152.5 - R10465 158.6 R10470 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 SUBGROUP 3 ANIMAL # DAY 1 DAY 8 Animal # DAY 1 1i10496 189.1 171.7 R10501 186.7 I10497 I10498 IR10499 1R10500 166.2 192.9 198.0 203.9 138.1 167.7 162.6 175.0I R10502 R10503 R10504 R10505 188.5 189.9 197.6 186.8 DAY 8 155.2 162.5 164.9 169,2 167.2 SUBGROUP 5 Animal # R10471 R10472 R10473 R10474 R10475 DAY 7 155.4 154.7 160.8 147.9 161.0 SUBGROUP 6 Animal # R10476 R10477 R10478 R10479 R10480 DAY 7 166.5 163.4 189.3 155.7 154.4 SUBGROUP 7 Animal # R10481 R10482 R10483 R 10484 R10485 DAY 7 142.5 148.6 162.4 154.5 177.6 SUBGROUP 4 Animal # R10506 R10507 R10508 R10509 R10510 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 R10511 203.4 R10512 173.0 R10513 191.2 R10514 184.1 R10515 190.7 DAY 8 171 150.0 17ns 169 .1 173 .7 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 * Hy-14,643, 100 ppm tsp 3H Corporate Toxicology 37 n n r n n n n n n n n n n r a c n n n i m i j i lj lj N -E--tFO--SE./ PFOS. PFOSA__________________________________________________________________________________________________________________________ TRC No. 1132-100 STUDY: 1132-100 SUBGROUP 6 ANIMAL # DAY 1 R10516 170.1 R10517 158.8 R10518 186.9 R10519 R10520 162.7 181.0 SEX: MALE DAY 8 154.0 137.8 156.9 138.9 164.4 APPENDIX TABLE 2 (Continued) INDIVIDUAL FEED CONSUMPTION ( G r a m s ) Cell Proliferation Studv with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP 7 ANIMAL # DAY 1 DAY 8 R10521 178.6 159.8 R10522 180.6 163.6 R10523 208.7 184.0 R10524 167.9 150.0 R10525 210.6 177.2 STUDY: 1132-100 SEX: MALE SUBGROUP 1 ANIMAL # DAY 1 DAY 8 DAY 15 R10526 175.5 200.9 169.2 R10527 222.6 239.8 206.7 R10528 212.5 248.9 209.2 R10529 182.0 233.3 193.5 R10530 185.7 188.8 165.1 R10531 R10532 R10533 181.0 190.4 209.2 215.4 191.1 191.2 178.2 183.0 172.8 R10534 178.3 203.2 176.9 R10535 213.2 16.56 199.7 GROUP: 4 (1-Week Recovery) SUBGROUP 2 ANIMAL # DAY 1 DAY 8 R10536 164.6 150.4 R10537 179.4 164.3 R10538 177.3 176.6 R10539 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 R10544 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 SUBGROUP 4 Animal # DAY 1 R10546 187.1 R10547 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 STUDY: 1132-100 SEX: MALE SUBGROUP 5 ANIMAL # DAY 1 DAY 8 DAY 15 R10551 180.7 179.1 165.0 R10552 192.0 190.6 158.9 R10553 190.9 192.9 158.4 R10554 194.4 200.5 174.6 R10555 196.9 203.8 180.9 GROUP: 4 (1-Week Recovery) SUBGROUP 6 ANIMAL # DAY 1 DAY 8 R10556 193.9 189.7 R10557 183.4 173.9 R10558 187.2 181.2 R10559 193.0 189.9 R10560 180.5 183.7 DAY 15 180.1 168.5 164.6 181.7 164.3 SUBGROUP 7 Animal # DAY 1 R10561 R10562 176.6 197.3 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 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = M-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 nnnaaaannnnannnnnnnc] N-EtFOSE. PFOS, PFOSA__________________________ _ _ ____________________________________________________________ ________________________________________________ TRC Wo. 1132-100 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 1 R10566 206.1 R10567 171.1 R10568 201.1 R10569 229.2 R10570 171.3 R10571 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 R10582 187.4 R10583 199.0 R10584 195.9 R10585 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 Proliferation Study with N-EtFOSE, PFOS. and PFOSA in Rats GROUP : 5 (4-Week Recovery) DAY 22 DAY 29 DAY 36 SUBGROUP 2 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 R10577 193.8 174.8 191.0 175.8 198.0 157.5 204.2 204.4 167.3 213.3 231.3 201.3 R10578 R10579 199.5 191.0 199.5 206.3 207.9 167.5 189.4 182.4 185.8 184.3 193.8 158.4 173.5 175.1 139.0 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 4 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 191.4 199.5 200.1 193.7 199.3 170.8 176.0 217.5 196.5 170.7 211.8 208.1 144.1 174.4 163.0 R10587 R10588 R10589 205.3 205.5 212.2 201.9 205.1 207.3 190.0 164.9 173.9 183.6 189.5 164.5 185.7 193.7 173.9 163.4 151.6 148.8 177.4 185.9 151.9 R10590 199.3 212.2 222.4 169.3 156.5 159.7 STUDY: 1132-100 SEX : MALE GROUP : 5 (4-Week Recovery) SUBGROUP 5 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 R10593 R10594 R 10595 177.3 201.8 201.1 201.5 184.3 180.2 210.3 207.2 189.9 209.9 26.4 219;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 STITOY: 1132-100 SEX : MALE GROUP : 5 SUBGROUP 7 ANIMAL # DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 R10601 R 10602 R10603 R10604 R10605 196.4 193.4 170.2 194.4 176.2 202.5 189.4 187.3 202.5 178.5 196.6 214.6 209.4 183.7 185.7 205.0 234.7 214.5 194.6 189.9 198.9 246.9 208.7 