Document 5LM2L99bymM2J6xM9v9kLJNY8

Study Title ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSOR'S STUDY NUMBER: T-6889.6 Data Requirement U.S. Environmental Protection Agency (1998). Health Effects Test Guidelines; Reproduction and Fertility Effects. Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3800, August, 1998. U.S. Environmental Protection Agency (1997). Toxic Substances Control Act (TSCA) Test Guidelines; Final Rule. Reproduction and Fertility Effects, 799.9380 (crossreferenced to OPPTS 870.3800). Federal Register, August 15, 1997. Author Raymond G. York, Ph.D., DABT (Study Director) Study Completed On 26 March, 2002 (Final Report) Performing Laboratory Argus Research 905 Sheehy Drive, Building A Horsham, Pennsylvania 19044-1297 Laboratory Project ID Argus Research Protocol Number: 418-020 Page 1 of 1245 ARGUS 418-020 Confidentiality Page This is a blank page to be inserted by the Sponsor. Page 2 ARGUS 418-020 GOOD LABORATORY PRACTICE STATEMENT This study was conducted according to U.S. Environmental Protection Agency (EPA FTFRA/TSCA) "Good Laboratory Practice Standards; Final Rule" (40 CFR Part 160/792) and the Organisation for Economic Co-operation and Development (OECD) "Principles of Good Laboratory Practice", with the exceptions in bulleted list below. Exceptions to GLP compliance: The Argus Study protocol 418-020, was approved by the Sponsor and signed by the Argus Study Director prior to the initiation of any work performed for this study. The Sponsor's analytical group developed a separate protocol [3M FACT-TCX-164] and assigned a Study Director for the work conducted at their site and viewed the analytical portion as a separate study. The Sponsor issued a report for this segment of the study (presented in Appendix I of this report) which addresses the following areas of non compliance: The analytical protocol identified a second Study Director rather than a Principal Investigator. The dose confirmation and stability analyses were conducted by the Sponsor prior to protocol 3M FACT-TCX-164 being approved and issued. The purity and stability of the surrogate THPFOS standard is not included in the full study report, as it is not known at this time. Submitter: Study Director: Sponsor: 3M Corporate Toxicology Page 3 Date ARGUS 418-020 Flagging Page This is a blank page to be supplied by the Sponsor Page 4 ARGUS 418-020 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSOR'S STUDY NUMBER: T-6889.6 TABLE OF CONTENTS SUBJECT l. SUMMARY AND CONCLUSION A. Methods B. Results C. Conclusion n. DESCRIPTION OF TEST PROCEDURES A. Conduct of Study B. Test Substance Information C. Vehicle Information D. Test Substance Preparation and Storage Conditions E. Test System F. Husbandry G. Methods m. RESULTS - P GENERATION RATS A. P Generation Male Rats B. P Generation Female Rats . PAGE 15 15 18 24 25 25 28 29 29 30 32 35 46 46 50 Page 5 ARGUS 418-020 SUBJECT PAGE IV. RESULTS - FIGENERATION RATS 55 A. FI Generation Male Rats 55 B. FI Generation Female Rats 62 REFERENCES 68 APPENDIX A - REPORT FIGURES 70 Figure 1. Body Weights - P Generation Male Rats 71 Figure 2. Body Weights - P Generation Female Rats 72 Figure 3. Body Weights - FI Generation Male Rats 73 Figure 4. Body Weights - FI Generation Female Rats 74 APPENDIX B - REPORT TABLES - P GENERATION MALE RATS 75 Table B l. Clinical Observations - Summary - P Generation Male Rats 76 Table B2. Body Weights - Summary - P Generation Male Rats 78 Table B3. Body Weight Changes - Summary - P Generation Male Rats 80 Table B4. Absolute Feed Consumption Values (g/day) - Summary P Generation Male Rats 82 Table B5. Relative Feed Consumption Values (g/kg/day) - Summaiy P Generation Male Rats 83 Table B6. Mating and Fertility - Summary - P Generation Male Rats 84 Table B7. Necropsy Observations - Summary - P Generation Male Rats 85 Table B8. Terminal Body Weights and Organ Weights - Summary P Generation Male Rats 86 Table B9. Ratios (%) of Organ Weight to Terminal Body Weight - Summary - P Generation Male Rats 88 Table BIO. Ratios (%) of Organ Weight to Brain Weight - Summary P Generation Male Rats 90 Page 6 ARGUS 418-020 SUBJECT PAGE Table B 11. Cauda Epididymal Sperm Motility, Count, Density and Spermatid Count - Summary - P Generation Male Rats 92 Table B 12. Cauda Epididymal Sperm Morphology - Summary - P Generation Male Rats 94 Table B 13. Clinical Observations - Individual Data - P Generation Male Rats 95 Table B 14. Body Weights - Individual Data - P Generation Male Rats 106 Table B 15. Feed Consumption Values - Individual Data - P Generation Male Rats 111 Table B 16 Mating and Fertility - Individual Data - P Generation Male Rats 116 Table B 17. Necropsy Observations - Individual Data - P Generation Male Rats 121 Table B 18. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data - P Generation Male Rats 127 Table B 19. Brain Weights and Organ Weights and Ratios (%) of Organ Weight to Brain Weight - Individual Data - P Generation Male Rats 145 Table B20. Cauda Epididymal Sperm Motility, Count, Density and Spermatid Count - Individual Data - P Generation Male Rats 163 Table B21. Cauda Epididymal Sperm Morphology - Individual Data P Generation Male Rats 169 APPENDIX C - REPORT TABLES - P GENERATION FEMALE RATS 174 Table Cl. Clinical Observations - Summary - P Generation Female Rats 175 Table C2. Body Weights - Precohabitation - Summary - P Generation Female Rats 178 Table C3. Body Weight Changes - Precohabitation - Summary - P Generation Female Rats 179 Table C4. Maternal Body Weights - Gestation - Summary - P Generation Female Rats 180 Table C5. Maternal Body Weight Changes - Gestation - Summary P Generation Female Rats 181 Page 7 ARGUS 418-020 SUBJECT PAGE Table C6. Maternal Body Weights - Lactation - Summary - P Generation Female Rats 182 Table Cl. Maternal Body Weight Changes - Lactation - Summary P Generation Female Rats 183 Table C8. Absolute Feed Consumption Values (g/day) - Precohabitation Summary - P Generation Female Rats 184 Table C9. Relative Feed Consumption Values (g/kg/day) - Precohabitation Summary - P Generation Female Rats 185 Table CIO. Maternal Absolute Feed Consumption Values (g/day) - Gestation - Summary - P Generation Female Rats 186 Table Cl 1. Maternal Relative Feed Consumption Values (g/kg/day) - Gestation Summary - P Generation Female Rats 187 Table C12. Maternal Absolute Feed Consumption Values (g/day) - Lactation Summary - P Generation Female Rats 188 Table C13. Maternal Relative Feed Consumption Values (g/kg/day) Lactation - Summary - P Generation Female Rats 189 Table C 14. Mating and Fertility, Estrous Cycling and Days in Cohabitation Summary - P Generation Female Rats 190 Table C l5. Necropsy Observations - Summary - P Generation Female Rats 192 Table C l6. Terminal Body Weights and Organ Weights - Summary P Generation Female Rats 193 Table C l7. Ratios {%) of Organ Weight to Terminal Body Weight - Summary - P Generation Female Rats 194 Table C l8. Ratios (%) of Organ Weight to Brain Weight - Summary P Generation Female Rats 195 Table C l9. Natural Delivery Observations - Summary - P Generation Female Rats 196 Table C20. Litter Observations (Naturally Delivered Pups) - Summary P Generation Female Rats 197 Page 8 ARGUS 418-020 SUBJECT PAGE Table C21. Clinical Observations from Birth to Day 22 Postpartum Summary - FI Generation Pups 200 Table C22. Necropsy Observations from Birth to Day 22 Postpartum Summary - FI Generation Pups 201 Table C23. Pup Organ Weights - Summary - FI Generation Pups 202 Table C24. Clinical Observations - Individual Data - P Generation Female Rats 205 Table C25. Body Weights - Precohabitation - Individual Data - P Generation Female Rats 215 Table C26. Maternal Body Weights - Presumed Gestation - Individual Data P Generation Female Rats 220 Table C27. Maternal Body Weights - Lactation - Individual Data P Generation Female Rats 225 Table C28. Feed Consumption Values - Precohabitation - Individual Data P Generation Female Rats 230 Table C29. Maternal Feed Consumption Values - Presumed Gestation Individual Data - P Generation Female Rats 235 Table C30. Maternal Feed Consumption Values - Lactation - Individual Data - P Generation Female Rats 240 Table C31. Mating and Fertility, Estrous Cycling and Days in Cohabitation Individual Data - P Generation Female Rats 245 Table C32. Necropsy Observations - Individual Data - P Generation Female Rats 250 Table C33. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data P Generation Female Rats 257 Table C34. Brain Weights, Organ Weights, and Ratios (%) of Organ Weight to Brain Weight - Individual Data - P Generation Female Rats 267 Table C35. Natural Delivery, Implantation Sites, and Pup Viability and Sex Individual Data - P Generation Female Rats 277 Page 9 ARGUS 418-020 SUBJECT PAGE Table C36. Pup Body Weight Litter Averages from Birth to Day 22 Postpartum - Individual Data - FI Generation Litters 282 Table C37. Pup Body Weights from Birth to Day 22 Postpartum Individual Data - FI Generation Pups 287 Table C38. Pup Vital Status and Sex from Birth to Day 22 Postpartum Individual Data - FI Generation Pups 312 Table C39. Clinical Observations from Birth to Day 22 Postpartum Individual Data - FI Generation Pups . 317 Table C40. Necropsy Observations from Birth to Day 22 Postpartum Individual Data - FI Generation Pups 320 Table C41. Pup Organ Weights - Individual Data - FI Generation Pups 330 APPENDIX D - REPORT TABLES - Fl GENERATION MALE RATS 335 Table Dl. Clinical Observations - Summary - FI Generation Male Rats 336 Table D2. Body Weights - Summary - FI Generation Male Rats 339 Table D3. Body Weight Changes - Summary - FI Generation Male Rats 341 Table D4. Absolute Feed Consumption Values (g/day) - Summary FI Generation Male Rats 343 Table D5. Relative Feed Consumption Values (g/kg/day) - Summary FI Generation Male Rats 345 Table D6. Sexual Maturation - Summary - FI Generation Male Rats 347 Table D7. Mating and Fertility - Summary - FI Generation Male Rats 348 Table D8. Necropsy Observations - Summary - FI Generation Male Rats 349 Table D9. Terminal Body Weights and Organ Weights - Summary FI Generation Male Rats 351 Table D10. Ratios (%) of Organ Weight to Terminal Body Weight - Summary - FI Generation Male Rats 353 Table D ll. Ratios (%) of Organ Weight to Brain Weight - Summary FI Generation Male Rats 355 Page 10 ARGUS 418-020 SUBJECT PAGE Table D12. Cauda Epididymal Sperm Motility, Count, Density and Spermatid Count - Summary - FI Generation Male Rats 357 Table D13. Cauda Epididymal Sperm Morphology - Summary - FI Generation Male Rats 359 Table D14. Clinical Observations - Individual Data - FI Generation Male Rats 360 Table D15. Body Weights - Individual Data - FI Generation Male Rats 378 Table D16. Feed Consumption Values - Individual Data - FI Generation Male Rats 398 Table D17. Sexual Maturation - Individual Data - FI Generation Male Rats 408 Table D18. Mating And Fertility - Individual Data - FI Generation Male Rats 410 Table D19. Necropsy Observations - Individual Data - FI Generation Male Rats 415 Table D20. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data FI Generation Male Rats 432 Table D21. Brain Weights, Organ Weights and Ratios (%) of Organ Weight to Brain Weight - Individual Data - FI Generation Male Rats 447 Table D22. Cauda Epididymal Sperm Motility, Count, Density and Spermatid Count - Individual Data - FI Generation Male Rats 462 Table D23. Cauda Epididymal Sperm Morphology - Individual Data FI Generation Male Rats 468 APPENDIX E - REPORT TABLES - FI GENERATIONFEMALE RATS 473 Table El. Clinical Observations - Summary - FI Generation Female Rats 474 Table E2. Body Weights - Precohabitation - Summary - FI Generation Female Rats 479 Table E3. Body Weight Changes - Precohabitation - Summary FI Generation Female Rats 481 Table E4. Maternal Body Weights - Gestation - Summary - FI Generation Female Rats 483 Page 11 ARGUS 418-020 SUBJECT PAGE Table E5. Maternal Body Weight Changes - Gestation - Summary Fl Generation Female Rats 484 Table E6. Maternal Body Weights - Lactation - Summary - Fl Generation Female Rats 485 Table E7. Maternal Body Weight Changes - Lactation - Summary FI Generation Female Rats 486 Table E8. Absolute Feed Consumption Values (g/day) - Precohabitation . Summary - FI Generation Female Rats 487 Table E9. Relative Feed Consumption Values (g/kg/day) - Precohabitation Summary - FI Generation Female Rats 488 Table E10. Maternal Absolute Feed Consumption Values (g/day) - Gestation - Summary - FI Generation Female Rats 489 Table E li. Maternal Relative Feed Consumption Values (g/kg/day) Gestation - Summary - FI Generation Female Rats 490 Table E l2. Maternal Absolute Feed Consumption Values (g/day) Lactation - Summary - FI Generation Female Rats 491 Table E13. Maternal Relative Feed Consumption Values (g/kg/day) Lactation - Summary - FI Generation Female Rats 492 Table E 14. Sexual Maturation - Summary - FI Generation Female Rats 493 Table E15. Mating and Fertility, Estrous Cycling and Days in Cohabitation Summary - FI Generation Female Rats 494 Table E l6. Necropsy Observations - Summary - FI Generation Female Rats 496 Table E l7. Terminal Body Weights and Organ Weights - Summary FI Generation Female Rats 498 Table E18. Ratios (%) of Organ Weight to Terminal Body Weight Summary - FI Generation Female Rats 499 Table E l9. Ratios (%) of Organ Weight to Brain Weight - Summary FI Generation Female Rats 500 Table E20. Natural Delivery Observations - Summary - FI Generation Female Rats 501 Page 12 ARGUS 418-020 SUBJECT PAGE Table E21. Litter Observations (Naturally Delivered Pups) - Summary F2 Generation Pups 502 Table E22. Clinical Observations from Birth to Day 22 Postpartum Summary - F2 Generation Pups 505 Table E23. Necropsy Observations - Summary - F2 Generation Pups 507 Table E24. Pup Organ Weights - Summary - F2 Generation Pups 508 Table E25. Anogenital Distance - Summary - F2 Generation Pups 511 Table E26. Clinical Observations - Individual Data - FI Generation Female Rats 512 Table E27. Body Weights - Precohabitation - Individual Data FI Generation Female Rats 527 Table E28. Maternal Body Weights - Presumed Gestation - Individual Data FI Generation Female Rats 537 Table E29. Maternal Body Weights - Lactation - Individual Data FI Generation Female Rats 542 Table E30. Feed Consumption Values - Precohabitation - Individual Data FI Generation Female Rats 547 Table E31. Maternal Feed Consumption Values - Presumed Gestation Individual Data - FI Generation Female Rats 557 Table E32. Maternal Feed Consumption Values - Lactation - Individual Data - FI Generation Female Rats 562 Table E33. Sexual Maturation - Individual Data - FI Generation Female Rats 567 Table E34. Mating and Fertility, Estrous Cycling and Days in Cohabitation Individual Data - FI Generation Female Rats 569 Table E35. Necropsy Observations - Individual Data - FI Generation Female Rats 574 Table E36. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data FI Generation Female Rats 586 Page 13 ARGUS 418-020 SUBJECT PAGE Table E37. Brain Weights, Organ Weights and Ratios (%) of Organ Weight to Brain Weight - Individual Data - FI Generation Female Rats 596 Table E38. Natural Delivery, Implantation Sites, and Pup Viability and Sex Individual Data - FI Generation Female Rats/F2 Generation Litters 606 Table E39. Pup Body Weight Litter Averages from Birth to Day 22 Postpartum - Individual Data - F2 Generation Pups 611 Table E40. Pup Body Weights from Birth to Day 22 Postpartum - Individual Data - F2 Generation Pups 616 Table E41. Pup Vital Status and Sex from Birth to Day 22 Postpartum Individual Data - F2 Generation Pups 641 Table E42. Clinical Observations from Birth to Day 22 Postpartum Individual Data - F2 Generation Pups 646 Table E43. Necropsy Observations - Individual Data - F2 Generation Pups 648 Table E44. Pup Organ Weights - Individual Data - F2 Generation Pups 658 Table E45. Anogenital Distance - Individual Data - F2 Generation Pups 663 APPENDIX F - PROTOCOL AND AMENDMENTS 683 APPENDIX G - DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY 742 APPENDIX H - CERTIFICATES OF ANALYSIS 755 APPENDIX I - ANALYTICAL REPORT 758 APPENDIX J - ENVIRONMENTAL AND HUSBANDRY REPORTS 869 APPENDIX K - HISTOPATHOLOGY REPORT 924 APPENDIX L - HISTORICAL CONTROL DATA 1230 APPENDIX M -QUALITY ASSURANCE STATEMENT 1242 Page 14 ARGUS 418-020 TITLE: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS ARGUS RESEARCH PROTOCOL NUMBER: 418-020 . SPONSOR'S STUDY NUMBER: T-6889.6 I. SUMMARY AND CONCLUSION A. Methods8 Crl:CD(SD)IGS BR VAF/Plus rats were used. The P generation consisted of 150 rats per sex assigned to five dosage groups (Groups I through V), 30 rats per sex per dosage group. Two FI generation pups per sex per litter per group (60 male and 60 female pups per group) were selected for continued evaluation, resulting in 300 rats per sex assigned to five dosage groups (Groups I through V). Solutions of ammonium perfluorooctanoate (APFO) in reverse osmosis membrane processed deionized water were administered to the P generation male and female rats, beginning at approximately six weeks of age and continuing until the day before sacrifice, at dosages of 0, 1, 3, 10 and 30 mg/kg/day. The dosage volume was 5 mL/kg, adjusted daily on the basis of the most recently recorded body weight. The FI generation rats were given the same dosage level of the test substance as their respective P generation sires and dams. Dosages were given once daily, beginning at weaning and continuing until the day before sacrifice. Dosages were adjusted at least weekly for body weight changes and given at approximately the same time each day. FI and F2 generation pups may have been exposed to the test substance during the maternal gestation (in utero exposure) or via maternal milk during the postpartum period. The P and FI generation rats were observed for viability at least twice each day. The rats were also examined for clinical observations of effects of the test substance, abortions, premature deliveries and deaths before dosage and 60 10 minutes after dosage during the dosage period. Body weights of the P generation male rats were recorded weekly during the dosage periods and on the day of sacrifice. Body weights of the FI generation male rats were recorded weekly during the postweaning period and on the day of sacrifice. Body weights of the P generation female rats were recorded weekly during the a. Detailed descriptions of all procedures used in the conduct of this study are provided in the appropriate sections of this report and in APPENDIX F (PROTOCOL AND AMENDMENTS). Page 15 ARGUS 418-020 precohabitation and cohabitation periods and on days of gestation (DGs) 0, 7, 10, 14, 18, 21 and 25 (if necessary) and on DLs 1,5, 8, 11, 15 and 22 (terminal body weight). Body weights of the FI generation female rats were recorded weekly during the postweaning period to cohabitation, and on DGs 0,7, 10, 14, 18, 21 and 25 (if necessary) and on DLs 1, 5, 8, 11,15 and 22. Feed consumption values for the P and FI generation male rats were recorded weekly during the dosage period. Feed consumption values for the P generation female rats were recorded weekly during the precohabitation period, on DGs 0, 7, 10, 14, 18, 21 and 25 and on DLs 1, 5, 8, 11 and 15. Feed consumption values for the FI generation female rats were recorded weekly during the postweaning period to cohabitation, on DGs 0, 7, 10, 14,18, 21 and 25 and on DLs 1, 5, 8, 11 and 15. During cohabitation, when two rats occupied the same cage with one feed jar, individual values were not recorded or tabulated. Because pups begin to consume maternal feed on or about DL 15, feed consumption values were not tabulated after DL 15. FI generation female rats were examined for age of vaginal patency, beginning on day 28 postpartum. FI generation male rats were evaluated for age of preputial separation, beginning on day 39 postpartum. Body weights were recorded when rats reached sexual maturation. Estrous cycling was evaluated daily by examination of vaginal cytology beginning 21 days before the scheduled cohabitation period and continuing until spermatozoa were observed in a smear of the vaginal contents and/or a copulatory plug was observed in situ during the cohabitation period. On the day of scheduled sacrifice, an examination of vaginal cytology was performed to determine the stage of estrous cycle. Within each dosage group, consecutive order was use to assign P generation rats to cohabitation, one male rat per female rat. A table of random units was used to assign FI generation rats to cohabitation, one male rat per female rat. If random assignment to cohabitation resulted in the pairing of FI generation siblings, an alternate assignment was made. The cohabitation period consisted of a maximum of 14 days. The P and FI generation female rats were evaluated for duration of gestation, fertility index, gestation index, number and sex of offspring per litter, number of implantation sites, general condition of the dam and litter during the postpartum period, litter size and viability, viability index, lactation index and percent survival and sex ratio. Maternal behavior of the dams was recorded on DLs 1, 5, 8, 15 and 22. Litters were examined after delivery to identify the number and sex of pups, stillbirths, liver births and gross alterations. Each litter was evaluated for viability at least twice each day of the 22-day postpartum period. The FI and F2 generation pups in each litter were counted once daily. Physical signs were recorded for the pups each day. Pup body weights were recorded on DLs 1, 5, 8, 15 and 22. On DL 12 all FI generation male pups were examined for the presence of nipples. Anogenital distance was measured for all live F2 generation pups on DLs 1 and 22. P and Flgeneration rats were sacrificed necropsied and examined for gross lesions. Gross lesions were examined histologically. Tissue trimming and histopathology was performed under the supervision of or by a Board Certified Veterinary Pathologist, At Page 16 ARGUS 418-020 scheduled sacrifice, after completion of the cohabitation period (male rats) and on DL 22 (female rats), blood samples were collected and centrifuged. The resulting serum was shipped to the Sponsor for analysis. The liver was excised, weighed, and a sample section shipped to the Sponsor for analysis. The following organs were individually weighed and organ-to-body weight and organ-tobrain weight ratios were calculated: brain, kidneys, spleen, ovaries, testes, thymus, liver, adrenal glands, pituitary, uterus with oviducts and cervix, left epididymis (whole and cauda), right epididymis, prostate and seminal vesicles (with coagulating glands and with and without fluid). The following tissues were retained for possible histological evaluation: pituitary, adrenal glands, vagina, uterus with oviducts, cervix and ovaries, right testis, seminal vesicles (with coagulating gland), right epididymis and prostate. Histological examination was performed on tissues from 10 randomly selected rats per sex from the control and high dosage groups. All gross lesions were examined histologically. Reproductive organs of the low and intermediate dosage group rats suspected of reduced fertility were subjected to histological evaluation. Male rats were sacrificed after completion of the cohabitation period. A portion of the left cauda epididymis was used for evaluation of cauda epididymal sperm concentration and motility. The remaining left cauda epididymis was used to manually evaluate sperm morphology and to prepare a homogenate to determine sperm concentration. The left testis was used for evaluation of testicular spermatid concentration. Female rats were sacrificed on day of day 22 of lactation (DL 22). The number and distribution of implantation sites were recorded. Pups that died before examination of the litter for pup viability on DL 1 were evaluated for vital status at birth. Pups found dead on DLs 2 to 22 were examined for gross lesions and for the cause of death. All pups culled on DL 22 were sacrificed. Three pups per sex per litter were examined for gross lesions. Necropsy included a single cross-section of the head at the level of the frontal-parietal suture and examination of the cross-sectioned brain for apparent hydrocephaly. The brain, spleen and thymus from one of the three selected pups per sex per litter were weighed and the brain, spleen and thymus from the three selected pups per sex per litter were retained for possible histological evaluation. All remaining pups were discarded without further examination. All FI generation rats were weaned on DL 22 based on observed growth and viability of these pups. At weaning, two FI generation pups per sex per litter per group (60 male and 60 female pups per group), resulting in a total of 600 rats (300 rats per sex) were chosen for continued evaluation. At least two male pups and two female pups per litter, when possible, were selected. FI generation pups not selected for continued observation for sexual maturation were sacrificed and a limited necropsy was performed. The thoracic, abdominal and pelvic cavities were examined for gross lesions. Gross lesions were preserved; all other tissues and the carcasses were discarded. Page 17 B. Results ARGUS 418-020 B.l. P Generation Male Rats One P generation male rat in the 30 mg/kg/day dosage group was moribund sacrificed on day 45 of the study (DS 45). The moribund condition was considered possibly related to the test substance because it occurred in the highest dosage group and this rat exhibited adverse clinical observations considered related to the test substance. Statistically significant increases in the incidences of dehydration, urine-stained abdominal fur and ungroomed coat occurred in the 30 mg/kg/day dosage group. The number of male rats with chromorhinorrhea was increased in the 3 mg/kg/day and higher dosage groups; however these increases were not statistically significant; all other clinical observations were considered unrelated to the test substance. Body weight gains for the entire dosage period before cohabitation were significantly reduced in the 3, 10 and 30 mg/kg/day dosage groups. As a result, body weight gains for the entire dosage period were significantly reduced in the 3, 10 and 30 mg/kg/day dosage groups. Body weights were significantly reduced in the 30 mg/kg/day dosage group on DS 8 through termination, in the 10 mg/kg/day dosage group on DS 15 through termination and in the 3 mg/kg/day dosage group on DS 50 through termination. Absolute feed consumption values were significantly reduced in the 30 mg/kg/day dosage group for the entire dosage period before cohabitation and the entire study period and at most tabulated intervals within these periods. Relative feed consumption values were significantly increased in the 3, 10 and 30 mg/kg/day dosage groups for the entire dosage period before cohabitation and the entire study. All mating and fertility parameters were unaffected by dosages of the test substance as high as 30 mg/kg/day. All necropsy observations were considered unrelated to the test substance. Terminal body weights were significantly reduced in the 3, 10 and 30 mg/kg/day dosage groups. Absolute weights of the epididymides, left cauda epididymis, seminal vesicles, prostate, pituitary, adrenals, spleen and thymus were significantly reduced in the 30 mg/kg/day dosage group. The absolute weight of the liver was significantly increased in the 1, 3, 10 and 30 mg/kg/day dosage groups. Weights of the kidneys were significantly increased in the 1,3 and 10 mg/kg/day dosage groups, while these weights were significantly reduced in the 30 mg/kg/day dosage group. The ratios of the organ weight to the terminal body weight were significantly increased in the 10 and 30 mg/kg/day dosage groups for the epididymides, left cauda epididymis (30 mg/kg/day only), testes and seminal vesicles. The ratio of the brain weight to the terminal body weight was significantly increased in the 3, 10 and 30 mg/kg/day dosage groups. The ratios of the liver and left and right kidney weights to the terminal body weight were significantly increased in the 1,3, 10 and 30 mg/kg/day dosage groups. The Page 18 ARGUS 418-020 ratio of the left adrenal weight to the terminal body weight was significantly increased in the 30 mg/kg/day dosage group. Ratios of the organ weight to the brain weight were significantly reduced in the 30 mg/kg/day dosage group for the epididymides, cauda epididymis, prostate, pituitary, spleen and thymus. The ratios of the liver weight to the brain weight were significantly increased in the 1, 3, 10 and 30 mg/kg/day dosage groups. The ratios of the kidneys weights to the brain weight were significantly increased in the 1,3 and 10 mg/kg/day dosage groups while the ratio of the left kidney weight to the brain weight was significantly reduced in the 30 mg/kg/day dosage group. All sperm parameters evaluated were unaffected by dosages of the test substance as high as 30 mg/kg/day. No treatment-related microscopic changes were observed in the reproductive organs of any of the male rats in the P generation. A treatment-related microscopic change was observed in the adrenal glands of the P generation male rats of the 10 and 30 mg/kg/day dosage groups. This change was characterized by hypertrophy and vacuolation of the cells of the zona glomerulosa of the adrenal cortex. All other microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be incidental and unrelated to treatment. B.2. P Generation Female Rats There were no P generation female rat deaths attributed to the test substance. All clinical observations during the precohabitation, gestation and lactation periods were considered unrelated to the test substance. Body weights and body weight gains during the precohabitation, gestation and lactation periods were unaffected by dosages of the test substance as high as 30 mg/kg/day. Absolute and relative feed consumption values during the precohabitation, gestation and lactation periods were unaffected by dosages of the test substance as high as 30 mg/kg/day. The average numbers of estrous stages per 21 days were comparable among the five dosage groups and did not significantly differ. Evaluation of estrous stages at sacrifice did not reveal any differences among the five dosage groups. All mating and fertility parameters were unaffected by dosages of the test substance as high as 30 mg/kg/day. All necropsy observations were considered unrelated to the test substance. Terminal body weights of the P generation female rats were comparable among the five dosage groups and did not significantly differ. The weights of the kidneys, the ratios of this organ weight to the terminal body weight and the ratio of the left kidney weight to the brain weight were significantly reduced in the 30 mg/kg/day dosage group. Page 19 ARGUS 418-020 Pregnancy occurred in 27 to 29 rats in each dosage group. Natural delivery observations were unaffected by dosages of the test substance as high as 30 mg/kg/day. No clinical or necropsy observations were attributable to dosages of the test substance as high as 30 mg/kg/day. Terminal body weights of the FI generation pups were comparable among the five dosage groups and did not significantly differ. The weights of the brain, spleen and thymus and the ratios of these organ weights to the terminal body weight and brain weight were unaffected by dosages of the test substance as high as 30 mg/kg/day. No treatment-related microscopic changes were observed in the reproductive organs of any of the female rats in the P generation. All microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be incidental and unrelated to treatment. B.3. FI Generation Male Rats Three, three, three, two and seven FI generation male rats in the 0, 1,3, 10 and 30 mg/kg/day dosage groups were moribund sacrificed or found dead. The increased incidence of mortality in the 30 mg/kg/day dosage group was considered treatmentrelated. Most deaths appeared to be related to a failure of the pups to thrive within a few days of weaning. This failure to thrive is common in this strain of rat when the weaning rats are small for weaning. The incidences of annular constriction of the tail of male FI generation rats were increased in the 1,3, 10 and 30 mg/kg/day dosage groups, reaching statistical significance in the 1, 10 and 30 mg/kg/day dosage groups. The number of male rats observed to be emaciated was significantly increased in the 10 and 30 mg/kg/day dosage groups, and the numbers of male rats with urine-stained abdominal fur, decreased motor activity and abdominal distention were significantly increased in the 30 mg/kg/day dosage group. The incidence of the observation of cold to touch was increased, albeit not significantly, in the 30 mg/kg/day dosage group. Body weights and body weight gains were reduced in a dosage-dependent pattern for the FI generation male rats before and after the cohabitation period at the 1,3, 10 and/or 30 mg/kg/day dosages of the test substance, as compared to the control group. Absolute feed consumption values for the FI generation male rats were significantly reduced and relative feed consumption values were significantly increased for the entire precohabitation period by dosages of APFO of 10 and 30 mg/kg/day. Page 20 ARGUS 418-020 Preputial separation of FI generation male rats was slightly delayed in the 30 mg/kg/day dosage group and above the Testing Facility historical control average and range for this parameter (see APPENDIX L). When this observation in the 30 mg/kg/day dosage group was covaried with the significantly reduced (p<0.01) body weight at time of acquisition to determine if the significantly reduced body weights were a factor, the difference was still significant, but at the p<0.05 level. When this observation in the 30 mg/kg/day dosage group was covaried with gestational age (calculated from the day of mating to the day of acquisition) at time of acquisition to determine if this group was younger and more immature than the control group, there was no significant difference in sexual maturation. Dosages of the test substance as high as 30 mg/kg/day did not affect any mating and fertility parameters evaluated in the FI generation male rats, of the male rats assigned to cohabitation, 93.3%, 96.6%, 93.3%, 93.3% and 96.7% impregnated the cohort female rat in the five dosage groups, respectively. Tan areas occurred in the left lateral and/or median lobes of the liver in 6,10 and 9 male rats in the 3, 10 and 30 mg/kg/day dosage groups, respectively. One of these rats in the 30 mg/kg/day dosage group also had a small spleen. One 30 mg/kg/day dosage group rat had an enlarged liver. Moderate to slight dilation of the pelvis of one or both kidneys occurred in 4 and 1 rats in the 10 and 30 mg/kg/day dosage groups, respectively. A tan area in the parenchyma of the spleen occurred in one 10 mg/kg/day dosage group rat. Terminal body weights of the FI generation male rats were significantly reduced in a dosage-dependent manner in the 1,3, 10 and 30 mg/kg/day dosage groups. The absolute weights of the liver were significantly increased and the absolute weights of the spleen were significantly decreased in the 1 mg/kg/day and higher dosage groups, compared to the control group values. The absolute weights of the left and/or right kidneys were significantly increased in the 1 and 3 mg/kg/day dosage groups and significantly decreased in the 30 mg/kg/day dosage group, compared to control group values. The absolute weight of the thymus was also significantly decreased in the 10 and 30 mg/kg/day dosage groups. The absolute weight of the prostate, brain and left adrenal gland were significantly decreased in the 30 mg/kg/day dosage group. The ratios of the weights of the seminal vesicles, with and without fluid, liver and left and right kidneys to the terminal body weights were significantly increased in the 1 mg/kg/day and higher dosage groups, compared to the control group values. The ratios of the weights of the left testis, with and without the tunica albuginea and the right testis to the terminal body weight, were significantly increased in the 3 mg/kg/day and higher dosage groups. The ratios of the weights of the left epididymis, left cauda epididymis, right epididymis and brain to the terminal body weight were significantly increased in the 10 mg/kg/day and higher dosage groups. The ratios of the weight of the seminal vesicles with fluid to the brain weight were increased in the 1 mg/kg/day and higher dosage groups, compared to the control group values. These ratios were significantly increased in the 1 and 10 mg/kg/day dosage groups. The ratios of the liver weight to the brain weight were significantly increased in the 1 mg/kg/day and higher dosage groups, and the ratios of the left and right kidney Page 21 ARGUS 418-020 weights to the brain weight were significantly increased in the 1,3 and 10 mg/kg/day dosage groups. The ratios of the spleen weight to the brain weight were significantly decreased in the 1 mg/kg/day and higher dosage groups, and the ratios of the thymus weight to the brain weight were significantly decreased in the 10 and 30 mg/kg/day dosage groups. The ratios of the left and right testes weight to the brain weight were increased in the 3 mg/kg/day and higher dosage groups. These ratios were significantly increased in the 10 mg/kg/day (right testis only) and 30 mg/kg/day dosage groups. No treatment-related microscopic changes were observed in the reproductive organs of any of the male rats in the FI generation. A treatment-related microscopic change was observed in the adrenal glands of the FI generation male rats of the 30 mg/kg/day dosage groups. This change was characterized by hypertrophy and vacuolation of the cells of the zona glomerulosa of the adrenal cortex. Microscopic examination of liver sections of the FI generation male rats which were observed grossly to be enlarged or have tan areas in the liver lobes showed up to marked diffuse hepatocellular hypertrophy. Single or lower incidences of hepatocellular necrosis also were observed in the male rats of these groups. All other microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be incidental and unrelated to treatment. No statistically significant or dosage-dependent differences occurred in the numbers of motile sperm, percentage of motile sperm, static count (nonmotile sperm), total count, sperm density, spermatid count or density. Sperm morphology was unaffected by dosages of the test substance as high as 30 mg/kg/day. B.4. FI Generation Female Rats Two, one, one and six FI generation female rats in the 1,3, 10 and 30 mg/kg/day dosage groups were found dead. The increased incidence of mortality in the 30 mg/kg/day dosage group was considered treatment-related. Most deaths appeared to be related to a failure of the pups to thrive within a few days of weaning. This failure to thrive is common in this strain of rat when the weaning rats are small for weaning. All clinical observations during the precohabitation, gestation and lactation periods were considered unrelated to the test substance. Body weights and body weight gains during the precohabitation period were significantly reduced by 30 mg/kg/day dosages of the test substance. Body weight gain for the entire precohabitation period was significantly reduced. Body weights during the gestation and lactation periods were significantly reduced in the 30 mg/kg/day dosage. Absolute feed consumption values were significantly reduced in the 30 mg/kg/day dosage group on DPs 1 to 8, 8 to 15 and 15 to 22 during the precohabitation period, on DGs 7 to 10 during the gestation period and on DLs 1 to 15 during the lactation period. Relative feed consumption values were comparable among the 0 ,1,3, 10 and 30 mg/kg/day dosage groups for the precohabitation, gestation and lactation periods and did not differ statistically. Page 22 ARGUS 418-020 The 30 mg/kg/day dosage group FI generation female rats had a small (approximately 1.7 days increase), but statistically significant delay in vaginal patency. The average day when vaginal patency was evident in the 30 mg/kg/day dosage group (36.6 days of age) significantly differed from the control group value (34.9 days of age) was above the Testing Facility historical control average and range for this parameter. When this observation in the 30 mg/kg/day dosage group was covaried with the significantly reduced (p<0.01) body weight at time of acquisition, to determine if the significantly reduced body weights were a factor, the difference was still significant, but at the p<0.05 level. When this observation in the 30 mg/kg/day dosage group was covaried with gestational age at time of acquisition, to determine if this group was younger and more immature than the control group, there was no significant difference in sexual maturation. The average numbers of estrous stages per 21 days were significantly increased in the 30 mg/kg/day dosage group. The Testing Facility historical control average and range for this parameter is 5.0 stages and 4.8 to 5.2 stages, respectively. When this observation was covaried with the day 64 body weight or age, the difference was still significant, but at the p<0.05 level. Evaluation of estrous stages at sacrifice did not reveal any differences among the five dosage groups. All mating and fertility parameters were unaffected by dosages of the test substance as high as 30 mg/kg/day. All necropsy observations for the FI generation female rats were considered unrelated to the test substance. Terminal body weights of the FI generation female rats were comparable among the five dosage groups and did not differ significantly. The absolute weights of the pituitary and the ratios of the pituitary weight to the terminal body weight and to the brain weight were significantly decreased in the 3 mg/kg/day and higher dosage groups, as compared to the control group values. No treatment-related microscopic changes were observed in the reproductive organs of any of the female rats in the FI generation. All microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be incidental and unrelated to treatment. Pregnancy occurred in 28 to 29 rats in each dosage group. Natural delivery observations including viability and lactation indices were unaffected by dosages of the test substance as high as 30 mg/kg/day. Anogenital distances measured for male and female pups on DLs 1 and 22 were comparable among the five dosage groups and did not significantly differ. No clinical or necropsy observations were attributable to maternal dosages of the test substance as high as 30 mg/kg/day. F2 generation rats had comparable terminal body weights on DL 22; the values did not significantly differ from the control group values. Absolute weights of the brain, spleen and thymus and ratios of these organ weights to terminal body weight and to brain weight were comparable among the five dosage groups and did not significantly differ. Page 23 ARGUS 418-020 C. Conclusion On the basis of these data, the P generation paternal no-observable-adverse-effect-level (NOAEL) for ammonium perfluorooctanoate is less than 1 mg/kg/day (the 1 mg/kg/day dosage caused significant increases in the liver and kidney weights to terminal body weight and to brain weight ratios). The maternal NOAEL is 10 mg/kg/day (the 30 mg/kg/day dosage significantly reduced kidney weight and kidney weight to terminal body weight and to brain weight ratios). The reproductive NOAEL in the males and female P generation rats is greater than 30 mg/kg/day (the 30 mg/kg/day dosage had no effect on mating, fertility or maternal delivery parameters). The FI generation paternal no-observable-adverse-effect-level (NOAEL) for ammonium perfluorooctanoate is less than 1 mg/kg/day (the 1 mg/kg/day and higher dosages caused significant decreases in body weights and body weight gain and changes in organ weights and ratios to terminal body and brain weights and the 30 mg/kg/day dosage delayed sexual maturation possibly due to decreased gestational age at acquisition). The FI generation maternal NOAEL is 10 mg/kg/day (the 30 mg/kg/day dosage increased postweaning mortality, decreased postweaning body weight, body weight gain and feed consumption, increased the number of estrous cycles per 21 days and delayed sexual maturation possibly due to decreased gestational age at acquisition). The reproductive NOAEL in the males and female FI generation rats is greater than 30 mg/kg/day (the 30 mg/kg/day dosage had no effect on mating, fertility or maternal delivery parameters). The F2 generation terminal body weights and organ weights did not differ among the groups. Associate Director onResearch and Study Director Page 24 ARGUS 418-020 H. DESCRIPTION OF TEST PROCEDURES A. Conduct of Study A.l. Sponsor 3M Corporate Toxicology, 3M Center, Building 220-2E-02, St. Paul, Minnesota 55144-1000 A.2. Testing Facility Argus Research, 905 Sheehy Drive, Building A, Horsham, Pennsylvania 19044-1297 A.3. Study Number 418-020 A.4. Sponsor's Study Number T-6889.6 A.5. Purpose of the Study The purpose of this study was to provide information concerning the effects of Ammonium Perfluorooctanoate (APFO) on the male and female reproductive systems in Crl:CD(SD)IGS BR VAF/Plus rats, including gonadal function, estrous cycles, mating behavior, conception, parturition, lactation, weaning and the growth and development of offspring. This study was also designed to provide information about effects on neonatal morbidity, mortality and preliminary data on potential prenatal developmental toxicity, as well as to serve as a guide for use in the design of subsequent tests. A.6. Study Design The requirements of the U.S. Environmental Protection Agency (EPA)(I,2) were used as the basis for study design. A.7. Regulatory Compliance The study was conducted in compliance with the Good Laboratory Practice (GLP) regulations of the U.S. Environmental Protection Agency (EPA)(3) and the Organisation for Economic Co-operation and Development (OECD)(4). There were no deviations from the GLP regulations that affected the quality or integrity of the study. Quality Assurance Unit findings derived from the inspections during the conduct of this study are documented and have been provided to the Study Director and the Testing Facility Management. Page 25 ARGUS 418-020 A.8. Ownership of the Study The Sponsor owns the study. All raw data, analyses, reports and preserved tissues are the property of the Sponsor. A.9. Study Monitor John Butenhoff, Ph.D., DABT, CIH (3M Corporate Toxicology, St. Paul, Minnesota 55144) A.10. Study Director Raymond G. York, Ph.D., DABT (Associate Director of Research, Argus Research, Horsham, Pennsylvania 19044) A.11. Technical Performance John F. Barnett, B.S. (Director of Laboratory Operations) Russell A. Gazzara, Ph.D. (Senior Research Associate) Joseph W. Lech, B.S. (Senior Research Associate) Alaine L. Casey, A.S. (Scheduling Coordinator/Blood Collection Coordinator) Allyson B. Hansell, B.S. (Laboratory Technician) Brian K. Kelsch (Necropsy Team Leader) Christopher K. Ruppert, B.S. (Formulation Laboratory Technician) A.12. Report Preparation Raymond G. York, Ph.D., DABT Valerie A. Sharper, M.S. (Director of Study Management) Jo Ann Frazee, M.S. (Study Coordinator) Elizabeth M. Wiley, B.S. (Data Management Specialist) JoAnne M. Conklin, B.S. (Data Management Specialist) Cristina Petrescu (Report Administrator) A.13. Report Review Alan M. Hoberman, Ph.D., DABT (Director of Research) Valerie A. Sharper, M.S. (Director of Study Management) A.14. Date Protocol Signed 7 November 2000 Page 26 A.15. Dates of Technical Performance A.15.a. P Generation Male Rats Rat Arrival Test Substance Dosage Period Male Rats Sacrificed A.15.b. P Generation Female Rats Rat Arrival Test Substance Dosage Period Precohabitation Estrous Cycle Evaluation Cohabitation Period Day 0 of Presumed Gestation3(DG 0) Delivery Period6 (Day 1 of lactation) DG 25 Sacrifice (Rats that did not deliver a litter) DLC22 Sacrifice (P generation dams and FI generation litters not selected for continued observation) A.15.C. FI Generation Male Rats Test Substance Dosage Period Male Rats Sacrificed - Interim (Rats not selected for continued observations following observations for sexual maturation) Male Rats Sacrificed - Scheduled ARGUS 418-020 07 NOV 00 13 NOV 00-01 MAR 01 26 FEB 01-02 MAR 01 07 NOV 00 13 NOV 00- 18 MAR Ol 01 JAN 01 -21 JAN 01 21 JAN 01 PM - 04 FEB 01 AM 22 JAN 01 - 04 FEB 01 12 FEB 01 - 26 FEB 01 16 FEB 01 - 18 FEB 01 05 MAROl - 19MAR01 06 MAROl -05 JUL01 13 APR 01 and 04 MAY 01 02 JUL 01 - 06 JUL 01 a. Gestation day 0 is defined as the day spermatozoa are observed in a smear of the vaginal contents and/or a copulatory plug observed in situ. b. The day of birth is designated postnatal day 0 (day 0 of lactation) in Addendum 10 to the Pesticide Assessment Guidelines of the U.S. Environmental Protection Agency (EPA). This same day is designated day 1 postpartum (day 1 of lactation) in the Standard Operating Procedures of the Testing Facility. Throughout this protocol, the day of birth will be designated day 1postpartum (day 1 of lactation) and all subsequent ages of the FI generation rats and days of the lactation period will be determined and cited accordingly. c. DL is an abbreviation used for day of lactation/postpartum. Page 27 ARGUS 418-020 A.15.d. FI Generation Female Rats Test Substance Dosage Period Precohabitation Estrous Cycle Evaluation Cohabitation Period Female Rats Sacrificed - Interim (Rats not selected for continued observation following observations for sexual maturation) DGO DL1 DG 25 Sacrifice (Rats that did not deliver a litter) DL 22 Sacrifice (FI generation dams and F2 generation pups) 06 MAR 01 -15 JUL01 08 MAY 01 -28 MAY 01 28 MAY 01 PM - 11 JUN 01 AM 06 APR 01 29 MAY 01 - 04 JUN 01 19 JUN 01 - 25 JUN 01 23 JUN 01 - 29 JUN 01 10 JUL 01 - 16 JUL01 A.16. Records Maintained The original report, raw data and reserve samples of the test substance and vehicle are retained in the archives of Argus Research. Any preserved tissues are retained in the archives of the Testing Facility for one year after the mailing of the draft final report, after which time the Sponsor will decide their final disposition. All unused prepared formulations were discarded at the Testing Facility. Unused bulk test substance was returned to the Sponsor. B. Test Substance Information B.l. Description Ammonium Perfluorooctanoate (APFO) - white powder B.2. Lot Number 332 B.3. Date Received and Storage Conditions The test substance was received on 7 November 2000 and stored at room temperature. B.4. Special Handling Instructions Standard safety precautions (use of protective clothing, gloves, dust-mist/HEPA-filtered mask, safety goggles or safety glasses and a face-shield) were taken when handling the prepared solutions. Tyvek sleeves and a half-face respirator were worn when using the bulk test substance and preparation was conducted under a chemical fume hood. Page 28 ARGUS 418-020 B.5. Analysis of Purity Information to document or certify the identity, composition, method of synthesis, strength and purity of the test substance was provided by the Sponsor to the Testing Facility. A Certificate of Analysis is available in APPENDIX H. C. Vehicle Information C.l. Description Reverse Osmosis Membrane Processed Deionized Water (R.O. deionized water). C.2. Storage Conditions R.O. deionized water is available from a continuous source at the Testing Facility and was maintained at room temperature. C.3. Special Handling Instructions Standard safety precautions (use of protective clothing, gloves, dust-mist/HEPA-filtered mask, safety goggles or safety glasses and a face-shield) were taken when handling the vehicle. C.4. Analysis of Purity Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to have been present in the vehicle that would have interfered with the results of this study. D. Test Substance Preparation and Storage Conditions Solutions o f the test substance were prepared weekly at the Testing Facility. Prepared formulations were stored refrigerated, protected from light. Page 29 ARGUS 418-020 D.l. Sample Information Sample Type Date Size Retained Storage/Shipping Conditions Shipped To Date Shipped Bulk Test Substance 1 g 15 JUL01 Room temperature Concentration 2 mL 10 NOV 00 Refrigerated, Sponsor Sponsor 16 JUL01 13 NOV 00 (all levels)3 12JUL01 protected from light 12JUL01 Stability 2mL 10 NOV 00 Refrigerated, Sponsor 13 NOV 00 (all levels)b protected from light Bulk Test Substance 1 g Reserve 10 NOV 00 Room temperature Testing Facility Archives 13 DEC 00 Vehicle Reserve 5 mL 10 NOV 00 Room temperature Testing Facility Archives 13 DEC 00 a. Duplicate samples were taken on the first and last days of preparation. One sample of each duplicate set was shipped for analysis. The remaining samples were retained at the Testing Facility as backup samples. b. Two sets of duplicate samples were taken on the first day of preparation. One sample of each duplicate set was shipped for analysis on the day of preparation. Samples were analyzed as soon as possible and 10 days after the first analysis. The remaining samples were retained at the Testing Facility as backup samples. D.2. Analytical Results The analytical results are available in APPENDIX I. E. Test System E.l. Species Rat E.2. Strain Crl:CD(SD)IGS BR VAF/Plus E.3. Supplier (Source) Charles River Laboratories, Inc., Kingston, New York (male rats) and Raleigh, North Carolina (female rats) Offspring were delivered at the Testing Facility by the pregnant P or FI generation dams in this study. E.4. Sex Male and Female rats Page 30 ARGUS 418-020 E.5. Rationale for Test System The Crl:CD(SD)IGS BR VAF/Plus rat was selected as the Test System because: 1) this strain of rat has been demonstrated to be sensitive to reproductive and developmental toxins and has been widely used throughout industry for reproductive and developmental toxicity evaluations and 2) historical data and experience exist at the Testing Facility*5'7*. E.6. Test System Data Number of Rats Approximate Date of Birth Approximate Age at Arrival Weight (g) on Day after Arrival Weight (g) at Study Assignment Male Rats 165 02 OCT 00 37 days 100 - 143 140 -164 Female Rats 165 01 OCT 00 38 days 88 - 132 120-144 E.7. Method of Randomization E.7.a. P Generation Rats Upon arrival, P generation rats were assigned to individual housing on the basis of computer-generated random units. After acclimation, rats were selected for study on the basis of physical appearance and body weight. Rats were assigned to five dosage groups (Groups I through V), 30 rats per sex per dosage group, using a computer-generated (weight-ordered) randomization procedure. E.7.b. FI Generation Pups/Rats Litters were not culled during the lactation period, because random selection of pups for culling could have resulted in potential biases in pup viabilities and body weight gains during this period. All FI generation rats were weaned on DL 22 based on observed growth and viability of these pups. At weaning, a table of random units was used to select two FI generation pups per sex per litter per group (60 male and 60 female pups per group), resulting in a total of 600 rats (300 rats per sex) chosen for continued evaluation. At least two male pups and two female pups per litter, when possible, were selected. Following sexual maturation, a table of random units was used to select one male and one female FI generation rat per litter per group when possible for continuation through mating to produce the F2 generation. Page 31 ARGUS 418-020 E.8. System of Identification E.8.a. P Generation Rats Male and female rats were assigned temporary numbers at receipt and given unique permanent identification numbers when assigned to the study before administration of the first dosage of the test substance or vehicle. Rats were permanently identified using Monel self-piercing ear tags (Gey Band and Tag Co., Inc., No. MSPT 20101) inscribed with the rat's designated unique permanent number. Cage tags were marked with the study number, permanent rat number, sex, test substance identification, generation and dosage level. E.8.b. FI Generation Pups/Rats Pups were not individually identified during the postpartum period; all parameters were evaluated in terms of the litter. At weaning, each FI generation rat selected for continued observation was identified with a Monel self-piercing ear tag. E. 8.c. F2 Generation Pups Pups were not individually identified during the postpartum period; all parameters were evaluated in terms of the litter. F. Husbandry F.l. Research Facility Registration USDA Registration No. 14-R-0122 under the Animal Welfare Act, 7 U.S.C. 2131 et seq. F.2. Study Rooms The study rooms were maintained under conditions o f positive airflow relative to a hallway and independently supplied with a minimum of ten changes per hour of 100% fresh air that had been passed through 99.97% HEPA filters. Room temperature and humidity were monitored constantly throughout the study. Room temperature was targeted at 64F to 79F (18C to 26C); relative humidity was targeted at 30% to 70%a. F.3. Housing All cage sizes and housing conditions were in compliance with the Guidefor the Care and Use o f Laboratory Animals(8). a. See APPENDIX J (ENVIRONMENTAL AND HUSBANDRY REPORTS). Page 32 ARGUS 418-020 F.3.a. P Generation Rats/Fl Generation Litters P generation rats were individually housed in stainless steel, wire-bottomed cages except during the cohabitation and postpartum periods. During cohabitation, each pair of rats was housed in the male rat's cage. Beginning no later than DG 20, female rats were individually housed in nesting boxes. Each dam and delivered litter was housed in a common nesting box during the postpartum period. F.3.b. FI Generation Rats/F2 Generation Litters After weaning, the FI generation rats were individually housed before cohabitation, housed in pairs (one male rat per female rat) during cohabitation, and individually housed after cohabitation. The same type of caging was used as described for the P generation rats. Beginning no later than DG 20, female rats were individually housed in nesting boxes. Each dam and delivered litter was housed in a common nesting box during the postpartum period. F.4. Lighting An automatically-controlled fluorescent light cycle was maintained at 12-hours light: 12-hours dark, with each dark period beginning at 1900 hours EST. The lights were turned on one hour early on 13 April 2001 in order to accommodate the necropsy schedule. F.5. Sanitization Cage pan liners were changed a minimum of three times weekly. Cages were changed approximately every other week. Bedding was changed as often as necessary to keep the rats dry and clean. F.6. Feed Rats were given ad libitum access to Certified Rodent Diet #5002 (PMI Nutrition International, St. Louis, Missouri) in individual feeders. F.7. Feed Analysis Analyses were routinely performed by the feed supplier. No contaminants at levels exceeding the maximum concentration limits for certified feed or deviations from expected nutritional requirements were detected by these analyses. Copies of the results of the feed analyses are available in the raw data and in APPENDIX J. Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to have been present in the feed that would have interfered with the results of this study. Page 33 ARGUS 418-020 F.8. Water Local water that had been processed by passage through a reverse osmosis membrane (R.O. water) was available to the rats ad libitum from individual bottles attached to the cages and/or from an automatic watering access system. Chlorine was added to the processed water as a bacteriostat. F.9. Water Analysis The processed water is analyzed twice annually for possible chemical contamination (Lancaster Laboratories, Lancaster, Pennsylvania) and monthly for possible bacterial contamination (Analytical Laboratories, Inc., Chalfont, Pennsylvania). Copies of the results of the water analyses are available in the raw data and in APPENDIX J. Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to have been present in the water that would have interfered with the results of this study. F.10. Bedding Material Bed-o'cobs bedding (The Anderson's Industrial Products Group, Maumee, Ohio) was used as the nesting material. F .ll. Bedding Analysis Analyses for possible contamination are conducted semi-annually. Copies of the results of the bedding analyses are available in the raw data and in APPENDIX J. Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to have been present in the bedding that would have interfered with the results of this study. Page 34 ARGUS 418-020 G. Methods G.l. Dosage Administration G.l.a. P Generation Rats Dosage Group I Dosage Concentration3 Dosage Volume (mg/kg/day) (mg/mL) (mL/kg) 00 5 Number of Rats per Sex 30 Assigned Rat Numbers Male Rats Female Rats 13601-13630 13801-13830 II 1 0.2 5 30 13631-13660 13831-13860 III 3 0.6 5 30 13661-13690 13861-13890 IV 10 2 5 30 13691-13720 13891-13920 V 30 6 5 30 13721-13750 13921-13950 a. The test substance was considered 100% pure for the purpose of dosage calculations. G.l.b. FI Generation Rats Dosage Dosage Concentration3 Dosage Volume Number of Rats Group (mg/kg/day) (mg/mL) (mL/kg) per Sexb I0 0 5 60 II 1 0.2 5 60 Assigned Rat Numbers Male Rats Female Rats 1001 -1017, 6553 - 6555c, 1021 -1060 1301 -1318, 19779", 19780", 1321- 1360 1061 - 1120 1361 - 1420 III 3 0.6 5 60 1121 - 1180 1421 - 1480 IV 10 2 5 60 1181 -1240 1481 - 1540 V 30 6 5 60 1241 - 1300 1541 - 1600 | a. The test substance was considered 100% pure for the purpose of dosage calculations. b. Sixty rats per sex were dosed until the time of interim sacrifice and 30 rats per sex were dosed after the interim sacrifice. c. Male rats 1018 - 1020 were moribund sacrificed and replaced by male rats 6553 - 6555, respectively. d. Female rats 1319 and 1320 were moribund sacrificed and replaced by female rats 19779 and 19780, respectively. G.2. Rationale for Dosage Selection Dosages were selected on the basis of prior dietary and gavage studies in rats performed by the Sponsor. The highest dosage was expected to produce some toxicity. The intermediate dosage levels were expected to produce minimal observable toxic effects, while the lowest dosage level was expected to produce no evidence of either systemic or reproductive toxicity [no-observable-adverse-effect level (NOAEL)]. Page 35 ARGUS 418-020 G.3. Route of Administration and Rationale for Route of Administration The oral (gavage) route was selected for use because: 1) in comparison with the dietary route, the exact dosage can be accurately administered; and 2) it is one possible route of human exposure. G.4. Frequency of Administration G.4.a. P Generation Rats Male and female rats were given the test substance or vehicle once daily, beginning at approximately six weeks of age (at least 70 days before cohabitation) and continuing until the day before sacrifice. The dosage volume was adjusted daily on the basis of the most recently recorded body weight3and given at approximately the same time each dayb. Dams in the process of delivering pups were not intubated until completion of parturition, in order to preclude possible disruption of maternal behavior and/or cannibalization of the pups. Consequently, some dams were not administered one daily dosage during the delivery period. No dam missed more than one daily intubation. G.4.b. FI Generation Rats FI generation pups may have been exposed to the test substance during maternal gestation (in utero exposure) or via maternal milk during the postpartum period. FI generation rats were given the same dosage level of the test substance as their respective P generation sires and dams. Dosages were given once daily, beginning at weaning (approximately 70 days before cohabitation) and continuing until the day before sacrificed Dosages were adjusted at least weekly for body weight changes and given at approximately the same time each dayd. G.4.c. F2 Generation Pups F2 generation pups may have been exposed to the test substance during maternal gestation (in utero exposure) or via maternal milk during the postpartum period. a. See APPENDIX G (DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY), item 1. b. See APPENDIX G, item 2. c. See APPENDIX G, item 3. d. See APPENDIX G, items 4 and 5. Page 36 ARGUS 418-020 G.5. Method of Study Performance G.5.a. P Generation Rats The P generation rats were observed for viability at least twice each day of the study and for general appearance weekly during the acclimation period. The rats were also examined for clinical observations of effects of the test substance, abortions, premature deliveries and deaths before and 60 10 minutes after dosage during the dosage period3. Body weights of the male rats were recorded weekly during the acclimation and dosage periods and on the day of sacrifice. Body weights of the female rats were recorded weekly during the acclimation, precohabitation and cohabitation periods and on DGs 0, 7, 10, 14, 18, 21 and 25 (if necessary) and on DLs 1, 5, 8, 11, 15 and 22 (terminal body weight). Feed consumption values for the male rats were recorded weekly during the dosage period. Feed consumption values for the female rats were recorded weekly during the precohabitation period, on DGs 0, 7, 10, 14, 18, 21 and 25 (if necessary) and on DLs 1, 5, 8, 11 and 15. Because pups begin to consume maternal feed on or about DL 15, feed consumption values were not tabulated after DL 15. During cohabitation, when two rats occupied the same cage with one feed jar, replenishment of the feed jars was documented but individual values were not recorded or tabulated. Estrous cycling was evaluated daily by examination of vaginal cytology beginning 21 days before the scheduled cohabitation period and continuing until spermatozoa were observed in a smear of the vaginal contents and/or a copulatory plug was observed in situ during the cohabitation period6. On the day of scheduled sacrifice, an examination of vaginal cytology was performed to determine the stage of estrous cycle. Within each dosage group, consecutive order was used to assign P generation rats to cohabitation, one male rat per female rat. The cohabitation period consisted of a maximum of 14 days. Female rats with spermatozoa observed in a smear of the vaginal contents and/or a copulatory plug in situ were considered to be at DG 0 and assigned to individual housing. If a female rat had not been mated after two weeks, the pair of rats was separated without further opportunity for mating. The P generation female rats were evaluated for duration of gestation (DG 0 to the day the first pup was observed), fertility index (percentage of matings that result in pregnancy), gestation index (percentage of pregnancies that result in birth of live litters), number and sex of offspring per litter (live and dead pups), number of implantation sites, general condition of the dam and litter during the postpartum period, litter size and viability (tabulated on DLs 1, 5, 8, 15 and 22), viability indices (percentages of pups bom that survive to DLs 1 and 5), lactation index (percentage of pups that survive from DLs 5 to 22) and percent survival and sex ratio (tabulated on DLs 1, 5, 8, 15 and 22). Maternal behavior of the P generation dams was recorded on DLs 1, 5, 8, 15 and 22c. a. See APPENDIX G, items 6 and 7. b. See APPENDIX G, item 8. c. See APPENDIX G, item 9. Page 37 ARGUS 418-020 Deviations from expected maternal behavior were recorded, if and when observed, on all other days of the postpartum period. G.5.b. FI Generation Pups/Litters Litters were examined after delivery to identify the number and sex of pups, stillbirths, live births and gross alterations. Day 1 of lactation [(postpartum), DL 1] was defined as the day of birth and was also the first day on which all pups in a litter were individually weighed (pup body weights were recorded after all pups in a litter were delivered and groomed by the dam). Each litter was evaluated for viability at least twice each day of the 22-day postpartum period. Dead pups observed at these times were removed from the nesting box. The FI generation pups in each litter were counted once daily. Physical signs (including variations from expected lactation behavior and gross external physical anomalies) were recorded for the pups each day3. Pup body weights were recorded on DLs 1, 5, 8, 15 and 22. On DL 12, all male pups were examined for the presence of nipples. The criterion of passing was met when no nipples were present. G.5.c. FI Generation Rats The FI generation rats were observed for viability at least twice each day of the study. The rats were also examined for clinical observations of effects of the test substance, abortions, premature deliveries and deaths before and 60 10 minutes after dosage during the dosage period15. Body weights of the male rats were recorded weekly during the postweaning period and on the day of sacrifice. Body weights of the female rats were recorded weekly during the postweaning period to cohabitation, and on DGs 0, 7, 10, 14, 18, 21 and 25 (if necessary) and on DLs 1, 5, 8, 11, 15 and 22 (terminal body weight)c. Feed consumption values for the male rats were recorded weekly during the dosage period. Feed consumption values for the female rats were recorded weekly during the postweaning period to cohabitation, on DGs 0, 7, 10, 14, 18, 21 and 25 (if necessary) and on DLs 1, 5, 8, 11 and 15d. Because pups begin to consume maternal feed on or about DL 15, feed consumption values were not tabulated after DL 15. During cohabitation, when two rats occupied the same cage with one feed jar, replenishment of the feed jars was documented but individual values were not recorded or tabulated. a. See APPENDIX G, item 10. b. See APPENDIX G, items 6, 7, 11 and 12. c. See APPENDIX G, item 13. d. See APPENDIX G, items 14 and 15. Page 38 ARGUS 418-020 Female rats were examined for age of vaginal patency, beginning on day 28 postpartum3. Male rats were evaluated for age of preputial separation, beginning on day 39 postpartumb. Body weights were recorded when rats reached sexual maturation. Estrous cycling was evaluated daily by examination of vaginal cytology beginning 21 days before the scheduled cohabitation period and continuing until spermatozoa were observed in a smear of the vaginal contents and/or a copulatory plug was observed in situ during the cohabitation period. On the day of scheduled sacrifice, an examination of vaginal cytology was performed to determine the stage of estrous cycle. A table of random units was used to assign FI generation rats to cohabitation, one male rat per female rat. If random assignment to cohabitation resulted in the pairing of FI generation siblings, an alternate assignment was made. The cohabitation period consisted of a maximum of 14 days. Female rats with spermatozoa observed in a smear of the vaginal contents and/or a copulatory plug in situ were considered to be at DG 0 and assigned to individual housing. If a female rat had not been mated after two weeks, the pair of rats was separated without further opportunity for mating. ' The FI generation female rats were evaluated for duration of gestation (DG 0 to the day the first pup was observed), fertility index (percentage of matings that result in pregnancy), gestation index (percentage of pregnancies that result in birth of live litters), number and sex of offspring per litter (live and dead pups), number of implantation sites, general condition of the dam and litter during the postpartum period, litter size and viability (tabulated on DLs 1, 5, 8, 15 and 22), viability indices (percentages of pups bom that survive to DLs 1 and 5), lactation index (percentage of pups that survive from DLs 5 to 22) and percent survival and sex ratio (tabulated on DLs 1,5, 8, 15 and 22). Maternal behavior of the FI generation dams was recorded on DLs 1, 5, 8, 15 and 22c. Deviations from expected maternal behavior were recorded, if and when observed, on all other days of the postpartum period. G.5.d. F2 Generation Pups Litters were examined after delivery to identify the number and sex o f pups, stillbirths, live births and gross alterations. Each litter was evaluated for viability at least twice each day of the 22-day postpartum period. Dead pups observed at these times were removed from the nesting box. The FI generation pups in each litter were counted once daily. Physical signs (including variations from expected lactation behavior and gross external physical anomalies) were recorded for the pups each dayd. Pup body weights were recorded on DLs 1, 5, 8, 15 and 22. Anogenital distance was measured for all live F2 generation pups on DLs 1 and 22e. a. See APPENDIX G, item 16. b. See APPENDIX G, items 17 and 18. c. See APPENDIX G, item 19. d. See APPENDIX G, item 20. e. See APPENDIX G, item 21. Page 39 ARGUS 418-020 G.6. Gross Necropsy G.6.a. P and FI Generation Rats P and FI generation rats were sacrificed by carbon dioxide asphyxiation, necropsied and examined for gross lesions. Representative photographs of paternal and maternal gross lesions are available in the raw data. Gross lesions were retained in neutral buffered 10% formalin and examined histologically. Tissue trimming and histopathology were performed under the supervision of or by a Board Certified Veterinary Pathologist. At scheduled sacrifice, after completion of the cohabitation period (male rats) and on DL 22 (female rats), blood samples (approximately 4 mL per rat) were collected from the inferior vena cava into serum separator tubes and centrifuged3. The resulting serum was immediately frozen on dry ice and maintained frozen (<-70C) until shipment to the Sponsor for analysis. The liver was excised, weighed, and a sample section (lateral lobe) frozen and retained at <-70C until shipment to the Sponsor for analysis. Gross necropsy included an initial physical examination of external surfaces and all orifices, as well as an internal examination of tissues and organs in situ. The following were examined: external and internal portions of all hollow organs; the external surfaces of the brain and spinal column, the nasal cavity and neck with associated organs and tissues; the thoracic, abdominal and pelvic cavities with associated organs and tissues; and the musculo/skeletal carcassb. The lungs of the FI generation male and female rats assigned to scheduled sacrifice were perfused with neutral buffered 10% formalin. The urinary bladder of FI generation rats was perfused with neutral buffered 10% formalin. The following organs were individually weighed and organ-to-body weight and organ-tobrain weight ratios were calculated: brain, kidneys, spleen, ovaries, testes, thymus, liver, adrenal glands, pituitary, uterus with oviducts and cervix, left epididymis (whole and cauda), right epididymis, prostate and seminal vesicles (with coagulating glands and with and without fluid). The following tissues were retained in neutral buffered 10% formalin for possible histological evaluation: pituitary, adrenal glands, vagina, uterus with oviducts, cervix and ovaries, right testis (initially fixed in Bourn's solution for 48 to 96 hours), seminal vesicles (with coagulating gland), right epididymis and prostate0. Histological examination was performed on tissues from 10 randomly selected rats per sex from the control and high dosage groups. All gross lesions were examined histologically. In addition to gross lesions such as atrophy or tumors, testicular histopathological examination was conducted to identify treatment-related effects such as retained spermatids, missing germ cell layers or types, multinucleated giant cells or sloughing of spermatogenic cells into the lumen. Examination of the intact epididymis included the caput, corpus and cauda (accomplished by evaluation of a longitudinal a. See APPENDIX G, item 22. b. See APPENDIX G, item 23. c. See APPENDIX G, items 24, 25 and 26. Page 40 ARGUS 418-020 section) and conducted in order to identify such lesions as sperm granulomas, leukocytic infiltration (inflammation), aberrant cell types within the lumen, or the absence of clear cells in the cauda epididymal epithelium. Reproductive organs of the low and intermediate dosage group rats suspected of reduced fertility (e.g., those rats that failed to mate, conceive, sire or deliver healthy offspring, or for which estrous cyclicity or sperm number, motility or morphology were affected) were subjected to histological evaluation3. Rats that died or were sacrificed because of moribund condition were examined for the cause of death or moribund condition on the day the observation was made. The rats were examined for gross lesions. Representative photographs of gross lesions are available in the raw data. Tissues of the P generation rats were weighed and retained and examined histologically as described for male rats sacrificed at the completion of the cohabitation period and female rats sacrificed on DL 22. G.6.a.l. Male Rats Male rats were sacrificed after completion of the cohabitation period [days of study (DSs) 106 to 110 and 109 to 120 for the P and FI generation rats, respectively]. A portion of the left cauda epididymis was used for evaluation of cauda epididymal sperm concentration and motility using computer assisted sperm analysis (CASA). Motility was evaluated by the Hamilton Thome IVOS by collection of a sample from the left cauda epididymis. The remaining left cauda epididymis was used to manually evaluate sperm morphology and to prepare a homogenate to be evaluated by the Hamilton Thome IVOS for a determination of sperm concentration (sperm per gram of tissue weight). Sperm morphology evaluations included the following: 1) determination of the percentage of normal sperm in a sample of at least 200; and 2) qualitative evaluation of abnormal sperm, including such categories as abnormal head, abnormal tail, and abnormal head and tail. The left testis was used for evaluation of testicular spermatid concentration using computer-assisted sperm analysis (CASA). The left testis was weighed (both before and after removal of the tunica albuginea) and then homogenized. A sample from the resulting homogenate was stained with an IDENT Stain Kit from Hamilton Thome Research and a slide was prepared for analysis by the Hamilton Thome IVOS. Ten fields were analyzed to determine testicular spermatid concentration (spermatids per gram of tissue weight). All images produced during analysis were retained as raw data. G.6.a.2. Female Rats P generation female rat 13822 in the vehicle control group was sacrificed on DL 8 and dam 13852 in the 1 mg/kg/day dosage group was sacrificed on DL 11. The litters from these two dams were inadvertently mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. a. See APPENDIX G, item 27. Page 41 ARGUS 418-020 All surviving P and FI generation female rats were sacrificed on DL 22. The number and distribution of implantation sites were recorded. Rats that did not deliver a litter were sacrificed on DG 25 and examined for pregnancy status. Uteri of apparently nonpregnant rats were examined while being pressed between glass plates to confirm the absence of implantation sites. A gross necropsy of the thoracic, abdominal and pelvic viscera was performed. Female rats without a confirmed mating date that did not deliver a litter were sacrificed on an estimated DG 25. The P generation dam with no surviving pups was sacrificed after the last pup was found dead. A gross necropsy of the thoracic, abdominal and pelvic viscera was performed. G.6.b. FI and F2 Generation Pups Pups that died before examination of the litter for pup viability on DL 1 were evaluated for vital status at birth. The lungs were removed and immersed in water. Pups with lungs that sank were identified as stillborn; pups with lungs that floated were identified as livebom, and to have died shortly after birth. When postmortem autolysis precluded these evaluations, it was noted in the necropsy data. Pups found dead on DLs 2 to 22 were examined for gross lesions and for the cause of death. When postmortem autolysis precluded these evaluations, it was noted in the necropsy data. All pups culled on DL 22 were sacrificed by carbon dioxide asphyxiation. Three pups per sex per litter, when possible, were randomly selected and examined for gross lesions. Necropsy included a single cross-section of the head at the level of the frontal-parietal suture and examination of the cross-sectioned brain for apparent hydrocephaly. The brain, spleen and thymus from one of the three selected pups per sex per litter were weighed and the brain, spleen and thymus from the three selected pups per sex per litter were retained in neutral buffered 10% formalin. Gross lesions from the three selected pups per sex per litter were retained in neutral buffered 10% formalin. Representative photographs of gross lesions are available in the raw data. All remaining pups were discarded without further examination. FI generation pups not selected for continued observation following continued observations for sexual maturation were sacrificed by carbon dioxide asphyxiation and a limited necropsy was performed. The thoracic, abdominal and pelvic cavities were examined for gross lesions. Gross lesions were preserved in neutral buffered 10% formalin. Representative photographs of gross lesions are available in the raw data. All other tissues and carcasses were discarded. Page 42 ARGUS 418-020 G.7. Data Collection and Statistical Analyses Data generated during the course of this study were recorded either by hand or using the Argus Automated Data Collection and Management System, the Vivarium Temperature and Relative Humidity Monitoring System and the Hamilton Thome IVOS. All data were tabulated, summarized and/or statistically analyzed using the Argus Automated Data Collection and Management System, the Vivarium Temperature and Relative Humidity Monitoring System, Microsoft Excel [part of Microsoft Office 97 (version SR-2)] and/or The SAS System (version 6.12). Page 43 ARGUS 418-020 The following schematic represents the statistical analyses of the data: Type of Test3 I. Parametric II. Nonparametricb A. Bartlett's Testc A. Kruskal-Wallis Test (<75% ties) Significant at p<0.001 Not Significant Significant at p<0.05 Not Significant Nonparametric Analysis o::Variance Dunn s Test Significant at p<0.05 Not Significant B. Fisher's Exact Test (>75% ties) Dumiett's Test ID. Test for Proportion Data Variance Test for Homogeneity of the Binomial Distribution a. Statistically significant probabilities are reported as either p<0.05 or p<0.01. b. Proportion data are not included in this category. c. Test for homogeneity of variance. Page 44 ARGUS 418-020 All adult and pup incidence data were analyzed using the Variance Test for Homogeneity of the Binomial Distribution^. Body weights, body weight changes, feed consumption data, durations of gestation and delivery, litter averages for pup body weights and percent male fetuses or pups and mortality, cumulative survival and parameters involving continuous data were analyzed using Bartlett's Test of Homogeneity of Variances00) and the Analysis of Variance00, when appropriate [i.e., Bartlett's Test was not significant (p>0.001], If the Analysis of Variance was significant (p<0.05), Dunnett's Test02) was used to identify the statistical significance of the individual groups. If the Analysis of Variance was not appropriate [i.e., Bartlett's Test was significant (p<0.001)], the Kruskal-Wallis Test3) was used, when 75% or fewer ties were present; when more than 75% ties were present; Fisher's Exact Test4) was used. In cases where the Kruskal-Wallis Test was statistically significant (p<0.05), Dunn's Method of Multiple Comparisons05>was used to identify the statistical significance of the individual groups. All other natural delivery data involving discrete data were evaluated using the KruskalWallis Test3) procedures previously described. Page 45 ARGUS 418-020 m . RESULTS - P GENERATION RATS A. P Generation Male Rats A.l. Mortality and Clinical Observations - P Generation Male Rats (Summary Table B l; Individual Data - Table B13) A.l.a. Mortality One P generation male rat in the 30 mg/kg/day dosage group was moribund sacrificed on day 45 of the study (DS 45). The moribund condition was considered possibly related to the test substance because it occurred in the highest dosage group and this rat exhibited adverse clinical observations considered related to the test substance. Observations in this rat are described below. All other P generation male rats survived to scheduled sacrifice. Male rat 13732 in the 30 mg/kg/day dosage group was moribund sacrificed on DS 45. This rat was administered 44 daily dosages of the test substance. Adverse clinical observations before sacrifice included dehydration on DSs 8 and 9, emaciation on DSs 18 to 34 and 41 to 45, cold to touch and urine-stained abdominal fur on DSs 44 and 45 and decreased motor activity on DS 45. This rat lost weight on DSs 1 to 8, 15 to 22 and 36 to 43 and feed consumption values were reduced on DSs 1 to 8, 15 to 22 and 36 to 43, compared to other rats in the dosage group. All lobes of the liver were pale and tan and both testes were red at necropsy; all other tissues examined appeared normal. A.l.b. Clinical Observations Statistically significant increases (p<0.01) in the incidences of dehydration, urine-stained abdominal fur and ungroomed coat occurred in the 30 mg/kg/day dosage group. The number of male rats with chromorhinorrhea was increased in the 3 mg/kg/day and higher dosage groups; however these increases were not statistically significant. All other clinical observations were considered unrelated to the test substance because: 1) the incidences were not dosage-dependent; and/or 2) the observation occurred in only one or two male rats in any dosage group. These observations included soft or liquid feces, emaciation, dried red or red perinasal substance, cold to touch, missing/broken and/or misaligned incisors, chromodacryorrhea, decreased motor activity, pale extremities, dried red substance on fur, no feces, scant feces, rales, swollen ears, abrasion on a limb, red substance on the penis and vocalization. The significant increases (p<0.05 or p<0.01) in the incidences of scabbing in the 1 and 3 mg/kg/day dosage groups were considered unrelated to the test substance because they were not dosage dependent. The significantly reduced (p<0.01) incidences of localized alopecia (total and limbs) in the 1,3, 10 and 30 mg/kg/day dosage groups were related to the increased incidence of this observation in the vehicle control group and were not test substance related. Page 46 ARGUS 418-020 A.2. Body Weights and Body Weight Changes - P Generation Male Rats (Figure 1; Summaries - Tables B2 and B3; Individual Data - Table B14) Body weight gains for the entire dosage period before cohabitation (DSs 1 to 70) were significantly reduced (p<0.05 or p<0.01) in the 3, 10 and 30 mg/kg/day dosage groups. Within this period, body weight gains were significantly reduced (p<0.05 or p<0.01) in the 30 mg/kg/day dosage group at almost all tabulated intervals before the cohabitation period, in the 10 mg/kg/day dosage group on DSs 8 tol5, 29 to 36,43 to 50 and 57 to 64, and in the 3 mg/kg/day dosage group on DSs 29 to 36 and 43 to 50. As a result, body weight gains for the entire dosage period (DSs 1 to 106 and DS 1 to termination) were significantly reduced (p<0.01) in the 3, 10 and 30 mg/kg/day dosage groups. Body weight gain was significantly reduced (p<0.05) in the 3 mg/kg/day dosage group on DSs 85 to 92. Body weights were significantly reduced (p<0.05 or p<0.01) in the 30 mg/kg/day dosage group on DS 8 through termination, in the 10 mg/kg/day dosage group on DS 15 through termination and in the 3 mg/kg/day dosage group on DS 50 through termination. Body weight gain was significantly increased (p<0.05) in the 3 mg/kg/day dosage group on DSs 1 to 8 but this increase was considered unrelated to the test substance because it did not persist. Body weights and body weight gains were unaffected by the 1 mg/kg/day dosage of the test substance. A.3. Absolute (g/day) and Relative (g/kg/day) Feed Consumption - P Generation Male Rats (Summaries - Tables B4 and B5; Individual Data Table B15) Absolute (g/day) feed consumption values were significantly reduced (p<0.01) in the 30 mg/kg/day dosage group for the entire dosage period before cohabitation (DSs 1 to 70) and the entire study period (DSs 1 to 106) and at most tabulated intervals within these periods. Relative (g/kg/day) feed consumption values were significantly increased (p<0.05 or /?<0.01) in the 3, 10 and 30 mg/kg/day dosage groups for the entire dosage period before cohabitation (DSs 1 to 70) and the entire study period (DSs 1 to 106). Within these periods, relative (g/kg/day) feed consumption values were significantly increased (p<0.05 or p<0.0l) in the 30 mg/kg/day dosage group at all tabulated intervals after DS 8, in the 10 mg/kg/day dosage group at all tabulated intervals after DS 15 and in the 3 mg/kg/day dosage group on DSs 29 to 36 and all tabulated intervals after DS 50. The relative (g/kg/day) feed consumption value was significantly reduced (p<0.01) on DSs 1 to 8 in the 30 mg/kg/day dosage group. Absolute and relative feed consumption were unaffected by the 1 mg/kg/day dosage of the test substance. Page 47 ARGUS 418-020 A.4. Mating and Fertility - P Generation Male Rats (Summary - Table B6; Individual Data - Table B16) All mating and fertility parameters (numbers of days to inseminate, rats that mated, fertility index, rats with confirmed mating dates during the first and second week of cohabitation and rats pregnant per rats in cohabitation) were unaffected by dosages of the test substance as high as 30 mg/kg/day. The significant reduction (p<0.05) in the number of days in cohabitation in the 1 mg/kg/day dosage group was considered unrelated to the test substance because it was not dosage dependent. A.5. Necropsy and Histopathology Observations - P Generation Male Rats (Summary - Table B7; Individual Data - Table B17; Histopathology APPENDIX K) All necropsy observations were considered unrelated to the test substance because: 1) the incidences were not dosage-dependent and/or 2) the observation occurred in only one or two male rats in any dosage group. These observations included small and flaccid testes and/or epididymides, large or red testes, slight or moderate dilation of the renal pelvis, dark red areas on the lung lobes and pale and tan areas on the liver. All male rats with gross lesions of the testes and/or epididymides impregnated the cohort female. No treatment-related microscopic changes were observed in the reproductive organs of any of the 10 male rats in the P generation selected for histopathologic evaluation that had been given up to 30 mg/kg/day of the test substance. A treatment-related microscopic change was observed in the adrenal glands of 2/10 and 7/10 male rats of the 10 and 30 mg/kg/day dosage groups. This change consisted of increased thickness and prominence of the zona glomerulosa due to cytoplasmic hypertrophy and vacuolation of the cells of the adrenal cortex. All other microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be incidental and unrelated to treatment. There were a few microscopic changes observed in rats designated as "reduced fertility", but these changes occurred spontaneously and were of the type that occur spontaneously in male rats of the age and strain and were not compound-related. A.6. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight and Brain Weight - P Generation Male Rats (Summaries - Tables B8 through B10; Individual Data - Tables B18 and B19) Terminal body weights were significantly reduced (p<0.01) in the 3, 10 and 30 mg/kg/day dosage groups. Absolute weights of the left epididymis, left cauda epididymis, seminal vesicles with and without fluid, right epididymis, prostate, pituitary, left and right adrenals, spleen and thymus were significantly reduced (p<0.05 or /?<0.01) in the 30 mg/kg/day dosage group. The absolute weight of the seminal vesicles without fluid was significantly reduced (p<0.05) in the 10 mg/kg/day dosage group. The absolute weight of the liver was significantly increased (p<0.01) in the 1,3, 10 and 30 mg/kg/day Page 48 ARGUS 418-020 dosage groups. Weights of the left and right kidneys were significantly increased (p<0.05 or p<0.01) in the 1,3 and 10 mg/kg/day dosage groups, while these weights were significantly reduced (p<0.5 or /?<0.01) in the 30 mg/kg/day dosage group. The weight of the pituitary was significantly reduced (p<0.05) in the 3 mg/kg/day dosage group but this reduction was not considered related to the test substance because the reduction was not dosage dependent. The ratios of the organ weight to the terminal body weight were significantly increased (p<0.01) in the 10 and 30 mg/kg/day dosage groups for the left epididymis, left cauda epididymis (30 mg/kg/day only), left testis, left testis minus tunica albuginea, seminal vesicles with and without fluid, right epididymis and right testis. The ratio of the seminal vesicles with fluid to the terminal body weight was also significantly increased (p<0.05) in the 3 mg/kg/day dosage group. The ratio of the brain weight to the terminal body weight was significantly increased (p<0.05 or p<0.01) in the 3, 10 and 30 mg/kg/day dosage groups. The ratios of the liver and left and right kidney weights to the terminal body weight were significantly increased (p<0.01) in the 1, 3, 10 and 30 mg/kg/day dosage groups. The ratio of the left adrenal weight to the terminal body weight was significantly increased (p<0.05) in the 30 mg/kg/day dosage group. Ratios of the organ weight to the brain weight were significantly reduced (/><0.01) in the 30 mg/kg/day dosage group for the left epididymis, left cauda epididymis, right epididymis, prostate, pituitary, spleen and thymus. The ratio of the pituitary weight to the brain weight was significantly reduced (p<0.05) in the 3 mg/kg/day dosage group. The ratios of the liver weight to the brain weight were significantly increased (p<0.01) in the 1,3,10 and 30 mg/kg/day dosage groups. The ratios of the left and right kidney weights to the brain weight were significantly increased (p<0.05 or p<0.01) in the 1,3 and 10 mg/kg/day dosage groups while the ratio of the left kidney weight to the brain weight was significantly reduced (p<0.05) in the 30 mg/kg/day dosage group. A.7. Sperm Evaluation (Summaries - Tables 611 and B12; Individual Data Tables B20 and B21) All sperm parameters evaluated were unaffected by dosages of the test substance as high as 30 mg/kg/day. Values for percent motile sperm, sperm density and spermatid density were comparable among the five dosage groups and did not significantly differ. The significant reduction (p<0.05) in the number of nonmotile sperm in the 10 mg/kg/day dosage group was considered unrelated to the test substance because it was not dosage dependent. The numbers of sperm with normal morphology and the percentages of sperm with abnormal morphology were comparable among the five dosage groups. Page 49 ARGUS 418-020 B. P Generation Female Rats B.l. Mortality and Clinical Observations - P Generation Female Rats (Summary Table Cl; Individual Data - Table C24) B.l.a. Mortality No deaths related to the test substance occurred. One P generation female rat in each of the 0 and 1 mg/kg/day dosage groups were moribund sacrificed. The moribund conditions of these rats were attributed to accidents resulting in a broken palate or a fractured limb, respectively. Observations in these rats are described below. All other P generation female rats survived to scheduled sacrifice. P generation female rat 13804 in the vehicle control group was moribund sacrificed on DS 68. This rat was administered 67 daily dosages of the vehicle. Adverse clinical observations before sacrifice included chromorhinorrhea, chromodacryorrhea, swollen snout, misaligned upper incisors and broken palate on DS 68. This rat gained weight from DSs 1 to 64 and feed consumption values were unremarkable. Necropsy confirmed the clinical signs. All other tissues examined appeared normal at necropsy. P generation female rat 13836 in the 1 mg/kg/day dosage group was moribund sacrificed on DS 59. This rat was administered 59 daily dosages of the test substance. Adverse clinical observations before sacrifice included a swollen left forelimb and paw on DSs 57 to 59 and fractured left forelimb on DS 59. This rat gained weight from DSs 1 to 57 and feed consumption values were unremarkable. Necropsy revealed a broken radius and ulna in the left forelimb. All other tissues examined appeared normal at necropsy. P generation female rat 13822 in the vehicle control group was sacrificed on DL 8 and dam 13852 in the 1 mg/kg/day dosage group was sacrificed on DL 11. The litters from these two dams were inadvertently mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. P generation female rat 13822 in the vehicle control group was sacrificed on DL 8. This rat was administered 101 daily dosages of the vehicle. Adverse clinical observations before sacrifice included a scab on a forelimb on DSs 15,16 and 22 to 26. Body weight gains and feed consumption values throughout the precohabitation, gestation and lactation periods were unremarkable. All tissues examined appeared normal at necropsy. This dam delivered 12 normal pups that appeared normal at necropsy. P generation female rat 13852 in the 1 mg/kg/day dosage group was sacrificed on DL 11. This rat was administered 102 daily dosages of the test substance. There were no adverse clinical observations before death. Body weight gains and feed consumption values throughout the precohabitation, gestation and lactation periods were unremarkable. All tissues examined appeared normal at necropsy. This dam delivered 12 pups, one pup had a mass on the forelimb on DLs 5 to 6. All pups appeared normal at necropsy. Page 50 ARGUS 418-020 B.l.b. Clinical Observations All clinical observations during the precohabitation, gestation and lactation periods were considered unrelated to the test substance because: 1) the incidences were not dosage- dependent; and/or 2) the observation occurred in only one or two female rats in any dosage group. These observations included missing/broken and/or misaligned incisors, chromorhinorrhea, ungroomed coat, scabbing, chromodacryorrhea, localized alopecia (limbs, underside and head), swollen forelimb and paw, soft or liquid feces, fractured forelimb, broken palate, swollen snout, swollen ears, mass on the head or the axilla, dried red perinasal substance, dried red substance on paws, abrasion on the paw, traumatized comea and swollen paw, eye or ear. . B.2. Body Weights and Body Weight Changes - P Generation Female Rats (Figure 2; Summaries - Tables C2 through C7; Individual Data - Tables C25 through C27) Body weights and body weight gains during the precohabitation, gestation and lactation periods were unaffected by dosages of the test substance as high as 30 mg/kg/day. Body weight gain was significantly reduced (p<0.05) during the precohabitation period on days 29 to 36 of study, and body weights were significantly reduced (p<0.05) on days 7 and 14 of gestation in the 30 mg/kg/day dosage group but these significant reductions were not considered toxicologically important because they did not persist. B.3. Absolute (g/day) and Relative (g/kg/day) Feed Consumption P Generation Female Rats (Summaries - Tables C8 through C13; Individual Data Tables C28 through C30) Absolute (g/day) and relative (g/kg/day) feed consumption values during the precohabitation, gestation and lactation periods were unaffected by dosages of the test substance as high as 30 mg/kg/day. Absolute feed consumption values were significantly reduced (p<0.05) during the precohabitation period on days 57 to 64 of study, and during the gestation period on days 10 to 14 and 0 to 21 in the 30 mg/kg/day dosage group but these significant reductions were not considered toxicologically important because they did not persist. The significant reduction (p<0.05) in the absolute feed consumption value on gestation days 10 to 14 in the 1 mg/kg/day dosage group was considered unrelated to the test substance because it was not dosage dependent. B.4. Estrous Cycling, Mating and Fertility - P Generation Female Rats (Summary - Table C14; Individual Data - Table C31) The average numbers of estrous stages per 21 days were comparable among the five dosage groups and did not significantly differ. Evaluation of estrous stages at sacrifice did not reveal any differences among the five dosage groups. All mating and fertility parameters (numbers of days in cohabitation, rats that mated, fertility index, rats with confirmed mating dates during the first and second week of Page 51 ARGUS 418-020 cohabitation and rats pregnant per rats in cohabitation) were unaffected by dosages of the test substance as high as 30 mg/kg/day. The significant reduction (p<0.05) in the number of days in cohabitation in the 1 mg/kg/day dosage group was considered unrelated to the test substance because it was not dosage dependent. B.5. Necropsy and Histopathology Observations - P Generation Female Rats (Summary - Table C15; Individual Data - Table C32; Histopathology APPENDIX K) All necropsy observations were considered unrelated to the test substance because: 1) the incidences were not dosage-dependent; and 2) the observation occurred in only one female rat in any dosage group. These observations included marked dilation of the renal pelvis and a broken ulna and radius. No treatment-related microscopic changes were observed in the reproductive organs of any of the 10 female rats in the P generation selected for histopathologic evaluation that had been given up to 30 mg/kg/day of the test substance. All microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be incidental and unrelated to treatment. There were a few microscopic changes observed in rats designated as "reduced fertility", but these changes occurred spontaneously and were of the type that occur spontaneously in female rats of the age and strain and were not compound-related. B.6. Terminal Body Weights, Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight and Brain Weight - P Generation Female Rats (Summaries - Tables C16 through C18; Individual Data - Tables C33 and C34) Terminal body weights of the P generation female rats were comparable among the five dosage groups and did not significantly differ. The weights of the left and right kidney, the ratios of these organ weights to the terminal body weight and the ratio of the left kidney weight to the brain weight were significantly reduced (p<0.05 or /?<0.01) in the 30 mg/kg/day dosage group. The ratios of the liver weight to the terminal body weight were significantly reduced (p<0.05 or p<0.01) in the 3 and 10 mg/kg/day dosage groups. All other organ weights (pituitary, brain, left and right adrenals, spleen, cervix, left and right ovary and uterus) and the ratios of these organ weights to the terminal body weight and the brain weight were unaffected by dosages of the test substance as high as 30 mg/kg/day. B.7. Natural Delivery and Litter Data - P Generation Female Rats (Summaries Tables C19 and C20; Individual Data - Tables C35 through C38) Pregnancy occurred in 27 to 29 rats in each dosage group. One pregnant dam (13862) in the 3 mg/kg/day dosage group did not deliver a litter by day 25 of presumed gestation. The litter consisted of one implantation site (identified at necropsy on day 25 of Page 52 ARGUS 418-020 gestation). Such events are relatively common in rats, and this nondosage-dependent event was unrelated to the test substance. One or more livebom pups were delivered by every other pregnant dam assigned to natural delivery (there were 27 to 29 litters delivered in each dosage group). Natural delivery observations were unaffected by dosages of the test substance as high as 30 mg/kg/day. Values for the numbers of dams delivering litters, the duration of gestation, averages for implantation sites per delivered litter, the gestation index (number of dams with one or more livebom pups/number of pregnant rats), the numbers of dams with stillborn pups, dams with all pups dying, livebom and stillborn pups, viability index, pup sex ratios and body weights were comparable among the five dosage groups and did not significantly differ. The lactation index was 98.1% and 96.3% in the 3 and 30 mg/kg/day dosage groups, respectively. These values were significantly reduced (p<0.05 and p<0.01, respectively) from the control group value of 99.7%. The Testing Facility historical control average and range for this parameter is 98.8% and 94.4% to 100.0%, respectively (77 studies; 1995 to 2000). The reductions in the lactation index in the 3 and 30 mg/kg/day dosage groups were not considered treatment-related because: 1) the reduction in the 3 mg/kg/day was not dosage-dependent; 2) this effect did not occur during lactation in the F2 pups; and 3) the reduction in the 30 mg/kg/day was within the historical control range for this facility. One dam in the 30 mg/kg/day dosage group delivered one pup that died on day 1 of lactation (DL 1). The numbers of pups found dead or presumed cannibalized were significantly increased in the 3 and 30 mg/kg/day dosage groups on days 6 to 8 of lactation. These increases were not considered related to the test substance because they did not affect any other measures of pup viability (surviving pups per litter, live litter size at weighing). Pup body weight per litter was significantly reduced (p<0.05 or p<0.01) in the 1 mg/kg/day dosage group on DL 1 and in the 30 mg/kg/day dosage group on DLs 1, 5 and 8. The pup body weight reduction in the 1 mg/kg/day dosage group on DL 1, however, was not considered treatment-related because it was not dosage-dependent. B.8. Clinical and Necropsy Observations - FI Generation Litters (Summaries Tables C21 and C22; Individual Data - Tables C39 and C40) No clinical or necropsy observations were attributable to dosages of the test substance as high as 30 mg/kg/day because: 1) the incidences were not dosage-dependent; and 2) the observation occurred in only one or two litters. These clinical observations included cold to touch, no milk in stomach, umbilical hernia, pale, mass on limb or mouth, not nesting, scab on the back, red perianal substance, not nursing, missing or black tip of tail, traumatized comea, rotated hindlimbs and absent tail. All male pups met the criterion (no nipples present) at nipple examination on DL 12. Necropsy observations included no milk in stomach and moderate dilation of the renal pelvis. Page 53 ARGUS 418-020 B.9. Terminal Body Weights, Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight and Brain Weight - FI Generation Litters (Summary - Table C23; Individual Data - Table C41) Terminal body weights of the FI generation pups were comparable among the five dosage groups and did not significantly differ. The weights of the brain, spleen and thymus and the ratios of these organ weights to the terminal body weight and brain weight were unaffected by dosages of the test substance as high as 30 mg/kg/day. The significant reduction (p<0.05) in the ratio of the thymus weight to the terminal body weight in the 3 mg/kg/day dosage group was unrelated to the test substance because the value was not dosage dependent. . B.10. PFOA Serum Levels (ug/mL) Data Summary (APPENDIX I) Group 1 0 mg/kg/day Group 1 0 mg/kg/day Group 4 10 mg/kg/day Group 4 10 mg/kg/day Group 5 30 mg/kg/day Group 5 30 mg/kg/day LOQ = Limit of Quantitation Gender/ Timepoint Female Lactation Day 22 Male End of Cohabitation Female Lactation Day 22 Male End of Cohabitation Female Lactation Day 22 Male End of Cohabitation PFOA Concentration Average SD Less than LOQ (0.00528) N=3 0.0344 0.0148 N=3 0.37 0.0805 N = 10 51.1 9.30 N = 10 1.02 0.425 N = 10 45.3 12.6 N = 10 Low levels of PFOA were detected in the sera of the control male rats. In general, PFOA levels found in sera of the female rats increased from 10 mg/kg/day dosage group to the 30 mg/kg/day dosage group. PFOA levels found in sera of the male rats remained the same between the 10.0 mg/kg/day dosage group and the 30 mg/kg/day dosage group. Page 54 ARGUS 418-020 IV. RESULTS - FI GENERATION RATS A. FI Generation Male Rats A.l. Mortality and Clinical Observations - FI Generation Male Rats (Summary Table D l; Individual Data - Table D14) A.l.a. Mortality Three, three, three, two and seven FI generation male rats in the 0, 1,3, 10 and 30 mg/kg/day dosage groups were moribund sacrificed or found dead. The increased incidence of mortality in the 30 mg/kg/day dosage group was considered treatmentrelated. Observations for these rats are described below. All other FI generation male rats survived to scheduled sacrifice. 0 mg/kg/day dosage group Rat 1024 was found dead on postweaning day (DP) 25, approximately one hour after the 25th daily dosage. There were no adverse clinical observations before death. This rat was one of the smallest in this group at weaning, weighing only 30 g. This rat gained weight on DPs 1 to 22. Feed consumption values were comparable to other rats in the dosage group. Necropsy revealed all lobes of the lungs to be mottled and dark red; all other tissues appeared normal. The death of this rat was considered to be due to an intubation accident. Rat 1029 was moribund sacrificed on DP 4, after the 4th daily dosage. Clinical observations before death included chromorhinorrhea on DPs 2 through 4 and decreased motor activity and cold to touch on DP 4. This rat weighed only 31 g at weaning. All tissues examined appeared normal at necropsy. The moribund condition was attributed to a failure to thrive postweaning. Rat 1039 was found dead on DP 42, approximately 33 minutes after the 42nd daily dosage. The only adverse clinical observation before death was vocalization on DP 34. Body weights and feed consumption were comparable to other control group male rats. All tissues examined appeared normal at necropsy. The death of this rat was considered to be due to an intubation accident because death occurred immediately after administration without any adverse clinical observations. 1 mg/kg/day dosage group Rat 1064 was found dead on the morning of DP 6. The rat was administered five daily dosages. Clinical observations before death included chromorhinorrhea and urine-stained abdominal fur on DP 5. This rat weighed 37 g at weaning. All tissues examined appeared normal at necropsy. No cause of death could be determined. Rat 1087 was found dead on DP 45 before administration of the 45th daily dosage. There were no adverse clinical observations before death. Body weights and feed consumption were comparable to other male rats in this dosage group. All tissues examined appeared normal at necropsy. No cause of death could be determined. Page 55 ARGUS 418-020 Rat 1104 was found dead on DP 2 before administration of the 2nd daily dosage. Clinical observations before death included decreased motor activity, cold to touch and emaciation on DP 1. This rat was one of the smallest in this group at weaning, weighing only 23 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. 3 mg/kg/day dosage group Rat 1121 was found dead on DP 5 before administration of the 5th daily dosage. There were no adverse clinical observations observed before death. This rat weighed 35 g at weaning. All tissues examined appeared normal at necropsy. No cause of death could be determined. Rat 1130 was found dead on DP 2 before administration of the 2nd daily dosage. There were no adverse clinical observations before death. This rat was one of the smallest in this group at weaning, weighing only 24 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Rat 1140 was found dead on DP 9 before administration of the 9th daily dosage. The only adverse clinical observation before death was emaciation on DP 3. This rat weighed only 37 g at weaning and 55 g on DP 8. Feed consumption on DPs 1 to 8 was reduced as compared to other rats in this group. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. 10 mg/kg/day dosage group Rat 1200 was moribund sacrificed on DP 40 before administration of the 40th daily dosage. Clinical observations before death included chromodacryorrhea on DP 24, dehydration on DPs 24 to 40, abdominal distention on DPs 25 to 40, urine-stained abdominal fur on DPs 29 to 32 and 39 to 40, and emaciation and cold to touch on DPs 29 to 40. This rat was eating and gaining weight through the first three weeks of dosage administration and then lost body weight over the next two weeks. Feed consumption was reduced on DPs 29 to 36. Necropsy revealed the intestines distended with gas, a small (0.02 g) thymus and numerous ulcerations (pinpoint to 0.1 cm in diameter) in one cardiac region of the stomach and five ulcerations (pinpoint) in a second cardiac region of the stomach; all other tissues examined appeared normal. Rat 1210 was found dead on DP 4 before administration of the 4th daily dosage. Clinical observations before death included decreased motor activity, cold to touch and emaciation on DP 3. This rat weighed 41 g at weaning. All tissues examined appeared normal at necropsy. No cause of death could be determined. 30 mg/kg/day dosage group Rat 1260 was found dead on the morning of DP 4. The rat was administered three daily dosages. Clinical observations before death included decreased motor activity, cold to touch and urine-stained abdominal fur on DP 3. This rat was one of the smallest in this group at weaning, weighing only 24 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Page 56 ARGUS 418-020 Rat 1263 was found dead on the morning of DP 2. The rat was administered one daily dosage. Clinical observations before death included decreased motor activity, comeal opacity, emaciation and cold to touch on DP 1. This rat was one of the smallest in this group at weaning, weighing only 25 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Rat 1264 was found dead on the morning of DP 2. The rat was administered one daily dosage. Clinical observations before death included decreased motor activity, comeal opacity, emaciation and cold to touch on DP 1. This rat was one of the smallest in this group at weaning, weighing only 24 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Rat 1275 was moribund sacrificed on DP 39 before administration of the 39th daily dosage. Clinical observations before death included chromorhinorrhea on DPs 26 to 33, dehydration on DPs 26 to 39, emaciation on DPs 29 to 39, decreased motor activity on DPs 32 to 39, urine-stained abdominal fur on DPs 32 to 39, cold to touch on DPs 33 to 39 and chromodacryorrhea on DP 39. This rat was eating and gaining weight through the first three weeks of dosage administration and then lost body weight over the next two weeks. Feed consumption was reduced on DPs 29 to 36. Necropsy revealed numerous tan areas (pinpoint to 0.1 cm) on the median lobe of the liver and a small (0.04 g) spleen; all other tissues appeared normal. Rat 1277 was found dead on the morning of DP 4. The rat was administered three daily dosages. Clinical observations before death included chromorhinorrhea on DPs 2 and 3 and decreased motor activity, cold to touch, emaciation and urine-stained abdominal fur on DP 3. This rat was one of the smallest in this group at weaning, weighing only 25 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Rat 1280 was found dead on DP 3 before administration of the 3rd daily dosage. The only adverse clinical observation before death was chromorhinorrhea on DP 2. This rat weighed 34 g at weaning. All tissues examined appeared normal at necropsy. No cause o f death could be determined. Rat 1296 was found dead on DP 107 before administration of the 107th daily dosage. Clinical observations before death included rales on DP 100, chromorhinorrhea on DPs 100 to 101, chromodacryorrhea and misaligned incisors on DPs 100 to 106, emaciation on DPs 103 to 106 and urine-stained abdominal fur on DPs 104 to 106. This rat gained weight similar to other rats in this group up to DP 99 after which it lost 130 g in body weight over the next week. Feed consumption values were unremarkable up to DP 70. All tissues examined appeared normal at necropsy. No cause of death could be determined. A.l.b. Clinical Observations The incidences of annular constriction of the tail of male FI generation rats were increased in the 1,3, 10 and 30 mg/kg/day dosage groups, reaching statistical significance (p<0.05 or p<0.01) in the 1, 10 and 30 mg/kg/day dosage groups. The number of male rats observed to be emaciated was significantly increased (p<0.05 or Page 57 ARGUS 418-020 p<0.01) in the 10 and 30 mg/kg/day dosage groups, and the numbers of male rats with urine-stained abdominal fur, decreased motor activity and abdominal distention were significantly increased (p<0.01) in the 30 mg/kg/day dosage group. The incidence of the observation of cold to touch was increased, albeit not significantly, in the 30 mg/kg/day dosage group. All other clinical observations were considered unrelated to the test substance because: 1) the incidences were not dosage-dependent; and/or 2) the observation occurred in only one to three male rats in any dosage group. These observations included chromorhinorrhea, chromodacryorrhea, missing/broken and/or misaligned incisors, scab located on the neck, head, back, mouth or ear, soft or liquid feces, localized alopecia on the limbs, back or head, corneal opacity, rales, dehydration, lacrimation, swollen eye, ears or snout, red substance on the penis, excess salivation, dried and red perinasal substance, vocalization, tip of tail missing or black, ulceration on the back, red perioral substance, ptosis, enophthalmos, abrasion on the head and enlarged eye. A.2. Body Weights and Body Weight Changes - FI Generation Male Rats (Figure 3; Summaries - Tables D2 and D3; Individual Data - Table D15) Body weights and body weight gains were reduced for the FI generation male rats before and after the cohabitation period at the 1,3, 10 and/or 30 mg/kg/day dosages of the test substance, as compared to the control group. Body weight gains for the entire dosage period (DPs 1 to 113) were significantly reduced (p<0.01) in a dosage-dependent manner in the 1,3, 10 and 30 mg/kg/day dosage groups. Body weight gains were also significantly reduced (p<0.01) in the 10 and 30 mg/kg/day dosage group for the entire precohabitation period (DP 1 to precohabitation). Within these periods, body weight gains were significantly reduced (p<0.05 or p<0.01) in the 1 and 3 mg/kg/day dosage groups on DPs 43 to 50, in the 3 mg/kg/day dosage group on DPs 57 to 64 and in the 1 mg/kg/day dosage group alone on DPs 15 to 22. Body weight gains in the 10 and 30 mg/kg/day dosage groups were significantly reduced (p<0.05 or p<0.01) on DPs 8 to 15, 22 to 29, 29 to 36,43 to 50 and 50 to 57. Body weight gains in the 30 mg/kg/day dosage group were also significantly reduced (p<0.05 or p<0.01) on DPs 1 to 8, 15 to 22, 36 to 43, 57 to 64 and 64 to 70. Body weights were significantly reduced (p<0.05 or p<0.01) on DPs 50, 57, 64, 70, 99, 106 and 113 in the 1 mg/kg/day dosage group, on DPs 106 and 113 in the 3 mg/kg/day dosage group and at all weekly intervals after DP 36 in the 10 mg/kg/day dosage group and DP 8 in the 30 mg/kg/day dosage group. A.3 Absolute (g/day) and Relative (g/kg/day) Feed Consumption - FI Generation Male Rats (Summaries - Tables D4 and D5; Individual Data - Table D16) Absolute (g/day) feed consumption values for the FI generation male rats were significantly reduced (p<0.01) and relative (g/kg/day) feed consumption values were significantly increased (p<0.05 or p<0.01) for the entire precohabitation period (DPs 1 to 70) by dosages of APFO of 10 (absolute only) and 30 mg/kg/day. Page 58 ARGUS 418-020 Absolute feed consumption values for the 30 mg/kg/day dosage group were significantly reduced (/?<0.05 or /?<0.01) on DPs 1 to 8, 8 to 15, 15 to 22, 22 to 29, 29 to 36,43 to 50 and 50 to 57. Relative feed consumption values were significantly reduced (p<0.05) in the 30 mg/kg/day dosage group on DPs 1 to 8. Relative feed consumption values were significantly increased (p<0.05) in the 10 mg/kg/day dosage group on DPs 29 to 36 and significantly increased (p<0.01) in the 30 mg/kg/day dosage group on DPs 22 to 29, 29 to 36, 36 to 43,43 to 50, 50 to 57, 57 to 64 and 64 to 70. Relative feed consumption values were significantly increased (p<0.01) in the 10 and 30 mg/kg/day dosage groups on DPs 99 to 106, 106 to 113 and 99 to 113. The significant reduction (p<0.05 or p<0.01) in the absolute feed consumption value on DPs 22 to 29, 29 to 36, 43 to 50 and 1 to 70 in the 1 mg/kg/day dosage group were considered unrelated to the test substance because they were not dosage dependent. A.4. Sexual Maturation - FI Generation Male Rats (Summary - Table D6; Individual Data - Table D17) Preputial separation of FI generation male rats was slightly delayed (approximately three and a half days later than the control group value) in the 30 mg/kg/day dosage group, compared to the control group. The Testing Facility historical control average and range for this parameter is 46.1 days and 43.9 to 47.7 days, respectively (42 studies; 1995 to 2000). The average day when preputial separation was evident in the 30 mg/kg/day dosage group (52.2 days of age) significantly differed (p<0.01) from the control group value (48.5 days of age). When this observation in the 30 mg/kg/day dosage group was covaried with the significantly reduced (p<0.01) body weight at time of acquisition, to determine if the significantly reduced body weights were a factor, the difference was still significant, but at the p<0.05 level. When this observation in the 30 mg/kg/day dosage group was covaried with gestational age at time of acquisition to determine if this group was younger and more immature than the control group, there was no significant difference in sexual maturation. A.5. Mating and Fertility - FI Generation Male Rats (Summary - Table D7; Individual Data - Table D18) Dosages of the test substance as high as 30 mg/kg/day did not affect any mating and fertility parameters evaluated in the FI generation male rats. Values for the fertility and pregnancy indices (number of pregnancies per number of rats that mated and rats in cohabitation, respectively), the number of days to inseminate, the number of rats that mated and the number of rats with confirmed mating dates during the first week of cohabitation were comparable among the five dosage groups. Of the male rats assigned to cohabitation, 93.3%, 96.6%, 93.3%, 93.3% and 96.7% impregnated the cohort female rat in the five dosage groups, respectively. A.6. Necropsy Observations - FI Generation Male Rats (Summary - Table D8 Individual Data - Table D19) The number of FI generation males that appeared normal at necropsy was significantly reduced (p<0.01) in the 10 and 30 mg/kg/day dosage groups, compared to the control group. Page 59 ARGUS 418-020 Tan areas occurred in the left lateral and/or median lobes of the liver in 6*, 10** and 9** male rats in the 3, 10 and 30 mg/kg/day dosage groups, respectively. One of these rats in the 30 mg/kg/day dosage group also had a small spleen. One 30 mg/kg/day dosage group rat had an enlarged liver. Moderate to slight dilation of the pelvis of one or both kidneys occurred in 4** and 1 rats in the 10 and 30 mg/kg/day dosage groups, respectively. A tan area in the parenchyma of the spleen occurred in one 10 mg/kg/day dosage group rat. All other necropsy observations were considered unrelated to the test substance because: 1) the incidences were not dosage-dependent; and 2) the observation occurred in only one male rat in any dosage group. These observations included small prostate for one 1 mg/kg/day dosage group rat, small and flaccid left testis and small left epididymides for another 1 mg/kg/day dosage group rat, large left testis for one 3 mg/kg/day dosage group rat, ulceration of the cardiac region of the stomach, intestines distended with gas and small thymus for one rat that was moribund sacrificed in the 10 mg/kg/day dosage group. Mottled dark red lung lobes occurred in one 0 mg/kg/day dosage group rat that was found dead. A.7. Terminal Body Weights, Organ Weights and Ratios (%) of Organ Weights to Terminal Body Weight and Brain Weight - FI Generation Male Rats (Summaries - Tables D9 through D ll; Individual Data - Tables D20 and D21) Terminal body weights of the FI generation male rats were significantly reduced (p<0.05 or p<0.01) in a dosage-dependent manner in the 1,3, 10 and 30 mg/kg/day dosage groups. The absolute weights of the liver were significantly increased (p<0.01) and the absolute weights of the spleen were significantly decreased (p<0.05 or /?<0.01) in the 1 mg/kg/day and higher dosage groups, compared to the control group values. The absolute weights of the left and/or right kidneys were significantly increased {p<0.05 or p<0.01) in the 1 and 3 mg/kg/day dosage groups and significantly decreased (p<0.01) in the 30 mg/kg/day dosage group, compared to control group values. The absolute weight of the thymus was also significantly decreased (p<0.01) in the 10 and 30 mg/kg/day dosage groups. The absolute weight of the prostate, brain and left adrenal gland were significantly decreased {p<0.05 orp<0.0l) in the 30 mg/kg/day dosage group. The ratios of the weights of the seminal vesicles, with and without fluid, liver and left and right kidneys to the terminal body weights were significantly increased (p<0.05 or p<0.01) in the 1 mg/kg/day and higher dosage groups, compared to the control group values. The ratios of the weights of the left testis, with and without the tunica albuginea and the right testis to the terminal body weight, were significantly increased (p<0.05 or p<0.01) in the 3 mg/kg/day and higher dosage groups. The ratios of the weights of the left epididymis, left cauda epididymis, right epididymis and brain to the terminal body weight were significantly increased (p<0.05 or p<0.01) in the 10 mg/kg/day and higher dosage groups. Significantly different from the Group I value (p<0.05). Significantly different from the Group I value (p<0.01). Page 60 ARGUS 418-020 The ratios of the weight of the seminal vesicles with fluid to the brain weight were increased in the 1 mg/kg/day and higher dosage groups, compared to the control group values. These ratios were significantly increased (p<0.05) in the 1 and 10 mg/kg/day dosage groups. The ratios of the liver weight to the brain weight were significantly increased (p<0.01) in the 1 mg/kg/day and higher dosage groups, and the ratios of the left and right kidney weights to the brain weight were significantly increased (p<0.05 or p<0.01) in the 1,3 and 10 mg/kg/day dosage groups. The ratios of the spleen weight to the brain weight were significantly decreased (p<0.05 or p<0.01) in the 1 mg/kg/day and higher dosage groups, and the ratios of the thymus weight to the brain weight were significantly decreased {p<0.05 or p<0.01) in the 10 and 30 mg/kg/day dosage groups. The ratios of the left and right testes weight to the brain weight were increased in the 3 mg/kg/day and higher dosage groups. These ratios were significantly increased {p<0.05 or p<0.01) in the 10 mg/kg/day (right testis only) and 30 mg/kg/day dosage groups. A.8. Histopathology (APPENDIX K) No treatment-related microscopic changes were observed in the reproductive organs of any of the 10 male rats in the FI generation selected for histopathologic evaluation that had been given up to 30 mg/kg/day of the test substance. A treatment-related microscopic change was observed in the adrenal glands of 7/10 male rats of the 30 mg/kg/day dosage group. This change consisted of increased thickness and prominence of the zona glomerulosa due to cytoplasmic hypertrophy and vacuolation of the cells of the adrenal cortex. Treatment-related microscopic changes also were observed in the liver sections of the FI generation male rats in the 3, 10 and 30 mg/kg/day dosage groups. Microscopically, these gross changes were due to diffuse hypertrophy of the hepatocytes. Hepatocytes in all areas (diffuse) of the hepatic lobules were enlarged due to an increased dense, eosinophilic cytoplasm. A very low incidences of single-cell or focal/multifocal hepatocellular necrosis also was observed in a few rats of these groups. Hepatic tissue was available for micropic examination only from rats with gross observations in the liver. All other microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be incidental and unrelated to treatment. There were a few microscopic changes observed in rats designated as "reduced fertility", but these changes occurred spontaneously and were of the type that occur spontaneously in male rats of the age and strain and were not compound-related. A.9. Cauda Epididymal Sperm Motility, Count, Density and Spermatid Count FI Generation Male Rats (Summary - Table DI2; Individual Data - Table D22) A.9.a. Cauda Epididymal Sperm Motility No statistically significant or dosage-dependent differences occurred in the numbers of motile sperm, percentage of motile sperm, static count (nonmotile sperm), total count or sperm density. Page 61 ARGUS 418-020 A.9.b. Cauda Epididymal Spermatid Count and Concentration Cauda epididymal spermatid count and density were unaffected by dosages of the test substance as high as 30 mg/kg/day. No statistically significant differences occurred. A. 10. Cauda Epididymal Sperm Morphology - FI Generation Male Rats (Summary - Table D13; Individual Data - Table D23) Sperm morphology was unaffected by dosages of the test substance as high as 30 mg/kg/day. The number of sperm with a broken flagellum was significantly reduced (p<0.05) in the 1 mg/kg/day dosage group, compared to the control group. This finding was not considered treatment-related because it was not dosage-dependent. B. FI Generation Female Rats B .l. Mortality and Clinical Observations - FI Generation Female Rats (Summary - Table El; Individual Data - Table E26) B.l.a. Mortality Two, one, one and six** FI generation female rats in the 1, 3,10 and 30 mg/kg/day dosage groups were found dead during the post-lactation period. All the deaths, except one in the 1 mg/kg/day dosage group, occurred postweaning days 2 to 8. This increased incidence of mortality in the 30 mg/kg/day dosage group was considered treatmentrelated and may have been related to their small size (5 of the 7 found dead pups were 28 g or less at weaning). Observations for these rats are described below. All other FI generation female rats survived to scheduled sacrifice. 1 mg/kg/day dosage group Rat 1365 was found dead on postweaning day (DP) 4 before administration of the fourth daily dosage. Clinical observations before death included tip of tail missing on DPs 1 to 3 and decreased motor activity, chromorhinorrhea and cold to touch on DP 3. This rat was one of the smallest in this group at weaning, weighing only 31 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Rat 1373 was found dead on DP 51 before administration of the 51st daily dosage. Clinical observations before death included chromorhinorrhea on DPs 28 to 35, dehydration on DPs 29 to 50, urine-stained abdominal fur on DPs 32 to 50, chromodacryorrhea on DP 35, emaciation on DPs 35 to 50 and decreased motor activity on DPs 45 to 50. This rat lost weight after DP 29. Feed consumption values were unremarkable. Necropsy revealed distended stomach and intestines and a depressed white area on the dorsal surface of the right apical lobe of the lungs. All other tissues appeared normal. No cause of death could be determined. Significantly different from the control group value (p<0.01). Page 62 ARGUS 418-020 3 mg/kg/day dosage group Rat 1432 was found dead on the morning of DP 7 before administration of the 7th daily dosage. Clinical observations before death included urine-stained abdominal fur and chromorhinorrhea on DPs 4 to 6 and emaciation on DP 6. This rat was one of the smallest in this group at weaning, weighing 31 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. 10 mg/kg/day dosage group Rat 1484 was found dead on the morning of DP 3 before administration of the third daily dosage. Clinical observations before death included urine-stained abdominal fur on DPs 1 and 2 and decreased motor activity, cold to touch and labored breathing on DP 2. This rat was one of the smallest in this group at weaning, weighing only 28 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. 30 mg/kg/day dosage group Rat 1549 was found dead on DP 8 before administration of the eighth daily dosage. Clinical observations before death included decreased motor activity on DPs 2 and 3, chromorhinorrhea on DPs 2 to 7, cold to touch on DPs 3 to 7 and urine-stained abdominal fur on DPs 5 to 7. This rat was one of the smallest in this group at weaning, weighing only 28 g and feed consumption was severely reduced on DPs 1 to 8. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Rat 1559 was found dead on DP 6 before administration of the sixth daily dosage. Clinical observations before death included urine-stained abdominal fur on DPs 3 to 5 and cold to touch and emaciation on DP 5. This rat was one of the smallest in this group at weaning, weighing only 22 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Rat 1562 was found dead on the morning of DP 2. The rat was not administered the test substance. No clinical observations, body weight or feed consumption values were recorded. All tissues examined appeared normal at necropsy. No cause of death could be determined. Rat 1563 was found dead on the morning of DP 2. The rat was not administered the test substance. No clinical observations, body weight or feed consumption values were recorded. All tissues examined appeared normal at necropsy. No cause of death could be determined. Rat 1574 was found dead on DP 3, approximately one hour after the third daily dosage. Clinical observations before death included cold to touch and urine-stained abdominal fur on DPs 2 and 3. This rat was one of the smallest in this group at weaning, weighing only 23 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Page 63 ARGUS 418-020 Rat 1575 was found dead on the morning of DP 3 before administration of the third daily dosage. There were no adverse clinical observations before death. This rat was one of the smallest in this group at weaning, weighing only 23 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. B.l.b. Clinical Observations All clinical observations during the precohabitation, gestation and lactation periods were considered unrelated to the test substance because: 1) the incidences were increased to statistically significant levels; 2) the incidences were not dosage-dependent; and/or 3) the observation occurred in only one to two female rats in any dosage group. These observations included abdominal distention, urine-stained abdominal fur, cold to touch, chromorhinorrhea, rales, tip of tail missing, scab on the head or back, localized alopecia on the limbs, neck or head, decreased motor activity, emaciation, bent tail, missing/broken and/or misaligned incisors, lacrimation, swollen eye, labored breathing, soft or liquid feces, chromodacryorrhea, swollen ear, dehydration, annular constriction of the tail, swollen head or snout, ptosis, mass in the right axilla and red perivaginal substance. A significant increase (p<0.01) in the incidence of red perivaginal substance in the 3 mg/kg/day dosage group during the lactation period was not considered treatmentrelated because it was not dosage-dependent. B.2. Body Weights and Body Weight Changes - FI Generation Female Rats (Figure 4; Summaries - Tables E2 through E7; Individual Data - Tables E27 through E29) B.2.a. Precohabitation Body weights and body weight gains during the precohabitation period were significantly reduced {p<0.05 or /?