199.3 195.4 152.1 197.1 169.9 161.9 151.9 a - Animal was moribund killed on Day 21. SUBGROUP 6 ANIMAL # DAY 1 R10596 186.8 R105.97 161.8 R10598 R10599 205.4 190.1 R10600 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 353 3M Corporate Toxicology 39 p N-EtFOSE, PFOS, PFOSA Lj TRC No. 1132-100 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 n R10381 Normal Lj Terminal Kill DAY 1-DAY 3 DAY 3 D R10382 Normal Terminal Kill R10383 Normal Thin Terminal Kill R 10384 Normal Thin Terminal Kill R 10385 Normal Thin Terminal Kill R10386 Normal D Thin Terminal Kill R10387 Normal Soft Feces Thin Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 DAY 1 DAY 3 . DAY 3 DAY 1 DAY 3 DAY 3 DAY 1 DAY 3 PAY 3 DAY 3 R10388 Normal Terminal Kill R 10389 Normal ni Lacrimation i_ Thin Terminal Kill R7, L7 DAY 1-DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 DAY 3 n R10390 Normal Thin DAY 1 DAY 3 Terminal Kill DAY 3 nu #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 R10392 Normal DAY 3 DAY 1-DAY 3 Terminal Kill DAY 3 R10393 Normal Lnj Thin Terminal Kill up , R10394 Normal Thin Terminal Kill p Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm L j Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm P Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm L j Subgroup 7 = Wy-14,643, 100 ppm DAY 1 DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 . : ; ; -, n R7 Right Eye L7 = Left Eye 3M Corporate Toxicology 40 3$ N-EtFOSE. PFOS. PFOSA 0 TRC Ho. 1132-100 APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Celt Proliferation Study with H-EtFOSE. PFOS. and PFOSA in Rats STUDY: 1132-100 GROUP;; 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 2 c ANIMAL # OBSERVATIONS R 10395 Normal Terminal Kill SEVERITY LOC TIME OCCURRED DAY 1-DAY 3 DAY 3 R10396 Normal Terminal Kill 0 R 10397 Normal Terminal Kill 0 R1039B Normal Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 R10399 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 D R10400 Normal Terminal Kill DAY 1-DAY 3 DAY 3 STUDY: 1132-100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 3 ANIMAL # OBSERVATIONS R10401 Discharge, Red SEVERITY -LOC H7 TIME OCCURRED DAY 1 Normal DAY 3 Terminal Kill DAY 3 R10402 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10403 Normal Terminal Kill R '10404 Normal D Terminal Kill R10405 Normal Terminal Kill R10406 Normal Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 R10407 Normal Terminal Kill R10408 Normal Thin Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 R10409 Normal Terminal Kill 0 R10410 Normal Thin Terminal Kill Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm 0 Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm D Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm M7 = Nose DAY 1-DAY 3 DAY 3 DAY 1 DAY 3 DAY 3 0 D 3M Corporate Toxicology D 41 3SS M-EtFOSE, PFOS, PFOSA__________________________________________ __ TRC Mo. 1152-100 APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS 0 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 up R10411 Normal Thin DAY 1 DAY 3 Terminat Kill DAY 3 LJn R10412 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10413 Normal D Terminal Kill Ft10414 Normal Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 0 R10415 Normal Terminal Kill DAY 1-DAY 3 DAY 3 n R10416 Normal U Terminal Kill DAY 1-DAY 3 DAY 3 R10417 Normal nLj Thin Terminal Kill DAY 1 DAY 3 DAY 3 It10418 Normal n(_s Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10419 Normal ln_! Rough Haircoat Thin Terminal Kill DAY 1 DAY 3 DAY 3 DAY 3 R10420 Normal Terminal Kill DAY 1-DAY 3 DAY 3 STUDY: 1132- 100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 5 n ANIMAL # OBSERVATIONS SEVERITY Loc Time occurred R10421 Normal DAY 1-DAY 3 Terminal Kill DAY 3 It10422 Normal Paraphimosis Terminal Kill DAY 1 DAY 3 DAY 3 Un 1110423 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 Lin R10424 Normal Thin Terminal Kill p R10425 Normal L Terminal Kill DAY 1 DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 It10426 Normal nu Terminal Kill Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm n Subgroup 3 = N-EtFOSE, 100 ppm LJ Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm 0 Subgroup 7 = Uy-14,643, 100 ppm DAY 1-DAY 3 DAY 3 0 3M Corporate Toxicology 42 N-EtFOSE, PFOS. PFOSA 0 TRC Wo. 1132-100 APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS 0 STUDY: 1132- 100 Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: S ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10427 Normal DAY 1 0 Thin DAY 3 Terminal Kill DAY 3 D R10428 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10429 Normal 0 Terminal Kill DAY 1-DAY 3 DAY 3 D R10430 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 C R10431 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10432 Normal G Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10433 Normal Terminal Kill DAY 1-DAY 3 DAY 3 0 R10434 Normal Terminal Kill DAY 1-DAY 3 DAY 3 D R1043S Normal Terminal Kill DAY 1-DAY 3 DAY 3 D R10436 Normal Thin Terminal Kill DAY 1 DAY 3 DAY 3 R10437 Normal 0 Terminal Kill R10438 Normal G Terminal Kill R10439 Normal Terminal Kill G R10440 Normal Terminal Kill DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 DAY 1-DAY 3 DAY 3 C S u b g r o u p 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm D Subgroup 5 PFOS, 20 ppm Subgroup 6 = PFOSA, 100 p p m Subgroup 7 = Wy-14,643, 100 ppm G D D 3M Corporate Toxicology 0 43 357 N-EtFOSE. PFOS. PFO--SA_______________-________-_._-_.__--__;___________._._._._._._._.__-____--__._._._._._.__--_._._._._._.__-_____ T'--RC -Mo-. 1-1--32-100 APPENDIX TABLE 3 (Continued) INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with M-EtFOSE, PFOS, and PFOSA in Rats STUDY: 1132- 100 GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP: 7 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED G R10441 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10442 Alopecia D Normal Terminal Kill V1 DAY 3 DAY 1 DAY 3 R10443 Normal Terminal Kill DAY 1-DAY 3 DAY 3 R10444 Normal Soft Feces D Thin Terminal Kill DAY 1 DAY 3 DAY 3 DAY 3 R10445 Normal DAY 1 Thin G Terminal Kill DAY 3 DAY 3 STUDY: 1132- 100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 1 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED G R10446 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R 10447 Normal G Terminal Kill R10448 Normal D Thin Terminal Kill R10449 Normal D R10450 Terminal Kill Normal Terminal Kill DAY 1-DAY 8 DAY 8 DAY 1 bAY 8 DAY 8 DAY t-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 0 R10451 Normal Terminal Kill DAY 1-DAY 8 DAY 8 D R10452 Normal Terminal Kill R10453 Normal Terminal Kill 0 R10454 Normal Terminal Kill D R10455 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 G Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm G Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm V1 = Ventral Front Right Area G G D 3M Corporate Toxicology 44 D 3S? c D D 0 0 0 0 0 D D 0 0 C 0 C 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 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10458 Normal Thin Terminal Kill DAY 1 DAY 8 DAY 8 R 10459 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10460 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 R 10461 Normal DAY 1-DAY 8 Terminal Kill DAY 8 R 10462 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10463 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10464 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10465 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 R10470 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 iV* 3M Corporate Toxicology 45 557 I N-EtFOSE. PFQS, PFOSA 0 TRC No. 1132-100 APPENDIX TABLE 3 (Continued) D 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 D R10471 Normal Terminal Kilt DAY 1-DAY 8 DAY 8 D R10472 Normal Terminal Kill R10473 Normal D R10474 Terminal Kill Normal Terminal Kill DAY 1-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 D R10475 Normal Terminal Kill DAY 1-DAY 8 DAY 8 STUDY: 1132-100 GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP: 6 G ANIMAL # OBSERVATIONS________________SEVERITY R10476 Lacrimation Normal LOC TIME OCCURRED_______ M7 DAY 1 DAY 8 Terminal Kill DAY 8 D R10477 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10478 Normal Terminal Kill DAY 1-DAY 8 DAY 8 R10479 Normal DAY 1-DAY 8 C Terminal Kill R10480 Normal Terminal Kill DAY 8 DAY 1-DAY 8 DAY 8 G 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 D R10482 Normal DAY 1-DAY 8 Terminal Kill DAY 8 D R10483 Normal Terminal Kill DAY -DAY 8 PAY 8 R 10484 Normal Terminal Kill R 10485 Normal Terminal Kill D Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm D Subgroup 3 * N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm D Subgroup 7 = Wy-14,643, 100 ppm M7 = Both Eyes DAY 1-DAY 8 DAY 8 DAY 1-DAY 8 DAY 8 D 0 G 0 3M Corporate Toxicology 46 3&0 M-EtFOSE. PFOS. PFOSA G TRC No. 1132-100 APPENDIX TABLE 3 (Continued) O 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________ D R10486 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10487 Normal G Soft Feces Normal Terminal Kill DAY 1 DAY 8 DAY 15 DAY 15 R10488 Normal Terminal Kill DAY 1-DAY 15 DAY 15 D R10489 Normal