<0.01) by 30 mg/kg/day dosages of the test substance. Body weight gain for the entire precohabitation period (DP 1 to precohabitation) was significantly reduced (p<0.05). Within this period, body weight gains were significantly reduced ip<0.01) on DPs 1 to 8 and 8 to 15. Body weights in this group were significantly reduced (p<0.05 or p<0.01) on DPs 8, 15, 22, 29, 50, 57 and precohabitation. Body weights and body weight gains during the precohabitation period were unaffected by dosages of the test substance as high as 10 mg/kg/day. Body weight gains in the 1 mg/kg/day dosage group were significantly reduced (p<0.05 or p<0.01) on DPs 1 to 8 and 8 to 15 and in the 10 mg/kg/day dosage group were significantly reduced (p<0.01) on DPs 8 tol5. Body weights in the 1 mg/kg/day dosage group were also significantly reduced (p<0.05 or p<0.01) on DPs 8, 15, 22 and 29. These reductions in the 1 and 10 mg/kg/day dosage groups were not considered treatment-related because: 1) they were not dosage-dependent; and 2) they did not persist. Page 64 ARGUS 418-020 B.2.b. Gestation Body weights during the gestation period were significantly reduced (p<0.05) in the 30 mg/kg/day dosage group on gestation days (DGs) 0, 7, 10 and 14, compared to the control group. Body weights and body weight gains during the gestation period were unaffected by dosages of the test substance as high as 10 mg/kg/day. B.2.c. Lactation Body weights during the lactation period were significantly reduced (p<0.05 or p<0.01) in the 30 mg/kg/day dosage group on lactation days (DLs) 5, 8, 11 and 15, compared to the control group. Body weights and body weight gains during the lactation period were unaffected by dosages of the test substance as high as 10 mg/kg/day. B.3. Absolute (g/day) and Relative (g/kg/day) Feed Consumption - FI Generation Female Rats (Summaries - Tables E8 through E13; Individual Data - Tables E30 through E32) Absolute (g/day) feed consumption values were significantly reduced (p<0.05 or p<0.01) in the 30 mg/kg/day dosage group on DPs 1 to 8, 8 to 15 and 15 to 22 during the precohabitation period, on DGs 7 to 10 during the gestation period and on DLs 1 to 15 during the lactation period. Relative (g/kg/day) feed consumption values were comparable among the 0, 1,3, 10 and 30 mg/kg/day dosage groups for the precohabitation, gestation and lactation periods and did not differ statistically. Absolute and relative feed consumption values during the precohabitation, gestation and lactation periods were unaffected by dosages of the test substance as high as 10 mg/kg/day. Absolute feed consumption values were significantly reduced (p<0.01) in the 1 mg/kg/day dosage group on DPs 1 to 8 and 8 to 15 during the precohabitation period. These significant reductions in the absolute feed consumption in the 1 mg/kg/day dosage group were considered unrelated to the test substance because they were not dosage dependent and did not persist. B.4. Sexual Maturation - FI Generation Female Rats (Summary - Table E14; Individual Data - Table E33) The 30 mg/kg/day dosage group FI generation female rats had a small (approximately 1.7 days increase from the control group value), statistically significant (p<0.01) delay in vaginal patency. The Testing Facility historical control average and range for this parameter is 32.1 days and 30.1 to 34.0 days, respectively (42 studies; 1995 to 2000). The average day when vaginal patency was evident in the 30 mg/kg/day dosage group (36.6 days of age) significantly differed (p<0.01) from the control group value (34.9 days of age). When this observation in the 30 mg/kg/day dosage group was covaried with the significantly reduced (p<0.01) body weight at time of acquisition, to determine if the significantly reduced body weights were a factor, the difference was still significant, but at the p<0.05 level. When this observation in the 30 mg/kg/day dosage group was Page 65 ARGUS 418-020 covaried with gestational age at time of acquisition, to determine if this group was younger and more immature than the control group, there was no significant difference in sexual maturation. B.5. Estrous Cycling, Mating and Fertility - FI Generation Female Rats (Summary - Table E15; Individual Data - Table E34) The average numbers of estrous stages per 21 days were significantly increased (p<0.01) in the 30 mg/kg/day dosage group (4.7 versus 5.4 stages). The Testing Facility historical control average and range for this parameter is 5.0 stages and 4.8 to 5.2 stages, respectively (7 studies; 1992 to 2002). When this observation in the 30 mg/kg/day dosage group was covaried with the day 64 body weight or age, the difference was still significant, but at the p<0.05 level. Evaluation of the number of rats with 6 or more consecutive days of diestrus or estrus and estrous stages at sacrifice did not reveal any differences among the five dosage groups. All mating and fertility parameters (numbers of days in cohabitation, rats that mated, fertility index, rats with confirmed mating dates during the first week of cohabitation and rats pregnant per rats in cohabitation) were unaffected by dosages of the test substance as high as 30 mg/kg/day. B.6. Necropsy Observations - FI Generation Female Rats (Summary - Table E16; Individual Data - Table E35) All necropsy observations for the FI generation female rats were considered unrelated to the test substance because: 1) the incidences were not dosage-dependent; and 2) the observation occurred in only one female rat in any dosage group. The observations included a small spleen for a 0 mg/kg/day dosage group rat, a mass on the left lateral lobe of the liver with adhesion of the caudate lobe for a 1 mg/kg/day dosage group rat; slight dilation of the pelvis of both kidneys for a 3 mg/kg/day dosage group rat; moderate dilation of the pelvis of the right kidney, thickened urinary bladder walls and moderate dilation of both ureters with one calculi at the caudal end for a 30 mg/kg/day dosage group rat. One rat in the 1 mg/kg/day dosage group that was found dead had distended stomach and intestines with a depressed white area on the lungs, as previously described B.7. Terminal Body Weights, Organ Weights and Ratios (%) of Organ Weights to Terminal Body Weight and Brain Weight - FI Generation Female Rats (Summaries - Tables E17 through E19; Individual Data - Tables E36 and E37) Terminal body weights of the FI generation female rats were comparable among the five dosage groups and did not differ significantly. The absolute weight of the pituitary and the ratios of the pituitary weight to the terminal body weight and to the brain weight were significantly (p<0.05 or p<0.01) decreased in the 3 mg/kg/day and higher dosage groups, as compared to the control group values. Page 66 ARGUS 418-020 The absolute weights of the brain, liver, kidneys, adrenals, spleen, thymus, ovaries and uterus and the ratios of these organ weights to the terminal body weight and the brain weight were unaffected by dosages of the test substance as high as 30 mg/kg/day. Primordial follicle count for ten FI generation female rats in the vehicle control and 30 mg/kg/day dosage groups were comparable and did not significantly differ. B.8. Histopathology (APPENDIX K) No treatment-related microscopic changes were observed in the reproductive organs of any of the 10 female rats in the FI generation selected for histopathologic evaluation that had been given up to 30 mg/kg/day of the test substance. All microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be incidental and unrelated to treatment. There were a few microscopic changes observed in rats designated as "reduced fertility", but these changes occurred spontaneously and were of the type that occur spontaneously in female rats of the age and strain and were not compound-related. B.9. Natural Delivery and Litter Data - FI Generation Female Rats (Summaries Tables E20, E21 and E25 ; Individual Data Tables E38 through E41 and E45) Pregnancy occurred in 28 to 29 rats in each dosage group. Natural delivery observations were unaffected by dosages of the test substance as high as 30 mg/kg/day. Values for the numbers of dams delivering litters, the duration of gestation, averages for implantation sites per delivered litter, the gestation index (number of dams with one or more livebom pups/number of pregnant rats), the numbers of dams with stillborn pups, dams with all pups dying and livebom and stillborn pups were comparable among the five dosage groups and did not significantly differ. The viability index (number of live pups on day 5 postweaning per number of livebom pups on day 1 postweaning) and lactation index (number of live pups on day 22 postweaning per number o f live pups on day 5 postweaning) were comparable and did not differ significantly. The numbers of pups found dead or presumed cannibalized were significantly increased (p<0.01) in the 3 and 10 mg/kg/day dosage groups on day 1 of lactation. These increases were not considered related to the test substance because: 1) they were not dosagedependent; and 2) they did not affect any other measures of pup viability (surviving pups per litter, live litter size at weighing). The number of pups surviving per litter, the percentage male pups, litter size and average pup body weight per litter were comparable and did not differ significantly on DLs 1, 5, 8, 15 or 22 for any of the dosage groups when compared to the control group. Anogenital distances measured for male and female pups on DLs 1 and 22 were comparable among the five dosage groups and did not significantly differ. Page 67 ARGUS 418-020 B.10. Clinical and Necropsy Observations F2 Generation Pups (Summaries Tables E22 and E23 ; Individual Data - Tables E42 and E43) No clinical or necropsy observations were attributable to maternal dosages of the test substance as high as 30 mg/kg/day because: 1) the incidences were not dosage- dependent; and 2) the observation occurred in only one or two litters. These clinical observations included cold to touch, absent tail or eye, tip of tail missing, scab on tail or back, pale in appearance, abrasion at the base of the tail, mass on the mouth, abrasion on the back or tail, emaciation, domed head, dehydration, tail bent or thread-like, no anal opening present, ungroomed coat and no milk present in the stomach. Necropsy observations were limited to no milk in stomach in pups that were found dead. In the pups examined at necropsy on DL 22, dilated kidneys occurred in the 0 mg/kg/day (1 pup in one litter), 1 mg/kg/day (1 pup in one litter) and 3 mg/kg/day (2 pups in 2 litters) dosage groups and marked dilation of the third and lateral ventricles of the brain occurred in the 10 mg/kg/day dosage group (1 pup in 1 litter). . B .ll. F2 Generation Terminal Body Weights and Selected Organ Weights and Ratios (%) of Organ Weights to Terminal Body Weights and Brain Weights (Table E24; Individual Data - Table E44) F2 generation rats had comparable terminal body weights on DL 22; the values did not significantly differ from the control group values. Absolute weights of the brain, spleen and thymus and ratios of these organ weights to terminal body weight and to brain weight were comparable among the five dosage groups and did not significantly differ. REFERENCES 1. U.S. Environmental Protection Agency (1998). Health Effects Test Guidelines; Reproduction and Fertility Effects. Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3800, August, 1998. 2. U.S. Environmental Protection Agency (1997). Toxic Substances Control Act (TSCA) Test Guidelines; Final Rule. Reproduction and Fertility Effects, 799.9380 (cross-referenced to OPPTS 870.3800). Federal Register, August 15, 1997. 3. U.S. Environmental Protection Agency. Federal Insecticide, Fungicide and Rodenticide Act/Toxic Substances Control Act (FIFRA/TSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160/Part 792. 4. Organisation for Economic Co-operation and Development (1998). The Revised OECD Principles of Good Laboratory Practices [C(97)186/Final]. Page 68 ARGUS 418-020 5. Christian, M.S. and Voytek, P.E. (1982). In Vivo Reproductive and Mutagenicity Tests. Environmental Protection Agency, Washington, D.C. National Technical Information Service, U.S. Department of Commerce, Springfield, VA 22161. 6. Christian, M.S. (1984). Reproductive toxicity and teratology evaluations of naltrexone (Proceedings of Naltrexone Symposium, New York Academy of Sciences, November 7, 1983), J. Clin. Psychiat. 45(9):7-10. 7. Lang, P.L. (1988). Embryo and Fetal Developmental Toxicity (Teratology) Control Data in the Charles River Crl:CDBR Rat. Charles River Laboratories, Inc., Wilmington, MA 01887-0630. (Data base provided by Argus Research Laboratories, Inc.) 8. Institute of Laboratory Animal Resources (1996). Guidefor the Care and Use o f Laboratory Animals. National Academy Press, Washington, D.C. 9. Snedecor, G.W. and Cochran, W.G. (1967). Variance test for homogeneity of the binomial distribution. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 240-241. 10. Sokal, R.R. and Rohlf, F.J. (1969). Bartlett's test of homogeneity of variances. Biometry, W.H. Freeman and Co., San Francisco, pp. 370-371. 11. Snedecor, G.W. and Cochran, W.G. (1967). Analysis of Variance. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 258-275. 12. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc. 50:1096-1121. 13. Sokal, R.R. and Rohlf, F.J. (1969). Kruskal-Wallis Test. Biometry, W.H. Freeman and Co., San Francisco, pp. 388-389. 14. Siegel, S. (1956). Nonparam etric Statistics f o r the Behavioral Sciences, McGraw-Hill, New York, pp. 96-104. 15. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6(3):241-252. Page 69 ARGUS 418-020 APPENDIX A REPORT FIGURES Page 70 PROTOCOL 418-020: REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE BODY WEIGHTS P GENERATION MALE RATS Figure 1 0 MG/KG/DAY 1 MG/KG/DAY 3 MG/KG/DAY 10 MG/KG/DAY 30 MG/KG/DAY * p<0.05 ** p<0.01 a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Terminal body weight. i i i i i ii i i i i i i i i I 1 8 15 22 29 36 43 50 57 64 70a 85b 92 99 106 c DAY OF STUDY ARGUS 418-020 PROTOCOL 418-020: ^ G A V A G E | ^ R EG EN ER ATIO N , REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE BODY WEIGHTS P GENERATION FEMALE RATS Figure 2 0 MG/KG/DAY 1 MG/KG/DAY 3 MG/KG/DAY 10 MG/KG/DAY 30 MG/KG/DAY * p<0.05 Last value recorded before cohabitation. ARGUS 418-020 PROTOCOL 418-020: OTAyQAVAEJ g(!J)p,)^J^||j^^R_P|F^ORRRR*TION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE BODY WEIGHTS F1 GENERATION MALE RATS Figure 3 0 (MG/KG/DAY) 1 (MG/KG/DAY) 3 (MG/KG/DAY) 10 (MG/KG/DAY) 30 (MG/KG/DAY) * p<0.05 ** p<0.01 a. Precohabitation body weight. b. First weekly value recorded alter cohabitation. ARGUS 418-020 PROTOCOL 418-020: ORAMGAVAGE^ GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE BODY WEIGHTS F1 GENERATION FEMALE RATS Figure 4 0 (MG/KG/DAY) 1 (MG/KG/DAY) 3 (MG/KG/DAY) etroi 10 (MG/KG/DAY) 30 (MG/KG/DAY) * p<0.05 ** p<0.01 a. Precohabitation body weight. ARGUS 418-020 ARGUS 418-020 APPENDIX B REPORT TABLES - P GENERATION MALE RATS Page 75 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B1 (PAGE 1) : CLINICAL OBSERVATIONS - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 76 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 MAXIMUM POSSIBLE INCIDENCE 3240/ 30 3240/ 30 3240/ 30 3240/ 30 MORIBUND SACRIFICED 0000 CHROMORHINORRHEA 3/ 2 10/ 2 26/ 7 15/ 5 DEHYDRATION 0/ 0 0/ 0 0/ 0 0/ 0 SOFT OR LIQUID FECES 17/ 7 12/ 8 3/ 2 11/ 3 LOCALIZED ALOPECIA: TOTAL LIMBS HEAD 396/ 396/ 0/ 8 8 0 63/ 2** 58/ l** 5/ 1 84/ 3** 84/ 3** 0/ 0 38/ 1** 38/ 1** 0/ 0 URINE-STAINED ABDOMINAL FUR 0/ 0 0/ 0 0/ 0 0/ 0 UNGROOMED COAT 0/ 0 0/ 0 0/ 0 0/ 0 EMACIATION 0/ 0 0/ 0 0/ 0 0/ 0 DRIED RED OR RED PERINASAL SUBSTANCE 0/ 0 0/ 0 0/ 0 0/ 0 COLD TO TOUCH 0/ 0 0/ 0 0/ 0 0/ 0 INCISORS: TOTAL MISSING/BROKEN MISALIGNED 16/ 1 16/ 1 0/ 0 85/ 4 36/ 4 53/ 2 153/ 3 56/ 2 120/ 2 35/ 2 16/ 2 19/ 1 CHROMODACRYORRHEA 0/ 0 35/ 2 124/ 2 21/ 1 DECREASED MOTOR ACTIVITY 0/ 0 0/ 0 0/ 0 0/ 0 PALE EXTREMITIES 0/ 0 0/ 0 0/ 0 ' 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION, a. Rat 13732 was moribund sacrificed on day 45 of study. ** Significantly different from the Group I value (p<0.01). V 30 3178/ 30 la 27/ 8 30/ 4**a 4/ 3 141/ 141/ 0/ 3** 3`* 0 13/ 3**a 21/ 3** 34/ 2a 8/ 2 6/ 2a 11/ 1 0/ 0 11/ 1 5/ 1 1/ la 6/ 1 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.G) TABLE B1 (PAGE 2) : CLINICAL OBSERVATIONS - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 77 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II h i IV 0 1 3 10 MAXIMUM POSSIBLE INCIDENCE 3240/ 30 3240/ 30 3240/ 30 3240/ 30 MORIBUND SACRIFICED 0000 DRIED, RED SUBSTANCE ON FUR b 0/ 0 0/ 0 0/ 0 0/ 0 NO FECES 0/ 0 0/ 0 0/ 0 0/ 0 SCANT FECES 0/ 0 0/ 0 0/ 0 0/ 0 RALES 0/ 0 0/ 0 0/ 0 0/ 0 RIGHT OR BOTH EARS: SWOLLEN SCAB C 15/ 1 0/ 0 38/ 2 46/ 4** 0/ 0 8/ 2* 11/ 1 0/ 0 RIGHT FORELIMB: ABRASION 0/ 0 4/ i 0/ 0 0/ 0 PENIS: RED SUBSTANCE 0/ 0 1/ i 0/ 0 0/ 0 VOCALIZATION 1/ 1 0/ 0 0/ 0 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rat 13732 was moribund sacrificed on day 45 of study. b . Located on both forepaws. c. Located on the nose, mouth, head, right forelimb or back. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p^O.Ol). V 30 3178/ 30 la 6/ 1 2/ 1 2/ 1 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B2 (PAGE 1) : BODY WEIGHTS - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 78 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED BODY WEIGHT (G) DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 DAY 43 DAY 50 DAY 57 DAY 64 I 0 N 30 MEANS.D . MEANS.D . MEANS.D . MEANS.D . MEANS.D. MEANS.D. MEANS.D . MEANS.D . MEANS.D. MEANS.D. 180.9 7.3 242.8 12.4 296.7 15.9 338.2 16.2 370.9 19.0 397.6 21.8 424.0 25.2 448.7 26.7 469.9 28.9 487.9 32.4 II 1 30 180.7 7.6 243.6 10.4 297.1 12.2 340.9 16.8 376.6 21.6 402.5 26.4 427.0 28.4 449.7 30.5 468.0 1 33.8 486.1 37.8 III 3 30 179.9 6.7 245.7 8.4 295.1 10.7 334.8 16.0 363.3 23.9 384.3 27.0 407.0 32.6 425.7 34.2* 444.8 36.9* 459.9 38.3* DAY = DAY OF STUDY ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). IV V 10 30 30 30 178.4 7.2 238.1 10.4 282.4 14.7** 316.8 22.6** 345.2 27.4** 363.4 31.9** 384.2 37.5** 404.2 39.0** 421.5 42.9** 434.1 44.9** 178.6 7.2 211.3 17.0 259.4 16.0 284.9 26.3 300.9 29.9 312.3 35.2 326.3 t 45.8 341.7 39.1 l 29]a 359.3 4 4 . 0 [ 29] a 367.6 49.3 ( 29] a PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B2 (PAGE 2) : BODY WEIGHTS - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS TESTED N 30 30 30 INCLUDED IN ANALYSES N 30 30 30 BODY WEIGHT (G) DAY 70b MEANS.D . 501.1 33.8 498.0 38.8 470.4 43.2* DAY 85c MEANS.D . 528.3 34.7 528.8 43.2 495.8 42.3* DAY 92 MEANS.D. 543.8 37.1 541.6 43.1 506.7 44.7** DAY 99 MEANS.D . 561.1 t 37.8 555.1 44.2 521.6 47.5** DAY 106 MEANS.D . 575.5 39.7 568.3 45.2 533.8 46.2** TERMINAL BODY WEIGHT d MEANS.D . 580.7 40.0 575.3 47.6 541.7 47.2** DAY = DAY OF STUDY a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. b. Last value recorded before cohabitation. c. First value recorded after cohabitation. d. Terminal body weights were recorded when the rats were day 106 to 109 of study. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). IV 10 30 30 444.2 46.2** 468.3 49.2** 479.9 52.0** 495.8 53.0** 504.9 54.4** 513.0 53.9** V 30 30 29a 375.0 54.0** 389.9 64.4** 400.9 69.2** 414.6 64.3** 424.3 62.9** 431.8 64.1** ARGUS 418-020 Page 79 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B3 (PAGE 1) : BODY WEIGHT CHANGES - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 80 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED BODY WEIGHT CHANGE (G) DAYS 1 - 8 DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 MEANS.D . MEANS.D. MEANS.D. MEANS.D. MEANS.D. MEANS.D . MEANS.D . MEANS.D . MEANS.D. I 0 30 +61.9 7.3 +53.9 12.5 +41.5 6.1 +32.7 7.9 +26.7 7.0 +26.4 6.6 +24.7 5.8 +21.3 6.4 +17.9 7.1 II 1 30 +63.0 4.7 +53.5 8.0 +43.8 7.9 +35.6 7.8 +26.0 8.3 +24.5 5.8 +22.7 5.0 +18.3 8.3 +18.1 6.6 III 3 30 +65.8 4.9* +49.4 7.8 +39.8 9.5 +28.5 i 10.7 +21.0 6.6** +22.7 9.7 +18.7 5.2** +19.1 8.3 +15.1 7.0 DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). IV 10 30 +59.7 6.2 +44.3 10.0** +34.4 12.6 +28.3 8.7 +18.3 6.0** +20.7 9.2 +20.0 9.8* +17.4 7.8 +12.6 6.0* V 30 30 +32.7 17.0** +48.1 10.8* +25.5 17.8** +16.0 16.5+* +11.4 10.5** +14.0 26.7** +10.7 16.5** ( 29] a +17.6 1 4 . 7 ( 29] a +8.2 9.6** ( 29] a PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B3 (PAGE 2) : BODY WEIGHT CHANGES - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS TESTED N 30 30 30 INCLUDED IN ANALYSES N 30 30 30 BODY WEIGHT CHANGE (G) DAYS 64 - 70b MEANS.D . +13.2 7.4 +11.9 10.8 +10.5 10.7 DAYS 1 - 70b MEANS.D. +320.2 30.8 +317.3 37.3 +290.5 43.1* DAYS 85c - 92 MEANS.D . +15.5 7.4 +12.8 5.4 +10.9 6.8* DAYS 92 - 99 MEANS .D . +17.3 5.8 +13.6 5.5 +14.9 7.6 DAYS 99 -106 M E A N S .D., +14.4 7.1 +13.2 6.1 +12.3 10.0 DAYS 1 -106 DAY 1 _ TERMINATION d MEANS.D ., +394.6 36.8 MEANS .D ,. +399.8 37.0 +387.7 43.4 +394.7 45.7 +353,9 46.6** +361.8 47.7** DAY (S ) = DAY (S ) OF STUDY a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. b. Last value recorded before cohabitation. c. First value recorded after cohabitation. d. Terminal body weights were recorded when the rats were day 106 to 109 of study. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). IV 10 30 30 +10.1 7.0 +265.8 44.5** +11.6 7.7 +15.9 6.7 +9.1 9.2 +326.5 53.1** +334.5 52.6** V 30 30 29a +7.4 9.8 +196.6 53.2** +11.0 18.4 +13.7 16.5 +9.7 11.3 +246.0 61.5** +253,4 62.9** ARGUS 418-020 Page 81 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B4 (PAGE 1) : ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 82 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED FEED CONSUMPTION (G/DAY) N I 0 30 II III 13 30 30 DAYS 1 - 8 DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 MEANS.D. MEANS.D . MEANS.D . MEANS.D. MEANS.D . MEANS.D . MEANS.D . MEANS.D . MEANS.D. 23.8 1.6 26.6 3.2 28.7 1.6 28.0 1.9 27.8 1.9 28.3 2.1 28.7 1.9 ( 29] a 29.4 1.8 [ 29] a 29.8 2.2 23.9 1.3 26.4 1.8 28.8 2.3 28.6 2.2 28.2 2.1 [ 29] a 28.3 2.3 28.6 2.4 29.6 3.0 29.9 2.5 23.9 1.2 26.1 2.2 [ 28] a 28.6 2.0 28.2 2.6 28.1 2.6 [ 28] a 28.4 1 2.7 28.4 2.7 [ 29] a 29.4 2.9 29.4 3.5 DAYS 64 - 70c DAYS 1 - 70c DAYS 85d- 92 DAYS 92 - 99 MEANS.D . MEANS.D . MEANS.D . MEANS.D . 28.2 2.1 [ 29] a 27.9 1.5 ( 29] a 29.9 2.4 [ 29] a 29.0 2.4 29.3 2.8 [ 29] a 28.1 1.8 l 29] a 29.8 3.1 29.2 2.8 29.3 4.0 [ 26] a 28.1 2.0 [ 26] a 29.7 3.0 29.1 3.2 DAYS 99 -106 DAYS 1 -106 MEANS.D . MEANS .D . 28.9 28.3 2.1 1.6 29.3 2.4 ( 29] a 28.3 1.8 [ 29] a 28.7 2.7 [ 27] a 28.1 2.2 ' [ 27] a DAYS - DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Excludes values that were associated with spillage. b. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. c. Last value recorded before cohabitation. d. First value recorded after cohabitation. ** Significantly different from the Group I value (p<0.01). IV 10 30 23.0 1.6 25.7 2.2 28.9 3.1 28.5 1 3.2 [ 29] a 28.4 3.4 28.5 3.4 28.7 3.4 [ 28] a 29.2 3.4 29.5 i 3.5 28.5 3.5 [ 29] a 27.9 2.7 t 29] a 29.5 3.9 28.9 3.8 28.2 3.8 t 29] a 28.1 2.8 [ 29] a 30 30 19.5 3.3** [ 29]a 25.1 2.4 26.7 4.6 26.0 2.7** 25.4 2.6** 25.2 5.0** 26.2 2.5** [ 28] a , b 26.8 2.9** ( 29]b 27.1 3.5** [ 29] b 25.8 3.2** [ 29] b 25.6 2.2** [ 2 9] b 26.3 5.3** [ 29] b 26.6 3.0** ( 29] b 25.8 3.2** t 29] b 25.7 2.2** [ 29] b PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B5 (PAGE 1) : RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 83 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED N FEED CONSUMPTION (G/KG/DAY) II III 13 30 30 DAYS 1 - 8 MEANS.D. 112.2 1 5.7 112.8 1 5.0 112.2 i 4.4 DAYS 8 - 15 DAYS 15 - 22 MEANlS.D. MEANS.D . 98.8 1 10.9 90.6 1 4.6 97.8 i 90.2 1 6.5 5.7 96.7 1 7.8 [ 28] a 90.7 1 5.4 DAYS 22 - 29 MEANiS.D . 78.8 1 3.8 79.6 1 4.5 80.8 i 5.4 DAYS 29 - 36 DAYS 36 - 43 MEANS.D. MEANlS.D. 72.4 1 69.0 1 3.1 3.6 71.9 1 3.4 ( 29] a 68.2 1 5.1 75.4 1 4.6* [ 28] a 71.7 1 5.3 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 MEANiS.D . MEANS.D. MEANS.D . 66.0 i 3.7 [ 29] a 64.0 i 2.9 [ 29] a 62.2 1 3.1 65.3 i 4.7 64.6 1 6.1 62.7 1 4.0 68.5 1 5.2 [ 29] a 67.6 i 5.5* 65.2 i 7.1* DAYS 64 - 70c DAYS 1 - 70c DAYS 85d.- 92 DAYS 92 - 99 MEANS.D. MEANS.D . MEANS.D. MEANiS.D . 57.1 i 2.4 [ 29] a 73.7 1 2.2 [ 29] a 55.7 i 3.5 ( 29] a 52.6 1 2.7 59.8 1 5.6 ( 29] a 74.3 1 3.7 [ 29] a 55.9 1 5.2 53.3 1 4.4 63.4 1 9.1** [ 26] a 77.1 1 4.7* [ 26] a 59.4 1 4.7** 56.7 1 4.8** DAYS 99 -106 DAYS 1 -106 MEANlS.D. MEANiS.D . 50.9 1 65.8 1 2.8 2.4 52.6 1 3.4 [ 29] a 66.4 1 3.6 [ 29] a 54.7 i 4.0** [ 27] a 69.2 i 4.3** [ 27] a DAYS = DAYS OF STUDY [ ] NUMBER OF VALUES AVERAGED a. Excludes values that were associated with spillage. b. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. c. Last value recorded before cohabitation. d. First value recorded after cohabitation. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). IV 10 30 110.6 1 5.6 98.6 1 6.4 96.2 1 7.4** 85.7 1 5.6** [ 29] a 80.0 1 6.4** 76.3 1 6.2** 73.4 1 7.7** [ 28] a 70.7 1 5.6** 69.1 1 5.8** 65.0 1 7.2** [ 29] a 80.5 1 4.7** [ 29] a 62.4 1 6.3** 59.3 1 5.5** 56.6 1 4.9** [ 29] a 72.6 1 4.4** [ 29] a V 30 30 99.8 14 .8** [ 29] a 107.1 10 . 9* * 97.9 15 3 * * 89.0 8 . 5 * * 83.2 6 2** 79.0 14 8** 7B.7 7 6** [ 28]a,b 76.7 t 7 4 * ( 29] b 74.8 7 0** ( 29] b 70.0 6 9 * * ( 29] b 84.8 6 6** [ 29] b 66.6 12 4 * * ( 29] b 66.5 10 5** [ 29] b 62.5 11 8** [ 29] b 77.6 6 3 * * [ 2 9] b PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B6 (PAGE 1) : MATING AND FERTILITY - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS IN COHABITATION N 29 29 30 DAYS IN COHABITATION a MEAN+S.D . 3.3 + 2.6 1.9 + 1.2* 2 . 4 + 1.7 ( 29) RATS THAT MATED N (%) 29(100.0) 29(100.0) 30 (100.0) FERTILITY INDEX b N/N 28/ 29 (%) ( 96.6) 27/ 29 ( 93.1) 30/ 30 (100.0) RATS WITH CONFIRMED MATING DATES N 29 29 29 RATS MATING C DAYS 1-7 DAYS 8-14 N (%) N (%) 27( 93.1) 2 1 6.9) 29(100.0) 0( 0.0) 28 ( 96.6) K 3.4) RATS PREGNANT/RATS IN COHABITATION N/N 28/ 29 (%) ( 96.6) 27/ 29 ( 93.1) 30/ 30 (100.0) ( ) = NUMBER OF VALUES AVERAGED a. Restricted to rats with a confirmed mating date and rats that did not mate. b. Number of pregnancies/number of rats that mated. c. Restricted to rats with a confirmed mating date. * Significantly different from the Group I value (p<0.05). IV 10 30 3.1 + 2.4 [ 28] 29{ 96.7) 29/ 29 (100.0) 27 27(100.0) 0( 0.0) 29/ 30 ( 96.7) V 30 29 2.6+ 1 ( 28] 29(100.0) 28/ 29 ( 96.6) 28 28 (100.0) 0( 0.0) 28/ 29 ( 96.6) ARGUS 418-020 Page 84 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B7 (PAGE 1) : NECROPSY OBSERVATIONS - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 85 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 RATS EXAMINED a N 30 30 30 30 MORIBUND SACRIFICED N0 0 0 0 APPEARED NORMAL N 29 28 28 28 TESTES : RIGHT OR BILATERAL, SMALL AND FLACCID N0 1 0 1 LEFT, LARGE N0 0 0 0 BILATERAL, RED N0 0 0 0 EPIDIDYMIDES : RIGHT, LEFT OR BILATERAL, SMALL AND FLACCID N0 1 0 1 KIDNEYS : RIGHT, PELVIS, SLIGHT OR MODERATE DILATION N0 1 2 1 LUNGS: ALL LOBES, NUMEROUS DARK RED AREAS N1 0 0 0 LIVER: ALL LOBES, TAN AND PALE N0 0 0 0 a. Refer to the individual clinical observations table (Table B12) for external observations confirmed at necropsy. b. Rat 13732 was moribund sacrificed on day 45 of study. V 30 30 lb 25 1 1 lb 2 2 0 lb PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B8 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 86 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 RATS TESTED N 30 30 30 30 TERMINAL BODY WEIGHT MEANS.D . 580.7 40.0 575.3 47.6 541.7 47.2** 513.0 53.9** EPIDIDYMIS LEFT MEANS.D. 0.7210 0.0599 0.6991 0.0468 0.6901 0.0477 0.7039 0.0476 CAUDA EPIDIDYMIS LEFT MEANS.D . 0.3320 0.0398 0.3172 0.0256 0.3148 0.0280 0.3215 0.0307 TESTIS LEFT MEANS.D . 1.7953 0.1369 1.8103 0.1477 1.7868 0.1312 1.8194 0.0995 LEFT TESTIS MINUS TUNICA ALBUGINEA MEANS.D . 1.6613 0.1410 1.6822 0.1356 1.6598 0.1268 1.6955 0.0943 SEMINAL VESICLES WITH FLUID SEMINAL VESICLES WITHOUT FLUID EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE MEANS.D . MEANS.D . MEANS.D . MEANS.D . MEANS.D. 2.2662 0.3478 [ 29) b 1.2686 0.1554 0.7187 0.0573 1.8173 0.1687 1.1378 0.1852 2.3326 0.3472 1.2539 0.1685 0.6891 0.0791 1.8398 0.3036 1.1426 0.2030 2.3550 0.3246 1.2789 0.1608 0.6930 0.0521 1.7915 0.1293 1.1181 0.1672 2.3052 0.3281 [ 28] b 1.2664 0.1670* 0.6771 0.0958 1.7660 0.2117 1.0368 0.2031 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . [ 1 = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. b. Excludes values for rats that had fluid loss prior to weighing or organs damaged * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). (weight affected). V 30 29a 431.8 64.1** 0.6322 0.0722** 0.2898 0.0374** 1.7878 0.2930 1.6361 0.3290 2.0652 0.2934* 1.1329 0.1545** 0.6366 0.0663** 1.7475 0.2063 0.8619 0.1841** PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.S) TABLE B8 (PAGE 2) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) i II III 013 RATS TESTED N 30 30 30 PITUITARY MEANS.D . 0.014 0.004 0.014 0.003 0.012 0.003* BRAIN MEANS.D . 2.26 0.17 2.28 0.10 2.26 0.12 LIVER MEANS.D . 20.30 2.46 24.27 3.22** 27.71 2.74** KIDNEY LEFT MEANS.D. 2.19 0.20 2.51 0.28** 2.51 0.21** KIDNEY RIGHT MEANS.D. 2.19 0.18 2.54 0.30** 2.50 0.18** ADRENAL LEFT MEANS.D . 0.032 0.005 0.032 0.004 0.030 0.006 ADRENAL RIGHT MEANS.D. 0.032 0.005 0.031 0.005 0.030 0.008 SPLEEN MEANS.D . 0.94 0.16 0.87 0.12 0.86 0.11 THYMUS MEANS.D . 0.44 0.10 0.38 0.08 0.38 0.10 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). IV 10 30 0.014 0.003 2.24 0.12 28.74 3.88** 2.34 0.24* 2.36 0.25** 0.030 0.006 0.031 0.007 0.87 0.14 0.40 0.14 V 30 29a 0.010 0.003** 2.20 0.14 27.49 3.68** 1.99 0.19** 2.06 0.20* 0.028 0.006** 0.026 0.007** 0.74 0.17** 0.30 0.09** ARGUS 418-020 Page 87 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B9 (PAGE 1) : RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 88 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 30 30 30 29a TERMINAL BODY WEIGHT MEANS.D . 580.7 40.0 575.3 47.6 541.7 47.2** 513.0 53.9** 431.8 64.1** EPIDIDYMIS LEFT MEANS.D . 0.123 0.013 0.123 0.010 0.127 0.011 0.138 0.015** 0.150 0.023** CAUDA EPIDIDYMIS LEFT TESTIS LEFT MEANS.D . MEANS .D . 0.058 0.007 0.311 0.025 0.055 0.007 0.316 0.031 0.057 0.006 0.332 0.036 0.062 0.008 0.358 0.042** 0.067 0.012** 0.419 0.080** LEFT TESTIS MINUS TUNICA ALBUGINEA MEANS.D . 0.287 0.026 0.294 0.030 0.307 0.034 0.333 0.040** 0.386 0.089** SEMINAL VESICLES WITH FLUID SEMINAL VESICLES WITHOUT FLUID EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE MEANS.D. MEANS.D . MEANS.D. MEANS.D . MEANiS.D . 0.397 0.062 [ 29] b 0.219 0.026 0.123 0.012 0.313 0.028 0.195 0.033 0.407 0.068 0.219 0.031 0.120 0.017 0.321 0.056 0.200 0.045 0.436 0.064* 0.237 0.034 0.128 0.012 0.334 0.036 0.207 0.033 0.465 0.062** ( 28] b 0.249 0.034** 0.133 0.022** 0.347 0.055** 0.202 0.038 0.484 0.076** 0.266 0.044** 0.149 0.022** 0.410 0.064** 0.199 0.035 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. b. Excludes values for rats that had fluid loss prior to weighing or organs damaged (weight affected). * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B9 (PAGE 2) : RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 89 DOSAGE GROUP DOSAGE (MG/KG/DAY) I ii III IV V 0 i 3 10 30 RATS TESTED N 30 30 30 30 29a TERMINAL BODY WEIGHT MEANS .D . 580.7 40.0 575.3 47.6 541.7 47.2** 513.0 53.9** 431.8 64.1** PITUITARY b MEANS .D . 2.409 0.607 2.435 0.533 2.248 0.543 2.752 0.748 2.476 0.749 BRAIN MEANS .D . 0.390 0.034 0.399 0.035 0.418 0.038* 0.442 0.056** 0.518 0.066** LIVER MEANS.D. 3.490 0.286 4.223 0.500** 5.131 0.472** 5.606 0.514** 6.420 0.729** KIDNEY LEFT MEANS .D . 0.378 0.036 0.437 0.047** 0.465 0.043** 0.457 0.040** 0.466 0.054** KIDNEY RIGHT MEANS.D . 0.379 0.030 0.443 0.048** 0.463 0.039** 0.462 0.034** 0.481 0.051** ADRENAL LEFT b ADRENAL RIGHT b SPLEEN THYMUS MEANS.D. MEANS .D . MEANS .D . MEANS.D . 5.562 0.786 5.439 0.852 0.161 0.027 0.075 0.017 5.575 0.749 5.361 1.016 0.152 0.020 0.066 0.012 5.594 1.125 5.513 1.361 0.160 0.024 0.071 0.017 5.879 1.094 6.157 1.646 0.169 0.025 0.079 0.027 6.593 1.776* 6.177 1.589 0.171 0.035 0.071 0.022 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. b. Value was multiplied by 1000. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B10 (PAGE 1): RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT SUMMARY - P GENERATION MALE RATS ARGUS 418-020 Page 90 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 30 30 30 29a BRAIN WEIGHT MEANS.D. 2.26 0.17 2.28 0.10 2.26 0.12 2.24 0.12 2.20 0.14 EPIDIDYMIS LEFT MEANS.D . 32.08 3.12 30.68 2.33 30.68 2.74 31.47 2.72 28.82 3.71** CAUDA EPIDIDYMIS LEFT MEANS.D . 14.75 1.80 13.92 1.32 13.99 1.38 14.37 1.58 13.21 1.88** TESTIS LEFT MEANS .D . 79.85 7.02 79.38 6.31 79.43 7.22 81.27 5.21 81.63 15.65 LEFT TESTIS MINUS TUNICA ALBUGINEA MEANlS.D. 73.91 7.27 73.76 5.75 73.79 6.84 75.74 5.08 74.85 17.14 SEMINAL VESICLES WITH FLUID SEMINAL VESICLES WITHOUT FLUID MEANS.D. MEANS.D. 101.29 19.24 [ 29] b 56.50 8.07 102.13 14.14 54.94 7.05 104.58 14.68 56.82 7.49 105.25 13.91 ( 28] b 56.65 8.37 94.09 14.20 51.62 7.45 EPIDIDYMIS RIGHT MEANS.D. 31.96 2.81 30.21 3.52 30.81 2.85 30.29 4.62 29.00 3.36** TESTIS RIGHT MEANS.D. 80.89 9.04 80.67 13.57 79.66 7.30 78.95 9.84 79.61 10.36 PROSTATE MEANS.D . 50.58 8.22 50.09 8.73 49.67 7.57 46.29 9.04 39.12 8.06** ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. [ 1 = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. b. Excludes values for rats that had fluid loss prior to weighing or organs damaged (weight affected). ** Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE BIO (PAGE 2) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 V 30 RATS TESTED N 30 30 30 30 29a BRAIN WEIGHT MEANS.D . 2.26 0.17 2.28 0.10 2.26 0.12 2.24 0.12 2.20 0.14 PITUITARY MEANS.D. 0.62 0.18 0.61 0.12 0.54 0.14* 0.62 0.14 0.48 0.14** LIVER MEANS.D. 903.14 118.64 1066.18 153.82** 1230.29 119.75** 1284.45 182.50** 1248.34 144.28** KIDNEY LEFT MEANS.D . 97.52 10.67 110.12 12.60** 111.70 10.49** 104.60 11.72* 90.41 8.68* KIDNEY RIGHT MEANS.D. 97.52 9.94 111.62 13.45** 110.97 9.45** 105.62 12.37** 93.51 8.68 ADRENAL LEFT MEANS.D. 1.43 0.20 1.40 0.19 1.34 0.26 1.34 0.26 1.28 0.30 ADRENAL RIGHT MEANS.D. 1.40 0.23 1.35 0.25 1.32 0.35 1.40 0.35 1.20 0.29 SPLEEN MEANS.D . 41.51 6.97 38.41 5.84 38.55 6.02 38.86 6.15 33.40 7.37** THYMUS MEANS.D . 19.38 4.57 16.89 3.73 17.11 4.59 18.08 6.17 13.73 4.01** ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100 a. Excludes values for rat 13732, which was moribund sacrificed ion day 45 of study. * Significantly different from the Group I value (p<0.05). * * Significantly different from the Group I value (p<0.01). ARGUS 418-1 Page 91 tOo PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Bll (PAGE 1) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED N I 0 30 II III 13 30 30 IV V 10 30 30 29a NUMBER MOTILE MEANiS.D. 354.0 98.9 346.5 118.4 373.3 102.5 338.2 89.0 327.4 130.2 MOTILE PERCENT MEANS.D. 82.6 1 11.1 84.7 7.0 86.8 6.7 87.4 4.0 83.9 8.8 STATIC COUNT (NONMOTILE) MEANiS.D. 73.3 44.0 63.0 33.9 56.7 32.4 48.4 20.3* 58.4 31.0 TOTAL COUNT b MEANiS.D. 427.2 105.5 409.6 135.6 430.0 112.6 386.6 100.6 385.8 138.3 ARGUS 418-020 Page 92 SPERM COUNT C MEANiS.D . 110.6 33.8 119.5 38.3 111.2 37.6 117.7 42.9 98.1 36.9 SPERM DENSITY d MEANiS.D. 962.65 279.89 1086.87 323.61 1016.78 322.39 1047.73 318.51 952.81 307.64 a. Excludes values for rat 13732 which was moribund sacrificed on day 45 of study. b. Sum of number motile and static count. Groups of five fields were evaluated until a sperm count of at least 200 was achieved or 20 fields were evaluated. c. Sperm count used in the calculation of sperm density. Ten fields were evaluated. d. The sperm density was calculated by dividing the sperm count by the volume in the image area (34.3 x 10'6 mL), multiplying by 2 (dilution factor) and multiplying by 10'6 to obtain the sperm concentration. The calculated sperm concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left cauda epididymis (see Table B17 for the weight of the left cauda epididymis) to obtain the sperm density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. * Significantly different from the Group I value (p <. 0.05). PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Bll (PAGE 2) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED N I 0 30 II III 13 30 30 IV V 10 30 30 29a SPERMATID COUNT b MEANS.D. 50.7 16.6 45.9 13.0 47.3 15.6 46.4 14.8 42.6 16.2 SPERMATID DENSITY C MEANlS.D. 91.99 t 30.26 79.83 21.97 82.38 25.57 a. Excludes values for rat 13732 which was moribund sacrificed on day 45 of study. 79.16 24.87 74.47 29.09 b. Spermatid count used in the calculation of spermatid density. Ten fields were evaluated. c. The spermatid density was calculated by dividing the spermatid count by the volume in the image area (34.3 x 10'6 m L ) , multiplying by 2 (dilution factor) and multiplying by 10"6 to obtain the spermatid concentration. The calculated spermatid concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left testis minus tunica albuginea (see Table B18 for the weight of the left testis minus tunica albuginea) to obtain the spermatid density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. ARGUS 418-020 Page 93 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B12 (PAGE 1) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS TESTED N 30 30 30 INCLUDED IN ANALYSES N 30 30 30 NORMAL MEANS.D . 187.1 24.4 191.4 7.0 191.2 5.3 PERCENT ABNORMAL MEAN%S.D. 6.4 12.2 4.3 3.5 4.4 2.6 DETACHED HEAD MEANS.D . 7.5 11.2 4 .4 3.8 4.5 2.8 NO HEAD MEANS.D. 5.2 13.3 3.5 3.5 3.7 2.9 BROKEN FLAGELLUM MEANS.D . 0.2 0.4 0.6 1.0 0.4 0.6 NO HOOK MEANS.D . 0.0 0.2 0.0 0.0 0.0 0.2 EXCESSIVE HOOK MEANS.D. 0.0 0.0 0.1 0.2 0.0 0.2 COILED FLAGELLUM MEANS.D. 0.0 0.0 0.0 0.0 0.0 0.2 BENT FLAGELLUM MEANS.D. 0.0 0.0 0.0 0.0 0.0 0.0 SHORT SPERM HEAD MEANS .D . 0.0 0.0 0.0 0.0 0.0 0.0 a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. IV 10 30 30 190.9 3.5 4.6 1.8 5.9 2.9 2.9 2.3 0.2 0.4 0.1 0.2 0.0 i 0.2 0.0 0.2 0.0 0.2 0.0 0.0 V 30 30 29a 178.6 48.7 9.7 21.0 7.4 14.9 6.1 17.0 1.1 3.1 0.1 0.3 0.1 0.2 0.0 0.2 0.0 0.0 0.1 0.2 ARGUS 418-020 Page 94 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 1) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 95 DOSAGE GROUP I 0 MG/KG/DAY RAT # DESCRIPTION 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 DS ( 60 ) DS( 67 ) DS ( 58- 59) DS ( 10 ) DS ( 30- 36) DS ( 18- 20) DS ( 88 ) DS ( 10- 49) DS ( 72- 85) DS( 93-107) DS( 22- 75) DS ( 44 ) DS ( 94- 96) DS ( 44- 84) DS ( 17 ) DS ( 17- 35) DS ( 25-108) DS ( 15- 17) DS ( 94-108) DS ( 22 ) SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES LOCALIZED ALOPECIA: LIMBS SOFT OR LIQUID FECES SOFT OR LIQUID FECES LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a LOCALIZED ALOPECIA: LIMBS SOFT OR LIQUID FECES LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a SOFT OR LIQUID FECES BOTH EARS: SWOLLEN a VOCALIZATION DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS DOSAGE GROUP I RAT # 13618 13619 13620 13621 13622 13623 13625 13626 13627 13628 13629 13630 DS( 69- 84) DS( 29-109) DS( 23- 60) DS( 39 ) DS( 86- 87) DS( 108 ) DS ( 8- 9) DS = DAY OF STUDY 0 MG/KG/DAY DESCRIPTION INCISORS: MISSING/BROKEN NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS SOFT OR LIQUID FECES SOFT OR LIQUID FECES SOFT OR LIQUID FECES CHROMORHINORRHEA ARGUS 418-020 Page 96 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 3) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 97 DOSAGE GROUP II 1 MG/KG/DAY RAT # DESCRIPTION 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 DS( 2- 3) DS ( 96- 97) DS ( 9 ) DS ( 24- 27) DS ( 24- 28) DS( 94-107) DS ( 59 ) DS ( 7 ) DS ( 18- 21) DS ( 22- 79) DS ( 72- 75) DS ( 86- 87) DS( 36- 60) DS ( 36- 62) DS ( 61-108) DS ( 88- 92) DS ( 94 ) DS ( 108 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA SOFT OR LIQUID FECES SOFT OR LIQUID FECES INCISORS: MISSING/BROKEN INCISORS: MISALIGNED NO ADVERSE FINDINGS BOTH EARS: SWOLLEN a SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES CHROMORHINORRHEA LOCALIZED ALOPECIA: LIMBS CHROMORHINORRHEA SOFT OR LIQUID FECES NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN CHROMODACRYORRHEA INCISORS: MISALIGNED a CHROMODACRYORRHEA CHROMODACRYORRHEA SOFT OR LIQUID FECES DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 4) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS DOSAGE GROUP II 1 MG/KG/DAY RAT # DESCRIPTION 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 D S (101-106) DS ( 46 ) DS ( 33- 36) DS ( 37- 39) DS ( 19- 43) DS ( 10 ) DS ( 31 ) DS( 86-109) DS( 83- 94) DS ( 95- 99) DS( 102 ) DS ( 59 ) DS { 72- 73) DS (105-110) DS ( 48 ) NOSE: SCAB (0.2 CM X 0.2 CM) NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS RIGHT FORELIMB: ABRASION (2.0 CM X 1.0 CM) RIGHT FORELIMB: SCAB (1.0 CM X 0.5 CM) NO ADVERSE FINDINGS BACK: SCAB (1.0 CM X 1.0 CM) SOFT OR LIQUID FECES SOFT OR LIQUID FECES RIGHT EAR: SWOLLEN a HEAD: SCAB (0.5 CM X 0.2 CM) LOCALIZED ALOPECIA: HEAD INCISORS : MISSING/BROKEN PENIS: RED SUBSTANCE, SLIGHT NO ADVERSE FINDINGS CHROMODACRYORRHEA NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN a SOFT OR LIQUID FECES DS DAY OF STUDY a. Observation confirmed at necropsy. ARGUS 418-020 Page 98 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 5) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 99 DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 DS( 74-106) DS ( 61 ) DS ( 31- 32) DS ( 31- S3) DS ( 31-106) DS ( 31-106) DS (101-106) DS ( 9- 10) DS ( 90- 94) DS ( 57- 69) DS ( 57-100) DS ( 72- 75) DS ( 77-107) NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN a SOFT OR LIQUID FECES CHROMORHINORRHEA INCISORS : MISSING/BROKEN CHROMODACRYORRHEA a INCISORS : MISALIGNED a LOCALIZED ALOPECIA: LIMBS a SOFT OR LIQUID FECES MOUTH: SCAB (0.2 CM X 0.2 CM) NO ADVERSE FINDINGS CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE G) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 DS( 16- 17) DS< 39-109) DS( 25- 27) DS( 51- 52) DS( 20 ) DS( 95- 97) DS ( 10- 23) DS( 59 ) DS ( 16- 22) DS ( 18 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA LOCALIZED ALOPECIA: LIMBS a CHROMORHINORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA NO ADVERSE FINDINGS NOSE: SCAB (0.2 CM X 0.2 CM) NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA LOCALIZED ALOPECIA: LIMBS CHROMORHINORRHEA DS = DAY OF STUDY a. Observation confirmed at necropsy. ARGUS 418-020 Page 100 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 7) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 101 DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 DS( 71 ) DS( 82- 84) DS( 64- 65) DS( 64- 78) DS( 65- 70) DS( 73- 76) DS( 79- 97) DS ( 95- 96) DS( 99-107) DS ( 2 ) DS ( 23- 28) DS ( 15- 18) DS ( 36 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA INCISORS: MISSING/BROKEN CHROMODACRYORRHEA CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA a CHROMORHINORRHEA CHROMORHINORRHEA NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 8) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 DS ( 108 ) DS ( 15- 16) DS ( 99-109) DS ( 72-109) DS ( 16- 18) DS ( 16- 17) DS ( 23 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN a CHROMORHINORRHEA BOTH OR RIGHT EARS: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES CHROMORHINORRHEA CHROMORHINORRHEA NO ADVERSE FINDINGS DS = DAY OF STUDY a. Observation confirmed at necropsy. ARGUS 418-020 Page 102 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 9) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 103 DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732 DS( 87 ) DS( 22 ) DS( 85 ) DS( 85 ) DS( 87- 92) DS ( 87- 99) DS ( 94- 95) DS ( 24- 26) DS ( 52- 53) DS ( 73- 84) DS ( 93- 99) DS ( 8 ) DS ( 16- 21) DS ( 3 ) DS ( 58- 68) DS ( 8- 9) DS ( 18- 34) DS ( 41- 45) DS ( 44- 45) DS ( 44- 45) DS ( 45 ) DS ( 45 ) NO ADVERSE FINDINGS SOFT OR LIQUID FECES RALES DEHYDRATION UNGROOMED COAT UNGROOMED COAT DEHYDRATION DRIED RED PERINASAL SUBSTANCE NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA SOFT OR LIQUID FECES LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA CHROMORHINORRHEA INCISORS: MISALIGNED DEHYDRATION EMACIATION EMACIATION a COLD TO TOUCH URINE-STAINED ABDOMINAL FUR DECREASED MOTOR ACTIVITY MORIBUND SACRIFICED DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 10) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 104 DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 13733 13734 13735 13736 13737 13738 13739 13740 13741 13742 DS ( 14- 17) DS( 23- 24) DS ( 85- 90) DS ( 85- 92) DS{ 92 ) DS ( 20- 23) DS ( 36- 100) D S (107- 109) DS ( 85- 94) DS ( 86- 91) DS ( 86- 91) DS ( 86- 91) DS ( 86- 92) DS ( 88- 91) DS ( 88- 93) DS ( 88- 99) DS ( 90- 91) DS ( 92- 93) DS ( 2- 3) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA DEHYDRATION UNGROOMED COAT DEHYDRATION CHROMORHINORRHEA NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a URINE-STAINED ABDOMINAL FUR DRIED, RED OR RED PERINASAL SUBSTANCE UNGROOMED COAT BOTH FOREPAWS: DRIED, RED SUBSTANCE ON FUR DEHYDRATION COLD TO TOUCH PALE EXTREMITIES EMACIATION NO FECES SCANT FECES CHROMORHINORRHEA DS = DAY OF STUDY a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B13 (PAGE 11) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 13743 13744 13745 13746 13747 13748 13749 13750 DS( 16 ) DS( 100 ) DS( 31- 60) DS( 78- 84) DS( 94-110) DS ( 17- 21) DS( 3- 5) DS { 72 ) NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMORHINORRHEA LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a CHROMODACRYORRHEA NO ADVERSE FINDINGS CHROMORHINORRHEA URINE-STAINED ABDOMINAL FUR DS = DAY OF STUDY a. Observation confirmed at necropsy. Page 105 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B14 (PAGE 1) : BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 106 DAY 1 8 15 22 29 36 43 RAT # DOSAGE GROUP I 0 MG/KG/DAY 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 166. 191. 187. 189. 166. 196. 178 . 182. 172. 184. 177. 177. 171. 181. 182 . 190. 178. 191. 176. 178. 174. 182. 181. 185. 180. 186. 176. 188 . 176. 187. 216. 252. 253 . 251. 225. 267. 232 . 243 . 233 . 244 . 247. 239. 226. 229. 238. 272 . 236. 253. 237 . 243 . 234 . 238 . 233 . 246 . 247 . 245. 244 . 256. 241. 263 . 275 . 315 . 312 . 313 . 279. 326. 288. 295 . 286. 304 . 314 . 286. 270 . 279. 294 . 270. 292 . 303 . 292 . 290. 276 . 290. 296. 293 . 311. 308 . 304 . 312. 297 . 331. 310. 362 . 351. 365. 327. 363 . 329. 336. 335. 341. 363. 332. 314 . 313 . 339. 317. 332 . 335. 334. 339. 323. 330. 336. 327. 341. 353. 348. 356. 326. 368. 340. 394 . 382. 401. 353. 399. 353 . 363 . 374 . 365. 402. 366. 343 . 344 . 379. 368 . 361. 366 . 366. 375. 358. 354. 374. 356. 361. 408. 374 . 377. 362. 408 . 369. 418. 409. 434 . 380. 432. 373. 400. 409. 3 92 . 425. 397. 359. 368. 410 . 404 . 378. 386 . 392. 406 . 381. 378 . 402 . 375 . 385 . 434 . 386. 423. 388. 434 . 398. 446. 432. 458. 402 . 461. 393. 411. 440. 431. 459. 419. 378. 398. 445 . 433 . 399. 412 . 409. 435 . 410. 399. 440. 400. 410. 463. 404 . 457 . 409. 469. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Laat value recorded before cohabitation. b. First value recorded after cohabitation. 50 431. 462 . 455. 4 90. 425. 489. 416. 428. 464 . 456. 489. 445 . 408 . 422. 457. 465. 429. 433 . 438. 462 . 423 . 424 . 458. 420 . 432 . 492 . 423 . 489. 437. 498. 57 455. 487 . 460 . 516. 440. 520. 438. 448. 486. 471. 509. 470. 432. 446. 471. 498 . 440. 444 . 455. 482 . 440. 454 . 486. 440. 461. 513 . 444 . 516. 454 . 522 . 64 480. 511. 484 . 537. 458. 546. 455. 478 . 502. 484 . 533 . 482. 450. 460. 493 . 514 . 441. 462 . 471. 495 . 453 . 460. 496. 458. 481. 545 . 449. 535. 476 . 547 . 70a 500. 520. 511. 556. 472 . 555. 463. 479. 515. 477. 542. 492. 470 . 462. 511. 537. 462. 472 . 485. 511. 472 . 472 . 514 . 467. 487. 566. 466. 555 . 485. 556. 77 507. 538. 508. 565. 487. 566. 481. 502 . 523. 500. 554. 504. 479. 473 . 511. 557. 471. 482 . 501. 517. 486 . 483 . 525. 482. 504 . 564 . 486. 570. 504 . 579. 85b 529. 553 . 517. 586. 494 . 598. 497. 505. 548. 518. 578. 509. 489. 493. 527. 570 . 478 . 499. 509. 536. 496. 504 . 531. 490. 532. 570. 510. 583 . 515. 586. 92 555. 576. 538. 604 . 514 . 610. 514. 522 . 565 . 534 . 597. 527. 514. 500. 542 . 590. 489. 510 . 526. 543 . 492 . 520. 534 . 502 . 544 . 606 . 523 . 599 . 529. 596. 99 567. 592. 552. 631. 530. 630. 529. 542 . 580. 554 . 616 . 543 . 528. 525. 562 . 614 . 494 . 525 . 543 . 565 . 513 . 544 . 555. 512 . 563 . 616 . 551. 604 . 540 . 614 . 106 592. 610 . 570 . 633 . 533 . 653. 545 . 562 . 604 . 567 . 632. 554 . 549. 527. 582 . 637 . 507. 540 . 564 . 570 . 523 . 554 . 580. 524 . 567 . 636. 564 . 617. 547. 622 . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.G) TABLE B14 (PAGE 2) : BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 107 RAT # DOSAGE GROUP II 29 36 43 1 MG/KG/DAY 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 163 . 194 . 180. 182 . 167. 193 . 183 . 181. 175. 190. 179. 176. 184. 186. 180. 184 . 173 . 188. 180. 187. 166. 181. 176. 188. 178 . 188. 174 . 182 . 175. 187. 225. 256. 241. 245. 221. 265. 251. 250. 244 . 259. 237. 242. 250. 249. 244 . 248 . 231. 247. 244 . 247 . 227. 243. 233. 253 . 244 . 246 . 232. 241. 234 . 260. 285. 317. 292. 301. 279. 313. 322. 296. 302 . 317. 300. 308. 305. 307. 285. 294. 288. 298. 294 . 290 . 287. 292. 275. 307. 296. 282 . 277. 300 . 294 . 311. 319. 359. 328. 358. 318. 360. 372 . 335. 360. 362. 340. 348. 350. 352. 335. 335. 339. 343. 334. 345. 337. 335. 313. 353 . 344 . 316. 305. 328 . 336. 369. 348. 394 . 362. 405 . 348. 386. 408. 370. 404 . 398 . 3 72 . 385. 389. 387. 374 . 370. 381. 387 . 353 . 376. 369. 370. 350. 388. 395. 343 . 322 . 363 . 385. 415 . 375. 417. 376. 433 . 362. 414 . 440. 398. 441. 429. 394. 403 . 422. 403. 400. 392 . 415. 419. 372 . 402 . 418. 405. 370. 407. 422. 367. 332. 394. 404 . 450. 396. 440 . 398. 462. 392. 429. 459. 432. 466. 465. 411. 420. 451. 428. 427. 422. 431. 452. 396. 430. 442. 429. 391. 434 . 454. 381. 355. 412. 427. 478. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation. 50 415. 459. 418. 484. 410. 438. 481. 460. 483. 485. 434. 443 . 482. 449. 455. 439. 453. 478. 416. 455. 467. 458. 414 . 460. 483. 400. 377. 431. 451. 512 . 57 433 . 465. 431. 509. 427. 468. 506. 482. 493 . 501. 456. 449. 496. 467. 455. 460. 476. 505. 431. 470. 500. 469. 429. 476. 515. 420. 385. 460 . 464 . 541. G4 453 . 476. 444 . 522. 441. 485. 524 . 517. 510. 531. 464. 471. 517. 488. 471. 479. 491. 523 . 442 . 483 . 519. 490. 439. 491. 540 . 437. 393 . 485. 484 . 573 . 70a 472. 486. 456. 499 . 454 . 514. 544 . 532. 499. 545. 477. 460. 517. 504. 486. 490. 507 . 542. 461. 501. 537. 502. 454 . 501. 565. 445 . 411. 494 . 490 . 594 . 77 481. 494 . 472. 478. 470. 524 . 556. 548. 521. 558. 488. 472 . 542. 515. 498. 497. 515. 539. 476. 502 . 545. 526. 468. 522 . 577. 458. 416. 508. 484 . 618 . 85b 502. 512. 485. 541. 485. 540. 584. 574. 536. 577. 502. 512. 562. 538. 512 . 516. 527. 562. 488 . 520 . 559. 538. 482. 546. 604 . 470 . 433 . 516 . 497. 643 . 92 512. 523. 498. 564. 503 . 551. 604. 592. 553 . 585. 516. 530. 571. 542. 527. 527. 537. 566 . 496. 544 . 570 . 553 . 488. 558 . 611. 488 . 440 . 527. 517. 654 . 532 . 546 . 498. 585 . 513 . 571. 622 . 605 . 564 . 600 . 523 . 547 . 586 . 560 . 541. 533 . 550. 588. 510. 563 . 575 . 562 . 499. 569. 627. 496. 455. 543 . 529. 662 . 548 . 558 . 502 . 607 . 526. 587. 640. 611. 562 . 614 . 536. 561. 593 . 583 . 560. 548 . 564 . 606 . 515 . 568 . 592 . 572 . 517. 578 . 635 . 514 . 462 . 566 . 545. 680. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B14 (PAGE 3) : BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 108 DAY RAT # 1 8 15 DOSAGE GROUP III 22 29 36 43 3 MG/KG/DAY 13661 13662 13663 13664 13665 13666 13667 136 68 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 171.. 195.. 181.. 180.. 171.. 191.. 182 . 182.. 170.. 187,. 174 . 184.. 168.. 185,. 175.. 184.. 175,. 182 ,. 178.. 182.. 172 ,. 177,. 180.. 185,. 172 ,. 188.. 175.. 187.. 178 ,. 186.. 231,. 260.. 250,. 245,. 235.. 257,. 250.. 242., 227., 247.. 243.. 240.. 232.. 244.. 246.. 258,. 244.. 251.. 248., 253., 240.. 253 ., 249,. 248., 232., 252.. 240.. 254 . 244 . 255.. 287. 305 . 306. 298. 290. 292. 307. 292. 279. 304 . 291. 284 . 282. 292. 301. 289. 293. 311. 284. 308. 288. 312. 287. 288. 275. 300. 288. 316. 293 . 310. 336. 333 . 347. 337. 338. 312. 356. 321. 303 . 341. 339. 326. 320. 319. 339. 318. 327. 356. 329. 359. 337. 357. 333. 330. 308. 325. 329. 358. 344 . 368. 368 . 361,. 378 ., 378 ., 360. 320., 391. 323 . 318., 365., 366. 361. 352.. 332. 363. 339., 363 . 404 . 362. 3 94 . 361. 400. 374 . 359. 342. 337 . 355. 386. 380. 408 . 3 94. 387. 398. 384. 376. 343. 415. 338. 336. 386. 375. 385. 374. 346. 385. 354. 381. 434 . 386. 417. 393 . 424 . 406 . 384 . 362. 346. 374 . 402. 411. 433 . 432. 411. 426. 403 . 398. 359. 441. 355. 369. 412. 391. 378. 399. 360. 410. 363. 404 . 468. 415. 434 . 412. 453. 426. 398. 382. 364. 394. 433. 441. 479. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation. 50 450 . 421. 448 . 422 . 412 . 373 . 468. 371. 392. 432. 405. 398. 421. 378. 428. 386 . 418. 485. 430 . 445. 425 . 483 . 444 . 420. 400 . 389. 408. 450 . 458. 511. 57 461. 445 . 472. 430 . 433 . 390. 460. 378 . 400. 450. 431. 420. 447. 401. 445. 398. 438 . 511. 452. 469. 439. 501. 471. 446 . 418. 409. 428 . 466. 490. 544 . 64 474 . 464 . 476. 441. 454. 406. 451. 385. 419. 468. 446. 440. 463 . 414 . 475. 410. 450. 532 . 472. 490. 452 . 520. 483 . 458. 431. 427. 445 . 488. 498. 565. 70a 486. 479. 494. 444 . 466. 418. 476. 402 . 385. 484 . 460. 454 . 477. 426. 473 . 418. 460. 550. 475. 493 . 460. 538. 495 . 469. 447 . 433. 450. 497. 507. 596. 77 509 . 447. 505. 442 . 472 . 422. 492. 408. 441. 498. 472 . 448 . 483 . 447. 492. 431. 479. 562. 502. 481. 466. 544 . 519. 477. 461. 450 . 456. 513. 524. 584 . 85b 532 . 488. 523. 470 . 480. 432. 516. 414 . 452. 520. 483. 466. 499. 460. 518. 447. 488. 574. 510. 506. 469. 504 . 532. 497. 472. 461. 472. 531. 534. 624 . 92 551. 502. 547. 475. 499 . 436. 519. 417. 462 . 534 . 488. 475. 516. 468. 524. 455. 492 . 589. 520 . 523 . 481. 533 . 554 . 499. 479. 470. 478 . 542 . 543. 629. 99 569. 515 . 567. 485. 507 . 459. 513. 425. 480 . 54 9. 501. 490 . 538. 484. 540. 458. 514 . 610. 540 . 540 . 490. 569. 563 . 515. 483 . 482 . 496. 558 . 557. 650 . 106 585 . 539. 567 . 511. 511. 481. 542 . 449. 502 . 555 . 526 . 497 . 551. 496 . 556. 464 . 522 . 617 . 546. 521. 507 . 584 . 572 . 525 . 487. 499 . 507 . 561. 562. 673 . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) 7ABLE B14 (PAGE 4) : BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 109 DAY 1 8 15 22 29 36 43 RAT # DOSAGE GROUP IV 10 MG/KG/DAY 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 166. 188. 178. 187 . 172 . 190 . 180. 184. 170. 190. 177. 168. 171. 175. 179. 183. 171. 188 . 180. 181. 170. 169. 176. 181. 175. 183. 178. 182 . 171. 190. 227. 241. 246. 254 . 233 . 253 . 234. 240. 228. 259. 240. 231. 226. 240. 241. 248 . 233 . 255. 234. 232 . 218 . 225 . 240 . 230. 239. 238. 226. 243 . 233. 257. 276 . 261. 300. 305 . 274 . 297. 279 . 269. 262 . 304 . 284 . 274 . 280. 285 . 289. 302 . 281. 300 . 296 . 253 . 256 . 261. 280. 278 . 296 . 293 . 278 . 294 . 277. 288 . 322. 293 . 353. 345. 300. 331. 303 . 315. 296. 347. 320. 310. 315. 339. 330. 334 . 324 . 350. 304. 275. 268 . 282 . 289. 307. 329. 321. 300. 340. 324. 339. 356. 317. 386. 383 . 334 . 353 . 333. 349. 310. 379. 351. 343 . 341. 385. 350. 362 . 363 . 390. 335. 290. 284 . 322 . 317. 314 . 361. 340 . 326. 368. 350. 363 . 369. 329. 413 . 410. 356. 376. 350. 372 . 322. 403 . 362. 355. 354. 406. 367. 384. 384. 413. 352. 300. 295 . 337. 334. 325. 378. 351. 343. 395. 375. 393. 392 345 433 429 386 411 366 3 94 343 433 387 381 371 436 396 399 404 433 373 305 300 355 323 339 404 380 369 421 396 421 DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. First value recorded after cohabitation. 50 57 64 70a 77 85b 92 99 106 414 . 356. 450. 460. 409. 442. 382. 411. 354 . 440. 412. 385. 401. 456. 414 . 424 . 424 . 453. 382. 316. 306. 378. 378. 369. 423. 400. 384. 439. 419. 444 . 429. 365. 483 . 489 . 408 . 469. 395. 434 . 366. 454 . 420 . 395. 414 . 482. 441. 442 . 440 . 472 . 396. 328 . 330. 385. 404 . 384 . 444 . 417. 392. 460. 441. 467. 444 . 378 . 4 94. 501. 426. 481. 410. 450. 383. 475. 428. 415. 422 . 489. 454 . 456. 459. 476. 401. 335 . 336. 392 . 420. 383 . 465. 433. 395 . 477. 458. 488 . 464. 388. 499. 519. 429 . 470. 419. 463 . 391. 481. 434 . 423 . 437. 510. 4 70. 462 . 467. 483 . 407. 347 . 340 . 407 . 423 . 390. 471. 440 . 414 . 493 . 477. 509. 468. 389. 520. 520. 440. 479. 424 . 480. 405. 488. 435. 435. 445 . 523. 476. 452. 487. 507. 392. 352 . 345. 427. 434 . 394 . 452. 448. 420. 498. 483. 512. 478 . 395. 543. 523. 469. 509. 439. 486. 424 . 498. 430. 450 . 460. 549. 499. 467. 499. 526. 412. 371. 364 . 441. 450 . 410 . 506. 481. 439. 503 . 494. 535. 496. 409. 552. 544 . 483 . 520. 441. 498. 430. 503. 460. 459. 469. 580. 509. 486 . 514 . 537. 421. 372 . 370. 436. 462. 423. 519. 494 . 452. 521. 495. 542 . 509. 433 . 556. 558. 498. 540. 456. 517. 446. 521. 462. 474 . 480. 598 . 540 . 513. 535. 552. 437. 381. 383. 449. 478 . 439. 533 . 514. 467. 521. 518. 565. 528 450 570 571 506 553 476 524 468 530 485 487 483 620 551 519 541 538 443 390 393 435 484 434 544 521 477 519 524 583 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B14 (PAGE 5) : BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 110 DAY 1 8 15 22 29 36 43 RAT # 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732 13733 13734 13735 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 DOSAGE GROUP V 166 ,. 193 . 178 . 185.. 170.. 179,. 182,. 183.. 172,. 186.. 175.. 186.. 171.. 188.. 178.. 181.. 171.. 183.. 174.. 188,. 171.. 185.. 169,. 176.. 176.. 190., 169.. 185.. 173.. 176 . 220.. 229.. 212.. 193., 203., 227.. 227.. 224., 221.. 236., 232.. 162. 198.. 233., 205., 214,. 206.. 218.. 192.. 206.. 211.. 216.. 187.. 191., 217., 237.. 209.. 190.. 217.. 206.. 263. 268. 252. 243. 235. 283. 286. 268. 272. 286. 280. 236. 254. 271. 249. 253. 232. 271. 251. 267. 257. 255. 232. 243. 259. 282. 255. 266. 268. 246. 30 MG/KG/DAY 299. 307. 254. 281. 259. 312 . 317. 293 . 298. 339. 296. 208. 313. 308. 275. 281. 263 . 284. 266. 300. 257. 283 . 263. 268. 277. 288. 253. 319. 305 . 282 . 331. 316. 260. 296. 256. 301. 320. 306. 309. 372. 321. 278 . 361. 313. 282 . 300. 277. 309. 271. 322. 262 . 283 . 287 . 274 . 276 . 311. 256. 353 . 321. 303 . 358. 315. 263. 298. 259. 306. 327. 315. 317. 392. 341. 311. 393. 317. 300. 292. 282 . 337. 282. 333 . 268. 281. 294 . 282. 301. 320. 258 . 367. 335. 326 . 381. 335. 267. 304 . 274 . 350. 334. 324. 329. 410. 360. 192. 418. 335. 336. 314. 290. 354 . 304 . 368 . 296. 291. 306. 295. 321. 335. 280. 392. 347. 348. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. First value recorded after cohabitation. 50 57 64 70a 77 85b 394. 417. 437. 444 . 450. 464 . 344. 355. 368. 385. 405. 414 . 283. 289. 286. 273 . 285. 295. 326. 350. 349. 361. 370. 386. 279. 288. 285. 298. 300. 331. 373. 378. 380. 394 . 345. 419. 338. 351. 363. 380. 390. 405. 346. 365. 363. 355. 371. 385. 342. 357. 369. 374. 381. 392 . 420. 440. 459. 456. 475. 486. 377. 389. 390. 402. 406. 424 . MORIBUND SACRIFICED ON DAY 45 OF STUDY 442 . 475. 480. 506. 518. 536. 353 . 378. 385. 374. 390. 396. 347. 356. 364. 369. 389. 400. 352. 337. 342. 352. 356. 362 . 302 . 320. 327. 345. 344 . 269. 373. 386. 399. 412 . 418. 431. 303. 331. 337. 334. 339. 353 . 377. 405 . 414 . 429. 433 . 449 . 308. 315. 310. 311. 312 . 268. 296. 302 . 304 . 306. 321. 325. 318. 331. 343. 344 . 360. 370. 315. 328. 337. 340. 349. 352 . 328. 353 . 358 . 360. 368. 370. 352. 370. 380. 386. 391. 415. 286. 297. 301. 305. 302. 301. 328 . 403 . 448. 475. 485. 501. 358. 375. 390. 400 . 383 . 409. 349. 380. 391. 404 . 390. 399. 92 481. 435 . 302. 388. 339. 438 . 413 . 388. 396. 499. 441. 547. 408. 408. 381. 345. 443 . 351. 464 . 217. 322. 390. 359. 379. 419. 306 . 517. 436. 414 . 99 498. 441. 312 . 407 . 353 . 451. 423. 392 . 413 . 520. 453 . 536. 428. 428 . 380. 365. 457. 354. 478 . 300. 335 . 373 . 370. 399. 429. 321. 548. 442. 418 . 106 511. 452 . 321. 378 . 361. 465 . 440. 411. 427. 515 . 462 . 550. 450. 437 . 389. 374 . 464 . 360. 486 . 341. 342 . 390 . 386 . 395. 442 . 323 . 547. 456 . 431. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B15 (PAGE 1) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 111 DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 50- 57 57- 64 64- 70a 85b-92 92- 99 99-106 RAT # DOSAGE GROUP I 0 MG/KG/DAY 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 148. 166. 183. 172. 164. 179. 154. 166. 168. 177. 189. 170. 153. 153 . 152. 190. 160. 166 . 164. 165 . 162. 158. 148 . 175. 176 . 164 . 159. 177. 172 . 166. 195. 209. 207. 211. 185. 203 . 199. 182. 175. 209. 218. 188. 161. 182. 168. 95. 186. 177 . 184 . 177. 170. 176. 189. 176. 195. 186. 189. 198. 202. 207. 190. 217. 225. 220. 207. 195. 198. 197. 201. 208. 221. 201. 186. 180. 197. 208. 182. 200. 204. 207. 199. 191. 201. 195. 196. 213. 207. 207. 189. 195. 178. 208. 212 . 210. 198. 216. 193. 187. 196 . 196. 229. 200. 185. 174 . 194 . 206. 191. 187 . 205. 208. 190. 179. 192. 183 . 173 . 212 . 187. 182. 196. 205 . 188. 201. 198. 210 . 195. 213 . 181. 201. 200. 212 . 214 . 202 . 170. 177. 189. 203 . 186 . 189. 188. 201. 186. 172 . 190. 188. 181. 207 . 174 . 220 . 195. 213 . 196. 196. 204 . 215 . 195. 220 . 192 . 196. 207. 230. 218. 200. 177 . 199. 197 . 195. 183 . 196. 189. 200 . 182 . 181. 193. 190. 183 . 206. 170 . 231. 197. 214 . 208. 198. 202 . 217. 198. 220. 205. 191. 210. 228. c 191. 186. 200. 186. 202. 188. 207 . 198. 200. 180. 187. 200. 189. 203 . 204 . 176. 223 . 213 . 219. 215. 206 . 198 . 226. 194 . 230. 207. 198. 219. 227. 224 . 199. 197. 203 . 190 . 217. 189. 205 . C 205 . 187 . 193. 206. 194 . 206. 215. 180. 214 . 205 . 219. 225 . 218. 210. 220. 204. 228. 199. 204 . 213. 239. 235. 206. 205. 198 . 207. 226 . 218031.. 199. 204 . 185. 184 . 209. 198. 203 . 232 . 177. 226. 204 . 218 . 188. 176. 174 . 185. 171. 188 . 165. 167. 166. c 187 . 168. 160 . 153 . 172 . 181. 160. 151. 166. 173 . 158. 157. 169. 159. 160. 180 . 139. 187 . 170 . 184 . 226. 213 . 205. 220. 223 . 247. 204 . 209. 222. 243. 239. 200. 192. 199. 198 . 218 . 185. 208. 192. 203 . 178. 202 . 187. c 199 . 225. 219291.. 210. 209. 214 . 208 . 201. 219. 197. 240 . 209. 201. 202 . 233 . 229. 199. 195. 192 . 194 . 225 . 180 . 202 . 187 . 198 . 171. 198 . 184 . 181. 194 . 234 . 197. 211. 198 . 207 . .2 2 0 .208. 202 203 . 193 . 219. 190 . .191. 212 231. .226 . 202 207. 190 . 206 . 221. 175. 209 . 198 . 188 . 178 . 198 . 192. 186 . 180 . 230 . 195. 208. .206 . 210 DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B15 (PAGE 2) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 112 DAYS RAT # 1- 8 8- 15 15- 22 DOSAGE GROUP II 22- 29 29- 36 36- 43 1 MG/KG/DAY 43- 50 50- 57 57- 64 64- 70a 85b-92 92- 99 99-106 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 160. 166. 173. 169. 156. 186. 172. 176. 167. 180. 160. 173. 171. 178. 167. 170. 159. 163. 170. 171. 165. 163 . 153 . 176. 173 . 148. 154 . 155. 169. 183 . 189. 189. 172 . 190. 207. 195. 206. 191. 182 . 199. 207 . 208 . 187. 193 . 178. 180 . 172 . 171. 188. 179. 182. 177. 163 . 176. 182 . 158. 177. 183 . 184 . 186. 183 . 211. 188. 222. 206. 230. 216. 203. 229. 215. 203 . 215. 191. 198. 200. 184 . 185. 195. 219. 209. 195. 214 . 181. 200. 204 . 164. 200. 173 . 198. 214 . 176. 197. 186. 228 . 198 . 210. 211. 206. 217 . 211. 193. 216. 201. 203. 215. 193. 190. 199. 196. 210. 197. 219. 174 . 190. 205. 156. 187. 192 . 207. 220 . 175. 195. 178. 228 . 200. 212. 212 . 204 . 216. 202 . 190. 194. 198. 195. 196. 186. 190. 203 . 186. 203. 206. 203. 171. 186. 213 . 162. c 191. 202. 222 . 182. 197. 180. 230. 207. 197. 205. 217. 210. 218 . 182. 196. 203 . 174. 203 . 185. 182. 201. 199. 213 . 212 . 206. 170. 191. 208 . 157. 200. 191. 201. 221. 189. 196. 186. 232. 217. 219. 215. 216. 210 . 216. 189. 189. 198. 192. 200. 187. 183. 201. 200. 221. 213 . 197. 170. 190. 209. 159. 195. 185. 210. 224 . 195. 199. 188 . 232. 212. 230. 215. 223 . 210. 220. 194. 197. 202. 196. 204 . 197. 190. 217. 196 . 216. 210 . 200. 175. 205. 226 . 167. 194 . 280. 200. 233 . 200. 205. 196. 233. 219. 231. 223 . 233. 220. 235. 190. 211. 216. 208. 197. 195. 196. 216. 200. 211. 221. 196. 172. 201. 227. 170. 200. 199. 209. 246 . 169. 174 . 166. 175. 182. 213 . c 194 . 172. 187. 164. 158. 174 . 182. 169. 161. 171. 179. 167. 174 . 184 . 169. 219. 165. 196. 143 . 152. 165. 168. 201. 197. 221. 192. 255. 217. 236 . 230. 238. 221. 231. 190. 227 . 209. 190. 203 . 195. 190. 206 . 195. 233. 198. 198. 169. 201. 228. 167 . 215. 185. 197 . 240 . 199. 210. 184 . 228 . 209. 240. 213 . 228 . 206. 218 . 170. 211. 206. 219. 191. 188. 182. 204 . 185 . 225 . 194 . 195 . 167. 198 . 226. 173 . 211. 198 . 211. 239. 193 . 219. 169. 224 . 210 . 235. 218 . 221. 202 . 220. 189. 209. 211. 226. 200. 193 . 196. 215. 181. 216 . 205 . 190 . 176. 199 . 218 . 181. 198 . 220 . 217 . c DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . . Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-G889.6) TABLE B15 (PAGE 3) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 113 DAYS RAT # 1- 8 8- 15 15- 22 DOSAGE GROUP III 22- 29 29- 36 36- 43 3 MG/KG/DAY 43- 50 50- 57 57- 64 64- 70a 85b-92 92- 99 99-106 13661 13662 1Jbb J 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 158. 178 . 162. 178. 169. 174 . 167. 172 . 152. 178. 168. 151. 165. 161. 167. 174. 164. 166. 166. 162 . 154 . 166. 165. 180. 161. 170. 169. 184. 159. 176. 179. 191. 176. 184 . 197. 177. 191. 197 . 208. 222. 185. 167. 175. 190. 195. c c 192. 162 . 184 . 169. 184 . 155. 172 . 155. 179. 176. 204 . 168. 193. 186. 203. 191. 220. 215. 196. 203. 204. 173. 237. 207. 183. 193. 198. 202. 184. 177. 200. 201. 200. 192. 210. 194. 199. 188. 193. 214 . 200. 200. 234. 189. 201. 193 . 239. 199. 174 . 209. 176. 172 . 239. 189. 193 . 192. 173. 208. 172. 207. 218 . 207. 209. 190. 215. 192. 191. 193 . 168. 201. 200. 190 . 227. 191. 205. 190. c 196. 181. 205. 183 . 160. 228. 179. 197. 199. 168. 207 . 161. 203 . 221. 209. c 201. 212 . 195. 196. 196. 176. 203 . 201. 200. 244 . 193. 209. 201. 215. 201. 194 . 212. 195. 188. 227. 186. 160. 198. 170. 203 . 158. 190 . 218. 220. 208 . 197. 215. 184 . 179. 191. 188 . 202. 206. 200. 251. 200. 201. 205. 215. 202. 190. 211. 204 . 190. 229. 190. 168. 195. 172. 214. 166. 191. 212 . c 191. 195. 217 . 178. 179. 188 . 203 . 199. 212. 203 . 259. 193. 213 . 205. 221. 210. 183 . 206. 207. 194 . 242. 201. 181. 208. 176. 218 . 159. 199. 221. 231. 205 . 202. 216. 189. 187. 196. 210. 207. 227. 204 . 261. 191. 223 . 212 . 221. 221. 181. 128 . 219. 195. 232. 205. 199. 206. 186. 226. 164 . 205. 215. 212. 228 . 198. 221. 192 . 191. 199. 209. 208 . 216. 203 . 274 . 168. 179. 173 . 198. 176. 151. 165. 172 . 203. 186. 138. c c c 130. 156. 202 . c 176. 157. 226. 181. 160. 153 . 164. 186. 174 . 186 . 180. 237. 209. 224. 216. 218. 213 . 174 . 180. 212. 187. 236. 197. 186. 206 . 185. 238. 167. 200. 229. 204. 214 . 201. 241. 208 . 196. 199. 204 . 204 . 225 . 209. 268. 200. 208 . 211. 207 . 197 . 176. 179. 209. 185. 228. 190. 178. 205. 181. 222. 162. 206. 216. 197. 218. 192 . 256. 201. 197 . 180 . 205. 211. 213 . 214 . 274 . 202 . 210 . 194 . 219. 187. 185 . 203 . 202 . 191. 216. 193 . 178 . 200 . 188. 212. 162 . 204 . 219. c c 195. c 195 . 185. 181. 202 . 210 . 216. 209. 267 . DAYS - DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B15 (PAGE 4) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 114 DAYS RAT # 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 50- 57 57- 64 64- 70a 85b-92 92- 99 99-106 DOSAGE GROUP IV 10 MG/KG/DAY 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 152. 155. 171. 167. 176. 174 . 156. 163. 162. 181. 163. 157. 147. 156. 166. 165. 157. 169. 165. 172 . 141. 144 . 164. 150. 174. 143. 150. 161. 157. 183 . 183 . 168 . 208. 199. 191. 189. 172. 144 . 162 . 187. 177. 176. 176. 174. 196. 195. 186. 185. 191. 180. 156. 144 . 169. 174 . 204 . 190. 184 . 183 . 173 . 182 . 200. 199. 234 . 210 . 214 . 230. 173 . 191. 194. 235. 219. 197. 185. 221. 229. 195. 208 . 222 . 178 . 171. 183 . 151. 179. 177. 202. 201. 190 . 219 . 215. 241. 200. 183 . 233 . 210 . 219. 207. 172 . 188. 182. 230. 195. 194. 179. 230. 225. 188. 225. 234 . 176. 165. 169. 162. 179. c 204 . 190 . 185. 218 . 207. 233 . 181. 186 . 235. 207. 230. 223 . 167. 189. 178. 241. 198. 190. 176. 229. 218. 188 . 226. 222 . 180. 178. 178. 160. 178. 171. 205. 191. 181. 210. 205 . 238 . 217 . 194 . 228 . 201. 235. 232. 174. 196. 183 . 243 . 197. 194 . 161. 221. 223 . 198 . 215. 209. 185. 179 . 170. 161. 157. 172. 207. 193. 185 . 217. 210 . 235. 209. 195 . c 229. c 238. 177. 194. 184. 233. 199. 194. 189. 218. 221. 204. 210. 217. 187. 173 . 198. 211. 204 . 173 . 202 . 168. 135. 204 . 222 . 246 . 200 . 186. 251. 224 . 231. 240. 188 . 197. 180. 243. 198 . 194 . 180. 221. 224 . 201. 214 . 220 . 182 . 176. 190. 159. 202 . 177. 213 . 197 . 177 . 211. 200 . 24 8 . 209. 192. 237. 229. 248 . 230. 191. 197. 183. 245. 198. 201. 179. 224. 221. 209. 222 . 207. 211. 176. 181. 148 . 199. 175. 219. 203 . 178 . 213 . 218. 258 . 178. 153. 207. 192. 204 . 193. 155. 167. 172. 119. 190. 148. 192 . 183. 184 . 172. 184 . 177. c 151. 153 . 137. 158. 145. 177. 161. 158. 175. 182 . 195 . 223 . 197. 245. 216. 256. 249. 177. 195. 187. 242. 191. 193. 139. 237 . 220 . 215. 218 . 224 . 195. 179. 185. 161. 195. 179. 215. 211. 186. 217 . 217. 243 . 214 . 194 . 229. 203 . 233 . 245. 172 . 184 . 175. 223 . 164. 192. 187. 239. 222 . 209. 227 . 227. 189. 165. 175 . 157 . 188. 186. 160. 217. 195 . 237. 223 . 243 . 216 . 190 . 220. 203. 219. 231. 181. 191. 182 . 227 . 176. 196. 177 . 245. 225. 203 . 215. 208. 175. 170 . 173 . 130. 190 . 165. c 210 . 191. 163 . 217 . 241. DAYS DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B15 (PAGE 5) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 115 DAYS ^ 18 15- 22 22- 29 29- 36 36- 43 43- 50 50- 57 57- 64 64- 70a 85b-92 92- 99 99-106 RAT # DOSAGE GROUP V 30 MG/KG/DAY 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732 13733 13734 13735 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 144. 137. 132. 184. 150. 162. 156. 152. 156. 153. 154. 74 . 108. 159. 116. 140. 124. 145. 130. 123 . c 135 . 100. 105. 162. 148 . 140 . 106 . 133 . 140 . 176. 174. 170. 190. 204 . 213 . 211. 186. 186. 186. 178. 184. 151. 164 . 157. 154 . 133 . 184 . 174 . 169. 194 . 172 . 158. 173. 179 . 177. 182. 163. 167. 172 . 189. 214 . 146. 232. 214. 217. 208. 200. 204. 228. 174. 59. 202. 214. 169. 181. 165. 169. 185. 203. 180. 189. 175. 191. 182. 152. 175. 217. 181. 202 . 183 . 176. 157. 205. 178. 189. 182. 193 . 195. 228. 175. 208. 205. 192. 157. 171. 165. 177. 163 . 184 . 155. 177. 182 . 169. 166. 190. 151. 208 . 170. 208. 189. 179. 146. 182. 160. 179. 176. 185. 196. 223. 165. 191. 200. 174. 169. 161. 145. 176. 172 . 191. 165. 171. 177. 169. 189. 180. 154. 209. 163. 210. 195. 188. 158. 194. 173. 210. 170. 182. 191. 221. 175. 19. 207. 167. 173 . 155. 147 . 181. 181. 199. 186. 169. 170. 176. 184. 182 . 166. 218. 158. 209. 191. 200 . 203 . 154. 206. 186. 168. 170. 162. 197. 156. 156. 149. 105. 145. 220 . 228. 219. 168 . 211. 171. 165. 165. 156. 185. 217. 203. 205. 174 . 233. 178. 189. 202 . 170. 193 . 195. 200. 194. 160. 201. 194. 208. 208. 162. 197 . 205. 219. 240. 166. 223 . 182. 180. 170. 154. 190. MORIBUND SACRIFICED ON DAY 45 OF STUDY 201. 206. 212. 188. 209. 189. 189. 191. 157. 169. 187. 184 . 190 . 148. 183 . 167. 171. 175. 147. 185. 147. 149. 159. 129. 183 . 177. 183 . 180. 150. 190. 169. 182. 172. 136 . 160. 202 . 205. 206. 172 . 215 . 175. 174 . 166. 139. 23 . 172 . 173 . 168. 146. 177. 184. 182 . 182 . 147. 197. 186 . 185. 197. 143. 176 . 182. 198 . 182 . 155. 177 . 183 . 181. 185. 155. 175. 166 . 159. 161. 129. 156. C 220 . 245. 200. 221. 159. 164 . 166. 138. 176. 200 . 213 . 233 . 181. 199. 201. 179. 146. 207 . 175. 217. 181. 187. 200. 224. 193. 190. 188. 181. 163. 171. 172. 166 . 210 . 198. 172 . 160. 184. 195. 182. 162. 235. 163 . 207. 192 180 205 111 168 206 190 187 201 203 178 166 190 175 166 162 180 154 201 225 170 168 175 178 179 148 204 163 209 DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B16 (PAGE 1) : MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 116 DOSAGE GROUP I 0 MG/KG/DAY RAT # 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630a DAYS IN COHABITATION 3 2 4 1 1 3 1 14 2 1 4 4 3 4 8 3 3 2 2 4 4 4 4 4 1 4 i i 4 - MATING ! M M M M M M M M M M M M M M M M M M M M M M M M M M M M M _ MATING DATE C C c C c c c c c c c c c c c c c c c c c c c c c c c c c FEMALE PREGNANCY STATUS P (13801) P (13802) P (13803) P (13805) P (13806) P (13807) P (13808) P (13809) P (13810) N P (13811) P (13812) P (13813) P (13814) P (13815) P (13816) P (13817) P (13818) P (13 819) P (13820) P (13821) P (13822) P (13823) P (13824) P (13825) P (13826) P (13827) P (13828) P (13829) P (13 830) M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P - PREGNANT NP = NOT PREGNANT a. Rat 13630 was not assigned to cohabitation because there were no available female rats. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B16 (PAGE 2) : MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 117 DOSAGE GROUP II 1 MG/KG/DAY RAT # 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660a DAYS IN COHABITATION 3 4 2 2 2 1 1 2 1 1 1 4 1 1 1 1 4 3 1 1 1 1 1 1 1 4 1 3 4 - MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M - MATING DATE C C C C C C C C C C C C C C C C C C C C C C C C C C C c c - FEMALE PREGNANCY STATUS P (13831) P (13832) P (13833) P (13834) P (13835) P (13837) P (13838) P (1383 9) N P (13840) P (13841) P(13842) P (13843) P (13844) P (13845) P (13846) P (13847) P (13848) P (13849) P (13850) N P (13851) P (13852) P (13 853) P (13 854) P (13 855) P (13 856) P (13857) P (13858) P (13859) P (13860) M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P > PREGNANT NP = NOT PREGNANT a. Rat 13660 was not assigned to cohabitation because there were no available female rats. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B16 (PAGE 3) : MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 118 DOSAGE GROUP III 3 MG/KG/DAY RAT # DAYS IN COHABITATION 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 1 14 2 5 1 2 4 4 4 1 2 4 8 2 1 1 3 1 1 1 1 3 1 4 i i 4 1 1 4 M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P - PREGNANT NP = NOT PREGNANT MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M MATING DATE C NC C C C C C C C C C C C C C C C C C C C C C C C C C c c c FEMALE PREGNANCY STATUS P (138S1) P (13862) P (13 863) P (13864) P (13865) P (13866) P (13867) P (13868) P (13869) P (13870) P (13871) P (13872) P (13873) P (13874) P (13875) P (13876) P (13877) P (13878) P (13879) P (13880) P (13881) P (13882) P (13 883) P (13884) P (13885) P (13886) P (13 887) P (13888) P (13889) P (13890) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B16 (PAGE 4) : MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 119 DOSAGE GROUP IV 10 MG/KG/DAY RAT # DAYS IN COHABITATION MATING STATUS 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 4 4 1 2 2 2 4 1 3 14 4 2 3 3 4 14 2 1 4 2 1 2 3 3 4 3 14 4 3 3 M M M M M' M M M M DID NOT MATE M M M M M M M M M M M M M M M M M M M M M - MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P PREGNANT NP * NOT PREGNANT MATING DATE C C C C C C C C C_ C c c c c NC C C C C C c c c c c NC C C C FEMALE PREGNANCY STATUS P (13891) P (13892) P (13893) P (13894) P(13895) P (13896) P (13897) P (13898) P (13899) -(13900) P (13 901) P (13 902) P (13903) P (13904) P (13 905) P (13 906) P(13907) P (13908) P (13 909) P (13910) P (13 911) P (13912) P (13913) P (13 914) P (13 915) P (13916) P (13917) P (13918) P (13919) P (13920) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B16 (PAGE 5) : MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 120 DOSAGE GROUP V 30 MG/KG/DAY RAT # 13721 13722 13723a 13723b 13724 13725 13726 13727 13728 13729 13730 13731 13732 13733 13734 13735 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 DAYS IN COHABITATION MATING STATUS MATING DATE 2M 2M 1M 3M 1M 4M 2M 2M 1M 3M 2M 4M MORIBUND SACRIFICED ON DAY 45 OF STUDY 3M 4M 14 M 2M 4M 3M 2M 2M 5M 1M 1M 1M 2M 6M 4M 1M 4M 3M C C C C C C C C C C C C C C NC C C c c c c c c c c c c c c c FEMALE PREGNANCY STATUS P (13 921) P (13922) P (13923) P (13950) P (13924) P (13925) P (13926) P (13927) P (13928) N P (13929) P (13930) P(13931) P (13 932) P (13 933) P (13934) P(13935) P (13936) P (13 937) P (13 938) P (13939) P (13940) P (13941) P (13942) P (13 943) P (13 944) P (13 94 5) P (13 946) P (13 947) P (13948) P (13949) . M * MATED ( ) = FEMALE RAT NUMBER C - CONFIRMED NC NOT CONFIRMED P = PREGNANT NP = NOT PREGNANT a. Result of first cohabitation period. b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B17 (PAGE 1) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 121 DOSAGE GROUP DOSAGE (MG/KG/DAY) I 0 RAT NUMBER 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 DAY OF NECROPSY DOSAGES ADMINISTERED OBSERVATIONS a DS 106 DS 106 DS 106 DS 106 DS 106 DS 106 DS 107 DS 107 DS 107 DS 107 DS 107 DS 107 DS 108 105 105 105 105 105 105 106 106 106 106 106 106 107 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13614 DS 108 107 LUNGS : ALL LOBES, NUMEROUS DARK RED AREAS (PINPOINT TO 2.0 CM X 2.0 C M ) . ALL OTHER TISSUES APPEARED NORMAL. 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 DS 108 DS 108 DS 108 DS 108 DS 109 DS 109 DS 109 DS 109 DS 109 DS 109 DS 110 DS 110 DS 110 DS 110 DS 110 DS 110 107 107 107 107 108 108 108 108 108 108 109 109 109 109 109 109 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS DAY OF STUDY a. Refer to the individual clinical observations table (Table B12) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B17 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 122 DOSAGE GROUP DOSAGE (MG/KG/DAY) II 1 RAT NUMBER 13631 13632 13633 13634 13635 DAY OF NECROPSY DOSAGES ADMINISTERED OBSERVATIONS a DS 106 DS 106 DS 106 DS 106 DS 106 105 105 105 105 105 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13636 DS 106 105 TESTES: RIGHT, SMALL AND FLACCID. EPIDIDYMIDES: RIGHT,, SMALL AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL. 13637 13638 DS 107 DS 107 106 106 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13639 DS 107 106 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 DS 107 DS 107 DS 107 DS 108 DS 108 DS 108 DS 108 DS 108 DS 108 DS 109 DS 109 DS 109 DS 109 DS 109 DS 109 DS 110 DS 110 DS 110 DS 110 DS 110 DS 110 106 106 106 107 107 107 107 107 107 108 108 108 108 108 108 109 109 109 109 109 109 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS = DAY OF STUDY a. Refer to the Individual clinical observations table (Table B12) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B17 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 123 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF NECROPSY DOSAGES ADMINISTERED OBSERVATIONS a III 3 13661 DS 106 105 ALL TISSUES APPEARED NORMAL. 13662 DS 106 105 ALL TISSUES APPEARED NORMAL. 13663 DS 106 105 ALL TISSUES APPEARED NORMAL. 13664 DS 106 105 ALL TISSUES APPEARED NORMAL. 13665 DS 106 105 ALL TISSUES APPEARED NORMAL. 13666 DS 106 105 ALL TISSUES APPEARED NORMAL. 13667 DS 107 106 ALL TISSUES APPEARED NORMAL. 13668 DS 107 106 ALL TISSUES APPEARED NORMAL. 13669 DS 107 106 ALL TISSUES APPEARED NORMAL. 13670 DS 107 106 KIDNEYS: RIGHT, PELVIS, MODERATE DILATION. ALL OTHER TISSUES APPEARED NORMAL. 13671 DS 107 106 ALL TISSUES APPEARED NORMAL. 13672 DS 107 106 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 DS 108 DS 108 DS 108 DS 108 DS 108 DS 108 DS 109 DS 109 DS 109 DS 109 DS 109 DS 109 DS 110 DS 110 DS 110 DS 110 DS 110 DS 110 107 107 107 107 107 107 108 108 108 108 108 108 109 109 109 109 109 109 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. . DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table B12) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B17 (PAGE 4) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 124 DOSAGE GROUP DOSAGE (MG/KG/DAY) IV 10 RAT NUMBER 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 DAY OF NECROPSY DOSAGES ADMINISTERED OBSERVATIONS a DS 106 DS 106 DS 106 DS 106 DS 106 DS 106 DS 107 DS 107 DS 107 DS 107 DS 107 DS 107 DS 108 DS 108 DS 108 105 105 105 105 105 105 106 106 106 106 106 106 107 107 107 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13706 DS 108 107 TESTES: RIGHT, SMALL AND FLACCID. EPIDIDYMIDES: RIGHT, SMALL AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL. 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 DS 108 DS 108 DS 109 DS 109 DS 109 DS 109 DS 109 DS 109 DS 110 DS 110 107 107 108 108 108 108 108 108 109 109 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13717 DS 110 109 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 13718 13719 13720 DS 110 DS 110 DS 110 109 109 109 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table B12) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B17 (PAGE 5) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) V 30 RAT NUMBER 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732 DAY OF NECROPSY DOSAGES ADMINISTERED OBSERVATIONS a DS 106 DS 106 DS 106 DS 106 DS 106 DS 106 DS 107 DS 107 DS 107 DS 107 DS 107 DS 45 105 105 105 105 105 105 106 106 106 106 106 44 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION ALL OTHER TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. MORIBUND SACRIFICED ON DAY 45 OF STUDY. LIVER: ALL LOBES, TAN AND PALE. TESTES: BILATERAL, RED. ALL OTHER TISSUES APPEARED NORMAL. ARGUS 418-020 Page 125 13733 DS 108 107 EPIDIDYMIDES: LEFT, SMALL AND FLACCID. KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 13734 13735 13736 13737 13738 13739 13740 DS 108 DS 108 DS 108 DS 108 DS 108 DS 109 DS 109 107 107 107 107 107 108 108 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS = DAY OF STUDY a. Refer to the Individual clinical observations table (Table B12) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B17 (PAGE 6) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF NECROPSY DOSAGES ADMINISTERED OBSERVATIONS a V 30 (Cont.) 13741 DS 109 108 TESTES: BILATERAL, SMALL AND FLACCID. EPIDIDYMIDES: BILATERAL, SMALL AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL. 13742 13743 13744 13745 13746 13747 13748 13749 DS 109 DS 109 DS 109 DS 110 DS 110 DS 110 DS 110 DS 110 108 108 108 109 109 109 109 109 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13750 DS 110 109 TESTES: LEFT, LARGE. ALL OTHER TISSUES APPEARED NORMAL. DS DAY OF STUDY a. Refer to the individual clinical observations table (Table B12) for external observations confirmed at necropsy. ARGUS 418-020 Page 126 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT . INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 127 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP I EPIDIDYMIS LEFT ABS. REL. W T . % TBW CAUDA EPIDIDYMIS LEFT ABS. REL. W T . % TBW 0 MG /KG/DAY TESTIS LEFT ABS. REL. WT. % TBW L . TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. WT. * TBW SEMINAL VESICLES WITHOUT FLUID A B S . REL. WT. % TBW 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 592. 610. 570. 633. 533 . 653. 543. 567. 609. 569. 634 . 557. 559. 536. 586. 639. 513 . 556. 571. 566. 527 . 559. 588. 527. 578 . 656. 568 . 635. 558. 628 . 0.6756 0.6786 0.7340 0.7152 0.7034 0.7420 0.6822 0.7947 0.5497 0.6732 0.6526 0.6830 0.6764 0.6695 0.7240 0.7570 0.7783 0.7269 0.7967 0.7542 0.6623 0.7321 0.7364 0.7481 0.7424 0.8408 0.7204 0.7515 0.6810 0.8494 0.11 0.11 0.13 0.11 0.13 0.11 0.12 0.14 0.09 0.12 0.10 0.12 0.12 0.12 0.12 0.12 0.15 0.13 0.14 0.13 0.12 0.13 0.12 0.14 0.13 0.13 0.13 0.12 0.12 0.14 0.2966 0.3086 0.3341 0.3136 0.3543 0.3611 0.3203 0.3453 0.2145 0.2883 0.3271 0.2887 0.3010 0.2733 0.3652 0.3567 0.3479 0.3458 0.3973 0.3459 0.3287 0.3161 0.3896 0.3361 0.2999 0.3786 0.3192 0.3760 0.3307 0.3993 0.05 0.05 0.06 0.05 0.07 0.06 0.06 0.06 0.04 0.05 0.05 0.05 0.05 0.05 0.06 0.06 0.07 0.06 0.07 0.06 0.06 0.06 0.07 0.06 0.05 0.06 0.06 0.06 0.06 0.06 1.5259 1.6647 1.7979 1.9262 1.8636 1.8832 1.8506 1.8574 1.6417 1.5787 1.7823 1.7653 1.7861 1.5910 1.9534 1.9754 1.7610 1.8719 1.9766 1.8314 1.6391 1.7766 1.6860 1.8174 1.7695 1.9527 1.6706 1.8851 1.6630 2.1140 0.26 0.27 0.32 0.30 0.35 0.29 0.34 0.33 0.27 0.28 0.28 0.32 0.32 0.30 0.33 0.31 0.34 0.34 0.35 0.32 0.31 0.32 0.29 0.34 0.31 0.30 0.29 0.30 0.30 0.34 1.2920 1.5221 1.6608 1.7009 1.7079 1.7583 1.7435 1.7354 1.4397 1.4846 1.6617 1.6275 1.6113 1.4794 1.8326 1.8243 1.6507 1.7273 1.8446 1.7046 1.5212 1.6795 1.5789 1.6876 1.6738 1.8342 1.5585 1.7864 1.5519 1.9567 0.22 0.25 0.29 0.27 0.32 0.27 0.32 0.31 0.24 0.26 0.26 0.29 0.29 0.28 0.31 0.28 0.32 0.31 0.32 0.30 0.29 0.30 0.27 0.32 0.29 0.28 0.27 0.28 0.28 0.31 1.3897 2.2138 2.2003 1.6708 2.1486 1.7423a 2.1930 2.1517 2.6536 2.7678 2.1404 2.4939 1.9469 2.2970 2.5074 2.5305 2.1888 2.3224 2.6549 2.1074 2.4345 2.2753 2.0262 1.8379 2.9931 2.6403 2.44 98 2.6437 2.3510 2.0128 0.23 0.36 0.39 0.26 0.40 0.27a 0.40 0.38 0.44 0.49 0.34 0.45 0.35 0.43 0.43 0.40 0.43 0.42 0.46 0.37 0.46 0.41 0.34 0.35 0.52 0.40 0.43 0.42 0.42 0.32 0.9914 1.2279 1.3738 1.1445 1.1320 1.2432 1.0702 1.2132 1.4047 1.3165 1.1786 1.3161 1.3192 1.0604 1.4403 1.3395 1.2973 1.3218 1.5503 1.0458 1.3000 1.2186 1.1769 0.9276 1.3586 1.4879 1.3752 1.5575 1.3665 1.3021 0.17 0.20 0.24 0.18 0.21 0.19 0.20 0.21 0.23 0.23 0.18 0.24 0.24 0.20 0.24 0.21 0.25 0.24 0.27 0.18 0.25 0.22 0.20 0.18 0.24 0.23 0.24 0.24 0.24 0.21 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Damaged during processing (some fluid loss prior to weighing); values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 2) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 128 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP I EPIDIDYMIS RIGHT ABS. REL. WT. % TBW TESTIS RIGHT ABS. REL. WT. % TBW 0 MG/KG/DAY PROSTATE ABS. WT. REL. % TBW PITUITARY ABS. WT. REL. TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. REL. W T . % TBW 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 592. 610. 570. 633 . 533 . 653. 543. 567. 609. 569. 634. 557. 559. 536. 586. 639. 513 . 556. 571. 566. 527. 559. 588. 527. 578. 656. 568. 635. 558. 628. 0.6727 0.6538 0.7422 0.7242 0.7013 0.7714 0.6884 0.7813 0.6624 0.6645 0.6452 0.7042 0.6920 0.6590 0.7307 0.7448 0.8023 0.6947 0.8216 0.6324 0.6737 0.6907 0.7404 0.7047 0.7624 0.8685 0.7318 0.7165 0.6744 0.8078 0.11 0.11 0.13 0.11 0.13 0.12 0.13 0.14 0.11 0.12 0.10 0.13 0.12 0.12 0.12 0.12 0.16 0.12 0.14 0.11 0.13 0.12 0.12 0.13 0.13 0.13 0.13 0.11 0.12 0.13 1.5705 1.5701 1.8434 1.8830 1.8294 1.9176 1.8831 1.9010 2.3432 1.5825 1.8363 1.8260 1.8150 1.5240 1.9427 1.9684 1.7778 1.7963 2.0150 1.7662 1.7174 1.6943 1.7379 1.8086 1.7619 1.9505 1.6434 1.8347 1.6857 2.0934 0.26 0.26 0.32 0.30 0.34 0.29 0.35 0.34 0.38 0.28 0.29 0.33 0.32 0.28 0.33 0.31 0.35 0.32 0.35 0.31 0.32 0.30 0.30 0.34 0.30 0.30 0.29 0.29 0.30 0.33 0.9769 1.0477 1.1461 1.2982 0.8545 1.2630 1.4560 1.3797 1.2521 1.1033 1.1326 1.0173 1.2060 1.2564 1.0383 0.9796 1.0554 1.0403 1.1757 1.3352 1.1837 1.2359 1.2678 0.9132 1.1731 1.6005 1.1031 0.8151 1.0534 0.7730 0.16 0.17 0.20 0.20 0.16 0.19 0.27 0.24 0.20 0.19 0.18 0.18 0.22 0.23 0.18 0.15 0.20 0.19 0.20 0.24 0.22 0.22 0.22 0.17 0.20 0.24 0.19 0.13 0.19 0.12 0.016 0.014 0.012 0.016 0.014 0.009 0.014 0.015 0.029 0.017 0.018 0.012 0.013 0.016 0.012 0.015 0.013 0.008 0.016 0.014 0.012 0.009 0.015 0.011 0.014 0.018 0.011 0.012 0.011 0.014 2.70 2.30 2.10 2.53 2.63 1.38 2.58 2.64 4.76 2.99 2.84 2.15 2.32 2.98 2.05 2.35 2.53 1.44 2.80 2.47 2.28 1.61 2.55 2.09 2.42 2.74 1.94 1.89 1.97 2.23 2.36 2.38 2.19 2.40 2.22 2.24 2.35 2.33 2.11 1.86 2.32 2.11 2.51 2.19 2.25 2.52 2.52 2.27 2.33 2.21 2.15 2.22 2.45 1.83 2.25b 2.33 2.172.10 2.10 2.43 0.40 0.39 0.38 0.38 0.42 0.34 0.43 0.41 0.35 0.33 0.36 0.38 0.45 0.41 0.38 0.39 0.49 0.41 0.41 0.39 0.41 0.40 0.42 0.35 0.39 0.36 0.38 0.33 0.38 0.39 23.61 22.78 18.43 20.30 15.86 22.82 18.53 19.26 23.25 22.41 22.68 17.03 21.60 20.68 20.97 25.02 16.93 19.31 21.32 20.80 16.17 18.88 19.31 18.10 19.76 24.67 17.86 22.09 18.41 20.24 3.99 3.73 3.23 3.21 2.98 3.49 3.41 3.40 3.82 3.94 3.58 3.06 3.86 3.86 3.58 3.92 3.30 3.47 3.73 3.67 3.07 3.38 3.28 3.43 3.42 3.76 3.14 3.48 3.30 3.22 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. a. Value was multiplied by 1000. b. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.S) TABLE B18 (PAGE 3) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 129 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP I KIDNEY LEFT A B S . REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW 0 MG/KG/DAY ADRENAL LEFT ABS. REL. WT. t TBW a ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS . R E L . WT. % TBW 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 592. 610. 570. 633. 533. 653. 543. 567. 609. 569. 634. 557. 559. 536. 586. 639. 513 . 556. 571. 566. 527. 559. 588. 527. 578. 656. 568. 635. 558. 628. 2.17 2.55 1.90 2.33 2.26 2.25 2.17 2.12 2.33 2.31 2.47 2.18 2.50 2.53 1.85 2.58 1.92 1.99 2.09 2.02 2.15 2.30 2.10 2.11 1.99 2.28 2.09 2.08 2.03 2.07 0.37 0.42 0.33 0.37 0.42 0.34 0.40 0.37 0.38 0.40 0.39 0.39 0.45 0.47 0.32 0.40 0.37 0.36 0.37 0.36 0.41 0.41 0.36 0.40 0.34 0.35 0.37 0.33 0.36 0.33 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. 2.19 2.55 1.96 2.28 2.25 2.39 2.14 2.15 2.43 2.29 2.38 2.21 2.32 2.31 2.03 2.61 2.05 1.89 2.03 1.99 2.12 2.20 2.30 2.15 2.09 2.34 2.05 2.01 1.99 2.03 0.37 0.42 0.34 0.36 0.42 0.37 0.39 0.38 0.40 0.40 0.38 0.40 0.42 0.43 0.35 0.41 0.40 0.34 0.36 0.35 0.40 0.39 0.39 0.41 0.36 0.36 0.36 0.32 0.36 0.32 0.030 0.032 0.031 0.026 0.029 0.044 0.046 0.031 0.031 0.028 0.035 0.033 0.029 0.028 0.035 0.042 0.032 0.032 0.035 0.028 0.027 0.035 0.033 0.027 0.027 0.034 0.032 0.035 0.029 0.032 5.07 5.24 5.44 4.11 5.44 6.74 8.47 5.47 5.09 4.92 5.52 5.92 5.19 5.22 5.97 6.57 6.24 5.76 6.13 4.95 5.12 6.26 5.61 5.12 4.67 5.18 5.63 5.51 5.20 5.10 0.031 0.035 0.026 0.033 0.028 0.039 0.021 0.033 0.029 0.028 0.038 0.032 0.033 0.027 0.039 0.035 0.031 0.036 0.033 0.029 0.023 0.045 0.031 0.022 0.027 0.036 0.036 0.031 0.033 0.028 5.24 5.74 4.56 5.21 5.25 5.97 3.87 5.82 4.76 4.92 5.99 5.74 5.90 5.04 6.66 5.48 6.04 6.47 5.78 5.12 4.36 8.05 5.27 4.17 4.67 5.49 6.34 4.88 5.91 4.46 0.75 0.96 0.69 1.11 1.00 1.20 0.83 0.90 1.04 0.76 0.94 0.79 0.98 0.98 1.01 1.26 1.12 0.80 0.93 1.32 0.85 0.68 0.80 0.87 0.87 0.96 0.94 1.07 0.68 0.97 0.13 0.16 0.12 0.18 0.19 0.18 0.15 0.16 0.17 0.13 0.15 0.14 0.18 0.18 0.17 0.20 0.22 0.14 0.16 0.23 0.16 0.12 0.14 0.16 0.15 0.15 0.16 0.17 0.12 0.15 0.38 0.63 0.38 0.69 0.45 0.55 0.41 0.52 0.42 0.32 0.29 0.34 0.49 0.49 0.40 0.41 0.50 0.32 0.39 0.52 0.40 0.44 0.33 0.57 0.31 0.49 0.42 0.50 0.26 0.46 0.06 0.10 0.07 0.11 0.08 0.08 0.08 0.09 0.07 0.06 0.04 0.06 0.09 0.09 0.07 0.06 0.10 0.06 0.07 0.09 0.08 0.08 0.06 0.11 0.05 0.07 0.07 0.08 0.05 0.07 ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/ TERM INAL BODY WEIGHT) X 100. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 4) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 130 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP II EPIDIDYMIS LEFT ABS. REL. W T . t TBW CAUDA EPIDIDYMIS LEFT ABS. REL. W T . % TBW 1 MG/KG/DAY TESTIS LEFT ABS. REL. WT. % TBW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. W T . % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % TBW 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 548. 558. 502. 607. 526. 587. 645. 624. 579. 623. 548. 572. 603 . 592. 567. 549. 577. 623 . 528. 584. 597. 569. 520. 589. 647. 517. 475. 576. 531. 697. 0.6495 0.7034 0.7044 0.7068 0.6053 0.7697 0.7061 0.6470 0.7020 0.7283 0.7490 0.7241 0.7330 0.7089 0.6784 0.6822 0.6658 0.6317 0.6941 0.7437 0.7134 0.7191 0.6303 0.6840 0.8054 0.7198 0.6277 0.6425 0.7407 0.7581 0.12 0.13 0.14 0.12 0.12 0.13 0.11 0.10 0.12 0.12 0.14 0.13 0.12 0.12 0.12 0.12 0.12 0.10 0.13 0.13 0.12 0.13 0.12 0.12 0.12 0.14 0.13 0.11 0.14 0.11 ALL WEIGHTS WERE RECORDED IN GRAMS (G) 0.2998 0.3166 0.3546 0.3369 0.2813 0.3525 0.3434 0.2792 0.2951 0.3536 0.3527 0.3150 0.3398 0.3200 0.3183 0.3463 0.2982 0.3064 0.3058 0.2876 0.3282 0.3231 0.2784 0.2935 0.3335 0.3468 0.3055 0.2637 0.3172 0.3225 0.05 0.06 0.07 0.06 0.05 0.06 0.05 0.04 0.05 0.06 0.06 0.06 0.06 0.05 0.06 0.06 0.05 0.05 0.06 0.05 0.05 0.06 0.05 0.05 0.05 0.07 0.06 0.04 0.06 0.05 1.6770 1.9768 1.7819 1.8226 1.6595 1.8739 1.6545 1.9344 2.0283 1.8745 1.8714 1.7279 1.9500 1.9383 1.6234 1.6999 1.7814 1.8391 1.7156 1.9510 1.9750 1.7946 1.8551 1.5110 2.1552 1.7050 1.7519 1.5617 1.9318 1.6871 0.31 0.35 0.35 0.30 0.32 0.32 0.26 0.31 0.35 0.30 0.34 0.30 0.32 0.33 0.29 0.31 0.31 0.30 0.32 0.33 0.33 0.32 0.36 0.26 0.33 0.33 0.37 0.27 0.36 0.24 1.5445 1.8290 1.6458 1.6586 1.5483 1.6712 1.5240 1.8105 1.8573 1.7670 1.7242 1.6227 1.8364 1.8199 1.5062 1.5800 1.6328 1.7159 1.6256 1.8355 1.8339 1.6913 1.6992 1.4044 1.9836 1.6041 1.6518 1.4618 1.8052 1.5755 0.28 0.33 0.33 0.27 0.29 0.28 0.24 0.29 0.32 0.28 0.31 0.28 0.30 0.31 0.26 0.29 0.28 0.28 0.31 0.31 0.31 0.30 0.33 0.24 0.31 0.31 0.35 0.25 0.34 0.23 2.4075 2.8763 3.2227 1.6848 1.4917 2.3337 2.5335 2.3501 2.3202 2.6251 2.3899 2.4003 2.5036 2.1300 2.4119 2.0676 2.6220 2.1504 2.2035 2.4213 2.5200 2.4900 1.6932 2.3628 2.8403 2.2805 2.1178 2.1529 2.1495 2.2241 0.44 0.52 0.64 0.28 0.28 0.40 0.39 0.38 0.40 0.42 0.44 0.42 0.42 0.36 0.42 0.38 0.45 0.34 0.42 0.41 0.42 0.44 0.32 0.40 0.44 0.44 0.44 0.37 0.40 0.32 1.5081 1.4047 1.5709 1.1637 0.8167 1.2939 1.3047 1.1924 1.0796 1.3840 1.2356 1.2870 1.2468 1.2740 1.2195 1.1076 1.4890 1.1768 1.1379 1.4614 1.4917 1.2234 1.0140 1.1243 1.4880 1.2083 1.0602 1.1517 1.2183 1.2827 0.28 0.25 0.31 0.19 0.16 0.22 0.20 0.19 0.19 0.22 0.22 0.22 0.21 0.22 0.22 0.20 0.26 0.19 0.22 0.25 0.25 0.22 0.20 0.19 0.23 0.23 0.22 0.20 0.23 0.18 ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE B18 (PAGE 5) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 131 RAT TERMINAL BODY NUMBER WEIGHT _________ ........ DOSAGE GROUP II EPIDIDYMIS RIGHT ABS. REL. WT. * TBW 1 MG/KG/DAY TESTIS RIGHT ABS. REL. WT. % TBW PROSTATE ABS. WT. REL. % TBW PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW 13631 1Jb 32 163J 13634 13635 lib36 13637 13 63 13639 13640 13641 13642 13 643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 548. 558. 502. 607. 526. 587. 645. 624 . 579. 623 . 548. 572 . 603 . 592. 567. 549. 577. 623 . 528. 584 . 597. 569. 520. 589. 647. 517. 475. 576. 531. 697. 0.6184 0.7187 0.7346 0.7092 0.6527 0.3677b 0.7132 0.6219 0.6966 0.6905 0.7322 0.7423 0.7523 0.7081 0.6380 0.6909 0.6756 0.6579 0.6966 0.7426 0.7281 0.7464 0.6316 0.6388 0.7879 0.7250 0.6460 0.6287 0.7940 0.7865 0.11 0.13 0.15 0.12 0.12 0.06 0.11 0.10 0.12 0.11 0.13 0.13 0.12 0.12 0.11 0.12 0.12 0.10 0.13 0.13 0.12 0.13 0.12 0.11 0.12 0.14 0.14 0.11 0.15 0.11 1.6665 2.0272 1.8301 1.8432 1.7937 0.8983b 1.6779 1.9129 2.0712 1.9493 1.8401 1.7467 2.5181 1.8376 1.5823 1.7069 2.6503 1.9075 1.6978 2.0238 1.9809 1.8349 1.7942 1.5501 2.1403 1.7659 1.7433 1.5591 2.0007 1.6440 0.30 0.36 0.36 0.30 0.34 0.15 0.26 0.31 0.36 0.31 0.34 0.30 0.42 0.31 0.28 0.31 0.46 0.31 0.32 0.35 0.33 0.32 0.34 0.26 0.33 0.34 0.37 0.27 0.38 0.24 1.2524 1.3965 1.1854 0.9863 1.1001 1.2274 1.1159 1.3568 1.0950 0.9987 0.9751 1.2793 1.1153 1.1768 1.0379 1.4184 0.6843 1.0489 1.4685 1.1363 0.8039 0.9861 1.1095 1.2735 0.9730 1.6851 1.1798 0.8826 1.1305 1.1982 0.23 0.25 0.24 0.16 0.21 0.21 0.17 0.22 0.19 0.16 0.18 0.22 0.18 0.20 0.18 0.26 0.12 0.17 0.28 0.19 0.13 0.17 0.21 0.22 0.15 0.32 0.25 0.15 0.21 0.17 0.016 0.015 0.020 0.015 0.010 0.012 0.016 0.017 0.008 0.017 0.015 0.012 0.016 0.009 0.019 0.012 0.013 0.011 0.015 0.012 0.013 0.016 0.010 0.015 0.014 0.014 0.013 0.016 0.013 0.014 2.92 2.69 3.98 2.47 1.90 2.04 2.48 2.72 1.38 2.73 2.74 2.10 2.65 1.52 3.35 2.18 2.25 1.76 2.84 2.05 2.18 2.81 1.92 2.55 2.16 2.71 2.74 2 .8 2.45 2.01 2.22 2.34 2.43 2.13 2.07 2.17 2.26 2.43 2.42 2.20 2.26 2.34 2.21 2.44 2.25 2.31 2.25 2.33 2.35 2.32 2.38 2.26 2.37 2.23 2.33 2.31 2.102.31 2.17c 2.28 0.40 0.42 0.48 0.35 0.39 0.37 0.35 0.39 0.42 0.35 0.41 0.41 0.37 0.41 0.40 0.42 0.39 0.37 0.44 0.40 0.40 0.40 0.46 0.38 0.36 0.45 0.44 0.40 0.41 0.33 23.73 26.29 20.13 24.69 23.30 27.55 25.31 26.08 26.73 32.23 25.22 19.48 25.04 24.65 23.13 22.38 25.86 22.58 29.17 22.99 22.73 22.86 17.07 26.32 29.05 19.16 23.90 22.05 21.10 27.36 4.33 A A r>i am A 47 4 69 7 97 4 18 4.67 6 17 4.60 7 40 4 16 4 16 4.08 4 08 4.48 3.62 5.52 3.94 3.81 4.02 3.28 4.47 4.49 3.70 5.03 3.83 3.97 3.92 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was multiplied by 1000. ABS. WT.. = ORGAN WEIGHT. b. Rat 13636 had a small and flaccid right epididymis and right testis. table (Table B16). c. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) See the individual necropsy observations X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 6) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 132 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP II KIDNEY LEFT ABS. REL. WT. % TBW 1 MG/KG/DAY KIDNEY RIGHT ABS. REL. W T . % TBW ADRENAL LEFT ABS. REL. WT. % TBW a ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. REL. WT. % TBW 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 548. 558. 502. 607. 526. 587. 645. 624. 579. 623 . 548. 572. 603 . 592. 567. 549. 577. 623. 528. 584 . 597. 569. 520. 589. 647. 517. 475. 576. 531. 697. 2.49 2.97 2.67 2.79 2.32 2.73 2.29 2.64 2.72 2.74 2.66 2.20 2.84 2.58 2.80 2.68 2.67 2.41 2.55 2.22 2.56 2.55 2.06 2.22 2.87 1.89 2.20 2.20 2.11 2.67 0.45 0.53 0.53 0.46 0.44 0.46 0.36 0.42 0.47 0.44 0.48 0.38 0.47 0.44 0.49 0.49 0.46 0.39 0.48 0.38 0.43 0.45 0.40 0.38 0.44 0.36 0.46 0.38 0.40 0.38 2.48 2.84 2.62 3.00 2.15 2.97 2.36 2.85 2.44b 2.79 2.57 2.15 2.68 2.71 2.77 2.67 2.70 2.56 2.72 2.36 2.80 2.35 2.30 2.20 3.18 1.92 2.17 2.32 2.10 2.63 0.45 0.51 0.52 0.49 0.41 0.50 0.36 0.46 0.42 0.45 0.47 0.38 0.44 0.46 0.49 0.49 0.47 0.41 0.52 0.40 0.47 0.41 0.44 0.37 0.49 0.37 0.46 0.40 0.40 0.38 0.034 0.038 0.032 0.037 0.028 0.029 0.036 0.027 0.036 0.037 0.032 0.032 0.034 0.033 0.038 0.026 0.031 0.027 0.032 0.031 0.029 0.033 0.024 0.040 0.027 0.029 0.029 0.036 0.030 0.031 6.20 6.81 6.37 6.10 5.32 4.94 5.58 4.33 6.22 5.94 5.84 5.59 5.64 5.57 6.70 4.74 5.37 4.33 6.06 5.31 4.86 5.80 4.62 6.79 4.17 5.61 6.10 6.25 5.65 4.45 0.034 0.038 0.031 0.036 0.028 0.030 0.037 0.022 0.029 0.033 0.032 0.031 0.033 0.032 0.036 0.024 0.030 0.026 0.042 0.028 0.025 0.032 0.022 0.041 0.024 0.025 0.032 0.027 0.029 0.030 6.20 6.81 6.18 5.93 5.32 5.11 5.74 3.52 5.01 5.30 5.84 5.42 5.47 5.40 6.35 4.37 5.20 4.17 7.95 4.79 4.19 5.62 4.23 6.96 3.71 4.84 6.74 4.69 5.46 4.30 0.95 0.92 0.68 1.06 0.70 0.94 1.05 0.98 0.90 0.75 1.02 1.08 0.72 0.75 1.02 0.71 0.95 0.81 0.80 1.01 0.93 0.84 0.74 0.89 0.88 0.72 0.86 . 0.70 0.87 1.01 0.17 0.16 0.14 0.17 0.13 0.16 0.16 0.16 0.16 0.12 0.19 0.19 0.12 0.13 0.18 0.13 0.16 0.13 0.15 0.17 0.16 0.15 0.14 0.15 0.14 0.14 0.18 0.12 0.16 0.14 0.39 0.38 0.26 0.50 0.41 0.52 0.47 0.42 0.25 0.29 0.35 0.29 0.45 0.49 0.31 0.32 0.52 0.33 0.44 0.39 0.43 0.30 0.36 0.42 0.36 0.32 0.31 0.43 0.31 0.51 0.07 0.07 0.05 0.08 0.08 0.09 0.07 0.07 0.04 0.05 0.06 0.05 0.07 0.08 0.05 0.06 0.09 0.05 0.08 0.07 0.07 0.05 0.07 0.07 0.06 0.06 0.06 0.07 0.06 0.07 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. A B S . WT. = ORGAN WEIGHT. b. Rat 13639 had slight dilation of the pelvis of the right kidney. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. See the individual necropsy observations table (Table B16 ) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 7) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT ' INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 133 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP III EPIDIDYMIS LEFT ABS. REL. W T . % TBW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % TBW 3 MG/KG/DAY TESTIS LEFT ABS. REL. W T . % TBW L . TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 585 . 539. 567. 511. 511. 481. 550. 453 . 502. 555. 536. 504 . 569. 498 . 563 . 475 . 535 . 628 . 555 . 536. 519. 596. 588. 536. 492. 508. 528. 582. 572. 676. 0.6912 0.6733 0.7359 0.6819 0.6495 0.6823 0.6787 0.5743 0.6734 0.7859 0.6692 0.6250 0.6469 0.6486 0.6728 0.7281 0.6628 0.6807 0.7220 0.7099 0.7653 0.7460 0.7294 0.7152 0.6832 0.6252 0.6735 0.7943 0.6982 0.6794 0.12 0.12 0.13 0.13 0.13 0.14 0.12 0.13 0.13 0.14 0.12 0.12 0.11 0.13 0.12 0.15 0.12 0.11 0.13 0.13 0.15 0.12 0.12 0.13 0.14 0.12 0.13 0.14 0.12 0.10 0.3254 0.3247 0.3684 0.3250 0.3010 0.2923 0.3297 0.2440 0.3213 0.3657 0.2917 0.2759 0.2756 0.2841 0.3345 0.3253 0.3048 0.3119 0.3292 0.3186 0.3366 0.3481 0.2949 0.2938 0.3172 0.2874 0.3194 0.3601 0.3340 0.3048 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.05 0.06 0.06 0.05 0.05 0.05 0.06 0.06 0.07 0.06 0.05 0.06 0.06 0.06 0.06 0.05 0.05 0.06 0.06 0.06 0.06 0.06 0.04 1.9614 1.7494 1.8987 1.8210 1.7079 1.8632 1.6308 1.6210 1.7453 1.8911 1.7697 1.8034 1.6549 1.6521 1.5921 1.9417 1.7046 1.7415 1.7870 1.9063 2.0456 2.0411 1.6796 1.7144 1.8082 1.7667 1.5957 2.0392 1.7096 1.7594 0.34 0.32 0.33 0.36 0.33 0.39 0.30 0.36 0.35 0.34 0.33 0.36 0.29 0.33 0.28 0.41 0.32 0.28 0.32 0.36 0.39 0.34 0.28 0.32 0.37 0.35 0.30 0.35 0.30 0.26 1.7444 1.6186 1.7604 1.7070 1.5898 1.7270 1.5095 1.4979 1.5993 1.7575 1.6395 1.6454 1.5520 1.5435 1.4762 1.8298 1.5908 1.5851 1.6515 1.7722 1.9325 1.9264 1.5543 1.5779 1.6956 1.6740 1.4880 1.9123 1.5964 1.6408 0.30 0.30 0.31 0.33 0.31 0.36 0.27 0.33 0.32 0.32 0.30 0.33 0.27 0.31 0.26 0.38 0.30 0.25 0.30 0.33 0.37 0.32 0.26 0.29 0.34 0.33 0.28 0.33 0.28 0.24 2.8329 1.7487 2.1959 2.3292 2.2164 2.1344 2.1297 1.8561 2.8444 2.8418 2.1255 2.5020 2.3554 2.1533 1.8019 2.3180 2.6193 2.1396 2.7896 2.0806 2.3093 2.5467 2.7770 2.2227 2.6755 2.0154 2.9111 2.2724 2.4406 2.4640 0.48 0.32 0.39 0.46 0.43 0.44 0.39 0.41 0.57 0.51 0.40 0.50 0.41 0.43 0.32 0.49 0.49 0.34 0.50 0.39 0.44 0.43 0.47 0.41 0.54 0.40 0.55 0.39 0.43 0.36 1.4299 0.9591 1.1255 1.2339 1.0909 1.0447 1.2414 1.0709 1.4370 1.4905 1.3067 1.2914 1.2487 1.3208 1.1959 1.3884 1.2994 1.0874 1.5101 1.2158 1.1777 1.3425 1.3745 1.2772 1.5985 1.1092 1.6056 1.2595 1.2353 1.3996 0.24 0.18 0.20 0.24 0.21 0.22 0.22 0.24 0.29 0.27 0.24 0.26 0.22 0.26 0.21 0.29 0.24 0.17 0.27 0.23 0.23 0.22 0.23 0.24 0.32 0.22 0.30 0.22 0.22 0.21 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 8) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 134 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP III EPIDIDYMIS RIGHT ABS. REL. WT. % TBW 3 MG/KG/DAY TESTIS RIGHT ABS. REL. W T . % TBW PROSTATE ABS. WT. REL. % TBW PITUITARY ABS. REL. WT. % TBW a BRAIN ABS. WT. ] % LIVER ABS. REL. W T . % TBW 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 585. 539. 567. 511. 511. 481. 550. 453. 502. S55. 536. 504 . 569. 498 . 563 . 475. 535. 628. 555. 536. 519. 596. 588. 536. 492. 508. 528. 582 . 572. 676. 0.6942 0.6884 0.7462 0.6483 0.6558 0.7041 0.6941 0.5695 0.7484 0.7844 0.6884 0.6282 0.6464 0.6375 0.6921 0.6965 0.6481 0.6848 0.7450 0.6700 0.7726 0.7609 0.7217 0.7096 0.6926 0.6045 0.7076 0.7951 0.6814 0.6736 0.12 0.13 0.13 0.13 0.13 0.15 0.13 0.12 0.15 0.14 0.13 0.12 0.11 0.13 0.12 0.15 0.12 0.11 0.13 0.12 0.15 0.13 0.12 0.13 0.14 0.12 0.13 0.14 0.12 0.10 1.9170 1.7684 1.9026 1.7742 1.7255 1.9202 1.6840 1.6580 1.8785 1.8798 1.7400 1.7492 1.6550 1.7158 1.5912 1.9457 1.7060 1.7331 1.7974 1.9337 2.0453 2.0193 1.6827 1.7016 1.8110 1.7715 1.5732 2.0475 1.6739 1.7440 0.33 0.33 0.34 0.35 0.34 0.40 0.31 0.37 0.37 0.34 0.32 0.35 0.29 0.34 0.28 0.41 0.32 0.28 0.32 0.36 0.39 0.34 0.29 0.32 0.37 0.35 0.30 0.35 0.29 0.26 1.1744 1.0222 0.9513 1.0531 1.0904 1.2313 1.1857 0.8687 1.3318 1.3966 1.0287 1.1247 0.9881 1.1467 0.9485 0.9484 1.4671 1.2232 1.4973 0.8157 0.9378 1.1773 1.2601 1.1324 1.1725 1.0562 1.0888 0.9953 1.2406 0.9884 0.20 0.19 0.17 0.21 0.21 0.26 0.22 0.19 0.26 0.25 0.19 0.22 0.17 0.23 0.17 0.20 0.27 0.19 0.27 0.15 0.18 0.20 0.21 0.21 0.24 0.21 0.21 0.17 0.22 0.15 0.014 0.018 0.008 0.013 0.013 0.010 0.012 0.009 0.013 0.014 0.011 0.011 0.003 0.010 0.014 0.010 0.013 0.011 0.011 0.016 0.010 0.012 0.013 0.009 0.014 0.017 0.013 0.014 0.012 0.016 2.39 3.34 1.41 2.54 2.54 2.08 2.18 1.99 2.59 2.52 2.05 2.18 0.53 2.01 2.49 2.10 2.43 1.75 1.98 2.98 1.93 2.01 2.21 1.68 2.84 3.35 2.46 2.40 2.10 2.37 2.24 2.11 2.32 2.39 2.40 2.00 2.23 2.13 2.34 2.12 2.36 2.22 2.07 2.36 2.22 2.14 2.31 2.35 2.41 2.29 2.42 2.45 2.19 2.20 2.12 2.30 2.34 . 2.08 2.27 2.28 0.38 0.39 0.41 0.47 0.47 0.42 0.40 0.47 0.47 0.38 0.44 0.44 0.36 0.47 0.39 0.45 0.43 0.37 0.43 0.43 0.47 0.41 0.37 0.41 0.43 0.45 0.44 0.36 0.40 0.34 28.39 28.59 26.16 28.39 28.78 24.12 31.05 25.21 29.67 27.92 24.03 26.01 28.10 24.17 28.39 22.77 27.65 26.48 27.01 29.45 29.31 29.50 28.45 22.94 26.28 28.94 29.66 25.96 34 .16 33.85b 4.85 5.30 4.61 5.56 5.63 5.01 5.64 5.56 5.91 5.03 4.48 5.16 4.94 4.85 5.04 4.79 5.17 4.22 4.87 5.49 5.65 4.95 4.84 4.28 5.34 5.70 5.62 4.46 5.97 5.01 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. A B S . WT. = ORGAN WEIGHT. b. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/ TERM INAL BODY WEIGHT) X 100 ` PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 9) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 135 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP III KIDNEY LEFT ABS. REL. W T . % TBW KIDNEY RIGHT ABS. REL. WT. % TBW 3 MG/KG/DAY ADRENAL LEFT ABS. REL. WT. % TBW a ADRENAL RIGHT ABS. REL. WT. TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. WT. REL. % TBW 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 585. 539. 567. 511. 511. 481. 550. 453. 502. 555. 536. 504. 569. 498. 563 . 475. 535. 628 . 555. 536. 519. 596. 588. 536. 492 . 508. 528 . 582. 572. 676. 2.49 2.50 2.20 2.26 2.36 2.29 2.43 2.39 2.60 2.29 2.47 2.42 2.54 2.48 2.49 2.33 2.78 2.44 2.41 2.57 2.69 2.52 2.44 2.33 2.65 2.76 2.45 2.75 2.88 3.19 0.42 0.46 0.39 0.44 0.46 0.48 0.44 0.53 0.52 0.41 0.46 0.48 0.45 0.50 0.44 0.49 0.52 0.39 0.43 0.48 0.52 0.42 0.41 0.43 0.54 0.54 0.46 0.47 0.50 0.47 2.45 2.45 2.34 2.24 2.50 2.41 2.48 2.49 2.50 2.31b 2.20 2.23c 2.60 2.27 2.56 2.37 2.55 2.62 2.67 2.56 2.66 2.62 2.33 2.34 2.58 2.75 2.43 2.55 2.82 3.03 0.42 0.45 0.41 0.44 0.49 0.50 0.45 0.55 0.50 0.42 0.41 0.44 0.46 0.46 0.45 0.50 0.48 0.42 0.48 0.48 0.51 0.44 0.40 0.44 0.52 0.54 0.46 0.44 0.49 0.45 0.038 0.040 0.031 0.033 0.042 0.027 0.026 0.026 0.029 0.023 0.034 0.029 0.021 0.025 0.025 0.034 0.035 0.032 0.042 0.026 0.027 0.023 0.025 0.029 0.021 0.030 0.029 0.031 0.029 0.044 6.50 7.42 5.47 6.46 8.22 5.61 4.73 5.74 5.78 4.14 6.34 5.75 3.69 5.02 4.44 7.16 6.54 5.10 7.57 4.85 5.20 3.86 4.25 5.41 4.27 5.90 5.49 5.33 5.07 6.51 0.044 0.046 0.034 0.032 0.044 0.026 0.021 0.021 0.021 0.021 0.030 0.029 0.022 0.034 0.028 0.032 0.027 0.031 0.034 0.025 0.029 0.024 0.045 0.030 0.019 0.026 0.025 0.031 0.022 0.043 7.52 8.53 6.00 6.26 8.61 5.40 3.82 4.64 4.18 3.78 5.60 5.75 3.87 6.83 4.97 6.74 5.05 4.94 6.13 4.66 5.59 4.03 7.65 5.60 3.86 5.12 4.73 5 .3 3.85 6.36 1.01 0.89 0.82 0.86 0.74 1.11 0.90 0.75 0.90 0.79 0.84 0.73 0.91 0.70 0.88 0.76 0.65 0.79 0.77 1.05 0.97 0.93 0.82 0.85 0.82 0.77 0.91 1.02 1.07 0.96 0.17 0.16 0.14 0.17 0.14 0.23 0.16 0.16 0.18 0.14 0.16 0.14 0.16 0.14 0.16 0.16 0.12 0.12 0.14 0.20 0.19 0.16 0.14 0.16 0.17 0.15 0.17 0.18 0.19 0.14 0.34 0.52 0.45 0.49 0.39 0.44 0.50 0.25 0.42 0.38 0.24 0.36 0.45 0.33 0.53 0.25 0.33 0.35 0.50 0.21 0.30 0.46 0.53 0.40 0.24 0.29 0.27 0.49 0.39 0.43 0.06 0.10 0.08 0.10 0.08 0.09 0.09 0.06 0.08 0.07 0.04 0.07 0.08 0.07 0.09 0.05 0.06 0.06 0.09 0.04 0.06 0.08 0.09 0.07 0.05 0.06 0.05 0.08 0.07 0.06 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. * TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. b. Rat 13670 had moderate dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16). c. Rat 13672 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 10) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 136 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP IV EPIDIDYMIS LEFT ABS. REL. W T . % TBW CAUDA EPIDIDYMIS LEFT ABS. REL. W T . % TBW 10 MG/KG/DAY TESTIS LEFT ABS. REL. WT. % TBW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. W T . % TBW SEMINAL VESICLES WITH FLUID ABS. REL. W T . % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT . % TBW 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 528. 450 . 570. 571. 506. 553 . 480. 533 . 466. 535. 490. 498 . 501. 624 . 551. 526 . 557. 563 . 451. 398. 401. 455 . 493 . 443 . 551. 528 . 489. 543 . 544 . 591. 0.6510 0.7089 0.6386 0.7488 0.6307 0.6652 0.7278 0.7380 0.6450 0.7382 0.6860 0.7634 0.7196 0.7761 0.6684 0.7169 0.7793 0.7390 0.6284 0.6303 0.6687 0.6542 0.6660 0.7452 0.6832 0.7514 0.7523 0.7349 0.7209 0.7415 0.12 0.16 0.11 0.13 0.12 0.12 0.15 0.14 0.14 0.14 0.14 0.15 0.14 0.12 0.12 0.14 0.14 0.13 0.14 0.16 0.17 0.14 0.14 0.17 0.12 0.14 0.15 0.14 0.13 0.12 0.2903 0.3304 0.2740 0.3793 0.2689 0.3142 0.3255 0.3381 0.2780 0.3455 0.2982 0.3364 0.3232 0.3537 0.2734 0.3511 0.3728 0.3343 0.2894 0.2903 0.3095 0.2903 0.3171 0.3291 0.2975 0.3387 0.3543 0.3363 0.3571 0.3476 0.05 0.07 0.05 0.07 0.05 0.06 0.07 0.06 0.06 0.06 0.06 0.07 0.06 0.06 0.05 0.07 0.07 0.06 0.06 0.07 0.08 0.06 0.06 0.07 0.05 0.06 0.07 0.06 0.06 0.06 1.7748 1.8786 1.8515 1.6795 1.6411 1.9205 1.8740 2.0329 1.7274 1.8932 1.7259 1.8769 1.7387 1.8951 1.8277 1.8320 1.6347 1.8899 1.6529 1.8617 1.6931 1.8646 1.7775 1.8785 1.7745 2.0020 1.8418 1.8380 1.8179 1.8847 0.34 0.42 0.32 0.29 0.32 0.35 0.39 0.38 0.37 0.35 0.35 0.38 0.35 0.30 0.33 0.35 0.29 0.34 0.37 0.47 0.42 0.41 0.36 0.42 0.32 0.38 0.38 0.34 0.33 0.32 1.6126 1.7780 1.7107 1.5725 1.5376 1.7789 1.7521 1.9220 1.5993 1.7207 1.5848 1.7673 1.6197 1.7609 1.6738 1.7076 1.5384 1.7878 1.5406 1.7607 1.5997 1.7482 1.6482 1.7562 1.6450 1.8087 1.7492 1.7356 1.6798 1.7681 0.30 0.40 0.30 0.28 0.30 0.32 0.36 0.36 0.34 0.32 0.32 0.35 0.32 0.28 0.30 0.32 0.28 0.32 0.34 0.44 0.40 0.38 0.33 0.40 0.30 0.34 0.36 0.32 0.31 0.30 1.8099 2.3515 1.7267a 2.4684 1.9912 2.0129 2.2800 2.6892 2.2776 2.4079 1.9875 2.3722 2.4935 2.3446 1.4559b 2.3625 2.7172 2.6176 2.5577 2.1083 2.1691 2.0146 2.1117 2.7024 2.2975 2.3873 2.4171 2.3115 2.7956 2.9170 0.34 0.52 0.30a 0.43 0.39 0.36 0.48 0.50 0.49 0.45 0.40 0.48 0.50 0.38 0.26b 0.45 0.49 0.46 0.57 0.53 0.54 0.44 0.43 0.61 0.42 0.45 0.49 0.42 0.51 0.49 1.1447 1.0306 1.0523 1.5301 1.2054 1.1453 1.2851 1.3437 1.2605 1.2589 1.0487 1.3402 1.5376 1.3177 1.0436 1.3581 1.4232 1.4343 1.4163 1.0055 1.1139 1.0707 1.1951 1.3951 1.1581 1.2017 1.3391 1.2358 1.5191 1.5807 0.22 0.23 0.18 0.27 0.24 0.21 0.27 0.25 0.27 0.24 0.21 0.27 0.31 0.21 0.19 0.26 0.26 0.25 0.31 0.25 0.28 0.24 0.24 0.31 0.21 0.23 0.27 0.23 0.28 0.27 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Damaged during processing (some fluid loss prior to weighing); values excluded from group averages and statistical analyses. b. Damaged during processing (weight affected); values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 11) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 137 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP IV EPIDIDYMIS RIGHT ABS. REL. W T . % TBW TESTIS RIGHT ABS. REL. WT. % TBW 10 MG/KG/DAY PROSTATE ABS. WT. REL. % TBW PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. ] % 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 528. 450. 570. 571. 506. 553. 480. 533. 466. 535. 490. 498. 501. 624. 551. 526. 557. 563. 451. 398. 401. 455. 493 . 443 . 551. 528 . 489. 543 . 544 . 591. 0.6462 0.6514 0.4308 0.7073 0.6242 0.6590 0.7200 0.7592 0.6287 0.7246 0.6728 0.7257 0.7072 0.7933 0.6890 0.3207b 0.7579 0.7502 0.6525 0.6630 0.6400 0.6336 0.6594 0.7495 0.6537 0.7396 0.7265 0.7409 0.7150 0.7717 0.12 0.14 0.08 0.12 0.12 0.12 0.15 0.14 0.13 0.14 0.14 0.14 0.14 0.13 0.12 0.06 0.14 0.13 0.14 0.17 0.16 0.14 0.13 0.17 0.12 0.14 0.15 0.14 0.13 0.13 1.6959 1.8472 1.5803 1.5982 1.5583 1.9059 1.8881 2.0050 1.6871 1.9501 1.7611 1.8833 1.7711 1.9822 1.8191 0.8699b 1.6624 1.9331 1.6711 1.8448 1.6398 1.8443 1.7083 1.8709 1.7351 2.0528 1.7853 1.8402 1.7551 1.8332 0.32 0.41 0.28 0.28 0.31 0.34 0.39 0.38 0.36 0.36 0.36 0.38 0.35 0.32 0.33 0.16 0.30 0.34 0.37 0.46 0.41 0.40 0.35 0.42 0.31 0.39 0.36 0.34 0.32 0.31 1.1002 0.6953 0.9426 0.8671 1.1675 1.1603 1.1685 1.2923 1.2763 0.8127 0.9267 0.9056 1.2401 1.4428 1.0972 1.1747 1.2753 0.8310 1.0523 0.7736 0.9264 0.8620 1.1091 1.0910 1.2177 1.0765 1.0506 0.6135 0.7355 1.2191 0.21 0.15 0.16 0.15 0.23 0.21 0.24 0.24 0.27 0.15 0.19 0.18 0.25 0.23 0.20 0.22 0.23 0.15 0.23 0.19 0.23 0.19 0.22 0.25 0.22 0.20 0.21 0.11 0.14 0.21 0.009 0.013 0.014 0.012 0.016 0.019 0.013 0.008 0.015 0.014 0.017 0.012 0.019 0.020 0.010 0.011 0.011 0.015 0.017 0.019 0.012 0.011 0.014 0.011 0.015 0.013 0.018 0.018 0.013 0.009 1.70 2.89 2.46 2.10 3.16 3.44 2.71 1.50 3.22 2.62 3.47 2.41 3.79 3.20 1.81 2.09 1.97 2.66 3.77 4.77 2.99 2.42 2.84 2.48 2.72 2.46 3.68 3.31 2.39 1.52 2.31 2.35 2.09 2.11 2.05 2.25 2.26 2.35 2.28 2.46 2.26 2.05 2.37 2.38 2.32 2.45 2.07 2.13 2.33 2.21 2.16 2.34 2.10 2.17 2.22 2.25 2.43 2.18 2.21 2.15 0.44 0.52 0.37 0.37 0.40 0.41 0.47 0.44 0.49 0.46 0.46 0.41 0.47 0.38 0.42 0.46 0.37 0.38 0.52 0.56 0.54 0.51 0.42 0.49 0.40 0.43 0.50 0.40 0.41 0.36 30.43 27.20 30.49 28.77 30.35 29.83 28.85 27.33 19.75 31.22 22.78 23.84 31.22 36.32 35.62 29.09 29.42 32.27 25.48 24.32 22.43 24.75 31.60 26.03 34.10 28.78 27.61 28.62 32.24 31.49 5.76 6.04 5.35 5.04 6.00 5.39 6.01 5.13 4.24 5.84 4.65 4.79 6.23 5.82 6.46 5.53 5.28 5.73 5.65 6.11 5.59 5.44 6.41 5.88 6.19 5.45 5.65 5.27 5.93 5.33 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. A B S . WT. = ORGAN WEIGHT. b. Rat 13706 had a small and flaccid right epididymis and right testis. table (Table B16). REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100 ' See the individual necropsy observations PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 12) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 138 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP IV KIDNEY LEFT ABS. REL. WT. * TBW KIDNEY RIGHT ABS. REL. WT. % TBW 10 MG/KG/DAY ADRENAL LEFT ABS. REL. WT. % TBW a ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. REL. W T . % TBW 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 528. 450. 570. 571. 506. 553. 480. 533. 466. 535. 490. 498. 501. 624. 551. 526. 557. 563 . 451. 398. 401. 455 . 493. 443 . 551. 528. 489. 543. 544. 591. 2.23 2.42 2.34 2.75 2.29 2.99 2.16 2.61 2.11 2.37 2.03 2.05 2.52 2.61 2.45 2.17 2.50 2.42 2.19 2.08 1.87 2.03 2.18 2.38 2.39 2.49 2.37 2.42 2.31 2.48 0.42 0.54 0.41 0.48 0.45 0.54 0.45 0.49 0.45 0.44 0.41 0.41 0.50 0.42 0.44 0.41 0.45 0.43 0.48 0.52 0.47 0.45 0.44 0.54 0.43 0.47 0.48 0.44 0.42 0.42 2.27 2.31 2.37 3.01 2.34 2.82 2.16 2.63 2.09 2.40 2.01 2.10 2.38 2.64 2.51 2.46 2.47 2.57 2.20 2.17 1.92 2.04 2.15 2.13 2.45 2.60 2.38b 2.33 2.42 2.56 0.43 0.51 0.42 0.53 0.46 0.51 0.45 0.49 0.45 0.45 0.41 0.42 0.48 0.42 0.46 0.47 0.44 0.46 0.49 0.54 0.48 0.45 0.44 0.48 0.44 0.49 0.49 0.43 0.44 0.43 0.018 0.026 0.036 0.025 0.028 0.035 0.032 0.034 0.019 0.030 0.022 0.028 0.043 0.036 0.033 0.031 0.032 0.038 0.031 0.029 0.028 0.030 0.025 0.026 0.035 0.028 0.030 0.037 0.033 0.022 3.41 5.78 6.32 4.38 5.53 6.33 6.67 6.38 4.08 5.61 4.49 5.62 8.58 5.77 5.99 5.89 5.74 6.75 6.87 7.29 6.98 6.59 5.07 5.87 6.35 5.30 6.13 6.81 6.07 3.72 0.043 0.029 0.038 0.037 0.030 0.033 0.033 0.040 0.016 0.030 0.021 0.024 0.034 0.030 0.026 0.026 0.030 0.038 0.019 0.025 0.039 0.033 0.027 0.051 0.033 0.026 0.032 0.033 0.037 0.026 8.14 6.44 6.67 6.48 5.93 5.97 6.88 7.50 3.43 5.61 4.28 4.82 6.79 4.81 4.72 4.94 5.38 6.75 4.21 6.28 9.72 7.25 5.48 11.51 5.99 4.92 6.54 6.08 6.80 4.40 1.01 0.83 0.97 0.81 0.79 1.04 0.90 0.82 0.81 0.99 0.71 0.84 0.95 1.15 0.90 0,79 0.79 0.76 0.74 0.66 0.83 1.11 0.72 0.52 0.98 0.79 0.87 ' 0.93 1.10 1.03 0.19 0.18 0.17 0.14 0.16 0.19 0.19 0.15 0.17 0.18 0.14 0.17 0.19 0.18 0.16 0.15 0.14 0.13 0.16 0.16 0.21 0.24 0.15 0.12 0.18 0.15 0.18 0.17 0.20 0.17 0.61 0.55 0.77 0.50 0.40 0.54 0.50 0.52 0.42 0.44 0.26 0.27 0.31 0.56 0.54 0.38 0.40 0.34 0.28 0.40 0.50 0.36 0.26 0.18 0.29 0.24 0.39 0.25 0.47 0.23 0.12 0.12 0.14 0.09 0.08 0.10 0.10 0.10 0.09 0.08 0.05 0.05 0.06 0.09 0.10 0.07 0.07 0.06 0.06 0.10 0.12 0.08 0.05 0.04 0.05 0.04 0.08 0.05 0.09 0.04 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. b. Rat 13717 had slight dilation of the pelvis of the right kidney. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. See the individual necropsy observations table (Table B1 6 ) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 13): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP V EPIDIDYMIS LEFT ABS. REL. WT. % TBW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % TBW 30 MG/KG/DAY TESTIS LEFT ABS. REL. WT. % TBW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % TBW 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732a 13733 13734 13735 511. 452. 321. 378. 361. 465. 443 . 418. 439. 522. 468. -- 554 . 456. 446. 0.6074 0.6274 0.6173 0.6288 0.5636 0.5924 0.6562 0.6189 0.6563 0.7344 0.6264 0.32 0.4488c 0.6218 0.6602 0.12 0.14 0.19 0.17 0.16 0.13 0.15 0.15 0.15 0.14 0.13 -- 0.08 0.14 0.15 0.2790 0.2822 0.2866 0.2856 0.2434 0.2529 0.3344 0.2708 0.2832 0.3692 0.2816 b 0.2281 0.3056 0.2885 0.05 0.06 0.09 0.08 0.07 0.05 0.08 0.06 0.06 0.07 0.06 -- 0.04 0.07 0.06 1.6557 2.0342 1.7454 1.7350 1.5799 1.6603 1.6767 1.8145 1.8213 1.9206 1.8082 1.57 1.5848 1.7707 1.6260 0.32 0.45 0.54 0.46 0.44 0.36 0.38 0.43 0.41 0.37 0.39 -- 0.29 0.39 0.36 1.5270 1.9065 1.6102 1.6175 1.4784 1.4205 1.5666 1.6036 1.7046 1.7641 1.6879 b 0.7696c 1.6457 1.4871 0.30 0.42 0.50 0.43 0.41 0.30 0.35 0.38 0.39 0.34 0.36 _______ 0.14 0.36 0.33 2.1394 1.9349 1.8187 1.8648 2.0211 2.3913 2.3512 1.6491 2.7535 2.7822 2.2953 0.41 1.9756 1.9533 2.0416 0.42 0.43 0.57 0.49 0.56 0.51 53 39 63 53 49 0.36 0.43 0.46 1.1271 0.9897 .0162 .0530 .1224 .3574 .2199 0.8819 1.6355 1.3529 1.3058 b 1.0945 1.0168 1.0459 22 22 32 28 31 29 0.28 0.21 0.37 0.26 0.28 0.20 0.22 0.23 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN ' a. Rat 13732 was moribund sacrificed on day 45 of study; values excluded from qroup averages X 100. b. Value was not recorded. c . Rat 13733 had a small and flaccid left epididymis and left testis minus tunica albuginea. See the individual necropsy observations table (Table B16). ARGUS 418-020 Page 139 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 14) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS LEFT ABS. REL. WT. % TBW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % TBW TESTIS LEFT ABS. REL. WT. % TBW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW DOSAGE GROUP V 30 MG/KG/DAY 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 398. 385. 475. 374. 497. 358. 345. 401. 394. 413. 438. 321. 570. 469. 449. 0.6673 0.6265 0.7368 0.6346 0.6890 0.4128a 0.6057 0.6398 0.6318 0.5971 0.6928 0.6158 0.7390 0.7383 0.6466 0.17 0.16 0.16 0.17 0.14 0.12 0.18 0.16 0.16 0.14 0.16 0.19 0.13 0.16 0.14 0.3010 0.2859 0.3496 0.2936 0.3195 0.1813a 0.2949 0.3157 0.2745 0.2785 0.2873 0.2828 0.3243 0.3499 0.2750 0.08 0.07 0.07 0.08 0.06 0.05 0.08 0.08 0.07 0.07 0.06 0.09 0.06 0.07 0.06 1.8057 1.8269 1.8806 1.7360 1.8928 0.9095a 1.5689 1.7613 1.7873 1.7386 1.7150 1.9071 2.0476 1.9514 2.8842b 0.45 0.47 0.40 0.46 0.38 0.25 0.45 0.44 0.45 0.42 0.39 0.59 0.36 0.42 0.64 1.6957 1.7194 1.7560 1.6485 1.7714 0.7763a 1.4689 1.6391 1.6903 1.6364 1.6329 1.7986 1.9007 1.8267 2.6964b 0.43 0.45 0.37 0.44 0.36 0.22 0.42 0.41 0.43 0.40 0.37 0.56 0.33 0.39 0.60 2.2496 1.7412 2.2771 2.1199 1.9407 1.5799 2.0911 2.2751 2.1831 1.6923 2.0396 1.8077 2.1969 2.0347 1.6893 0.56 0.45 0.48 0.57 0.39 0.44 0.61 0.57 0.55 0.41 0.46 0.56 0.38 0.43 0.38 1.2149 1.1388 1.1760 1.1596 1.0294 1.0094 1.1513 1.1189 1.2490 0.9536 1.1029 0.8948 1.2020 1.1848 1.0501 0.30 0.30 0.25 0.31 0.21 0.28 0.33 0.28 0.32 0.23 0.25 0.28 0.21 0.25 0.23 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT . = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT)1 X 100. a. Rat 13741 had small and flaccid epididymides and testes. See the individual necropsy observations table (Table B16). b. Rat 13750 had a large left epididymis and left testis minus tunica albuginea. See the individual necropsy observations table (Table B16). ARGUS 418-020 Page 140 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 15) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS RIGHT ABS. REL. WT. % TBW TESTIS RIGHT ABS. REL. WT. % TBW PROSTATE ABS. WT. REL. % TBW PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. * TBW LIVER ABS. WT. REL. % TBW DOSAGE GROUP V 30 MG/KG/DAY 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732b 13733 13734 13735 511. 452. 321. 378. 361. 465. 443 . 418. 439. 522. 468. -- 554. 456. 446. 0.5828 0.6248 0.6269 0.6778 0.6145 0.5830 0.6714 0.5943 0.6131 0.7137 0.6397 0.31 0.7056 0.6340 0.6247 0.11 0.14 0.20 0.18 0.17 0.12 0.15 0.14 0.14 0.14 0.14 -- 0.13 0.14 0.14 1.6442 2.0050 1.6768 1.7229 1.6811 1.6140 1.6811 1.7995 1.7874 1.9707 1.7492 1.54 1.8567 1.7743 1.6311 0.32 0.44 0.52 0.46 0.46 0.35 0.38 0.43 0.41 0.38 0.37 -- 0.34 0.39 0.36 0.8431 0.8430 0.5950 0.6971 0.7775 1.1966 1.1502 0.8251 0.8078 0.8931 0.6744 0.34 0.9479 1.2570 0.9716 0.16 0.19 0.18 0.18 0.22 0.26 0.26 0.20 0.18 0.17 0.14 -- 0.17 0.28 0.22 0.015 0.013 0.010 0.009 0.005 0.011 0.009 0.011 0.008 0.011 0.011 0.006 0.012 0.007 0.007 2.94 2.88 3.12 2.38 1.38 2.36 2.03 2.63 1.82 2.11 2.35 -- 2.17 1.54 1.57 2.32 2.12 2.18 2.22 2.05 2.39 2.09 2.40 2.26 2.18 2.10 1.83 2.41 2.25 2.22 0.45 0.47 0.68 0.59 0.57 0.51 0.47 0.57 0.5 0.42 0.45 -- 0.44 0.49 0.50 32.46 26.38 25.29 20.55 24.05 26.25 27.77 33.99 30.46 36.40 27.84 15.94 34.60 28.30 26.33 6.35 5.84 7.88 5.44 6.66 5.64 6.27 8.13 6.94 6.97 5.95 -- 6.24 6.21 5.90 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Value was multiplied by 1000. b. Rat 13732 was moribund sacrificed on day 45 of study; values excluded from group averages and statistical analyses. ARGUS 418-020 Page 141 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 16) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS RIGHT ABS. REL. WT. % TBW TESTIS RIGHT ABS. REL. WT. % TBW PROSTATE ABS. WT. REL. % TBW PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW DOSAGE GROUP V 30 MG/KG/DAY 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 398. 385. 475. 374. 497. 358. 345. 401. 394. 413. 438. 321. 570 . 469. 449. 0.6535 0.6117 0.7239 0.6380 0.6731 0.3794b 0.6017 0.6511 0.6378 0.5834 0.6752 0.6142 0.7365 0.7260 0.6502 0.16 0.16 0.15 0.17 0.14 0.10 0.17 0.16 0.16 0.14 0.15 0.19 0.13 0.15 0.14 1.7745 1.7991 1.9556 1.7722 1.8953 0.8606b 1.5535 1.7824 1.8145 1.7338 1.6953 1.8456 2.0122 1.8831 1.7065 0.44 0.47 0.41 0.47 0.38 0.24 0.45 0.44 0.46 0.42 0.39 0.57 0.35 0.40 0.38 1.1293 0.6582 0.9491 0.6872 1.0956 0.5990 0.7266 0.8984 0.7553 0.8432 0.8258 0.5597 1.0400 0.8505 0.8981 0.28 0.17 0.20 0.18 0.22 0.17 0.21 0.22 0.19 0.20 0.19 0.17 0.18 0.18 0.20 0.010 0.009 0.012 0.015 0.010 0.007 0.007 0.008 0.012 0.009 0.015 0.016 0.013 0.011 0.013 2.51 2.34 2.53 4.01 2.01 1.96 2.03 2.00 3.04 2.18 3.42 4.98 2.28 2.34 2.90 1.95 2.09 2.25 2.16 2.47 2.18 2.06 2.27 2.25 2.32 2.20 1.88 2.28 2.27 2.04 0.49 0.54 0.47 0.58 0.50 0.61 0.60 0.57 0.57 0.56 0.50 0.58 0.40 0.48 0.45 26.04 25.32 27.00 23.10 29.12 27.33 25.57 23.40 24.04 29.53 28.24 23.29 31.63 27.03 25.92 6.54 6.58 5.68 6.18 5.86 7.63 7.41 5.84 6.10 7.15 6.45 7.26 5.55 5.76 5.77 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . W T . = ORGAN WEIGHT, REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Value was multiplied by 1000. b. Rat 13741 had small and flaccid epididymides and testes. See the individual necropsy observations table (Table B16 ) . ARGUS 418-020 Page 142 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 17) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 143 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP V KIDNEY LEFT A B S . REL. W T . % TBW KIDNEY RIGHT ABS. REL. W T . % TBW 30 MG/KG/DAY ADRENAL LEFT ABS. REL. WT. % TBW a ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. REL. W T . % TBW THYMUS ABS . R E L . WT. % TBW 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732c 13733 13734 13735 511. 452. 321. 378. 361. 465. 443 . 418. 439. 522. 468. -- 554. 456. 446. 2.04 1.97 1.96 2.05 1.65 2.21 2.08 1.89 2.13 2.44 2.02 1.22 2.19 2.22 2.06 0.40 0.44 0.61 0.54 0.46 0.48 0.47 0.45 0.48 0.47 0.43 -- 0.40 0.49 0.46 2.19 2.19 1.94 2.01 1.73 2.20 2.16 1.94 2.05b 2.45 2.05 1.25 2.3 Id 2.30 2.23 0.43 0.48 0.60 0.53 0.48 0.47 0.49 0.46 0.47 0.47 0.44 -- 0.42 0.50 0.50 0.035 0.035 0.033 0.042 0.028 0.029 0.026 0.028 0.020 0.035 0.028 0.026 0.032 0.022 0.030 6.85 7.74 10.28 11.11 7.76 6.24 5.87 6.70 4.56 6.70 5.98 -- 5.78 4.82 6.73 0.040 0.035 0.028 0.037 0.026 0.039 0.024 0.025 0.014 0.031 0.026 0.026 0.035 0.023 0.014 7.83 7.74 8.72 9.79 7.20 8.39 5.42 5.98 3.19 5.94 5.56 -- 6.32 5.04 3.14 0.76 0.80 0.72 0.79 0.45 0.93 0.75 0.67 0.52 0.70 0.57 0.13 0.94 0.69 0.97 0.15 0.18 0.22 0.21 0.12 0.20 0.17 0.16 0.12 0.13 0.12 -- 0.17 0.15 0.22 0.36 0.49 0.37 0.49 0.20 0.51 0.28 0.25 0.25 0.38 0.18 0.12 0.28 0.32 0.40 0.07 0.11 0.12 0.13 0.06 0.11 0.06 0.06 0.06 0.07 0.04 -- 0.05 0.07 0.09 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. b. Rat 13729 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16 ) . c. Rat 13732 was moribund sacrificed on day 45 of study; values excluded from group averages and statistical analyses. d. Rat 13733 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16 ) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B18 (PAGE 18) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (t) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION MALE RATS RAT TERMINAL BODY NUMBER WEIGHT KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. TBW THYMUS ABS. WT. REL. % TBW DOSAGE GROUP V 30 MG/KG/DAY 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 398. 385. 475. 374. 497. 358. 345. 401. 394. 413. 438. 321. 570. 469. 449. 1.85 1.73 1.98 1.95 1.98 1.82 1.60 1.87 1.80 1.92 2.27 1.89 2.20 1.79 2.07 0.46 0.45 0.42 0.52 0 .40 0.51 0.46 0.47 0.46 0.46 0.52 0.59 0.38 0.38 0.46 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. 1.99 1.79 1.95 2.01 2.15 2.02 1.64 1.93 1.94 2.07 2.20 1.93 2.43 1.78 2.04 0.50 0.46 0.41 0.54 0.43 0.56 0.48 0.48 0.49 0.50 0.50 0.60 0.43 0.38 0.45 0.030 0.021 0.037 0.026 0.024 0.009 0.027 0.020 0.029 0.026 0.028 0.031 0.032 0.029 0.021 7.54 5.45 7.79 6.95 4.83 2.51 7.83 4.99 7.36 6.30 6.39 9.66 5.61 6.18 4.68 0.023 0.017 0.032 0.025 0.027 0.014 0.029 0.026 0.028 0.026 0.025 0.020 0.030 0.028 0.020 5.78 4.42 6.74 6.68 5.43 3.91 8.40 6.48 7.11 6.30 5.71 6.23 5.26 5.97 4.45 0.72 0.65 0.73 0.69 0.80 0.42 0.86 0.62 0.58 0.73 0.74 0.51 1.09 0.87 1.06 0.18 0.17 0.15 0.18 0.16 0.12 0.25 0.15 0.15 0.18 0.17 0.16 0.19 0.18 0.24 0.28 0.20 0.32 0.25 0.27 0.20 0.17 0.20 0.29 0.28 0.35 0.27 0.38 0.29 0.27 0.07 0.05 0.07 0.07 0.05 0.06 0.05 0.05 0.07 0.07 0.08 0.08 0.07 0.06 0.06 ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. ARGUS 41B-020 Page 144 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 1) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 145 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP I EPIDIDYMIS LEFT ABS. REL. WT. % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. W T . % BRW 0 MG/KG/DAY TESTIS LEFT ABS. REL. W T . % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % BRW 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 2.36 2.38 2.19 2.40 2.22 2.24 2.35 2.33 2.11 1.86 2.32 2.11 2.51 2.19 2.25 2.52 2.52 2.27 2.33 2.21 2.15 2.22 2.45 1.83 2.25b 2.33 2.17 2.10 2.10 2.43 0.6756 0.6786 0.7340 0.7152 0.7034 0.7420 0.6822 0.7947 0.5497 0.6732 0.6526 0.6830 0.6764 0.6695 0.7240 0.7570 0.7783 0.7269 0.7967 0.7542 0.6623 0.7321 0.7364 0.7481 0.7424 0.8408 0.7204 0.7515 0.6810 0.8494 28.63 28.51 33.52 29.80 31.68 33.12 29.03 34.11 26.05 36.19 28.13 32.37 26.95 30.57 32.18 30.04 30.88 32.02 34.19 34.13 30.80 32.98 30.06 40.88 33.00 36.08 33.20 35.78 32.43 34.95 0.2966 0.3086 0.3341 0.3136 0.3543 0.3611 0.3203 0.3453 0.2145 0.2883 0.3271 0.2887 0.3010 0.2733 0.3652 0.3567 0.3479 0.3458 0.3973 0.3459 0.3287 0.3161 0.3896 0.3361 0.2999 0.3786 0.3192 0.3760 0.3307 0.3993 12.57 12.97 15.26 13.07 15.96 16.12 13.63 14.82 10.16 15.50 14.10 13.68 11.99 12.48 16.23 14.15 13.80 15.23 17.05 15.65 15.29 14.24 15.90 18.37 13.33 16.25 14.71 17.90 15.75 16.43 1.5259 1.6647 1.7979 1.9262 1.8636 1.8832 1.8506 1.8574 1.6417 1.5787 1.7823 1.7653 1.7861 1.5910 1.9534 1.9754 1.7610 1.8719 1.9766 1.8314 1.6391 1.7766 1.6860 1.8174 1.7695 1.9527 1.6706 1.8851 1.6630 2.1140 64.66 69.94 82.10 80.26 83.94 84.07 78.75 79.72 77.80 84.88 76.82 83.66 71.16 72.65 86.82 78.39 69.88 82.46 84.83 82.87 76.24 80.03 68.82 99.31 78.64 83.81 76.99 89.77 79.19 87.00 1.2920 1.5221 1.6608 1.7009 1.7079 1.7583 1.7435 1.7354 1.4397 1.4846 1.6617 1.6275 1.6113 1.4794 1.8326 1.8243 1.6507 1.7273 1.8446 1.7046 1.5212 1.6795 1.5789 1.6876 1.6738 1.8342 1.5585 1.7864 1.5519 1.9567 54.74 63.95 75.84 70.87 76.93 78.50 74.19 74.48 68.23 79.82 71.62 77.13 64.20 67.55 81.45 72.39 65.50 76.09 79.17 77.13 70.75 75.65 64.44 92.22 74.39 78.72 71.82 85.07 73.90 80.52 1.3897 58.88 2.2138 93.02 2.2003 100.47 1.6708 69.62 2.1486 96.78 1.7423a 77.78a 2.1930 93.32 2.1517 92.35 2.6536 125.76 2.7678 148.81 2.1404 92.26 2.4939 118.19 1.9469 77.56 2.2970 104.88 2.5074 111.44 2.5305 100.42 2.1888 86.86 2.3224 102.31 2.6549 113.94 2.1074 95.36 2.4345 113.23 2.2753 102.49 2.0262 82.70 1.8379 100.43 2.9931 133.03 2.6403 113.32 2.44 9.8 112.89 2.6437 125.89 2.3510 111.95 2.0128 82.83 0.9914 1.2279 1.3738 1.1445 1.1320 1.2432 1.0702 1.2132 1.4047 1.3165 1.1786 1.3161 1.3192 1.0604 1.4403 1.3395 1.2973 1.3218 1.5503 1.0458 1.3000 1.2186 1.1769 0.9276 1.3586 1.4879 1.3752 1.5575 1.3665 1.3021 42.01 51.59 62.73 47.69 50.99 55.50 45.54 52.07 66.57 70.78 50.80 62.37 52.56 48.42 64.01 53.15 51.48 58.23 66.54 47.32 60.46 54.89 48.04 50.69 60.38 63.86 63.37 74.17 65.07 53.58 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Damaged during processing (some fluid loss prior to weighing); values excluded from group averages and statistical analyses. b. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 2) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 146 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP I EPIDIDYMIS RIGHT A B S . REL. WT. % BRW TESTIS RIGHT ABS. REL. W T . % BRW 0 MG/KG/DAY PROSTATE ABS. WT. REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. 1 WT. % 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 2.36 2.38 2.19 2.40 2.22 2.24 2.35 2.33 2.11 1.86 2.32 2.11 2.51 2.19 2.25 2.52 2.52 2.27 2.33 2.21 2.15 2.22 2.45 1.83 2.25a 2.33 2.17 2.10 2.10 2.43 0.6727 0.6538 0.7422 0.7242 0.7013 0.7714 0.6884 0.7813 0.6624 0.6645 0.6452 0.7042 0.6920 0.6590 0.7307 0.7448 0.8023 0.6947 0.8216 0.6324 0.6737 0.6907 0.7404 0.7047 0.7624 0.8685 0.7318 0.7165 0.6744 0.8078 28.50 27.47 33.89 30.18 31.59 34.44 29.29 33.53 31.39 35.72 27.81 33.37 27.57 30.09 32.48 29.56 31.84 30.60 35.26 28.62 31.33 31.11 30.22 38.51 33.88 37.27 33.72 34.12 32.11 33.24 1.5705 66.55 1.5701 65.97 1.8434 84.17 1.8830 78.46 1.8294 82.40 1.9176 85.61 1.8831 80.13 1.9010 81.59 2.3432 111.05 1.5825 85.08 1.8363 79.15 1.8260 86.54 1.8150 72.31 1.5240 69.59 1.9427 86.34 1.9684 78.11 1.7778 70.55 1.7963 79.13 2.0150 86.48 1.7662 79.92 1.7174 79.88 1.6943 76.32 1.7379 70.93 1.8086 98.83 1.7619 78.31 1.9505 83.71 1.6434 75.73 1.8347 87.37 1.6857 80.27 2.0934 86.15 0.9769 1.0477 1.1461 1.2982 0.8545 1.2630 1.4560 1.3797 1.2521 1.1033 1.1326 1.0173 1.2060 1.2564 1.0383 0.9796 1.0554 1.0403 1.1757 1.3352 1.1837 1.2359 1.2678 0.9132 1.1731 1.6005 1.1031 0.8151 1.0534 0.7730 41.39 44.02 52.33 54.09 38.49 56.38 61.96 59.21 59.34 59.32 48.82 48.21 48.05 57.37 46.15 38.87 41.88 45.83 50.46 60.42 55.06 55.67 51.75 49.90 52.14 68.69 50.83 38.81 50.16 31.81 0.016 0.014 0.012 0.016 0.014 0.009 0.014 0.015 0.029 0.017 0.018 0.012 0.013 0.016 0.012 0.015 0.013 0.008 0.016 0.014 0.012 0.009 0.015 0.011 0.014 0.018 0.011 0.012 0.011 0.014 0.68 0.59 0.55 0.67 0.63 0.40 0.60 0.64 1.37 0.91 0.78 0.57 0.52 0.73 0.53 0.60 0.52 0.35 0.69 0.63 0.56 0.40 0.61 0.60 0.62 0.77 0.51 0.57 0.52 0.58 23.61 22.78 18.43 20.30 15.86 22.82 18.53 19.26 23.25 22.41 22.68 17.03 21.60 20.68 20.97 25.02 16.93 19.31 21.32 20.80 16.17 18.88 19.31 18.10 19.76 24.67 17.8622.09 18.41 20.24 1000.42 957.14 841.55 845.83 714.41 1018.75 788.51 826.61 1101.9 1204.84 977.59 807.11 860.56 944.29 932.00 992.86 671.82 850.66 915.02 941.18 752.09 850.45 788.16 989.07 878.22 1058.80 823.04 1051.90 876.67 832.92 2.17 2.55 1.90 2.33 2.26 2.25 2.17 2.12 2.33 2.31 2.47 2.18 2.50 2.53 1.85 2.58 1.92 1.99 2.09 2.02 2.15 2.30 2.10 2.11 1.99 2.28 2.09 2.08 2.03 2.07 91.95 107.14 86.76 97.08 101.80 100.45 92.34 90.99 110.43 124.19 106.46 103.32 99.60 115.52 82.22 102.38 76.19 87.66 89.70 91.40 100.00 103.60 85.71 115.30 88.44 97.85 96.31 99.05 96.67 85.18 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.S) TABLE B19 (PAGE 3) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 147 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP I KIDNEY RIGHT ABS. REL. WT. % BRW 0 MG/KG/DAY ADRENAL LEFT ABS. REL. WT. % BRW ADRENAL RIGHT ABS. REL. WT. % BRW SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. 1 % 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 2.36 2.38 2.19 2.40 2.22 2.24 2.35 2.33 2.11 1.86 2.32 2.11 2.51 2.19 2.25 2.52 2.52 2.27 2.33 2.21 2.15 2.22 2.45 1.83 2.25a 2.33 2.17 2.10 2.10 2.43 2.19 2.55 1.96 2.28 2.25 2.39 2.14 2.15 2.43 2.29 2.38 2.21 2.32 2.31 2.03 2.61 2.05 1.89 2.03 1.99 2.12 2.20 2.30 2.15 2.09 2.34 2.05 2.01 1.99 2.03 92.80 107.14 89.50 95.00 101.35 106.70 91.06 92.27 115.16 123.12 102.59 104.74 92.43 105.48 90.22 103.57 81.35 83.26 87.12 90.04 98.60 99.10 93.88 117.49 92.89 100.43 94.47 95.71 94.76 83.54 0.030 0.032 0.031 0.026 0.029 0.044 0.046 0.031 0.031 0.028 0.035 0.033 0.029 0.028 0.035 0.042 0.032 0.032 0.035 0.028 0.027 0.035 0.033 0.027 0.027 0.034 0.032 0.035 0.029 0.032 1.27 1.34 1.42 1.08 1.31 1.96 1.96 1.33 1.47 1.50 1.51 1.56 1.16 1.28 1.56 1.67 1.27 1.41 1.50 1.27 1.26 1.58 1.35 1.48 1.20 1.46 1.47 1.67 1.38 1.32 0.031 0.035 0.026 0.033 0.028 0.039 0.021 0.033 0.029 0.028 0.038 0.032 0.033 0.027 0.039 0.035 0.031 0.036 0.033 0.029 0.023 0.045 0.031 0.022 0.027 0.036 0.036 0.031 0.033 0.028 1.31 1.47 1.19 1.38 1.26 1.74 0.89 1.42 1.37 1.50 1.64 1.52 1.31 1.23 1.73 1.39 1.23 1.58 1.42 1.31 1.07 2.03 1.26 1.20 1.20 1.54 1.66 1.48 1.57 1.15 0.75 0.96 0.69 1.11 1.00 1.20 0.83 0.90 1.04 0.76 0.94 0.79 0.98 0.98 1.01 1.26 1.12 0.80 0.93 1.32 0.85 0.68 0.80 0.87 0.87 0.96 0.94 1.07 0.68 0.97 31.78 40.34 31.51 46.25 45.04 53.57 35.32 38.63 49.29 40.86 40.52 37.44 39.04 44.75 44.89 50.00 44.44 35.24 39.91 59.73 39.53 30.63 32.65 47.54 38.67 41.20 43.32 50.95 32.38 39.92 0.38 0.63 0.38 0.69 0.45 0.55 0.41 0.52 0.42 0.32 0.29 0.34 0.49 0.49 0.40 0.41 0.50 0.32 0.39 0.52 0.40 0.44 0.33 0.57 0.31 0.49 0.420.50 0.26 0.46 16.10 26.47 17.35 28.75 20.27 24.55 17.45 22.32 19.90 17.20 12.50 16.11 19.52 22.37 17.78 16.27 19.84 14.10 16.74 23.53 18.60 19.82 13.47 31.15 13.78 21.03 19.35 23.81 12.38 18.93 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 4) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 148 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP II EPIDIDYMIS LEFT ABS. REL. W T . % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. W T . % BRW 1 MG/KG/DAY TESTIS LEFT ABS. REL. WT. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. W T . % BRW SEMINAL VESICLES WITH FLUID ABS. REL. W T . % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % BRW 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 2.22 2.34 2.43 2.13 2.07 2.17 2.26 2.43 2.42 2.20 2.26 2.34 2.21 2.44 2.25 2.31 2.25 2.33 2.35 2.32 2.38 2.26 2.37 2.23 2.33 2.31 2.10 2.31 2.17a 2.28 0.6495 0.7034 0.7044 0.7068 0.6053 0.7697 0.7061 0.6470 0.7020 0.7283 0.7490 0.7241 0.7330 0.7089 0.6784 0.6822 0.6658 0.6317 0.6941 0.7437 0.7134 0.7191 0.6303 0.6840 0.8054 0.7198 0.6277 0.6425 0.7407 0.7581 29.26 30.06 28.99 33.18 29.24 35.47 31.24 26.62 29.01 33.10 33.14 30.94 33.17 29.05 30.15 29.53 29.59 27.11 29.54 32.06 29.97 31.82 26.59 30.67 34.57 31.16 29.89 27.81 34.13 33.25 0.2998 0.3166 0.3546 0.3369 0.2813 0.3525 0.3434 0.2792 0.2951 0.3536 0.3527 0.3150 0.3398 0.3200 0.3183 0.3463 0.2982 0.3064 0.3058 0.2876 0.3282 0.3231 0.2784 0.2935 0.3335 0.3468 0.3055 0.2637 0.3172 0.3225 13.50 13.53 14.59 15.82 13.59 16.24 15.19 11.49 12.19 16.07 15.61 13.46 15.38 13.11 14.15 14.99 13.25 13.15 13.01 12.40 13.79 14.30 11.75 13.16 14.31 15.01 14.55 11.42 14.62 14.14 1.6770 1.9768 1.7819 1.8226 1.6595 1.8739 1.6545 1.9344 2.0283 1.8745 1.8714 1.7279 1.9500 1.9383 1.6234 1.6999 1.7814 1.8391 1.7156 1.9510 1.9750 1.7946 1.8551 1.5110 2.1552 1.7050 1.7519 1.5617 1.9318 1.6871 75.54 84.48 73.33 85.57 80.17 86.35 73.21 79.60 83.81 85.20 82.80 73.84 88.24 79.44 72.15 73.59 79.17 78.93 73.00 84.09 82.98 79.41 78.27 67.76 92.50 73.81 83.42 67.61 89.02 74.00 1.5445 1.8290 1.6458 1.6586 1.5483 1.6712 1.5240 1.8105 1.8573 1.7670 1.7242 1.6227 1.8364 1.8199 1.5062 1.5800 1.6328 1.7159 1.6256 1.8355 1.8339 1.6913 1.6992 1.4044 1.9836 1.6041 1.6518 1.4618 1.8052 1.5755 69.57 78.16 67.73 77.87 74.80 77.01 67.43 74.51 76.75 80.32 76.29 69.35 83.10 74.59 66.94 68.40 72.57 73.64 69.17 79.12 77.05 74.84 71.70 62.98 85.13 69.44 78.66 63.28 83.19 69.10 2.4075 108.44 2.8763 122.92 3.2227 132.62 1.6848 79.10 1.4917 72.06 2.3337 107.54 2.5335 112.10 2.3501 96.71 2.3202 95.88 2.6251 119.32 2.3899 105.75 2.4003 102.58 2.5036 113.28 2.1300 87.30 2.4119 107.20 2.0676 89.51 2.6220 116.53 2.1504 92.29 2.2035 93.76 2.4213 104.37 2.5200 105.88 2.4900 110.18 1.6932 71.44 2.3628 105.96 2.8403 121.90 2.2805 98.72 2.1178 100.85 2.1529 93.20 2.1495 99.06 2.2241 97.55 1.5081 1.4047 1.5709 1.1637 0.8167 1.2939 1.3047 1.1924 1.0796 1.3840 1.2356 1.2870 1.2468 1.2740 1.2195 1.1076 1.4890 1.1768 1.1379 1.4614 1.4917 1.2234 1.0140 1.1243 1.4880 1.2083 1.0602 1.1517 1.2183 1.2827 67.93 60.03 64.65 54.63 39.45 59.63 57.73 49.07 44.61 62.91 54.67 55.00 56.42 52.21 54.20 47.95 66.18 50.51 48.42 62.99 62.68 54.13 42.78 50.42 63.86 52.31 50.48 49.86 56.14 56.26 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE . (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 5) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 149 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP II EPIDIDYMIS RIGHT ABS. REL. WT. % BRW TESTIS RIGHT ABS. REL. WT. % BRW 1 MG/KG/DAY PROSTATE ABS. WT. REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. 1 WT. % 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 2.22 2.34 2.43 2.13 2.07 2.17 2.26 2.43 2.42 2.20 2.26 2.34 2.21 2.44 2.25 2.31 2.25 2.33 2.35 2.32 2.38 2.26 2.37 2.23 2.33 2.31 2.10 2.31 2.17b 2.28 0.6184 27.86 0.7187 30.71 0.7346 30.23 0.7092 33.30 0.6527 31.53 0.3677a 16.94 0.7132 31.56 0.6219 25.59 0.6966 28.78 0.6905 31.39 0.7322 32.40 0.7423 31.72 0.7523 34.04 0.7081 29.02 0.6380 28.36 0.6909 29.91 0.6756 30.03 0.6579 28.24 0.6966 29.64 0.7426 32.01 0.7281 30.59 0.7464 33.03 0.6316 26.65 0.6388 28.64 0.7879 33.82 0.7250 31.38 0.6460 30.76 0.6287 27.22 0.7940 36.59 0.7865 34.50 1.6665 75.07 2.0272 86.63 1.8301 75.31 1.8432 86.54 1.7937 86.65 0.8983a 41.40 1.6779 74.24 1.9129 78.72 2.0712 85.59 1.9493 88.60 1.8401 81.42 1.7467 74.64 2.5181 113.94 1.8376 75.31 1.5823 70.32 1.7069 73.89 2.6503 117.79 1.9075 81.87 1.6978 72.25 2.0238 87.23 1.9809 83.23 1.8349 81.19 1.7942 75.70 1.5501 69.51 2.1403 91.86 1.7659 76.44 1.7433 83.01 1.5591 67.49 2.0007 92.20 1.6440 72.10 1.2524 1.3965 1.1854 0.9863 1.1001 1.2274 1.1159 1.3568 1.0950 0.9987 0.9751 1.2793 1.1153 1.1768 1.0379 1.4184 0.6843 1.0489 1.4685 1.1363 0.8039 0.9861 1.1095 1.2735 0.9730 1.6851 1.1798 0.8826 1.1305 1.1982 56.41 59.68 48.78 46.30 53.14 56.56 49.38 55.84 45.25 45.40 43.15 54.67 50.47 48.23 46.13 61.40 30.41 45.02 62.49 48.98 33.78 43.63 46.81 57.11 41.76 72.95 56.18 38.21 52.10 52.55 0.016 0.015 0.020 0.015 0.010 0.012 0.016 0.017 0.008 0.017 0.015 0.012 0.016 0.009 0.019 0.012 0.013 0.011 0.015 0.012 0.013 0.016 0.010 0.015 0.014 0.014 0.013 0.016 0.013 0.014 0.72 0.64 0.82 0.70 0.48 0.55 0.71 0.70 0.33 0.77 0.66 0.51 0.72 0.37 0.84 0.52 0.58 0.47 0.64 0.52 0.55 0.71 0.42 0.67 0.60 0.61 0.62 0.69 0.60 0.61 23.73 26.29 20.13 24.69 23.30 27.55 25.31 26.08 26.73 32.23 25.22 19.48 25.04 24.65 23.13 22.38 25.86 22.58 29.17 22.99 22.73 22.86 17.07 26.32 29.05 19.16 23.90. 22.05 21.10 27.36 1068.92 1123.50 828.40 1159.15 1125.60 1269.58 1119.91 1073.25 1104.54 1465.00 1115.93 832.48 1133.03 1010.24 1028.00 968.83 1149.33 969.10 1241.28 990.95 955.04 1011.50 720.25 1180.27 1246.78 829.44 1138.10 954.54 972.35 1200.00 2.49 2.97 2.67 2.79 2.32 2.73 2.29 2.64 2.72 2.74 2.66 2.20 2.84 2.58 2.80 2.68 2.67 2.41 2.55 2.22 2.56 2.55 2.06 2.22 2.87 1.89 2.20 2.20 2.11 2.67 112.16 126.92 109.88 130.98 112.08 125.81 101.33 108.64 112.40 124.54 117.70 94.02 128.51 105.74 124.44 116.02 118.67 103.43 108.51 95.69 107.56 112.83 86.92 99.55 123.18 81.82 104.76 95.24 97.24 117.10 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13636 had a small and flaccid right epididymis and right testis. See the individual necropsy observations table (Table B16). b. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) rABLE B19 (PAGE 6): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL P GENERATION MALE RATS ARGUS 418-020 Page 150 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP II KIDNEY RIGHT ABS. REL. W T . % BRW 1 MG/KG/DAY ADRENAL LEFT ABS. REL. W T . BRW ADRENAL RIGHT ABS. REL. WT. * BRW SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL. % BRW 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 2.22 2.34 2.43 2.13 2.07 2.17 2.26 2.43 2.42 2.20 2.26 2.34 2.21 2.44 2.25 2.31 2.25 2.33 2.35 2.32 2.38 2.26 2.37 2.23 2.33 2.31 2.10 2.31 2.17b 2.28 2.48 2.84 2.62 3.00 2.15 2.97 2.36 2.85 2.44a 2.79 2.57 2.15 2.68 2.71 2.77 2.67 2.70 2.56 2.72 2.36 2.80 2.35 2.30 2.20 3.18 1.92 2.17 2.32 2.10 2.63 111.71 121.37 107.82 140.84 103.86 136.87 104.42 117.28 100.83 126.82 113.72 91.88 121.27 111.06 123.11 115.58 120.00 109.87 115.74 101.72 117.65 103.98 97.05 98.65 136.48 83.12 103.33 100.43 96.77 115.35 0.034 0.038 0.032 0.037 0.028 0.029 0.036 0.027 0.036 0.037 0.032 0.032 0.034 0.033 0.038 0.026 0.031 0.027 0.032 0.031 0.029 0.033 0.024 0.040 0.027 0.029 0.029 0.036 0.030 0.031 1.53 1.62 1.32 1.74 1.35 1.34 1.59 1.11 1.49 1.68 1.42 1.37 1.54 1.35 1.69 1.12 1.38 1.16 1.36 1.34 1.22 1.46 1.01 1.79 1.16 1.26 1.38 1.56 1.38 1.36 0.034 0.038 0.031 0.036 0.028 0.030 0.037 0.022 0.029 0.033 0.032 0.031 0.033 0.032 0.036 0.024 0.030 0.026 0.042 0.028 0.025 0.032 0.022 0.041 0.024 0.025 0.032 0.027 0.029 0.030 1.53 1.62 1.28 1.69 1.35 1.38 1.64 0.90 1.20 1.50 1.42 1.32 1.49 1.31 1.60 1.04 1.33 1.12 1.79 1.21 1.05 1.42 0.93 1.84 1.03 1.08 1.52 1.17 1.34 1.32 0.95 0.92 0.68 1.06 0.70 0.94 1.05 0.98 0.90 0.75 1.02 1.08 0.72 0.75 1.02 0.71 0.95 0.81 0.80 1.01 0.93 0.84 0.74 0.89 0.88 0.72 0.86 0.70 0.87 1.01 42.79 39.32 27.98 49.76 33.82 43.32 46.46 40.33 37.19 34.09 45.13 46.15 32.58 30.74 45.33 30.74 42.22 34.76 34.04 43.53 39.08 37.17 31.22 39.91 37.77 31.17 40.95 30.30 40.09 44.30 0.39 0.38 0.26 0.50 0.41 0.52 0.47 0.42 0.25 0.29 0.35 0.29 0.45 0.49 0.31 0.32 0.52 0.33 0.44 0.39 0.43 0.30 0.36 0.42 0.36 0.32 0.31 . 0.43 0.31 0.51 17.57 16.24 10.70 23.47 19.81 23.96 20.80 17.28 10.33 13.18 15.49 12.39 20.36 20.08 13.78 13.85 23.11 14.16 18.72 16.81 18.07 13.27 15.19 18.83 15.45 13.85 14.76 18.61 14.28 22.37 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. W T . = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13639 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16) . b. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 7) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 151 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP III EPIDIDYMIS LEFT ABS. REL. WT. % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % BRW 3 MG/KG/DAY TESTIS LEFT ABS. REL. WT. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % BRW 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 2.24 2.11 2.32 2.39 2.40 2.00 2.23 2.13 2.34 2.12 2.36 2.22 2.07 2.36 2.22 2.14 2.31 2.35 2.41 2.29 2.42 2.45 2.19 2.20 2.12 2.30 2.34 2.08 2.27 2.28 0.6912 0.6733 0.7359 0.6819 0.6495 0.6823 0.6787 0.5743 0.6734 0.7859 0.6692 0.6250 0.6469 0.6486 0.6728 0.7281 0.6628 0.6807 0.7220 0.7099 0.7653 0.7460 0.7294 0.7152 0.6832 0.6252 0.6735 0.7943 0.6982 0.6794 30.86 31.91 31.72 28.53 27.06 34.11 30.43 26.96 28.78 37.07 28.36 28.15 31.25 27.48 30.31 34.02 28.69 28.96 29.96 31.00 31.62 30.45 33.30 32.51 32.23 27.18 28.78 38.19 30.76 29.80 0.3254 0.3247 0.3684 0.3250 0.3010 0.2923 0.3297 0.2440 0.3213 0.3657 0.2917 0.2759 0.2756 0.2841 0.3345 0.3253 0.3048 0.3119 0.3292 0.3186 0.3366 0.3481 0.2949 0.2938 0.3172 0.2874 0.3194 0.3601 0.3340 0.3048 14.53 15.39 15.88 13.60 12.54 14.62 14.78 11.46 13.73 17.25 12.36 12.43 13.31 12.04 15.07 15.20 13.19 13.27 13.66 13.91 13.91 14.21 13.46 13.35 14.96 12.50 13.65 17.31 14.71 13.37 1.9614 1.7494 1.8987 1.8210 1.7079 1.8632 1.6308 1.6210 1.7453 1.8911 1.7697 1.8034 1.6549 1.6521 1.5921 1.9417 1.7046 1.7415 1.7870 1.9063 2.0456 2.0411 1.6796 1.7144 1.8082 1.7667 1.5957 2.0392 1.7096 1.7594 87.56 82.91 81.84 76.19 71.16 93.16 73.13 76.10 74.58 89.20 74.99 81.23 79.95 70.00 71.72 90.73 73.79 74.11 74.15 83.24 84.53 83.31 76.69 77.93 85.29 76.81 68.19 98.04 75.31 77.17 1.7444 1.6186 1.7604 1.7070 1.5898 1.7270 1.5095 1.4979 1.5993 1.7575 1.6395 1.6454 1.5520 1.5435 1.4762 1.8298 1.5908 1.5851 1.6515 1.7722 1.9325 1.9264 1.5543 1.5779 1.6956 1.6740 1.4880 1.9123 1.5964 1.6408 77.87 76.71 75.88 71.42 66.24 86.35 67.69 70.32 68.35 82.90 69.47 74.12 74.98 65.40 66.50 85.50 68.86 67.45 68.53 77.39 79.86 78.63 70.97 71.72 79.98 72.78 63.59 91.94 70.32 71.96 2.8329 126.47 1.7487 82.88 2.1959 94.65 2.3292 97.46 2.2164 92.35 2.1344 106.72 2.1297 95.50 1.8561 87.14 2.8444 121.56 2.8418 134.05 2.1255 90.06 2.5020 112.70 2.3554 113.79 2.1533 91.24 1.8019 81.17 2.3180 108.32 2.6193 113.39 2.1396 91.05 2.7896 115.75 2.0806 90.86 2.3093 95.42 2.5467 103.95 2.7770 126.80 2.2227 101.03 2.6755 126.20 2.0154 87.63 2.9111 124.40 2.2724 109.25 2.4406 107.52 2.4640 108.07 1.4299 0.9591 1.1255 1.2339 1.0909 1.0447 1.2414 1.0709 1.4370 1.4905 1.3067 1.2914 1.2487 1.3208 1.1959 1.3884 1.2994 1.0874 1.5101 1.2158 1.1777 1.3425 1.3745 1.2772 1.5985 1.1092 1.6056 1.2595 1.2353 1.3996 63.83 45.45 48.51 51.63 45.45 52.24 55.67 50.28 61.41 70.31 55.37 58.17 60.32 55.97 53.87 64.88 56.25 46.27 62.66 53.09 48.66 54.80 62.76 58.05 75.40 48.23 68.62 60.55 54.42 61.38 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 8) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 152 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP III EPIDIDYMIS RIGHT ABS. REL. WT. % BRW 3 MG/KG/DAY TESTIS RIGHT ABS. REL. WT. % BRW PROSTATE ABS. WT. REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 2.24 2.11 2.32 2.39 2.40 2.00 2.23 2.13 2.34 2.12 2.36 2.22 2.07 2.36 2.22 2.14 2.31 2.35 2.41 2.29 2.42 2.45 2.19 2.20 2.12 2.30 2.34 2.08 2.27 2.28 0.6942 0.6884 0.7462 0.6483 0.6558 0.7041 0.6941 0.5695 0.7484 0.7844 0.6884 0.6282 0.6464 0.6375 0.6921 0.6965 0.6481 0.6848 0.7450 0.6700 0.7726 0.7609 0.7217 0.7096 0.6926 0.6045 0.7076 0.7951 0.6814 0.6736 30.99 32.62 32.16 27.12 27.32 35.20 31.12 26.74 31.98 37.00 29.17 28.30 31.23 27.01 31.18 32.55 28.06 29.14 30.91 29.26 31.92 31.06 32.95 32.25 32.67 26.28 30.24 38.22 30.02 29.54 1.9170 1.7684 1.9026 1.7742 1.7255 1.9202 1.6840 1.6580 1.8785 1.8798 1.7400 1.7492 1.6550 1.7158 1.5912 1.9457 1.7060 1.7331 1.7974 1.9337 2.0453 2.0193 1.6827 1.7016 1.8110 1.7715 1.5732 2.0475 1.6739 1.7440 85.58 83.81 82.01 74.23 71.90 96.01 75.52 77.84 80.28 88.67 73.73 78.79 79.95 72.70 71.68 90.92 73.85 73.75 74.58 84.44 84.52 82.42 76.84 77.34 85.42 77.02 67.23 98.44 73.74 76.49 1.1744 1.0222 0.9513 1.0531 1.0904 1.2313 1.1857 0.8687 1.3318 1.3966 1.0287 1.1247 0.9881 1.1467 0.9485 0.9484 1.4671 1.2232 1.4973 0.8157 0.9378 1.1773 1.2601 1.1324 1.1725 1.0562 1.0888 0.9953 1.2406 0.9884 52.43 48.44 41.00 44.06 45.43 61.56 53.17 40.78 56.91 65.88 43.59 50.66 47.73 48.59 42.72 44.32 63.51 52.05 62.13 35.62 38.75 48.05 57.54 51.47 55.31 45.92 46.53 47.85 54.65 43.35 0.014 0.018 0.008 0.013 0.013 0.010 0.012 0.009 0.013 0.014 0.011 0.011 0.003 0.010 0.014 0.010 0.013 0.011 0.011 0.016 0.010 0.012 0.013 0.009 0.014 0.017 0.013 0.014 0.012 0.016 0.62 0.85 0.34 0.54 0.54 0.50 0.54 0.42 0.56 0.66 0.47 0.50 0.14 0.42 0.63 0.47 0.56 0.47 0.46 0.70 0.41 0.49 0.59 0.41 0.66 0.74 0.56 0.67 0.53 0.70 28.39 1267.41 28.59 1354.98 26.16 1127.59 28.39 1187.87 28.78 1199.17 24.12 1206.00 31.05 1392.38 25.21 1183.57 29.67 1267.95 27.92 1316.98 24.03 1018.22 26.01 1171.62 28.10 1357.49 24.17 1024.15 28.39 1278.83 22.77 1064.02 27.65 1196.97 26.48 1126.81 27.01 1120.75 29.45 1286.03 29.31 1211.16 29.50 1204.08 28.45 1299.09 22.94 1042.73 26.28 1239.62 28.94 1258.26 29.66- 1267.52 25.96 1248.08 34.16 1504.84 33.85a 1484.65 2.49 2.50 2.20 2.26 2.36 2.29 2.43 2.39 2.60 2.29 2.47 2.42 2.54 2.48 2.49 2.33 2.78 2.44 2.41 2.57 2.69 2.52 2.44 2.33 2.65 2.76 2.45 2.75 2.88 3.19 111.16 118.48 94.83 94.56 98.33 114.50 108.97 112.21 111.11 108.02 104.66 109.01 122.70 105.08 112.16 108.88 120.35 103.83 100.00 112.23 111.16 102.86 111.42 105.91 125.00 120.00 104.70 132.21 126.87 139.91 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. t BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-S889.6) TABLE B19 (PAGE 9) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 153 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP III KIDNEY RIGHT ABS. REL. WT. % BRW 3 MG/KG/DAY ADRENAL LEFT ABS. REL. WT. t BRW ADRENAL RIGHT ABS. REL. WT. % BRW SPLEEN ABS. WT. REL. t BRW THYMUS ABS. WT. REL. % BRW 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 13689 13690 2.24 2.11 2.32 2.39 2.40 2.00 2.23 2.13 2.34 2.12 2.36 2.22 2.07 2.36 2.22 2.14 2.31 2.35 2.41 2.29 2.42 2.45 2.19 2.20 2.12 2.30 2.34 2.08 2.27 2.28 2.45 2.45 2.34 2.24 2.50 2.41 2.48 2.49 2.50 2.31a 2.20 2.23b 2.60 2.27 2.56 2.37 2.55 2.62 2.67 2.56 2.66 2.62 2.33 2.34 2.58 2.75 2.43 2.55 2.82 3.03 109.38 116.11 100.86 93.72 104.17 120.50 111.21 116.90 106.84 108.96 93.22 100.45 125.60 96.19 115.32 110.75 110.39 111.49 110.79 111.79 109.92 106.94 106.39 106.36 121.70 119.56 103.85 122.60 124.23 132.89 0.038 0.040 0.031 0.033 0.042 0.027 0.026 0.026 0.029 0.023 0.034 0.029 0.021 0.025 0.025 0.034 0.035 0.032 0.042 0.026 0.027 0.023 0.025 0.029 0.021 0.030 0.029 0.031 0.029 0.044 1.70 1.90 1.34 1.38 1.75 1.35 1.16 1.22 1.24 1.08 1.44 1.31 1.01 1.06 1.13 1.59 1.52 1.36 1.74 1.14 1.12 0.94 1.14 1.32 0.99 1.30 1.24 1.49 1.28 1.93 0.044 0.046 0.034 0.032 0.044 0.026 0.021 0.021 0.021 0.021 0.030 0.029 0.022 0.034 0.028 0.032 0.027 0.031 0.034 0.025 0.029 0.024 0.045 0.030 0.019 0.026 0.025 0.031 0.022 0.043 1.96 2.18 1.46 1.34 1.83 1.30 0.94 0.98 0.90 0.99 1.27 1.31 1.06 1.44 1.26 1.50 1.17 1.32 1.41 1.09 1.20 0.98 2.05 1.36 0.90 1.13 1.07 1.49 0.97 1.88 1.01 0.89 0182 0.86 0.74 1.11 0.90 0.75 0.90 0.79 0.84 0.73 0.91 0.70 0.88 0.76 0.65 0.79 0.77 1.05 0.97 0.93 0.82 0.85 0.82 0.77 0.91 1.02 1.07 0.96 45.09 42.18 35.34 35.98 30.83 55.50 40.36 35.21 38.46 37.26 35.59 32.88 43.96 29.66 39.64 35.51 28.14 33.62 31.95 45.85 40.08 37.96 37.44 38.64 38.68 33.48 38.89 49.04 47.14 42.10 0.34 0.52 0.45 0.49 0.39 0.44 0.50 0.25 0.42 0.38 0.24 0.36 0.45 0.33 0.53 0.25 0.33 0.35 0.50 0.21 0.30 0.46 0.53 0.40 0.24 0.29 0.270.49 0.39 0.43 15.18 24.64 19.40 20.50 16.25 22.00 22.42 11.74 17.95 17.92 10.17 16.22 21.74 13.98 23.87 11.68 14.28 14.89 20.75 9.17 12.40 18.78 24.20 18.18 11.32 12.61 11.54 23.56 17.18 18.86 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) a. Rat 13670 had moderate dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16 ) . b. Rat 13672 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 10) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA , P GENERATION MALE RATS ARGUS 418-020 Page 154 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP IV EPIDIDYMIS LEFT ABS. REL. WT. % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. t BRW 10 MG/KG/DAY TESTIS LEFT ABS. REL. WT. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. W T . % BRW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % BRW 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 2.31 2.35 2.09 2.11 2.05 2.25 2.26 2.35 2.28 2.46 2.26 2.05 2.37 2.38 2.32 2.45 2.07 2.13 2.33 2.21 2.16 2.34 2.10 2.17 2.22 2.25 2.43 2.18 2.21 2.15 0.6510 0.7089 0.6386 0.7488 0.6307 0.6652 0.7278 0.7380 0.6450 0.7382 0.6860 0.7634 0.7196 0.7761 0.6684 0.7169 0.7793 0.7390 0.6284 0.6303 0.6687 0.6542 0.6660 0.7452 0.6832 0.7514 0.7523 0.7349 0.7209 0.7415 28.18 30.16 30.56 35.49 30.76 29.56 32.20 31.40 28.29 30.01 30.35 37.24 30.36 32.61 28.81 29.26 37.65 34.69 26.97 28.52 30.96 27.96 31.71 34.34 30.77 33.40 30.96 33.71 32.62 34.49 0.2903 0.3304 0.2740 0.3793 0.2689 0.3142 0.3255 0.3381 0.2780 0.3455 0.2982 0.3364 0.3232 0.3537 0.2734 0.3511 0.3728 0.3343 0.2894 0.2903 0.3095 0.2903 0.3171 0.3291 0.2975 0.3387 0.3543 0.3363 0.3571 0.3476 12.57 14.06 13.11 17.98 13.12 13.96 14.40 14.39 12.19 14.04 13.19 16.41 13.64 14.86 11.78 14.33 18.01 15.69 12.42 13.14 14.33 12.40 15.10 15.16 13.40 15.05 14.58 15.43 16.16 16.17 1.7748 1.8786 1.8515 1.6795 1.6411 1.9205 1.8740 2.0329 1.7274 1.8932 1.7259 1.8769 1.7387 1.8951 1.8277 1.8320 1.6347 1.8899 1.6529 1.8617 1.6931 1.8646 1.7775 1.8785 1.7745 2.0020 1.8418 1.8380 1.8179 1.8847 76.83 79.94 88.59 79.60 80.05 85.36 82.92 86.51 75.76 76.96 76.37 91.56 73.36 79.63 78.78 74.78 78.97 88.73 70.94 84.24 78.38 79.68 84.64 86.57 79.93 88.98 75.79 84.31 82.26 87.66 1.6126 1.7780 1.7107 1.5725 1.5376 1.7789 1.7521 1.9220 1.5993 1.7207 1.5848 1.7673 1.6197 1.7609 1.6738 1.7076 1.5384 1.7878 1.5406 1.7607 1.5997 1.7482 1.6482 1.7562 1.6450 1.8087 1.7492 1.7356 1.6798 1.7681 69.81 75.66 81.85 74.53 75.00 79.06 77.53 81.79 70.14 69.95 70.12 86.21 68.34 73.99 72.15 69.70 74.32 83.93 66.12 79.67 74.06 74.71 78.48 80.93 74.10 80.39 71.98 79.61 76.01 82.24 1.8099 78.35 2.3515 100.06 1.7267ai 82.62a 2.4684 116.98 1.9912 97.13 2.0129 89.46 2.2800 100.88 2.6892 114.43 2.2776 99.89 2.4079 97.88 1.9875 87.94 2.3722 115.72 2.4935 105.21 2.3446 98.51 1.4559b 62.75b 2.3625 96.43 2.7172 131.26 2.6176 122.89 2.5577 109.77 2.1083 95.40 2.1691 100.42 2.0146 86.09 2.1117 100.56 2.7024 124.53 2.2975 103.49 2.3873 106.10 2.4171 99.47 2.3115 106.03 2.7956 126.50 2.9170 135.67 1.1447 1.0306 1.0523 1.5301 1.2054 1.1453 1.2851 1.3437 1.2605 1.2589 1.0487 1.3402 1.5376 1.3177 1.0436 1.3581 1.4232 1.4343 1.4163 1.0055 1.1139 1.0707 1.1951 1.3951 1.1581 1.2017 1.3391 1.2358 1.5191 1.5807 49.55 43.86 50.35 72.52 58.80 50.90 56.86 57.18 55.28 51.17 46.40 65.38 64.88 55.36 44.98 55.43 68.75 67.34 60.78 45.50 51.57 45.76 56.91 64.29 52.17 53.41 55.11 56.69 68.74 73.52 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Damaged during processing (some fluid loss prior to weighing); values excluded from group averages and statistical analyses. b. Damaged during processing (weight affected); values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 11) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 155 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP IV EPIDIDYMIS RIGHT ABS. REL. WT. % BRW TESTIS RIGHT ABS. REL. WT. % BRW 10 MG/KG/DAY PROSTATE ABS. WT. REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. ] WT. % 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 2.31 2.35 2.09 2.11 2.05 2.25 2.26 2.35 2.28 2.46 2.26 2.05 2.37 2.38 2.32 2.45 2.07 2.13 2.33 2.21 2.16 2.34 2.10 2.17 2.22 2.25 2.43 2.18 2.21 2.15 0.6462 27.97 0.6514 27.72 0.4308 20.61 0.7073 33.52 0.6242 30.45 0.6590 29.29 0.7200 31.86 0.7592 32.31 0.6287 27.57 0.7246 29.46 0.6728 29.77 0.7257 35.40 0.7072 29.84 0.7933 33.33 0.6890 29.70 0.3207a 13.09 0.7579 36.61 0.7502 35.22 0.6525 28.00 0.6630 30.00 0.6400 29.63 0.6336 27.08 0.6594 31.40 0.7495 34.54 0.6537 29.44 0.7396 32.87 0.7265 29.90 0.7409 33.99 0.7150 32.35 0.7717 35.89 1.6959 73.42 1.8472 78.60 1.5803 75.61 1.5982 75.74 1.5583 76.01 1.9059 84.71 1.8881 83.54 2.0050 85.32 1.6871 74.00 1.9501 79.27 1.7611 77.92 1.8833 91.87 1.7711 74.73 1.9822 83.28 1.8191 78.41 0.8699a 35.51 1.6624 80.31 1.9331 90.76 1.6711 71.72 1.8448 83.48 1.6398 75.92 1.8443 78.82 1.7083 81.35 1.8709 86.22 1.7351 78.16 2.0528 91.24 1.7853 73.47 1.8402 84.41 1.7551 79.42 1.8332 85.26 1.1002 0.6953 0.9426 0.8671 1.1675 1.1603 1.1685 1.2923 1.2763 0.8127 0.9267 0.9056 1.2401 1.4428 1.0972 1.1747 1.2753 0.8310 1.0523 0.7736 0.9264 0.8620 1.1091 1.0910 1.2177 1.0765 1.0506 0.6135 0.7355 1.2191 47.63 29.59 45.10 41.09 56.95 51.57 51.70 54.99 55.98 33.04 41.00 44.18 52.32 60.62 47.29 47.95 61.61 39.01 45.16 35.00 42.89 36.84 52.81 50.28 54.85 47.84 43.23 28.14 33.28 56.70 0.009 0.013 0.014 0.012 0.016 0.019 0.013 0.008 0.015 0.014 0.017 0.012 0.019 0.020 0.010 0.011 0.011 0.015 0.017 0.019 0.012 0.011 0.014 0.011 0.015 0.013 0.018 0.018 0.013 0.009 0.39 0.55 0.67 0.57 0.78 0.84 0.58 0.34 0.66 0.57 0.75 0.58 0.80 0.84 0.43 0.45 0.53 0.70 0.73 0.86 0.56 0.47 0.67 0.51 0.68 0.58 0.74 0.8'2 0.59 0.42 30.43 27.20 30.49 28.77 30.35 29.83 28.85 27.33 19.75 31.22 22.78 23.84 31.22 36.32 35.62 29.09 29.42 32.27 25.48 24.32 22.43 24.75 31.60 26.03 34.10 28.78 27.61. 28.62 32.24 31.49 1317.32 1157.45 1458.85 1363.51 1480.49 1325.78 1276.55 1162.98 866.23 1269.10 1007.96 1162.93 1317.30 1526.05 1535.34 1187.35 1421.26 1515.02 1093.56 1100.45 1038.43 1057.69 1504.76 1199.54 1536.04 1279.11 1136.21 1312.84 1458.82 1464.65 2.23 2.42 2.34 2.75 2.29 2.99 2.16 2.61 2.11 2.37 2.03 2.05 2.52 2.61 2.45 2.17 2.50 2.42 2.19 2.08 1.87 2.03 2.18 2.38 2.39 2.49 2.37 2.42 2.31 2.48 96 64 1 0 2 9ft 111.96 130 33 11 1 .71 132.89 95 5ft 11 1 06 92 54 96.34 89.82 100.00 106.33 109.66 105.60 Rft 6 7 120.77 113.62 93.99 94.12 86.57 86.75 103.81 109.68 107.66 110.67 97.53 1 1 1 .01 104.52 115.35 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. W T . = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13706 had a small and flaccid right epididymis and right testis. See the individual necropsy observations table (Table B16). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 12) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 156 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP IV KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW 10 MG/KG/DAY ADRENAL RIGHT ABS. WT. REL. % BRW SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL. % BRW 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 13719 13720 2.31 2.35 2.09 2.11 2.05 2.25 2.26 2.35 2.28 2.46 2.26 2.05 2.37 2.38 2.32 2.45 2.07 2.13 2.33 2.21 2.16 2.34 2.10 2.17 2.22 2.25 2.43 2.18 2.21 2.15 2.27 2.31 2.37 3.01 2.34 2.82 2.16 2.63 2.09 2.40 2.01 2.10 2.38 2.64 2.51 2.46 2.47 2.57 2.20 2.17 1.92 2.04 2.15 2.13 2.45 2.60 2.38a 2.33 2.42 2.56 98.27 98.30 113.40 142.65 114.15 125.33 95.58 111.91 91.67 97.56 88.94 102.44 100.42 110.92 108.19 100.41 119.32 120.66 94.42 98.19 88.89 87.18 102.38 98.16 110.36 115.56 97.94 106.88 109.50 119.07 0.018 0.026 0.036 0.025 0.028 0.035 0.032 0.034 0.019 0.030 0.022 0.028 0.043 0.036 0.033 0.031 0.032 0.038 0.031 0.029 0.028 0.030 0.025 0.026 0.035 0.028 0.030 0.037 0.033 0.022 0.78 1.11 1.72 1.18 1.36 1.56 1.42 1.45 0.83 1.22 0.97 1.36 1.81 1.51 1.42 1.26 1.54 1.78 1.33 1.31 1.30 1.28 1.19 1.20 1.58 1.24 1.23 1.70 1.49 1.02 0.043 0.029 0.038 0.037 0.030 0.033 0.033 0.040 0.016 0.030 0.021 0.024 0.034 0.030 0.026 0.026 0.030 0.038 0.019 0.025 0.039 0.033 0.027 0.051 0.033 0.026 0.032 0.033 0.037 0.026 1.86 1.23 1.82 1.75 1.46 1.47 1.46 1.70 0.70 1.22 0.93 1.17 1.43 1.26 1.12 1.06 1.45 1.78 0.82 1.13 1.80 1.41 1.28 2.35 1.49 1.16 1.32 1.51 1.67 1.21 1.01 0.83 0.97 0.81 0.79 1.04 0.90 0.82 0.81 0.99 0.71 0.84 0.95 1.15 0.90 0.79 0.79 0.76 0.74 0.66 0.83 1.11 0.72 0.52 0.98 0.79 0.87 0.93 1.10 1.03 43.72 35.32 46.41 38.39 38.54 46.22 39.82 34.89 35.53 40.24 31.42 40.98 40.08 48.32 38.79 32.24 38.16 35.68 31.76 29.86 38.42 47.44 34.28 23.96 44.14 35.11 35.80 42.66 49.77 47.91 0.61 0.55 0.77 0.50 0.40 0.54 0.50 0.52 0.42 0.44 0.26 0.27 0.31 0.56 0.54 0.38 0.40 0.34 0.28 0.40 0.50 0.36 0.26 0.18 0.29 0.24 0.390.25 0.47 0.23 26.41 23.40 36.84 23.70 19.51 24.00 22.12 22.13 18.42 17.89 11.50 13.17 13.08 23.53 23.28 15.51 19.32 15.96 12.02 18.10 23.15 15.38 12.38 8.29 13.06 10.67 16.05 11.47 21.27 10.70 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. W T . = ORGAN WEIGHT. REL. BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13717 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16 ) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 13) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS RAT NUMBER BRAIN WEIGHT DOSAGE GROUP V EPIDIDYMIS LEFT ABS. REL. WT. % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % BRW 30 MG/KG/DAY TESTIS LEFT ABS. REL. WT. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. W T . % BRW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % BRW 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732a 13733 13734 13735 2.32 2.12 2.18 2.22 2.05 2.39 2.09 2.40 2.26 2.18 2.10 1.83 2.41 2.25 2.22 0.6074 26.18 0.6274 29.59 0.6173 28.32 0.6288 28.32 0.5636 27.49 0.5924 24.79 0.6562 31.40 0.6189 25.79 0.6563 29.04 0.7344 33.69 0.6264 29.83 0.32 0.4488c 18.62 0.6218 27.64 0.6602 29.74 0.2790 0.2822 0.2866 0.2856 0.2434 0.2529 0.3344 0.2708 0.2832 0.3692 0.2816 b 0.2281 0.3056 0.2885 12.02 13.31 13.15 12.86 11.87 10.58 16.00 11.28 12.53 16.94 13.41 -- 9.46 13.58 13.00 1.6557 2.0342 1.7454 1.7350 1.5799 1.6603 1.6767 1.8145 1.8213 1.9206 1.8082 1.57 1.5848 1.7707 1.6260 71.37 95.95 80.06 78.15 77.07 69.47 80.22 75.60 80.59 88.10 86.10 -- 65.76 78.70 73.24 1.5270 65.82 1.9065 89.93 1.6102 73.86 1.6175 72.86 1.4784 72.12 1.4205 59.44 1.5666 74.96 1.6036 66.82 1.7046 75.42 1.7641 80.92 1.6879 80.38 b 0.7696c 31.93 1.6457 73.14 1.4871 66.99 2.1394 92.22 1.9349 91.27 1.8187 83.43 1.8648 84.00 2.0211 98.59 2.3913 100.05 2.3512 112.50 1.6491 68.71 2.7535 121.84 2.7822 127.62 2.2953 109.30 0.41 1.9756 81.98 1.9533 86.81 2.0416 91.96 1.1271 0.9897 1.0162 1.0530 1.1224 1.3574 1.2199 0.8819 1.6355 1.3529 1.3058 48.58 46.68 46.61 47.43 54.75 56.79 58.37 36.74 72.37 62.06 62.18 1.0945 45.41 1.0168 45.19 1.0459 47.11 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13732 was moribund sacrificed on day 45 of study; values excluded from group averages and statistical analyses. b. Value was not recorded. c. Rat 13733 had a small and flaccid left epididymis and left testis minus tunica albuginea. See the individual necropsy observations table (Table B16). ARGUS 418-020 Page 157 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 14) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS RAT NUMBER BRAIN WEIGHT DOSAGE GROUP V EPIDIDYMIS LEFT ABS. REL. W T . % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. W T . % BRW 30 MG/KG/DAY TESTIS LEFT ABS. REL. W T . % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. W T . % BRW SEMINAL VESICLES WITH FLUID ABS. REL. W T . % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % BRW 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 1.95 2.09 2.25 2.16 2.47 2.18 2.06 2.27 2.25 2.32 2.20 1.88 2.28 2.27 2.04 0.6673 34.22 0.6265 29.98 0.7368 32.75 0.6346 29.38 0.6890 27.89 0.4128a. 18.94 0.6057 29.40 0.6398 28.18 0.6318 28.08 0.5971 25.74 0.6928 31.49 0.6158 32.76 0.7390 32.41 0.7383 32.52 0.6466 31.70 0.3010 15.44 0.2859 13.68 0.3496 15.54 0.2936 13.59 0.3195 12.94 0.1813a 8.32 0.2949 14.32 0.3157 13.91 0.2745 12.20 0.2785 12.00 0.2873 13.06 0.2828 15.04 0.3243 14.22 0.3499 15.41 0.2750 13.48 1.8057 92.60 1.8269 87.41 1.8806 83.58 1.7360 80.37 1.8928 76.63 0.9095a 41.72 1.5689 76.16 1.7613 77.59 1.7873 79.44 1.7386 74.94 1.7150 77.95 1.9071 101.44 2.0476 89.81 1.9514 85.96 2.8 8 4 2 b l 4 1 .3 8 1.6957 86.96 1.7194 82.27 1.7560 78.04 1.6485 76.32 1.7714 71.72 0.7763a 35.61 1.4689 71.30 1.6391 72.21 1.6903 75.12 1.6364 70.53 1.6329 74.22 1.7986 95.67 1.9007 83.36 1.8267 80.47 2.6964bl32.18 2.2496 115.36 1.7412 83.31 2.2771 101.20 2.1199 98.14 1.9407 78.57 1.5799 72.47 2.0911 101.51 2.2751 100.22 2.1831 97.03 1.6923 72.94 2.0396 92.71 1.8077 96.15 2.1969 96.36 2.0347 89.63 1.6893 82.81 1.2149 1.1388 1.1760 1.1596 1.0294 1.0094 1.1513 1.1189 1.2490 0.9536 1.1029 0.8948 1.2020 1.1848 1.0501 62.30 54.49 52.27 53.68 41.68 46.30 55.89 49.29 55.51 41.10 50.13 47.60 52.72 52.19 51.48 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW - (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13741 had small and flaccid epididymides and testes. See the individual necropsy observations table (Table B16). b. Rat 13750 had a large left epididymis and left testis minus tunica albuginea. See the individual necropsy observations table (Table B16). ARGUS 418-020 Page 158 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 15) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS RAT NUMBER BRAIN WEIGHT EPIDIDYMIS RIGHT ABS. REL. WT. % BRW TESTIS RIGHT ABS. REL. WT. % BRW PROSTATE ABS. WT. REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW DOSAGE GROUP V 30 MG/KG/DAY 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732a 13733 13734 13735 2.32 2.12 2.18 2.22 2.05 2.39 2.09 2.40 2.26 2.18 2.10 1.83 2.41 2.25 2.22 0.5828 0.6248 0.6269 0.6778 0.6145 0.5830 0.6714 0.5943 0.6131 0.7137 0.6397 0.31 0.7056 0.6340 0.6247 25.12 29.47 28.76 30.53 29.98 24.39 32.12 24.76 27.13 32.74 30.46 29.28 28.18 28.14 1.6442 2.0050 1.6768 1.7229 1.6811 1.6140 1.6811 1.7995 1.7874 1.9707 1.7492 1.54 1.8567 1.7743 1.6311 70.87 94.58 76.92 77.61 82.00 67.53 80.44 74.98 79.09 90.40 83.30 -- 77.04 78.86 73.47 0.8431 0.8430 0.5950 0.6971 0.7775 1.1966 1.1502 0.8251 0.8078 0.8931 0.6744 0.34 0.9479 1.2570 0.9716 36.34 39.76 27.29 31.40 37.93 50.07 55.03 34.38 35.74 40.97 32.11 -- 39.33 55.87 43.76 0.015 0.013 0.010 0.009 0.005 0.011 0.009 0.011 0.008 0.011 0.011 0.006 0.012 0.007 0.007 0.65 0.61 0.46 0.40 0.24 0.46 0.43 0.46 0.35 0.50 0.52 0.50 0.31 0.32 32.46 26.38 25.29 20.55 24.05 26.25 27.77 33.99 30.46 36.40 27.84 15.94 34.60 28.30 26.33 1399.14 1244.34 1160.09 925.68 1173.17 1098.33 1328.71 1416.25 1347.79 1669.72 1325.71 1435.68 1257.78 1186.04 2.04 1.97 1.96 2.05 1.65 2.21 2.08 1.89 2.13 2.44 2.02 1.22 2.19 2.22 2.06 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. W T . = ORGAN WEIGHT, REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13732 was moribund sacrificed on day 45 of study; values excluded from group averages and statistical analyses. 87.93 92.92 89.91 92.34 80.49 92.47 99.52 78.75 94.25 111.93 96.19 90.87 98.67 92.79 ARGUS 418-020 Page 159 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 16) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS RAT NUMBER BRAIN WEIGHT EPIDIDYMIS RIGHT ABS. REL. WT. % BRW TESTIS RIGHT ABS. REL. WT. BRW PROSTATE ABS. WT. REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW DOSAGE GROUP V 30 MG/KG/DAY 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 1.95 2.09 2.25 2.16 2.47 2.18 2.06 2.27 2.25 2.32 2.20 1.88 2.28 2.27 2.04 0.6535 33.51 0.6117 29.27 0.7239 32.17 0.6380 29.54 0.6731 27.25 0.3794a 17.40 0.6017 29.21 0.6511 28.68 0.6378 28.35 0.5834 25.15 0.6752 30.69 0.6142 32.67 0.7365 32.30 0.7260 31.98 0.6502 31.87 1.7745 91.00 1.7991 86.08 1.9556 86.92 1.7722 82.05 1.8953 76.73 0.8606a 39.48 1.5535 75.41 1.7824 78.52 1.8145 80.64 1.7338 74.73 1.6953 77.06 1.8456 98.17 2.0122 88.25 1.8831 82.96 1.7065 83.65 1.1293 0.6582 0.9491 0.6872 1.0956 0.5990 0.7266 0.8984 0.7553 0.8432 0.8258 0.5597 1.0400 0.8505 0.8981 57.91 31.49 42.18 31.81 44.36 27.48 35.27 39.58 33.57 36.34 37.54 29.77 45.61 37.47 44.02 0.010 0.009 0.012 0.015 0.010 0.007 0.007 0.008 0.012 0.009 0.015 0.016 0.013 0.011 0.013 0.51 0.43 0.53 0.69 0.40 0.32 0.34 0.35 0.53 0.39 0.68 0.85 0.57 0.48 0.64 26.04 25.32 27.00 23.10 29.12 27.33 25.57 23.40 24.04 29.53 28.24 23.29 31.63 27.03 25.92 1335.38 1211.48 1200.00 1069.44 1178.95 1253.67 1241.26 1030.84 1068.44 1272.84 1283.64 1238.83 1387.28 1190.75 1270.59 1.85 1.73 1.98 1.95 1.98 1.82 1.60 1.87 1.80 1.92 2.27 1.89 2.20 1.79 2.07 94.87 82.78 88.00 90.28 80.16 83.49 77.67 82.38 80.00 82.76 103.18 100.53 96.49 78.85 101.47 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT, REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13741 had small and flaccid epididymides and testes. See the individual necropsy observations table (Table B1 6 ) . ARGUS 418-020 Page 160 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 17) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS ARGUS 418-020 Page 161 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP V KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW 30 MG/KG/DAY ADRENAL RIGHT ABS. REL. WT. % BRW SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. 1 % 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732b 13733 13734 13735 2.32 2.12 2.18 2.22 2.05 2.39 2.09 2.40 2.26 2.18 2.10 1.83 2.41 2.25 2.22 2.19 2.19 1.94 2.01 1.73 2.20 2.16 1.94 2.05a 2.45 2.05 1.25 2.31c 2.30 2.23 94.40 103.30 88.99 90.54 84.39 92.05 103.35 80.83 90.71 112.38 97.62 95.85 102.22 100.45 0.035 0.035 0.033 0.042 0.028 0.029 0.026 0.028 0.020 0.035 0.028 0.026 0.032 0.022 0.030 1.51 1.65 1.51 1.89 1.36 1.21 1.24 1.17 0.88 1.60 1.33 -- 1.33 0.98 1.35 0.040 0.035 0.028 0.037 0.026 0.039 0.024 0.025 0.014 0.031 0.026 0.026 0.035 0.023 0.014 1.72 1.65 1.28 1.67 1.27 1.63 1.15 1.04 0.62 1.42 1.24 -- 1.45 1.02 0.63 0.76 0.80 0.72 0.79 0.45 0.93 0.75 0.67 0.52 0.70 0.57 0.13 0.94 0.69 0.97 32.76 37.74 33.03 35.58 21.95 38.91 35.88 27.92 23.01 32.11 27.14 39.00 30.67 43.69 0.36 0.49 0.37 0.49 0.20 0.51 0.28 0.25 0.25 0.38 0.18 0.12 0.28 0.32 0.40 15.52 23.11 16.97 22.07 9.76 21.34 13.40 10.42 11.06 17.43 8.57 -- 11.62 14.22 18.02 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X a. Rat 13729 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16 ) . b. Rat 13732 was moribund sacrificed on day 45 of study; values excluded from group averages and statistical analyses, c. Rat 13733 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16 ) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B19 (PAGE 18) : BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION MALE RATS RAT NUMBER BRAIN WEIGHT KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW ADRENAL RIGHT ABS. REL. WT. % BRW SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL. % BRW DOSAGE GROUP V 30 MG/KG/DAY 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 1.95 2.09 2.25 2.16 2.47 2.18 2.06 2.27 2.25 2.32 2.20 1.88 2.28 2.27 2.04 1.99 1.79 1.95 2.01 2.15 2.02 1.64 1.93 1.94 2.07 2.20 1.93 2.43 1.78 2.04 102.05 85.64 86.67 93.06 87.04 92.66 79.61 85.02 86.22 89.22 100.00 102.66 106.58 78 .41 100.00 0.030 0.021 0.037 0.026 0.024 0.009 0.027 0.020 0.029 0.026 0.028 0.031 0.032 0.029 0.021 1.54 1.00 1.64 1.20 0.97 0.41 1.31 0.88 1.29 1.12 1.27 1.65 1.40 1.28 1.03 0.023 0.017 0.032 0.025 0.027 0.014 0.029 0.026 0.028 0.026 0.025 0.020 0.030 0.028 0.020 1.18 0.81 1.42 1.16 1.09 0.64 1.41 1.14 1.24 1.12 1.14 1.06 1.32 1.23 0.98 0.72 0.65 0.73 0.69 0.80 0.42 0.86 0.62 0.58 0.73 0.74 0.51 1.09 0.87 1.06 36.92 31.10 32.44 31.94 32.39 19.27 41.75 27.31 25.78 31.46 33.64 27.13 47.81 38.32 51.96 0.28 0.20 0.32 0.25 0.27 0.20 0.17 0.20 0.29 0.28 0.35 0.27 0.38 0.29 0.27 14.36 9.57 14.22 11.57 10.93 9.17 8.25 8.81 12.89 12.07 15.91 14.36 16.67 12.78 13.24 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. Page 162 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B20 (PAGE 1) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS (See footnotes at the end of this table.) ARGUS 418-020 Page 163 DOSAGE GROUP I RAT NUMBER NUMBER MOTILE 13601 267 13602 189 13603 392 13604 408 13605 400 13606 502 13607 380 13608 359 13609 123 13610 409 13611 247 13612 458 13613 360 13614 428 13615 375 13616 269 13617 548 13618 229 13619 155 13620 372 13621 413 13622 286 13623 267 13624 398 13625 392 13626 454 13627 355 13628 373 13629 394 13630 417 MOTILE PERCENT 92 87 86 92 85 84 92 88 34 88 76 89 88 79 89 80 81 85 63 77 87 88 83 89 91 85 85 84 75 76 STATIC COUNT (NONMOTILE) 22 29 64 37 72 93 34 50 240 58 76 54 50 112 47 68 127 42 91 113 60 40 53 47 38 83 61 73 131 133 0 MG/KG/DAY TOTAL COUNT a 289 218 456 445 472 595 414 409 363 467 323 512 410 540 422 337 675 271 246 485 473 326 320 445 430 537 416 446 525 550 SPERM COUNT b 79 111 89 77 118 136 128 143 38 132 91 120 95 60 145 129 117 117 89 95 146 147 137 205 83 63 83 133 125 88 SPERM SPERMATID DENSITY c COUNT d 770.5 38 1040.5 36 770.6 45 710.3 33 963.4 66 1089.5 36 1156.0 75 1198.0 68 512.5 27 1324.4 59 804.8 91 1202.4 56 913.0 67 635.1 52 1148.5 67 1046.1 71 972.8 47 978.7 38 648.0 50 794.5 53 1284.9 29 1345.2 82 1017.2 50 1764.4 45 800.6 . 56 '481.4 37 752.2 44 1023.2 37 1093.4 37 637.5 30 SPERMATID DENSITY e 85.1 68.4 78.4 56.1 111.8 59.2 124.4 113.3 54.2 115.0 158.4 99.S 120.3 101.7 105.8 112.6 82.4 63.6 78.4 89.9 161.0 141.2 91.6 77.1 96.8 58.4 81.7 59.9 69.0 44.4 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) . TABLE B20 (PAGE 2): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS (See footnotes at the end of this table .) ARGUS 418-020 Page 164 DOSAGE GROUP II RAT NUMBER NUMBER MOTILE 13631 530 13632 274 13633 403 13634 264 13635 178 13636 440 13637 554 13638 350 13639 244 13640 198 13641 541 13642 407 13643 302 13644 177 13645 272 13646 225 13647 328 13648 430 13649 410 13650 305 13651 300 13652 205 13653 370 13654 227 13655 562 13656 470 13657 417 13658 490 13659 280 13660 243 MOTILE PERCENT 87 84 89 83 70 82 88 78 92 85 86 84 93 80 84 69 67 80 79 84 92 95 89 88 89 93 91 84 88 89 STATIC COUNT (NONMOTILE) 82 51 49 56 77 96 75 101 21 35 89 78 22 45 52 101 159 110 109 56 27 10 48 31 66 37 43 95 39 31 1 MG/KG/DAY TOTAL COUNT a 612 325 452 320 255 536 629 451 265 233 630 485 324 222 324 326 487 540 519 361 327 215 418 258 628 507 460 585 319 274 SPERM COUNT b 101 101 69 103 98 93 98 54 147 130 104 114 138 112 130 199 104 135 132 78 180 212 117 99 162 170 110 72 152 71 SPERM DENSITY C 974.5 922.8 562.9 884.4 1007.8 763.2 825.5 559.5 1441.0 1063.5 853.0 1046.9 1174.8 1012.4 1181.4 1662.3 1008.9 1274.5 1248.7 784.5 1586.5 1898.0 1215.7 975.7 1405.2 1418.0 1041.6 789.8 1386.2 636.8 SPERMATID COUNT d 40 45 44 56 49 42 42 39 51 56 47 40 49 49 32 31 68 48 28 65 59 50 62 60 . 72 41 40 24 30 18 SPERMATID DENSITY e 74.9 71.2 77.3 97.7 91.5 72.7 79.7 62.3 113.5 91.7 78.9 71.3 77.2 77.9 61.5 56.8 120.5 80.9 49.8 102.4 93.1 85.5 105.5 123.6 105.0 73.9 70.0 47.5 48.1 33.0 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B20 (PAGE 3) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS (See footnotes at the end of this table.) ARGUS 418-020 Page 165 DOSAGE GROUP III RAT NUMBER NUMBER MOTILE 13661 261 13662 387 13663 258 13664 288 13665 424 13666 392 13667 508 13668 423 13669 424 13670 298 13671 503 13672 270 13673 451 13674 549 13675 512 13676 523 13677 376 13678 358 13679 293 13680 269 13681 235 13682 391 13683 453 13684 549 13685 221 13686 411 13687 357 13688 245 13689 252 13690 317 MOTILE PERCENT 94 87 87 63 82 89 93 92 86 91 92 83 90 83 90 92 93 79 90 88 73 87 91 87 94 88 81 82 85 93 STATIC COUNT (NONMOTILE) 17 59 40 172 94 46 37 37 70 31 43 54 48 112 56 47 27 94 33 36 85 60 44 84 13 57 83 54 45 24 3 MG/KG/DAY TOTAL COUNT a 278 446 298 460 518 438 545 460 4 94 329 546 324 499 661 568 570 403 452 326 305 320 451 497 633 234 468 440 299 297 341 SPERM COUNT b 87 132 118 95 86 77 78 72 117 173 85 64 90 87 131 121 139 76 134 107 79 183 214 105 180 82 107 100 138 78 SPERM SPERMATID DENSITY C COUNT d 773.4 40 1176.0 48 926.5 48 845.6 49 826.5 53 762.0 43 684.4 39 853.6 56 1053.4 63 1368.4 98 842.9 50 671.0 29 944.6 47 885.8 64 1132.9 32 1076.0 59 1319.2 46 704.9 39 1177.5 27 971.5 43 678.9 80 1520.7 50 2099.2 54 1033.8 42 1641.5 . 43 '825.3 57 969.1 34 803.3 37 1195.2 26 740.3 24 SPERMATID DENSITY e 66.3 85.8 78.9 83.0 96.4 72.0 74.7 108.1 114.0 161.3 88.2 51.0 87.6 119.9 62.7 93.3 83.6 71.2 47.3 70.2 119.8 75.1 100.5 77.0 73.4 98.5 66.1 56.0 47.1 42.3 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B20 (PAGE 4) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS > (See footnotes at the end of this table.) ARGUS 418-020 Page 166 DOSAGE GROUP IV RAT NUMBER NUMBER MOTILE 13691 353 13692 328 13693 368 13694 202 13695 517 13696 305 13697 248 13698 467 13699 283 13700 334 13701 237 13702 355 13703 385 13704 305 13705 456 13706 241 13707 401 13708 334 13709 251 13710 535 13711 294 13712 396 13713 302 13714 247 13715 447 13716 273 13717 210 13718 412 13719 13720 397 264 MOTILE PERCENT 85 86 89 83 82 83 86 88 91 89 81 93 86 88 90 85 93 92 85 87 94 93 89 80 86 87 83 87 96 86 STATIC COUNT (NONMOTILE) 61 55 45 40 116 64 40 61 29 40 54 27 65 40 51 44 30 30 43 82 20 32 39 63 74 41 43 63 15 44 10 MG/KG/DAY TOTAL COUNT a 414 383 413 242 633 369 288 528 312 374 291 382 450 345 507 285 431 364 294 617 314 428 341 310 521 314 253 475 412 308 SPERM COUNT b 103 101 78 157 94 72 109 136 106 100 86 121 129 278 92 89 162 152 69 86 143 84 139 121 72 128 160 81 179 105 SPERM DENSITY C 1026.3 884.3 823.5 1197.4 1011.2 662.9 968.7 1163.6 1103.0 837.3 834.2 1040.5 1154.6 2273.6 973.4 733.3 1257.0 1315.3 689.7 857.0 1336.5 837.0 1268.0 1063.6 700.1 1093.2 1306.3 696.7 1450.0 873.8 SPERMATID COUNT d 26 40 63 46 30 33 62 59 48 70 36 51 55 42 46 71 59 52 51 69 43 55 58 38 . 30 59 29 19 26 25 SPERMATID DENSITY e 46.6 65.1 106.5 84.6 56.4 53.7 102.4 88.8 86.8 117.7 65.7 83.5 98.2 69.0 79.5 120.3 110.9 84.1 95.8 113.4 77.8 91.0 101.8 62.6 52.8 94.4 48.0 31.7 44.8 40.9 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B20 (PAGE 5) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS (See footnotes at the end of this table.) ARGUS 418-020 Page 167 DOSAGE GROUP V RAT NUMBER MOTILE STATIC COUNT NUMBER MOTILE PERCENT (NONMOTILE) 13721 498 92 44 13722 375 82 81 13723 386 84 71 13724 208 75 68 13725 457 81 105 13726 368 77 107 13727 243 89 29 13728 420 88 59 13729 188 80 46 13730 345 90 37 13731 477 86 78 13732 MORIBUND SACRIFICED ON DAY 45 OF STUDY 13733 106 90 12 13734 321 90 34 13735 320 81 73 13736 710 92 60 13737 2 94 65 158 13738 266 78 73 13739 262 86 41 13740 388 86 61 13741 108 58 79 13742 179 68 83 13743 320 96 15 13744 392 93 31 13745 440 89 53 13746 273 90 31 13747 228 82 49 13748 218 84 42 13749 470 90 51 13750 235 91 23 30 MG/KG/DAY TOTAL COUNT a 542 456 457 276 562 475 272 479 234 382 555 118 355 393 770 452 339 303 449 187 262 335 423 493 304 277 260 521 258 SPERM COUNT b 82 87 64 105 57 80 134 70 107 157 118 1 115 69 85 122 173 105 101 13 113 119 91 130 102 77 131 125 113 SPERM DENSITY C 850.2 891.8 646.0 1063.5 677.4 915.1 1159.2 747.7 1092.9 1230.1 1212.1 12.7 1088.6 691.8 816.9 1234.4 1431.5 1034.5 914.4 207.4 1108.4 1090.4 959.0 1350.3 1027.0 787.6 1168.5 1033.4 1188.6 SPERMATID COUNT d 40 44 39 48 41 36 82 43 49 51 52 2 74 44 66 52 55 38 41 3 42 41 41 37 41 39 39 34 23 SPERMATID DENSITY e 75.8 66.8 70.1 85.8 80.2 73.3 151.4 77.6 83.2 83.6 89.1 7.5 130.1 85.6 112.6 87.5 90.6 66.7 67.0 11.2 82.7 72.4 70.2 65.4 72.6 62.7 59.4 53.8 24.7 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B20 (PAGE 6) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS FOOTNOTES:______________________________________ _ __ ____ ____ __ _ __________ _____ ____ __ __ _ __ ___ _ _ a. Sum of number motile and static count. Groups of five fields were evaluated until a sperm count of at least 200 was achieved or 20 fields were evaluated. b. Sperm count used in the calculation of sperm density. Ten fields were evaluated. c. The sperm density was calculated by dividing the sperm count by the volume in the image area (34.3 x 10`6 mL) , multiplying by 2 (dilution factor) and multiplying by 10'6 to obtain the sperm concentration. The calculated sperm concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left cauda epididymis (see Table B17 for the weight of the left cauda epididymis) to obtain the sperm density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. d. Spermatid count used in the calculation of spermatid density. Ten fields were evaluated. e. The spermatid density was calculated by dividing the spermatid count by the volume in the image area (34.3 x 10"6 m L), multiplying by 2 (dilution factor) and multiplying by 10"6 to obtain the spermatid concentration. The calculated spermatid concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left testis minus tunica albuginea (see Table B18 for the weight of the left testis minus tunica albuginea) to obtain the spermatid density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. ARGUS 418-020 Page 168 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B21 (PAGE 1) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 169 RAT NUMBER DETACHED NORMAL HEAD NO HEAD BROKEN FLAGEL- LUM DOSAGE GROUP I 0 MG/KG/DAY 13601 193 6 1 13602 199 0 1 13603 192 34 13604 189 9 2 13605 189 8 3 13606 190 7 3 13607 197 2 1 13608 194 4 1 13609 60 64 75 13610 189 6 5 13611 179 15 6 13612 186 9 5 13613 197 2 1 13614 187 6 7 13615 189 9 2 13616 188 10 2 13617 193 6 1 13618 181 10 9 13619 192 5 2 13620 191 8 1 13621 193 52 13622 191 3 4 13623 192 6 2 13624 191 6 3 13625 196 2 2 13626 195 4 1 13627 195 2 2 13628 197 2 1 13629 196 1 3 13630 192 5 3 0 0 1 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 1 0 0 0 NO HOOK 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 EXCES SIVE HOOK COILED BENT SHORT FLAGEL FLAGEL SPERM LUM LUM HEAD OTHER 00000 00000 00000 00000 00000 00000 00000 0000 0 00000 00000 0000 0 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 PERCENT ABNORMAL 3.5 0.5 4.0 5.5 5.5 5.0 1.5 3.0 70.0 5.5 10.5 7.0 1.5 G.5 5.5 6.0 3.5 9.5 4.0 4.5 3.5 4.5 4.0 4.5 2.0 2.5 2.5 1.5 2.0 4.0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B21 (PAGE 2) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 170 RAT DETACHED NO NUMBER NORMAL HEAD HEAD BROKEN FLAGEL- LUM DOSAGE GROUP II 1 MG/KG/DAY 13631 194 3 3 13632 191 6 3 13633 193 52 13634 185 4 8 13635 188 7 2 13636 195 3 2 13637 195 3 2 13638 160 20 19 13639 196 12 13640 187 6 7 13641 195 14 13642 196 2 2 13643 197 3 0 13644 194 32 13645 197 1 1 13646 195 2 3 13647 197 0 3 13648 186 8 6 13649 197 2 1 13650 192 4 3 13651 190 54 13652 191 5 4 13653 185 10 2 13654 191 4 2 13655 196 12 13656 196 1 3 13657 193 70 13658 191 2 6 13659 189 74 13660 191 5 3 0 0 0 3 3 0 0 1 1 0 0 0 0 1 1 0 0 0 0 1 1 0 2 3 1 0 0 1 0 0 NO HOOK 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 EXCESSIVE HOOK COILED BENT FLAGEL- FLAGEL- LUM LUM SHORT SPERM HEAD OTHER 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00 000 00000 00000 00000 00 000 00 000 00 000 00 000 00000 10000 00000 00000 00000 00000 00000 00000 1 0 0 0 '0 - PERCENT ABNORMAL 30 45 35 75 60 25 2.5 20.0 20 6.5 2.5 2.0 1.5 3.0 1.5 2.5 1.5 7.0 1.5 4.0 5.0 4.5 7.5 4.5 2.0 2.0 3.5 4.5 5.5 4.5 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B21 (PAGE 3) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 171 RAT NUMBER DETACHED NORMAL HEAD NO HEAD BROKEN FLAGEL LUM DOSAGE GROUP III 3 MG/KG/DAY 13661 198 2 0 13662 195 4 1 13663 196 2 2 13664 185 5 8 13665 190 4 5 13666 189 6 2 13667 193 0 6 13668 194 2 4 13669 193 42 13670 188 4 8 13671 189 4 7 13672 194 4 2 13673 191 7 2 13674 172 13 13 13675 194 4 1 13676 189 8 3 13677 194 24 13678 195 1 4 13679 187 7 5 13680 195 2 2 13681 197 2 1 13682 194 51 13683 187 7 6 13684 191 6 2 13685 195 3 2 13686 181 11 8 13687 194 31 13688 194 3 3 13689 193 4 3 13690 189 74 0 0 0 1 1 2 1 0 1 0 0 0 0 1 1 0 0 0 1 1 0 0 0 1 0 0 2 0 0 0 NO HOOK 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 EXCESSIVE HOOK COILED FLAGEL- LUM BENT FLAGEL- LUM SHORT SPERM HEAD OTHER 00 0 00 00 0 00 00000 01000 000 00 000 00 000 00 00000 000 00 00000 00000 00000 00000 100 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 000 00 PERCENT ABNORMAL 1.0 2.5 2.0 7.5 5.0 5.5 3.5 3.0 3.5 6.0 5.5 3.0 4.5 14.0 3.0 5.5 3.0 2.5 6.5 2.5 1.5 3.0 6.5 4.5 2.5 9.5 3.0 3.0 3.5 5.5 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B21 (PAGE 4) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 172 RAT NUMBER DETACHED NORMAL HEAD NO HEAD BROKEN FLAGEL- LUM DOSAGE GROUP IV 10 MG/KG/DAY 13691 195 5 0 0 13692 193 7 0 0 13693 193 5 10 13694 186 6 8 0 13695 193 2 5 0 13696 186 9 4 0 13697 194 3 3 0 13698 194 4 2 0 13699 192 6 1 0 13700 192 5 2 1 13701 184 11 4 1 13702 196 2 2 0 13703 189 9 2 0 13704 191 8 0 0 13705 193 4 3 0 13706 187 9 4 0 13707 190 10 0 0 13708 183 8 9 0 13709 189 5 6 0 13710 188 9 1 1 13711 194 3 2 1 13712 192 7 1 0 13713 194 1 4 1 13714 194 1 50 13715 185 11 3 1 13716 193 2 50 13717 193 5 2 0 13718 193 6 1 0 13719 193 5 2 0 13720 188 8 4 0 NO HOOK 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 EXCES SIVE HOOK COILED BENT SHORT FLAGEL FLAGEL SPERM LUM LUM HEAD OTHER 00000 00000 00000 00000 00000 00000 00000 00000 00100 00000 00000 00000 00000 10000 00000 00000 00000 00000 00000 01000 00000 00000 00000 00000 00000 00000 00000 00000 00000 00000 PERCENT ABNORMAL 2.5 3.5 3.5 7.0 3.5 7.0 3.0 3.0 4.0 4.0 8.0 2.0 5.5 4.5 3.5 6.5 5.0 8.5 5.5 6.0 3.0 4.0 3.0 3.0 7.5 3.5 3.5 3.5 3.5 6.0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE B21 (PAGE 5) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION MALE RATS ARGUS 418-020 Page 173 RAT DETACHED NO NUMBER NORMAL HEAD HEAD BROKEN FLAGEL LUM NO HOOK DOSAGE GROUP V 30 MG/KG/DAY 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 13732 13733 13734 13735 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 13749 13750 195 4 1 0 0 193 4 2 1 0 187 7 5 1 0 196 1 3 0 0 193 2 3 2 0 196 3 1 0 0 190 8 2 0 0 190 3 6 1 0 194 3 2 1 0 190 7 3 0 0 191 5 4 0 0 MORIBUND SACRIFICED ON DAY 45 OF STUDY 4 6300 196 1 3 0 0 188 11 1 0 0 190 5 3 2 0 189 3 7 1 0 191 2 7 0 0 194 2 2 1 0 191 5 4 0 0 3 83 94 17 1 192 5 2 1 0 191 7 2 0 0 192 6 1 1 0 194 4 2 0 0 187 9 3 0 0 197 1 1 0 1 198 1 1 0 0 194 2 2 0 1 175 15 8 2 0 EXCES SIVE HOOK COILED BENT SHORT FLAGEL FLAGEL SPERM LUM LUM HEAD OTHER 00 0 0 0 000 0 0 00000 00000 00000 00000 00000 00000 00000 00000 00000 000 00 00000 00000 00000 00000 00000 100 00 00 0 0 0 11000 00000 00000 00000 00000 000 10 00000 00000 00010 00000 PERCENT ABNORMAL 20 50 50 30 50 4.5 69.2 2.0 60 5.0 5.5 4.5 3.0 4.5 98.5 4.0 4.5 4.0 3.0 6.5 1.5 1.0 3.0 12.5 ARGUS 418-020 APPENDIX C REPORT TABLES - P GENERATION FEMALE RATS Page 174 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Cl (PAGE 1) : CLINICAL OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 175 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION) MAXIMUM POSSIBLE INCIDENCE 2098/ 30 2089/ 30 2100/ 30 2100/ 30 MORIBUND SACRIFICED la lb 0 0 INCISORS: TOTAL MISSING/BROKEN MISALIGNED 13/ 3 12/ 2 1/ la 6/ 1 6/ 1 0/ 0 16/ 1 0/ 0 16/ 1 26/ 1 13/ 1 13/ 1 CHROMORHINORRHEA 1/ la 6/ 1 5/ 3 1/ 1 UNGROOMED COAT 0/ 0 0/ 0 0/ 0 0/ 0 SCAB(S) c CHROMODACRYORRHEA LOCALIZED ALOPECIA: TOTAL LIMBS UNDERSIDE 7/ 1 1/ la 84/ 2 84/ 2 0/ 0 0/ 0 0/ 0 51/ 2 39/ 1 12/ 1 0/ 0 3/ 1 0/ 0 0/ 0 0/ 0 7/ 1 13/ 1 0/ 0 0/ 0 0/ 0 LEFT FORELIMB AND FOREPAW: SWOLLEN 0/ 0 3/ lb 0/ 0 0/ 0 SOFT OR LIQUID FECES 0/ 0 3/ 1 0/ 0 0/ 0 LEFT FORELIMB: FRACTURED 0/ 0 1/ lb 0/ 0 0/ 0 PALATE: BROKEN SWOLLEN SNOUT 1/ la 1/ la 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rat 13804 was moribund sacrificed on day 68 of study. b. Rat 13836 was moribund sacrificed on day 59 of study. c. Located on the back, right forelimb or left forelimb. V 30 2100/ 30 0 48/ 2 27/ 2 39/ 1 2/ 1 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Cl (PAGE 2) : CLINICAL OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 176 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 PRESUMED GESTATION: a MAXIMUM POSSIBLE INCIDENCE 640/ 29 642/ 29 641/ 29 595/ 27 MORTALITY 0000 LOCALIZED ALOPECIA: TOTAL LIMBS UNDERSIDE 26/ 3 26/ 3 0/ 0 37/ 2 22/ 1 15/ 1 7/ 1 7/ 1 0/ 0 17/ 1 17/ 1 0/ 0 RIGHT OR BOTH EARS: SWOLLEN 18/ 1 0/ 0 15/ 1 15/ 1 INCISORS: TOTAL MISSING/BROKEN MISALIGNED CHROMORHINORRHEA HEAD: MASS CHROMODACRYORRHEA 19/ 1 0/ 0 19/ 1 0/ 0 0/ 0 19/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 22/ 1 0/ 0 22/ 1 0/ 0 0/ 0 3/ 1 42/ 3 20/ 2 22/ 1 1/ 1 0/ 0 4/ 2 DRIED, RED PERINASAL SUBSTANCE 0/ 0 0/ 0 0/ 0 1/ 1 BOTH FOREPAWS: DRIED, RED SUBSTANCE 0/ 0 0/ 0 0/ 0 1/ 1 LEFT HINDPAW: SWOLLEN 0/ 0 0/ 0 18/ 1 0/ 0 LEFT HINDPAW OR LOWER MIDLINE: SCAB 0/ 0 6/ 1 4/ 1 0/ 0 LEFT HINDPAW: ABRASION 0/ 0 0/ 0 3/ 1 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION, a. Restricted to rats with a confirmed mating date. V 30 640/ 29 0 15/ 2 15/ 2 0/ 0 28/ 2 21/ 1 13/ 1 21/ 1 1/ 1 3/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Cl (PAGE 3): CLINICAL OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 177 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 LACTATION: MAXIMUM POSSIBLE INCIDENCE 602/ 28 583/ 27 638/ 29 638/ 29 617/ 29 MORTALITY SACRIFICED a lb 1c 0 0 0 LOCALIZED ALOPECIA: TOTAL LIMBS UNDERSIDE HEAD 34/ 3 34/ 3 0/ 0 0/ 0 49/ 3 42/ 3 22/ 1 0/ 0 2/ 2 2/ 2 0/ 0 0/ 0 22/ 1 22/ 1 0/ 0 0/ 0 30/ 4 23/ 3 0/ 0 7/ 1 RIGHT OR BOTH EARS: SWOLLEN 27/ 2 19/ 1 0/ 0 32/ 3 49/ 3 INCISORS: TOTAL MISSING/BROKEN MISALIGNED 22/ 1 0/ 0 22/ 1 0/ 0 0/ 0 0/ 0 22/ 1 16/ 1 22/ 1 31/ 2 9/ 1 22/ 1 16/ 1 16/ 1 14/ 1 CHROMODACRYORRHEA 22/ 1 0/ 0 0/ 0 4/ 1 10/ 1 HEAD OR RIGHT AXILLA: MASS 0/ 0 0/ 0 0/ 0 3/ 1 4/ 1 HEAD: SCAB 0/ 0 0/ 0 0/ 0 0/ 0 7/ 1 SOFT OR LIQUID FECES TRAUMATIZED CORNEA RIGHT E YE: SWOLLEN TEAT: SWOLLEN 8/ 5 0/ 0 0/ 0 0/ 0 4/ 2 0/ 0 0/ 0 0/ 0 2/ 1 19/ 1 10/ 1 2/ 1 6/ 2 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS) /NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. b. Dam 13822 was sacrificed on day 8 of lactation. c. Dam 13852 was sacrificed on day 11 of lactation. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C2 (PAGE 1) : BODY WEIGHTS - PRECOHABITATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 178 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 30 30 BODY WEIGHT <G) DAY 1 MEANS.D. 147.8 7.3 148.0 5.7 DAY 8 DAY 15 DAY 22 MEANS.D . MEANS.D . MEANS.D . 177.7 9.1 202.4 12.2 218.5 15.0 175.3 7.3 199.2 11.1 214.5 14.1 DAY 29 DAY 36 DAY 43 DAY 50 DAY 57 DAY 64 DAY 70b MEANS.D. MEANS.D. MEANS.D . MEANS.D . MEANS.D. MEANS.D. MEANS.D . 234.5 18.5 243.7 18.2 252.8 20.9 262.8 20.4 268.9 22.4 274.4 22.2 276.8 22.7 [ 29] a 228.0 15.5 236.7 16.6 245.9 16.1 255.8 17.6 261.3 17.4 268.5 18.2 t 29] a 271.8 1 8 . 1 I 29] a DAY = DAY OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were moribund sacrificed. b. Last value recorded before cohabitation. hi 3 30 149.3 6.5 181.3 8.2 206.9 11.8 224.1 15.8 239.8 19.6 249.2 21.5 259.7 24.2 269.0 25.5 276.9 25.9 284.2 27.1 287.2 27.6 IV 10 30 149.4 6.5 180.6 9.3 205.9 12.0 223.1 14.7 238.4 i 15.8 247.9 16.9 257.8 17.2 268.3 18.0 272.8 19.0 279.7 19.2 284.4 21.8 V 30 30 14 8.9 6.7 178.8 7.0 202.7 8.2 217.4 9.6 233.0 10.2 238.9 10.1 250.1 11.1 258.8 11.7 264.0 13.3 267.5 13.0 271.8 14.0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C3 (PAGE 1) : BODY WEIGHT CHANGES - PRECOHABITATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 179 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 30 30 BODY WEIGHT CHANGE (G) DAYS 1 - 8 MEANS.D. +30.0 7.5 +27.3 5.2 DAYS 8 - 15 MEANS.D . +24.6 6.0 +23.9 5.4 DAYS 15 - 22 MEANS.D . +16.1 5.5 +15.3 5.2 DAYS 22 - 29 MEANS.D. +16.0 7.0 +13.5 4.0 DAYS 29 - 36 MEANS.D. +9.2 6.9 +8.8 5.4 DAYS 36 - 43 MEANS.D . +9.1 5.3 +9.1 5.3 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70b DAYS 1 - 70b MEANS.D. MEANS.D . MEANS.D. MEANS.D . MEANS.D. +10.0 5.8 +6.1 5.7 +5.5 5.8 +2.6 5.4 [ 29] a +129.3 21.7 [ 29] a +9.9 4.5 +5.5 4.4 +6.4 4.9 ( 29] a +3.3 3.6 [ 29] a +124.1 17.1 [ 29] a DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were moribund sacrificed. b. Last value recorded before cohabitation. * Significantly different from the Group I value (p<0.05). III 3 30 +32.0 4.7 +25.6 4.9 +17.2 7.0 +15.7 5.6 +9.5 4.5 +10.5 5.2 +9.2 5.1 +7.9 5.1 +7.3 3.8 +3.1 5.0 +138. 0 24.1 IV 10 30 +31.2 4.8 +25.3 5.8 +17.2 6.0 +15.3 3.9 +9.5 3.6 +9.9 4.1 +10.4 4.8 +4.6 5.0 +6.9 5.9 +4.7 5.6 +134 .9 18.7 V 30 30 +30.0 +23.8 +14.7 +15.6 +6.0 +11.1 +8.7 +5.2 +3.5 +4.3 + 1 2 3 ,0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C4 (PAGE 1) : MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 180 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 29a 29a PREGNANT N 28 27 INCLUDED IN ANALYSES N 28 27 MATERNAL BODY WEIGHT (G) DAY 0 MEANiS.D. 280.3 24.2 272.0 19.2 DAY 7 MEANS.D . 310.3 2 4 . 9 299.6 21.8 DAY 10 MEANlS.D . 320.6 25.5 310.5 22.6 DAY 14 MEANS.D. 337.7 26.3 324.7 22.2 DAY 18 DAY 21 MEANS.D . MEANiS.D . 377.4 29.3 [ 27] C 405.4 46.0 [ 27] d 371.6 26.8 389.0 51.5 DAY = DAY OF GESTATION [ 1 = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes rats that did not have a confirmed mating date. c. Excludes values that were not recorded. d. Excludes values for rats that delivered. * Significantly different from the Group I value (p<0.05). III 3 30 30 29b 283.5 27.3 313.6 30.0 325.4 31.3 343.3 32.8 386.4 35.6 414.7 47.2 IV 10 30 29 27b 279.7 22.7 309.6 22.2 322.7 23.7 337.3 2 4 . 4 378.8 26.8 415.3 29.8 [ 26] d V 30 30 29 28b 269.8 14.8 295.1 15.5* 306.4 16.2 320.5 19.7* 363.3 25.7 381.4 4 3 . 1 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C5 (PAGE 1) : MATERNAL BODY WEIGHT CHANGES - GESTATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 181 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 29a 29a PREGNANT N 28 27 INCLUDED IN ANALYSES N 28 27 MATERNAL BODY WEIGHT CHANGE (G) DAYS 0 - 7 MEANS.D . +30.0 9.3 +27.6 7.1 DAYS 7 - 10 MEANS.D. +10.3 6.0 +10.9 6.3 DAYS 10 - 14 MEANS.D . +17.1 6.2 +14.2 4.3 DAYS 14 - 18 DAYS 18 - 21 DAYS 0 - 21 MEANS.D . MEANS.D . MEANS.D . +39.1 11.2 [ 27] c +29.5 31.6 [ 26]C,d +126.0 33.2 ( 27] d +46.9 8.9 +17.4 38.2 +117.1 40.8 DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes rats that did not have a confirmed mating date. c. Excludes values that were not recorded. d. Excludes values for rats that delivered. III 3 30 30 29b +30.1 9.0 +11.8 5.3 +17.9 5.4 +43.0 12.1 +28.3 24.6 +131.2 29.4 IV 10 30 29 27b +29.9 10.4 +13.1 5.2 +14.6 6.2 +41.5 9.3 +36.6 1 2 . 0 ( 26] d +134.8 20.5 t 26] d V 30 30 29 28b +25.3 8.3 +11.3 6.4 +14.0 9.4 +42.8 15.0 +18.1 35.7 +111.5 38.9 PROTOCOL 4X8-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C6 (PAGE 1) : MATERNAL BODY WEIGHTS - LACTATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 182 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS TESTED N 29a 29a 30 PREGNANT N 28 27 30 DELIVERED A LITTER N 28 27 29 MATERNAL BODY WEIGHT (G) DAY 1 MEANS.D. 313.1 24.7 303.2 1 9 . 8 321.2 28.8 DAY 5 MEANS.D. 322.8 1 28.6 310.2 22.0 327.3 29.1 DAY 8 DAY 11 DAY 15 DAY 22 MEANS.D . MEANS.D. MEANS.D . MEANS.D . 341.0 26.3 t 24)b 351.5 28.2 ( 25]b,C 354.4 29.5 [ 27] C 345.0 29.1 [ 27] c 327.8 24.3 [ 23]b 339.4 29.7 [ 22]b,c 345.3 26.8 [ 26] C 339.5 23.6 [ 26] c 337.7 27.6 ( 25] b 351.4 31.2 [ 28] b 357.7 28.9 351.4 23.0 DAY = DAY OF LACTATION t ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes values that were not recorded. c. Excludes values for rats that were sacrificed or sacrificed due to no surviving pups. IV 10 30 29 29 312.2 2 4 . 1 318.8 25.4 339.8 28.2 [ 21] b 345.2 2 4 . 9 349.9 27.8 342.1 26.1 V 30 30 29 29 300.3 19.9 308.3 18.8 [ 27]b,c 322.8 19.4 ( 25]b,c 332.3 20.5 [ 27]b,c 344.2 18.1 ( 28] C 345.0 17.7 I 28] C PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C7 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - LACTATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 183 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED PREGNANT DELIVERED A LITTER INCLUDED IN ANALYSES MATERNAL BODY WEIGHT CHANGE (G) N N N N I 0 29a 28 28 28 II III 13 29a 30 27 30 27 29 27 29 DAYS 1 - 5 MEANS.D . +9.7 11.8 +7.0 14.5 +6.1 11.0 DAYS 5 - 8 DAYS 8 - 11 DAYS 11 - 15 DAYS 1 - 1 5 DAYS 15 - 22 DAYS 1 - 2 2 MEANS.D . MEANS.D. MEANS .D. MEANS.D. MEANS.D . MEANS.D. +12.4 13.1 [ 24] C +14.9 1 2 . 9 [ 21] b, C +4.3 15.9 [ 25] b, c +41.8 14.5 [ 27]b -9.4 25.2 [ 27] b +32.4 23.0 [ 27] b +16.0 10.6 [ 23] C +9.8 14.9 [ 18] b, c +8.5 19.3 [ 22]b,c +42.8 17.5 [ 26] b -5.8 22.5 ( 26] b +37.0 21.7 [ 26] b +14.1 1 0 . 7 [ 25] c +9.6 13.2 ( 24] c +6.0 16.1 ( 28] C +36.5 13.0 -6.3 16.5 +30.2 19.4 DAYS = DAYS OF LACTATION ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were moribund sacrificed prior to cohabitation. b. Excludes values for rats that were sacrificed or sacrificed due to no surviving pups. c. Excludes values that were not recorded. IV 10 30 29 29 29 +6.6 12.8 +18.8 8.4 [ 21] C +7.1 22.6 ( 21] C +4.8 19.1 +37.8 16.0 -7.9 22.9 +29.9 21.3 V 30 30 29 29 28b +7.4 13.0 ( 27] c +12.5 9.8 I 24] c +9.1 15.2 ( 24] c +12.6 1 3 . 4 [ 27] c +42.9 17.2 +0.8 16.8 +43.7 15.8 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C8 (PAGE 1) : ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - PRECOHABITATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 184 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 30 30 30 30 FEED CONSUMPTION (G/DAY) DAYS 1 - 8 DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70c DAYS 1 - 70c MEANS.D. MEANS.D . MEANS.D. MEANS.D . MEANS.D . MEANS.D . MEANS.D . MEANS.D . MEANS.D. MEANS.D . MEANS.D . 18 .8 1.8 20 .8 2.4 21 .5 2.0 I 28] a 21 .3 2.2 [ 28] a 21 .4 2.4 21 .6 2.5 [ 29] a 22 .6 2.8 ( 27] a 21 .0 2.3 [ 28] a 21 .8 2.8 ( 27] a 21 .3 2.0 [ 27] a, b 21 .3 1.6 ( 27] a, b 19.2 t 2.1 l 29] a 21.0 2.9 ( 29] a 21.2 2.3 1 29] a 20.7 2.2 21.0 1.8 21.5 1.9 [ 29] a 21.7 1.8 ( 29] a 21.2 2.0 21.1 1.6 [ 29] b 21.1 2.3 [ 29] b 21.0 1.7 ( 29] b 19.9 1.4 21.8 2.7 [ 29] a 21.8 2.2 [ 29] a 22.3 2.8 21.8 2.1 [ 29] a 22.6 2.7 22.8 2.5 [ 29] a 22.2 2.2 [ 27] a 22.1 1.8 21.4 2.0 21.9 2.0 19.7 1.7 21.7 2.4 22.2 1.9 [ 29] a 22.1 2.9 [ 29] a 22.0 2.3 ( 29] a 22.2 t 2.2 [ 29] a 22.5 2.4 [ 28] a 22.2 2.8 [ 29] a 21.8 2.2 [ 29] a 21.2 t 2.4 [ 29] a 21.8 1.9 [ 29] a 19.6 1.5 ( 29] a 21.2 1.8 20.9 1.6 [ 25] a 21.2 1.6 ( 28] a 21.0 1.9 [ 29] a 21.4 1.8 ( 29] a 22.0 3.0 21.2 2.3 [ 28] a 20.5 1.7* 20.1 2.0 21.0 1.5 DAYS = DAYS OF STUDY ( J = NUMBER OF VALUES AVERAGED a. Excludes values that were not recorded or appeared incorrectly recorded, as well as those associated with spillage. b. Excludes values for rats that were moribund sacrificed. c. Last value recorded before cohabitation. . * Significantly different from the Group I value (p<0.05). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C9 (PAGE I) : RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - PRECOHABITATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 185 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV v 0 1 3 10 30 RATS TESTED N 30 30 30 30 30 FEED CONSUMPTION (G/KG/DAY) DAYS 1 - 8 DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70c DAYS 1 - 70c MEANS.D . MEANS.D . MEANS.D.. MEANS.D . M E A N S .D, MEANS.D. MEANS.D ., MEANS.D . MEANS.D .. MEANS.D . MEANS.D., 115.6 9.4 110.0 14.4 102.4 8.4 [ 28]a 94.3 8.9 l 28] a 89.3 5.8 86.9 6.9 1 29] a 87.8 7.2 [ 27] a 79.6 6.4 I 28] a 81.1 9.2 ( 27] a 76.6 5.4 [ 27] a,b 91.1 4.1 t 27] a,b 118.9 :11.6 [ 29] a 112.0 :13.7 ( 29] a 102.2 7.4 [ 29] a 93.5 6.7 90.7 5.9 88.8 6.4 [ 29] a 86.7 5.3 [ 29] a 82.1 6.2 79.7 5.0 [ 29] b 78.1 7.8 [ 29]b 92.2 5.4 [ 29]b 120.4 6.5 112.8 13.5 ( 29] a 101.3 7.6 [ 29] a 96.0 9.1 89.2 4.8 [ 29] a 88.7 7.2 86.0 6.2 [ 29] a 80.7 5.8 ( 27] a 78.9 4.8 75.3 6.3 91.8 5.7 119.6 7.8 112.1 9.5 103.7 7.1 [ 29] a 95.2 10.7 t 29] a 90.5 6.4 [ 29] a 87.6 6.1 [ 29] a 85.6 5.8 [ 28] a 82.1 7.2 [ 29] a 78.7 5.8 [ 29] a 75.2 5.2 ( 29] a 91.9 4.8 [ 29] a 120.0 8.0 [ 29] a 111.2 8.9 100.0 6.0 [ 25] a 94.1 6.4 ( 28] a 89.2 8.0 t 29] a 87.5 5.6 [ 29] a 86.3 :10.3 81.0 7.0 [ 28] a 77.3 4.8 74.3 5.7 91.0 4.7 DAYS = DAYS OF STUDY [ ) = NUMBER OF VALUES AVERAGED a . Excludes values that were not recorded or appeared incorrectly :recorded, b. Excludes values for rats that were moribund sacrificed. c. Last value recorded before cohabitation. as well as those associated with spillage. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE CIO (PAGE 1) : MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - GESTATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 186 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 29a 29a PREGNANT N 28 27 INCLUDED IN ANALYSES N 28 27 MATERNAL FEED CONSUMPTION (G/DAY) DAYS 0 - 7 DAYS 7 - 1 0 MEANS.D . MEANS.D . 25.9 3.2 ( 27) c 27.0 3.7 25.7 2.4 25.7 2.5 DAYS 10 - 14 DAYS 14 - 18 DAYS 18 - 21 DAYS 0 - 2 1 MEANS.D. MEANS.D. MEANS.D. MEANS.D. 27.6 3.5 26.1 2.8 23.6 2.4 1 25) d 26.1 2.6 ( 25] d 25.8 2.4* [ 26] C 26.8 2.7 [ 26) C 23.2 3.1 [ 23] d 25.6 1.9 ( 23 ]d DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes rats that did not have a confirmed mating date. c. Excludes values that were associated with spillage. d. Excludes values for rats that delivered. * Significantly different from the Group I value (p<0.05). III 3 30 30 29b 26.0 3.1 l 26) c 28.0 2.9 28.4 3.5 [ 28] C 27.3 3.1 24.5 2.8 [ 28] d 26.7 2.3 [ 28] d IV 10 30 29 27b 25.0 2.5 26.8 2.8 [ 26] C 26.2 3.3 t 26] C 26.1 2.5 [ 26] C 23.5 3.6 [ 26] d 25.6 2.2 ( 26] d V 30 30 29 28b 24.1 2.3 t 27] c 25.5 2.5 25.4 3.0* 25.6 3.7 23.0 3.9 [ 27] d 24.6 2.2* [ 27] d PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Cll (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - GESTATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 187 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS TESTED N 29a 29a 30 PREGNANT N 28 27 30 INCLUDED IN ANALYSES N 28 27 29b MATERNAL FEED CONSUMPTION (G/KG/DAY) DAYS 0 - 7 DAYS 7 - 1 0 MEANS.D . MEANS.D. 87.5 9.5 ( 27] c 85.4 8.3 90.1 8.3 84.5 7.0 87.0 7.6 ( 26] C 87.7 7.1 DAYS 1 0 - 1 4 DAYS 14 - 18 DAYS 18 - 21 DAYS 0 - 21 MEANS.D. MEANS.D. MEANS.D . MEANS.D . 84.0 7.7 73.3 6.2 [ 27] c 59.7 8.5 [ 24] C,,d 77.0 5.5 [ 25] d 81.5 7.3 [ 26] c 77.1 7.7 [ 26] C 59.9 7.7 ! 23] d 77.3 5.7 [ 23] d 84.4 8.0 [ 28] C 75.1 8.6 61.3 6.0 [ 28] d 77.7 4.4 l 28] d DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes rats that did not have a confirmed mating date. c. Excludes values that were not recorded, as well as those associated with spillage. d. Excludes values for rats that delivered. IV 10 30 29 27b 84.8 7.4 85.1 6.5 ( 26] c 79.6 6.5 ( 26] C 73.2 5.4 [ 26] C 59.1 7.7 l 26] d 75.0 4.4 ( 26] d V 30 30 29 28b 85.3 7.1 [ 27] c 84.8 6.4 81.0 7.6 74.7 9.4 61.7 9.2 [ 27] d 76.0 5.3 [ 27] d PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C12 (PAGE 1) : MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - LACTATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 188 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 V 30 RATS TESTED N 29a 29a 30 30 30 PREGNANT N 28 27 30 29 29 DELIVERED A LITTER N 28 27 29 29 29 INCLUDED IN ANALYSES N 28 27 29 29 28b MATERNAL FEED CONSUMPTION (G/DAY) DAYS 1 - 5 DAYS 5 - 8 DAYS 8 - 11 DAYS 11 - 15d DAYS 1 - 15d MEANS.D . MEANS.D . MEANS.D . MEANS.D. MEANS.D . 31.8 6.4 [ 25] c 51.2 8.6 [ 26]b,c 61.8 10.6 [ 25]b,c 69.4 11.1 [ 26]b,c 54.1 7.5 ( 26] b, C 31.9 4.6 49.6 7.2 58.7 :10.5 [ 25] b ,C 68.2 8.6 ( 25] b ,c 51.8 5.7 [ 25]b,C 33.1 7.1 ( 28] c 50.0 10.8 62.2 13.1 69.0 14.0 [ 28] c 53.6 10.7 [ 28] c 31.0 t 6-3 [ 25] c 50.9 8.9 ( 28] c 59.6 8.4 [ 28] c 67.6 12.8 53.1 9.3 29.6 6.1 [ 26] c 47.6 10.0 55.2 10.6 [ 27] C 66.2 7.7 50.0 7.3 DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes values for rats that were sacrificed or sacrificed due to no surviving pups. c. Excludes values that were associated with spillage. d. Because it is presumed that the pups begin to consume maternal feed after day 15 of lactation, were not tabulated on days 15 to 22 of lactation. maternal feed consumption values PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C13 (PAGE 1) : MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - LACTATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 189 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 29a 29a 30 30 30 PREGNANT N 28 27 30 29 29 DELIVERED A LITTER N 28 27 29 29 29 INCLUDED IN ANALYSES N 28 27 29 29 28b MATERNAL FEED CONSUMPTION (G/KG/DAY) DAYS 1 - 5 DAYS 5 - 8 DAYS 8 - 1 1 DAYS 11 - 15d DAYS 1 - 15d MEANS.D. MEANlS.D. MEANS.D . MEANS.D. MEANS.D . 100.3 17.5 [ 25] C 152.3 21.9 [ 22]b,C 175.9 27.4 [ 19] b, c 194.2 27.5 [ 24]b , C 161.0 18.7 ( 26]b,c 104.0 13.6 153.3 15.8 ( 23] c 176.6 27.6 [ 17]b,C 197.9 21.4 [ 21] b, c 159.9 13.8 [ 25] b, c 102.9 21.8 [ 28] c 145.1 27.2 ( 25] c 173.7 31.3 ( 24] C 193.2 34.7 [ 27] c 157.2 26.4 [ 28] c 98.1 19.6 ( 25] C 154.4 22.6 [ 20] c 176.7 19.8 t 20] c 194.2 33.6 159.8 26.2 96.4 20.5 ( 25] C 151.5 30.6 [ 24] c 168.3 29.0 ( 23] C 196.7 22.4 [ 27] c 155.5 20.6 DAYS = DAYS OF LACTATION [ ) = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes values for rats that were sacrificed or sacrificed due to no surviving pups. c. Excludes values that were not recorded, as well as those associated with spillage. d. Because it is presumed that the pups begin to consume maternal feed after day 15 of lactation, were not tabulated on days 15 to 22 of lactation. maternal feed consumption values PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-S889.6) STABLE C14 (PAGE 1) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 190 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 ESTROUS CYCLING OBSERVATIONS PRECOHABITATION ESTROUS CYCLING RATS EVALUATED N 29a 29a ESTROUS STAGES/ 21 DAYS MEAN+S.D. 5.2 + 1.0 5.2 + 0.6 RATS WITH 6 OR MORE CONSECUTIVE DAYS OF DIESTRUS N 2 0 RATS WITH 6 OR MORE CONSECUTIVE DAYS OF ESTRUS N 0 0 ESTROUS STAGE AT SACRIFICE RATS EVALUATED N 28b 28b DIESTRUS PROESTRUS ESTRUS METESTRUS N7 N 21 N0 N0 9 16 2 1 a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes values for rats1 that did not have a value recorded. Ill 3 30 5.0 + 0.8 0 2 30 13 14 1 2 IV 10 30 4.9 + 1.0 1 1 30 11 16 1 2 V 30 30 5.2 + 0.7 0 1 29b 8 20 1 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C14 (PAGE 2): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 191 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS IN COHABITATION N 29a 29a 30 DAYS IN COHABITATION b MEAN+S.D. 3.3 + 2.G 1.9 + 1.2* 2 . 4 + 1.7 [ 29] RATS THAT MATED N (%) 29(100.0) 29(100.0) 30(100.0) FERTILITY INDEX c N/N 28/ 29 (%) ( 96.6) 27/ 29 ( 93.1) 30/ 30 (100.0) RATS WITH CONFIRMED MATING DATES N 29 29 29 RATS MATING d DAYS 1-7 DAYS 8-14 N (%) N (%) 27( 93.1) 2( 6.9) 29(100.0) 0( 0.0) 28 ( 96.6) K 3.4) RATS PREGNANT/RATS IN COHABITATION N/N 28/ 29 (%) ( 96.6) 27/ 29 ( 93.1) 30/ 30 (100.0) [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Restricted to rats with a confirmed mating date and rats that did not mate. c. Number of pregnancies/number of rats that mated. d. Restricted to rats with a confirmed mating date. * Significantly different from the Group I value (p<0.05). IV 10 30 3.1 + 2.4 [ 28] 29( 96.7) 29/ 29 (100.0) 27 27(100.0) 0( 0.0) 29/ 30 ( 96.7) V 30 30 2.6 + 1.4 t 29] 30(100.0) 29/ 30 ( 96.7) 29 29(100.0) 0( 0.0) 29/ 30 ( 96.7) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-G889.6) TABLE C15 (PAGE 1) : NECROPSY OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS EXAMINED a N 30 30 30 30 30 MORIBUND SACRIFICED N lb 1c 0 0 0 SACRIFICED d N le if 0 0 0 APPEARED NORMAL N 29e 29f 29 30 30 KIDNEYS: LEFT, PELVIS, MARKED DILATION N 0 0 1 0 0 LEFT FORELIMB: ULNA AND RADIUS, BROKEN N 0 lc 0 0 0 a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. b. Rat 13804 was moribund sacrificed on day 68 of study. c. Rat 13836 was moribund sacrificed on day 59 of study. d. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. e. Rat 13822 was sacrificed on day 8 of lactation. f. Rat 13852 was sacrificed on day 11 of lactation. Page 192 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C16 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 193 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 RATS TESTED N 30 30 30 29a PREGNANT N 28 27 30 29 INCLUDED IN ANALYSES N 27b 26b 29c 29 TERMINAL BODY WEIGHT MEANS.D . 345.0 29.1 339.5 23.6 351.4 23.0 342.1 26.1 PITUITARY BRAIN MEANS.D . MEANS.D. 0.018 0.005 [ 26] d 2.22 0.13 0.019 0.005 2.21 0.14 0.017 0.004 2.22 0.13 0.016 0.006 2.22 0.08 LIVER MEANS.D . 18.69 2.49 17.97 2.13 17.85 1.78 17.25 1.94 KIDNEY LEFT KIDNEY RIGHT M E A N S .D. MEANS.D. 1.57 0.16 1.57 0.18 1.58 0.14 1.61 0.14 1.58 0.18 1.62 0.16 1.52 0.14 1.55 0.13 ADRENAL LEFT MEANS.D . 0.045 0.010 0.051 0.009 0.048 0.010 0.046 0.007 ADRENAL RIGHT SPLEEN CERVIX OVARY LEFT OVARY RIGHT UTERUS NON-GRAVID MEANS.D . MEANS.D. MEANS.D . MEANS .D . MEANS .D . MEANS.D. 0.045 0.007 0.67 0.10 0.22 0.12 0.052 0.011 0.053 0.011 0.52 0.14 0.046 0.008 0.69 0.09 0.19 0.05 0.055 0.016 0.057 0.018 0.59 0.21 0.043 0.006 0.71 0.11 0.20 0.08 0.054 0.014 0.057 0.013 0.53 0.15 0.042 0.009 0.69 0.09 0.20 0.10 0.049 0.010 0.054 0.012 0.58 0.19 [ ] = NUMBER OF VALUES AVERAGED ' ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes rat 13900, which did not have organ weight values recorded. b. Excludes values for rats that were sacrificed, moribund sacrificed or sacrificed due to no surviving pups. c. Excludes dam 13862, which was pregnant but did not deliver a litter. d. Excludes values that appeared incorrectly recorded. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). V 30 30 29 28b 345.0 17.7 0.016 0.006 [ 27] d 2.17 0.11 18.08 1.71 1.44 1 0.10** 1.49 0.10* 0.046 0.010 0.042 0.010 [ 27] d 0.72 0.10 0.17 0.06 0.053 0.016 0.049 0.014 0.50 0.11 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C17 (PAGE 1) : RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 194 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 30 30 29a 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 27b 26b 29c 29 28b TERMINAL BODY WEIGHT PITUITARY d BRAIN MEANS.D. MEANS.D. MEANlS.D . 345.0 29.1 5.311 1.260 [ 26] e 0.648 i 0.057 339.5 23.6 5.506 1.457 0.654 0.054 351.4 23.0 4.933 1.064 0.634 0.050 342.1 26.1 4.674 2.089 0.653 0.053 345.0 17.7 4.547 1.735 [ 27] e 0.630 0.034 LIVER KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT d ADRENAL RIGHT d SPLEEN CERVIX OVARY LEFT d OVARY RIGHT d UTERUS NON-GRAVID MEANS.D . MEANS.D . MEANS.D . MEANS .D . MEANS.D . MEANS .D . MEANS.D . MEANS.D . MEANS.D. MEANS.D . 5.405 0.425 0.455 0.042 0.456 0.044 13.162 2.855 13.042 2.341 0.195 0.026 0.063 0.031 15.227 3.484 15.417 2.965 0.154 0.043 5.284 0.422 0.465 0.041 0.474 i 0.042 14.963 2.401 13.642 2.274 0.204 0.026 0.057 0.014 16.053 4.570 16.886 5.250 0.175 0.063 5.088 0.481* 0.449 0.040 0.461 0.037 13.614 2.787 12.230 1.775 0.203 0.029 0.058 0.026 15.333 4.080 16.271 3.379 0.151 0.044 5.047 0.455** 0.443 0.032 0.454 0.032 13.438 2.221 12.418 2.418 0.200 0.023 0.058 0.027 14.289 3.173 15.903 3.306 0.170 0.049 5.244 0.461 0.418 0.032** 0.431 0.029* 13.312 3.037 12.042 2.869 ( 27] e 0.207 0.028 0.049 0.017 15.446 4.566 14.108 3.631 0.146 0.033 [ J = NUMBER OF VALUES AVERAGED ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Excludes rat 13900, which did not have organ weight values recorded. b. Excludes values for rats that were sacrificed, moribund sacrificed or sacrificed due to no surviving pups. c. Excludes dam 13862, which was pregnant but did not deliver a litter. d. Value was multiplied by 1000. e. Excludes values that appeared incorrectly recorded. * Significantly different from the Group I value (p<0.05). * * Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C18 (PAGE 1) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 195 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 30 30 29a 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 27b 26b 29c 29 28b BRAIN WEIGHT MEANS.D. 2.22 0.13 2.21 0.14 2.22 0.13 2.22 0.08 2.17 0.11 PITUITARY LIVER MEANS.D. MEANS.D. 0.82 0.20 [ 26] d 839.90 101.30 0.85 0.23 814.22 93.64 0.78 i 0.16 806.07 98.78 0.71 0.27 776.69 90.72 0.72 0.28 [ 27] d 834.10 80.85 KIDNEY LEFT MEANS.D . 70.57 7.47 71.66 7.89 71.24 8.32 68.35 6.17 66.42 4.29* KIDNEY RIGHT MEANS.D. 70.80 7.55 73.06 7.36 73.00 7.24 69.80 6.03 68.59 4.86 ADRENAL LEFT MEANS.D. 2.03 0.42 2.31 0.44 2.14 0.43 2.06 0.30 2.11 0.48 ADRENAL RIGHT SPLEEN MEANS.D . MEANS.D. 2.01 0.33 30.28 3.63 2.10 0.39 31.47 4.70 1.94 0.31 32.14 5.27 1.91 0.38 30.94 3.74 1.92 0.46 [ 27] d 33.18 4.83 CERVIX MEANS.D . 9.76 5.09 8.80 2.28 9.21 i 3.79 9.00 4.37 7.90 2.68 OVARY LEFT MEANS.D. 2.35 0.49 2.48 0.74 2.43 0.65 2.19 0.46 2.46 0.76 OVARY RIGHT MEANS.D. 2.40 0.55 2.58 0.78 2.58 0.57 2.45 0.54 2.25 0.59 UTERUS NON-GRAVID MEANS .D . 23.74 6.45 26.97 10.31 23.93 6.55 26.16 8.39 23.15 5.23 l ] = NUMBER OF VALUES AVERAGED ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) a. Excludes rat 13900, which did not have organ weight values recorded. ' b. Excludes values for rats that were sacrificed, moribund sacrificed or sacrificed due to no surviving pups. c. Excludes dam 13862, which was pregnant but did not deliver a litter. d. Excludes values that appeared incorrectly recorded. * Significantly different from the Group I value (p<0.05). X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Cl9 (PAGE 1) : NATURAL DELIVERY OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 196 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS ASSIGNED TO NATURAL DELIVERY N 29a 29a 30 30 30 PREGNANT N (% ) 28( 96.6) 27( 93.1) 30(100.0) 29( 96.7) 29( 96.7) DELIVERED A LITTER N(%) 28(100.0) 27(100.0) 29 ( 96.7) 29(100.0) 29(100.0) DURATION OF GESTATION b MEANS .D . IMPLANTATION SITES N PER DELIVERED LITTER MEANS.D . 22.6 0.5 428 15.3 1.9 22.5 0.5 421 15.6 2.1 22.8 0.5 442 15.2 2.3 22.6 0.6 ( 27) c 453 15.6 2.0 22.7 0.5 [ 28] C 445 15.3 2.0 DAMS WITH STILLBORN PUPS N (%) 3( 10.7) 4( 14.8) 5( 17.2) 3 ( 10.3) 4( 13.8) DAMS WITH NO LIVEBORN PUPS N (%> 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) GESTATION INDEX d % N/N 100.0 28/ 28 100.0 27/ 27 96.7 29/ 30 100.0 29/ 29 100.0 29/ 29 DAMS WITH ALL PUPS DYING DAYS 1-4 POSTPARTUM N (%) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) M 3.4) DAMS WITH ALL PUPS DYING DAYS 5-21 POSTPARTUM N (%) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Calculated as the time (in days) elapsed between confirmed mating (arbitrarily defined as day 0) and the time the first pup was delivered. c. Excludes values for rats that did not have a confirmed mating date. d. Number of rats with live offspring/number of pregnant rats. (in days) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C20 (PAGE 1) : LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 197 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 28 27 29 PUPS DELIVERED (TOTAL) N MEANS.D. 402 14.4 2.1 395 14.6 2.2 393 13.6 3.6 LIVEBORN MEANS.D. N (%) 14.2 2.2 397( 98.8) 14.2 2.6 384( 97.2) 13.4 3.6 388( 98.7) STILLBORN MEANS.D . N (%) 0.1 0.3 3( 0.7) 0.4 1.4 10( 2.5) 0.2 0.4 5( 1.3) UNKNOWN VITAL STATUS N 2 1 0 PUPS FOUND DEAD OR PRESUMED CANNIBALIZED DAY 1 DAYS 2 - 5 DAYS 6- 8 DAYS 9-15 DAYS 16-22 N / N (%) N / N (%) N / N (%) N / N (%) N / N (%) 2/397( 7/395 ( 1/388( 0/3751 0/375( 0.5) 1.8) 0.2) 0.0) a 0.0)a 2/384( 6/382( 2/3761 1/362 ( 0/361 ( 0.5) 1.6) 0.5) 0.3)b 0.0)b 3/3881 7/385( 5/378 ( 1/373( 1/372 ( 0.8) 1.8) 1.3)* 0.3) 0.3) VIABILITY INDEX c % 97.7 N/N 388/397 98.2 377/384 97.4 378/388 LACTATION INDEX d % 99.7 98.9 98.1* N/N 375/376a 361/365b 371/378 D A Y (S ) = D A Y (S ) POSTPARTUM a. Excludes litter 13822; all pups were sacrificed due to sacrifice of dam. b. Excludes litter 13852; all pups were sacrificed due to sacrifice of dam. c. Number of live pups on day 5 postpartum/Number of liveborn pups on day 1 postpartum. d. Number of live pups on day 22 postpartum/Number of live pups on day 5 postpartum. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). IV 10 29 404 13.9 3.0 13.8 3.0 400( 99.0) 0.1 0.4 4( 1.0) 0 0/400( 5/4001 2/395( 3/393 1 0/3901 0.0) 1.2) 0.5) 0.8) 0.0) 98.8 395/400 98.7 390/395 V 30 29 3 94 13.6 3.3 13.4 3.3 388( 98.5) 0.2 0.6 6 ( 1.5) 0 3/3881 11/3851 10/3741 2/3641 0/3621 0.8) 2.8) 2.7)** 0.5) 0.0) 96.9 376/388 96.3** 362/376 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C20 (PAGE 3) : LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 199 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 28 27 29 LIVE LITTER SIZE AT WEIGHING DAY 1 DAY 5 DAY 8 DAY 15 DAY 22 MEANS .D . MEANS.D . MEANS.D. MEANS.D . MEANS.D . 14.1 1 2.2 13.8 1 2.1 13.9 1 2.0 1 27) b 13.9 1 2.0 [ 27] b 13.9 1 2.0 I 27] b 14.1 1 2.7 13.9 1 2.5 13.8 1 2.5 13.9 1 2.5 t 26] b 13.9 1 2.5 ( 26] b 13.3 3.6 13.0 3.4 12.9 3.4 12.8 1 3.3 12.8 3.4 PUP WEIGHT/LITTER (GRAMS) DAY 1 DAY 5 MEANS.D. MEANlS.D . 6.3 1 0.5 9.4 i 1.3 6 . 0 1 0.4* 8 . 8 l 0.8 6.2 0.5 9.5 1.5 DAY 8 DAY 15 DAY 22 MEANlS.D . MEANlS.D . MEANlS. D. 13.3 1 2.0 l 27] b 25.0 1 4.0 ! 27] b 37.4 1 6.5 [ 27] b 12.7 1 1.3 24.2 1 2.8 ( 26] b 36.7 1 5.5 [ 26] b 13.5 1 2.2 26.4 1 4.7 39.7 8.3 DAY = DAY POSTPARTUM [ ] = NUMBER OF VALUES AVERAGED a. Excludes litter 13947, which had no surviving pups on day 1 of lactation. b. Excludes litters in which the dam was sacrificed. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). IV 10 29 13.8 3.0 13.6 2.8 13.6 2.9 13.4 2.8 13.4 2.8 6.2 0.4 9.3 0.9 13.0 1.6 24.8 1 4.0 38.8 6.1 V 30 29 13.8 1 2.5 I 28] a 13.4 1 2.8 [ 28] a 13.0 1 2.7 [ 28] a 12.9 1 2.8 [ 28] a 12.9 2.8 [ 28] a 5.7 i 0.5** [ 28] a 8.5 1 1.3** ( 28]a 11.9 2.1** [ 28] a 22.9 4.3 [ 28] a 35.7 7.0 [ 28] a PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C21 (PAGE 1) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - SUMMARY - FI GENERATION PUPS ARGUS 418-020 Page 200 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTERS EXAMINED (N) I II III 013 28 27 29 IV 10 29 TRANSIENT CLINICAL OBSERVATIONS: a COLD TO TOUCH N/N BRUISE b N/N NO MILK IN STOMACH N/N UMBILICAL HERNIA N/N PALE N/N LEFT FORELIMB OR MOUTH: MASS N/N 22/5 0/0 1/1 0/0 0/0 0/0 TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS 5/4 29/5 3/2 0/0 0/0 6/1 0/0 0/0 3/2 2/1 0/0 1/1 0/0 0/0 1/1 2/1 0/0 0/0 NOT NESTING N/N 3/1 0/0 0/0 1/1 BACK: SCAB N/N 0/0 0/0 0/0 1/1 RED PERIANAL SUBSTANCE N/N 0/0 0/0 1/1 0/0 NOT NURSING N/N 3/1 0/0 0/0 0/0 PERSISTENT CLINICAL OBSERVATIONS:: a TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH[ OBSERVATIONS TIP OF TAIL MISSING N/N 0/0 18/1 2/1 22/1 LEFT EYE: TRAUMATIZED CORNEA N/N 0/0 0/0 0/0 2/1 TIP OF TAIL BLACK N/N 0/0 0/0 20/1 0/0 HINDLIMBS ROTATED INWARD N/N 0/0 22/1 0/0 0/0 NO TAIL PRESENT N/N 0/0 22/1 0/0 ' 0/0 STATISTICAL ANALYSES WERE RESTRICTED TO THE NUMBER OF LITTERS WITH OBSERVATIONS. a. Tabulation restricted to adverse observations; all other pups appeared normal. b. Located on the head, back, chest and/or lower midline. ** Significantly different from the vehicle control group value (p<0.01). V 30 29 81/4 12/4** 2/2 14/2 1/1 11/1 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6B89.6) TABLE C22 (PAGE 1) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - SUMMARY - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 LITTERS EXAMINED N 28 27 28 28 29 TOTAL PUPS STILLBORN OR FOUND DEAD a,b STILLBORN FOUND DEAD N6 N3 N3 8 10 15 75 8 17 46 4 11 NO MILK IN STOMACH c N(%) 2( 66.7) 2( 28.6) 0( 0.0) 2( 50.0) 5 ( 45.4) PUPS SACRIFICED AND NECROPSIED ON DAYS 8, 11 AND 22 POSTPARTUM b LITTERS EVALUATED PUPS EVALUATED N 28 27 28 28 28 N 163 156 148 161 145 APPEARED NORMAL LITTER INCIDENCE PUP INCIDENCE N (%) 28(100.0) N (%) 163(100.0) 27(100.0) 156(100.0) 28(100.0) 148(100.0) 28(100.0) 161(100.0) 27 ( 96.4) 144 ( 99.3) KIDNEYS: RIGHT, PELVIS, MODERATE DILATION LITTER INCIDENCE N(%) PUP INCIDENCE N (%) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) M 3.6) M 0.7) a. Restricted to pups in which complete necropsies were performed. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. b. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. c. Analysis restricted to pups found dead and necropsied. ARGUS 418-020 Page 201 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C23 (PAGE 1) : PUP ORGAN WEIGHTS - SUMMARY - FI GENERATION PUPS ARGUS 418-020 Page 202 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 V 30 LITTERS EXAMINED N 27 26 28 28 28 TERMINAL BODY WEIGHT WEIGHT/LITTER MALE PUPS FEMALE PUPS BRAIN MEAN+S.D . MEAN+S.D . MEAN+S.D . 36.84 + 6.61 ( 25]a 38.26 + 6.52 [ 24]a,b 35.63 + 7.11 [ 25]a 35.52 + 5.41 [ 22] a 36.82 + 5.08 ( 22] a 34.23 + 6.42 [ 22] a 39.21 + 8.24 [ 26] a 40.01 + 8.36 [ 22] a, b 37.92 + 7.73 [ 24]a,c 36.68 + 5.84 [ 24] a 37.78 + 6.82 [ 24] a 35.59 + 5.25 [ 24] a 34.25 + 6.60 [ 22] a 35.53 + 6.79 ( 21] a 33.22 + 7.23 [ 2 1 ]a, c WEIGHT/LITTER MALE PUPS FEMALE PUPS SPLEEN MEAN+S.D . MEAN+S.D . MEAN+S.D . 1.40 + 0.10 1.42 + 0.11 [ 26] b 1.38 + 0.12 1.43 + 0.10 1.45 + 0.12 1.41 + 0.10 1.42 + 0.11 1.45 + 0.13 [ 24] b 1.40 + 0.11 ( 26] C 1.40 + 0.09 1.42 + 0.12 1.38 + 0.09 1.38 + 0.12 1.40 + 0.13 [ 26] b 1.36 + 0.11 ( 27] C WEIGHT/LITTER MALE PUPS FEMALE PUPS THYMUS MEAN+S.D . MEAN+S.D . MEAN+S.D . 0.14 + 0.05 0.15 + 0.06 [ 26]b 0.13 + 0.05 0.12 + 0.03 0.12 + 0.04 0.12 + 0.04 0.13 + 0.05 0.13 + 0.06 t 24] b 0.13 + 0.04 [ 26] C 0.14 + 0.04 0.13 + 0.05 0.14 + 0.05 0 . 1 2 + 0.04 0.11 + 0.04 [ 26] b 0.12 + 0.04 [ 27] C WEIGHT/LITTER MEAN+S.D . 0.16 + 0.05 0.16 + 0.04 0.14 + 0.05 0.17 + 0.05 0.14 + 0.05 MALE PUPS FEMALE PUPS MEAN+S.D . MEAN+S.D. 0.16 + 0.05 [ 26] b 0.16 + 0.06 0.16 + 0.04 0.15 + 0.05 0.14 + 0.05 [ 24]b 0.14 + 0.04 ( 26] C ' 0.17 + 0.05 0.16 + 0.05 0.14 + 0.05 [ 26] b 0.14 + 0.05 ( 27] C ALL WEIGHTS WERE RECORDED IN GRAMS (G) . [ ] NUMBER OF VALUES AVERAGED a. Excludes values for pups in which the terminal body weight could not be determined because pup identification was not recorded or appeared incorrectly recorded. b. Excludes values for litter(s) that had no male pups examined. c. Excludes values for litter(s) that had no female pups examined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C23 (PAGE 2) : PUP ORGAN WEIGHTS - SUMMARY - FI GENERATION PUPS ARGUS 418-020 Page 203 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 LITTERS EXAMINED N 27 26 28 28 28 INCLUDED IN ANALYSES N 25a 22a 26a 24a 22a RATIOS (%) OF BRAIN TO TERMINAL BODY WEIGHT WEIGHT/LITTER MEAN+S.D . 3.93 + 0.64 4.07 + 0.43 3.77 + 0.61 3.88 + 0.48 4.11 + 0.62 MALE PUPS FEMALE PUPS MEAN+S.D. MEAN+S.D . 3.83 + 0.G3 ( 24]b 4.02 + 0.70 RATIOS (%) OF SPLEEN TO TERMINAL BODY WEIGHT 3.95 + 0.36 4.18 + 0.59 3.75 + 0.56 [ 22] b 3.84 + 0.65 [ 24] C 3.82 + 0.50 3.94 + 0.58 4 . 0 0 + 0.51 C 21] b 4.23 + 0.86 ( 21] C WEIGHT/LITTER MEAN+S.D . 0.38 + 0.11 0.33 + 0.07 0.33 + 0.10 0.36 + 0.09 0.33 + 0.06 MALE PUPS FEMALE PUPS MEAN+S.D. MEAN+S.D. 0.40 + 0.13 I 24 ]b 0.37 + 0.11 RATIOS (%) OF THYMUS TO TERMINAL BODY WEIGHT 0.33 + 0.09 0.33 + 0.09 0.31 + 0.11 [ 22] b 0.34 + 0.10 [ 24] C 0.35 + 0.11 0.38 + 0.10 0.31 + 0.08 [ 21] b 0.34 + 0.07 [ 21] C WEIGHT/LITTER MEAN+S.D . 0.44 + 0.12 0.42 + 0.07 0.36 + 0.09* 0.45 + 0.12 0.39 + 0.09 MALE PUPS FEMALE PUPS MEAN+S .D . MEAN+S.D. 0.42 + 0.11 [ 24] b 0.46 + 0.16 0.42 + 0.09 0.42 + 0.10 0.35 + 0.09 [ 22] b 0.37 + 0.10 [ 24] C 0.46 + 0.13 0.45 + 0.13 0.37 + 0.11 [ 21] b 0.41 + 0.10 ( 21] C ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for pups in which the terminal body weight could not be determined because pup identification was not recorded or appeared incorrectly recorded. b. Excludes values for litter(s) that had no male pups examined. c. Excludes values for litter(s) that had no female pups examined. * Significantly different from the Group I value (p<0.05). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C23 (PAGE 3) : PUP ORGAN WEIGHTS - SUMMARY - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTERS EXAMINED N RATIOS (%) OF SPLEEN TO BRAIN WEIGHT WEIGHT/LITTER MEAN+S .D . MALE PUPS MEAN+S.D. FEMALE PUPS MEAN+S.D. I 0 27 9.74 + 3.30 10.42 + 4.21 [ 26) a 9.26 + 2.95 II 1 26 8.34 + 2.16 8.60 + 2.60 8.08 + 2.74 RATIOS {%) OF THYMUS TO BRAIN WEIGHT WEIGHT/LITTER MEAN+S.D. MALE PUPS MEAN+S.D. FEMALE PUPS MEAN+S.D. 11.17 + 3.28 11.02 + 3.45 [ 26] a 11.46 + 3.69 10.80 + 2.35 10.95 + 2.60 10.66 + 3.07 ALL WEIGHTS WERE RECORDED IN GRAMS (G) ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for litter(s) that had no male pups examined, b. Excludes values for litter(s) that had no female pups examined III IV V 3 10 30 28 28 28 8.98 + 3.17 8.62 + 3.75 l 24] a 8.94 + 2.68 ( 26] b 9.64 + 2.74 9.36 + 3.05 9.91 + 3.04 8.59 + 2.48 8.02 + 2.41 [ 26] a 8.83 + 2.50 ( 27] b 9.84 + 2.94 11.88 + 3.33 9.82 + 2.86 9.62 + 3.24 [ 241a 9.92 + 2.82 I 26]b 12.23 + 3.71 11.53 + 3.45 9.46 + 3.22 [ 26] a 10.06 + 3.02 [ 27] b RATIOS (%) a (ORGAN WEIGHT/BRAIN WEIGHT) X 100. ARGUS 418-020 Page 204 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 1) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 205 DOSAGE GROUP I 0 MG/KG/DAY RAT # DESCRIPTION 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 DS ( 48- 56) DS( 59- 72) DG ( 0- 20) DL( 1- 22) DL( 5 ) DL( 14 ) DS ( DS ( DS ( DS ( DS( DS ( 68 ) 68 ) 68 ) 68 ) 68 ) 68 ) DS ( 15- 17) DL( 20- 21) DS ( 37- 45) DS ( 8- 71) DG ( 0 ) DL( 18- 22) DL( 9 ) LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMORHINORRHEA a CHROMODACRYORRHEA a PALATE : BROKEN a SWOLLEN SNOUT INCISORS: MISALIGNED MORIBUND SACRIFICED NO ADVERSE FINDINGS INCISORS : MISSING/BROKEN LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RIGHT EAR: SWOLLEN a NO ADVERSE FINDINGS SOFT OR LIQUID FECES DS = DAY OF STUDY DG DAY OF PRESUMED GESTATION a. Observation confirmed at necropsy. DL = DAY OF LACTATION PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 206 DOSAGE GROUP I 0 MG/KG/DAY RAT # DESCRIPTION 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 DL ( 12 ) DL( 14 ) DG ( 3- 21) DG ( 3- 21) DL ( 1- 22) DL( 1- 22) DL( 11- 12) DS ( 15- 16) DS ( 22- 26) DL ( 8 ) DL( 14 ) DG ( 4- 21) DL ( 1- 22) DG ( 3- 6) DL ( 13- 22) NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA a INCISORS: MISALIGNED a SOFT OR LIQUID FECES LEFT FORELIMB: SCAB (0.5 CM X 0.5 CM) RIGHT FORELIMB: SCAB (0.2 CM X 0.2 CM) SACRIFICED b NO ADVERSE FINDINGS SOFT OR LIQUID FECES BOTH EARS : SWOLLEN BOTH EARS: SWOLLEN a NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. because it was not possible to identify to which litter the pups belonged. Both dams and litters were sacrificed PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 3): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP II 1 MG/KG/DAY RAT # DESCRIPTION 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 DS( 40- 45) DS( 57- 59) DS ( 59 ) DS ( 59 ) DL( 17- 21) DS ( 32- 71) DG ( 0- 21) DL( 1- 22) DL( 12 ) DS ( 1- 5) DS ( 7 ) INCISORS: MISSING/BROKEN NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LEFT FORELIMB AND FOREPAW: SWOLLEN a LEFT FORELIMB : FRACTURED MORIBUND SACRIFICED LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA DS DAY OF STUDY DG = DAY OF PRESUMED GESTATION a. Observation confirmed at necropsy. DL = DAY OF LACTATION ARGUS 418-020 Page 207 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 4) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP II 1 MG/KG/DAY RAT # DESCRIPTION 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 DL( 11 ) DG ( 16- 21) DL( 4- 22) DL( 8 ) DL( 12- 13) DS( 30- 32) DS( 59- 73) DG ( 0- 13) DG ( 20 ) DL( 1- 22) DL( 8- 22) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SACRIFICED b NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOWER MIDLINE: SCAB (0.5 CM X 0.2 CM) RIGHT EAR: SWOLLEN a SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES LOCALIZED ALOPECIA: UNDERSIDE LOCALIZED ALOPECIA: UNDERSIDE LOCALIZED ALOPECIA: UNDERSIDE LOCALIZED ALOPECIA: UNDERSIDE a LOCALIZED ALOPECIA: LIMBS a DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. because it was not possible to identify to which litter the pups belonged. Both dams and litters were sacrificed ARGUS 418-020 Page 208 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 5) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 DS ( 77-109) DS ( 5 ) DS ( 73 ) DG ( 0- 17) DG ( 4- 6) DG ( 7- 10) DG ( 11- 17) DL ( 4- 13) DL( 4- 22) DL( 7- 8) DL ( 22 ) NO ADVERSE FINDINGS BOTH EARS: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA LEFT HINDPAW : SWOLLEN LEFT HINDPAW : SWOLLEN LEFT HINDPAW: ABRASION (0.3 CM X 0.2 CM) LEFT HINDPAW: SCAB (0.3 CM X 0.2 CM) LOCALIZED ALOPECIA: LIMBS RIGHT EYE : SWOLLEN TRAUMATIZED CORNEA a NO ADVERSE FINDINGS NO ADVERSE FINDINGS TEAT: SWOLLEN NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION a. Observation confirmed at necropsy. DL = DAY OF LACTATION ARGUS 418-020 Page 209 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 6) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 DS( 8- 9) DG ( 7- 21) DS ( 55- 73) DS( 68- 73) DG ( 0- 2) DG ( 0- 21) DL ( 1- 22) DL( 7- 22) DL( 14- 15) DS ( 2- 3) DL( 22 ) CHROMORHINORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RIGHT EAR: SWOLLEN INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA INCISORS: MISALIGNED INCISORS: MISALIGNED a INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS SOFT OR LIQUID FECES CHROMORHINORRHEA LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION a. Observation confirmed at necropsy. DL = DAY OF LACTATION ARGUS 418-020 Page 210 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 7) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 211 DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 DG ( 2 ) DG( 3- 20) DL( 1- 9) DL( 12- 14) DG ( 19- 20) DS( 37- 49) DS( 58- 71) DS ( 58- 71) DG ( 0- 2) DG ( 0- 21) DL ( 1- 22) DL ( 19- 22) DS ( 7 ) DG ( 11 ) DG ( 7- 21) DL ( 1- 22) DL ( 22 ) NO ADVERSE FINDINGS CHROMODACRYORRHEA INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN NO ADVERSE FINDINGS RIGHT AXILLA: MASS (2.5 CM X 1.0 CM X 1.0 CM) INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN CHROMODACRYORRHEA INCISORS : MISALIGNED CHROMODACRYORRHEA INCISORS: MISALIGNED INCISORS : MISALIGNED a CHROMODACRYORRHEA a CHROMORHINORRHEA CHROMORHINORRHEA RIGHT EAR: SWOLLEN RIGHT EAR: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS RIGHT EAR: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION a. Observation confirmed at necropsy. DL = DAY OF LACTATION PROTOCOL 418-020: ORAL (GAVAGE) TWO -GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 8) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION 13904 13 905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 DL ( 5 ) DS ( 87- 95) DL ( 12- 16) DG ( 14 ) DG ( 14 ) DL( 14- 22) DG ( 5- 21) DL ( 1- 22) DS ( 22- 28) SOFT OR LIQUID FECES NO ADVERSE FINDINGS BOTH EARS : SWOLLEN SOFT OR LIQUID FECES DRIED, RED PERINASAL SUBSTANCE BOTH FOREPAWS: DRIED, RED SUBSTANCE RIGHT EAR: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS BACK: NUMEROUS SCABS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION a. Observation confirmed at necropsy. DL = DAY OF LACTATION ARGUS 418-020 Page 212 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 9) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 DS ( 24 ) DG ( 7- 21) DL ( 1- 22) DL( 6- 10) DG ( 12- 21) DL( 1- 10) DS ( 46- 54) DG ( 4- 8) DG ( 14 ) DG { 19- 21) DL( 1- 4) DL ( 5- 11) DL( 12- 18) NO ADVERSE FINDINGS NO ADVERSE FINDINGS UNGROOMED COAT NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RIGHT EAR: SWOLLEN RIGHT EAR: SWOLLEN a RIGHT EAR: SWOLLEN NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN LOCALIZED ALOPECIA: LIMBS CHROMORHINORRHEA HEAD: MASS (0.7 CM X 0.5 CM X 0.3 CM) HEAD: MASS (0.7 CM X 0.5 CM X 0.3 CM) HEAD: SCAB (DID NOT EXCEED 0.5 CM X 0.5 CM) LOCALIZED ALOPECIA: HEAD DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION a. Observation confirmed at necropsy. DL = DAY OF LACTATION ARGUS 418-020 Page 213 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C24 (PAGE 10) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 DL ( 13- 22) DS ( 16- 17) DL ( 12- 22) DG ( 9- 21) DL( 1- 22) DL( 1 ) DS ( 30- 50) DS ( 53- 73) DS ( 53- 73) DG ( 0- 12) DG ( 0- 20) DL ( 7- 22) DL ( 9- 22) DL ( 8- 9) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMODACRYORRHEA a CHROMORHINORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS BOTH EARS: SWOLLEN BOTH EARS: SWOLLEN a SACRIFICED DUE TO NO SURVIVING PUPS INCISORS MISALIGNED INCISORS MISSING/BROKEN INCISORS MISALIGNED INCISORS MISSING/BROKEN INCISORS MISALIGNED INCISORS MISSING/BROKEN a INCISORS MISALIGNED a NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION a. Observation confirmed at necropsy. DL = DAY OF LACTATION ARGUS 418-020 Page 214 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C25 (PAGE 1) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 215 DAY 1 8 15 22 29 36 43 RAT # DOSAGE GROUP I 0 MG/KG/DAY 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 131. 154. 154. 155 . 141. 155. 149. 145. 140. 154. 145. 152. 136. 155. 147. 152. 138. 156. 143. 134. 144 . 151. 148. 154 . 142. 160. 147. 153 . 145. 153 . 149 . 183. 177. 187. 173 . 182 . 186 . 181. 168. 194 . 177. 178. 167. 177. 186. 171. 164. 179. 174 . 187. 170. 186 . 175. 186. 175. 188 . 188 . 176. 175. 173 . 177 . 216. 216. 209. 194 . 200. 215. 204 . 190. 225. 200. 195. 187. 204. 214. 197. 187. 212 . 195. 216 . 196. 215. 199. 216 . 193. 216. 214 . 196. 185. 188. 187 . 240. 227. 227. 216. 217. 234. 224 . 202. 249. 215. 209. 203. 225. 239. 202 . 204. 219. 210. 233 . 212. 232. 217. 232 . 219. 230. 229. 213. 198. 191. 194. 260. 242. 250. 256. 229. 254 . 239. 218 . 261. 214 . 224. 218 . 240. 256 . 223 . 213 . 229. 222 . 251. 227. 254 . 240. 248 . 237. 248 . 253 . 226. 209. 200. 205. 262 . 256. 257. 240 . 236. 264. 250. 226. 265. 236. 233 . 230. 251. 264 . 216. 222. 236. 232. 265 . 240. 265. 254 . 262 . 254. 258. 266. 233 . 221. 211. 217 . 282. 272. 263 . 248 . 245. 275. 256. 237 . 279. 238. 241. 240. 257. 283 . 227. 226. 236. 236. 278. 251. 273 . 263 . 284 . 260. 261. 277. 236. 227. 216. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. Rat 13804 was moribund sacrificed on day 68 of study. 50 227. 297. 283 . 270. 267. 261. 281. 264. 242 . 297. 251. 254. 248. 274 . 292 . 233 . 233 . 251. 253 . 288 . 252 . 268. 268. 285. 274 . 271. 280. 252 . 242. 225 . 57 225. 296. 288 . 279. 275 . 258. 290. 266. 245. 296. 266. 262. 255. 274 . 308. 239. 227 . 253 . 256. 293 . 261. 278 . 279. 296. 283 . 288. 290. 263 . 249. 229 . 64 238. 293 . 301. 281. 280. 264. 290. 267. 258. 298. 264. 278. 265. 280. 310. 239. 235. 260. 250. 299. 267. 286. 290. 303. 292 . 285 . 307 . 268. 250. 235. 70a 246. 308. 303. b 278 . 268. 301. 270. 253. 309. 271. 278. 266. 280. 315. 239. 239. 264. 261. 300. 268. 283. 292 . 299. 288. 292. 298. 273 . 252 . 234 . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C25 (PAGE 2) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 216 DAY RAT # 1 8 15 DOSAGE GROUP II 22 29 36 43 1 MG/KG/DAY 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 139.. 159.. 147.. 150.. 142., 155., 144 ., 149., 138.. 156.. 150., 153 . 140., 157., 153.. 149., 141., 156., 146., 147., 141., 149.. 145., 152.. 143.. 151. 145., 151. 144. 148., 171 . 191.. 173 . 179.. 177,. 171,. 163,. 179,. 166.. 185,. 174,. 176.. 162.. 189.. 179,. 167,. 175,. 185.. 176,. 176,. 167,. 172.. 176,. 190., 177.. 174 ,. 172,, 174 .. 171., 171., 193. 219. 205. 204. 197. 188. 179. 202. 194. 209. 195. 207. 179. 216. 200. 186. 194 . 215. 204 . 199. 187. 192. 197. 225. 206. 207. 202. 194 . 193 . 187. 214. 241. 216. 221. 212. 197. 195. 222. 210. 225. 215. 213. 185. 234. 207. 198. 211. 227. 220. 212 . 202 . 211. 214 . 249. 233 . 227. 215. 210. 204 . 195. 219. 249.. 233 . 230., 224 ., 207., 209., 234 . 226., 240 . 227. 229. 197. 253 . 224 . 210. 224 . 245. 235. 229. 211. 232 . 233 . 266 . 247 . 241. 222 . 227 . 212 . 204 . 242 . 263. 233. 230. 226. 214. 217. 251. 227. 242 . 235. 235. 205. 262. 230. 221. 238 . 257. 253. 243 . 223. 240. 244 . 272 . 254 . 251. 233 . 235. 216. 210. 260. 263 . 249. 249. 242 . 217. 219. 256. 242 . 252 . 245. 243 . 214 . 266. 234 . 230. 249. 273 . 268 . 252 . 234. 246. 249. 276. 257. 256. 245. 238. 229. 223 . DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. 50 264. 268. 255. 266. 252. 227. 230 . 275. 254. 260. 258 . 250. 215. 276. 241. 250. 260. 280. 283 . 267 . 237 . 257. 262 . 288. 267 . 268 . 254 . 244 . 235. 231. 57 259 269 258 269 255 237 236 284 260 259 266 256 221 283 244 252 261 285 283 274 240 271. 264 296 278 278 258 259 245 238 64 70a 266. 273. 283. 283. 260. 267. 267. 274. 256. 268. MORIBUND SACRIFICED ON DAY 59 OF STUDY 244. 249 300. 307 263. 272 264. 265 272. 273 258. 261 227. 229 286. 287 251. 252 256. 256 274. 276 292 . 294 297. 306 278 . 280 251. 257 283 . 280 271. 272 302. 302 278 . 280 284 . 289 267. 266 265. 265 241. 248 251. 252 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C25 (PAGE 3): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 217 DAY 1 8 15 22 29 36 43 RAT # DOSAGE GROUP III 3 MG/KG/DAY 13861 13862 13863 13864 13B65 13866 13867 13868 13869 13B70 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 130. 161. 14 9. 149. 141. 161. 149. 146. 145. 154. 148. 154 . 142. 156. 143. 155. 144 . 149. 144. 155. 146. 158. 152. 150. 147. 155. 144 . 153. 148. 150. 157. 193 . 177. 181. 181. 194 . 176. 173 . 178 . 180. 185. 182. 174. 200. 174 . 192. 185. 179. 176. 188 . 173. 190. 179. 188 . 183. 184 . 174 . 181. 183. 178. 177. 227 . 207. 207. 202 . 223 . 199. 203 . 210. 200 . 209. 207. 192. 234 . 190 . 220. 214. 205. 195. 216. 192 . 220 . 197 . 216. 208 . 210. 200. 209. 210. 208. 189. 248. 215. 212 . 219. 257. 215. 212. 226. 221. 225. 216. 215. 249. 208. 249. 241. 221. 215. 232. 198. 239. 212. 237. 232. 223 . 206. 233 . 233 . 225. 198. 269. 222 . 234. 236. 277. 230. 223 . 249. 237. 238. 233. 221. 278 . 225. 278. 256. 233 . 222 . 253 . 213 . 258 . 226. 248. 245. 236. 218 . 248 . 248 . 241. 206 . 279 . 228 . 238. 245. 283 . 237. 238. 261. 248. 236. 242 . 231. 294. 232. 293 . 270 . 241. 239. 266. 211. 272 . 234 . 261. 253 . 245 . 230 . 255. 256. 253 . 213. 290. 239. 254. 244. 307. 250. 250. 272. 260. 239. 253. 241. 309. 240. 306. 293. 252. 248. 281. 224 . 281. 238. 272. 258. 251. 235. 265. 264. 263. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. 50 220. 297 . 248 . 261. 262. 309. 254 . 254 . 278 . 271. 254 . 255. 246. 322. 251. 328. 300 . 264 . 261. 300 . 228. 292. 252. 278. 270. 254 . 245. 275. 272. 268 . 57 232. 302 . 251. 261. 282. 325. 256. 264 . 290. 277. 256. 266. 252. 321. 263. 338. 308 . 267. 270. 314 . 240 . 292 . 262 . 286 . 281. 260. 246. 286 . 283 . 275. 64 236. 313 . 253 . 265. 288. 333 . 268. 267. 299. 283 . 259. 275. 266. 336. 268. 347. 319. 277. 280. 320. 243 . 296 . 268. 287. 291. 266. 259. 292 . 286 . 285. 70a 236. 315. 264 . 265. 291. 334. 269. 269. 290. 283 . 273 . 276 . 263. 337. 267. 351. 326. 289. 280. 327. 248. 306. 270 . 296. 297. 269. 257. 298 . 289. 282 . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C25 (PAGE 4) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 218 DAY 1 8 15 22 29 36 43 RAT # DOSAGE GROUP IV 10 MG/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 136.. 160,. 155.. 152.. 141.. 157,. 151.. 159.. 140,. 155.. 150.. 145.. 140.. 151.. 149.. 153 . 140.. 155.. 147,. 151.. 145., 159.. 142.. 153., 148 ., 156.. 146,. 154., 143.. 150.. 160.. 192,. 192.. 186.. 176,. 191,. 192.. 191.. 165.. 184.. 174.. 171.. 173.. 174.. 188,. 193.. 167.. 188., 177,. 186.. 177., 189.. 173.. 183., 182., 191.. 176., 182., 167.. 179., 178. 215. 225. 214 . 208. 215. 225. 220. 185. 210. 197. 196. 198. 185. 207. 216. 190. 212. 200. 219. 202. 211. 199. 212. 204 . 215. 218. 206. 196. 199. 190. 233. 249. 237. 223 . 229. 231. 248. 203. 222. 214. 212. 216. 201. 230. 231. 206. 240. 211. 249. 213. 234. 215. 235. 218. 234. 227. 215. 215. 212. 210 . 250. 273 . 252 . 236. 247 . 251. 264 . 210 . 237. 225. 227. 229. 214 . 249 . 248 . 227. 260. 229. 258 . 231. 248 . 229. 250. 236. 247. 237. 228 . 226. 224 . 218. 260. 281. 265. 238. 255. 262. 279. 213. 247. 237. 236. 240. 224 . 251. 263. 235. 266. 241. 270 . 244 . 258 . 243 . 257. 246. 264 . 245. 236. 233 . 231. 227. 268. 286. 283. 248. 270. 276. 287. 223. 255. 250. 253. 251. 232. 267. 271. 241. 274 . 249. 282. 252. 263. 252. 264. 246. 278. 251. 245. 244. 247. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. 50 234 . 274 . 297. 298. 264 . 287. 283 . 293 . 233 . 263 . 260. 263. 269. 250. 273 . 271. 256. 290. 251. 300. 257. 278 . 260. 275. 253 . 290. 263. 255. 252. 256. 57 234. 289. 305. 301. 262. 290. 293 . 299. 239. 266. 255. 274. 276. 246. 278 . 282. 263 . 293 . 261. 300. 263 . 283 . 258. 284 . 264. 287. 270. 257. 253 . 260. 64 246. 292. 312. 303. 265. 277. 304. 304 . 239. 272. 262. 281. 285. 261. 280. 294. 262 . 301. 268. 315 . 271. 285 . 270. 291. 277. 304. 276. 261. 262. 271. 70a 243 . 294 . 321. 320. 265. 283. 310. 310. 244 . 272. 267. 286. 295. 271. 291. 296. 269. 303. 268 . 323 . 275 . 294 . 276 . 301. 263 . 312. 277. 260 . 269. 273 . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C25 (PAGE 5) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 219 DAY 1 8 15 22 29 36 43 RAT # DOSAGE GROUP V 30 MG/KG/DAY 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 141. 164. 146. 150. 138. 158. 153. 152. 140. 160. 147. 147. 139. 156. 149. 155. 137. 145. 148. 148. 146. 149. 148. 152. 148. 152. 144 . 159. 142 . 153 . 174. 191. 178 . 180. 169. 190. 181. 183. 163. 191. 178. 169. 173. 186. 181. 188. 167. 174. 185. 185 . 181. 176. 179. 173 . 178. 178. 179. 182. 173 . 180. 203. 204 . 202. 203. 189. 216. 207. 200. 185. 222 . 205. 195. 195. 206. 207. 210. 189. 199. 218. 210. 204 . 195. 194 . 202 . 206 . 200. 201. 208 . 205 . 200. 224. 219. 216. 221. 199. 228. 232. 216. 198. 233. 207. 213. 212. 215. 217. 225. 199. 220. 230. 230. 224 . 209. 207. 217. 229. 210. 218. 223 . 217. 214 . 240 237 228 237 212 237 250 231 214 247 231 223 227 233 234 239 211 232 249 245 250 224 231 235 241 225 230 232 236 228 244 . 239. 238 . 243 . 220. 238. 246. 245. 220. 253. 238. 224. 223 . 247. 239. 245. 222. 235. 250 . 254 . 258. 235. 235. 234. 248 . 233 . 234 . 249. 244 . 235. 258. 249. 246. 247. 228. 256. 265. 247. 224. 265. 251. 241. 236. 255. 255. 258. 236. 251. 265. 263. 265. 246. 251. 242. 259. 241. 240. 260. 261. 241. DAY - DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. 50 57 64 70a 270 . 263 . 261. 261. 230. 267. 270. 270. 235. 275. 257. 248 . 245. 258. 258 . 256. 242 . 258. 275. 266. 272 . 258. 253 . 256. 271. 247. 249. 266. 274. 252 . 276. 258. 269. 272 . 232 . 272 . 274 . 274 . 240 . 280. 262. 252. 244 . 265. 266. 265. 244 . 261. 284 . 272 . 281. 266. 267 . 263 . 275 . 249. 250. 267 . 284 . 256. 279. 261. 270. 277. 239. 272 . 269. 281. 243 . 276. 271. 255. 250. 276. 268. 279. 253. 257. 283 . 268 . 285. 257. 271. 258 . 276. 254 . 255 . 278 . 293 . 272 . 284 268 277 275 243 284 278 287 245 286 273 263 247 270 280 278 264 271 294 275 288 262 267 261 284 256 254 275 298 268 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C26 (PAGE 1) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 220 PREGNANCY STATUS DAY 0 7 10 14 18 21 RAT # DOSAGE GROUP I 0 MG/KG/DAY 13801 P 13802 P 13803 P 13804 " 13805 P 13806 P 13807 P 13808 P 13809 P 13810 P 13811 NP 13812 P 13813 P 13814 P 13815 P 13816 P 13817 P 13818 P 13819 P 13820 P 13821 P 13822 P 13823 P 13824 P 13825 P 13826 P 13827 P 13828 P 13829 P 13830 P 238. 276. 289. 310. 310. 306. 352 . 372. 380. 418 . 319. 348. 356. 378. 421. MORIBUND SACRIFICED ON DAY 68 OF STUDY 278. 267. 324 . 305. 334 . 313 . 352 . 334 . 396. 379. 306. 324 . 330. 354 . 408. 272. 293 . 298. 317. 361. 276. 297. 308. 322 . a 300. 340. 350. 365. 407 . 264. 297. 301. 305. 304 . 275. 295. 307. 328. 362. 279. 306. 328. 348 . 381. 290. 316. 325. 336. 360. 324 . 345. 366. 378 . 411. 238. 271. 284 . 295 . 338. 241. 270. 281. 292 . 340. 266. 297. 312. 332 . 376. 261. 291. 300. 312 . 360. 292. 299. 319. 322 . 362. 268. 306. 308 . 336. 374 . 292. 327. 330. 354 . 385 . 302 . 327. 342. 359. 385. 299. 339. 350 . 368. 407 . 290. 313. 327. 342. 385. 290 . 326. 325. 343 . 405 . 311. 338. 339. 370 . 414 . 274 . 315. 320. 330. 370 . 252. 286. 291. 305. 349. 243 . 262 . 273 . 293 . 326 . 350. 468. 464 . 421. 318. 312 . 397. 458. 302 . 409. 421. 416. 438 . 388 . 389. 425. 347. 412. 417 . 421. 415. 449. 422. 437. 459. 410. 389 . 293 . P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was not recorded. 25 309. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C26 (PAGE 2) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 221 PREGNANCY STATUS DAY 0 7 10 RAT # DOSAGE GROUP II 14 18 1 MG/KG/DAY 21 13831 P 13832 P 13833 P 13834 P 13835 P 13836 13837 P 13838 P 13839 P 13840 NP 13841 P 13842 P 13843 P 13844 P 13845 P 13846 P 13847 P 13848 P 13849 P 13850 P 13851 NP 13852 P 13853 P 13854 P 13855 P 13856 P 13857 P 13858 P 13859 P 13860 P 283. 294. 271. 323 . 324 . 291. 337. 332. 298. 354. 348 . 306. 403 . 390. 358. 275. 298. 305. 315. 352. 272. 296. 318. 329. 380. MORIBUND SACRIFICED ON DAY 59 OF STUDY 244 . 275. 280. 303 . 341. 303. 333. 344 . 366. 428. 258. 292. 304 . 314 . 356. 260. 282 . 288. 286 . 282. 278. 298. 309. 322. 374. 262. 284 . 289. 303 . 353. 224. 247. 258. 282. 312. 287. 304 . 312. 322. 379. 245. 274 . 290 . 307 . 352. 253 . 285 . 296. 311. 359. 271. 297. 303. 313. 370. 295. 333 . 341. 354. 408. 298 . 334 . 341. 359. 389. 276. 286. 320. 331. 377. 259. 267. 270. 270. 276. 282. 308. 324 . 335. 390. 273 . 306. 316 . 330. 381. 289. 328. 342. 353. 410. 276. 310. 326 . 337. 386. 292. 321. 332 . 348 . 398. 278 . 303. 310. 329. 365. 270. 293. 296 . 306. 356. 246. 268 . 278. 294. 342. 248 . 278. 282 . 297. 325. 438. 447. 404 . 388. 429. 303. 467. 390. 284. 396. 400. 282. 406. 388. 394 . 402 . 455. 425. 324 . 275 . 413 . 303. 455. 339. 417. 417. 309. 378. 335. P *= PREGNANT NP NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C26 (PAGE 3) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 222 PREGNANCY STATUS DAY 0 7 10 14 18 21 RAT # DOSAGE GROUP :III 3 MG/KG/DAY 13861 P 13862 P 13863 P 13864 P 13865 P 13866 P 13867 P 13868 P 13869 P 13870 P 13871 P 13872 P 13873 P 13874 P 13875 P 13876 P 13877 P 13878 P 13879 P 13880 P 13881 P 13882 P 13883 P 13884 P 13885 P 13886 P 13887 P 13888 P 13889 P 13890 P 234. 257. 265. DID NOT DELIVER A LITTER 249. 281. 291. 261. 296. 310. 286. 339. 347. 328. 358. 379. 275. 296. 308. 275. 302. 310. 292. 304. 326. 282. 307. 310. 262. 294. 301. 281. 311. 316. 281. 289. 301. 334. 366. 374 . 265. 301. 323 . 349. 385. 401. 324. 357. 372 . 274. 293. 305. 273 . 304 . 322 . 321. 364. 376. 244 . 277. 294 . 301. 335. 347. 265. 302 . 311. 292. 314. 329. 284 . 320 . 336 . 256. 287. 291. 266. 290. 300. 293 . 320. 330. 296. 325. 328 . 278. 320 . 334 . 282 . 312., 328.. 363 . 397 . 326.. 335., 356., 336.. 319., 335., 310., 390. 338., 422., 391., 323.. 334 . 404 . 306.. 374.. 320., 340,. 352 . 310,, 318.. 347,. 341.. 348.. 312. 362. 340. 423 . 438. 369. 373. 389. 373 . 385. 379. 370. 438 . 399. 474. 433. 358. 376. 450. 348. 403 . 372. 371. 374 . 358. 352. 403. 389. 394. 339. 416. 358. 420 . 488. 416. 407. 437. 399. 351. 417. 424. 487. 436. 520. 482 . 388. 411. 496. 355. 433 . 409. 403 . 367. 372. 390 . 430. 343 . 432. P = PREGNANT NP NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY - DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C26 (PAGE 4) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 223 PREGNANCY STATUS DAY 0 7 10 RAT # DOSAGE GROUP IV 14 18 10 MG/KG/DAY 21 13891 P 13892 P 13893 P 13894 P 13895 P 13896 P 13897 P 13898 P 13899 P 13900 NP 13901 P 13902 P 13903 P 13904 P 13905 P 13906 P 13907 P 13908 P 13909 P 13910 P 13911 P 13912 P 13913 P 13914 P 13915 P 13916 P 13917 P 13918 P 13919 P 13920 P 246. 260., 273 . 301. 315. 325. 319. 330.. 337. 305. 337. 355. 261. 2 94 . 302. 248. 303 . 322. 316. 340.. 351. 300. 336.. 355. 246. 270., 271. MATING NOT CONFIRMED 274. 310.. 321. 277. 305., 320. 293. 309.. 327. 254. 299., 314. 289. 327., 338. NO CONFIRMED MATING DATE 257. 288., 307. 302. 342. 356. 273. 302.. 316. 309. 353 . 366. 269. 301., 316. 284 . 311.. 321. 271. 309.. 326. 296. 318. 323 . 269. 306., 312. 307. 326.. 349. NO CONFIRMED MATING DATE 268. 290.. 305 . 250. 281., 289. 267. 296.. 315 . 283 . 341. 349. 364. 319. 332. 376. 366. 290. 339. 328. 339. 339. 352. 325. 364 . 328. 383 . 320. 333 . 334 . 356. 325. 370. 319. 305. 328 . 316. 388 . 396. 414 . 333. 367. 411. 417. 336. 386. 370. 382. 375. 389. 381. 387. 371. 424 . 364. 375. 364. 410. 369. 418. 359. 357. 368 . 348. 413 . 427. 448. 379. 403 . 449. 457. 3 72. 432. 418. 419. 411. 430. 384. 407. 463 . 381. 417. 386. 455. 419. 459. 410. 388. 423 . P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). 25 - ----- PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C26 (PAGE 5) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 224 PREGNANCY STATUS DAY 0 7 10 14 18 21 RAT # DOSAGE GROUP V 30 MG/KG/DAY 13921 P 13922 P 13923 P 13924 P 13925 P 13926 P 13927 P 13928 P 13929 NP 13930 P 13931 P 13932 P 13933 P 13934 P 13935 P 13936 P 13937 P 13938 P 13939 P 13940 P 13941 P 13942 P 13943 P 13944 P 13945 P 13946 P 13947 P 13948 P 13949 P 13950 P 276. 296. 310. 257. 296. 303 . 273 . 297. 304 . 268. 295. 298. 241. 252. 265. 272. 294. 317. 277. 310. 319. 284. 313. 317. 249. 252 . 249. 279. 311. 328. 276. 302. 311. 268. 287. 306. 249. 268. 278. NO CONFIRMED MATING DATE 268. 291. 308. 297. 309. 338. 248. 268. 276. 262. 286. 299. 292 . 307. 317. 278. 310. 310. 286. 315. 325. 253. 292. 295 . 252. 29 9. 302. 263. 289. 305 . 281. 309. 320. 258. 281. 296. 248 . 278. 289. 281. 297. 313. 289. 316. 325. 279. 296. 306. 328. 312. 321. 322. 282. 332. 339. 344. 254. 341. 330. 284 . 285. 314. 359. 295. 308 . 327. 328 . 346. 319. 316. 312. 331. 314 . 293. 320. 346. 325. 390. 323 . 373 . 370. 327 . 380. 386. 400. 243. 367. 375. 345. 329. 357. 400. 347. 372. 374 . 370. 398. 373 . 360. 337. 376. 349. 304 . 324 . 393 . 373. 428. 282. 316. 421. 358. 333 . 412. 439. 243 . 427. 388. 368. 373 . 402 . 430. 393 . 310. 407. 414 . 450. 411. 381. 375. 395. 375. 306 . 368. 348. 368. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C27 (PAGE 1) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 225 DAM # DAY 1 5 DOSAGE GROUP I 8 ii 15 0 MG/KG/DAY 22 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 294. 365. 346. 287. 376. 366. 302. 386. 372 . 309. 390. 372 . 322 . 396. 402. 338. 367. 366. MORIBUND SACRIFICED ON DAY 68 OF STUDY 320. 336. 346. 352. 370. 302 . 308. 337. a 341. 348. 340. 315. 302. 298. 344 . 298. 316. 369. 316. 348. 376. a 345 . 376. 331. 354. 367. 286. 355. 355. 357. 382. 389. 3 94. 370. NOT PREGNANT 299. 322. 337. 341. 354. 326. 316. 342. 363. 390. 349. 393. 301. 313 . a 343 . 351. 359. 340. 332. 332. 356. 367. 370. 285. 294. 292 . 321. 326. 320. 272 . 271. a 293 . 314. 302. 296. 303 . a 336. 328 . 376. 299. 314 . 331. 327. 321. 344 . 312 . 337. 343 . 369. 381. 317. 304 . 334 . 352 . 364 . 344 . 328 . 327 . 342 . 330. SACRIFICED ON DAY 8 OF LACTATION 338. 348 . 336. 364 . 353. 339. 330. 342 . 351. 379. 400. 385. 317. 318. 342 . 355. 338. 350. 328. 349. 341. 356 . 380. 376. 351. 347. 368. 394 . 404 . 377. 306 . 297 . 328 . 340 . 351. 309. 284 . 280 . 279. 324 . 312. 301. 265. 265 . a 303 . 309. 306. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C27 (PAGE 2) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 226 DAY 1 5 8 il 15 22 DAM # DOSAGE GROUP II i MG/KG/DAY 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 321. 322. a 375. 365. 361. 342. 329. 373. 368. 380. 357. 293. 307. 310. 343. 344 . 343 . 294. 293 . 304 . 320. 316. 310. 304 . 326. 336. 336. 360. 318. MORIBUND SACRIFICED ON DAY 59 OF STUDY 289. 293 . 307. a 329. 359. 335. 331. 355. 385. 382. 375. 301. 314. 327. 335. 340. 361. NOT PREGNANT 290. 320. 312. 332. 362 . 347. 293. 306. 324 . 338., 362. 351. 260. 276. 287. 299.. 301. 317. 292. 315. 332. 331.. 361. 368. 283. 277. 298. 305.. 323. 352. 290. 292. 297. 276.. 326. 336. 289. 296 . 314 . 322 . 338. 314 . 319. 335. 353 . 385 . 377. 331. 314 . 320. a 349 . 319. 336. 320 . 296 . 322 . a 350. 341. NOT PREGNANT 322 . 301. 317. SACRIFICED ON DAY 11 OF LACTATION 296. 309. 322 . a 331. 331. 340 . 358. 375. 372 . 379. 381. 317. 338. 356. 371 . 379. 330. 318. 342. 358. 347 . 386. 367. 305. 328. 335. 358 . 337. 295. 301. 288 . 325. a 314 . 338. 282. 295. a 320 . 323. 316. 277 . 268. a 299 . 294. 293 . DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C27 (PAGE 3) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 227 DAY 1 5 8 11 15 DAM # DOSAGE GROUP III 3 MG/KG/DAY 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 275. 274 . 285 . 276. PREGNANT;: DID NOT DELIVER A LITTER 297. 320. 336. 335. 312. 310. 311. 344 . 340. 332. 339. 344 . 368. 366. 392 . 406. 293 . 302. 322 . 328. 304. 308. a 348. 318. 337. 349. 361. 319. 320. 330. 327. 315. 313. 343. 323 . 308. 322 . 335. 344. 301. 324. 334 . 355.. 368. 379. a 401., 309. 306 . 327 . 332 . 398. 413. 427. 438.. 373. 376. a 388.. 309. 312. 335. 330,. 308. 368 . 329. 366 . 342 . 366 . 337.. 374 . 291. 298. 313 . 321 . 332. 341. a 381 . 303 . 322 . 343 . 347 . 316. 335. 325. 347 . 323 . 336. 340. 351 . 300 . 299. 338. 364 . 295. 309. 316. 341 . 327. 303. 306 . 339 . 333 . 326. 352. a 312. 315. 336 . 356 . 305. 334 . 334 . 364 . 408. 355. 354. 372 . 366 . 337. 353. 350. 403. 360. 441. 404. 352. 360. 377 . 318. 361. 331. 363. 349. 340. 322. 337. 367. 357. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was not recorded. 22 312. 352. 335. 353 . 401. 335. 356. 357. 386. 366. 347. 346. 368. 358. 399. 383 . 352. 328 . 363 . 323. 355. 342. 368. 336. 322 . 310. 335. 340 . 364. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C27 (PAGE 4) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 228 DAY 1 5 8 il 15 DAM # DOSAGE GROUP IV 10 MG/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 264 . 260. 275. 285 . 336. 334. a 361. 319. 330. 352. 380. 332. 350. 371. 389. 301. 310. 339. 352. 311. 329. 334. 347. 351. 338. 359. 368. 350. 369. 405. 328. 268. 284. a 288. NOT PREGNANT; MATING NOT CONFIRMED 303. 313. 329. 348 . 304. 301. 322. 314 . 317. 339. 349. 356. 306. 316. 342. 359. 321. 338. 364. 350. 316. 317. 337. 359. 301. 308. 317. 315. 343. 343. 343. 359. 294. 317. 331. 347. 350. 361. 382 . 371. 294. 276. 297 . 320. 316. 324. 337. 351. 305. 321. a 336. 326. 340. a 365. 281. 293. 316. 346. 356. 336. a 379. 312. 288. a 325. 290. 309. 335. 342. 285. 287. a 330. 301. 315. a 340. 285. 364 . 370. 399. 354 . 363 . 376. 408. 308 . 344 . 333 . 336. 364 . 360. 352. 318. 374. 355. 381. 325. 341. 363 . 371. 335. 371. 330. 336. 324 . 308 . DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was not recorded. 22 300. 366. 332. 386. 334. 376. 361. 395. 320. 350. 311. 318. 354. 351. 355. 337. 366. 356. 353 . 327. 355. 317. 294. 323 . 376. 327. 302. 329. 349. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C27 (PAGE 5) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 229 DAY 1 5 8 ii 15 22 DAM # DOSAGE GROUP V 30 MG/KG/DAY 13921 13922 13923 13924 13 925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13 942 13943 13944 13945 13946 13947 13948 13949 13950 311. 310. 320. 346. 368. 357. 274. 304 . 307. 318. 334. 352. 305. 291. 287. 316. 303. 327. a 342. 325. 350. 320. 341. 273 . 278 . 298. 310. 311. 318. 324. 289. 320. 293. 338. 298. 349. 308 . 366 . 334. 353 . 331. 317. 330. 346. 358. 359. 368 . NOT PREGNANT 318. 321. 325. 341. 369. 350. 318. 300. a 324 . 339. 368. 275. 297. a 323 . 331. 357. 276. 285. 286. 293 . 328 . 326 . 303 . 306. 322. 327 . 327. 340. 294. 313 . 308. 313. 315. 318. 321.. 337. 353 . 352. 360. 349. 286. 303 . 317. 311. 318. 306. 298. 290. 301. 316. 343. 343. 301. 308. 331. 342. 370. 349. 304. 324 . 316. 352. 351. 353. 341. 353 . 352 . 304 . 335. 383 . 298 . 313 . 334. 361. 345. 344 . 308. 316. 337. 350. 359. 349. 291. 279. 302. 299. 336. 341. 312.. a 341. 351. 360. 342. 292. 312. 327. 338. 327. 353 . 273 . SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 267. 289. 322. 338. 346. 323 . 345. 342. 359. 366. 3 74. 365. 304 . 298. a 340. 357. 361. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C28 (PAGE 1) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 230 DAYS RAT # 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 50- 57 57- 64 64- 70a DOSAGE GROUP I 0 MG/KG/DAY 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 100. 132. 133. 148. 111. 140. 133. 142. 131. 142. 125. 126. 123. 125. 147. 164 . 121. 132. 126. 143 . 116. 139. 131. 130. 14 3. 140. 138. 114. 137. 124 . 188. 161. 158. 148. 122 . 143 . 148. 158. 142. 156. 133. 130. 143. 154. 156. 193 . 123 . 149. 137. 158 . 137. 144 . 144 . 138 . 144 . 142 . 14 9. 127. 133 . 120. 126. 168. 154. 162 . 154. 147. 152. 158. 143. 218.C 163. 154 . 142. 160. 165. 126 . 124 . 150. 138 . 165 . 137. 152 . 145 . 154 . 155. 139. 168. b 178. 129. 109. 167. 156. 162. 152. 146. 151. 160. 146. 157. 140. 155. 146. 14 5. 174. 137. 123 . 141. 134. b 136. 153 . 14 5. 152 . 157. 141. 173 . b 184 . 139. 120 . 160. 159. 161. 150. 147 . 159. 158. 140. 167. 144 . 147. 147 . 145. 171. 123 . 129. 143 . 147 . 184 . 143 . 173 . 157 . 149. 166. 144 . 174 . 117. 144 . 122 . 124 . 177 . 151. 159. 175. 154 . 143 . 156. 149. 179. 141. 144 . 160. 167. 183 . 130. 117. 140 . 146. 178 . b 150. 149. 148. 163. 140 . 166. 129. 142 . 126. 133 . 181. 172 . b 177. 165. 158. 158 . 152. 176. 168. 154. 159. 169. 181. 132 . 115. 149. 161. 191. 143 . 140. 148 . 202 . 166. 145 . b 147 . b 138. 119. b 150 . 154. 158. 144 . 146 . 144 . 146. 159. 152. 141. 157. 149 . 177 . 128. 110. 143. 136. 173 . 137. 138 . 148. 153 . 163 . 143 . b 182 . 135 . 134 . 136. 149.C 158.C 156. 162 . 147. 145. 148. 151. 174. 152. 172 . 216. 151. 175 . 130. 117. 144 . 138. 163 . 144 . b 150. 148. 173 . 139. 179. 140. 153 . 126 . 119. 137. 145. MORIBUND SACRIFICED ON DAY 68 OF STUDY 133. 133 . 124 . 123 . 120. 152. 119. 134 . 133 . 135. 141. 108 . b 117. 133. 139 . 110. 115. 123 . 118. 127 . 124. 145. 130 . b 106 . DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value. c. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C28 (PAGE 2) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 231 DAYS RAT # 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 50- 57 57- 64 64- 70a DOSAGE GROUP II 1 MG/KG/DAY 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 139. 134. 133. 158. 145. 125. 110. 127. 129. 141. 136. 139. 131. 165. 139. 118. 109. 153 . 134 . 147. 124. 120. 135. 139. 139. b 111. 170. 133. 125. 146. 145. 145. 154 . 142. 134 . 117. 136. 136. 160. 142. 156. 133. 176. 149. 125. 128. 149. 149. 203 . 132 . 130 . 141. 155. 153 . 211. 146. b 147. 128 . 148. 146. 142. 172 . 144 . 134 . 138. 141. b 164. 151. 142. 129. 169. 144 . 123. 140. 147. 149. 148 . 146. 158. 146. 206. 160. 149. 143. 158 . 139. 124. 149. 144 . 145. 151. 140 . 127 . 123 . 136. 139. 149. 146. 155. 121. 176. 142 . 125. 130. 150. 153. 182 . 146. 140 . 147 . 173. 157. 159. 130. 151. 138. 125 . 166. 148. 146. 145. 140 . 134. 123. 14 7. 145. 151. 142. 137. 139. 172. 138. 130. 137. 150. 166. 174 . 155. 149. 148 . 159. 151. 166. 150. 147. 139. 130. 163. 141. 156. 165. 148. b 122. 145. 149. 151. 163 . 160. 134. 176. 142 . 134. 138. 147. 167. 163 . 150. 141. 150. 156. 150. 183 . 142 . 150. 142 . 138. b 141. 153 . 178. 146. 146. 135. 159. 148. 149. 160. 158. 138. 174 . 148 . 143 . 142 . 152. 166. 178 . 134 . 157. 153 . 169. 154 . 164 . 138. 152 . 138 . 139. 181. 147. 150. 150. 141. 141. 129. 146. 149. 143 . 144 . 134. 131. 169. 144 . 134. 136. 152. 156. 190. 138. 160. 145. 165. 146. 160 . 138. 156. 139. 143 . 166. 123. 146. 119. 148. 135. 146. 126. 141. 125. MORIBUND SACRIFICED ON DAY 59 OF STUDY 133. 120. 158. 129. 151. 136. 141. 114. 141. 146. 135. 102. 129. 112. 166. 136. 147. 130. 134 . 106. 136. 122. 144 . 122 . 168. 141. 170 . 130. 142 . 118. 155. 132. 154. 120 . 151. 127. 148 . 129. 159. 175. 134 . 111. 154. 137. 149. 128 . 145. 114 . DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C28 (PAGE 3) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 232 DAYS RAT # 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 50- 57 57- 64 64- 70a DOSAGE GROUP III 3 MG/KG/DAY 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 123. 149. 142. 132. 148. 159. 135. 133 . 145. 139. 128. 136. 124 . 152. 130. 145. 150. 125. 131. 143 . 127. 140 . 141. 158. 140. 136. 135. 139. 14 9. 14 9. 136. 152. 154 . 142. 147. b 140 . 148. 161. 155. 139. 161. 134 . 163 . 154 . 164 . 161. 145. 148. 160 . 120. 153 . 145. 158. 141. 141. 159. 159. 160. 235. 131. 169. 145. 139. 170. 180. 144 . 176. 166. 162. 143. 141. 124. 161. 150. 173. 168. 137. 147. 151. 131. 161. 147. 154. 150. 142. 136. 174 . 162. 250.C 136. 177. 14 3 . 14 9. 159. 191. 145. 157. 194. 158. 138. 144. 138. 170. 145. 178. 162 . 148. 127. 162 . 130. 162. 142. 161. 142. 143 . 137. 167. 166. 213 . 133. 160. 149. 147. 160. 181. 141. 160. 162. 160 . 131. 141. 134. 177. 152. 171. 174 . 153 . 145. 162 . 115. 171. 145 . 160. 156. 145. 141. 154. 152 . b 136. 163 . 161. 159. 153 . 194 . 152. 167. 165. 172 . 133 . 147. 138. 175. 158. 196. 186. 146 . 143. 170. 129. 157. 149. 153. 143 . 137. 136. 166 . 158. 202 . 142 . 168. 150. 154 . 175. 184 . 136. 166. 173 . 168. 132. b 136. 178. 158. 198. 167. 155. 158 . 186 . 127 . 163 . 154 . 153 . 150. 139. 144. 163. 161. 184 . 142 . 163 . 145 . 142. 174 . 176. 144 . 164. 170. 167. 121. b 139. 168 . 153 . 188 . 166. 145 . 144 . 176 . b 146 . 160. 152 . 157. 131. 135. 166 . 157. b 145. 167. 150. 153 . 169. 172 . 156. 152. 159. 161. 129. 147. 145. 170 . 148. 166 . 168 . 154. 146. 167. 128. 166. 154. 147. 160 . 138. 131. 162. 157. 174 . 119 . 144 . 133 . 118 . 142 . 142. 124 . 133 . 129. 112. 148. 111. 116. 146. 132. 141. 142 . 126. 122 . 137. 104 . 129. 127. 121. 128. 113 . 110. 138. 130. 144 . DAYS DAYS OF STUDY ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value. c. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C28 (PAGE 4) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 233 DAYS RAT # 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 50- 57 57- 64 64- 70a DOSAGE GROUP IV 10 MG/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 129. 152. 155. 145. 14 9. 13 9. 153. 147. 131. 145. 125. 126. 129. 116. 156. 167. 121. 133 . 124 . 146 . 139. 144 . 130. 133 . 146. 143. 135. 134. 123. 135. 131. 162. 178. 163 . 163 . 150. 166. 159. 140. 148. 134. 142 . 163 . 104. 178. 184 . 133 . 140 . 147 . 160 . 143 . 147 . 152 . 139. 151. 174 . 168. 156. 138. 144 . 165. 179. 188. 169. 161. 156. 156. 167. 141. 147. 137. 138. 141. 145. 165. 177. 149. 154 . 136. 170. 150. 163 . 151. 159. 152. 155. 158. 143 . 148 . b b 172 . 193 . 166. 163 . 159. 155 . 171. 135. 151. 142. 137. 142. 110. 170. 173. 143. 156. 138 . 166. 154. 159. 155 . 158 . 156. 109. 185. 122. 189. 156. 147. 167. 183. 174. 157. 164. 166. 179. 142. 150. 147. 150. 133 . 109. 159. b 141. 147 . 133 . 167. 148 . 157. 157. 161. 148. 188. 159. 140. 150. 144 . 143. 167. 182. 188. 153. 167. 159. 171. 146. 156. 136. 154. 149. 131. 187. 163. 137. 159. 132. 165. 142. 163 . 159. 157. 136. 163. b 145. 163 . 133. 147. 176. 180. 193 . 172. 180. 162. 175. 146. 151. 138. 140. 160. 141. 183. 161. 140. 169. 130. b 143. 168 . 153. 162 . 141. 166. b 141. 144 . 148 . 139. 181. 174 . 228. 157. 170. 158. 160. 148. 151. 131. 147. 154. 132. 172. 167. 141. 155. 138 . 180. 136. 150 . 144 . 167. 161. 156. b 142 . 136 . 14 7. 136. 162. 172. 186. 155. 121. 158 . 158. b 163. 138. 162. 158. 137. 162. 172 . 128. 156. 139. 171. 128 . 151. 153 . 166. 148 . 168. 151. 135. 145 . 158. 109. 134. 144. 167. 131. 118. 128. 133 . 118. 120. 113 . b 129. 115. 147. 139. 120. 129. 115. 152. 116. 128 . 118. 149. 110. 139. 123 . 108 . 118 . 122 . DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C28 (PAGE 5) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 234 DAYS RAT # 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 50- 57 57- 64 64- 70a DOSAGE GROUP V 30 MG/KG/DAY 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 144 . 154 . 149. 141. 128. 138. 126. 160. 120. 141. 138. 123. 154. 146. 144 . 141. 121. 125. 144 . 134 . b 134 . 140. 128. 137. 125. 134 . 144 . 131. 14 9. 152 . 149. 164 . 162 . 138. 146. 141. 145. 131. 152 . 169. 139. 163 . 155. 154. 142. 123 . 131. 153. 155. 182 . 144 . 134 . 162. 150. 138. 132 . 149. 148. 154 . 155. 153. 163. 162. 136. 146. 151. 165. 128. 149. b 137. 133. 151. 148. 156. 136. 142. b c b 142. 141. b 166. 131. 133. 147. 149. 140. 150. 161. 165. 157. 132. 150. 156. 130. 133 . 13 9. b 138. 143 . 162. 148. 150. 138. 137. 174 . 143 . b 141. 157. 158. 151. 153. 136. 144 . 164 . 141. 142. 156. 167. 157. 135. 149. 143 . 157. 138. 155. 140. 128. 181. 178. 152. 134 . 133. 134. 145. 146. 156. 144 . 140. 142. 156. b 123. 140. 158. 144 . 157. 167. 172. 156. 132. 163. 153. 156. 130. 160. 142. 144 . 135. 161. 142. 136. 130. 143 . 150. 144 . 163 . 151. 144 . 150. 169. 145. 133 . 161. 163 . b 159. 153. 191. 185. 130. 157. 152. 169. 131. 156. 149. 141. 139. 169. 150. 135. 124 . 139. 153 . 228 . 150. 160 . 144 . 149 . 176. 141. 129. 155. 161. 145. 148. 146. 191. 179. 126 . 149. 141. 147. 132. 161. 140 . 136. 138. 163 . 151. 143 . 125. 135. 14 5. 150 . b 156. 167. 141. 163 . 133 . 127. 151. 166. b 147. 150. 170. 165. 126. 155. 140. 154. 137. 149. 142. 136. 134 . 156. 143 . 138. 135. 131. 138. 136. 153 . 129. 144 . 138. 160. 132 . 121. 150. 162 . 145 . 124. 127. 147. 140. 104. 133. 110. 129. 112. 122. 110. 120. 100. 123 . 132. 118. 104 . 113. 127. 117. 135. 120. 118 . 112. 137. 109. 95. 119. 132 . 122 . DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value. c. Value was not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.G) TABLE C29 (PAGE 1) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 235 PREGNANCY STATUS DAYS 0 - 7 7 - 10 10 - 14 14 - 18 18 - 21 21 - 25 RAT # DOSAGE! GROUP I 0 MG/KG/DAY 13801 P 13802 P 13803 P 13804 13805 P 13806 P 13807 P 13808 P 13809 P 13810 P 13811 NP 13812 P 13813 P 13814 P 13815 P 13816 P 13817 P 13818 P 13819 P 13820 P 13821 P 13822 P 13823 P 13824 P 13825 P 13826 P 13827 P 13828 P 13829 P 13830 P 180. 82. 113. 79. 82 . 221. 187. 103. 93. 135. 118. 119. 110. 73 . 71. MORIBUND SACRIFICED ON DAY 68 OF STUDY 208. 97. 134. 122. 67. 207. 81. 115. 110. 157. 66. 103. 102. 157. 72. 108. 116. 173 . 66. 84. 91. 84 . 218. 97. 131. 120. 79. 180. 74. 108. 67. 55. 160. 85. 119. 113. 79. 207. 92. 125. 117. 76. 183. 79. 102. 90. 74 . 187. 95. 117. 108 . 63 . 164. 72 . 102 . 102 . 71. a 67. 82. 94 . 74 . 173 . 76. 102. 97. 75. 164. 81. 98. 113 . 83 . 133. 64. 92 . 100. 65. 172 . 76 . 115. 91. 65. 182. 85. 114 . 103 . 68. 180. 85. 118. 106. 67. 197. 89. 124. 108 . 61. 176. 78 . 112. 104 . 62. 168. 69. 100. 102. 64 . 218 . 96. 126. 119. 76. 204 . 80. 113. 107. 66. 176. 72 . 96. 94 . 66. 153. 68. 99. 84. 58. 90. P = PREGNANT NP => NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDEDi IN GRAMS (G) . a. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C29 (PAGE 2) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 236 PREGNANCY STATUS DAYS 0 - 7 7 - 10 10 - 14 14 - 18 18 - 2 1 21 - 25 RAT # DOSAGE GROUP II 1 MG/KG/DAY 13831 P 13832 P 13833 P 13834 P 13835 P 13836 13837 P 13838 P 13839 P 13840 NP 13841 P 13842 P 13843 P 13844 P 13845 P 13846 P 13847 P 13848 P 13849 P 13850 P 13851 NP 13852 P 13853 P 13854 P 13855 P 13856 P 13857 P 13858 P 13859 P 13860 P 215. 94 . 120. 102. 74. 201. 81. a 107. 70. 185. 72 . 100. 114 . 81. 177. 70. 95. 99. 68. 221. 85. 115. 113 . 75. MORIBUND SACRIFICED ON DAY 59 OF STUDY 170. 70. 99. 112 . 176. 83. 115. 125. 82 . 184. 79. 107. 111. 71. 154. 68. 88. 77. 61. 162. 73. 105. a 58. 156. 71. 100. 104. 78. 166. 72 . 107. 100. 69. 180. 90. 109. 115. 51. 180. 80. 112. 120. 65. 149. 76. 97. 110 . 68. 159. 59. 78. 99. 69. 177. 78. 96. 118. 86. 202 . 76. 111. 88 . 63. 199. 80. 115. 114. 150. 61. 80. 82 . 50. 180. 80. 102. 114 . 70. 176. 77. 106. 108. 189. 89. 106. 101. 85. 177. 84 . 105. 130. 73 . 182. 79. 104 . 107 . 69. 182 . 74 . 99. 92. 56. 171. 77. 93. 98. 183. 68. 94. 94 . 63. 160. 68. 88. 89 . 55. 79. 58. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C29 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 237 PREGNANCY STATUS DAYS 0 - 7 7 - 10 10 - 14 14 - 18 18 - 21 21 - 25 RAT # DOSAGE GROUP III 3 MG/KG/DAY 13861 P 13862 P 13863 P 13864 P 13865 P 13866 P 13867 P 13868 P 13869 P 13870 P 13871 P 13872 P 13873 P 13874 P 13875 P 13876 P 13 877 P 13878 P 13879 P 13880 P 13881 P 13882 P 13883 P 13884 P 13885 P 13886 P 13887 P 13888 P 13889 P 13890 P 140. 76. a DID NOT DELIVER A LITTER 168. 82. 111. a 89. 105. 224 . 98. 125. 194. 87. 111. 178 . 77 . 103. a 84. 118. 177. 93. 128. 173. 87. 128. 158. 72. 100. 173. 87. 112. 157. 68. 77. 194. 91. 123. 197. 93. 123. 193 . 92. 136. 204 . 99. 125. 158. 70. 101. 170. 83 . 98. 202. 91. 128. 159. 79. 94. 214 . 92. 136. 178. 76. 107. 217. 79. 103. a 89. 120. 155. 66 . 97 . 176. 80. 120. 176. 86. 120. 196. 80. 109. 208. 87. 123. 113 . 110 . 82 . 125. 101. 100. 105. 116. 136. 106. 105. 95. 119. 122 . 121. 116. 103 . 110 . 125. 106. 113. 110. 85. 121. 104 . 90. 117. 114 . 97. 66. 79. 69. 71. 81. 80. 70. 70. 82. 74 . 71. 77. 83. 74 . 94 . 91. 83 . 69. 73 . 63 . 66. 74 . 67. 55. 71. 68. 66 . 74. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Spilled feed precluded the calculation of this value. . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C29 (PAGE 4) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 238 PREGNANCY STATUS DAYS 0 - 7 7 - 1 0 1 0 - 1 4 14 - 18 18 - 21 21 - 25 RAT # DOSAGE GROUP IV 10 MG/KG/DAY 13891 P 13892 P 13893 P 13894 P 13895 P 13896 P 13897 P 13898 P 13899 P 13900 NP 13901 P 13902 P 13903 P 13904 P 13905 P 13906 P 13907 P 13908 P 13909 P 13910 P 13911 P 13912 P 13913 P 13914 P 13915 P 13916 P 13917 P 13918 P 13919 P 13920 P 139. 72 . 93. 168. 72 . 104. 167. 74 . 97. 207. a 130. 202 . 82. 108. 186. 84. 111. 172 . 82. 115. 185. 99. a 153. 69. 87. MATING NOT CONFIRMED 174. 70. 105. 165. 78. 91. 147. 75 . 99. 170. 81. 108. 207. 92. 125. NO CONFIRMED MATING DATE 164. 74 . 94. 193 . 94 . 115. 169. 74 . 90. 208 . 97 . 132. 163 . 81. 88. 173 . 80. 106. 185. 94 . 115. 170. 84. 114 . 174. 79. 99. 175. 78. 112. NO CONFIRMED MATING DATE 172 . 73. 102. 157. 72. 81. 173 . 82 . 103. 89. 110. 95. a 95. 107. 116. 117. 99., 105., 83 ., 107,. 128.. 107 ,. 106 112 . 97.. 121 . 93 . 110 . 97 . 108 . 103 . 113 . 95 . 102 . 101 64 . 71. 59. 96. 57. 67. 75 . 80. 77. 73 . 83 . 76. 71. 67. 46. 63. 77. 48. 76. 64 . 76. 71. 83. 73. 68. 70. P = PREGNANT NP * NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS - DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. , PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C29 (PAGE 5) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 239 PREGNANCY STATIJS DAYS 0 - 7 7 - 10 10 - 14 14 - 18 18 - 21 RAT # DOSAGE GROUP V 30 MG/KG/DAY 13 921 P 13 922 P 13 923 P 13 924 P 13 925 P 13 926 P 13 927 P 13928 P 13929 NP 13 930 P 13 931 P 13 932 P 13 933 P 13 934 P 13 935 P 13 936 P 13 937 P 13 938 P 13 939 P 13 940 P 13 941 P 13 942 P 13 943 P 13 944 P 13 945 P 13 946 P 13 947 P 13 948 P 13 949 P 13 950 P 164 . 73 . 104. 187. 87. 111. 196. 87. 95. 196. 78. 128. 140 . 63 . 84. 176. 82. 116. 176. 86. 103. 181. 74. 108. 135. 58. 84. 181. 82. 113. 176. 74 . 106. 171. 80. 75. 139. 61. 86. NO CONFIRMED MATING DATE 157. 72 . 92. 165. 84. 119. 134. 63 . 87. 149. 70. 94. 159. 76. 89. 169. 71. 95. 171. 85. 108. 167. 75. 106. 185. 79. 112. 183 . 84 . 105. 184 . 88. 107. 164 . 74 . 103. 157. 75 . 92. 155. 72. 96. 177 . 83. 116. a 68. 95. 115. 99. 130. 111. 95. 111. 101. 124 . 61. 108. 115. 104 . 84. 95. 102 . 98. 102 . 102 . 88. 115. 116. 110 . 98. 101. 88. 90 . 51. 113 . 97. 75. 35. 75. 66. 78. 62. 77. 48 . 87. 71. 72. 65. 67. 67. 72. 71. 61. 68. 90. 72 . 77. 80. 56. 66. 53 . 72 . 83 . 49. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C30 (PAGE 1) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 240 DAY 1 - 5 5 - 8 8 - 1 1 1 1 - 1 3 13 - 15a DAM # DOSAGE GROUP I 0 MG/KG/DAY 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 86. 171. 152. 126. 163. 187. 165. 215. 126. 112. 147. 109. 143 . 138. 141. MORIBUND SACRIFICED ON DAY 68 OF STUDY b b 207. 128. 152 . 135. 161. 116. 178 . 177. 144 . 229. 208. 188. 146. 134 . 142. 168. 156. 139. 156. 156. b 148 . 140. 117. 167. 226. 153 . 157. NOT PREGNANT b 189. 198. 132. 98 . 173. 193 . 229. 46. 300. 130. 166 . 214. 164 . 174 . 101. 142. 147. 133. 160 . 148. 109. 165. 118. b 106. 134 . 160. 125. 136 . 122 . 169. 180. 85. 111. 140 . 148. 164. 69. 89. 138 . 151. 214 . 137. 172 . 128 . 171. 220. 134. 166. b SACRIFICED ON DAY 8 OF :LACTATION 122 . 123. 153. 96. 144 . 145. 169. 210. 143 . 170. 101. 139. 193 . 150. 157. 141. 131. 122 . 119. 139. 117. 180. b 177. 172. 84. 149. 184 . 138. 148. 107. 85. 156. 118. 136. 89. 148. 165. 87. 141. r = DAY OF LACTATION , WEIGHTS WERE RECORDED IN GRAMS (G) . a. It is presumed that the pups begin to consume the maternal feed after day 15 of lactation. b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C30 (PAGE 2) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 241 DAY 1 - 5 5-8 8 - 11 11 - 13 13 - 15a DAM # DOSAGE GROUP II 1 MG/KG/DAY 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13 846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 154. 204. 222 . 153. 165. 107. 159. 169. 133 . 170. 138. 154 . 219 . 135. 145. 109. 127. 181. 124. 123. 138. 171. 212 . 140. 162. MORIBUND SACRIFICED ON DAY 59 OF STUDY 115. 136. 164 . 128. 128. 123. 168. b 158. 173 . 137. 167. 183 . 77. 121. NOT PREGNANT 129. 112. 131. 132. 151. 140. 143 . 190 . 139. 137. 121. 128. 152. 123 . 131. 162. 168. 174 . 112 . b 107. 139. 172 . 138. 150. 116. 131. 142. 117. 122. 104 . 119. 152. 107 . 129. 133. 178. 221. 135. 189. 103 . 140. 173 . 120. 121. 152. 117. 193 . 139 . 148 . NOT PREGNANT 100. 127. SACRIFICED ON DAY 11 OF LACTATION 129. 151. 194 . 139. 138. 147. 168. 172 . 103. 118. 158. 159. 205 . 149. 160. 145. 127. 144 . 164. 121. 201. 115. 148. 154 . 155 . 114. 132. 156. 152. 205 . 102. 150. 111. 146. 134. 103. 132 . 154. 98 . 144 . DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. It is presumed that the pups begin to consume the maternal feed after day 15 of lactation. b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C30 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 242 DAY 1 - 5 5 - 8 8 - 11 11 - 13 13 - 15a DAM # DOSAGE GROUP III 3 MG/KG/DAY 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 93 . 121. 141. 86. PREGNANT; DID NOT DELIVER A LITTER 151. 178. 208. 92 . 100 . 126. 144 . 111. 114 . 129. 133. 93 . b 225. 276. 135 . 148. 133 . 148. 126. 131. 188. 216. 161. 138. 121. 171. 140 . 109. 114. 141. 111. 117. 151. 148. 84. 151. 154. 166. 141. 169. 162. 199. 137. 188. 209. 232. 161. 128. 161. 196. 146. 126. 155. 197. 145. 119. 159. 196. 159. 152. 157. 189. 130. 137. 152. 183. 115. 135 . 127 . 204. 141. 122 . 131. 157. 127. 198. 194 . 238. 155. 165. 181. 246. 124. 133. 118. 172. 141. 99. 87. 101. 62 . 126. 153. 196. 128 . 114 . 130. 174 . 128 . 64. 92. 181. 140. 127 . 173. 244 . 167. 154. 166. 214 . 160. 122. 116. 117. 119. 195. 159. 187. 159. 122 . 104 . 157. b 167. 164 . 152. 177. 148. 145. 205 . 119. 167. 162 . 172 . 65. 95. 147. 137. 149. 191. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . . It is presumed that the pups begin to consume the maternal feed after day 15 of lactation, b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C30 (PAGE 4) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 243 DAY 1 - 5 5 - 8 8 - 1 1 11 - 13 13 - 15a DAM # DOSAGE GROUP IV 10 MG/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13 907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 b 138. 164 . 139. 132. 152. 187. 143 . 130. 150. b 146. b 156. 217 . 142. b 203 . 227. 138. 128. 141. 175. 110 . 101. 136. 186. 153 . 133. 157. 171. 136. 130. 134. 133. 91. NOT PREGNANT; MATING NOT CONFIRMED 127. 132. 190. 129. 112. 153 . 186. 129. 140. 156. 173. 105. 123 . b 175. b 133 . 159. 170. 132. 139. 158. 208. 146 . 149. 176. 160. 85. 94 . 115. 136. 92 . 115. 163 . 167. 141. 157. 183 . 185. 90 . 76. 107. 162. 128 . 131. 157. 184 . 131. 148. 173 . 198. 143. 154 . 217. 198. 138. 137. 139. 190. 131. b 191. 220. 14 9. 49. 107. 116. 88. 147. 173 . 194 . 137. 102. 124 . 174. 122. 109 . 126. 158. 57. 124 . 155. 151. 193. 169. 123 . 179. 151. 118. 165. 164 . 158. 161. 158. 168 . 99. 99. 166. 127. 137. 132. 162. 156 . 168. 158. 99. 155. 143. 66. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . . It is presumed that the pups begin to consume the maternal feed after day 15 of lactation, b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C30 (PAGE 5) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 244 DAY 1 - 5 5 - 8 8 - 1 1 11 - 13 13 - 15a DAM # DOSAGE GROUP 'V 30 MG/KG/DAY 13921 13922 13923 13924 13 925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 108. 92. 80. 147. 122. 91. 120. 97. 116. 149. 135. 147. 172. 106 . 174 . 199. 147. 164 . 114. 82. 95. 148. 126. 144. 140. 90. 136. 132. 146. 145. 112. b 123 . 170. 127. 217 . 103 . 152. 122. 171. NOT PREGNANT 121. 68. 124. 143 . 98. 159. 158. 126. 168. 119. 94 . 134. 138. 111. 142. b 94 . 118. 103. 180. 89. 249. b 108. 183 . 135. 151. 203 . 110. 126. 139. 145. 152. 132. 153 . 158. 168. 168. 122. 158. 92. 123 . 126. 115. 133. 103. 167. 221. 138. 162. 121. 133. 166. 135. 130. 140. 153 . 198. 148. 141. 157. 166. 201. 137. 144 . 131. 128 . 166. 118. 127 . 140. 150. 108. 115. 142 . 141. 137. 168. 131. 184 . 166. 147. 128. 136. 141. SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 118. 139. 170. 126. 151. 120. 151. 193. 129. 155. 88. 127. 171. 126. 136. DAY = DAY OF' LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 15 of lactation. b. Spilled feed precluded the calculation of this value. " ------ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C31 (PAGE 1) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 245 RAT # ESTROUS STAGES/ 21 DAYS DAYS IN COHABITATION MATING STATUS MATING DATE PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE GROUP I 0 MG/KG/DAY 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 5 6 5 5a 5 4 5 5 6 5 4b 3b 6 4 5 5 6 5 5 7 6 5 6 7 3 6 6 5 5 6 3M 2M 4M MORIBUND SACRIFICED ON DAY 68 OF STUDY 1M 1M 3M 1M 14 M 2M 1M 4M 4M 3M 4M 8M 3M 3M 2M 2M 4M 4M 4M 4M 4M 1M 4M iM iM 4M C C c C C C C C C C C C C C C C C c c c c c c c c c c c c P P P P P P P P P NP P P P P P P P P P P P P P P P P P P P. PRO PRO D PRO PRO PRO PRO D PRO D D D PRO PRO D PRO PRO PRO PRO PRO c PRO PRO PRO D PRO PRO PRO PRO M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP NOT PREGNANT PRO - PROESTRUS E ESTRUS MET = METESTRUS D = DIESTRUS a. Rat 13804 was moribund sacrificed on day 68 of study (day 19 of estrous evaluation); values excluded from group averages and statistical analyses. b. Six or more consecutive days of diestrus were observed. c. Estrous stage was not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C31 (PAGE 2) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 246 RAT # ESTROUS STAGES/ 21 DAYS GROUP II DAYS IN COHABITATION 1 MG/KG/DAY MATING STATUS MATING DATE PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 5 6 5 5 5 3a 6 3 5 5 5 5 6 5 5 5 5 6 5 6 6 5 5 5 5 5 5 5 5 6 M M M M M ON DAY 59 OF STUDY M M M M M M M M M M M M M M M M M M M M M M M M C C C C C C C C C C C C C C C C C C C C C C C C C C c c c p p p p p p p p NP P P P P P P P P P P NP P P P P P P P P P. PRO PRO PRO PRO PRO PRO D D E MET D PRO D D D PRO PRO PRO PRO E b PRO D D D PRO PRO PRO PRO M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP = NOT PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS a. Rat 13836 was moribund sacrificed on day 59 of study (day 11 of estrous evaluation); values excluded from group averages and statistical analyses. b. Estrous stage was not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C31 (PAGE 3) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 247 RAT # ESTROUS STAGES/ 21 DAYS DAYS IN COHABITATION MATING STATUS MATING DATE GROUP III 3 MG/KG/DAY 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 4 6 5 5 5 4 5 6 6 5 5 6 6 4 5 5 5 5 6 5 5 5a 5 5 2b 4b 6 5 5 6 1 14 2 5 1 2 4 4 4 1 2 4 8 2 1 1 3 1 1 1 1 3 1 4 i i 4 1 1 4 MC M NC MC MC MC MC MC MC MC MC MC MC MC MC MC MC MC MC Mc Mc Mc Mc Mc Mc Mc Mc Mc Mc Mc Mc M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP = NOT PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS a. Eatrous stage was not recorded on day 19 of estrous evaluation. b. Six or more consecutive days of estrus were observed. PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P. D PRO PRO D D D PRO PRO PRO PRO PRO D D PRO D MET D PRO E PRO D D PRO PRO PRO D D D PRO MET PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C31 (PAGE 4): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 248 RAT # ESTROUS STAGES/ 21 DAYS DAYS IN COHABITATION MATING STATUS MATING DATE GROUP IV 10 MG/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 6 6 5 5 5 5 6 5 5 3a 5 5 5 2 4 6 4 5 6 5 5 5 4b 4 6 5 3 6 5 5 4 4 1 2 2 2 4 1 3 14 4 2 3 3 4 14 2 1 4 2 1 2 3 3 4 3 14 4 3 3 M M M M M M M M M DID NOT MATE M M M M M M M M M M M M M M M M M M M M C C C C C C C C C - C c c c c NC C C c c c c c c c c NC C C c M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS a. Six or more consecutive days of estrus were observed. b. Six or more consecutive days of diestrus were observed. NP = NOT PREGNANT PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE P P P P P P P P P _ P P P P P P P P P P P P P P P P P P P P PRO PRO D MET D PRO PRO D PRO E PRO D PRO D PRO PRO D D D PRO D PRO PRO PRO MET D PRO PRO PRO D PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.S) TABLE C31 (PAGE 5) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 249 RAT # GROUP V ESTROUS STAGES/ 21 DAYS DAYS IN COHABITATION 30 MG/KG/DAY MATING STATUS 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 5 5 5 6 7 5 5 5 3a 5 6 5 5 6 5 6 5 4 5 5 5 4 5 5 5 6 5 6 5 6 2 2 1 1 4 2 2 1 3 2 4 3 4 14 2 4 3 2 2 5 1 1 1 2 6 4 1 4 3 3 M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS a. Six or more consecutive days of estrus were observed. b. Estrous stage was not recorded. MATING DATE C C C C C C C C C C C C C NC C C C C C C C C C C C C C C c c NP = NOT PREGNANT PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE p p p p p p p p NP P P P P P P P P P P P P P P P P P P P P P- PRO D PRO D PRO PRO PRO PRO E PRO PRO PRO PRO D PRO D PRO PRO D D PRO PRO PRO PRO D PRO b PRO D PRO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C32 (PAGE 1) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 250 DOSAGE GROUP DOSAGE (MG/KG/DAY) I 0 RAT NUMBER 13801 13802 13803 DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED DL 22 DL 22 DL 22 P P P 114 114 116 OBSERVATIONS a ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13804 DS 68 - 67 MORIBUND SACRIFICED ON DAY 68 OF STUDY. ALL TISSUES APPEARED NORMAL. 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DG 25 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 P P P P P P NP P P P P P P P P P P 114 112 114 112 126 113 95 116 116 115 116 119 114 115 113 113 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-S889.6) TABLE C32 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a I 13822 c CD P 101 SACRIFICED ON DAY 8 OF LACTATION.b ALL TISSUES APPEARED NORMAL. 13823 13824 13825 13826 13827 13828 13829 13830 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 P P P P P P P P 116 115 115 112 116 113 113 114 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. Page 251 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C32 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 252 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a II 1 13831 DL 22 P 115 ALL TISSUES APPEARED NORMAL. 13832 DL 22 P 115 ALL TISSUES APPEARED NORMAL. 13833 DL 22 P 113 ALL TISSUES APPEARED NORMAL. 13834 DL 22 P 114 ALL TISSUES APPEARED NORMAL. 13835 DL 22 P 114 ALL TISSUES APPEARED NORMAL. 1383S DS 59 - 59 MORIBUND SACRIFICED ON DAY 59 OF STUDY. LEFT FORELIMB : ULNA AND RADIUS, BROKEN. ALL OTHER TISSUES APPEARED NORMAL. 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 DL 22 DL 22 DL 22 DG 25 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DG 25 P P P NP p P p p P p P p p p NP 112 113 113 95 113 113 115 112 113 113 113 115 114 112 95 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C32 (PAGE 4) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a II 13852 DL 11 P 102 SACRIFICED ON DAY 11 OF LACTATION.b ALL TISSUES APPEARED NORMAL. 13853 13854 13855 13856 13857 13858 13859 13860 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 P P P P P P P P 112 113 113 113 115 112 115 114 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. ARGUS 418-020 Page 253 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C32 (PAGE 5): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 254 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a III 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 DL 22 DG 25 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 to to P P P P P P P P P P P P P P P P P P P P P P P P 112 108 114 116 112 113 116 114 116 113 112 116 120 114 113 112 114 114 113 113 112 114 113 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL.b ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13885 DL 22 P 114 KIDNEYS: LEFT, PELVIS, MARKED DILATION ALL OTHER TISSUES APPEARED NORMAL. 13886 13887 13888 13889 13890 DL 22 DL 22 DL 22 DL 22 DL 22 P P P P P 112 116 112 112 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. b. Rat 13862 had one implantation site present. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C32 (PAGE 6): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a ARGUS 418-020 Page 255 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DS109 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 P P P P P P P P P NP P P P P P P P P P P P P P P P P P P P P 115 114 113 114 113 114 115 112 114 108 116 113 115 115 115 115 112 113 116 114 113 114 114 114 116 114 114 116 114 115 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT . a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C32 (PAGE 7) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 256 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a V 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DG 25 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 P P P P P P P P NP P P P P P P P P P P P P P P P P P 114 113 112 113 115 112 114 113 97 114 114 114 115 115 114 116 115 112 113 117 112 113 113 113 118 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 13947 DL 1 P 93 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION. ALL TISSUES APPEARED NORMAL. 