Terminal Kill R10490 Normal Terminal Kill 0 R10491 Normal Terminal Kill D R10492 Normal Terminal Kill DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 D R10493 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R 10494 Normal DAY 1-DAY 15 D R10495 Termi nal Kill Normal DAY 15 DAY 1-DAY 8 Thin DAY 15 Terminal Kill DAY 15 0 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 0 R10497 Normal Terminal Kill D R10498 Normal Terminal Kill DAY 1-pAY 15 DY 15 DAY 1-DAY 15 DAY 15 D R10499 Normal Terminal Kill R10500 Normal D Terminal Kill Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm G Subgroup 4 = N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm G Subgroup 7 = Wy-14,643 100 ppm DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 D D D D 3M Corporate Toxicology 47 3C,/ i D N-EtFOSE. PFOS, PFOSA TRC No. 1132-100 APPENDIX TABLE 3 (Continued) D 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________ D R10501 Normal Thin DAY 1-DAY 8 DAY 15 Terminal Kill DAY 15 R10502 Normal 0 Terminal Kill DAY 1-DAY 15 DAY 15 D R10503 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10504 Normal D R10505 Terminal Kill Normal Terminal Kill DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 STUDY: 1132-100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 4 0 ANIMAL # OBSERVATIONS R10506 Normal SEVERITY LOC TIME OCCURRED DAY 1-DAY 15 Terminal Kill DAY 15 0 R10507 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10508 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10509 Normal C R10510 Terminal Kill Normal Terminal Kill DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 STUDY: 1132-100 GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP: 5 0 ANIMAL # OBSERVATIONS________________SEVERITY R10511 Normal LOC TIME OCCURRED________ DAY 1-DAY 15 Terminal Kill DAY 15- 0 R10512 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10513 Normal 0 Soft Feces Thin Terminal Kill D R10514 Normal Terminal Kill D R10515 Normal Terminal Kill DAY 1-DAY 8 DAY 15 DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 Subgroup 1 = 0 ppm (Controt) Subgroup 2 = N-EtFOSE, 300 ppm 0 Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm D Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm C 0 D 3M Corporate Toxicology 48 3 ^L N-EtFOSE. PFOS. PFOSA 0 TRC Wo. 1132-100 APPENDIX TABLE 3 (Continued) c 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________ R10516 Normal DAY 1-DAY 15 0 Terminal Kill DAY 15 R10517 Normal D Thin Terminal Kill DAY 1-DAY 8 DAY 15 DAY 15 R10518 Normal Terminal Kill R10519 Normal Terminal Kill DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 DAY 15 0 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 0 ANIMAL it OBSERVATIONS________________SEVERITY LOC TIME OCCURRED_________ R 10521 Normal D R10522 Terminal Kill Normal DAY 1-DAY 15 DAY 15 DAY 1-DAY 15 Terminal Kill DAY 15 R10523 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10524 Normal Terminal Kill DAY 1-DAY 15 DAY 15 R10525 Normal DAY 1-DAY 15 D Terminal Kill DAY 15 STUDY: 1132- 100 GROUP: 4 (1-Week Recovery) SUBGROUP;,'I ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R 10526 Normal 0 Terminal Kill R 10527 Normal DAY 1-DAY 22 DAY 22 DAY 1-DAY 22 Terminal Kill DAY 22 R10528 Normal Terminal Kill DAY 1-DAY 22 DAY 22 D R10529 Normal Diarrhea Terminal Kill DAY 1-DAY 15 DAY 22 DAY 22 D R10530 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10531 Normal D Terminal Kill R10532 Normal Terminal Kill DAY 1-DAY 22 DAY 22; DAY 1-DAY 22 DAY 22 0 R10533 Normal Terminal Kill C R.10534 Normal Terminal Kill DAY 1-DAY 22 DAY 22 DAY 1-DAY 22 DAY 22 D R10535 Normal Terminal Kill Subgroup 1 = 0 ppm (Control) DAY 1-DAY 22 DAY 22 Subgroup 4 = N-EtFOSE, 30 ppm Subgroup 7 = Wy-14,643, 100 ppm Subgroup 2 = N-EtFOSE;, 300 ppm Subgroup 5 = PFOS, 20 ppm D Subgroup 3 N-EtFOSE,, 100 ppm Subgroup 6 = PFOSA, 100 ppm D 3M Corporate Toxicology 49 D N-EtFOSE, PFOS. PFOSA TRC WO. 1132-100 APPENDIX TABLE 3 (Continued) D 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 R10536 Normal DAY 1-DAY 8 Thin DAY 15 Thin Terminal Kill 0 R10537 Normal DAY 22 DAY 22 DAY 1-DAY 6 Diarrhea DAY 15 Normal DAY 22 Terminal Kill DAY 22 R10538 Normal DAY 1-DAY 15 D Thin Terminal Kill DAY 22 DAY 22 R10539 Normal DAY 1-DAY 15 Thin 0 Terminal Kilt DAY 22 DAY 22 R10540 Normal DAY 1-DAY 22 Terminal Kill DAY 22 0 STUDY: 1132-100 GROUP: 4 (1-Week Recovery) SUBGROUP: 3 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10541 Normal DAY 1-DAY 22 Terminal Kill DAY 22 0 R10542 Normal Terminal Kill D R10543 Normal Thin Terminal Kill DAY 1-DAY 22 DAY 22 DAY 1-DAY 15 DAY 22 DAY 22 R10544 Normal Terminal Kill DY 1-DAY 22 DAY 22 R10545 Normal Terminal Kill STUDY: 1132-100 GROUP: 4 (1-Week Recovery) DAY 1-DAY 22 DAY 22 SUBGROUP: 4 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED 0 R10546 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10547 Normal D Terminal Kill R1054S Normal Terminal Kill D R10549 Normal Terminal Kill DAY 1-DAY 22 DAY 22 DAY 1-DAY 22 DAY 22 DAY 1-DAY 22 PAY 22 C R10550 Normal Terminal Kill DAY 1-DAY 22 DAY 22 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm 0 Subgroup 3 N-EtFOSE, 100 ppm Subgroup 4 = N-EtFOSE, 30 ppm D Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm D _______ 3M Corporate Toxicology 0 N-EtFOSE. PFOS. PFOSA D APPENDIX TABLE 3 (Continued) D INDIVIDUAL CLINICAL OBSERVATIONS STUDY: 1132-100 GROUP: A (1-Week Recovery) SUBGROUP: 5 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED D R10551 Normal Lacrimai ion DAY 1 R7 DAY 8 Normal DAY 15-DAY 22 Terminal Kill DAY 22 R10552 Normal DAY 1-DAY 22 Terminal Kill DAY 22 R10553 Normal Terminal Kill DAY 1-DAY 22 DAY 22 R10554 Normal D Terminal Kill DAY 1-DAY 22 DAY 22 R10555 Normal Terminal Kill DAY 1-DAY 22 DAY 22 STUDY: 1132-100 GROUP: 4 (1-Week Recovery) SUBGROUP: 6 0 ANIMAL # 13BSERVATIONS SEVERITY LOC TIME OCCURRED R10556 Normal DAY 1-DAY 15 D R10557 Terminal Kill Normal Abrasion D Thin Terminal Kill DAY 22 DAY 1 M1 DAY 8-DAY 15 DAY 22 DAY 22 R10558 Normal D Terminal Kill R10559 Normal Terminal Kill Y 1tDAY 22 DAY 22 DAY 1-DAY 22 DAY 22 0 R10560 Normal Terminal Kill DAY 1-DAY 22 DAY 22 STUDY: 1132-100 GROUP: 4 (1-Week Recovery) SUBGROUP: 7 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED 0 R10561 Normal Abrasion DAY 1 Ml DAY 8-DAY 22 Terminal Kill D R10562 Normal DAY 22 DAY 1-DAY 15 Thin DAY 22 Terminal Kill DAY 22 D R10563 Normal Thin DAY 1-DAY 15 DAY 22 Terminal Kill D R10564 Normal DfcV 22 DAY 1-DAY 22 Terminal Kill DAY 22 C R10565 Normal Terminal Kill DAY 1-DAY 22 DAY 22 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE, 300 ppm 0 Subgroup 3 = N-EtFOSE, 100 ppm Subgroup 4 N-EtFOSE, 30 ppm D Subgroup 5 = PFOS, 20 ppm Subgroup 6 = PFOSA, 100 ppm Subgroup 7 = Wy-14,643, 100 ppm D R7 = Right Eye M1 = Ventral side of Neck D 3M Corporate Toxicology 0 51 3X> TRC Mo. 1132-100 N-EtFOSE. PFOS. PFOSA 0 TRC No. 1132-100 APPENDIX TABLE 3 (Continued) D INDIVIDUAL CLINICAL OBSERVATIONS Cell Proliferation Study with N-EtFOSE , PFOS, and PFOSA in Rats STUDY: 1132- 100 GROUP: 5 (4-Ueek Recovery) SUBGROUP: 1 ANIMAL # OBSERVATIONS SEVERITY L0C TIME OCCURRED D R10566 Normal Terminal Kill DAY 1-DAY 43 DAY 43 D R10567 Normal Abrasion Alopecia Alopecia D R1C568 Terminal Kill Normal Terminal Kill D R10569 Normal Terminal Kill DAY 1 M1 DAY 8-DAY 36 R7 DAY 22-DAY 36 M7 DAY 43 DAY 43 DAY 1-DAY 43 DAY 43 DAY 1-DAY 43 DAY 43 D R10570 Normal Lacrimation Normal Terminal Kill D R10571 Normal Moribund Kill R7.L7 DAY 1 DAY 8 DAY 15- DAY 43 DAY 43 DAY 1-DAY 15 DAY 21 D R10572 Normal Reddened Normal Terminal Kill R10573 Normal Abrasion Terminal Kill 0 R10574 Normal Terminal Kill DAY 1-DAY 29 M6 DAY 36 DAY 43 DAY 43 DAY 1-DAY 22 Ml DAY 29-DAY 43 DAY 43 DAY 1-DAY 43 DAY 43 R10575 Normal DAY 1-DAY 43 0 Terminal Kill STUDY: 1132- 100 GROUP: 5 (4-Ueek Recovery) DAY 43 SUBGROUP: 2 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED 0 R10576 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10577 Normal C Terminal Kill R10578 Normal Terminal Kill R10579 Normal Terminal Kill DAY 1-DAY 43 DAY 43 DAY 1-DAY 43 DY 43 DAY 1-DAY 43 DAY 43 D R10580 Normal Terminal Kill DAY 1-DAY 43 DAY 43 Subgroup 1 = 0 ppm (Control) D 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 0 Subgroup 7 = Wy-14,643, 100 ppm Ml = Ventral Side of Neck M6 = Inguinal Ventral side 0 M7 = Dorsal Side of Neck R7 = Right Eye, Right Front Leg 1.7 = Left Eye D 3M Corporate Toxicology 52 326 0 D 0 D 0 0 0 D 0 D 0 0 0 0 D c 0 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: 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 Terminal Kill DAY 1-DAY 43 DAY 43 R10584 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R 10585 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 DY 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 Norma1 Thin Norma l 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 pfxn R7 = Right Eye, Right Front Leg L7 = Left Eye, Left Front Leg DAY 1-DAY 8 Da y 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 3<27 N-EtFOSE. PFOS. PFOSA 0 TRC Wo. 1132-100 APPENDIX TABLE 3 (Continued) D 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 # OBSERVATIONS D R10596 Normal Terminal Kill SEVERITY