13948 13949 13950 DL 22 DL 22 DL 22 P P P 115 113 114 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DS DAY OF STUDY DG DAY OF PRESUMED GESTATION DL DAY OF LACTATION P - PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 257 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP I PITUITARY BRAIN ABS. WT. REL. % TBW a ABS. WT. REL. % TBW 0 MG/KG/DAY LIVER ABS. WT. REL. % TBW KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW , 13801 13802 13803 13804c 13805 13806 13807 13808 13809 13810 13811e 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822f 13823 13824 13825 13826 13827 13828 13829 13830 338. 367. 366. -- 348. 340. 367. 286. 355. 370. -- 326. 393. 359. 370 . 320 . 302. 376. 344 . 317. 328. -- 339. 385. 350. 376. 377 . 309. 301. 306. 0.020 0.014b 0.021 0.008 0.013 0.019 0.106d 0.013 0.015 0.031 0.130 0.013 0.022 0.017 0.017 0.018 0.018 0.014 0.018 0.012 0.016 0.023 0.018 0.016 0.018 0.027 0.025 0.022 0.015 0.023 5.92 3.81 5.74 -- 3.74 5.59 28.88d 4.54 4.22 8.38 -- 3.99 5.60 4.74 4.59 5.62 5.96 3.72 5.23 3.78 4.88 -- 5.31 4.16 5.14 7.18 6.63 7.12 4.98 7.52 2.20 2.30 2.18 1.95 2.22 2.13 2.39 2.27 2.08 2.27 2.10 2.21 2.18 2.26 2.26 2.15 2.31 2.53 2.30 2.06 1.86 2.31 2.30 2.31 2.19 2.21 2.40 2.28 2.07 2.18 0.65 0.63 0.60 -- 0.64 0.63 0.65 0.79 0.58 0.61 -- 0.68 0.55 0.63 0.61 0.67 0.76 0.67 0.67 0.65 0.57 -- 0.68 0.60 0.62 0.59 0.64 0.74 0.69 0.71 17.78 21.16 20.36 11.13 16.85 20.35 19.10 13.72 18.47 20.44 13.44 15.92 22.84 19.92 20.15 17.21 17.80 24.99 19.63 16.32 17.26 13.61 17.43 20.80 16.81 21.80 18.52 16.69 15.27 17.04 5.26 5.76 5.56 -- 4.84 5.98 5.20 4.80 5.20 5.52 -- 4.88 5.81 5.55 5.44 5.38 5.89 6.65 5.71 5.15 5.26 -- 5.14 5.40 4.80 5.80 4.91 5.40 5.07 5.57 1.70 1.92 1.44 1.21 1.85 1.61 1.45 1.45 1.27 1.74 1.35 1.48 1.61 1.67 1.77 1.52 1.30 1.75 1.49 1.57 1.53 1.15 1.45 1.60 1.58 1.74 1.49 1.50 1.34 1.51 0.50 0.52 0.39 -- 0.53 0.47 0.40 0.51 0.36 0.47 -- 0.45 0.41 0.46 0.48 0.48 0.43 0.46 0.43 0.50 0.47 -- 0.43 0.42 0.45 0.46 0.40 0.48 0.4'4 0.49 1.86 2.08 1.54 1.14 1.64 1.48 1.58 1.55 1.31 1.67 1.31 1.44 1.70 1.70 1.60 1.46 1.33 1.92 1.52 1.50 1.58 1.13 1.54 1.61 1.47 1.71 1.53 1.43 . 1.32 1.44 0.55 0.57 0.42 _______ 0.47 0.44 0.43 0.54 0.37 0.45 -- 0.44 0.43 0.47 0.43 0.46 0.44 0.51 0.44 0.47 0.48 -- 0.45 0.42 0.42 0.45 0.40 0.46 0.44 0.47 0.040 0.043b 0.045 0.031 0.042 0.051 0.072 0.047 0.037 0.067 0.035 0.034 0.045 0.032 0.045 0.059 0.043 0.059 0.041 0.038 0.043 0.048 0.035 0.040 0.047 0.046 0.056 0.050 0.041 0.026 11.83 11.72 12.30 12.07 15.00 19.62 16.43 10.42 18.11 10.43 11.45 8.91 12.16 18.44 14.24 15.69 11.92 11.99 13.11 10.32 10.39 13.43 12.23 14.85 16.18 13.62 8.50 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. b . Fixed weight. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) c. Rat 13804 was moribund sacrificed on day 68 of study; values excluded from group averages and statistical analyses d. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. e. Rat was not pregnant; values excluded from group averages and statistical analyses. f. Rat 13822 was sacrificed on day 8 of lactation; values excluded from group averages and statistical analyses. X 100 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 2) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 258 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP I ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW 0 MG/KG/DAY THYMUS ABS. WT. REL. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. W T . % TBW UTERUS NON-GRAVID ABS. REL. WT. % TBW 13801 13802 13803 13804c 13805 13806 13807 13808 13809 13810 13811d 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822e 13823 13824 13825 13826 13827 13828 13829 13830 338. 367. 366. -- 348. 340. 367. 286. 355. 370. -- 326. 393. 359. 370. 320 . 302 . 376. 344. 317. 328. -- 339. 385. 350. 376. 377. 309. 301. 306. 0.042b 0.040b 0.038 0.032 0.038 0.058 0.056 0.046 0.042 0.051 0.032 0.037 0.047 0.050 0.041 0.051 0.041 0.057 0.040 0.047 0.042 0.059 0.032 0.038 0.047b 0.043 0.047 0.050 0.054 0.032 12.43 10.90 10.38 10.92 17.06 15.26 16.08 11.83 13.78 11.35 11.96 13.93 11.08 15.94 13.58 15.16 11.63 14.83 12.80 9.44 9.87 13.43 11.44 12.47 16.18 17.94 10.46 0.68 0.78 0.72 0.56 0.66 0.74 0.74 0.72 0.52 0.75 0.73 0.53 0.60 0.73 0.86 0.52 0.55 0.75 0.73 0.66 0.57 0.65 0.73 0.70 0.74 0.62 0.81 0.70 0.54 0.57 0.20 0.21 0.20 -- 0.19 0.22 0.20 0.25 0.15 0.20 -- 0.16 0.15 0.20 0.23 0.16 0.18 0.20 0.21 0.21 0.17 -- 0.22 0.18 0.21 0.16 0.21 0.23 0.18 0.19 0.24 0.70 0.18 0.55 0.26 0.09 0.06 0.20 0.07 0.26 0.46 0.14 0.28 0.21 0.23 0.26 0.13 0.15 0.19 0.17 0.22 0.23 0.19 0.26 0.26 0.18 0.36 0.22 0.17 0.19 0.07 0.19 0.05 _______ 0.07 0.03 0.02 0.07 0.02 0.07 ___ 0.04 0.07 0.06 0.06 0.08 0.04 0.04 0.06 0.05 0.07 -- 0.06 0.07 0.07 0.05 0.10 0.07 0.06 0.06 0.060b 0.047b 0.061 0.054 0.045 0.04 9 0.040 0.054 0.038 0.062 0.033 0.046 0.055 0.041 0.038 0.047 0.043 0.070 0.044 0.040 0.058 0.063 0.071 0.068 0.052 0.056 0.04 9 0.080 0.054 0.042 17.75 12.81 16.67 12 .93 1 4 ,. 4 1 10 .90 18 .88 1 0 ,. 7 0 16 .76 1 4 ,. 1 1 13 ,. 9 9 1 1 ,. 4 2 1 0 ,. 2 7 14 ., 6 9 1 4 .. 2 4 1 8 ,. 6 2 1 2 ,. 7 9 1 2 ,. 6 2 17 .68 2 0 ,. 94 1 7 ,. 6 6 14 . 86 14 ,. 8 9 13 ,. 0 0 2 5 ,. 8 9 1 7 ,. 9 4 1 3 .. 7 2 0.072b 0.061b 0.036 0.061 0.046 0.056 0.046 0.047 0.044 0.052 0.055 0.042 0.056 0.064 0.062 0.047 0.036 0.051 0.042 0.051 0.072 0.076 0.04 9 0.071 0.053 0.073 0.069 0.054 0.048 0.037 21.30 16.62 9.84 13.22 16.47 12.53 16.43 12.39 14.05 12.88 14.25 17.83 16.76 14.69 11.92 13.56 12.21 16.09 21.95 14.45 18.44 15.14 19.41 18.30 17.48 15.95 12.09 0.52 0.54 0.51 0.29 0.68 0.51 0.45 0.57 0.42 0.73 0.54 0.48 0.63 0.51 0.58 0.47 0.52 0.05 0.51 0.54 0.61 0.53 0.53 0.41 0.65 0.30 0.65 0.54 0.48 0.77 0.15 0.15 0.14 -- 0.20 0.15 0.12 0.20 0.12 0.20 -- 0.15 0.16 0.14 0.16 0.15 0.17 0.01 0.15 0.17 0.18 -- 0.16 0.11 0.18 0.08 0.17 0.17 0.16 0.25 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a . Value was multiplied by 1000 ABS. WT . = ORGAN WEIGHT., REL. % TBW = b . Fixed weight. c. Rat 13804 was moribund sacrificed on day 68 of study; values excluded from d. Rat was not pregnant; values excluded from group averages and statistical ; e. Rat 13822 was sacrificed on day 8 of lactation; values excluded from group (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 3) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 259 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP II PITUITARY ABS. REL. WT. % TBW a 1 MG/KG/DAY BRAIN ABS. REL. W T . % TBW LIVER ABS. WT. 1 t KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a 13831 13832 13833 13834 13835 13836b 13837 13838 13839 13840c 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851c 13852d 13853 13854 13855 13856 13857 13858 13859 13860 361. 357. 343. 310. 318. -- 359. 375. 361. -- 347. 351. 317. 368. 352. 336. 314. 331. 336. 341. -- -- 331. 381. 330. 367. 295. 338. 316. 293. 0.026 0.015 0.019 0.013 0.019 0.017 0.024 0.021 0.013 0.018 0.016 0.017 0.015 0.023 0.026 0.013 0.019 0.018 0.027 0.020 0.017 0.017 0.018 0.014 0.018 0.025 0.009 0.011 0.024 0.023 7.20 4.20 5.54 4.19 5.97 -- 6.68 5.60 3.60 -- 4.61 4.84 4.73 6.25 7.39 3.87 6.05 5.44 8.04 5.86 -- -- 5.44 3.67 5.45 6.81 3.05 3.25 7.59 7.85 2.17 2.31 2.23 2.26 2.38 1.91 2.07 2.45 2.30 1.98 2.18 2.20 2.20 2.18 2.40 2.26 2.26 1.75 2.20 2.39 1.91 2.15 2.03 2.32 2.23 2.19 2.04 2.15 2.10 2.22 0.60 0.65 0.65 0.73 0.75 -- 0.58 0.65 0.64 -- 0.63 0.63 0.69 0.59 0.68 0.67 0.72 0.53 0.65 0.70 -- -- 0.61 0.61 0.68 0.60 0.69 0.64 0.66 0.76 21.35 18.12 17.51 16.32 20.02 10.07 20.19 18.97 19.83 11.67 18.14 18.85 14.05 22.15 19.06 16.47 16.51 15.39 18.37 19.60 10.61 13.39 16.88 20.77 15.43 18.95 15.95 17.69 16.36 14.25 5.91 5.08 5.10 5.26 6.30 -- 5.62 5.06 5.49 -- 5.23 5.37 4.43 6.02 5.41 4.90 5.26 4.65 5.47 5.75 -- -- 5.10 5.45 4.68 5.16 5.41 5.23 5.18 4.86 1.63 1.48 1.48 1.32 1.74 1.28 1.49 1.73 1.58 1.28 1.75 1.62 1.41 1.86 1.56 1.64 1.51 1.67 1.57 1.79 1.19 1.32 1.64 1.70 1.39 1.43 1.29 1.60 1.58 1.57 0.45 0.41 0.43 0.42 0.55 -- 0.42 0.46 0.44 -- 0.50 0.46 0.44 0.50 0.44 0.49 0.48 0.50 0.47 0.52 -- -- 0.50 0.45 0.42 0.39 0.44 0.47 0.50 0.54 1.67 1.51 1.57 1.38 1.61 1.24 1.60 1.80 1.57 1.52 1.81 1.73 1.51 1.86 1.67 1.49 1.68 1.58 1.50 1.87 1.16 1.28 1.63 1.80 1.29 1.49 1.531.53 1.59 1.58 0.46 0.42 0.46 0.44 0.51 -- 0.44 0.48 0.43 -- 0.52 0.49 0.48 0.50 0.47 0.44 0.54 0.48 0.45 0.55 -- -- 0.49 0.47 0.39 0.40 0.52 0.45 0.50 0.54 0.048 0.049 0.055 0.040 0.059 0.038 0.04 9 0.050 0.055 0.053 0.077 0.052 0.039 0.061 0.047 0.050 0.033 0.051 0.039 0.058 0.034 0.058 0.053 0.059 0.040 0.059 0.044 0.057 0.050 0.048 13.30 13.72 16.03 12.90 18.55 13.65 13.33 15.24 22.19 14.81 12.30 16.58 13.35 14.88 10.51 15.41 11.61 17.01 16.01 15.48 12.12 16.08 14.92 16.86 15.82 16.38 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) b. Rat 13836 was moribund sacrificed on day 59 of study; values excluded from group averages and statistical analyses. c. Rat was not pregnant; values excluded from group averages and statistical analyses. d. Rat 13852 was sacrificed on day 11 of lactation; values excluded from group averages and statistical analyses. X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 4) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 260 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP II ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW 1 MG/KG/DAY THYMUS ABS. REL. WT. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. WT . % TBW 13831 13832 13833 13834 13835 13836b 13837 13838 13839 13840c 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851c 138S2d 13853 13854 13855 13856 13857 13858 13859 13860 361. 357. 343. 310. 318. -- 359. 375. 361. -- 347. 351. 317. 368. 352. 336. 314. 331. 336. 341. -- -- 331. 381. 330. 367. 295 . 338. 316. 293. 0.040 0.040 0.052 0.038 0.046 0.039 0.042 0.055 0.051 0.049 0.060 0.046 0.030 0.047 0.049 0.042 0.034 0.046 0.035 0.050 0.039 0.043 0.061 0.052 0.048 0.059 0.036 0.043 0.050 0.052 11.08 11.20 15.16 12.26 14.46 11.70 14.67 14.13 17.29 13.10 9.46 12.77 13.92 12.50 10.83 13.90 10.42 14.66 18.43 13.65 14.54 16.08 12.20 12.72 15.82 17.75 0.74 0.79 0.72 0.67 0.64 0.49 0.81 0.66 0.82 0.59 0.65 0.67 0.54 0.79 0.51 0.48 0.71 0.61 0.68 0.64 0.60 0.59 0.70 0.83 0.78 0.79 0.69 0.71 0.75 0.62 0.20 0.22 0.21 0.22 0.20 -- 0.22 0.18 0.23 -- 0.19 0.19 0.17 0.21 0.14 0.14 0.23 0.18 0.20 0.19 -- -- 0.21 0.22 0.24 0.22 0.23 0.21 0.24 0.21 0.14 0.14 0.24 0.15 0.21 0.34 0.29 0.20 0.21 0.35 0.18 0.22 0.19 0.15 0.17 0.14 0.24 0.21 0.10 0.20 0.27 0.24 0.22 0.29 0.16 0.22 0.21 0.22 0.13 0.20 0.04 0.04 0.07 0.05 0.07 -- 0.08 0.05 0.06 -- 0.05 0.06 0.06 0.04 0.05 0.04 0.08 0.06 0.03 0.06 -- -- 0.07 0.08 0.05 0.06 0.07 0.06 0.04 0.07 0.072 0.051 0.050 0.050 0.037 0.049 0.055 0.062 0.046 0.064 0.066 0.077 0.047 0.042 0.094 0.037 0.054 0.049 0.034 0.034 0.033 0.049 0.082 0.075 0.077 0.045 0.032 0.053 0.046 0.053 19.94 14.28 14.58 16.13 11.64 15.32 16.53 12.74 19.02 21.94 14.83 11.41 26.70 11.01 17.20 14.80 10.12 9.97 24.77 19.68 23.33 12.26 10.85 15.68 14.56 18.09 0.065 0.041 0.065 0.074 0.045 0.057 0.065 0.050 0.051 0.064 0.111 0.050 0.057 0.051 0.102 0.036 0.060 0.046 0.043 0.066 0.039 0.066 0.037 0.043 0.066 0.055 0.041 0.062 0.044 0.060 18.00 11.48 18.95 23.87 14.15 18.10 13.33 14.13 31.99 14.24 17.98 13.86 28.98 10.71 19.11 13.90 12.80 19.35 11.18 11.29 20.00 14.99 13.90 18.34 13.92 20.48 0.58 0.62 0.41 0.37 0.50 0.53 1.10 0.60 0.48 0.59 0.55 0.75 0.63 0.51 0.32 0.64 0.72 0.36 0.43 0.84 1.24 0.45 1.23 0.54 0.64 0.52 0.47 0.47 0.43 0.70 0.16 0.17 0.12 0.12 0.16 -- 0.31 0.16 0.13 -- 0.16 0.21 0.20 0.14 0.09 0.19 0.23 0.11 0.13 0.25 -- -- 0.37 0.14 0.19 0.14 0.16 0.14 0.14 0.24 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) b. Rat 13836 was moribund sacrificed on day 59 of study; values excluded from group averages and statistical analyses. c. Rat was not pregnant; values excluded from group averages and statistical analyses. d. Rat 13852 was sacrificed on day 11 of lactation; values excluded from group averages and statistical analyses. X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 5) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 261 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP III PITUITARY ABS. REL. WT. % TBW a 3 MG/KG/DAY BRAIN ABS. REL. W T . % TBW LIVER ABS. WT. REL. % TBW KIDNEY LEFT ABS. REL. W T . % TBW KIDNEY RIGHT ABS. REL. W T . % TBW ADRENAL LEFT ABS . R E L . WT. % TBW a 13861 13862b 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 312. -- 352. 335. 353. 401. 335. 356. 357. 386. 366. 347. 346. 368 . 358. 399. 383. 352. 328 . 363 . 323. 355. 342. 368. 336. 322 . 310. 335. 340. 364. 0.014 0.014 0.014 0.011 0.014 0.018 0.014 0.028 0.016 0.020 0.014 0.022 0.016 0.023 0.018 0.020 0.024 0.017 0.020 0.016 0.022 0.018 0.011 0.019 0.014 0.019 0.015 0.015 0.015 0.016 4.49 -- 3.98 3.28 3.97 4.49 4.18 7.86 4.48 5.18 3.82 6.34 4.62 6.25 5.03 5.01 6.27 4.83 6.10 4.41 6.81 5.07 3.22 5.16 4.17 5.90 4.84 4.48 4.41 4.40 2.11 2.16 2.12 2.03 2.28 1.94 2.19 2.22 2.25 2.36 2.30 2.33 2.15 2.46 2.07 2.48 2.29 2.22 2.37 2.29 2.24 2.35 2.26 2.07 2.23 2.24 2.14 2.25 2.25 2.00 0.68 -- 0.60 0.60 0.64 0.48 0.65 0.62 0.63 0.61 0.63 0.67 0.62 0.67 0.58 0.62 0.60 0.63 0.72 0.63 0.69 0.66 0.66 0.56 0.66 0.70 0.69 0.67 0.66 0.55 17.99 15.04 20.98 16.43 17.78 20.32 15.19 18.68 17.99 21.82 19.76 17.22 17.19 15.63 18.99 17.31 17.66 18.85 17.67 17.99 18.95 18.41 18.20 18.27 13.77 16.87 15.59 19.46 14.98 17.82 5.77 -- 5.96 4.90 5.04 5.07 4.53 5.25 5.04 5.65 5.40 4.96 4.97 4.25 5.30 4.34 4.61 5.36 5.39 4.96 5.87 5.18 5.32 4.96 4.10 5.24 5.03 5.81 4.40 4.90 1.59 1.58 1.48 1.33 1.53 1.86 1.54 1.69 1.63 2.11 1.55 1.44 1.54 1.61 1.48 1.84 1.79 1.78 1.61 1.39 1.57 1.57 1.49 1.40 1.72 1.37 1.31 1.50 1.46 1.67 0.51 -- 0.42 0.40 0.43 0.46 0.46 0.47 0.46 0.55 0.42 0.41 0.44 0.44 0.41 0.46 0.47 0.50 0.49 0.38 0.49 0.44 0.44 0.38 0.51 0.42 0.42 0.45 0.43 0.46 1.58 1.66 1.67 1.35 1.59 1.75 1.56 1.77 1.62 2.03 1.65 1.48 1.64 1.70 1.58 1.88 1.81 1.77 1.69 1.52 1.60 1.47 1.63 1.37 1.60 1.58 1.311.61 1.44 1.75 0.51 ---0.47 0.40 0.45 0.44 0.46 0.50 0.45 0.52 0.45 0.43 0.47 0.46 0.44 0.47 0.47 0.50 0.52 0.42 0.50 0.41 0.48 0.37 0.48 0.49 0.42 0.48 0.42 0.48 0.044 0.033 0.044 0.039 0.049 0.031 0.052 0.073 0.045 0.048 0.065 0.050 0.065 0.050 0.056 0.047 0.044 0.045 0.044 0.032 0.045 0.052 0.040 0.048 0.044 0.051 0.030 0.048 0.059 0.043 14.10 12.50 11.64 13.88 7.73 15.52 20.50 12.60 12.44 17.76 14.41 18.79 13.59 15.64 11.78 11.49 12.78 13.41 8.82 13.93 14.65 11.70 13.04 13.10 15.84 9.68 14.33 17.35 11.81 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. b. Rat 13862 was pregnant, but did not deliver a litter; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 6) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 262 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP III ADRENAL RIGHT ABS. REL. WT. % TBW a 3 MG/KG/DAY SPLEEN ABS. WT. REL. % TBW THYMUS ABS. WT. REL. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. W T . % TBW 13861 13862b 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 312. -- 352. 335. 353. 401. 335. 356. 357. 386. 366. 347. 346. 368. 358. 399. 383 . 352. 328. 363 . 323 . 355. 342. 368. 336. 322 . 310. 335. 340. 364. 0.032 0.032 0.047 0.037 0.045 0.043 0.043 0.050 0.043 0.043 0.048 0.041 0.055 0.045 0.046 0.037 0.050 0.039 0.035 0.035 0.049 0.049 0.038 0.038 0.040 0.037 0.030 0.050 0.051 0.049 10.26 13.35 11.04 12.75 10.72 12.84 14.04 12.04 11.14 13.11 11.82 15.90 12.23 12.85 9.27 13.05 11.08 10.67 9.64 15.17 13.80 11.11 10.33 11.90 11.49 9.68 14.92 15.00 13.46 0.66 0.80 0.72 0.60 0.63 0.85 0.76 0.64 0.49 0.90 0.89 0.69 1.02 0.72 0.56 0.64 0.75 0.70 0.69 0.78 0.65 0.60 0.75 0.66 0.78 0.68 0.75 0.72 0.70 0.68 0.21 -- 0.20 0.18 0.18 0.21 0.23 0.18 0.14 0.23 0.24 0.20 0.29 0.20 0.16 0.16 0.20 0.20 0.21 0.21 0.20 0.17 0.22 0.18 0.23 0.21 0.24 0.21 0.20 0.19 0.10 0.51 0.19 0.12 0.18 0.23 0.20 0.12 0.14 0.35 0.19 0.16 0.18 0.16 0.19 0.22 0.30 0.09 0.30 0.19 0.12 0.12 0.25 0.22 0.43 0.17 0.29 0.40 0.16 0.17 0.03 0.05 0.04 0.05 0.06 0.06 0.03 0.04 0.09 0.05 0.05 0.05 0.04 0.05 0.06 0.08 0.02 0.09 0.05 0.04 0.03 0.07 0.06 0.13 0.05 0.09 0.12 0.05 0.05 0.035 0.040 0.042 0.045 0.047 0.066 0.064 0.046 0.049 0.069 0.037 0.050 0.074 0.056 0.054 0.061 0.046 0.031 0.077 0.045 0.04 9 0.056 0.093 0.059 0.055 0.064 0.035 0.049 0.039 0.068 11.22 11.93 13.43 13.31 16.46 19.10 12.92 13.72 17.88 10.11 14.41 21.39 15.22 15.08 15.29 12.01 8.81 23.48 12.40 15.17 15.77 27.19 16.03 16.37 19.88 11.29 14.63 11.47 18.68 0.024 0.054 0.050 0.047 0.051 0.074 0.053 0.049 0.058 0.079 0.059 0.047 0.068 0.074 0.058 0.069 0.051 0.046 0.087 0.04 9 0.053 0.062 0.060 0.078 0.058 0.053 0.046 0.04 9 0.059 0.052 7.69 -- 14.20 14.03 14.4 5 18.45 15.82 13.76 16.25 20.47 16.12 13.54 19.65 20.11 16.20 17.29 13.32 13.07 26.52 13.50 16.41 17.46 17.54 21.20 17.26 16.46 14.84 14.63 17.35 14.28 0.32 0.83 0.54 0.47 0.51 0.48 0.50 0.46 0.38 0.72 0.40 0.44 0.44 0.39 0.56 0.69 0.62 0.66 0.50 0.78 0.20 0.76 0.52c 0.44 0.59 0.73 0.77 0.67 0.31 0.57 0.10 _______ 0.15 0.14 0.14 0.12 0.15 0.13 0.11 0.19 0.11 0.13 0.13 0.10 0.16 0.17 0.16 0.19 0.15 0.21 0.06 0.21 0.15 0.12 0.18 0.23 0.25 0.20 0.09 0.16 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100 ' b. Rat 13862 was pregnant, but did not deliver a litter; values excluded from group averages and statistical analyses. c. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 7) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 263 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP IV PITUITARY BRAIN ABS. REL. WT. TBW a ABS. WT. REL. % TBW 10 MG/KG/DAY LIVER ABS. WT. ] % KIDNEY LEFT ABS. REL. W T . % TBW KIDNEY RIGHT ABS. REL. W T . % TBW ADRENAL LEFT ABS. REL. WT. % TBW a 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900b 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 300. 366. 332. 386. 334. 376. 361. 395. 320. -- 350. 311. 318. 354 . 351. 355. 337. 366. 356. 353. 327. 355. 317. 294. 323 . 376. 327. 302. 329. 349. 0.013 0.023 0.022 0.017 0.018 0.016 0.006 0.018 0.010 0.016 0.012 0.012 0.009 0.018 0.012 0.007 0.011 0.013 0.016 0.015 0.016 0.022 0.035 0.012 0.013 0.022 0.021 0.025 0.007 4.33 6.28 6.63 4.40 5.39 4.26 1.66 4.56 3.12 -- 4.57 3.86 3.77 2.54 5.13 3.38 2.08 3.00 3.65 4.53 4.59 4.51 6.94 11.90 3.72 3.46 6.73 6.95 7.60 2.00 2.26 2.20 2.19 2.28 2.17 2.16 2.15 2.27 2.19 2.32 2.11 2.02 2.39 2.14 2.18 2.24 2.22 2.16 2.20 2.26 2.24 2.24 2.29 2.10 2.40 2.31 2.22 2.30 2.28 0.75 0.60 0.66 0.59 0.65 0.57 0.60 0.57 0.68 0.66 0.68 0.64 0.68 0.61 0.61 0.66 0.61 0.61 0.62 0.69 0.63 0.71 0.78 0.65 0.64 0.71 0.74 0.70 0.65 15.62 21.99 16.27 16.90 17.85 18.63 17.38 22.41 18.65 14.85 17.66 15.13 15.55 17.49 19.00 18.99 16.18 16.55 18.53 16.78 16.86 15.08 15.28 14.92 18.53 17.29 14.35 17.02 18.54 5.21 6.01 4.90 4.38 5.34 4.95 4.81 5.67 5.83 4.24 5.68 4.76 4.39 4.98 5.35 5.64 4.42 4.65 5.25 5.13 4.75 4.76 5.20 4.62 4.93 5.29 4.75 5.17 5.31 1.36 1.75 1.42 1.83 1.46 1.60 1.73 1.60 1.57 1.51 1.38 1.31 1.61 1.42 1.73 1.38 1.49 1.46 1.56 1.58 1.61 1.35 1.54 1.40 1.61 1.55 1.30 1.32 1.63 0.45 0.48 0.43 0.47 0.44 0.42 0.48 0.40 0.49 0.43 0.44 0.41 0.45 0.40 0.49 0.41 0.41 0.41 0.44 0.48 0.45 0.42 0.52 0.43 0.43 0.47 0.45 0.40 0.47 1.34 1.83 1.47 1.81 1.56 1.64 1.75 1.69 1.62 1.56 1.40 1.38 1.63 1.52 1.50 1.35 1.55 1.50 1.63 1.59 1.66 1.52 1.58 1.51 1.60 1.44 1.39 1.34 1.62 0.45 0.50 0.44 0.47 0.47 0.44 0.48 0.43 0.51 0.44 0.45 0.43 0.46 0.43 0.42 0.40 0.42 0.42 0.46 0.49 0.47 0.48 0.54 0.47 0.42 0.44 0.46 0.41 0.46 0.048 0.047 0.038 0.058 0.041 0.045 0.043 0.060 0.042 0.048 0.036 0.048 0.044 0.053 0.039 0.061 0.045 0.041 0.050 0.042 0.040 0.047 0.060 0.040 0.038 0.046 0.042 0.045 0.040 16.00 12.84 11.44 15.02 12.28 11.97 11.91 15.19 13.12 13.71 11.58 15.09 12.43 15.10 10.98 18.10 12.30 11.52 14.16 12.84 11.27 14.83 20.41 12.38 10.11 14.07 13.91 13.68 11.46 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. a. Value was multiplied by 1000. b. Rat was not pregnant; values were not recorded. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 8) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 264 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP IV ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. * TBW 10 MG/KG/DAY THYMUS ABS. REL. WT. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. W T . % TBW 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900b 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 300. 366. 332. 386. 334. 376. 361. 395. 320. -- 350. 311. 318. 354 . 351. 355. 337. 366. 356. 353 . 327. 355. 317. 294 . 323 . 376. 327. 302. 329. 349. 0.042 0.048 0.048 0.057 0.034 0.040 0.043 0.072 0.034 -- 0.039 0.034 0.030 0.045 0.049 0.038 0.045 0.040 0.038 0.047 0.035 0.043 0.040 0.059 0.045 0.038 0.038 0.038 0.040 0.032 14.00 13.11 14.46 14.77 10.18 10.64 11.91 18.23 10.62 -- 11.14 10.93 9.43 12.71 13.96 10.70 13.35 10.93 10.67 13.31 10.70 12.11 12.62 20.07 13.93 10.11 11.62 12.58 12.16 9.17 0.61 0.80 0.58 0.77 0.77 0.69 0.70 0.92 0.74 0.72 0.55 0.57 0.76 0.62 0.64 0.70 0.76 0.71 0.65 0.70 0.67 0.80 0.69 0.67 0.69 0.68 0.65 0.48 0.66 0.20 0.22 0.17 0.20 0.23 0.18 0.19 0.23 0.23 0.20 0.18 0.18 0.21 0.18 0.18 0.21 0.21 0.20 0.18 0.21 0.19 0.25 0.23 0.21 0.18 0.21 0.22 0.14 0.19 0.11 0.30 0.21 0.33 0.31 0.20 0.18 0.16 0.13 0.17 0.19 0.12 0.31 0.27 0.15 0.06 0.54 0.16 0.16 0.23 0.16 0.19 0.17 0.29 0.14 0.20 0.18 0.09 0.08 0.04 0.08 0.06 0.08 0.09 0.05 0.05 0.04 0.04 0.05 0.06 0.04 0.09 0.08 0.04 0.02 0.15 0.04 0.04 0.07 0.04 0.06 0.06 0.09 0.04 0.06 0.06 0.03 0.02 0.035 0.057 0.033 0.047 0.056 0.048 0.047 0.040 0.047 0.058 0.037 0.032 0.048 0.057 0.044 0.062 0.066 0.033 0.063 0.051 0.040 0.063 0.051 0.054 0.033 0.061 0.046 0.056 0.045 11.67 15.57 9.94 12.18 16.77 12.76 13.02 10.13 14.69 16.57 11.90 10.06 13.56 16.24 12.3 9 18.40 18.03 9.27 17.85 15.60 11.27 19.87 17.35 16.72 8.78 18.65 15.23 17.02 12.89 0.044 0.054 0.050 0.086 0.054 0.048 0.041 0.057 0.046 0.061 0.058 0.058 0.065 0.074 0.048 0.066 0.065 0.057 0.052 0.028 0.053 0.059 0.053 0.071 0.050 0.052 0.049 0.038 0.038 14.67 14.75 15.06 22.28 16.17 12.76 11.36 14.43 14.3 8 17.43 18.65 18.24 18.36 21.08 13.52 19.58 17.76 16.01 14.73 8.56 14.93 18.61 18.03 21.98 13.30 15.90 16.22 11.55 10.89 0.41 0.99 0.55 1.03 0.40 0.51 0.49 0.56 0.44 0.39 0.49 0.51 0.62 0.50 0.57 0.37 1.09 0.55 0.45 0.71 0.81 0.66 0.44 0.69 0.61 0.46 0.57 0.52 0.47 0.14 0.27 0.16 0.27 0.12 0.14 0.14 0.14 0.14 0.11 0.16 0.16 0.18 0.14 0.16 0.11 0.30 0.15 0.13 0.22 0.23 0.21 0.15 0.21 0.16 0.14 0.19 0.16 0.13 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. b. Rat was not pregnant; values were not recorded. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 9) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 265 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP V PITUITARY BRAIN ABS. WT. REL. % TBW a ABS. WT. REL. % TBW 30 MG/KG/DAY LIVER ABS. WT. REL. TBW KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. W T . % TBW ADRENAL LEFT ABS. REL. WT. % TBW a 13921 13922 13923 13924 13925 13926 13927 13928 13929b 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13 947d 13 948 13949 13950 357. 352. 320. 341. 318. 353. 331. 368. -- 350. 368. 357. 326. 340. 318. 349. 306. 343 . 349. 353 . 383. 344 . 349. 341. 342. 353 . -- 323. 365. 361. 0.019 0.010 0.012 0.020 0.009 0.027 0.011 0.028 0.015 0.019 0.022 0.016 0.018 0.012 0.010 0.017 0.005 0.016 0.016 0.030 0.017 0.006 0.011 0.092c 0.021 0.009 0.015 0.017 0.013 0.016 5.32 2.84 3.75 5.86 2.83 7.65 3.32 7.61 -- 5.43 5.98 4.48 5.52 3.53 3.14 4.87 1.63 4.66 4.58 8.50 4.44 1.74 3.15 26.98c 6.14 2.55 -- 5.26 3.56 4.43 2.33 2.16 2.15 2.11 2.12 2.19 2.07 2.30 1.94 2.24 2.09 2.18 1.99 2.16 2.08 2.29 2.03 2.25 2.29 2.24 2.39 2.19 2.30 2.01 2.29 2.04 2.05 2.20 2.09 2.02 0.65 0.61 0.67 0.62 0.67 0.62 0.62 0.62 -- 0.64 0.57 0.61 0.61 0.64 0.65 0.66 0.66 0.66 0.66 0.63 0.62 0.64 0.66 0.59 0.67 0.58 -- 0.68 0.57 0.56 19.21 16.31 20.04 20.95 15.19 20.53 18.60 18.93 12.06 20.69 19.14 20.55 17.15 15.00 17.57 18.04 16.74 19.00 16.45 18.92 19.38 17.21 17.70 16.38 17.42 17.13 11.28 15.10 18.90 18.17 5.38 4.63 6.26 6.14 4.78 5.82 5.62 5.14 -- 5.91 5.20 5.76 5.26 4.41 5.52 5.17 5.47 5.54 4.71 5.36 5.06 5.00 5.07 4.80 5.09 4.85 -- 4.67 5.18 5.03 1.54 1.37 1.41 1.47 1.31 1.63 1.47 1.58 1.20 1.47 1.29 1.53 1.28 1.42 1.39 1.37 1.51 1.58 1.49 1.34 1.55 1.46 1.52 1.43 1.45 1.22 1.18 1.35 1.53 1.39 0.43 0.39 0.44 0.43 0.41 0.46 0.44 0.43 -- 0.42 0.35 0.43 0.39 0.42 0.44 0.39 0.49 0.46 0.43 0.38 0.40 0.42 0.44 0.42 0.42 0.34 -- 0.42 0.42 0.38 1.59 1.37 1.38 1.61 1.34 1.58 1.60 1.60 1.27 1.62 1.33 1.53 1.43 1.50 1.46 1.38 1.40 1.63 1.51 1.46 1.65 1.37 1.45 1.53 1.57 1.33 1.11. 1.36 1.55 1.52 0.44 0.39 0.43 0.47 0.42 0.45 0.48 0.43 -- 0.46 0.36 0.43 0.44 0.44 0.46 0.40 0.46 0.48 0.43 0.41 0.43 0.40 0.42 0.45 0.46 0.38 -- 0.42 0.42 0.42 0.052 0.038 0.042 0.053 0.040 0.071 0.069 0.050 0.039 0.039 0.042 0.051 0.045 0.039 0.053 0.053 0.029 0.056 0.039 0.048 0.045 0.030 0.034 0.056 0.051 0.032 0.048 0.044 0.046 0.037 14.56 10.80 13.12 15.54 12.58 20.11 20.84 13.59 11.14 11.41 14.28 13.80 11.47 16.67 15.19 9.48 16.33 11.17 13.60 11.75 8.72 9.74 16.42 14.91 9.06 13.62 12.60 10.25 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. b. Rat was not pregnant; values excluded from group averages and statistical analyses. c . Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. d. Rat 13947 was sacrificed due to no surviving pups on day 1 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C33 (PAGE 10) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 266 RAT TERMINAL BODY NUMBER WEIGHT DOSAGE GROUP V ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW 30 MG/KG/DAY THYMUS ABS. WT. REL. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. WT . % TBW 13921 13922 13923 13924 13925 13926 13927 13928 13929b 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947c 13948 13949 13950 357. 352. 320. 341. 318. 353. 331. 368. -- 350. 368. 357. 326. 340 . 318. 349. 306. 343 . 349. 353. 383 . 344 . 349. 341. 342. 353. -- 323 . 365. 361. 0.042 11.76 0.041 11.65 0.041 12.81 0.045 13.20 0.033 10.38 0.04 9 13.88 0.052 15.71 0.036 9.78 0.033 -- 0.037 10.57 0.039 10.60 0.046 12.88 0.060 18.40 0.029 8.53 0.056 17.61 0.044 12.61 0.031 10.13 0.049 14.28 0.037 10.60 0.039 11.05 0.059 15.40 0.035 10.17 0.042 12.03 0.052 15.25 0.039 11.40 0.024 6.80 0.040 -- 0.810d 250.77d 0.023 6.30 0.041 11.36 0.71 0.72 0.74 0.52 0.56 0.90 0.79 0.84 0.46 0.80 0.82 0.62 0.66 0.68 0.61 0.74 0.50 0.83 0.75 0.66 0.71 0.70 0.75 0.82 0.69 0.89 0.66 0.80 0.62 0.72 0.20 0.20 0.23 0.15 0.18 0.25 0.24 0.23 -- 0.23 0.22 0.17 0.20 0.20 0.19 0.21 0.16 0.24 0.21 0.19 0.18 0.20 0.21 0.24 0.20 0.25 -- 0.25 0.17 0.20 0.15 0.08 0.10 0.16 0.10 0.19 0.20 0.20 0.24 0.13 0.20 0.15 0.28 0.22 0.06 0.05 0.17 0.19 0.21 0.15 0.21 0.21 0.15 0.21 0.28 0.17 0.26 0.22 0.17 0.18 0.04 0.02 0.03 0.05 0.03 0.05 0.06 0.05 _______ 0.04 0.05 0.04 0.08 0.06 0.02 0.01 0.06 0.06 0.06 0.04 0.05 0.06 0.04 0.06 0.08 0.05 -- 0.07 0.05 0.05 0.069 0.073 0.030 0.106 0.040 0.061 0.062 0.049 0.036 0.034 0.056 0.041 0.052 0.052 0.056 0.055 0.059 0.050 0.055 0.033 0.056 0.027 0.059 0.066 0.047 0.058 0.085 0.035 0.050 0.060 19.33 20.74 9.38 31.08 12.58 17.28 18.73 13.32 -- 9.71 15.22 11.48 15.95 15.29 17.61 15.76 19.28 14.58 15.76 9.35 14.62 7.85 16.90 19.35 13.74 16.43 -- 10.84 13.70 16.62 0.033 0.060 0.020 0.055 0.043 0.070 0.058 0.060 0.028 0.047 0.050 0.049 0.036 0.043 0.046 0.040 0.030 0.039 0.074 0.039 0.086 0.060 0.052 0.054 0.050 0.044 0.058 0.047 0.038 0.046 9.24 17.04 6.25 16.13 13.52 19.83 17.52 16.30 13.43 13.59 13.72 11.04 12.65 14.46 11.46 9.80 11.37 21.20 11.05 22.45 17.44 14.90 15.84 14.62 12.46 14.55 10.41 12.74 0.54 0.52 0.45 0.40 0.40 0.47 0.27 0.60 0.86 0.46 0.58 0.56 0.51 0.51 0.76 0.56 0.49 0.43 0.43 0.60 0.45 0.54 0.51 0.57 0.28 0.45 2.00 0.65 0.39 0.65 0.15 0.15 0.14 0.12 0.12 0.13 0.08 0.16 -- 0.13 0.16 0.16 0.16 0.15 0.24 0.16 0.16 0.12 0.12 0.17 0.12 0.16 0.15 0.17 0.08 0.13 -- 0.20 0.11 0.18 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. ' b. Rat was not pregnant; values excluded from group averages and statistical analyses. c. Rat 13947 was sacrificed due to no surviving pups on day 1 of lactation; values excluded from group averages and statistical analyses. d. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 1) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 267 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP I PITUITARY ABS. WT. REL. % BRW 0 MG/KG/DAY LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW ADRENAL RIGHT ABS. REL. WT. % BRW 13801 13802 13803 13804b 13805 13806 13807 13808 13809 13810 13811d 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822e 13823 13824 13825 13826 13827 13828 13829 13830 2.20 2.30 2.18 1.95 2.22 2.13 2.39 2.27 2.08 2.27 2.10 2.21 2.18 2.26 2.26 2.15 2.31 2.53 2.30 2.06 1.86 2.31 2.30 2.31 2.19 2.21 2.40 2.28 2.07 2.18 0.020 0.014a 0.021 0.008 0.013 0.019 0.106c 0.013 0.015 0.031 0.130 0.013 0.022 0.017 0.017 0.018 0.018 0.014 0.018 0.012 0.016 0.023 0.018 0.016 0.018 0.027 0.025 0.022 0.015 0.023 0.91 0.61 0.96 -- 0.58 0.89 4.44c 0.57 0.72 1.36 -- 0.59 1.01 0.75 0.75 0.84 0.78 0.55 0.78 0.58 0.86 -- 0.78 0.69 0.82 1.22 1.04 0.96 0.72 1.06 17.78 21.16 20.36 11.13 16.85 20.35 19.10 13.72 18.47 20.44 13.44 15.92 22.84 19.92 20.15 17.21 17.80 24.99 19.63 16.32 17.26 13.61 17.43 20.80 16.81 21.80 18.52 16.69 15.27 17.04 808.18 920.00 933.94 759.01 955.40 799.16 604.40 887.98 900.44 720.36 1047.71 881.42 891.59 800.46 770.56 987.75 853.48 792.23 927.96 757.83 900.43 767.58 986.42 771.67 732.02 737.68 781.65 1.70 1.92 1.44 1.21 1.85 1.61 1.45 1.45 1.27 1.74 1.35 1.48 1.61 1.67 1.77 1.52 1.30 1.75 1.49 1.57 1.53 1.15 1.45 1.60 1.58 1.74 1.49 1.50 1.34 1.51 77.27 83.48 66.06 83.33 75.59 60.67 63.88 61.06 76.65 66.97 73.85 73.89 78.32 70.70 56.28 69.17 64.78 76.21 82.26 63.04 69.26 72.15 78.73 62.08 65.79 64.73 69.27 1.86 2.08 1.54 1.14 1.64 1.48 1.58 1.55 1.31 1.67 1.31 1.44 1.70 1.70 1.60 1.46 1.33 1.92 1.52 1.50 1.58 1.13 1.54 1.61 1.47 1.71 1.53 1.43 1.32 1.44 84.54 90.43 70.64 73.87 69.48 66.11 68.28 62.98 73.57 65.16 77.98 75.22 70.80 67.91 57.58 75.89 66.09 72.82 84.95 66.96 69.70 67.12 77.38 63.75 62.72 63.77 66.06 0.040 0.043a 0.045 0.031 0.042 0.051 0.072 0.047 0.037 0.067 0.035 0.034 0.045 0.032 0.045 0.059 0.043 0.059 0.041 0.038 0.043 0.048 0.035 0.040 0.047 0.046 0.056 0.050 0.041 0.026 1.82 1.87 2.06 1.89 2.39 3.01 2.07 1.78 2.95 __ 1.54 2.06 1.42 1.99 2.74 1.86 2.33 1.78 1.84 2.31 ___ 1.52 1.73 2.15 2.08 2.33 2.19 1.98 1.19 0.042a 0.040a 0.038 0.032 0.038 0.058 0.056 0.046 0.042 0.051 0.032 0.037 0.047 0.050 0.041 0.051 0.041 0.057 0.040 0.047 0.042 0.059 0.032 0.038 0.047a 0.043 0.047 0.050 0.054 0.032 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Fixed weight. A B S . WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. ' b. Rat 13804 was moribund sacrificed on day 68 of study; values excluded from group averages and statistical analyses. c. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. d. Rat was not pregnant; values excluded from group averages and statistical analyses. e. Rat 13822 was sacrificed on day 8 of lactation; values excluded from group averages and statistical analyses. 1.91 1.74 1.74 1.71 2.72 2.34 2.03 2.02 2.25 1.67 2.16 2.21 1.81 2.37 1.77 2.25 1.74 2.28 2.26 1.39 1.64 2.15 1.94 1.96 2.19 2.61 1.47 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 2) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 268 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP I SPLEEN THYMUS ABS. WT. REL. BRW ABS. WT. REL. % BRW 0 MG/KG/DAY OVARY LEFT ABS. REL. WT. % BRW OVARY RIGHT ABS. REL. WT. % BRW UTERUS NON-GRAVID ABS. REL. WT. % BRW 13801 13802 13803 13804b 13805 13806 13807 13808 13809 13810 13811c 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822d 13823 13824 13825 13826 13827 13828 13829 13830 2.20 2.30 2.18 1.95 2.22 2.13 2.39 2.27 2.08 2.27 2.10 2.21 2.18 2.26 2.26 2.15 2.31 2.53 2.30 2.06 1.86 2.31 2.30 2.31 2.19 2.21 2.40 2.28 2.07 2.18 0.68 0.78 0.72 0.56 0.66 0.74 0.74 0.72 0.52 0.75 0.73 0.53 0.60 0.73 0.86 0.52 0.55 0.75 0.73 0.66 0.57 0.65 0.73 0.70 0.74 0.62 0.81 0.70 0.54 0.57 30.91 33.91 33.03 29.73 34.74 30.96 31.72 25.00 33.04 23.98 27.52 32.30 38.05 24.19 23.81 29.64 31.74 32.04 30.64 31.74 30.30 33.79 28.05 33.75 30.70 26.09 26.15 0.24 0.70 0.18 0.55 0.26 0.09 0.06 0.20 0.07 0.26 0.46 0.14 0.28 0.21 0.23 0.26 0.13 0.15 0.19 0.17 0.22 0.23 0.19 0.26 0.26 0.18 0.36 0.22 0.17 0.19 10.91 30.43 8.26 -- 11.71 4.22 2.51 8.81 3.36 11.45 -- 6.33 12.84 9.29 10.18 12.09 5.63 5.93 8.26 8.25 11.83 -- 8.26 11.26 11.87 8.14 15.00 9.65 8.21 8.72 0.060a 0.047a 0.061 0.054 0.045 0.049 0.040 0.054 0.038 0.062 0.033 0.046 0.055 0.041 0.038 0.047 0.043 0.070 0.044 0.040 0.058 0.063 0.071 0.068 0.052 0.056 0.049 0.080 0.054 0.042 2.73 2.04 2.80 -- 2.03 2.30 1.67 2.38 1.83 2.73 -- 2.08 2.52 1.81 1.68 2.19 1.86 2.77 1.91 1.94 3.12 -- 3.09 2.94 2.37 2.53 2.04 3.51 2.61 1.93 0.072a 0.061a 0.036 0.061 0.046 0.056 0.046 0.047 0.044 0.052 0.055 0.042 0.056 0.064 0.062 0.047 0.036 0.051 0.042 0.051 0.072 0.076 0.04 9 0.071 0.053 0.073 0.069 0.054 0.048 0.037 3.27 2.65 1.65 _______ 2.07 2.63 1.92 2.07 2.12 2.29 _______ 1.90 2.57 2.83 2.74 2.19 1.56 2.02 1.83 2.48 3.87 -- 2.13 3.07 2.42 3.30 2.88 2.3} 2.32 1.70 0.52 0.54 0.51 0.29 0.68 0.51 0.45 0.57 0.42 0.73 0.54 0.48 0.63 0.51 0.58 0.47 0.52 0.05 0.51 0.54 0.61 0.53 0.53 0.41 0.65 0.30 0.65 0.54 0.48 0.77 23.64 23.48 23.39 30.63 23.94 18.83 25.11 20.19 32.16 21.72 28.90 22.57 25.66 21.86 22.51 1.98 22.17 26.21 32.80 23.04 17.75 29.68 13.57 27.08 23.68 23.19 35.32 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a . Fixed weight. ABS. WT . ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. b. Rat 13804 was moribund sacrificed on day 68 of study; values excluded from group averages and statistical analyses. c. Rat was not pregnant; values excluded from group averages and statistical analyses. d. Rat 13822 was sacrificed on day 8 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 3) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 269 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP II PITUITARY ABS. WT. REL. t BRW 1 MG/KG/DAY LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. W T . % BRW KIDNEY RIGHT ABS. REL. W T . % BRW ADRENAL LEFT ABS. :REL. WT. % BRW ADRENAL RIGHT ABS. REL. W T . * BRW 13831 13832 13833 13834 13835 13836a 13837 13838 13839 13840b 13841 13842 13843 13844 13845 13846 13847 1384B 13849 13850 13851b 13852c 13853 13854 13855 13856 13857 13858 13859 13860 2.17 2.31 2.23 2.26 2.38 1.91 2.07 2.45 2.30 1.98 2.18 2.20 2.20 2.18 2.40 2.26 2.26 1.75 2.20 2.39 1.91 2.15 2.03 2.32 2.23 2.19 2.04 2.15 2.10 2.22 0.026 0.015 0.019 0.013 0.019 0.017 0.024 0.021 0.013 0.018 0.016 0.017 0.015 0.023 0.026 0.013 0.019 0.018 0.027 0.020 0.017 0.017 0.018 0.014 0.018 0.025 0.009 0.011 0.024 0.023 1.20 0.65 0.85 0.58 0.80 -- 1.16 0.86 0.56 -- 0.73 0.77 0.68 1.06 1.08 0.58 0.84 1.03 1.23 0.84 -- -- 0.89 0.60 0.81 1.14 0.44 0.51 1.14 1.04 21.35 18.12 17.51 16.32 20.02 10.07 20.19 18.97 19.83 11.67 18.14 18.85 14.05 22.15 19.06 16.47 16.51 15.39 18.37 19.60 10.61 13.39 16.88 20.77 15.4 3 18.95 15.95 17.69 16.36 14.25 983.87 784.42 785.20 722.12 841.18 975.36 774.28 862.17 832.11 856.82 638.64 1016.06 794.17 728.76 730.53 879.43 835.00 820.08 831.53 895.26 691.93 865.30 781.86 822.79 779.05 641.89 1.63 1.48 1.48 1.32 1.74 1.28 1.49 1.73 1.58 1.28 1.75 1.62 1.41 1.86 1.56 1.64 1.51 1.67 1.57 1.79 1.19 1.32 1.64 1.70 1.39 1.43 1.29 1.60 1.58 1.57 75.12 64.07 66.37 58.41 73.11 71.98 70.61 68.70 80.28 73.64 64.09 85.32 65.00 72.57 66.81 95.43 71.36 74.90 80.79 73.28 62.33 65.30 63.24 74.42 75.24 70.72 1.67 1.51 1.57 1.38 1.61 1.24 1.60 1.80 1.57 1.52 1.81 1.73 1.51 1.86 1.67 1.49 1.68 1.58 1.50 1.87 1.16 1.28 1.63 1.80 1.29 1.49 1.53 1.53 1.59 1.58 76.96 65.37 70.40 61.06 67.65 77.29 73.47 68.26 83.03 78.64 68.64 85.32 69.58 65.93 74.34 90.28 68.18 78.24 80.30 77.59 57.85 68.04 75.00 71.16 75.71 71.17 0.048 0.04 9 0.055 0.040 0.059 0.038 0.049 0.050 0.055 0.053 0.077 0.052 0.039 0.061 0.047 0.050 0.033 0.051 0.039 0.058 0.034 0.058 0.053 0.059 0.040 0.059 0.044 0.057 0.050 0.048 2.21 2.12 2.47 1.77 2.48 2.37 2.04 2.39 3.53 2.36 1.77 2.80 1.96 2.21 1.46 2.91 1.77 2.43 ___ ___ 2.61 2.54 1.79 2.69 2.16 2.65 2.38 2.16 0.040 0.040 0.052 0.038 0.046 0.039 0.042 0.055 0.051 0.049 0.060 0.04 6 0.030 0.047 0.049 0.042 0.034 0.046 0.035 0.050 0.039 0.043 0.061 0.052 0.04 8 0.059 0.036 0.043 0.050 0.052 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13836 was moribund sacrificed on <day 59 of study; values excluded from group averages and statistical analyses. b. Rat was not pregnant? values excluded from group averages and statistical analyses c. Rat 13852 was sacrificed on. day 11 of lactation; values excluded from group averages and statistical analyses. 1.84 1.73 2.33 1.68 1.93 2.03 2.24 2.22 2.75 2.09 1.36 2.16 2.04 1.86 1.50 2.63 1.59 2.09 ____ 3.00 2.24 2.15 2.69 1.76 2.00 2.38 2.34 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 4) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 270 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP II SPLEEN THYMUS ABS. WT. REL. % BRW ABS. WT. REL. t BRW 1 MG/KG/DAY OVARY LEFT ABS. REL. WT. % BRW OVARY RIGHT ABS. REL. WT. !% BRW UTERUS NON-GRAVID ABS. REL. WT. % BRW 13831 13832 13833 13834 13835 13836a 13837 13838 13839 13840b 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851b 13852c 13853 13854 13855 13856 13857 13858 13859 13860 2.17 2.31 2.23 2.26 2.38 1.91 2.07 2.45 2.30 1.98 2.18 2.20 2.20 2.18 2.40 2.26 2.26 1.75 2.20 2.39 1.91 2.15 2.03 2.32 2.23 2.19 2.04 2.15 2.10 2.22 0.74 0.79 0.72 0.67 0.64 0.49 0.81 0.66 0.82 0.59 0.65 0.67 0.54 0.79 0.51 0.48 0.71 0.61 0.68 0.64 0.60 0.59 0.70 0.83 0.78 0.79 0.69 0.71 0.75 0.62 34.10 34.20 32.29 29.65 26.89 39.13 26.94 35.65 29.82 30.45 24.54 36.24 21.25 21.24 31.42 34.86 30.91 26.78 34.48 35.78 34.98 36.07 33.82 33.02 35.71 27.93 0.14 0.14 0.24 0.15 0.21 0.34 0.29 0.20 0.21 0.35 0.18 0.22 0.19 0.15 0.17 0.14 0.24 0.21 0.10 0.20 0.27 0.24 0.22 0.29 0.16 0.22 0.21 0.22 0.13 0.20 6.45 6.06 10.76 6.64 8.82 -- 14.01 8.16 9.13 -- 8.26 10.00 8.64 6.88 7.08 6.19 10.62 12.00 4.54 8.37 -- -- 10.84 12.50 7.17 10.04 10.29 10.23 6.19 9.01 0.072 0.051 0.050 0.050 0.037 0.049 0.055 0.062 0.046 0.064 0.066 0.077 0.047 0.042 0.094 0.037 0.054 0.049 0.034 0.034 0.033 0.049 0.082 0.075 0.077 0.045 0.032 0.053 0.046 0.053 3.32 2.21 2.24 2.21 1.55 -- 2.66 2.53 2.00 -- 3.03 3.50 2.14 1.93 3.92 1.64 2.39 2.80 1.54 1.42 -- -- 4.04 3.23 3.45 2.05 1.57 2.46 2.19 2.39 0.065 0.041 0.065 0.074 0.045 0.057 0.065 0.050 0.051 0.064 0.111 0.050 0.057 0.051 0.102 0.036 0.060 0.046 0.043 0.066 0.039 0.066 0.037 0.043 0.066 0.055 0.041 0.062 0.044 0.060 3.00 1.77 2.91 3.27 1.89 _______ 3.14 2.04 2.22 __ 5.09 2.27 2.59 2.34 4.25 1.59 2.65 2.63 1.95 2.76 _______ -- 1.82 1.85 2.96 2.51 2.01 2.88 2.10 2.70 0.58 0.62 0.41 0.37 0.50 0.53 1.10 0.60 0.48 0.59 0.55 0.75 0.63 0.51 0.32 0.64 0.72 0.36 0.43 0.84 1.24 0.45 1.23 0.54 0.64 0.52 0.47 0.47 0.43 0.70 26.73 26.84 18.38 16.37 21.01 53.14 24.49 20.87 25.23 34.09 28.64 23.39 13.33 28.32 31.86 20.57 19.54 35.15 60.59 23.28 28.70 23.74 23.04 21.86 20.48 31.53 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13836 was moribund sacrificed on day 59 of study; values excluded from group averages and statistical analyses. b. Rat was not pregnant; values excluded from group averages and statistical analyses c. Rat 13852 was sacrificed on day 11 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 5) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 271 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP III PITUITARY ABS. WT. REL. % BRW 3 MG/KG/DAY LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW ADRENAL RIGHT ABS. REL. WT. % BRW 13861 13862a 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 2.11 2.16 2.12 2.03 2.28 1.94 2.19 2.22 2.25 2.36 2.30 2.33 2.15 2.46 2.07 2.48 2.29 2.22 2.37 2.29 2.24 2.35 2.26 2.07 2.23 2.24 2.14 2.25 2.25 2.00 0.014 0.014 0.014 0.011 0.014 0.018 0.014 0.028 0.016 0.020 0.014 0.022 0.016 0.023 0.018 0.020 0.024 0.017 0.020 0.016 0.022 0.018 0.011 0.019 0.014 0.019 0.015 0.015 0.015 0.016 0.66 -- 0.66 0.54 0.61 0.93 0.64 1.26 0.71 0.85 0.61 0.94 0.74 0.93 0.87 0.81 1.05 0.76 0.84 0.70 0.98 0.76 0.49 0.92 0.63 0.85 0.70 0.67 0.67 0.80 17.99 15.04 20.98 16.43 17.78 20.32 15.19 18.68 17.99 21.82 19.76 17.22 17.19 15.63 18.99 17.31 17.66 18.85 17.67 17.99 18.95 18.41 18.20 18.27 13.77 16.87 15.59 19.46 14.98 17.82 852.61 989.62 809.36 779.82 1047.42 693.61 841.44 799.56 924.58 859.13 739.06 799.53 635.36 917.39 697.98 771.18 849.10 745.57 785.59 845.98 783.40 805.31 882.61 617.49 753.12 728.50 864.89 665.78 891.00 1.59 1.58 1.48 1.33 1.53 1.86 1.54 1.69 1.63 2.11 1.55 1.44 1.54 1.61 1.48 1.84 1.79 1.78 1.61 1.39 1.57 1.57 1.49 1.40 1.72 1.37 1.31 1.50 1.46 1.67 75.36 69.8.1 65.52 67.10 95.88 70.32 76.13 72.44 89.41 67.39 61.80 71.63 65.45 71.50 74.19 78.16 80.18 67.93 60.70 70.09 66.81 65.93 67.63 77.13 61.16 61.21 66.67 64.89 83.50 1.58 1.66 1.67 1.35 1.59 1.75 1.56 1.77 1.62 2.03 1.65 1.48 1.64 1.70 1.58 1.88 1.81 1.77 1.69 1.52 1.60 1.47 1.63 1.37 1.60 1.58 1.31 1.61 1.44 1.75 74.88 78.77 66.50 69.74 90.21 71.23 79.73 72.00 86.02 71.74 63.52 76.28 69.10 76.33 75.81 79.04 79.73 71.31 66.38 71.43 62.55 72.12 66.18 71.75 70.54 61.21 71.56 64.00 87.50 0.044 0.033 0.044 0.039 0.049 0.031 0.052 0.073 0.045 0.048 0.065 0.050 0.065 0.050 0.056 0.047 0.044 0.045 0.044 0.032 0.045 0.052 0.040 0.048 0.044 0.051 0.0300.048 0.059 0.04 3 2.08 -- 2.08 1.92 2.15 1.60 2.37 3.29 2.00 2.03 2.83 2.14 3.02 2.03 2.70 1.90 1.92 2.03 1.86 1.40 2.01 2.21 1.77 2.32 1.97 2.28 1.40 2.13 2.62 2.15 0.032 0.032 0.04 7 0.037 0.045 0.043 0.043 0.050 0.043 0.043 0.048 0.041 0.055 0.045 0.046 0.037 0.050 0.039 0.035 0.035 0.049 0.049 0.038 0.038 0.040 0.037 0.030 0.050 0.051 0.04 9 1.52 ___ 2.22 1.82 1.97 2.22 1.96 2.25 1.91 1.82 2.09 1.76 2.56 1.83 2.22 1.49 2.18 1.76 1.48 1.53 2.19 2.08 1.68 1.84 1.79 1.65 1.40 2.22 2.27 2.45 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13862 was pregnant, but did not deliver a litter,- values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 6) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 272 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP III SPLEEN ABS. WT. REL. % BRW 3 MG/KG/DAY THYMUS ABS. WT. REL. % BRW OVARY LEFT ABS. REL. WT. % BRW OVARY RIGHT ABS. WT. 1 UTERUS NON-GRAVID ABS. REL. WT. % BRW 13861 13862a 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 2.11 2.16 2.12 2.03 2.28 1.94 2.19 2.22 2.25 2.36 2.30 2.33 2.15 2.46 2.07 2.48 2.29 2.22 2.37 2.29 2.24 2.35 2.26 2.07 2.23 2.24 2.14 2.25 2.25 2.00 0.66 0.80 0.72 0.60 0.63 0.85 0.76 0.64 0.49 0.90 0.89 0.69 1.02 0.72 0.56 0.64 0.75 0.70 0.69 0.78 0.65 0.60 0.75 0.66 0.78 0.68 0.75 0.72 0.70 0.68 31.28 33.96 29.56 27.63 43.81 34.70 28.83 21.78 38.14 38.70 29.61 47.44 29.27 27.05 25.81 32.75 31.53 29.11 34.06 29.02 25.53 33.18 31.88 34.98 30.36 35.05 32.00 31.11 34.00 0.10 0.51 0.19 0.12 0.18 0.23 0.20 0.12 0.14 0.35 0.19 0.16 0.18 0.16 0.19 0.22 0.30 0.09 0.30 0.19 0.12 0.12 0.25 0.22 0.43 0.17 0.29 0.40 0.16 0.17 4.74 -- 8.96 5.91 7.89 11.86 9.13 5.40 6.22 14.83 8.26 6.87 8.37 6.50 9.18 8.87 13.10 4.05 12.66 8.30 5.36 5.11 11.06 10.63 19.28 7.59 13.55 17.78 7.11 8.50 0.035 0.040 0.042 0.045 0.047 0.066 0.064 0.046 0.04 9 0.069 0.037 0.050 0.074 0.056 0.054 0.061 0.046 0.031 0.077 0.045 0.04 9 0.056 0.093 0.059 0.055 0.064 0.035 0.049 0.039 0.068 1.66 -- 1.98 2.22 2.06 3.40 2.92 2.07 2.18 2.92 1.61 2.14 3.44 2.28 2.61 2.46 2.01 1.40 3.25 1.96 2.19 2.38 4.12 2.85 2.47 2.86 1.64 2.18 1.73 3.40 0.024 0.054 0.050 0.047 0.051 0.074 0.053 0.049 0.058 0.079 0.059 0.047 0.068 0.074 0.058 0.069 0.051 0.046 0.087 0.049 0.053 0.062 0.060 0.078 0.058 0.053 0.046 0.049 0.059 0.052 1.14 -- 2.36 2.32 2.24 3.81 2.42 2.21 2.58 3.35 2.56 2.02 3.16 3.01 2.80 2.78 2.23 2.07 3.67 2.14 2.37 2.64 2.65 3.77 2.60 2.37 2.15 2.18 2.62 2.60 0.32 0.83 0.54 0.47 0.51 0.48 0.50 0.46 0.38 0.72 0.40 0.44 0.44 0.39 0.56 0.69 0.62 0.66 0.50 0.78 0.20 0.76 0.52b 0.44 0.59 0.73 0.77. 0.67 0.31 0.57 15.16 25.47 23.15 22.37 24.74 22.83 20.72 16.89 30.51 17.39 18.88 20.46 15.85 27.05 27.82 27.07 29.73 21.10 34.06 8.93 32.34 23.01 21.26 26.46 32.59 35.98 29.78 13.78 28.50 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100 a. Rat 13862 was pregnant, but did not deliver a litter; values excluded from group averages and statistical analyses b. Damaged during processing (weight not affected). ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 7) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA ' P GENERATION FEMALE RATS ARGUS 418-020 Page 273 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP IV PITUITARY LIVER ABS. WT. REL. % BRW ABS. WT. REL. % BRW 10 MG/KG/DAY KIDNEY LEFT ABS. REL. WT. % BRW KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. t BRW ADRENAL RIGHT ABS. REL. WT. % BRW 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900a 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 2.26 2.20 2.19 2.28 2.17 2.16 2.15 2.27 2.19 -- 2.32 2.11 2.02 2.39 2.14 2.18 2.24 2.22 2.16 2.20 2.26 2.24 2.24 2.29 2.10 2.40 2.31 2.22 2.30 2.28 0.013 0.023 0.022 0.017 0.018 0.016 0.006 0.018 0.010 0.016 0.012 0.012 0.009 0.018 0.012 0.007 0.011 0.013 0.016 0.015 0.016 0.022 0.035 0.012 0.013 0.022 0.021 0.025 0.007 0.58 1.04 1.00 0.74 0.83 0.74 0.28 0.79 0.46 -- 0.69 0.57 0.59 0.38 0.84 0.55 0.31 0.50 0.60 0.73 0.66 0.71 0.98 1.53 0.57 0.54 0.95 0.94 1.09 0.31 15.62 21.99 16.27 16.90 17.85 18.63 17.38 22.41 18.65 -- 14.85 17.66 15.13 15.55 17.49 19.00 18.99 16.18 16.55 18.53 16.78 16.86 15.08 15.28 14.92 18.53 17.29 14.35 17.02 18.54 691.15 999.54 742.92 741.23 822.58 862.50 808.37 987.22 851.60 -- 640.09 836.97 749.01 650.63 817.29 871.56 847.77 728.83 766.20 842.27 742.48 752.68 673.21 667.25 710.48 772.08 748.48 646.40 740.00 813.16 1.36 1.75 1.42 1.83 1.46 1.60 1.73 1.60 1.57 -- 1.51 1.38 1.31 1.61 1.42 1.73 1.38 1.49 1.46 1.56 1.58 1.61 1.35 1.54 1.40 1.61 1.55 1.30 1.32 1.63 60.18 79.54 64.84 80.26 67.28 74.07 80.46 70.48 71.69 65.09 65.40 64.85 67.36 66.36 79.36 61.61 67.12 67.59 70.91 69.91 71.88 60.27 67.25 66.67 67.08 67.10 58.56 57.39 71.49 1.34 1.83 1.47 1.81 1.56 1.64 1.75 1.69 1.62 1.56 1.40 1.38 1.63 1.52 1.50 1.35 1.55 1.50 1.63 1.59 1.66 1.52 1.58 1.51 1.60 1.44 1.39 1.34 1.62 59.29 83.18 67.12 79.38 71.89 75.92 81.40 74.45 73.97 67.24 66.35 68.32 68.20 71.03 68.81 60.27 69.82 69.44 74.09 70.35 74.11 67.86 69.00 71.90 66.67 62.34 62.61 58.26 71.05 0.048 0.047 0.038 0.058 0.041 0.045 0.043 0.060 0.042 2.12 2.14 1.74 2.54 1.89 2.08 2.00 2.64 1.92 0.048 0.036 0.048 0.044 0.053 0.039 0.061 0.045 0.041 0.050 0.042 0.040 0.047 0.060 0.040 0.038 0.046 0.042 0.045 0.040 2.07 1.71 2.38 1.84 2.48 1.79 2.72 2.03 1.90 2.27 1.86 1.78 2.10 2.62 1.90 1.58 1.99 1.89 1.96 1.75 0.042 0.048 0.048 0.057 0.034 0.040 0.043 0.072 0.034 0.039 0.034 0.030 0.045 0.049 0.038 0.045 0.040 0.038 0.047 0.035 0.043 0.040 0.059 0.045 0.038 0.038 0.038 0.040 0.032 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. - ORGAN WEIGHT. a. Rat was not pregnant; values were not recorded. REL. % BRW =. (ORGAN WEIGHT/BRAIN WEIGHT) X 100. 1.86 2.18 2.19 2.50 1.57 1.85 2.00 3.17 1.55 1.68 1.61 1.48 1.88 2.29 1.74 2.01 1.80 1.76 2.14 1.55 1.92 1.78 2.58 2.14 1.58 1.64 1.71 1.74 1.40 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 8) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 274 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP IV SPLEEN THYMUS ABS. WT. REL. % BRW ABS. WT. REL. % BRW 10 MG/KG/DAY OVARY LEFT ABS. REL. WT. % BRW OVARY RIGHT ABS. REL. WT. BRW UTERUS NON-GRAVID ABS. REL. WT. % BRW 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900a 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 2.26 2.20 2.19 2.28 2.17 2.16 2.15 2.27 2.19 -- 2.32 2.11 2.02 2.39 2.14 2.18 2.24 2.22 2.16 2.20 2.26 2.24 2.24 2.29 2.10 2.40 2.31 2.22 2.30 2.28 0.61 0.80 0.58 0.77 0.77 0.69 0.70 0.92 0.74 0.72 0.55 0.57 0.76 0.62 0.64 0.70 0.76 0.71 0.65 0.70 0.67 0.80 0.69 0.67 0.69 0.68 0.65 0.48 0.66 26.99 36.36 26.48 33.77 35.48 31.94 32.56 40.53 33.79 31.03 26.07 28.22 31.80 28.97 29.36 31.25 34.23 32.87 29.54 30.97 29.91 35.71 30.13 31.90 28.75 29.44 29.28 20.87 28.95 0.11 0.30 0.21 0.33 0.31 0.20 0.18 0.16 0.13 0.17 0.19 0.12 0.31 0.27 0.15 0.06 0.54 0.16 0.16 0.23 0.16 0.19 0.17 0.29 0.14 0.20 0.18 0.09 0.08 4.87 13.64 9.59 14.47 14.28 9.26 8.37 7.05 5.94 7.33 9.00 5.94 12.97 12.62 6.88 2.68 24.32 7.41 7.27 10.18 7.14 8.48 7.42 13.81 5.83 8.66 8.11 3.91 3.51 0.035 0.057 0.033 0.047 0.056 0.048 0.047 0.040 0.047 0.058 0.037 0.032 0.048 0.057 0.044 0.062 0.066 0.033 0.063 0.051 0.040 0.063 0.051 0.054 0.033 0.061 0.046 0.056 0.045 1.55 2.59 1.51 2.06 2.58 2.22 2.19 1.76 2.15 2.50 1.75 1.58 2.01 2.66 2.02 2.77 2.97 1.53 2.86 2.26 1.78 2.81 2.23 2.57 1.38 2.64 2.07 2.43 1.97 0.044 0.054 0.050 0.086 0.054 0.048 0.041 0.057 0.046 0.061 0.058 0.058 0.065 0.074 0.048 0.066 0.065 0.057 0.052 0.028 0.053 0.059 0.053 0.071 0.050 0.052 0.04 9 0.038 0.038 1.95 2.45 2.28 3.77 2.49 2.22 1.91 2.51 2.10 2.63 2.75 2.87 2.72 3.46 2.20 2.95 2.93 2.64 2.36 1.24 2.37 2.63 2.31 3.38 2.08 2.25 2.21 1.65 1.67 0.41 0.99 0.55 1.03 0.40 0.51 0.49 0.56 0.44 18.14 45.00 25.11 45.18 18.43 23.61 22.79 24.67 20.09 0.39 0.49 0.51 0.62 0.50 0.57 0.37 1.09 0.55 0.45 0.71 0.81 0.66 0.44 0.69 0.61 0.46 0.57 0.52 0.47 16.81 23.22 25.25 25.94 23.36 26.15 16.52 49.10 25.46 20.45 31.42 36.16 29.46 19.21 32.86 25.42 19.91 25.68 22.61 20.61 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A BS. WT. a. Rat was not pregnant; values were not recorded. ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 9) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 275 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP V PITUITARY LIVER ABS. WT. REL. * BRW ABS. WT. REL. % BRW 30 MG/KG/DAY KIDNEY LEFT ABS. REL. WT. % BRW KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW ADRENAL RIGHT ABS. REL. WT. % BRW 13921 13922 13923 13924 13925 13926 13927 13928 13929a 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947c 13948 13949 13950 2.33 2.16 2.15 2.11 2.12 2.19 2.07 2.30 1.94 2.24 2.09 2.18 1.99 2.16 2.08 2.29 2.03 2.25 2.29 2.24 2.39 2.19 2.30 2.01 2.29 2.04 2.05 2.20 2.09 2.02 0.019 0.010 0.012 0.020 0.009 0.027 0.011 0.028 0.015 0.019 0.022 0.016 0.018 0.012 0.010 0.017 0.005 0.016 0.016 0.030 0.017 0.006 0.011 0.092b 0.021 0.009 0.015 0.017 0.013 0.016 0.82 0.46 0.56 0.95 0.42 1.23 0.53 1.22 -- 0.85 1.05 0.73 0.90 0.56 0.48 0.74 0.25 0.71 0.70 1.34 0.71 0.27 0.48 4.58b 0.92 0.44 -- 0.77 0.62 0.79 19.21 16.31 20.04 20.95 15.19 20.53 18.60 18.93 12.06 20.69 19.14 20.55 17.15 15.00 17.57 18.04 16.74 19.00 16.45 18.92 19.38 17.21 17.70 16.38 17.42 17.13 11.28 15.10 18.90 18.17 824.46 755.09 932.09 992.89 716.51 937.44 898.55 823.04 923.66 915.79 942.66 861.81 694.44 844.71 787.77 824.63 844.44 718.34 844.64 810.88 785.84 769.56 814.92 760.70 839.70 686.36 904.31 899.50 1.54 1.37 1.41 1.47 1.31 1.63 1.47 1.58 1.20 1.47 1.29 1.53 1.28 1.42 1.39 1.37 1.51 1.58 1.49 1.34 1.55 1.46 1.52 1.43 1.45 1.22 1.18 1.35 1.53 1.39 66.09 63.42 65.58 69.67 61.79 74.43 71.01 68.70 65.62 61.72 70.18 64.32 65.74 66.83 59.82 74.38 70.22 65.06 59.82 64.85 66.67 66.09 71.14 63.32 59.80 61.36 73.20 68.81 1.59 1.37 1.38 1.61 1.34 1.58 1.60 1.60 1.27 1.62 1.33 1.53 1.43 1.50 1.46 1.38 1.40 1.63 1.51 1.46 1.65 1.37 1.45 1.53 1.57 1.33 1.11 1.36 1.55 1.52 68.24 63.42 64.19 76.30 63.21 72.15 77.29 69.56 72.32 63.64 70.18 71.86 69.44 70.19 60.26 68.96 72.44 65.94 65.18 69.04 62.56 63.04 76.12 68.56 65.20 61.82 74.16 75.25 0.052 0.038 0.042 0.053 0.040 0.071 0.069 0.050 0.039 0.039 0.042 0.051 0.04 5 0.039 0.053 0.053 0.029 0.056 0.039 0.048 0.045 0.030 0.034 0.056 0.051 0.032 0.048 0.044 0.046 0.037 2.23 1.76 1.95 2.51 1.89 3.24 3.33 2.17 -- 1.74 2.01 2.34 2.26 1.80 2.55 2.31 1.43 2.49 1.70 2.14 1.88 1.37 1.48 2.79 2.23 1.57 -- 2.00 2.20 1.83 0.042 0.041 0.041 0.04 5 0.033 0.04 9 0.052 0.036 0.033 0.037 0.039 0.046 0.060 0.029 0.056 0.044 0.031 0.049 0.037 0.039 0.059 0.035 0.042 0.052 0.039 0.024 0.040 0.810b 0.023 0.041 1.80 1.90 1.91 2.13 1.56 2.24 2.51 1.56 -- 1.65 1.87 2.11 3.02 1.34 2.69 1.92 1.53 2.18 1.62 1.74 2.47 1.60 1.83 2.59 1.70 1.18 -- 36.82b 1.10 2.03 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat was not pregnant; values excluded from group averages and statistical analyses. b. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. c. Rat 13947 was sacrificed due to no surviving pups on day 1 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C34 (PAGE 10) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA P GENERATION FEMALE RATS ARGUS 418-020 Page 276 RAT NUMBER BRAIN WEIGHT DOSAGE GROUP V SPLEEN THYMUS ABS. WT. REL. % BRW ABS. WT* REL. % BRW 30 MG/KG/DAY OVARY LEFT ABS. REL. WT. % BRW OVARY RIGHT ABS. REL. WT. % BRW UTERUS NON-GRAVID ABS. REL. WT. % BRW 13921 13922 13923 13924 13925 13926 13927 13928 13929a 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947b 13948 13949 13950 2.33 2.16 2.15 2.11 2.12 2.19 2.07 2.30 1.94 2.24 2.09 2.18 1.99 2.16 2.08 2.29 2.03 2.25 2.29 2.24 2.39 2.19 2.30 2.01 2.29 2.04 2.05 2.20 2.09 2.02 0.71 0.72 0.74 0.52 0.56 0.90 0.79 0.84 0.46 0.80 0.82 0.62 0.66 0.68 0.61 0.74 0.50 0.83 0.75 0.66 0.71 0.70 0.75 0.82 0.69 0.89 0.66 0.80 0.62 0.72 30.47 33.33 34.42 24.64 26.42 41.10 38.16 36.52 35.71 39.23 28.44 33.16 31.48 29.33 32.31 24.63 36.89 32.75 29.46 29.71 31.96 32.61 40.80 30.13 43.63 36.36 29.66 35.64 0.15 0.08 0.10 0.16 0.10 0.19 0.20 0.20 0.24 0.13 0.20 0.15 0.28 0.22 0.06 0.05 0.17 0.19 0.21 0.15 0.21 0.21 0.15 0.21 0.28 0.17 0.26 0.22 0.17 0.18 6.44 3.70 4.65 7.58 4.72 8.68 9.66 8.70 -- 5.80 9.57 6.88 14.07 10.18 2.88 2.18 8.37 8.44 9.17 6.70 8.79 9.59 6.52 10.45 12.23 8.33 -- 10.00 8.13 8.91 0.069 0.073 0.030 0.106 0.040 0.061 0.062 0.049 0.036 0.034 0.056 0.041 0.052 0.052 0.056 0.055 0.059 0.050 0.055 0.033 0.056 0.027 0.059 0.066 0.047 0.058 0.085 0.035 0.050 0.060 2.96 3.38 1.40 5.02 1.89 2.78 3.00 2.13 -- 1.52 2.68 1.88 2.61 2.41 2.69 2.40 2.91 2.22 2.40 1.47 2.34 1.23 2.56 3.28 2.05 2.84 -- 1.59 2.39 2.97 0.033 0.060 0.020 0.055 0.043 0.070 0.058 0.060 0.028 0.047 0.050 0.049 0.036 0.043 0.046 0.040 0.030 0.039 0.074 0.039 0.086 0.060 0.052 0.054 0.050 0.044 0.058 0.047 0.038 0.046 1.42 2.78 0.93 2.61 2.03 3.20 2.80 2.61 -- 2.10 2.39 2.25 1.81 1.99 2.21 1.75 1.48 1.73 3.23 1.74 3.60 2.74 2.26 2.69 2.18 2.16 -- 2.14 1.82 2.28 0.54 0.52 0.45 0.40 0.40 0.47 0.27 0.60 0.86 0.46 0.58 0.56 0.51 0.51 0.76 0.56 0.49 0.43 0.43 0.60 0.45 0.54 0.51 0.57 0.28 0.45 2.00. 0.65 0.39 0.65 23.18 24.07 20.93 18.96 18.87 21.46 13.04 26.09 20.54 27.75 25.69 25.63 23.61 36.54 24.45 24.14 19.11 18.78 26.78 18.83 24.66 22.17 28.36 12.23 22.06 29.54 18.66 32.18 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat was not pregnant; values excluded from group averages and statistical analyses. b. Rat 13947 was sacrificed due to no surviving pups on day 1 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C35 (PAGE 1) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 277 DOSAGE GROUP I 0 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 1 MF 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822a 13823 13824 13825 13826 13827 13828 13829 13830 22 909 45 22 14 0 14 86 23 16 0 16 6 10 MORIBUND SACRIFICED ON DAY 68 OF STUDY 23 13 0 13 67 22 17 0 17 6 11 22 17 0 17 89 22 12 1 13 66 23 13 0 13 94 23 14 (1) 1 15 58 NOT PREGNANT 23 14 0 14 95 23 12 0 13(1] 57 22 17 0 17 11 6 23 15 0 15 10 5 23 15 0 16(1] 5 10 23 15 0 15 87 23 16 0 16 88 22 13(1) 0 13 48 23 14 0 14 59 22 17 0 17 89 23 12 0 12 39 23 909 45 23 16 0 16 88 23 15 0 15 2 13 23 16 0 16 88 23 16 0 16 10 6 23 14 0 14 59 22 13 0 13 85 22 13 1 14 76 NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 45 86 6 10 45 86 69 45 86 69 45 86 69 67 5 11 89 66 94 48 67 5 11 89 66 94 48 67 5 11 89 66 94 48 67 5 11 89 66 94 48 95 57 11 5 10 5 5 10 86 86 48 59 89 39 45 88 2 13 88 96 59 85 76 95 57 11 5 10 5 5 10 86 86 48 59 89 39 45 88 2 13 88 96 59 85 76 95 57 11 5 10 5 5 10 86 86 48 59 89 -- 45 88 2 13 88 96 59 85 76 95 57 11 5 10 5 5 10 86 86 48 59 89 -- 45 88 2 13 88 96 59 '8 5 76 . M = MALE F FEMALE ( ) NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. [ ] = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY, a. Dam 13822 was sacrificed on day 8 of lactation. TOTAL IMPLAN TATIONS N 11 14 16 13 17 17 16 14 18 15 16 18 16 17 16 17 14 16 17 12 11 16 15 16 16 16 13 15 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C35 (PAGE 2): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 278 DOSAGE GROUP II 1 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 1 MF NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852a 13853 13854 13855 13856 13857 13858 13859 13860 22 17 0 17 13 4 23 14 0 14 10 4 22 15 0 15 69 22 13 0 13 49 22 18 0 18 6 12 MORIBUND SACRIFICED ON DAY 59 OF STUDY 22 11 1 12 56 23 18 0 18 7 11 23 12 0 12 66 NOT PREGNANT 22 11(1) 0 12 [1] 55 22 13 0 13 67 22 10 0 10 55 23 17 0 17 6 11 23 12 0 12 75 23 14 0 14 77 23 8 7 15 44 23 16 0 16 12 4 23 16 0 16 11 5 22 12 1 13 66 NOT PREGNANT 23 12 0 12 84 22 17 0 17 10 7 23 17 0 17 11 6 22 16(1) 0 16 96 22 16 0 16 97 23 14 1 15 4 10 22 17 0 17 98 23 15 0 15 69 22 13 0 13 94 13 4 10 4 68 49 6 10 56 7 10 66 55 67 55 6 11 75 76 44 12 4 11 5 66 84 10 7 11 6 95 97 4 10 98 69 94 13 4 10 4 68 49 6 10 56 7 10 66 55 57 55 6 10 75 76 44 12 4 11 5 66 84 10 7 11 6 95 97 4 10 98 69 94 13 4 10 4 68 49 6 10 56 7 10 66 55 57 55 6 10 75 76 44 12 4 11 5 66 -- 10 7 11 6 95 97 4 10 98 68 94 13 4 10 4 68 49 6 10 56 7 10 66 55 57 55 6 10 75 76 44 12 4 11 5 66 -- 10 7 11 6 95 97 4 10 98 '6 8 94 - M * MALE F FEMALE ( ) - NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. [ ] = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY, a. Dam 13852 was sacrificed on day 11 of lactation. TOTAL IMPLANTATIONS N 17 16 17 15 18 13 20 13 14 14 10 17 13 14 17 17 17 15 15 17 17 17 17 15 17 15 14 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C35 (PAGE 3) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 279 DOSAGE GROUP III 3 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 23 PREGNANT; 23 23 22 23 23 22 23 23 22 23 23 23 23 23 23 23 23 23 22 22 23 23 24 22 23 23 22 23 10 0 10 DID NOT DELIVER A LITTER 16 0 16 6 17 17(1) 0 17 18 0 18 15 1 16 16 0 16 16 0 16 8 08 15 0 15 17 0 17 17 0 17 17 0 17 16 0 16 14 (1) 1 15 13 1 14 909 11 0 11 13 0 13 11 0 11 16 0 16 15(1) 0 15 11 0 11 3 03 12 0 12 11 0 11 14 1 15 16 0 16 15 0 15 1 MF 82 5 11 42 79 8 10 96 88 79 26 5 10 98 89 5 12 88 76 76 27 65 94 65 10 6 77 65 21 75 83 2 12 10 6 1 14 NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 82 82 82 82 5 10 42 79 8 10 96 88 78 26 49 98 88 5 11 88 76 76 27 65 94 65 10 5 77 65 21 75 83 2 12 10 6 1 14 5 10 42 79 89 75 88 78 26 48 98 88 5 11 88 76 76 27 65 94 65 10 5 77 65 21 75 83 2 12 10 6 1 14 5 10 42 79 79 75 88 78 26 48 98 88 5 11 88 76 76 27 65 94 65 10 5 77 65 21 75 83 2 12 10 6 1 14 5 10 42 79 79 75 88 78 26 47 98 88 5 11 88 76 76 27 65 94 65 10 5 77 65 21 75 83 2 12 10 6 1 14 M - MALE F FEMALE ( ) - NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. TOTAL IMPLANTATIONS N 12 17 13 17 18 16 16 16 11 16 17 18 18 17 18 17 11 14 16 12 16 15 11 16 13 13 16 16 16 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C35 (PAGE 4) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 280 DOSAGE GROUP IV 10 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN NNN 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 23 10 1 11 22 15 1 16 22 15 0 15 23 14 0 14 22 15 0 15 23 12 0 12 23 12 0 12 23 17 0 17 22 11 0 11 NOT PREGNANT; MATING NOT CONFIRMED 23 16 0 16 23 15 0 15 23 14 0 14 23 14 0 14 23 16 0 16 a 14 2 16 21 16 0 16 23 4 0 4 23 14 0 14 22 15 0 15 23 12 0 12 22 14 0 14 22 13 0 13 23 18 0 18 23 17 0 17 23 16 0 16 a 707 23 14 0 14 22 14 0 14 23 16 0 16 1 MF 46 78 78 77 ii 4 57 66 7 10 65 79 78 4 10 95 5 11 68 10 6 22 59 69 84 77 76 8 10 98 79 34 59 68 79 NUMBER OF LIVE PUPS AT COMPLETION OF' DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 46 78 78 67 11 4 57 66 79 65 46 78 78 67 11 4 57 66 79 65 46 78 78 67 11 4 57 66 79 65 46 78 78 67 11 4 57 66 79 65 79 78 4 10 95 5 11 58 10 6 22 59 69 84 77 76 89 98 79 34 59 68 78 78 78 4 10 95 5 11 57 10 6 22 59 69 84 77 76 89 98 79 34 59 68 78 78 78 4 10 95 5 11 57 10 6 22 59 69 84 77 76 89 98 79 34 59 68 66 78 78 4 10 95 5 11 57 10 22 59 69 84 77 76 89 98 79 34 59 '6 8 66 M MALE F FEMALE a. Dam did not have a confirmed mating date, which precludes the calculation of the duration of gestation. TOTAL IMPLAN TATIONS N 13 17 15 15 17 12 13 18 16 16 15 17 16 16 16 18 13 16 18 13 15 15 19 17 17 11 15 17 17 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C35 (PAGE 5) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS ARGUS 418-020 Page 281 DOSAGE GROUP V 30 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947b 13948 13949 13950 23 22 22 23 23 22 23 23 NOT PREGNANT 22 22 23 23 a 23 23 23 22 23 23 23 23 23 22 23 23 24 22 22 22 LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 15 9(2) 14 17 13 14 16 16 0 0 0 0 0 1 0 0 15 9 14 17 13 15 16 16 18 15 14 13 15 15 14 15 16 14 15 13 16 7 12 14 11 1(1) 12 13 11 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 3 18 15 14 13 15 15 14 15 16 15 15 14 16 7 12 14 11 1 12 13 14 1 MF 96 52 77 10 7 67 86 79 6 10 99 87 86 58 3 12 78 li 3 69 88 77 69 94 11 5 25 48 95 56 -- 75 94 65 NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 96 477 10 7 67 86 79 5 10 86 4_ 77 10 7 67 86 78 4 10 86 4 77 10 7 67 86 78 4 10 86 4 77 10 7 67 86 78 4 10 98 86 86 58 2 12 78 11 3 69 78 77 69 94 11 5 25 38 95 56 -- 74 94 64 87 64 86 58 2 11 78 11 3 69 78 77 69 94 11 5 25 38 95 56 -- 74 94 64 87 64 86 58 1 11 78 11 3 69 78 77 69 94 11 5 25 37 95 56 -_ 74 94 64 87 64 86 58 1 11 78 11 3 69 78 77 69 94 11 5 25 37 95 56 __ 74 '9 4 64 M = MALE F = FEMALE ( ) - NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. a. Dam did not have a confirmed mating date, which precludes the calculation of the duration of gestation. b. Dam 13947 was sacrificed due to no surviving pups on day 1 of lactation. TOTAL IMPLANTATIONS N 15 13 16 17 13 19 17 18 19 15 14 13 18 15 15 15 17 16 15 14 17 13 13 16 11 15 17 14 15 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-G889.6) TABLE C36 (PAGE 1) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS ARGUS 418-020 Page 282 MATERNAL DOSAGE GROUP I 0 MG/KG/DAY RAT/ LITTER NUMBER 13801 13802 13803 13804 13 805 13 806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 DAY 1 M FT DAY 5 M FT DAY 8 M FT DAY 15 M FT 5.5 5.3 5.4 8.8 8.5 8.6 13.2 6.9 6.2 6.6 12.1 11.2 11.7 17.5 7.4 7.0 7.1 11.3 10.8 11.0 15.8 MORIBUND SACRIFICED ON DAY 68 OF STUDY 13.2 16.8 15.4 13.2 17.2 15.6 29.2 30.8 23.2 28.7 30.1 23.0 28.9 30.5 23.1 7.2 6.8 7.0 5.8 5.7 5.7 6.3 6.0 6.2 6.5 5.8 6.2 6.7 6.2 6.5 6.4 6.0 6.1 NOT PREGNANT 10.6 8.3 9.1 10.2 9.9 9.8 10.0 8.2 8.8 9.9 9.2 9.4 10.3 8.2 9.0 10.0 9.7 9.6 15.4 11.9 12.2 14.5 13.9 14.7 14.0 12.2 12.0 14.3 13.0 14.0 14.6 12.1 12.1 14.4 13.6 14.2 28.8 24.4 23.1 29.7 28.4 31.2 26.4 24.6 23.0 29.3 26.5 29.8 27.5 24.5 23.0 29.5 27.8 30.3 6.5 6.4 6.5 10.5 10.4 10.4 15.3 15.0 15.2 27.2 26.4 26.9 7.4 7.0 7.2 11.6 11.6 11.6 17.2 17.0 17.1 32.2 31.1 31.6 5.8 5.2 5.6 8.0 7.4 7.8 11.1 10.5 10.9 22.8 21.5 22.4 5.8 5.5 5.7 8.2 7.9 8.1 11.2 10.5 10.9 21.0 19.8 20.6 6.5 6.1 6.3 8.9 8.4 8.6 11.5 10.9 11.1 20.0 17.4 18.3 6.8 6.4 6.6 9.3 8.6 9.0 12.6 12.0 12.4 23.9 22.7 23.4 6.2 5.5 5.8 7.4 7.0 7.2 11.0 9.8 10.5 18.4 16.9 17.8 6.3 5.5 5.8 9.7 8.4 8.8 13.6 12.3 12.8 21.0 19.6 20.1 6.7 6.2 6.4 9.0 8.7 8.8 13.5 12.1 12.6 26.9 24.7 25.5 5.7 5.3 5.5 9.5 8.9 9.2 14.0 13.0 13.5 26.3 25.0 25.6 7.2 6.7 6.8 12.1 11.3 11.5 SACRIFICED ON DAY 8 OF LACTATION 7.0 6.9 6.9 12.8 12.8 12.8 18.8 18.7 18.7 33.2 32.9 33.0 6.6 6.1 6.4 9.7 8.9 9.3 13.2 12.8 13.0 25.8 24.7 25.2 6.4 6.3 6.3 8.1 8.2 8.1 12.0 11.9 11.9 24.8 23.7 23.9 6.8 6.2 6.5 9.9 9.0 9.5 12.9 12.2 12.6 20.0 18.2 19.1 6.4 5.6 6.1 9.6 9.1 9.4 13.9 13.3 13.6 26.2 25.1 25.7 6.6 6.3 6.4 8.7 8.4 8.5 12.5 12.0 12.2 25.4 24.5 24.8 6.7 6.3 6.5 10.0 9.5 9.8 11.9 11.1 11.6 23.8 21.4 22.9 5.5 5.3 5.4 8.0 7.8 7.9 11.4 11.6 11.5 22.7 22.7 22.7 DAY 22 M FT 45.6 43.9 42.0 43.6 41.9 40.8 44.4 43.0 41.3 45.7 33.9 25.6 40.9 36.0 45.6 41.4 34.4 24.8 40.2 34.2 42.7 43.4 34.2 25.2 40.5 35.5 43.6 43.3 43.8 34.0 32.8 33.1 38.2 28.6 30.5 26.8 40.5 41.2 43.3 32.6 31.0 29.3 37.0 26.6 28.9 29.0 38.5 42.6 43.5 33.5 32.2 30.6 37.7 27.8 29.4 28.2 39.5 54.0 40.4 35.5 32.0 41.7 41.3 41.2 35.5 53.3 39.1 34.2 28.7 39.9 39.3 37.5 35.1 53.6 39.7 34.3 30.4 41.0 40.0 39.8 35.3 M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C36 (PAGE 2) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS ARGUS 418-020 Page 283 MATERNAL DOSAGE GROUP II 1 MG/KG/DAY RAT/ LITTER NUMBER 13831 13832 13833 13834 13835 13836 13837 13838 13839 13 840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 DAY 1 MFT DAY S M FT DAY 8 MF T 6.3 5.9 6.2 9.4 8.6 9.2 13.1 6.8 6.5 6.7 9.9 9.8 9.9 14.2 5.7 5.6 5.6 9.0 8.7 8.8 12.8 6.3 5.9 6.0 10.0 9.5 9.7 14.0 6.0 5.4 5.6 8.7 8.2 8.4 12.9 MORIBUND SACRIFICED ON DAY 59 OF STUDY 6.2 5.7 5.9 8.5 7.8 8.1 12.6 6.5 5.8 6.1 9.1 8.2 8.6 13.3 6.6 6.4 6.5 9.4 10.1 9.7 15.5 NOT PREGNANT 5.9 5.6 5.8 9.4 9.1 9.2 12.7 6.1 5.9 6.0 8.5 8.1 8.3 12.9 6.7 5.9 6.3 8.0 7.2 7.6 11.2 6.0 5.7 5.8 7.8 7.2 7.4 11.8 6.7 6.6 6.7 9.7 9.8 9.7 13.8 6.1 5.6 5.8 9.2 8.6 9.0 12.6 5.7 5.9 5.8 10.5 10.1 10.3 15.8 6.7 6.2 6.6 9.4 9.0 9.3 13.7 6.2 5.9 6.1 8.2 7.7 8.1 11.4 5.9 5.5 5.7 8.5 8.2 8.3 12.0 NOT PREGNANT 6.3 6.2 6.3 9.3 9.2 9.3 13.3 5.2 4.6 5.0 7.8 7.6 7.7 11.1 6.1 6.0 6.1 9.4 9.0 9.2 13.5 5.7 5.5 5.6 9.6 9.4 9.6 14.3 5.7 5.1 5.4 9.2 8.1 8.7 13.2 6.8 6.3 6.4 10.2 9.8 9.9 14.9 5.5 5.2 5.3 7.8 7.5 7.6 11.1 6.1 5.7 5.9 8.6 8.3 8.4 12.6 5.7 5.7 5.7 8.5 8.4 8.5 11.9 12.3 13.7 12.2 13.7 12.2 11.7 11.6 14.3 12.5 12.1 10.1 10.5 14.1 12.2 15.0 13.3 11.0 11.1 13.6 10.8 12.6 14.4 11.8 14.4 11.2 11.8 12.2 12.9 14.0 12.4 13.8 12.5 12.1 12.3 14.9 12.6 12.4 10.6 11.0 13.9 12.4 15.4 13.6 11.3 11.5 13.4 10.9 13.2 14.4 12.6 14.6 11.2 12.2 12.0 DAY 15 M FT DAY 22 M FT 25.1 25.4 26.2 26.6 25.4 24.2 23.9 25.1 25.6 23.8 24.9 25.0 25.6 25.9 24.4 34.6 41.8 43.0 37.3 35.9 32.6 39.1 40.0 35.9 32.8 34.1 41.0 41.3 36.3 34.0 26.4 25.4 25.8 25.3 23.3 24.2 24.7 22.9 23.8 39.6 36.7 36.1 37.6 34.0 33.1 38.5 35.1 34.6 23.7 27.0 23.7 21.7 27.8 23.4 31.9 26.0 21.2 25.2 22.5 24.6 22.7 19.8 28.8 22.2 31.3 25.4 20.5 24.1 23.1 25.6 23.2 20.5 28.2 22.8 31.6 25.8 21.0 24.6 41.6 40.5 34.5 35.4 43.1 35.3 54.6 42.6 26.2 38.0 39.2 36.6 32.4 29.1 43.3 32.7 52.3 39.7 26.0 34.9 40.4 38.2 33.4 31.4 43.2 34.1 53.4 41.8 26.2 36.4 SACRIFICED ON DAY 11 OF LACTATION 21.9 20.2 21.2 32.7 29.9 31.5 20.0 18.2 19.3 29.5 27.2 28.7 28.4 28.0 28.2 39.2 38.8 39.0 21.0 18.8 20.0 33.5 28.7 31.4 27.4 26.6 26.9 43.0 40.6 41.3 23.0 22.6 22.8 33.2 33.6 33.4 22.7 22.1 22.4 40.4 39.2 39.7 23.4 22.8 23.2 36.7 37.5 37.0 MALE F = FEMALE T - TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C36 (PAGE 3) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS ARGUS 418-020 Page 284 MATERNAL DOSAGE GROUP III 3 MG/KG/DAY RAT/ LITTER NUMBER 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 DAY 1 M FT DAY 5 M FT 6.0 5.5 5.9 9.8 9.0 9.6 PREGNANT; DID NOT DELIVER A LITTER 6.0 5.5 5.7 9.3 9.1 9.2 6.4 6.4 6.4 11.4 11.3 11.4 5.4 5.4 5.4 8.4 8.5 8.4 6.6 6.2 6.3 8.9 8.5 8.7 6.0 5.9 5.9 6.5 6.8 6.7 5.7 5.4 5.6 9.2 8.6 8.9 6.4 6.1 6.3 8.3 8.1 8.2 7.2 6.6 6.8 9.2 9.1 9.2 6.3 6.0 6.1 7.9 7.5 7.6 5.7 5.4 5.6 7.7 7.5 7.6 6.2 5.9 6.0 8.6 8.8 8.7 7.3 6.3 6.6 11.7 10.2 10.6 6.1 6.0 6.0 8.9 8.6 8.7 6.6 6.2 6.4 10.2 9.9 10.1 7.1 6.4 6.7 9.8 8.3 9.1 7.5 7.3 7 .4 9.9 10.6 10.4 7.1 6.7 6.9 11.6 11.4 11.5 6.7 6.4 6.6 11.7 11.6 11.7 6.5 6.0 6.2 11.0 10.0 10.5 5.8 5.2 5.6 9.5 8.9 9.3 6.8 6.6 6.7 10.3 10.3 10.3 6.5 6.1 6.3 9.8 8.9 9.4 7.4 7.4 7.4 13.9 13.7 13.8 6.3 6.2 6.3 9.4 9.3 9.3 6.3 5.9 6.2 11.2 10.2 10.9 6.6 6.1 6.2 9.2 8.7 8.8 5.6 5.3 5.5 8.7 7.8 8.3 6.5 5.9 5.9 9.5 9.1 9.1 DAY 8 M FT 14.2 12.9 14.0 13.8 18.3 11.5 10.8 9.6 13.5 10.8 13.2 12.2 11.2 12.5 17.2 12.5 15.7 13.5 14.8 15.7 15.5 15.4 14.4 14.6 12.0 19.0 13.9 16.0 11.2 12.5 13.6 13.6 18.5 11.6 10.4 9.6 12.7 10.6 13.1 11.8 10.7 13.2 14.7 12.5 15.0 12.0 15.4 16.0 15.3 14.5 13.1 14.8 11.1 18.5 13.4 15.1 10.8 11.8 12.6 13.7 18.4 11.6 10.6 9.6 13.1 10.7 13.1 11.9 11.0 12.8 15.5 12.5 15.4 12.8 15.3 15.8 15.4 15.0 14.0 14.7 11.6 18.9 13.7 15.7 10.9 12.2 12.7 DAY 15 MFT 26.8 26.0 26.7 22.0 38.8 19.0 22.2 20.8 26.0 20.7 27.9 19.7 21.4 23.3 32.1 25.4 30.1 30.0 31.2 31.8 29.6 29.3 27.2 27.2 28.2 33.8 25.8 32.2 25.1 26.3 26.9 22.0 38.2 18.6 21.4 21.2 25.9 18.0 28.0 19.0 20.2 24.5 28.2 24.0 29.0 27.0 32.0 31.2 30.2 29.3 26.2 27.5 26.4 32.0 24.4 30.2 22.3 24.7 24.8 22.0 38.6 18.8 21.8 20.9 25.9 19.3 27.9 19.2 20.8 23.9 29.4 24.7 29.6 28.6 31.9 31.5 29.7 29.3 26.9 27.3 27.4 33.2 25.2 31.7 22.7 25.7 24.9 ' DAY 22 MF T 34.6 33.6 34.4 32.1 59.6 29.9 35.1 29.4 34.4 31.9 39.6 28.0 31.0 35.1 50.7 37.3 48.2 46.2 48.8 48.4 48.3 39.7 41.6 46.3 43.2 53.5 42.9 50.8 36.4 35.6 43.1 31.4 60.6 29.0 31.7 29.1 33.9 27.7 40.1 28.3 28.7 35.4 44.5 37.4 45.9 41.6 48.4 48.7 47.9 38.1 39.2 46.4 39.5 53.5 40.2 47.3 30.7 32.2 38.1 31.6 60.0 29.4 33.2 29.3 34.1 29.6 40.0 28.2 29.9 35.2 46.4 37.3 47.1 44.1 48.5 48.6 48.2 39.0 40.8 46.3 41.5 53.5 41.8 49.9 31.5 .34.3 38.5 M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C36 (PAGE 4) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS ARGUS 418-020 Page 285 MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY RAT/ LITTER NUMBER 13891 13892 13893 13894 13895 1389S 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 DAY 1 M FT DAY 5 M FT 6.9 6.8 6.9 11.1 10.8 10.9 5.8 5.6 5.7 9.0 8.6 8.8 6.7 6.1 6.4 10.4 9.8 10.1 6.7 5.9 6.3 8.6 7.6 8.1 5.5 5.4 5.5 7.9 8.0 7.9 6.8 6.3 6.6 10.5 9.8 10.1 7.0 6.5 6.7 10.1 9.5 9.8 6.4 5.9 6.1 8.9 8.4 8.6 6.4 5.9 6.2 10.0 9.4 9.7 NOT PREGNANT; MATING NOT CONFIRMED 6.3 5.9 6.1 7.8 7.0 7.3 6.7 6.7 6.7 9.9 9.2 9.5 6.7 6.7 6.7 10.9 10.7 10.8 6.8 6.3 6.6 9.8 9.1 9.6 6.1 5.3 5.6 9.7 9.0 9.2 6.3 6.0 6.1 10.0 9.5 9.7 5.7 5.4 5.6 8.6 8.2 8.4 7.2 7.0 7.1 11.2 11.2 11.2 5.6 5.5 5.5 8.7 8.6 8.6 6.1 5.8 5.9 10.0 10.0 10.0 6.5 6.2 6.4 9.7 9.4 9.6 5.9 5.4 5.7 8.7 8.0 8.3 6.1 5.7 5.9 10.4 9.8 10.1 5.9 5.7 5.8 8.8 8.5 8.6 6.2 6.0 6.0 8.9 8.8 8.8 6.2 5.8 6.0 8.8 8.0 8.3 6.6 6.3 6.4 10.0 9.2 9.5 6.4 6.1 6.2 10.3 9.6 9.9 6.1 5.9 6.0 9.6 8.6 9.1 6.3 6.1 6.2 8.8 8.3 8.5 DAY 8 MF T 15.4 13.0 14.9 12.6 12.0 14.8 14.3 12.0 13.5 15.3 12.4 13.9 11.1 12.4 14.2 14.1 10.9 12.7 15.3 12.7 14.4 11.8 12.1 14.5 14.2 11.4 13.1 10.5 13.7 14.6 11.6 14.3 15.1 12.4 16.7 12.8 14.9 12.5 12.6 15.1 12.0 12.0 13.2 13.7 15.7 11.9 10.3 9.3 12.7 14.4 10.0 13.2 14.8 12.1 16.4 12.5 14.9 12.0 11.5 14.3 11.7 11.8 12.1 13.1 14.6 10.6 10.0 9.9 13.2 14.5 11.0 13.6 15.0 12.3 16.5 12.6 14.9 12.4 12.0 14.8 11.8 11.9 12.6 13.3 15.0 11.2 10.1 DAY 15 MFT 30.5 25.4 26.9 25.7 24.9 26.5 29.8 22.3 21.7 29.2 24.5 25.6 23.1 26.0 24.7 28.3 20.7 20.1 29.7 24.9 26.2 24.3 25.2 25.5 29.1 21.4 21.0 22.2 26.6 26.0 19.6 25.3 30.5 18.6 36.3 24.2 22.1 26.6 25.8 29.1 23.5 22.1 27.6 28.1 29.0 24.0 16.9 19.8 23.9 25.6 17.3 23.9 30.3 18.2 36.0 23.5 23.4 25.6 24.4 28.6 22.9 21.3 24.3 27.3 27.1 21.8 15.2 20.9 25.2 25.7 18.8 24.3 30.4 18.5 36.1 23.7 22.9 26.2 25.1 28.9 23.2 21.7 25.7 27.6 27.8 22.7 16.1 DAY 22 MFT 48.6 39.2 43.0 38.5 38.4 42.2 46.8 29.9 34.8 45.8 37.0 41.0 34.9 39.2 38.1 43.0 27.5 32.5 46.9 38.0 41.9 36.6 38.6 39.8 44.9 28.6 33.8 31.7 42.4 40.3 35.1 38.0 48.3 27.9 55.4 39.4 36.8 42.4 39.5 45.4 32.5 36.2 44.4 43.9 44.6 39.0 31.8 28.7 39.2 41.0 31.5 37.4 48.1 27.0 55.0 38.3 37.5 41.1 37.8 43.2 31.9 34.2 39.0 43.5 40.8 35.7 30.0 30.1 40.7 40.8 33.8 37.6 48.2 27.6 55.2 38.7 37.2 42.0 38.7 44.4 32.2 35.3 41.4 43.7 42.2 37.1 30.9 M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE . (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C36 (PAGE 5) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS ARGUS 418-020 Page 286 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY RAT/ LITTER NUMBER DAY 1 M FT DAY 5 M FT DAY 8 M FT DAY 15 M FT DAY 22 MFT 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13 940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 6.3 5.6 6.1 4.3 4.0 4.2 6.0 5.6 5.8 5.8 5.8 5.8 8.7 7.6 8.3 11.8 10.2 11.1 23.8 6.7 -- 6.7 9.0 -- 9.0 22.2 8.4 8.2 8.3 11.1 10.8 10.9 21.0 8.5 8.0 8.3 12.3 11.1 11.8 22.4 6.0 5.5 5.7 7.9 7.4 7.7 10.4 10.5 10.5 20.3 5.5 5.2 5.4 5.7 5.4 5.6 7.3 7.2 7.2 11.0 10.8 10.9 23.3 8.9 8.1 8.4 11.5 11.3 11.4 15.3 6.9 6.4 6.6 9.1 8.5 8.7 13.1 11.6 12.0 26.9 NOT PREGNANT 5.7 5.2 5.4 6.6 6.1 6.4 9.8 9.0 9.4 19.2 5.2 5.0 5.1 6.2 6.0 6.1 7.1 6.8 7.0 17.2 6.1 5.6 5.9 8.7 8.0 8.4 12.5 11.5 12.0 23.0 6.6 6.0 6.2 9.4 9.0 9.1 12.0 11.6 11.7 17.2 5.3 5.3 5.3 6.5 6.9 6.8 7.9 9.7 9.4 15.4 5.6 5.4 5.5 8.9 8.4 8.6 12.4 11.5 12.0 22.0 5.8 5.4 5.7 9.6 9.2 9.6 13.6 13.3 13.6 25.1 7.3 6.8 7.0 11.2 10.6 10.9 15.3 14.4 14.7 26.0 5.6 5.4 5.4 7.1 7.1 7.1 10.1 10.3 10.2 17.0 5.6 5.5 5.5 8.6 8.3 8.4 13.0 12.4 12.7 25.6 5.7 5.4 5.5 9.1 8.4 8.7 12.4 11.3 11.7 23.4 6.2 5.9 6.1 9.7 9.1 9.5 13.6 13.0 13.4 24.7 5.8 5.4 5.6 9.3 8.9 9.2 13.4 13.0 13.2 24.1 7.2 6.7 6.8 12.6 11.4 11.7 18.7 16.4 17.1 36.5 5.8 5.5 5.6 7.0 6.5 6.7 10.2 9.2 9.5 22.2 5.5 5.7 5.6 9.4 9.6 9.5 13.9 14.0 13.9 25.7 6.5 6.1 6.3 10.2 9.4 9.8 15.0 14.0 14.4 30.0 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF :LACTATION 5.9 5.5 5.7 8.8 8.1 8.6 12.8 11.4 12.3 26.4 5.6 5.4 5.5 9.2 8.8 9.1 13.3 12.6 13.1 27.8 6.0 5.5 5.8 9.2 9.0 9.1 13.4 13.3 13.4 28.2 20.4 -- 19.4 20.7 20.4 23.0 14.3 25.0 18.8 16.6 22.2 17.2 20.0 20.7 23.9 24.2 17.1 24.2 21.3 22.8 23.4 35.8 21.5 25.3 27.8 25.1 27.2 27.2 22.3 22.2 20.2 21.7 20.4 23.2 14.8 25.5 19.1 16.9 22.6 17.2 19.6 21.3 24.9 24.9 17.0 24.8 22.2 24.1 23.9 36.0 21.7 25.5 28.8 26.0 27.6 27.8 40.0 39.0 32.6 33.0 33.2 32.8 24.8 41.6 33.3 __ 30.2 29.9 32.8 32.0 23.2 38.3 37.1 39.0 31.4 31.7 33.0 32.5 23.9 39.2 24.8 26.1 33.4 28.5 29.4 33.6 41.2 41.7 27.0 41.4 32.2 39.4 36.3 57.4 37.3 39.3 44.8 23.2 25.7 32.6 27.6 32.5 32.0 37.3 40.4 27.6 39.9 29.1 35.1 35.5 54.1 34.8 39.4 42.4 24.1 25.9 33.0 27.9 32.3 32.8 40.4 40.9 27.3 40.6 30.3 38.1 36.0 55.0 35.5 39.4 43.5 43.2 40.8 42.3 42.2 40.1 41.6 45.2 44.7 45.0 M > MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 1) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 287 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 1 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 5.5 5.5 5.2 5.9 5.1 5.4 5.6 7.0 6.8 7.1 6.7 7.0 7.1 6.7 7.6 6.6 7.6 8.7 5.4 8.3 7.8 MORIBUND SACRIFICED ON DAY 68 OF STUDY 7.1 6.5 6.9 7.4 7.4 7.8 6.7 5.9 5.6 6.0 5.9 6.2 5.1 5.5 6.7 6.8 6.1 6.2 6.1 6.0 6.4 7.1 6.6 6.5 5.9 6.4 6.6 MS 6.4 6.7 6.1 6.6 7.1 6.6 7.0 6.6 6.5 6.1 6.7 6.1 MS 5.9 NOT PREGNANT 6.2 6.2 6.7 6.2 6.7 6.9 6.4 7.5 7.5 8.1 6.0 8.1 7.5 6.7 5.7 5.9 5.9 5.8 6.2 5.4 5.4 5.7 5.9 6.0 5.4 5.6 6.1 5.9 6.5 6.4 6.9 6.2 6.7 6.3 6.3 7.2 7.0 6.9 6.8 6.6 7.1 6.9 5.9 6.1 6.3 5.6 6.4 6.4 6.4 6.0 6.2 6.3 6.6 MD 1 5.6 5.5 6.2 7.2 6.4 7.1 6.5 6.1 5.7 5.9 5.7 5.4 6.0 6.0 5.6 5.4 7.1 7.5 7.1 6.6 7.2 6.9 6.5 7.5 6.9 6.7 7.0 7.0 6.7 6.4 7.0 6.6 6.3 7.0 6.6 6.9 6.3 6.2 6.5 6.3 6.7 6.2 6.0 6.6 7.3 6.2 6.2 6.4 6.7 6.7 7.4 6.9 6.1 6.5 6.4 6.3 6.2 6.5 7.1 6.3 6.5 6.8 6.5 6.6 6.3 6.7 6.7 6.3 6.7 6.5 7.3 6.5 5.7 5.4 5.4 5.3 5.4 5.8 5.3 5.3 7.0 7.2 6.1 5.1 6.0 5.7 6.6 6.1 6.5 7.2 5.8 5.7 6.0 6.0 6.2 5.3 6.3 5.3 6.7 7.0 6.4 5.7 7.2 5.8 6.5 6.7 MS 5.1 5.8 6.4 7.3 6.0 6.5 5.4 6.9 6.5 6.7 6.9 6.2 6.2 5.8 6.4 5.5 5.4 6.2 5.2 6.4 7.2 6.3 5.7 6.3 7.1 6.7 6.0 5.4 5.9 7.4 6.7 5.8 6.2 6.8 6.4 5.6 6.2 7.6 5.3 5.3 6.2 6.3 5.8 5.7 5.7 5.6 6.7 6.2 6.6 6.4 6.5 5.6 5.9 5.2 6.6 6.0 7.3 5.4 6.0 5.8 6.2 5.6 6.2 6.9 6.1 5.5 6.4 7.1 5.5 5.7 6.6 5.5 6.6 5.9 6.1 6.8 6.0 6.6 6.6 5.5 6.7 7.7 6.7 5.5 6.0 5.8 6.2 6.4 6.3 6.4 5.8 5.3 5.8 5.7 5.1 5.9 6.4 4.9 6.5 6.8 7.0 6.2 6.3 6.1 6.3 5.1 5.9 8.0 6.7 6.1 6.6 5.2 5.8 5.7 6.6 UU 4.8 5.6 6.3 6.5 5.1 4.9 6.1 5.8 5.6 6.1 6.0 3.4 5.9 6.5 4.7 6.1 5.6 6.8 5.5 6.1 6.4 5.4 5.9 FD 1 6.7 5.4 5.5 5.9 5.4 6.0 6.2 6.0 6.5 5.5 5.8 6.4 5.0 5.4 5.4 6.1 6.1 6.5 5.8 6.3 6.5 5.5 6.5 5.7 6.6 5.5 5.4 5.5 UU 5.4 5.3 6.5 5.9 6.1 6.0 5.8 4.0 5.0 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 2) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 288 PUP # 1 2 3 4 S 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 1 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 5.9 6.3 6.6 6.5 5.9 6.9 6.3 7.0 6.6 7.0 6.6 7.5 7.1 6.6 6.3 5.8 5.8 6.1 5.2 5.2 5.5 6.4 6.6 6.7 5.6 6.2 6.4 5.2 5.7 6.5 6.0 5.8 6.0 6.1 4.2 MORIBUND SACRIFICED ON DAY 59 OF STUDY 6.2 5.6 6.3 6.3 6.4 5.1 5.6 6.2 6.4 6.5 6.6 7.1 6.3 6.4 6.9 6.3 6.6 6.3 7.0 6.5 6.4 NOT PREGNANT 5.9 5.8 5.5 6.5 5.9 5.8 5.9 5.8 6.7 6.1 5.8 6.2 6.0 6.7 6.5 6.8 6.4 6.6 7.0 5.7 5.2 6.4 5.8 6.0 6.2 6.0 5.8 5.3 6.8 6.9 6.9 6.9 6.3 6.8 6.6 5.9 6.3 6.0 6.4 5.8 6.2 6.3 6.4 6.0 5.3 MS MS MS MS 6.8 6.6 6.9 6.3 6.6 6.7 7.0 6.7 6.1 6.1 5.4 6.5 6.4 5.8 5.9 5.9 5.9 6.0 6.1 5.8 5.0 NOT PREGNANT 6.5 5.5 7.0 6.2 6.5 6.2 6.7 4.9 5.2 5.2 5.3 5.1 4.8 5.4 6.3 6.8 5.9 6.2 5.9 6.4 6.3 5.8 4.8 5.8 5.7 6.2 6.0 5.6 5.8 5.8 6.0 5.7 5.5 5.4 5.2 6.7 6.8 6.6 7.2 5.9 6.7 5.8 5.7 5.0 5.5 5.5 5.6 5.6 5.1 6.0 6.3 5.8 6.3 6.0 6.3 5.5 5.4 6.2 5.5 5.7 5.7 6.0 5.8 6.4 6.8 5.6 5.5 5.8 5.8 5.7 5.8 5.6 5.7 6.1 5.7 6.5 6.1 5.2 6.4 6.8 5.4 6.1 5.5 6.1 5.9 6.3 6.0 5.2 5.8 5.8 6.1 6.2 6.1 6.8 5.5 6.2 6.1 6.6 5.7 5.7 5.8 5.5 6.7 5.8 5.7 6.3 5.6 5.5 6.0 5.1 6.4 5.9 5.4 6.5 6.2 5.3 5.4 6.7 6.7 5.8 5.6 5.7 6.2 5.6 6.5 4.9 5.5 6.5 5.7 6.5 5.9 6.1 6.6 6.3 6.0 6.6 5.1 5.9 5.1 4.7 6.4 5.3 5.7 5.7 6.3 6.8 4.9 6.0 5.6 5.3 5.9 6.8 FD 5.7 5.5 6.1 5.8 5.9 7.3 6.3 5.5 6.2 4.7 5.4 5.4 5.0 5.7 5.2 6.0 5.4 6.1 6.2 5.6 5.8 6.0 FS 5.0 6.1 UU 6.0 5.8 7.1 3.5 6.0 7.1 6.1 5.7 5.8 4.9 5.4 5.6 5.5 6.5 5.1 5.8 5.7 6.1 6.5 5.8 5.4 4.4 6.3 5.8 6.1 5.9 FS 6.1 5.9 FS 3.7 6.6 5.5 5.0 6.5 5.1 5.7 5.9 5.6 6.5 5.4 5.2 5.9 6.3 6.1 FS 6.4 6.0 4.5 6.3 5.4 4.4 6.7 5.0 5.5 6.4 6.1 5.6 5.4 5.6 6.5 5.7 5.5 5.5 FS 6.4 5.9 5.6 6.1 5.0 4.9 5.9 5.6 6.1 FD 1 5.4 5.5 FS 5.0 5.6 5.9 5.4 5.6 5.9 5.7 4.9 6.1 5.0 5.4 5.6 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 3) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 289 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 1 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 6.3 5.7 5.8 6.2 6.2 6.0 6.0 6.2 5.1 5.9 PREGNANT; DID NOT DELIVER A LITTER 5.7 6.5 6.0 5.7 6.3 5.8 6.1 5.9 3.5 5.3 5.5 5.6 5.8 5.7 5.7 5.5 7.1 6.8 5.9 5.8 6.4 6.4 FS 5.3 5.6 4.3 5.6 5.7 5.1 5.9 MD 1 4.9 5.4 5.7 5.8 5.4 5.6 5.5 5.1 4.8 6.2 6.1 6.5 6.3 6.7 6.8 7.4 6.5 6.1 6.2 6.1 6.2 6.2 6.4 6.1 6.1 6.2 5.9 6.5 5.7 6.1 6.2 5.8 5.1 6.3 5.6 6.5 MS 5.6 6.0 5.8 5.8 5.7 6.3 5.5 5.6 6.1 5.7 5.5 5.5 5.8 5.7 5.5 5.7 5.3 5.1 5.0 5.7 5.6 5.5 6.4 6.2 7.0 6.2 6.2 6.1 7.1 6.4 6.7 6.1 5.7 6.0 6.1 6.0 6.1 6.1 7.0 7.5 7.2 6.6 6.2 6.1 6.5 7.0 6.4 5.9 6.3 6.6 6.2 5.7 6.0 6.2 6.3 6.0 6.3 6.0 6.0 4.7 6.3 5.1 5.7 5.8 5.6 6.3 5.6 6.0 5.7 5.7 6.4 5.6 6.0 5.0 4.7 5.0 5.2 5.7 6.0 5.9 7.1 6.0 4.7 6.6 6.5 6.5 6.1 5.5 6.0 6.3 5.5 5.7 5.6 6.2 6.2 7.4 7.8 7.4 6.9 7.2 6.6 6.4 6.4 6.5 6.4 6.9 5.8 7.0 6.7 6.7 6.2 4.5 6.5 6.6 6.3 5.0 6.1 5.7 6.1 6.5 6.3 5.9 5.7 5.6 5.5 6.2 6.3 6.4 6.5 6.6 6.1 6.8 6.9 6.6 6.5 6.2 6.7 6.1 5.6 6.1 6.5 FS FD 1 7.3 7.1 7.2 7.3 6.5 7.0 7.1 6.0 6.1 6.5 6.7 6.7 6.2 FS 7.7 7.3 7.5 7.3 7.7 6.6 7.3 7.4 7.4 7.0 7.4 6.7 6.7 7.5 7.5 6.8 6.1 6.2 7.2 7.0 6.6 7.4 7.4 6. 