LOC TIME OCCURRED DAY 1-DAY 43 DAY 43 R10597 Normal Thin Normal Terminal Kill C R10598 Normal Terminal Kill DAY 1-DAY 15 DAY 22 DAY 29-DAY 43 DAY 43 DAY 1-DAY 43 DAY 43 D R10599 Normal Terminal Kill DAY 1-DAY 43 DAY 43 R10600 Normal DAY 1-DAY 43 0 Terminal Kill DAY 43 STUDY: 1132- 100 GROUP: 5 (4-Week Recovery) SUBGROUP; 7 ANIMAL # OBSERVATIONS SEVERITY LOC TIME OCCURRED R10601 Normal DAY 1 D Lacrimation Normal Terminal Kill R7 DAY 8 DAY 15-DAY 43 DAY 43 R 10602 Normal 0 Terminal Kill R 10603 Normal 0 Thin Terminal Kill R10604 Normal Thin Terminal Kill R10605 Normal Terminal Kill 0 Subgroup 1 = 0 ppm (Control) Subgroup 2 = N-EtFOSE 300 ppm Subgroup 3 = N-EtFOSE 100 ppm 0 Subgroup 4 N-EtFOSE 30 ppm Subgroup 5 = PFOS 20 ppm n Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm R7 = Right Eye 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 D D D D D D 3M Corporate Toxicology 54 3 z8 ocinannruaanaam cifnanocinc] N"-,ET,:t7.F-O-STEf, 'PF*OmS.f 'PFOSA________________________________________________________________________________________________________________________________TRC NO. 1152-100 STUDY: 1132-100 SUBGROUP 1 AMIHAL # DAY 2 R10381 0.0 R 10382 0.0 R10383 0.0 R 10384 0.0 R10385 R10386 0.0 0.0 R10387 0.0 R10388 0.0 R10389 R10390 0.0 0.0 APPENDIX TABLE 4 INDIVIDUAL TEST MATERIAL CONSUMPTION (PPM) Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats SEX: HALE GROUP: 1 (48-Hour Post Dose Sacrifice) SUBGROUP 2 Animal # DAY 2 SUBGROUP 3 Animal # DAY 2 SUBGROUP 4 Animal # DAY 2 SUBGROUP 5 Animal # DAY 2 R10391 R10392 R10393 R10394 R10395 R 10396 R10397 R10398 R10399 R10400 34.1 29.6 31.8 40.9 32.2 33.6 37.8 35.3 34.0 33.5 R 10401 R10402 R10403 R10404 R10405 R1040& R10407 R10408 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 R10416 R1Q417 R10418 R10419 R10420 3.6 3.2 3.5 3.0 3.6 3.2 3.4 2.6 3.4 3.1 R10421 R10422 R10423 R10424 R10425 R10426 R10427 R10428 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 R10434 R10435 R10436 R10437 R10438 R10439 R10440 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 # R10441 R10442 R10443 R10444 R 10445 DAY 2 11.0 9.8 9.1 11.1 11.5 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 7 R10446 R10447 0.0 0.0 R10448 0.0 R10449 R10450 R10451 0.0 0.0 0.0 R10452 0.0 R10453 R10454 0.0 0.0 R10455 0.0 SEX: HALE GROUP: 2 (7-Day Post Dose Sacrifice) SUBGROUP 2 SUBGROUP 3 SUBGROUP 4 Animal # DAY 7 Animal # DAY 7 Animal # 0AY 7 R10456 31.1 R10461 11.8 R10466 3.4 R10457 36.0 R 10462 12.4 R10467 3.6 R10458 38.1 R10463 12.4 R10468 3.6 R10459 33.3 R10464 10.2 R10469 3.3 R10460 32.3 R10465 11.7 R10470 3.5 SUBGROUP 5 Animal # R10471 R10472 R10473 R10474 R10475 DAY 7 2.2 2.3 2.3 2.1 2.3 SUBGROUP 6 Animal # R10476 R10477 R10478 R10479 R10480 DAY 7 10.8 11.3 12.2 11.0 11.6 SUBGROUP 7 Animal # R10481 R 10482 R10483 R10484 R10485 DAY 7 10.2 10.8 10.9 12.0 11.4 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 8 R10486 0.0 R10487 R104B8 0.0 0.0 R10489 0.0 R10490 0.0 R10491 0.0 R10492 0.0 R10493 0.0 R10494 R10495 0.0 0.0 SEX: HALE 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 # R10496 29.9 27.2 R10501 R10497 R10498 R10499 35.8 33.9 35.2 28.6 28.9 28.3 R10502 R10503 R10504 R10500 34.9 29.5 R10505 DAY 8 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 R10507 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 # R10511 R10512 R10513 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 L r 3H Corporate Toxicology 55 onnaoanncnannna-nn N -EtFO SE, PFOS, PFOSA STUDY: 1132-100 SUBGROUP 6 ANIMAL # DAY 8 R10516 11.5 R10517 R10518 11.0 11.7 R10519 10.2 R10520 11.0 SEX: HALE 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-EtFQSE, PFOS, and PFOSA in Rats GROUP: 3 (14-Day Post Dose Sacrifice) SUBGROUP 7 ANIMAL # DAY 8 DAY 14 R10521 R 10522 R10523 R10524 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 R10535 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 # R10536 32.2 25.3 R10541 R10537 31.1 25.5 R10542 R10538 33.1 28.8 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 # R10546 R10547 R10548 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 R10560 11.0 SEX: MALE DAY 15 9.7 9.4 9.1 9.5 9.4 GROUP: 4 SUBGROUP: 7 Animal # DAY 8 R10561 R10562 R10563 11.3 12.6 11.7 R10564 11.5 R 10565 12.3 DAY 15 10.1 10.1 10.0 10.8 10.7 mnnnn TRC No. 1132-100 SUBGROUP 5 Animal # R10551 R10552 R 10553 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 = 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 56 nnnnnnonnaanaanciaoaoc] N-EtFOSE, PFOS, PFOSA____________________________________________________________;___________________________________ _____________________ _________ TRC No. 1132-100 STUDY: 1132-100 SUBGROUP 1 ANIMAL # DAY 8 R10566 0.0 R10567 0.0 R10568 0.0 R10569 0.0 R 10570 0.0 R10571 0.0 R10572 0.0 R10573 0.0 R10574 0.0 R10575 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 R10578 34.4 36.9 26.9 30.4 R10582 R10583 11.5 13.0 R10579 33.2 27.6 R 10584 12.2 R10580 29.9 28.0 R10585 10.6 DAY 15 10.3 9.4 11.3 10.7 9.2 SUBGROUP 4 ANIMAL # R10586 R10587 R10588 R10589 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 R10598 12.3 R10599 15.5 R10600 11.7 SEX: HALE DAY 15 10.1 9.1 9.6 10.5 9.5 GROUP: 5 (4-Week Recovery) SUBGROUP 7 ANIMAL # DAY 8 DAY 15 R10601 11.6 10.0 R10602 11.9 9.4 R10603 11.5 10.7 R10603 11.8 10.2 R10604 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 33/ 3M Corporate Toxicology 57 nnn N-EtFOSE, PFOS, PFOSA noaaaaanaaa STUDY: 1132-100 Subgroup: 1 ANIMAL ID: SEX: HALE APPENDIX TABLE 5 INDIV1DUAL ASSOLUTE LIVER WEIGHTS (GRAMS) AMD ORGAN TO BODY WEIiSHT RATIOS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 1 (48 Hour Post Dose) R10381 R10382 R10383 R10384 R10385 R10386 R10387 R10388 BODY UEIGHT (G) 211.4 Liver (G) % BODY UEIGHT 8.186 3.872 232.2 8.454 3.641 200.8 7.254 3.613 214.9 6.922 3.221 197.1 7.356 3.732 190.1 6.978 3.671 199.1 6.828 3.429 196.5 6.914 3.519 STUDY: 1132-100 SEX: MALE GROUP: 1 (48 Hour Post Dose) Subgroup: 2 ANIMAL ID: R10391 R10392 R10393 R10394 R10395 R10396 R10397 R10398 BODY UEIGHT (G) 195.8 219.3 195.7 176.1 226.2 206.3 224.8 226.9 Liver (G) % BODY UEIGHT 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: HALE GROUP: 1 (48 Hour Post Dose) Subgroup: 3 ANIMAL ID: R10401 R10402 R10403 R10404 R10405 R10406 R10407 R10408 80DY UEIGHT (G) Liver (G) % BODY UEIGHT 224.6 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 UEIGHT (G) 196.6 215.9 199.4 215.5 202.2 204.5 203.8 200.0 Liver (G) % BODY UEIGHT 7.739 3.936 8.269 3.830 7.061 3.541 7.843 3.639 7.953 3.933 8.746 4.277 7.224 3.545 7.268 3.634 STUDY: 1132-100 SEX: MALE GROUP: 1 (48 Hour Post Dose) Subgroup: 5 ANIMAL ID: R10421 R10422 R10423 R10424 R10425 R10426 R10427 R10428 BODY UEIGHT (G) 220.6 Liver (G) % BODY UEIGHT 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-EtFOSE300 ppm =N-EtFOSE100 ppm =N-EtFOSE30 ppm Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm aaaaa TRC Mo. 1132-100 R10389 207.9 8.067 3.880 R10390 225.8 8.180 3.623 R 10399 202.7 7.581 3.740 R10400 213.3 8.466 3.969 R10409 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 R10429 198.1 6.633 3.348 R10430 212.4 7.206 3.393 3M Corporate Toxicology 58 D D 0 D 333 n N-EtFOSE, PFOS. PFOSA 0 0 a a anna a a STUDY: 1132-100 Subgroup: 6 ANIMAL ID: SEX: MALE APPENDIX TABLE 5 (Continued) INDIVIDUAL ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO BODY WEIGH) KlIOs Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats GROUP: 1 (48 Hour Post Dose) R10431 R 10432 R10433 R10434 R10435 R10436 R10437 R10438 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 R10442 R10443 R10444 R10445 BODY WEIGHT (G) 211.9 Liver (G) % BODY WEIGHT 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 STUDY: 1132-100 SEX: MALE GROUP: 2 (7 Day Post Dose) Subgroup: 1 ANIMAL ID: R10446 R10447 R10448 R10449 R10450 R10451 R10452 R10453 BODY WEIGHT (G) 240.7 Liver (G) % BODY WEIGHT 7.397 3.073 230.0 8.437 3.668 270.8 10.213 3.771 253.3 8.259 3.261 230.2 7.160 3.110 236.9 7.894 3.332 256.6 8.914 3.474 239.2 7.852 3.283 STUDY: 1132-100 SEX: MALE GROUP: 2 (7 Day Post Dose) Subgroup: 2 ANIMAL ID: R10456 R10457 R10458 R10459 R10460 Subgroup: 3 R10461 R10462 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 4.185 242.7 9.459 3.897 275.0 9.288 3.377 264.0 9.923 3.759 STUDY: 1132-100 SEX: MALE GROUP: 2 (7 Day Post Dose) Subgroup: 4 ANIMAL ID: R10466 R10467 R10468 R10469 R10470 Subgroup:: 5 R10471 R10472 BODY WEIGHT (G) 225.5 Liver (G) % BODY WEIGHT 8.224 3.647 256.5 9.225 3.596 253.4 8.820 3.481 248.8 9.030 3.629 236.8 7.408 3.128 247.1 8.531 3.452 232.6 8.558 3.679 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 aaaa a TRC Ho. 1132-100 R 10439 219.2 7.910 3.609 R10440 207.2 8.349 4.029 R10454 258.7 9.101 3.518 R10463 272.1 10.994 4.040 R10473 237.0 8.575 3.618 R10455 264.3 9.526 3.604 R10464 249.6 9.144 3.663 R10474 241.9 9.240 3.820 R10465 232.4 8.974 3.861 R10475 258.3 9.247 3.580 a n N-EtFOSE, PFOS. PFOSA aaa 0 O r~i o a a n STUDY: 1132-100 Subgroup: 6 ANIMAL ID: APPENDIX TABLE 5 (Continued) INDIVIDUAL ABSOLUTE LIVER WEIGHTS (GRAMS) AND ORGAN TO 80DY WEIGHT RATIOS Cell Proliferation Study with N-EtFOSE, PFOS, and PFOSA in Rats SEX; MALE GROUP: 2 (7 Days Post Dose) Subgroup: 7 R10476 R10477 R 10478 R10479 R10480 R10481 R10482 BODY WEIGHT (G) . 270.9 247.9 283.1 244.9 240.5 240.9 249.3 Liver (G) % BODY WEIGHT 10.791 3.983 9.282 3.744 12.088 4.270 9.361 3.822 9.441 3.926 14.415 5.984 15.569 6.245 STUDY: 1132-100 SEX: MALE GROUP: 3 (14 Days Post Dose) Subgroup: 1 ANIMAL ID: R10486 R10487 R10488 R10489 R10490 R10491 R10492 R10493 BODY WEIGHT (G) 300.3 279.5 322.4 297.5 270.8 326.6 259.6 311.4 Liver (G) % BODY WEIGHT 10.763 3.582 8.629 3.087 11.274 3.497 9.459 3.179 8.485 3.133 11.300 3.460 8.723 3.360 10.192 3.273 STUDY: 1132-100 SEX: MALE GROUP: 3 (14 Days Post Dose) Subgroup: 2 ANIMAL ID: R10496 R 10497 R10498 R10499 R10500 Subgroup: 3 R10501 R10502 BODY WEIGHT (G) 319.3 245.3 292.7 286.5 294.8 276.5 299.8 Liver (G) % BODY WEIGHT 16.134 5.053 11.055 4.507 15.086 5.154 14.856 5.185 13.611 4.617 11.837 4.281 10.967 3.658 STUDY: 1132-100 SEX: MALE GROUP: 3 (14 Days Post Dose) Subgroup: 4 ANIMAL ID: R10506 R10507 R10508 R10509 R10510 Subgroup: 5 R10511 R10512 BODY WEIGHT (G) 314.6 %Liver (G) 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: R10516 R10517 R10518 R10519 R10520 Subgroup: 7 R10521 R10522 BODY WEIGHT (G) 266.9 %Liver (G) BODY WEIGHT 11.929 4.469 253.5 9.689 3.822 275.4 10.807 3.924 263.4 10.022 3.805 281.5 11.383 4.044 273.5 19.233 7.032 279.6 21.012 7.515 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 60 na a a a TRC No. 1132-100 R10483 269.9 16.419 6.083 R10494 330.3 10.084 3.053 R10503 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 R10504 294.4 12.437 4.225 R10514 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 N -EtFOSE, PFOS, PFOSA_________________________________________________________________________________________________________ STUDY: 1132-100 Subgroup: 1 ANIMAL ID: SEX: HALE 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 Ueek Recovery) R10526 R10527 R10528 R10529 R10530 R10531 R10532 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: R 10536 R10537 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 R10549 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 R10561 R10562 BODY WEIGHT (G) 324.3 293.2 304.5 318.9 307.9 286.7 300.4 Liver (G) % BODY WEIGHT 13.898 4.286 12.498 4.263 12.203 4.008 12.907 4.047 11.899 3.865 13.896 4.847 13.225 4.402 STUDY: 1132-100 SEX: MALE GROUP: 5 (4 Week Recovery) Subgroup: 1 ANIMAL ID: R10566 R10567 R10568 R10569 R10570 R10572 R10573 R10574 BODY WEIGHT (G) 419.6 Liver (G) % BODY WEIGHT 12.914 3.078 410.4 13.400 3.265 430.1 12.560 2.920 478.5 20.255 4.233 349.9 11.635 3.325 369.6 9.622 2.603 425.4 14.000 3.291 391.0 10.276 2.628 Subgroup 1 Subgroup 2 Subgroup 3 Subgroup 4 =0 ppm (Control) =N-EtFOSE300 ppm =N-EtFOSE100 ppm =N-EtFOSE30 ppm 3H Corporate Toxicology Subgroup 5 = PFOS 20 ppm Subgroup 6 = PFOSA 100 ppm Subgroup 7 = Wy-14,643 100 ppm 61 R10534 314.6 10.006 3.181 R10543 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 Wo. 1132-100 R10535 356.4 12.421 3.485 R10544 309.6 11.404 3.683 R10554339.9 11.776 3.465 R10564 306.0 11.826 3.865 R10545 314.2 10.325 3.286 R10555 336.7 12.298 3.653 R10565 304.6 11.654 3.826 n n n n n n m c i n n n n n n n n n n n n r -] N-EtFOSE. PFOS, PFOSA______________________________________________ _____________________________________________________________.____________________TRC No. 1132-100 STUDY: 1132-100 Subgroup: 2 ANIMAL ID: APPENDIX TABLE 5 (Continued) INDIVIDUAL ABSOLUTE LIVER HEIGHTS (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) R10576 R10577 R10578 R10579 R10580 Si&group: 3 R10581 R10582 BODY WEIGHT (G) 394.9 390.8 389.7 385.6 416.3 404.3 369.6 Liver (G) % BODY WEIGHT 18.930 4.794 17.760 4.545 14.301 3.670 16.167 4.193 18.573 4.461 13.739 3.398 11.940 3.231 STUDY: 1132-100 SEX: MALE GROUP: 4 (1 Week Recovery) Subgroup: 4 ANIMAL ID: R10586 R10587 R10588 R10589 R10590 Subgroup: 5 R10591 R10592 BODY WEIGHT (G) 400.3 419.5 403.5 334.1 410.5 359.4 392.8 Liver (G) % BODY WEIGHT 13.786 3.444 13.145 3.133 13.568 3.363 12.480 3.735 12.535 3.054 11.787 3.280 14.189 3.612 STUDY: 1132-100 SEX: MALE GROUP: 4 (1 Week Recovery) Subgroup: 6 ANIMAL ID: R10596 R1Q597 R10598 R10599 R1060Q Subgroup: 7 R10601 - R10602 BODY WEIGHT (G) 391.6 Liver (G) % BODY WEIGHT 14.315 3.656 378.1 13.607 3.599 397.6 17.252 4.339 396.2 16.640 4.200 350.0 13.945 3.984 409.6 14.885 3.634 451.5 16.676 3.693 R10583 406.9 14.615 3.592 R10593 386.0 12.789 3.313 R10603 363.3 12.285 3.382 R10584 390.1 12.139 3.112 R10594 432.7 14.176 3.276 R10604 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 = 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 62
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