6.6 7.2 6.7 6.9 5.5 6.3 6.8 6.0 6.3 5.3 6.9 7.1 6.4 6.6 6.7 6.0 5.9 5.4 6.1 6.4 5.3 5.6 6.1 5.9 5.9 6.0 5.5 6.1 5.5 5.7 4.8 5.0 6.3 5.3 5.6 4.4 6.7 6.3 7.5 6.9 6.1 6.6 7.3 6.3 5.9 7.2 7.2 6.1 6.6 6.7 FD 1 7.2 6.6 6.5 5.4 7.0 6.4 6.6 5.0 6.2 6.4 6.3 6.9 8.0 7.4 6.3 5.9 6.7 6.3 6.1 6.5 6.4 5.8 6.6 6.0 6.2 6.4 6.4 6.4 6.5 5.9 6.8 6.1 5.9 6.3 5.7 6.0 6.1 7.0 6.1 6.0 5.7 6.1 6.0 6.1 6.1 6.1 6.6 6.4 6.1 6.6 5.7 FS 5.7 5.7 5.7 5.4 5.9 5.7 5.7 5.0 5.3 5.7 5.3 5.3 5.7 5.2 4.9 5.2 6.5 6.1 5.6 6.0 5.4 5.9 6.1 5.2 6.0 6.7 6.0 5.7 6.3 6.0 5.5- ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 4) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 290 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 1 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 6.7 6.9 6.9 7.2 MS 7.2 6.8 6.5 6.7 6.8 7.0 6.1 5.8 5.9 5.8 5.8 5.6 5.6 5.7 6.1 5.5 5.4 5.4 5.3 6.1 5.1 FS 7.0 6.5 6.8 6.2 6.7 6.5 7.3 5.5 5.6 5.6 6.0 6.2 6.6 6.9 6.6 6.5 7.2 5.8 6.9 6.3 6.4 7.7 5.9 4.4 6.0 6.5 6.3 6.2 6.0 5.7 6.2 5.4 5.1 5.6 4.2 5.5 5.8 6.3 5.2 5.9 5.3 5.3 5.6 5.2 5.9 7.0 7.1 6.9 7.3 6.5 6.9 6.7 6.1 6.0 6.3 5.9 7.4 7.3 7.0 6.6 6.8 6.7 7.2 6.5 5.8 6.3 6.2 6.9 6.3 6.8 6.8 6.3 6.8 6.0 5.6 6.5 5.7 6.3 5.8 5.4 6.2 5.5 5.7 6.0 6.4 6.4 6.3 6.4 6.0 6.6 6.3 6.0 5.9 5.6 5.9 NOT PREGNANT; MATING NOT CONFIRMED 6.4 6.0 6.4 6.4 6.5 6.7 5.7 5.7 6.2 5.6 5.3 6.2 6.2 5.9 5.9 6.3 6.5 6.6 7.1 6.7 6.6 7.4 6.1 7.4 6.4 6.2 6.9 6.5 6.4 6.9 6.6 6.3 6.5 6.7 7.3 6.8 7.0 6.7 7.4 7.0 6.3 5.3 6.5 7.3 6.7 7.4 7.1 5.9 6.8 7.2 7.1 6.5 7.1 6.4 6.1 6.5 6.2 6.2 6.3 6.7 6.0 4.6 7.3 6.0 5.1 5.6 5.0 4.8 5.7 5.3 5.1 4.9 5.3 6.3 5.6 5.7 6.7 5.8 6.7 6.0 6.7 MS MS 6.3 5.6 6.2 6.0 6.5 5.3 6.4 5.8 5.9 5.8 5.9 5.8 5.5 6.1 5.1 5.5 5.5 5.6 5.7 4.8 5.3 5.6 5.5 5.3 7.5 6.9 5.9 8.1 5.6 5.9 5.8 5.1 5.4 5.2 5.8 5.5 5.4 5.9 5.9 5.5 5.5 5.0 5.3 6.2 6.3 6.7 6.7 5.5 5.7 6.0 5.5 6.0 6.0 5.7 5.7 6.1 5.5 6.5 6.5 6.5 6.7 6.6 6.5 6.3 6.7 6.3 6.4 5.8 6.4 5.9 6.7 5.7 5.1 6.0 6.5 5.7 5.5 5.2 5.4 5.3 5.4 5.4 5.5 6.2 6.3 6.0 6.1 5.9 6.0 6.2 6.4 5.3 5.9 5.9 5.4 5.3 6.0 5.6 5.3 6.1 5.9 5.9 6.7 5.6 6.3 6.0 6.2 5.5 6.0 5.4 5.7 5.2 6.3 6.5 6.1 5.5 6.6 5.8 5.8 6.8 6.0 5.4 5.9 5.9 5.9 6.1 5.9 6.2 6.5 6.1 6.8 6.4 6.1 5.6 6.1 5.8 5.7 5.9 5.8 5.9 5.4 6.3 6.1 5.8 6.3 7.0 6.6 6.0 6.1 6.9 6.1 6.6 6.3 6.4 6.1 6.5 6.6 5.5 6.7 6.4 6.3 5.8 6.1 5.6 5.7 6.2 6.0 6.5 6.3 5.6 6.0 6.3 5.9 5.8 4.9 6.6 5.4 5.8 6.6 7.1 6.5 6.6 6.6 4.9 6.4 6.2 5.9 5.7 6.4 6.0 6.1 5.7 6.1 6.6 6.1 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) , X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 17 6.3 5.3 6.3 18 5.7 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 5) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 291 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 1 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 6.5 6.0 6.0 6.5 6.1 5.8 7.5 6.5 6.2 5.5 6.2 6.2 5.0 5.6 5.4 3.9 4.1 4.4 4.7 4.5 MD 1 MD 1 4.3 3.8 5.3 6.0 6.3 6.5 5.9 6.3 5.8 5.3 6.2 5.8 5.5 5.3 5.6 5.9 6.0 6.1 6.1 5.2 5.9 5.4 5.5 5.9 6.0 6.4 6.3 5.7 5.8 6.1 5.8 5.4 6.8 6.3 6.3 4.7 5.5 6.4 5.6 4.9 6.0 5.3 5.8 5.5 5.5 5.4 5.8 5.7 5.5 5.0 5.0 5.5 5.8 MS 4.8 5.2 5.0 5.3 5.3 5.7 6.1 5.3 5.7 6.0 5.4 6.1 5.6 5.9 5.7 5.5 4.4 5.5 5.1 6.0 5.6 5.4 6.9 6.8 6.6 7.3 6.5 7.1 6.4 6.8 6.0 7.2 6.0 5.9 6.1 6.7 6.0 6.6 NOT PREGNANT 5.4 5.5 5.0 5.8 5.6 6.1 6.0 6.0 5.9 5.3 5.5 4.9 4.4 5.2 5.4 5.7 5.2 5.6 5.5 5.7 5.3 4.9 5.4 4.4 4.7 5.1 5.2 4.5 5.2 5.1 5.1 6.4 5.6 6.6 6.2 6.3 6.0 5.9 5.9 5.3 5.6 5.6 5.7 5.9 5.6 6.6 6.2 6.6 6.9 6.7 6.5 6.6 6.2 5.8 5.4 5.6 5.6 6.4 5.7 5.1 5.1 5.2 5.9 5.3 5.4 5.4 4.8 5.5 5.2 5.4 5.6 5.4 4.4 5.6 5.7 5.9 5.4 5.6 5.4 5.8 5.7 5.7 5.3 4.9 5.3 5.1 5.3 5.9 6.2 5.9 6.1 6.4 6.0 6.4 5.3 6.1 6.1 5.4 4.2 5.4 5.8 4.9 7.5 7.8 6.9 7.2 7.4 6.9 7.3 6.7 7.2 7.4 7.1 6.4 6.6 6.2 6.7 5.8 6.0 5.3 5.6 5.6 5.4 5.2 5.5 5.4 5.0 5.7 5.3 5.6 5.3 5.3 5.3 5.6 6.0 5.9 5.1 5.8 5.3 5.2 5.9 5.4 5.7 4.7 5.3 5.9 5.5 FS 5.7 5.2 5.6 6.0 5.9 5.6 6.2 5.2 4.8 5.4 5.7 5.3 5.8 5.2 5.5 5.2 6.7 5.6 6.3 6.2 6.3 7.0 6.1 6.6 6.3 5.9 6.0 5.4 FS 6.0 5.8 5.6 5.0 6.2 6.2 5.7 6.1 5.2 5.6 6.1 5.4 5.4 5.3 5.6 5.3 7.7 6.6 6.1 7.0 7.0 5.9 7.7 5.8 5.6 6.0 6.0 5.5 5.5 5.4 5.6 6.1 5.5 5.2 5.5 5.5 5.6 5.8 5.5 5.5 5.4 5.3 5.6 5.4 5.4 5.8 5.8 5.7 5.6 6.7 6.6 6.4 6.4 6.2 6.0 5.9 6.1 6.1 6.4 6.2 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 6.6 5.2 6.1 6.1 5.6 6.3 5.7 5.3 5.7 5.4 5.6 5.3 5.5 5.4 5.2 5.5 6.3 5.8 5.4 5.2 6.0 5.3 5.3 5.4 5.6 5.8 6.2 6.2 6.0 5.8 5.7 MS 5.3 5.5 5.2 6.0 5.6 FS ,FS ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 6) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 292 PUP # 1 2 3 4 5 6 7 8 9 10 il 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 5 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 9.5 8.1 9.2 8.4 7.9 8.5 9.2 12.0 12.4 12.5 12.2 12.2 12.2 11.4 11.3 9.6 9.4 11.8 11.4 14.1 10.7 MORIBUND SACRIFICED ON DAY 68 OF STUDY 10.2 10.3 11.7 10.1 10.6 10.8 9.8 7.7 8.7 8.2 8.7 8.3 MM 3 8.6 9.5 9.4 9.2 9.0 9.3 9.0 9.2 10.7 10.5 9.4 10.4 10.6 9.3 MS 9.7 10.2 9.8 10.6 9.6 10.4 10.2 10.3 10.3 9.9 8.9 MD 3 MS 8.4 NOT PREGNANT 10.6 9.6 9.1 10.7 10.7 10.1 10.6 12.6 12.4 11.5 11.7 9.6 10.4 10.9 7.8 8.3 7.6 8.4 7.9 8.2 8.1 8.7 8.4 8.6 7.9 7.6 8.3 7.6 9.0 9.1 8.5 9.4 8.6 8.9 8.5 9.3 9.2 9.3 9.7 9.4 8.4 9.7 7.3 7.8 7.3 7.9 7.8 7.6 6.4 10.4 9.4 9.1 9.9 MD 1 8.8 9.2 9.3 8.6 9.9 8.4 8.7 9.5 8.5 10.7 9.7 9.6 8.9 8.8 8.9 9.9 11.6 12.1 12.5 11.7 11.4 11.3 11.1 13.1 13.3 12.0 12.6 13.3 12.4 12.8 10.2 9.6 9.8 9.9 9.5 9.2 8.5 8.3 7.9 9.0 7.6 8.2 9.0 8.6 9.9 8.5 10.6 10.2 10.2 10.1 9.8 9.8 8.9 9.7 9.5 10.4 9.4 9.4 9.1 8.0 8.7 8.9 8.6 9.1 8.5 10.1 8.9 9.7 10.3 9.8 10.2 9.9 8.4 7.7 7.9 8.3 7.4 8.3 7.8 8.2 11.6 12.1 10.0 8.4 8.5 9.8 9.0 9.7 11.2 11.6 9.0 8.3 8.0 9.3 7.3 9.2 8.4 9.5 11.6 12.7 11.0 7.3 9.8 9.7 8.4 10.8 MS 8.5 11.9 10.7 7.1 10.7 10.1 8.1 9.6 10.7 9.6 9.2 9.9 8.4 8.6 9.6 9.3 9.2 11.6 12.7 8.0 8.4 8.9 8.6 7.1 7.5 7.5 9.0 11.8 12.8 8.9 8.3 9.2 MM 2 7.9 9.0 8.3 10.6 11.3 8.7 8.2 8.1 9.0 7.2 8.3 9.7 8.9 10.6 9.0 7.6 8.9 9.4 8.3 9.1 7.7 11.9 12.1 11.1 7.7 8.4 10.1 8.6 10.5 10.4 11.7 6.6 7.7 8.2 8.6 6.2 6.8 8.3 9.5 11.2 8.6 6.6 8.4 9.1 8.5 9.1 7.9 11.6 12.0 9.0 8.4 7.9 9.0 9.3 9.6 9.9 12.3 7.2 8.3 8.2 8.8 6.8 8.0 8.8 8.6 10.9 9.2 7.9 9.0 9.1 7.2 10.3 7.2 10.9 9.3 10.1 7.6 8.9 10.1 9.6 9.6 10.1 UU 8.1 7.5 8.3 8.9 7.6 9.2 9.2 8.7 9.3 8.2 9.6 9.3 8.6 10.0 7.7 10.1 11.8 8.0 8.1 9.0 10.9 7.2 .5 8.9 8.0 7.2 8.3 8.8 9.0 8.6 9.5 9.3 8.7 ,8.0 11.8 8.4 9.8 FD 1 7.7 7.4 8.2 FD 2 FM 4 8.6 9.2 9.1 9.4 8.8 10.5 8.2 8.6 6.7 UU FD 2 9.7 7.8 8.4 8.9 8.5 9.2 FM 2 8.5 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 7) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 293 PUP # RAT/ LITTER # 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 5 9.6 10.2 9.2 9.0 9.4 9.0 10.6 8.6 10.3 8.7 9.6 10.7 9.4 10.6 8.6 9.7 9.7 8.1 10.1 8.2 9.8 8.0 9.8 10.3 9.1 8.6 10.4 9.0 10.1 8.3 9.5 10.4 9.3 9.4 8.6 MORIBUND SACRIFICED ON DAY 59iOF STUDY 8.5 9.2 8.5 8.0 8.1 8.0 8.0 9.9 9.5 8.8 8.3 8.9 8.9 9.4 10.4 10.3 9.3 8.7 10.0 7.4 9.0 NOT PREGNANT 8.7 10.4 9.9 9.1 8.9 9.7 9.5 8.7 7.9 6.9 9.7 9.8 7.9 7.7 7.9 7.6 8.3 8.0 8.4 7.2 6.5 7.3 7.9 6.9 7.3 8.7 8.5 8.3 10.6 9.6 9.2 8.5 10.2 9.9 10.0 8.9 10.1 8.9 8.3 9.5 9.6 9.5 10.6 9.9 10.7 MS MS MS MS 9.8 10.2 9.5 8.5 8.6 8.8 10.2 8.9 8.2 8.4 7.7 7.8 8.3 8.3 8.9 8.1 8.4 8.5 8.7 8.6 7.6 NOT PREGNANT 8.5 9.4 9.3 9.8 10.2 10.0 8.3 7.8 8.5 7.7 8.1 7.2 7.0 8.5 8.5 9.0 9.4 8.7 9.5 9.4 10.1 10.0 9.5 10.2 9.7 10.1 7.6 9.1 8.7 8.6 9.0 9.7 9.3 9.7 8.9 9.7 10.7 10.3 10.3 10.0 9.4 9.8 7.4 7.9 7.5 8.6 8.3 8.0 8.0 9.0 8.2 8.8 8.8 8.1 8.4 8.6 8.9 9.1 8.0 8.2 8.3 8.7 7.7 8.8 9.2 9.1 9.2 8.5 8.0 8.2 10.0 9.0 8.4 6.8 8.2 10.0 9.3 10.7 8.6 8.9 8.4 9.0 8.5 9.3 10.5 10.0 10.0 7.0 8.3 9.0 9.2 10.4 9.3 8.7 8.3 7.0 8.5 10.2 7.8 8.4 7.4 7.0 9.1 8.5 10.1 9.2 8.3 7.6 9.7 8.0 10.1 10.2 8.7 9.3 7.3 7.2 8.7 9.8 9.6 8.1 9.2 6.9 7.2 8.8 9.9 9.4 7.4 8.1 7.3 10.1 8.7 11.1 9.1 8.5 8.1 9.4 7.1 9.2 9.7 9.1 10.0 8.3 8.5 8.0 9.6 9.3 9.1 9.8 8.0 8.9 8.7 10.8 FD 7.8 8.0 9.9 8.5 9.6 10.2 7.3 8.1 9.4 8.2 9.7 9.2 7.3 10.0 7.8 7.7 8.7 10.5 10.7 7.6 9.8 8.3 FS 8.4 10.8 UU 7.7 6.2 9.8 8.3 9.6 10.4 7.5 9.1 8.4 7.3 9.8 9.7 8.7 9.9 7.6 8.9 8.5 8.6 10.1 9.1 9.1 9.1 6.0 9.1 5.9 8.5 FS 9.1 7.9 FS 7.9 9.1 8.4 7.0 10.2 7.6 8.4 8.5 9.4 9.1 8.3 8.0 9.0 7.0 FM 2 FS 8.8 8.1 7.9 9.6 9.9 8.5 9.2 7.8 8.2 9.0 FM 3 8.1 8.0 6.7 FS 9.0 7.6 7.2 8.8 FD 5 7.5 FS 7.4 8.7 7.5 8.0 8.2 7.0 9.3 7.5 7.2 8.0 FD 1 8.9 6.9 8.6 FD 3 8.7 8.0 7.4 8.7 6.8 FD 2 FD 4 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 8) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 n CO Page 294 PUP # RAT/ LITTER # 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 10 11 12 13 14 15 16 17 MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 5 10.5 10.2 10.6 10.4 8.3 9.4 8.7 PREGNANT: DID NOT DELIVER A LITTER 9.4 9.0 9.2 9.1 10.0 9.7 10.7 12.4 12.2 10.4 12.1 10.5 8.8 FS 9.2 9.2 7.9 8.6 6.5 8.7 8.6 10.2 8.1 8.1 9.3 9.2 9.0 8.8 6.1 7.4 6.9 7.1 7.3 6.9 7.1 9.9 8.3 8.9 9.8 9.3 8.6 10.1 7.6 8.7 8.5 8.7 9.3 7.3 8.3 9.3 9.2 8.4 8.5 7.5 10.4 10.0 8.8 7.5 7.4 8.0 MD 3 8.6 7.9 7.6 7.6 7.9 7.4 8.0 7.6 7.7 8.9 5.7 9.4 9.1 10.2 9.0 7.3 10.8 12.4 11.5 11.9 11.7 10.3 8.5 10.1 8.9 8.7 9.0 9.3 9.6 9.0 10.0 10.4 10.1 10.3 10.0 10.6 10.3 9.6 9.3 10.6 9.8 10.3 9.4 9.3 10.5 9.3 11.1 11.3 10.4 11.3 9.2 11.2 11.5 12.2 11.9 11.5 11.6 11.3 12.1 12.3 9.7 13.0 12.2 12.5 11.7 11.6 11.5 11.4 8.9 10.4 11.9 10.5 9.1 8.6 9.8 9.9 9.2 9.5 10.0 9.6 11.5 10.6 11.2 9.9 9.3 10.2 10.3 10.3 9.8 10.6 9.9 7.9 9.1 14.3 13.5 13.7 10.0 9.0 9.1 9.4 8.8 9.5 9.7 11.0 11.0 10.7 11.5 11.1 11.2 10.9 9.0 9.5 9.0 9.5 8.5 8.6 8.3 7.8 8.9 9.3 8.7 8.6 8.1 8.7 9.5 10.1 8.4 9.7 9.0 9.5 8.8 10.3 9.5 MD 1 8.4 4.5 8.9 8.3 10.0 8.0 8.0 8.8 10.4 6.7 9.6 8.3 10.5 11.8 11.1 9.9 9.9 9.8 10.0 9.5 11.8 9.2 9.1 9.0 7.7 9.4 9.4 8.9 5.6 8.5 8.6 7.9 7.6 7.8 10.5 9.1 9.3 8.9 10.3 10.7 11.0 10.4 10.2 10.8 9.8 10.4 11.1 8.6 8.7 9.5 10.4 9.0 8.8 8.7 MS 8.7 7.7 7.2 8.7 9.1 9.6 7.8 10.8 8.3 11.3 11.4 10.0 8.9 11.5 9.6 8.1 9.6 8.7 8.8 9.6 8.4 9.3 8.6 7.1 8.4 8.5 7.7 7.9 8.7 10.1 9.9 10.1 8.3 11.9 10.9 9.3 10.8 10.2 6.2 8.6 9.8 8.7 7.9 9.0 8.8 8.2 8.1 6.5 8.4 8.2 7.3 7.4 8.6 11.1 9.3 9.8 7.4 11.2 8.1 10.9 9.9 8.7 7.9 9.9 9.5 8.8 8.3 6.5 8.4 8.6 4.8 7.6 8.4 9.9 7.1 10.0 8.6 12.8 10.2 8.9 7.8 5.9 8.1 8.1 8.4 7.2 8.5 7.5 7.8 7.7 9.1 10.5 9.2 FS FS 7.3 9.9 8.8 7.2 9.7 9.5 FM 3 8.8 7.7 8.1 8.3 7.3 6.5 8.4 9.3 7.5 FD 4 7.3 8.9 FD 4 6.9 9.4 10.8 8.5 FD 1 6.8 9.5 10.3 7.5 6.7 FM 4 FD 2 8.1 FD 3 FD 1 FS 7.6 8.3 9.1 - ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 18 8.8 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 9) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 295 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 5 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 10.0 11.5 11.2 11.6 MS 10.9 10.8 9.4 8.8 8.6 9.2 9.4 9.1 8.7 10.8 10.4 9.4 9.9 11.1 11.2 9.8 10.8 7.6 8.9 8.0 8.0 8.6 MM 4 9.4 9.3 7.9 6.9 6.6 8.7 7.5 10.6 9.6 10.7 10.6 11.1 9.2 9.5 11.3 9.4 10.2 9.8 9.2 10.9 10.1 8.8 9.2 9.8 9.9 8.4 7.6 8.7 10.1 9.6 10.6 10.1 10.1 9.4 8.7 NOT PREGNANT; MATING NOT CONFIRMED 7.8 8.1 8.0 7.8 8.0 7.7 7.1 10.1 9.7 9.1 10.5 9.7 9.7 10.5 10.3 11.3 11.6 10.4 10.6 11.8 11.2 10.0 9.2 10.5 10.0 10.7 9.6 9.0 11.3 10.1 6.6 9.7 11.0 8.5 9.7 10.8 10.2 9.3 10.7 8.8 MD 3 MS 9.1 8.8 8.5 8.3 9.2 9.0 8.5 11.7 10.7 12.4 10.0 8.7 8.7 8.2 9.0 9.0 8.9 8.4 8.5 10.8 10.2 10.6 9.3 10.7 8.5 9.3 9.3 9.9 9.7 9.7 10.0 10.2 8.2 7.8 9.3 8.8 9.5 8.2 9.1 9.6 10.2 10.0 10.8 10.9 10.5 10.5 7.9 8.8 8.2 9.0 8.8 8.8 9.8 9.6 8.3 9.0 9.2 9.2 8.2 9.2 9.4 8.3 8.9 7.9 9.4 9.3 8.7 9.7 10.2 10.0 9.5 10.2 8.2 8.8 9.6 10.3 11.3 9.6 10.6 10.3 10.3 9.3 9.7 9.5 9.9 9.2 10.3 9.4 7.3 9.2 9.0 8.3 8.9 8.9 9.7 11.3 9.0 9.6 8.2 8.1 9.2 10.2 8.5 9.3 7.5 8.7 8.2 10.0 9.2 MS 6.9 8.1 10.4 9.6 7.8 11.6 9.0 9.5 8.2 9.9 9.4 8.7 10.2 9.3 9.9 8.6 9.8 10.3 9.3 8.8 8.8 7.1 9.0 10.8 9.6 8.4 9.9 8.1 7.9 9.8 9.5 8.3 10.6 8.1 8.2 8.3 8.8 9.1 8.2 10.2 8.4 9.6 7.4 5.1 10.5 10.1 8.9 10.8 7.2 9.5 11.4 9.1 11.0 10.8 9.2 9.1 9.9 9.6 8.5 10.3 8.4 9.1 8.5 9.7 7.9 8.8 11.2 8.9 9.1 8.5 7.2 9.7 8.6 8.1 9.4 6.8 9.5 11.7 9.2 8.1 9.5 7.7 8.6 10.3 9.6 8.6 8.7 8.3 8.8 7.4 9.3 8.2 8.6 8.5 11.1 8.2 8.0 10.4 8.5 7.7 6.0 9.5 10.6 9.2 9.1 10.0 8.6 8.9 10.7 9.1 7.5 8.6 9.2 8.4 8.1 8.7 7.5 8.2 8.2 9.1 7.5 8.0 8.6 7.5 9.8 10.4 9.6 8.6 9.3 8.6 8.8 10.4 6.8 8.7 8.9 9.1 7.4 10.1 8.9 8.8 7.9 9.0 4.9 7.2 7.7 6.3 9.2 10.3 8.6 7.7 7.9 8.2 8.9 11.2 8.3 8.1 8.6 7.6 9.7 8.8 7.0 8.6 10.9 8.6 FS 8.9 8.2 FD 3 7.4 6.9 8.6 9.0 9.7 8.6 10.2 8.6 7.7 9.2 8.9 7.9 8.8 9.1 8.6 8.4 7.4 8.7 8.0 FD 3 FM 3 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.G) TABLE C37 (PAGE 10) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 296 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 5 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 8.4 7.1 9.2 9.3 9.6 9.7 9.0 8.9 7.3 7.3 7.0 5.8 6.8 7.3 MM 2 MD 1 MD 1 FM 2 FM 2 8.8 7.6 8.2 8.1 8.4 9.2 8.8 7.6 8.0 8.6 8.9 9.0 9.0 8.7 7.7 7.4 7.9 9.0 8.4 8.7 8.7 6.7 8.7 7.1 7.7 8.7 7.3 7.6 7.1 6.9 7.4 6.9 7.6 7.3 7.7 6.3 8.0 7.4 MS 7.4 9.1 9.4 8.6 9.1 8.7 8.2 9.0 8.6 8.4 9.2 8.5 9.1 10.4 9.0 8.3 MD 3 8.6 9.3 9.0 8.0 NOT PREGNANT 7.1 6.1 6.7 7.2 6.6 8.0 6.5 5.2 6.5 3.9 6.9 7.1 4.8 6.6 6.1 5.3 6.5 6.7 5.9 6.3 8.3 8.7 8.2 8.9 8.5 8.7 9.2 8.8 7.6 7.9 9.3 10.1 9.8 8.2 9.6 9.3 8.2 8.3 8.7 9.8 6.2 6.8 MM 4 7.4 7.0 6.5 7.2 6.2 7.5 5.4 8.7 8.8 9.3 8.9 8.9 9.2 8.4 6.6 8.2 8.4 10.6 8.5 10.2 10.0 10.1 9.9 10.3 10.0 10.7 7.5 10.9 11.5 11.4 11.1 11.2 11.1 9.6 10.7 11.5 11.6 7.0 6.5 7.6 7.4 6.7 7.0 7.6 MD 2 6.8 7.6 7.4 8.5 8.9 8.9 8.4 8.6 9.5 7.8 9.0 8.3 8.8 9.4 8.8 8.9 8.9 9.7 9.5 9.1 8.0 8.1 10.3 10.6 10.6 8.6 9.9 9.7 9.7 9.7 8.5 7.9 9.0 9.5 9.7 9.8 10.1 9.8 9.4 6.8 10.1 9.0 12,1 13.1 11.7 13.8 9.2 11.9 10.3 6.9 6.6 7.6 MM 5 5.3 6.6 6.3 5.7 7.5 6.2 9.1 9.5 9.8 9.3 9.5 9.4 9.2 9.6 9.6 9.8 11.2 9.6 10.0 9.9 10.4 9.4 9.6 9.0 9.2 9.5 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 9.6 8.3 8.5 8.7 9.6 9.2 8.1 7.6 8.3 7.7 9.0 10.0 9.6 8.9 8.6 9.1 9.3 9.1 9.6 8.6 10.2 8.2 9.5 9.6 8.9 8.7 MS 10.0 8.6 8.7 8.5 7.5 8.6 8.1 6.4 8.9 7.6 6.7 6.1 8.1 9.1 7.2 8.7 8.4 10.4 6.7 8.2 9.1 9.5 8.9 7.5 9.2 9.6 8.7 8.8 8.8 7.9 8.2 8.1 7.1 8.0 5.4 7.5 6.5 6.1 7.9 9.1 6.2 8.8 7.9 9.7 7.0 8.9 7.0 9.4 8.6 7.2 9.3 FM 3 9.1 FD 2 5.4 8.7 8.5 8.1 6.9 8.0 9.4 5.9 5.7 8.1 9.3 7.6 9.0 9.5 10.6 7.7 6.8 8.3 9.6 8.5 9.7 8.8 FS 8.2 9.1 6.4 7.1 7.7 8.9 6.8 5.9 8.4 7.5 8.3 10.1 10.6 6.8 9.2 8.9 FS 9.6 9.8 FS 8.3 7.8 7.2 7.8 7.6 6.1 FM 2 7.3 9.3 11.0 7.1 FS 8.1 9.1 7.8 9.0 8.7 6.6 7.0 8.7 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 17 18 8.8 6.1 FM 5 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE II) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 297 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY' 8 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 13.1 13.4 12.9 13.2 13.2 12.3 12.8 17.2 18.1 18.2 17.8 17.5 16.1 17.1 16.3 15.3 16.0 19.9 13.3 13.9 17.2 MORIBUND SACRIFICED ON DAY 68 OF STUDY 16.5 16.0 14.9 14.7 14.7 15.4 13.7 12.6 11.3 10.6 11.7 13.1 MM 3 12.3 13.0 12.6 10.9 13.0 11.6 11.6 12.9 14.2 15.2 15.0 15.7 13.4 13.4 MS 15.1 13.9 14.0 14.2 13.2 12.4 14.8 14.2 15.3 13.7 15.5 MD 3 MS 14.8 NOT PREGNANT 16.0 15.9 14.6 15.4 15.8 14.6 14.1 17.5 18.1 17.4 14.6 18.5 17.0 16.9 11.3 10.8 10.9 11.5 9.1 12.1 10.5 12.0 10.0 11.6 11.4 11.5 10.9 11.3 12.6 11.9 11.2 11.2 10.8 10.6 11.7 12.6 12.9 13.1 12.5 13.0 12.9 11.8 10.6 11.2 9.1 11.3 12.0 11.4 10.9 13.1 14.2 14.0 13.2 MD 1 12.0 12.9 14.5 13.4 11.9 13.4 14.1 13.0 13.8 13.0 13.8 14.4 15.5 14.2 12.9 15.2 MX 8 MX 8 MX 8 FX 8 FX 8 FX 8 FX 8 18.4 19.3 19.3 18.0 18.8 18.6 18.4 12.9 14.2 14.9 13.7 13.2 10.8 13.5 12.0 11.9 12.6 11.8 12.0 12.1 11.8 13.3 13.6 9.7 13.8 14.6 13.4 13.3 14.5 13.3 13.7 13.9 14.6 15.2 13.6 13.0 12.8 13.0 12.9 11.0 12.8 12.7 11.8 10.3 11.8 12.0 12.2 12.6 11.5 11.6 12.1 11.1 12.5 10.4 10.4 11.9 14.2 17.7 16.8 13.2 12.2 12.0 14.7 14.6 12.3 16.5 15.2 12.2 10.4 10.0 12.0 11.2 10.7 13.1 12.9 FX 8 19.9 12.2 12.3 11.6 13.5 9.4 12.7 MS 13.3 17.6 12.8 13.8 12.3 11.7 13.4 13.3 14.2 15.1 16.5 10.8 10.4 10.1 12.5 9.0 13.4 11.2 13.9 FX 8 18.0 13.1 13.1 11.2 MM 2 10.5 10.7 12.2 16.1 FM 7 12.8 11.8 13.8 13.9 13.8 13.7 15.0 18.4 11.2 12.1 11.3 10.8 10.5 13.8 12.0 12.8 FX 8 12.3 11.6 12.9 12.7 12.3 10.9 11.7 17.7 14.9 14.4 12.0 13.3 14.0 12.9 14.4 15.5 17.0 11.7 11.4 11.3 12.6 11.4 10.4 12.3 12.1 FX 8 12.9 11.4 13.4 14.1 12.0 10.6 11.1 18.0 17.0 15.0 11.7 10.8 15.0 11.7 15.4 14.8 18.0 11.2 9.2 10.6 12.3 8.6 13.4 11.5 13.9 FX 8 13.1 13.1 12.2 12.7 13.5 12.1 11.1 15.3 16.0 15.1 11.6 11.8 14.7 13.4 14.0 14.3 UU 11.7 10.3 11.8 11.9 9.6 12.0 11.5 13.6 13.4 10.8 12.5 13.1 12.6 11.1 11.1 16.2 14.2 11.8 10.6 13.0 15.6 8.0 10.3 11.0 12.0 9.7 10.3 12.8 11.4 9.9 12.2 12.6 12.3 12.1 14.1 12.0 12.6 FD 1 10.6 11.3 10.7 FD 2 FM 4 12.8 13.6 12.5 11.4 13.6 16.0 13.7 11.2 11.0 UU FD 2 12.0 12.6 12.0 13.5 12.7 12.7 FM 2 13.4 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 12) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 298 PUP # RAT/ LITTER # 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 8 13.2 13.4 13.8 12.7 14.0 14.1 12.5 13.8 13.2 15.2 14.6 13.5 13.0 15.1 12.9 13.1 14.0 12.0 12.9 11.8 11.6 12.9 14.5 14.5 14.2 13.6 13.1 14.1 12.6 12.7 12.9 13.4 13.2 12.5 11.6 MORIBUND SACRIFICED ON DAY 59 OF STUDY 13.4 11.8 13.1 12.2 12.6 11.8 10.7 14.8 11.9 13.0 13.6 12.8 13.2 13.9 13.9 16.2 16.4 15.0 15.7 15.9 14.7 NOT PREGNANT 12.7 13.7 14.1 11.8 11.4 10.7 12.4 14.1 12.6 12.0 14.3 11.7 MD 7 12.9 11.1 11.7 10.4 11.0 11.9 9.4 12.0 13.8 10.9 12.3 10.5 10.7 12.3 12.2 14.0 14.5 11.9 13.9 13.1 14.6 14.5 12.4 13.2 12.3 12.1 13.3 11.9 13.3 16.1 16.0 15.0 MS MS MS MS 14.7 14.8 13.4 14.0 12.8 15.0 13.1 12.4 11.6 12.0 11.2 12.2 9.6 12.3 12.4 11.8 12.1 11.7 11.8 12.0 10.8 NOT PREGNANT 13.8 13.6 13.6 13.2 13.2 14.7 12.2 12.5 11.3 10.8 10.6 10.8 11.5 11.2 13.5 14.4 13.2 14.7 13.5 13.5 13.2 14.9 14.6 15.6 12.1 14.0 14.5 14.8 12.8 13.1 14.6 12.5 14.6 12.7 13.3 13.9 15.1 14.8 15.7 13.3 13.9 13.6 10.2 11.7 10.4 11.0 9.5 11.7 11.1 13.3 13.2 12.6 11.6 12.4 12.7 11.7 12.3 12.0 12.0 11.9 11.9 12.3 12.2 12.3 14.3 12.7 12.5 12.8 12.0 12.5 15.4 13.2 13.3 10.3 10.1 14.4 13.3 16.1 12.2 12.6 11.1 12.4 9.9 13.3 14.9 12.3 14.4 13.4 12.7 11.1 15.2 14.7 13.0 13.6 12.8 10.9 12.6 14.4 13.1 11.1 8.7 11.5 14.3 12.7 15.5 13.7 10.1 11.0 12.9 9.7 11.3 13.7 12.7 14.1 11.2 12.1 11.7 14.4 14.4 13.2 14.1 11.7 13.1 12.4 12.0 13.0 12.1 10.0 9.7 14.6 12.5 15.9 12.9 11.0 11.9 13.5 12.4 14.8 15.8 10.2 15.4 11.2 9.6 13.2 11.1 13.1 12.3 14.7 13.7 11.9 11.8 15.5 FD 10.5 10.2 14.3 11.2 14.0 14.0 11.0 9.6 14.1 10.1 12.8 15.2 12.4 16.3 12.3 12.6 11.1 11.7 15.7 10.5 14.0 10.8 FS 7.0 13.9 UU 12.4 9.6 13.0 11.5 14.7 13.5 11.9 12.0 13.8 10.6 13.5 14.5 13.8 15.6 11.1 12.2 12.6 12.1 14.3 11.4 13.7 11.4 12.0 12.2 9.7 12.0 FS 12.5 11.2 FS 10.3 12.9 12.7 10.5 14.0 10.5 9.6 12.0 13.8 11.7 13.0 12.8 12.1 12.4 FM 2 FS 13.6 10.5 9.9 10.5 13.9 12.4 13.7 10.9 13.3 13.0 FM 3 12.2 11.8 11.3 FS 13.4 11.5 10.5 12.3 FD 5 10.7 FS 11.0 12.7 11.2 12.7 13.0 8.6 13.6 10.1 11.7 14.2 FD 1 12.5 11.8 11.1 FD 3 11.1 FD 8 12.2 12.0 10.8 FD 2 FD 4 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM ' NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C20 (PAGE 2) : LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - P GENERATION FEMALE RATS ARGUS 418-020 Page 198 DOSAGE (MG/KG/DAY) DELIVERED LITTERS WITH ONE OR MORE LIVEBORN 1PUPS SURVIVING PUPS/LITTER a N 28 hi 3 27 29 DAY 1 b DAY 5 DAY 8 DAY 15 DAY 22 MEANS.D. MEANS.D . MEANS.D . MEANS.D . MEANS.D. PERCENT MALE PUPS PER NUMBER OF PUPS SEXED 14.2 2.2 13.8 2.1 13.9 2.0 1 27] c 13.9 2.0 [ 27] c 13.9 2.0 [ 27] c 14.2 2.6 13.9 2.5 13.8 2.5 13.9 2.5 [ 26] c 13.9 2.5 [ 26] c 13.4 3.6 13.0 3.4 12.9 3.4 12.8 3.3 12.8 3.4 DAY 1 b DAY 5 DAY 8 DAY 15 DAY 22 MEANS.D . MEANS.D . MEANS.D . MEANS.D . MEANS.D . 46.9 13.2 47.0 13.9 47.8 13.4 [ 27] c 47.8 13.4 [ 27] c 47.8 13.4 [ 27] c 52.2 13.6 53.1 13.3 53.0 13.3 52.6 13.2 ! 26] c 52.6 13.2 t 26] c 48.6 17.5 49.1 17.6 49.3 17.4 49.2 17.5 49.2 17.4 DAY = DAY POSTPARTUM l ] NUMBER OF VALUES AVERAGED a. Average number of live pups per litter, including litters with no surviving pups. b. Includes pups born alive, found dead on day 1 postpartum. c. Excludes litters in which the dam was sacrificed. d. Excludes litter 13947, which had no surviving pups on day 1 of lactation. IV 10 29 13.8 3.0 13.6 2.8 13.6 2.8 13.4 2.8 13.4 2.8 47.1 10.2 47.1 10.2 47.3 10.1 47.4 10.1 47.4 10.1 V 30 29 13.4 3.3 12.9 3.7 12.6 3.6 12.5 3.6 12.5 3.6 49.9 16.9 52.4 17.2 ( 28] d 52.4 17.3 ( 28] d 52.2 17.8 [ 28] d 52.2 17.8 ( 28] d PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 13) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 299 PUP # RAT/ LITTER # 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 8 15.3 12.1 12.2 15.7 14.0 15.4 14.4 PREGNANT; DID NOT DELIVER A LITTER 14.5 12.8 13.7 14.2 14.0 13.4 13.3 16.8 19.8 17.3 19.4 19.3 17.7 FS 9.5 11.8 11.8 12.4 12.2 12.3 10.6 9.7 10.6 9.9 12.7 10.8 11.7 10.0 11.1 10.7 10.1 8.0 9.4 9.1 9.0 13.8 14.3 13.8 14.6 11.9 12.3 14.0 10.4 11.1 11.8 11.1 11.0 9.8 10.7 13.3 13.0 14.6 12.4 15.1 14.5 11.5 13.1 11.4 12.2 11.9 MD 3 12.0 12.3 10.6 10.0 12.4 11.1 11.5 11.6 11.2 13.3 11.5 13.7 9.9 13.5 15.5 13.9 16.6 17.5 17.5 16.3 18.0 15.8 14.8 12.7 12.3 14.0 14.4 12.6 12.7 12.2 15.2 15.0 15.5 15.3 15.9 16.4 16.4 12.5 12.9 14.4 15.3 12.9 14.1 12.7 14.1 15.6 16.2 15.4 15.0 16.0 13.7 16.4 18.0 13.3 16.1 15.3 15.3 16.2 16.0 16.6 16.3 16.2 16.2 15.7 13.0 15.8 15.8 13.0 16.7 14.7 16.5 15.3 14.3 14.4 14.4 15.1 15.1 14.8 15.1 14.6 15.9 14.0 14.2 12.3 14.5 16.4 8.6 12.7 11.1 12.8 12.5 14.3 12.7 19.4 18.7 18.5 14.0 13.8 13.7 14.7 13.9 13.9 13.4 16.9 16.0 15.5 15.3 15.6 16.0 15.7 10.9 11.6 11.1 10.7 11.5 10.7 10.9 12.3 13.4 13.2 11.3 12.5 11.5 12.5 13.6 13.4 13.5 10.9 12.7 12.9 14.0 14.8 14.0 MD 1 11.3 MD 7 13.4 10.2 10.6 11.5 11.1 8.8 11.9 8.9 14.7 13.1 16.4 15.6 15.1 14.9 12.7 14.4 12.3 13.2 16.9 10.6 13.3 12.3 15.2 13.8 11.7 11.1 MD 6 12.5 10.8 11.1 11.6 11.3 15.9 13.0 14.7 11.6 15.0 16.1 14.3 14.4 14.9 12.9 12.6 14.4 16.3 10.3 12.1 13.2 10.6 14.6 10.9 11.9 MS 13.3 10.8 11.9 12.6 12.3 15.5 13.7 13.8 10.7 15.3 16.0 13.3 13.0 15.6 11.1 14.1 14.3 10.5 12.7 12.5 12.0 12.5 10.6 10.4 12.1 9.8 12.0 9.1 13.5 13.4 11.0 16.4 10.8 16.8 15.0 14.7 11.8 16.0 6.9 14.2 14.6 11.2 11.6 13.1 13.4 13.0 10.8 9.9 13.1 10.8 12.0 10.7 15.1 15.7 14.1 15.5 12.5 15.2 15.9 16.1 11.1 10.8 12.0 13.8 12.7 11.9 8.8 9.9 12.9 11.3 11.7 10.6 12.8 15.4 11.2 14.8 13.0 14.9 15.1 14.8 10.7 11.1 13.2 14.7 13.8 FM 3 11.7 9.2 9.3 12.8 10.6 9.6 11.1 8.7 12.9 10.7 13.0 11.2 FD 6 12.2 FD 4 FM 7 11.2 13.1 14.3 13.9 FS FS FD 4 11.3 13.6 14.6 11.8 FD 1 11.1 13.5 14.8 11.0 12.1 10.7 FD 3 14.1 FD 1 10.7 11.7 13.6 FS 12.5 11.8 7.4 10.5 9.3 8.7 FM 4 FD 2 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 14) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 300 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 8 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 15..2 13 ,.8 16 .3 16,.3 MS 15 .4 15..9 12..8 13 .1 12 .3 13 ,.9 13..0 13,.7 12.,2 14..5 15..5 15 .4 16.,5 14 .3 15,.1 13 .,0 15,.1 12..5 11 .1 13,.0 11 .5 12 .5 MM 4 12..8 10,.2 14 .6 8,.3 11..7 13 .7 13 .,9 13..3 15..6 14 .5 15,.4 15,.4 13 ,.1 15..2 15..6 14 .1 14 .7 14 .3 14 .4 12 .9 13 ,.2 12..1 13..7 10 .3 11..8 11..8 13 .4 11.,0 13..5 14 ,.3 13 .4 13..5 13,.6 12,.6 13 .4 NOT PREGNANT; MATING NOT CONFIRMED 10..7 9,.9 10 .7 10,.3 10,.3 11 .3 10. 2 13..6 13 .6 12 .7 14..4 14,.6 14 .0 13 .2 15..2 16..0 14 .9 12,.3 15,.3 11,.1 12. 8 12 ,.5 1 1 ..0 10 .2 12 .6 11 .3 7 .9 12 ,4 16..1 9..8 16 .8 13 .3 15..5 12,.5 1 1 .,6 14..3 16..4 15 .0 15..8 14 .0 MD 3 MS 10. 8 1 1 ..8 13 .6 12..2 13 ,.4 13 ,.1 1 1 .8 16,.4 17,.0 14 .5 18,.2 12 ,.9 13 .1 13 .5 12 .5 11 .9 11..7 13 .2 15,.8 15 ,.8 15 .3 15. 4 13 .7 13 .2 14 .0 12 ,.3 12 .7 12 .2 11,.8 13 .2 13 .4 12 .7 13 .1 11,.9 12 .6 13 .4 11 .0 13..8 12 .,4 15 ,.0 15 ,.7 13 .7 15 ,6 15..6 15,.3 15..1 12..2 13 .1 13 .0 11.,3 11, 8 13 ,.2 11..4 11,.3 13 .3 10 .8 11..3 12..0 12 .3 11.,7 13 .5 14 .4 12 .0 14 ,.6 12..9 12..1 12.,9 13 .4 12..9 14 .7 13 .2 14,.6 13,.1 11..4 16,.7 14 .5 15 .0 16 .1 16 .1 15 .1 14 .5 1 1 ..3 12..4 12 .4 1 1 ..5 11 .7 12 .2 1 1 .,7 9..3 10..9 10 .3 1 1 ,.1 1 1 ,.2 8..7 10.,5 14 .3 11.,7 13 .9 11.,1 11. 3 14 .1 13 .,2 11. 8 12..1 10.,6 14 ..4 15. 2 12..1 16.,5 MS 13 .4 12 .8 14 .0 11.,9 11. 5 12 .,5 10. 1 13 .,0 12..5 14 .4 1 1 .,6 10.,7 16..1 11..9 13 .2 10 .9 12,.4 14 ,.6 13 .7 11 .8 12,.6 10 .0 12,.8 15..4 14 .1 14 .2 15..8 12..2 13 .2 14 ,5 12,.1 10..2 15,.2 12,.3 12 .2 11 .9 12 .8 11 .1 8..1 14 .5 11 .1 13 .1 11 .9 9 .2 14 .3 15 .0 9 .9 12 .7 9 .1 13 .0 14 .4 8 .8 11 .2 15 .2 12 .1 12 .7 14..4 11 .6 12 .4 16 .3 12 .6 11 .7 12 .1 14 .0 9 .9 10 .2 15 .5 13 .6 15,.7 12 .1 13 .9 14 .0 14 .6 11,.0 12,.6 8 .0 12,.5 15,.4 10 .0 15 .1 14..6 12 .2 11..5 15.,6 12,.1 11,.5 16 ,.3 12 .5 12 .8 12 .5 15 .9 8 .4 10..0 12 ,.7 13.,3 11,.8 12..3 14 ,.4 15 .1 11,.6 9..6 10..7 14 ,.2 11 .9 12 ,.8 15..0 11,.8 12 .,7 16.,2 12,.3 11,.5 13.,1 12 .5 11..3 13 .0 15..1 9..9 10 ,.6 12 ,.0 15..0 12..8 13 .4 10 .1 9 .1 13 .2 14 ,.6 9 .7 13 ,.8 13 ..3 11,.6 12 ..7 15.,5 11.,9 12 ..6 11,.4 12 ,.6 12 ,.1 14 .4 1 1 .. 1 9..7 13 .9 12,.5 7 .1 12 .1 9 .8 9 .1 11,.8 16..1 9 .7 13,.3 15 ,.6 13 ,.3 12 .,3 14 .,8 11. 4 10..0 12 .0 11,.1 14 .9 11 .1 10..7 12 .5 14 .5 11 .9 FS 10,.7 11. 4 9..1 10. 6 13 .4 13..2 1 1 . 3 14 .4 FD 8 11 .0 12. 7 15 .,0 10,.9 12 .3 10..8 11. 5 12 .6 10. 8 10,.0 .FD 3 FM 3 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 15) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 301 PUP # RAT/ LITTER # 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13 93 9 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 1 2 3 4 56 8 9 10 11 12 13 14 15 16 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 8 13.4 8.3 12.7 9.7 9.4 7.2 10.7 10.2 10.8 13.6 12.6 11.0 13.2 9.7 9.0 9.2 11.3 11.3 11.3 10.3 12.1 12.5 12.9 14.1 NOT PREGNANT 8.0 9.5 11.4 12.8 9.4 11.2 12.5 12.9 13.3 MM 2 11.0 13.0 12.9 12.1 11.9 MD 8 13.5 MD 1 11.2 11.3 8.3 10.0 11.7 MD 3 12.7 MD 1 12.2 12.6 10.9 11.4 10.8 13.4 12.9 FM 2 10.7 10.4 12.2 11.9 10.8 11.7 MM 6 FM 2 11.5 12.4 7.8 MS 10.7 10.5 12.8 10.8 12.9 12.5 10.4 11.7 11.6 9.8 7.2 12.9 10.8 6.9 12.4 10.6 5.3 11.6 9.7 7.7 13.8 9.8 7.5 12.2 10.0 8.0 12.1 7.2 10.4 MD 8 MD 8 MD 6 6.4 12.1 12.6 11.8 8.5 6.8 11.4 12.0 10.7 12.0 13.0 12.1 12.1 12.3 12.0 12.3 11.2 7.8 8.0 MM 4 9.9 10.3 7.3 11.0 8.2 11.1 10.2 11.7 12.0 13.4 12.3 11.6 12.8 13.3 12.9 12.0 10.5 11.5 14.3 14.6 15.0 12.3 11.5 14.5 13.0 14.7 14.1 15.4 16.2 15.4 15.3 14.7 14.7 15.5 15.2 15.1 13.5 11.1 10.3 9.6 9.5 10.1 9.0 11.0 MD 2 9.8 9.8 13.3 13.7 13.7 13.4 12.1 12.3 12.6 12.7 12.9 12.4 13.3 11.8 12.4 12.3 11.6 12.7 10.5 12.5 11.6 12.0 14.1 12.1 12.3 13.7 14.3 14.1 14.5 14.1 13.4 13.5 12.0 14.1 14.8 14.0 13.1 9.0 14.3 13.3 14.5 14.5 17.4 20.0 18.0 17.4 15.2 13.7 17.8 10.3 11.1 9.1 MM 5 11.3 9.2 11.0 6.0 9.4 7.7 14.3 13.9 13.4 13.5 13.6 14.3 14.1 14.4 13.6 14.7 14.2 15.3 14.7 16.2 14.5 14.1 13.1 14.1 14.2 13.9 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 13.6 11.4 13.6 13.9 12.0 11.6 13.9 11.4 10.4 11.8 12.6 14.5 13.0 13.4 13.6 13.0 12.7 13.0 14.0 12.5 13.3 13.0 14.8 12.9 14.3 12.4 MS 13.0 14.8 12.4 12.1 10.1 13.0 8.1 12.2 11.4 11.7 9.0 6.9 12.0 10.8 8.9 12.5 14.6 14.5 10.5 12 .4 10.1 13.5 13.4 9.4 13.4 14.4 12.0 12.9 12.9 10.9 11.0 11.9 10.3 11.0 11.7 12.6 8.7 7.0 11.8 11.5 10.4 12.4 13.7 14.1 11.2 11.0 12.6 11.6 12.4 9.6 13.5 FM 3 12.7 FD 2 12.7 10.8 11.8 11.8 11.0 10.5 10.7 9.0 FD 6 11.2 10.4 8.1 11.7 12.0 13.5 9.7 13.5 10.5 13.3 11.8 14.4 12.2 FS 5.5 10.5 11.3 9.3 12.0 11.5 8.4 FD 6 10.8 11.7 8.7 14.2 14.0 10.1 12.2 11.2 FS 13.9 14.1 FS 6.9 10.2 10.7 11.3 12.0 9.9 FM 2 FM 6 11.5 13.9 10.1 FS 10.6 13.6 8.3 FD 7 9.8 9.9 10.9 13.1 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) , X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 17 18 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 1G) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 302 PUP # RAT/ LITTER # 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 15 28.6 30.0 29.2 29.0 27.6 30.3 29.1 31.6 30.8 31.4 29.8 31.4 33.1 30.6 27.0 23.0 23.6 21.3 21.1 23.1 22.6 MORIBUND SACRIFICED ON DAY 68 OF STUDY 28.3 29.4 28.5 27.5 28.9 29.9 26.8 26.1 23.1 23.3 25.3 24.3 MM 3 23.6 24.7 24.3 24.3 25.1 22.8 22.4 23.2 30.5 30.6 29.2 27.4 31.1 29.3 MS 27.8 29.2 26.1 30.0 29.0 28.2 27.2 31.7 29.6 32.1 31.2 MD 3 MS 29.2 NOT PREGNANT 28.2 28.6 26.0 26.6 26.7 27.8 27.7 33.9 31.4 32.7 33.2 29.7 33.0 30.9 22.6 23.8 23.3 25.3 24.6 24.9 21.9 21.6 20.6 21.3 20.8 21.9 19.8 20.5 21.6 20.6 19.2 19.5 19.2 15.5 16.3 25.5 23.3 23.9 22.0 24.9 24.1 24.0 20.8 17.6 20.4 18.8 20.6 16.5 15.5 22.1 22.3 20.4 19.1 MD 1 18.1 18.6 26.9 26.1 26.3 28.2 26.8 24.9 24.8 28.7 26.0 27.5 22.6 30.9 24.5 24.4 MX 8 MX 8 MX 8 FX 8 FX 8 FX 8 FX 8 32.3 32.4 34.3 33.6 32.3 34.6 31.8 25.8 27.0 28.9 20.3 25.3 26.2 23.8 24.8 24.7 23.8 24.1 22.6 24.5 25.2 22.3 21.5 20.5 16.4 21.9 19.3 23.2 27.9 23.9 25.7 27.4 23.3 26.2 27.1 25.6 21.8 25.3 28.0 26.5 20.0 24.4 25.2 25.0 23.3 23.8 23.0 23.6 24.3 23.1 23.2 22.7 24.2 21.6 22.8 21.4 28.0 28.1 24.4 26.0 22.8 17.7 30.6 28.7 31.8 27.1 30.5 23.1 21.6 19.6 23.6 17.0 20.5 25.5 26.1 FX 8 32.9 28.7 20.8 14.9 28.2 26.0 22.4 MS 28.6 31.0 23.2 29.6 27.1 25.2 29.2 29.1 29.1 26.2 30.7 18.3 19.9 16.2 21.8 16.6 20.3 24.9 23.1 FX 8 33.0 25.1 24.8 16.0 MM 2 22.3 20.5 23.0 27.7 FM 7 25.5 25.4 23.1 30.9 26.3 29.9 25.5 29.0 22.5 22.4 20.0 22.5 17.8 19.3 22.4 23.8 FX 8 26.2 24.3 16.6 25.8 24.6 23.3 24.3 32.3 21.4 27.8 25.6 23.2 29.1 25.0 31.3 25.7 32.6 20.7 22.6 16.8 23.1 17.8 20.1 26.7 27.1 FX 8 23.3 21.7 16.9 25.8 27.3 20.0 22.8 29.0 22.8 25.0 23.9 23.1 28.0 27.8 27.1 26.9 31.2 22.5 19.1 15.6 23.1 16.1 20.8 22.0 22.9 FX 8 26.8 24.8 18.9 25.6 24.4 18.6 21.7 29.3 23.2 24.5 24.6 25.3 27.9 27.0 29.5 26.9 UU 22.4 19.5 20.0 23.4 14.8 19.2 24.9 28.3 21.8 22.7 18.7 24.9 26.0 24.8 22.6 31.3 24.8 25.2 21.8 30.9 26.9 18.8 16.5 19.6 22.5 18.4 26.5 25.6 25.3 25.8 20.1 23.9 25.5 21.7 21.9 23.6 22.1 FD 1 23.3 21.5 14.7 FD 2 FM 4 23.9 24.6 23.3 17.9 25.4 22.8 24.7 23.3 20.4 UU FD 2 25.3 24.2 20.6 25.1 23.9 20.4 FM 2 25.4 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 18 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-G889.G) TABLE C37 (PAGE 17) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 303 PUP # RAT/ LITTER # 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 15 26.3 25.4 23.0 27.1 24.8 26.5 26.2 25.9 24.1 26.0 26.4 22.6 25.8 24.9 26.5 25.8 25.7 25.0 26.2 27.9 25.9 27.6 26.4 25.6 26.9 25.8 25.5 26.1 24.6 24.0 27.4 26.4 26.2 24.1 25.6 MORIBUND SACRIFICED ON DAY 59 OF STUDY 27.2 25.7 27.3 25.1 26.6 27.7 25.8 25.4 24.3 24.8 23.8 28.1 25.7 25.1 24.5 26.4 24.7 24.3 24.2 24.2 23.6 NOT PREGNANT 23.9 26.1 20.1 24.7 23.5 25.1 17.5 25.8 23.8 29.6 26.5 29.5 MD 7 23.0 24.4 22.7 23.7 24.0 23.9 22.1 25.0 19.6 25.6 22.9 20.2 22.0 20.0 21.6 29.6 27.5 30.0 27.9 28.7 22.7 28.3 23.4 22.8 23.9 23.4 25.2 24.1 20.7 29.9 32.2 33.0 MS MS MS MS 24.1 24.0 25.6 24.9 29.4 27.8 25.6 22.6 20.8 20.2 21.5 20.5 21.2 19.7 24.9 25.9 25.1 25.2 24.9 25.0 23.6 NOT PREGNANT MX11 MX11 MX11 MX11 MX11 MX11 MX11 21.1 22.6 24.5 24.5 18.9 23.3 21.2 21.3 19.6 21.0 20.7 19.2 20.9 18.6 29.2 30.8 29.1 28.8 28.6 27.3 28.5 22.9 20.1 23.0 21.0 20.6 19.4 20.5 27.4 27.3 26.7 28.2 26.5 24.4 27.4 25.5 21.7 24.5 23.6 24.9 24.2 21.8 22.0 23.6 23.7 22.4 22.3 22.2 19.5 24.2 24.0 22.2 24.8 23.5 23.7 22.7 26.4 27.2 26.6 26.6 23.5 24.0 24.9 23.2 25.6 22.6 22.0 20.4 28.6 23.1 32.6 28.8 22.6 24.2 MX11 19.9 17.9 27.6 21.4 25.3 19.8 21.9 22.9 26.6 24.0 24.2 24.6 25.7 24.2 24.8 24.8 20.8 24.4 21.3 19.5 30.1 21.3 31.6 24.3 22.5 22.8 FX11 21.4 22.2 25.6 19.9 26.1 21.2 22.2 22.3 26.1 27.0 25.1 26.8 24.7 25.6 23.7 17.4 23.4 24.4 23.1 18.9 28.8 22.2 29.7 25.7 21.7 24.9 FX11 21.5 19.6 30.4 16.5 27.7 21.6 23.0 22.2 22.0 27.0 22.4 24.6 20.2 25.2 24.3 23.6 FD 25.0 22.0 27.3 20.5 32.1 26.2 20.4 25.5 FX11 24.1 18.9 26.1 20.2 26.6 23.3 22.9 24.1 23.4 23.5 26.7 26.3 25.4 FS 13.9 25.0 UU 27.3 19.7 29.3 23.1 31.7 25.7 21.0 23.5 FX11 19.1 16.5 27.0 22.5 29.6 19.1 22.0 21.0 23.1 23.1 24.9 24.5 22.5 25.9 25.9 17.1 23.0 FS 24.4 22.1 FS 19.8 18.8 29.9 19.4 26.7 22.9 22.8 23.9 22.6 22.0 24.8 22.0 24.2 22.7 FM 2 FS 23.3 19.0 22.4 17.5 26.5 15.5 26.2 23.9 22.6 24.6 FM 3 26.2 24.6 18.3 FS 27.9 21.1 19.0 18.7 FD 5 20.2 FS 21.3 FD11 21.9 22.0 23.2 17.6 25.8 19.2 18.7 18.5 FD 1 17.3 24.7 27.7 FD 3 23.9 FD 8 18.7 19.0 23.7 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 18) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 304 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 15 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 28.3 28.0 24.8 26.9 25.6 24.5 28.6 PREGNANT; DID NOT DELIVER A LITTER 21.7 22.6 22.2 21.7 21.6 19.8 22.1 40.5 40.3 36.3 38.2 38.1 38.2 FS 18.1 20.2 17.2 19.6 18.9 19.5 19.7 23.2 26.8 21.0 24.7 21.5 14.4 23.9 21.7 20.2 21.8 22.2 17.9 20.2 21.3 27.2 27.3 25.1 27.7 29.5 20.5 24.1 21.4 20.2 19.6 22.1 19.5 21.1 21.3 29.1 26.7 25.4 30.8 25.7 31.1 30.3 19.1 18.5 21.0 20.2 MD 3 20.2 18.8 22.9 22.4 20.3 20.3 22.6 23.2 20.1 19.9 23.9 29.6 20.1 25.8 26.3 24.4 31.8 31.8 32.2 32.3 32.4 25.9 29.9 24.4 24.4 25.9 27.5 28.9 18.9 28.9 31.2 31.8 30.8 28.7 29.2 28.8 30.1 29.8 29.9 29.8 32.5 30.0 29.1 28.9 30.4 32.0 33.8 32.8 31.7 32.6 30.0 32.6 32.5 32.0 31.6 28.8 33.0 31.0 30.7 29.8 32.0 29.7 30.2 32.4 28.0 29.8 31.1 30.1 28.6 27.9 28.5 28.4 27.8 27.5 25.1 27.2 25.9 29.4 24.6 28.1 23.6 30.6 24.7 28.3 29.6 25.2 32.3 29.1 30.8 26.1 23.1 28.0 30.2 33.1 34.6 32.0 25.5 27.5 25.7 26.0 25.2 25.4 25.4 31.4 31.7 31.8 31.2 34.0 33.8 32.6 25.3 24.9 22.0 21.7 23.8 21.7 21.4 25.8 25.7 24.8 24.9 25.8 28.7 27.0 26.9 25.6 25.4 24.3 26.5 12.8 22.4 28.1 22.5 MD 1 MD15 MD 7 26.4 20.8 24.4 18.4 21.2 16.3 29.0 24.4 29.7 27.3 31.7 31.2 24.8 29.5 28.0 26.5 27.5 24.7 31.5 22.1 27.7 24.0 28.0 23.1 17.5 25.9 MD 6 26.0 21.0 20.3 19.5 20.6 28.2 22.5 29.7 28.0 31.8 31.4 28.4 28.2 28.3 26.2 28.5 25.3 29.3 24.0 26.8 27.7 24.0 20.6 18.9 23.3 MS 26.4 15.2 20.3 20.1 26.0 27.1 22.4 28.8 27.3 33.1 30.0 30.8 28.7 30.5 28.5 21.9 32.3 24.1 25.6 26.8 22.5 20.0 19.1 21.7 26.4 15.4 20.1 19.5 24.1 26.7 26.9 25.5 26.6 29.3 29.2 29.6 22.8 29.2 17.2 25.3 29.0 19.8 24.9 25.6 22.1 15.3 10.4 21.1 27.2 18.6 17.0 22.6 25.2 28.6 19.8 29.9 26.2 31.3 23.7 29.4 25.0 22.9 25.1 25.6 23.6 18.8 19.7 20.0 24.7 15.1 17.0 21.2 24.9 30.3 26.5 30.4 26.7 30.1 30.2 27.4 20.5 26.8 27.0 22.3 18.8 22.7 20.8 26.3 18.6 FM 7 19.9 24.5 27.8 22.3 FS FS 25.0 23.4 23.8 22.7 2,6.6 21.7 19.8 26.7 22.3 23.1 19.5 FD 4 21.9 26.2 28.0 25.6 FD 1 29.1 FD 1 FS 24.6 26.6 FM 3 20.2 24.5 FD 6 26.9 FD 4 19.3 24.7 28.9 25.7 FD 3 24.3 17.7 20.3 17.2 FM 4 FD 2 FD 8 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 19) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 305 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 15 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 31. 0 32. 3 30. 0 28. 7 MS 29. 3 29. 7 27. 8 26. 1 24 .0 26. 8 23 .0 24 .6 25. 3 27. 5 26. 5 28. 6 25. 3 29. 1 25. 7 25 .9 26. 3 26. 1 24 .0 25. 0 28. 6 24 .0 MM 4 28. 6 28. 3 12. 7 22. 4 28. 2 28. 6 24 .1 27. 9 23. 9 25. 8 27. 5 27. 5 23. 6 24. 4 30. 2 30. 8 27.,9 30. 0 32. 2 28. 0 26. 9 22. 1 18. 2 21. 6 25. 3 21. 1 23 .5 24 .4 22. 7 22. 4 21. 8 22. 6 20. 8 20. 0 19.,1 NOT PREGNANT; MATING NOT CONFIRMED 21. 9 23.,1 20.,0 23 .8 23. 1 21.,9 21..7 26.,9 27. 8 26..6 24 .9 26.,1 28. 6 25.,7 27. 8 26. 4 26..8 22,.8 21,.8 25,,6 28..0 20..8 20..2 21,.5 15.,2 22 .1 20. 4 17..8 23..9 28..2 27,.5 27.,1 19..7 21..7 23 .7 32 .2 31..2 30 .1 28,.4 30,.6 MD 3 MS 18,.7 17,.7 18 .0 16 .0 20,.7 18.,3 19.,5 35 .1 37 .5 33 .1 38 .8 25 .0 24 .7 23 .3 23 ,1 24 .9 25 ,.2 23 ,.3 23 .6 20 .0 23 .8 22 .0 22 .1 21 .0 22 .1 28 .9 27 .7 25 .6 27 .3 27 .0 26,.0 24..2 25 .9 26 .1 24 .2 25 .6 24 .2 25 .9 29 .0 30 .7 29 .3 28 .4 27 .7 29 .9 28 .3 29 .6 22 .1 25 .2 20 .1 25 .1 22 .5 21 .8 25 .7 22 .5 19 .3 24 .8 21 .6 22 .4 22 .6 22 .7 29 .3 24 .7 26 .3 25 .4 27 .5 30 .4 29 .5 28 .2 25 .8 30 .2 28 .2 25 .8 30 .0 25 .1 31 .9 30 .3 26 .5 27 .2 29 .2 26 .4 28 .4 22 .8 24 .4 24 .9 23 .1 23 .4 25 .2 22 .3 17 .3 17 .9 17 .4 14 .1 17 .5 17 .4 MD 9 29. 0 23. 6 27. 0 23. 8 25. 4 25. 5 30. 5 19. 2 19. 3 19. 4 23. 7 26..1 20.,7 23 .,0 MS 18 .1 25.,1 24,.0 25..7 24 .5 32,.2 25 .5 18 .6 26 .0 28 .4 20 .0 11 .9 28. 0 24. 4 24. 4 24. 3 19. 2 25. 6 29. 0 22. 6 20. 4 15. 6 25. 4 25..8 18.,2 26..2 27..3 19.,1 24 .1 24 ,.3 25,.4 23 .3 26,.0 21 .8 24 .6 23 .7 26 .9 18 .1 16 .8 30. 2 24 .0 23 .3 24. 3 28.,0 26. 0 27 ..1 20..2 19.,9 18..8 23 ..4 26,.4 17..2 23 .6 29,.8 20 .2 21..6 25 .0 26 .5 21 .8 30 .8 22 .2 21 .3 21 .2 28 .0 24 .7 16 .4 28. 7 25. 0 27. 8 25. 1 28. 3 21. 2 27. 8 20. 8 21.,9 22. 6 25. 6 24..3 20.,3 21,.4 30.,9 17 ,.9 22 .7 22 ,.3 25,.5 25,.1 25,.9 21 .9 20 .2 26 .1 27 .3 18 .8 16 .1 23. 0 23. 7 17. 6 26. 7 26. 9 28. 6 21. 6 22.,6 24. 5 26.,8 13.,6 22.,5 29..9 19,.0 22 .,7 24 .4 25 ,.0 25..1 26,.5 20 .2 21 .8 22 .1 26 .7 22 .3 15 .0 25. 8 26. 3 23. 3 25. 7 21. 1 20..3 23 .8 28..8 16.,7 22 .7 30..4 16 ,.9 21..8 22 ,.4 25..7 30..0 25 .8 21 .0 25 .6 27 .2 23 .6 15 .1 25. 4 24. 3 23 .4 26. 2 19..1 19..0 24 .4 22..9 18.,5 25,.2 31,.6 18..6 24..8 22,.5 25..5 23 .8 22 .2 23 .4 24 .3 24 .7 FD 9 25. 0 27. 6 25. 4 FS 18. 4 23 .0 20. 0 FD 7 20. 3 27 .,0 25. 9 32. 2 FD 8 17 .,0 19. 9 24 .1 22,.8 24 .3 20,.9 21. 3 25 .8 24 .9 FD 9 FD 3 FD 3 23 .2 21 .9 FM 3 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 20) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 306 PUP # RAT/ LITTER # 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13 943 13944 13945 13946 13947 13948 13949 13950 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 15 26.3 16.4 28.0 26.7 25.6 26.4 26.9 13.7 MM 6 24.7 23.0 21.3 22.8 23.8 20.8 23.9 23.8 21.1 21.1 18.3 21.9 24.5 MM 2 MD 1 MD 1 20.7 21.0 20.0 20.6 25.3 17.8 FM 2 19.5 20.9 FM 2 20.0 23.5 20.7 23.2 18.3 21.1 18.8 25.3 13.9 24.5 14.7 15.2 21.0 22.5 24.9 23.9 23.8 23.8 24.1 22.3 23.8 19.9 MS 22.9 15.9 15.6 15.1 13.8 17.1 14.5 15.0 15.3 14.3 16.5 26.7 26.8 27.7 26.4 MD 8 MD 3 26.8 25.8 24.6 24.7 NOT PREGNANT 20.6 19.4 20.4 13.9 19.6 20.8 19.1 20.2 MD 8 19.3 18.2 19.9 15.9 11.9 19.8 17.2 MD 8 MD 6 17.2 16.7 23.4 22.0 23.6 22.7 22.8 23.9 22.9 22.4 21.2 22.8 18.2 18.5 16.1 15.4 18.0 15.5 16.7 17.6 16.3 16.8 15.4 MM12 MM 4 24.2 20.9 23.1 25.4 15.1 21.0 14.5 22.0 20.7 24.1 19.7 22.1 22.8 22.6 20.2 14.9 21.8 26.5 27.1 27.0 22.9 26.2 25.6 23.0 26.2 26.2 22.6 26.8 26.6 26.2 24.9 25.3 26.0 26.9 22.9 24.5 21.8 17.5 16.9 14.3 18.8 17.5 17.9 16.3 MD 2 16.8 17.0 27.0 24.1 26.1 26.5 24.5 24.0 26.7 23.6 24.6 25.6 22.8 23.6 25.8 22.8 21.9 23.7 23.0 21.6 21.1 19.8 25.7 25.7 24.2 25.8 23.4 24.0 24.9 22.9 25.4 19.9 23.2 22.8 26.2 28.1 25.0 24.5 25.9 26.5 25.8 20.8 37.1 35.9 36.8 40.5 36.6 31.0 34.3 20.4 24.1 22.1 MM 5 21.6 24.3 20.7 24.9 20.9 16.5 25.2 25.3 25.3 26.3 26.4 25.4 25.0 25.9 26.4 24.1 31.8 30.4 29.8 29.3 28.6 28.4 28.2 27.7 27.9 27.6 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 27.1 28.1 27.9 27.6 24.6 25.5 24.4 25.4 24.9 27.1 27.0 28.2 27.0 28.2 27.4 27.1 27.8 28.4 29.4 27.5 28.9 28.6 28.4 30.3 25.7 27.5 MS 26.9 26.1 27.0 23.8 19.7 21.3 23.2 23.5 14.6 23.8 19.6 14.9 20.8 19.3 13.0 19.4 23.2 24.7 17.2 23.4 22.2 23.5 16.4 21.4 25.5 26.8 23.1 27.3 29.0 25.6 20.1 22.6 23.7 23.1 14.7 23.6 16.5 17.5 23.3 17.7 18.1 22.5 22.9 22.7 17.7 24.9 22.7 24.2 23.6 FM10 24.3 FM 3 27.3 FD 2 10.0 19.1 24.4 22.4 24.6 13.7 27.6 19.0 FD 6 23.0 18.1 20.3 23.0 23.4 24.0 17.6 22.3 18.4 23.4 22.8 25.3 26.7 FS 13.1 17.1 19.0 21.1 12.8 21.7 19.6 FD 6 22.2 24.6 21.8 25.3 24.9 17.7 24.7 20.7 FS 27.2 27.1 FS 25.5 19.3 23.0 12.6 25.0 18.4 FM 2 FM 6 22.1 25.8 16.7 FS 22.4 20.3 15.5 FD 7 26.1 19.6 15.9 23.0 23.1 FD 6 FM 5 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 21) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 307 PUP tt RAT/ LITTER # 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 22 45.0 44.6 47.5 45.2 40.6 42.5 44.3 44.3 45.4 43.0 43.1 46.5 40.5 44.7 43.9 40.0 40.7 40.6 48.3 38.8 42.1 MORIBUND SACRIFICED ON DAY 68 OF STUDY 48.1 44.9 46.6 46.3 45.3 43.2 41.0 32.7 35.4 32.1 35.0 34.4 MM 3 34.2 27.4 26.4 26.8 20.1 25.4 26.5 26.2 40.9 41.1 42.8 36.6 39.5 44.4 MS 32.2 38.5 36.9 35.9 34.6 36.5 37.3 48.3 45.4 43.4 45.1 MD 3 MS 43.5 NOT PREGNANT 43.2 42.0 41.4 44.7 41.9 42.5 44.9 43.9 40.1 44.2 45.2 45.8 44.0 39.5 37.1 31.8 36.4 35.3 38.8 35.5 32.7 36.2 33.4 32.8 33.8 32.2 33.5 31.7 32.8 32.2 31.8 34.4 34.4 25.6 32.5 36.0 36.2 39.9 37.9 41.0 37.5 36.7 31.9 24.3 27.1 31.8 28.1 31.2 28.9 31.7 29.1 30.6 30.6 MD 1 30.0 29.8 27.2 25.0 26.1 27.8 27.7 20.8 23.4 36.4 43.0 48.9 40.6 35.0 36.9 44.7 MX 8 MX 8 MX 8 FX 8 FX 8 FX 8 FX 8 57.2 53.3 52.0 53.4 52.9 53.0 54.1 31.7 49.1 40.5 43.7 40.7 41.7 37.0 36.1 34.9 29.1 35.9 34.6 32.7 36.1 26.4 34.9 32.0 27.7 31.8 33.3 35.2 42.5 40.3 39.8 45.0 37.9 42.4 42.9 39.3 35.8 47.0 42.2 42.0 40.8 41.1 42.8 42.0 45.5 40.6 39.0 38.2 40.8 38.5 34.6 35.3 36.7 35.0 33.2 35.4 46.3 43.5 36.9 43.0 32.4 26.1 39.8 35.3 41.2 40.7 46.4 33.2 31.6 27.9 40.7 25.8 27.8 21.8 38.7 FX 8 55.1 38.4 34.3 35.1 43.7 35.8 40.6 MS 44.1 37.3 44.5 38.3 33.4 24.8 42.2 37.3 45.3 48.6 43.1 31.9 30.8 30.9 33.3 28.5 27.8 25.7 35.1 FX 8 51.3 37.0 32.9 23.6 MM 2 40.7 32.8 32.9 41.3 FM 7 45.2 36.4 23.5 36.4 34.5 41.4 39.6 40.6 34.1 32.4 27.3 39.7 26.0 29.9 36.4 40.6 FX 8 33.3 31.1 28.8 41.1 32.5 42.4 35.8 44.9 42.5 39.0 32.8 26.0 37.7 36.2 43.1 41.5 42.9 26.9 34.9 29.1 36.7 27.3 26.4 32.1 43.1 FX 8 37.6 37.4 27.8 42.1 40.2 42.5 36.9 42.1 42.0 40.0 35.5 24.8 43.2 32.4 41.7 42.4 46.6 36.5 28.4 27.1 38.2 26.5 29.6 34.2 39.2 FX 8 41.1 35.6 33.9 37.5 42.7 33.5 38.0 44.4 41.9 43.4 31.4 23.4 41.8 33.8 41.6 40.1 UU 32.9 34.0 32.4 37.1 24.6 29.8 33.4 39.6 41.2 36.4 27.2 40.6 39.6 36.5 34.2 41.6 39.7 33.7 27.3 43.5 42.4 32.5 31.3 30.4 36.8 26.6 32.8 35.7 40.2 33.4 29.9 41.2 40.2 32.7 38.9 35.3 25.2 FD 1 34.5 26.5 29.9 FD 2 FM 4 39.7 38.8 34.6 30.1 38.3 38.4 36.2 22.3 26.6 UU FD 2 37.5 43.7 28.0 39.7 36.6 25.8 FM 2 36.4 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 18 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 22) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 308 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 22 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 39.4 36.2 30.8 33.6 34.3 32.1 41.4 40.3 45.0 43.3 42.3 45.2 46.0 37.6 50.2 40.0 40.9 43.0 40.5 43.7 39.1 36.2 40.5 34.5 38.0 37.3 34.0 31.8 36.7 35.2 36.9 33.0 35.7 37.8 34.4 MORIBUND SACRIFICED ON DAY 59 OF STUDY 37.8 39.4 41.1 38.5 41.1 36.1 41.6 36.0 41.6 37.8 33.3 37.6 32.8 38.0 37.0 36.1 32.6 37.5 34.0 39.3 40.0 NOT PREGNANT 46.5 45.2 36.3 38.8 41.4 37.0 33.0 37.2 43.4 39.0 43.4 39.4 MD 7 34.2 35.1 33.2 35.3 34.6 34.3 33.7 30.1 42.9 32.0 33.6 34.5 37.3 32.0 30.1 45.3 33.8 45.1 42.7 42.7 48.4 43.6 36.2 37.2 35.7 31.2 35.1 35.3 36.3 55.0 51.4 55.4 MS MS MS MS 39.3 43.8 43.3 40.9 43.2 43.1 42.7 27.5 26.5 23.7 25.3 26.3 28.1 25.5 37.4 37.7 38.4 39.0 37.3 38.5 33.8 NOT PREGNANT MX11 MX11 MX11 MX11 MX11 MX11 MX11 33.4 37.8 32.2 32.9 31.4 35.0 33.7 30.1 26.5 35.2 28.8 29.6 29.5 29.6 40.2 38.9 34.0 42.0 39.5 38.8 39.3 32.9 31.6 29.8 38.6 32.7 33.6 33.0 39.6 44.1 43.9 44.2 42.7 41.2 38.6 30.5 35.3 33.8 33.2 35.2 32.7 31.3 37.4 40.3 39.6 40.1 43.4 41.5 40.1 33.9 36.6 39.5 37.3 37.5 35.4 36.1 33.6 35.3 38.8 37.7 30.4 37.6 36.6 39.0 44.3 33.7 34.0 30.5 44.5 31.0 56.6 39.2 24.3 35.6 MX11 28.3 25.9 39.4 35.5 42.3 34.6 35.9 39.0 30.6 40.1 40.7 32.4 35.6 37.6 21.7 22.0 39.5 37.2 30.6 26.9 43.3 35.8 50.4 49.5 25.6 38.0 FX11 29.7 30.8 40.4 34.0 41.4 32.1 39.0 35.4 32.6 43.4 39.9 41.2 30.5 38.1 35.0 32.7 42.2 37.1 33.5 26.5 40.4 28.8 52.7 45.0 28.4 34.6 FX11 32.4 29.2 37.0 22.7 41.5 33.6 42.7 38.7 35.6 39.8 43.7 34.3 33.5 34.9 35.8 31.9 FD 39.2 29.7 45.6 32.9 53.5 37.9 27.6 33.4 FX11 32.8 29.7 36.7 31.1 39.8 30.6 38.5 38.3 33.1 44.0 36.0 36.7 31.1 FS 34.7 33.0 UU 37.7 34.8 42.8 33.7 52.5 43.1 29.6 33.8 FX11 34.1 30.3 39.9 25.6 38.4 30.7 38.3 35.9 36.5 37.0 40.0 37.7 37.3 33.0 37.2 28.4 34.1 FS 40.6 26.7 FS 29.8 23.8 39.6 29.9 41.8 33.2 38.6 37.0 32.6 35.5 41.8 28.7 34.9 27.6 FM 2 FS 41.1 23.6 28.1 29.0 40.8 36.0 38.3 35.7 40.7 32.6 FM 3 35.7 36.0 27.8 FS 38.4 24.9 27.5 25.4 FD 5 31.8 FS 36.4 FD11 28.7 31.0 34.6 28.4 38.6 25.3 27.1 27.3 FD 1 23.6 36.2 36.7 FD 3 37.7 FD 8 30.0 27.1 32.3 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE C37 (PAGE 23) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 309 PUP # RAT/ LITTER # 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 22 32.8 33.1 32.0 36.5 36.2 36.8 36.0 PREGNANT; DID NOT DELIVER A LITTER 32.2 30.8 32.5 32.1 33.0 30.3 33.9 57.8 60.2 61.1 59.3 61.5 59.8 FS 26.9 29.5 30.9 30.4 28.5 31.9 31.4 18.1 35.8 36.3 39.3 33.8 43.5 39.1 26.2 30.2 28.0 29.4 29.9 31.2 30.9 37.6 33.8 26.6 37.4 34.5 35.6 34.3 27.0 33.3 29.7 31.7 33.7 33.0 34.8 41.6 37.7 36.3 44.6 37.7 44.4 42.3 26.9 26.1 32.3 26.8 MD 3 31.4 23.6 30.7 34.1 27.8 29.5 29.8 30.8 32.2 39.1 24.5 29.8 35.3 31.0 39.5 41.9 49.1 50.0 48.5 51.3 54.7 44.0 43.4 41.2 33.0 35.3 28.9 38.1 37.3 44.4 49.0 50.3 47.2 50.2 47.0 45.3 48.1 48.5 47.2 43.9 45.8 46.7 45.6 46.0 48.9 48.8 52.3 51.8 42.4 48.0 52.3 48.7 50.2 48.0 46.1 48.8 48.8 51.6 45.0 40.0 44.8 47.6 49.9 52.6 47.1 41.4 40.1 39.1 39.1 37.7 40.9 40.8 37.6 44.0 37.4 39.3 42.2 43.9 46.3 43.6 47.3 48.0 41.9 45.9 44.4 52.9 36.4 51.3 42.3 43.5 39.9 46.1 27.4 55.5 51.5 53.5 43.9 38.8 40.3 44.3 42.4 47.9 42.6 47.7 49.9 52.4 51.7 53.8 50.4 50.0 36.3 36.5 31.4 30.7 29.7 29.6 30.2 35.4 34.4 32.2 34.1 35.8 34.1 36.9 43.1 39.0 20.4 31.1 42.3 40.5 42.5 33.8 32.0 34.3 30.5 MD 1 MD15 MD 7 35.2 23.2 35.5 29.9 33.7 39.4 42.5 40.1 41.1 42.2 46.7 47.9 52.8 37.2 43.3 48.0 43.1 26.2 10.4 MD 6 33.0 29.8 26.6 30.6 40.1 40.6 31.8 47.0 32.9 45.2 48.9 55.2 37.6 41.6 3B.2 41.9 40.6 50.7 31.3 38.9 38.8 44.2 45.3 25.9 35.0 42.0 35.2 28.6 27.7 38.6 MS 32.8 24.1 27.9 33.4 35.6 47.0 31.0 45.0 41.2 47.7 52.0 36.3 40.5 45.8 44.0 41.0 50.3 34.2 39.1 38.2 30.2 30.3 27.6 30.0 33.3 27.2 29.4 27.0 36.8 50.1 39.9 48.7 42.5 47.4 42.9 38.8 34.1 51.4 40.9 41.4 46.3 32.7 32.1 35.6 27.3 28.6 30.3 27.7 34.9 29.0 29.1 27.6 28.3 46.1 40.7 46.4 43.7 47.4 34.8 51.4 33.9 30.7 35.1 38.6 34.6 25.3 37.9 28.2 34.5 31.6 FD20 27.7 36.8 46.0 44.4 47.2 47.4 49.3 44.5 42.3 29.7 31.7 42.0 33.0 31.5 FM 3 30.7 34.0 28.2 32.1 33.9 30.8 38.3 31.6 35.6 22.7 31.5 32.4 FD 6 35.0 FD 4 FM 7 30.1 34.0 42.2 33.5 FS FS FD 4 30.0 34.3 42.6 42.9 FD 1 26.7 37.2 45.1 35.0 37.3 45.1 FD 3 47.6 FD 1 32.5 32.3 38.9 FS 32.4 29.6 44.0 - 29.8 35.8 27.1 FM 4 FD 2 FD 8 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 24) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 310 PUP # RAT/ LITTER # 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 22 47.8 51.6 49.0 46.0 MS 47.2 44.1 36.8 38.7 35.3 41.1 44.3 39.5 38.5 44.1 39.1 46.4 46.1 42.2 42.5 40.9 40.2 36.9 35.9 46.0 34.9 36.9 MM 4 40.1 30.3 33.0 22.7 41.0 42.2 43.6 44.5 41.7 39.8 44.3 40.7 37.6 40.6 44.9 48.6 48.5 48.8 44.4 45.6 41.0 23.7 33.2 27.9 28.9 32.9 29.0 33.6 32.4 35.1 34.4 32.8 37.1 36.9 32.5 NOT PREGNANT; MATING NOT CONFIRMED 28.3 30.6 35.5 29.3 30.7 34.7 32.7 39.7 43.3 42.2 44.3 41.9 41.5 43.7 39.6 40.4 38.8 42.3 42.0 40.9 36.4 28.1 31.3 38.9 35.6 36.9 36.2 34.0 38.4 29.2 44.2 42.3 36.1 44.8 36.6 49.8 47 .4 50.3 48.1 45.9 MD 3 MS 26.7 30.9 23.2 26.4 30.4 28.3 25.7 51.3 59.5 59.5 50.5 36.1 42.5 37.3 41.4 39.8 38.4 39.1 32.3 39.5 36.0 36.2 35.8 40.9 36.6 39.0 43.4 43.4 40.3 42.5 46.3 41.3 39.3 35.7 39.7 43.6 40.0 38.4 39.9 43.2 44.8 46.2 44.1 46.9 47.0 45.9 29.3 35.9 29.8 34.4 29.3 33.3 33.4 27.8 39.5 31.8 36.6 37.0 34.9 41.6 40.7 47.2 43.2 39.7 49.3 46.0 44.9 41.3 44.3 46.2 40.8 48.0 41.5 43.6 46.7 40.0 45.3 46.3 44.8 40.5 37.1 38.2 39.6 40.0 39.6 38.1 38.4 30.2 26.9 32.5 32.3 33.6 32.6 33.1 MD 9 46.1 37.9 41.2 26.9 39.2 39.0 42.2 25.1 32.2 30.8 42.6 46.4 37.3 32.2 MS 28.1 41.8 38.0 43.3 40.8 48.2 34.4 38.6 42.6 43.1 29.7 32.2 45.5 37.8 38.7 37.0 43.8 37.1 45.5 24.0 30.5 22.5 31.9 42.4 37.4 34.9 46.3 30.3 33.6 35.3 40.7 36.8 37.2 32.2 38.5 32.8 41.7 32.9 23.7 47.8 36.3 44.0 37.3 45.5 33.9 42.3 28.5 35.8 28.4 40.1 41.8 26.9 34.9 43.0 29.2 41.4 35.3 39.8 38.7 40.8 30.6 33.4 40.5 43.5 40.2 29.9 43.8 37.8 37.8 35.7 41.3 37.4 43.1 25.4 31.7 25.9 40.2 44.1 36.3 33.5 48.3 26.9 37.1 36.1 43.0 37.4 41.0 28.9 37.8 40.2 38.4 41.9 30.9 35.7 42.0 38.9 39.9 41.0 44.1 28.1 31.8 38.8 44.7 30.3 34.2 50.1 25.4 39.2 38.0 40.9 35.3 49.6 35.0 33.8 37.6 42.7 36.1 31.7 37.4 43.4 34.2 39.6 29.9 29.5 39.6 38.4 31.5 41.0 46.5 31.6 35.6 38.0 37.1 42.6 26.5 35.8 39.6 39.1 37.3 31.5 36.5 37.0 34.5 40.0 36.7 43.5 37.3 FS 29.6 28.1 29.0 FD 3 32.8 42.3 32.4 32.3 37.0 52.1 28.5 27.6 37.9 41.0 50.5 25.9 FD 7 41.6 FD 8 23.4 38.7 41.2 39.0 38.9 37.0 32.2 32.7 32.1 35.0 34.9 29.3 33.3 37.4 38.9 41.6 41.3 37.4 FD 9 FD 9 . FD 3 FM 3 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C37 (PAGE 25) : PUP BODY WEIGHTS PROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 311 PUP # RAT/ LITTER # 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 10 11 12 13 14 15 16 17 18 DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 22 41.8 27.6 23.2 42.0 40.9 40.4 31.5 33.4 33.5 33.5 32.3 30.2 32.9 31.0 40.8 34.6 33.2 33.3 25.3 27.1 23.9 42.1 40.7 40.3 NOT PREGNANT 46.1 32.8 33.0 29.8 40.8 30.0 22.3 43.1 47.0 MM 2 31.9 28.6 31.0 32.3 24.0 MD 8 45.6 MD 1 31.6 34.5 23.0 34.4 25.4 MD 3 46.5 MD 1 33.6 34.3 24.0 30.9 25.7 43.2 42.1 FM 2 29.6 34.3 36.7 34.0 18.9 36.8 MM 6 FM 2 28.4 37.2 26.2 MS 20.6 34.7 40.7 29.4 35.4 37.2 32.3 24.7 38.2 19.3 19.9 31.3 27.9 29.4 31.6 38.2 24.2 28.3 33.4 26.7 MM12 30.7 45.2 25.6 24.9 34.9 25.5 MM 4 36.1 38.0 26.4 29.3 36.5 29.6 24.9 34.3 37.6 27.3 26.3 31.5 32.6 27.3 36.3 44.1 25.2 27.7 33.1 27.5 35.7 33.4 38.5 25.1 MD 8 33.6 26.7 26.8 32.9 44.3 25.3 MD 6 32.7 27.6 33.3 30.4 42.4 MD 8 25.2 31.0 24.6 33.9 21.5 42.6 25.2 26.2 32.7 29.8 35.2 33.4 39.4 40.0 21.7 42.1 35.7 42.1 40.7 41.2 28.0 42.4 34.0 38.5 24.3 44.9 29.2 38.4 30.0 36.8 35.7 43.5 25.3 40.1 30.2 38.5 32.6 41.5 28.9 38.1 31.0 39.8 38.9 39.0 30.0 44.3 32.0 42.4 39.3 40.0 26.1 44.3 26.8 41.4 38.0 42.8 MD 2 41.1 28.7 39.6 35.5 38.6 31.4 37.6 26.2 35.9 34.3 40.4 25.9 41.6 27.3 31.9 40.0 57.5 57.2 46.9 61.7 51.9 53.6 56.4 35.1 39.7 37.2 MM 5 27.9 34.1 36.5 34.7 37.3 38.3 37.6 38.7 41.5 38.7 39.0 39.7 39.5 39.3 40.0 40.0 43.2 44.1 46.2 44.5 45.8 40.9 43.1 41.7 43.1 42.3 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 48.4 40.2 46.1 43.4 44.8 39.9 39.9 41.7 37.1 41.9 44.2 40.8 40.9 42.9 43.0 42.3 41.5 43.6 40.9 42.2 44.1 40.7 47.3 44.2 47.5 47.4 MS 45.4 44.7 42.0 13.6 30.7 25.2 38.2 34.9 27.6 38.4 21.4 26.4 31.2 26.9 30.6 31.3 43.2 42.0 26.4 38.8 31.8 36.3 39.9 34.6 39.3 43.2 42.4 40.1 46.6 19.5 30.7 30.7 32.8 28.7 22.5 40.7 21.3 24.9 33.7 30.0 38.5 35.6 35.2 40.4 27.3 39.6 30.7 35.2 30.4 FM10 37.0 FM 3 39.9 FD 2 40.6 30.3 32.3 34.7 31.9 22.5 36.6 25.2 FD 6 33.1 27.6 33.7 33.5 40.4 38.1 26.0 38.5 31.0 37.1 36.1 42.8 38.3 FS 41.7 32.5 26.1 31.2 23.4 37.7 24.9 FD 6 33.9 38.1 35.7 36.4 41.3 28.1 42.0 27.2 FS 35.5 38.0 FS 43.9 34.3 32.8 25.3 38.8 20.5 FM 2 FM 6 34.7 39.9 26.0 FS 32.1 40.1 32.6 FD 7 37.6 24.3 29.5 35.4 27.9 FD 6 FM 5 ALL WEIGHTS WERE RECORDED IN GRAMS (G) MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C38 (PAGE 1) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 312 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY 13801 M A M A M A M A F A F A F A F A F A 13802 13803 13804 M A M A M A M A M A M A MA M A FA FA FA FA FA FA M A M A M A M A M A M A F A F A F A FM 7 F A F A F A F A F A F A MORIBUND SACRIFICED ON DAY 68 OF STUDY 13805 13806 13807 13808 M A M A M A MA M A M A FA FA FA FA FA FA FA M A M A M A M A M A MM 3 F A F A F A F A F A F A F A F A F A F A F A M A M A MA MA M A MA MA MA FA FA FA FA FA FA FA FA FA M A MA MA MA MA MA MS FA FA FA FA FA FA 13809 M A M A M A M A M A M A M A M A M A F A F A F A F A 13810 M A M A M A M A MD 3 M S F A F A F A F A F A F A F A F A FD 1 13811 NOT PREGNANT 13812 M A M A M A M A M A M A M A M A M A F A F A F A F A F A 13813 M A M A M A M A M A F A F A F A F A F A F A F A U U 13814 13815 M A M A M A M A M A M A M A M A M A M A M A F A F A FA FA FAFM2 M A M A M A M A M A M A M A M A M A M A F A F A F A FA FA 13816 M A M A M A M A M A F A F A F A F A F A F A F A F A F A F A U U 13817 M A M A M A M A M A M A M A M A F A F A F A F A F A F A FD 2 13818 M A M A M A M A M A M A M A M A F A F A F A F A F A F A FM 4 FD 2 13819 M A M A M A M A MD 1 F A F A F A F A F A F A F A F A 13820 M A M A M A M A M A F A F A F A F A F A F A F A F A F A 13821 M A M A M A M A M A M A M A M A F A F A F A F A F A F A F A F A F A 13822 MX 8 MX 8 MX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 13823 M A M A M A M A F A F A F A F A F A 13824 M A M A M A M A M A M A M A M A F A F A F A F A F A F A F A F A 13825 M A M A F A F A F A F A F A F A F A F A F A F A F A F A F A 13826 M A M A M A M A M A M A M A M A F A F A F A F A F A F A F A F A 13827 M A M A M A M A M A M A M A M A MM 2 M A F A F A F A F A F A F A 13828 M A M A M A M A M A F A F A F A F A F A F A F A F A F A 13829 M A M A M A M A M A M A M A M A F A F A F A F A F A 13830 M A M A M A M A M A M A M A M S F A F A F A F A F A F A FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C38 (PAGE 2) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 313 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 MA M A M A MA MA MA MA M A MA M A MA M A MA M A MA MA MA MA MA MA MA M A FA FA MA MA MA MA MA MA FA FA FA FA FA FA M A M A M A M A FA FA FA F A FA F A FA F A M A M A M A M A M A M A FA F A FA F A FA F A MORIBUND SACRIFICED ON DAY 59 OF STUDY MA M A MA MA M A FA FA FA FA FA FA F S MA M A MA MA MA MA MA FA FA FA FA FA MA M A M A M A MA MA FA FA FA FA FA FA NOT PREGNANT MA MA M A M A M A FA FA FA FA FA FD U U M A M A M A M A M A MD 7 F A F A F A F A F A F A M A M A M A MA M A FA FA FA FA FA M A MA MA MA MA MA FA FA FA FA FA FA MA MA MA MA MA MA MA FA FA FA FA FA MA MA MA MA MA MA MA FA FA FA FA FA MA MA MA M S M S M S MS MA FA FA FA FA MA MA MA MA MA MA MA M A MA MA MA M A MA MA MA MA MA MA MA MA MA MA MA FA M A M A M A M A M A M A FA F A FA FA FA FA NOT PREGNANT MX11 MX11 MX11 MX11 1MX11 MX11 MX11 MX11 FX11 FX11 FX11 FX11 MA MA MA MA MA MA MA MA MA MA FA FA MA MA MA MA MA MA MA MA MA MA MA FA MA MA MA MA MA MA MA MA MA FA FA FA MA MA MA MA MA MA MA MA MA FA FA FA MA M A MA MA FA FA FA FA FA FA FA FA MA M A MA MA MA MA MA M A MA FA FA FA M A M A MA MA MA MA FA FA FA FA FA FA MA M A MA MA MA MA MA MA M A FA FA FA MA FA FA FA FA FA FA F A F A FM 3 FA F A F A F A F A FD 3 FD F A F A F A F A F A FD FA F A F A F A F A FD 8 F A FM 2 FS FS Fs FA FA FA FA FA FA FA FA FS FA FA FA FA FA FA FA FA FA FA F A F A FD 5 FD 1 FA FA FA FA FA FA FS FA FA FA FA FA F A F A FD11 FA FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C38 (PAGE 3) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 314 PUP # 1 2 3 4 S 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 MA MA MA MA MA MA MA MA FA PREGNANT: DID NOT DELIVER A LITTER M A M A M A M A M A FA FA FA FA MA M A MA MA FA FA FS M A M A M A M A M A M A M A MD 1 F A M A M A M A M A M A M A M A MD15 F A M A M A M A M A M A M A M A MD 7 MD 6 MA MA MA MA MA MA MA MA FA MA MA MA MA MA MA MA FA FA MA MA FA FA FA FA FA FA M A M A M A M A MD 3 F A F A F A F A MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA M A M A MA MA M A FA FA FA FA MA MA MA MA MA MA MA MA FA MA MA M A MA MA MA MA FA FA MA MA MA MA MA MA MA FA FA MA MA FA FA FA FA FA FA FA MA MA M A MA MA MA FA FA FA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA FA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA MA MA MA MA MA MA FA FA FA MA MA FA MA MA MA MA MA MA MA FA FA MA MA MA MA MA MA MA MA FA M A M A FA FA FA FA FA FA FA MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA FA MS FA FA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A F A F A FM 3 FA FA FA FA FA FA F A F A F A F A F A F A FD F A F A F A F A FD 6 FA FA FA FA FA F A F A F A F A FD 4 F A FD20 FM 7 FD 4 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A F S FD 1 FA FA FS FA FA F A FM 4 F A FD 2 FA FA FA F A F A F A F A FD 3 F A F A F A FD 1 FA FA FA FA FS FA FA FA FA FA FA FA FA FA FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C38 (PAGE 4) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 315 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 13920 M A M A M A M A M S FA FA FA FA FA FA M A M A M A MA M A MA MA FA FA FA FA FA FA FA FA FS M A M A M A MA M A MA MA FA FA FA FA FA F A FA FA M A M A M A M A M A M A MM 4 F A F A F A F A F A F A F A M A MA MA M A M A MA MA MA MA MA MA FA FA FA FA M A M A M A M A M A FA FA FA FA FA FA FA M A M A M A M A M A MA FA FA FA FA FA FA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA M A M A M A M A M A MA FA FA FA FA FA NOT PREGNANT; MATING NOT CONFIRMED M A M A M A M A M A M A M A F A F A F A F A F A F A F A F A FD 7 M A M A M A M A M A MA MA FA FA FA FA FA FA FA FA M A M A M A M A FA FA FA FA FA FA FA FA F A FA M A M A M A M A M A MA MA MA MA FA FA FA FA FA MA MA M A M A M A FA FA FA FA FA FA FA FA FA FA FA M A M A M A M A M A MD 3 M S M S F A F A F A F A F A F A F A FD 8 M A M A M A M A M A MA MA MA MA MA FA FA FA FA FA FA MA MA FA FA M A M A M A M A M A FA FA FA FA FA FA FA FA FA M A M A M A M A M A MA FA FA FA FA FA FA FA FA FA MA MA M A MA MA MA MA MA FA FA FA FA MA MA MA MA M A MA MA FA FA FA FA FA FA FA MA MA MA MA M A MA MA FA FA FA FA FA FA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA M A M A M A M A MA M A MA MA M A FA FA FA FA FA FA FA MA MA MA MA M A MA MA FA FA FA FA FA FA FA FA FA MA MA MA FA FA FA FA MA MA MA MA MA FA FA FA FA FA FA FA FA FA M A M A M A M A MA M A FA FA FA FA FA FA FA FA M A M A M A M A M A M A MD 9 F A F A F A F A F A F A FD 9 FD 9 FD 3 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C38 (PAGE 5) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 316 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 M A M A M A M A M A M A M A M A MM 6 M A M A M A M A MM 2 MD 1 MD 1 FM 2 FM 2 MA MA MA MA MA MA MA FA FA MA MA MA MA MA MA MA MA MA M A MA MA MA MA MA FA FA FA MA MA MA MA MA MA MA MA M S MA MA MA MA MA MA MA FA FA M A M A M A M A MD 8 MD 3 F A F A F A NOT PREGNANT M A M A M A M A M A M A M A M A MD 8 M A M A M A M A M A M A MD 8 MD 6 F A MA MA M A M A MA MA MA MA FA MA MA MA MA MA FA FA FA FA M A MM12 MM 4 F A F A F A F A F A F A MA MA MA MA MA MA MA FA FA MA MA MA MA MA MA MA MA MA M A M A M A M A MA MA FA FA FA M A M A M A M A M A M A M A MD 2 F A MA M A MA MA MA MA MA FA FA M A M A M A M A MA MA FA FA FA MA MA MA MA MA MA MA MA M A MA MA MA MA MA MA MA MA MA M A M A F A FA FA FA FA M A M A M A MM 5 F A F A F A F A F A M A M A MA MA MA M A MA M A M A M A M A M A M A M A F A FA F A F A FD 1 M A M A M A MA MA MA MA FA FA M A M A MA MA M A M A MA M A M A M A M A MA MA MA MA MS FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FA FA FA FA FA FA FA FA FA FA FA F A F A F A F A F A FD 7 FA FA FA FA FA FA FA FA FA FA FA FA F A F A FD 6 FD 6 FM 2 FA FA FA FA FA FA FA F A F A F A F A FM 6 FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FS FA FA FA FA FA FA FA FA FS MA FA FA FA FA FA F A FM10 FA FA FA FA FA F A FM 3 FA FA FA F A FD 2 F S F S FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C39 (PAGE 1) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 317 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY (S) POSTPARTUM OBSERVATIONS a I 0 13807 5 3/17 PUPS: COLD TO TOUCH; NOT NESTING; NOT NURSING. 13817 1 1/15 PUPS: COLD TO TOUCH; NO MILK IN STOMACH. 13820 5 1/14 PUPS: COLD TO TOUCH. 13824 2 16/16 PUPS: COLD TO TOUCH. 13827 1 1/16 PUPS: COLD TO TOUCH. II 1 13833 8, 9 1/14 PUPS: UMBILICAL HERNIA. 13837 1 1/12 PUPS: COLD TO TOUCH. 13839 1-22 4 1/12 PUPS: NO TAIL PRESENT b; HINDLIMBS ROTATED INWARD. 1/12 PUPS: COLD TO TOUCH. 13849 13850 3 1 5-22 1/16 PUPS: COLD TO TOUCH. 2/13 PUPS: COLD TO TOUCH. 1/12 PUPS: TIP OF TAIL MISSING. 13852 5- 6 1/12 PUPS: LEFT FORELIMB, MASS (0.3 CM IN DIAMETER). NIPPLE EXAMINATIONS FOR ALL MALE PUPS APPEARED NORMAL. a. Tabulation restricted to adverse observations; all other pups appeared normal. b. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C39 (PAGE 2): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 318 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY (S) POSTPARTUM OBSERVATIONS a III 3 13868 1 16/16 PUPS: COLD TO TOUCH. 13873 7 1/16 PUPS: COLD TO TOUCH. 13877 3 1/13 PUPS: COLD TO TOUCH. 13878 1 9/ 9 PUPS: COLD TO TOUCH. 13887 1-20 21,22 1/11 PUPS: TIP OF TAIL BLACK. 1/11 PUPS: TIP OF TAIL MISSING.b 13888 12 1/14 PUPS: RED PERIANAL SUBSTANCE. 13889 7 2/16 PUPS: COLD TO TOUCH. IV 10 13894 1- 4 1/14 PUPS: TIP OF TAIL MISSING. 5-22 1/13 PUPS: TIP OF TAIL MISSING. 13895 13898 13905 13906 13912 1- 6 5 21,22 7 5 12 1/15 PUPS: BRUISE, BACK (DID NOT EXCEED 2.0 CM X 1.0 C M ) . 1/16 PUPS: COLD TO TOUCH. 1/16 PUPS: LEFT EYE, TRAUMATIZED CORNEA.b 1/13 PUPS: PALE; NO MILK IN STOMACH; NOT NESTING. 1/14 PUPS: SCAB, BACK (0.2 CM IN DIAMETER). 1/14 PUPS: UMBILICAL HERNIA. 13914 1,2 1/18 PUPS: COLD TO TOUCH; NO MILK IN STOMACH. NIPPLE EXAMINATIONS FOR ALL MALE PUPS APPEARED NORMAL. a. Tabulation restricted to adverse observations; all other pups appeared normal. b. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C39 (PAGE 3): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 319 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY (S) POSTPARTUM OBSERVATIONS a V 30 13921 12-22 1/14 PUPS- MOUTH, MASS (DID NOT EXCEED 0.2 CM X 0.3 CM X 0.1 CM ) . 13922 13927 1 15-19 4- 7 8- 9 1/ 9 PUPS- COLD TO TOUCH. 1/ 9 PUPS UMBILICAL HERNIA. 1/16 PUPS BACK, BRUISE (DID NOT EXCEED 1.0 CM X 0.5 CM) . 1/15 PUPS BACK, BRUISE (0.2 CM IN DIAMETER) . 13930 1, 2 3 4 5 12-20 18/18 PUPS 3/18 PUPS 18/18 PUPS 1/18 PUPS 1/15 PUPS COLD TO TOUCH. COLD TO TOUCH. COLD TO TOUCH. BACK, BRUISE (0.5 CM IN DIAMETER) . UMBILICAL HERNIA. 13931 1 1/15 PUPS NO MILK IN STOMACH. 4,5 1/14 PUPS BACK, BRUISE (1.0 CM X 0.5 CM) . 13934 1,2 1/15 PUPS HEAD, BRUISE (0.5 CM IN DIAMETER), BACK, BRUISE (2.0 CM X 1.0 CM ) . 3 1/15 PUPS HEAD AND BACK, BRUISE (1.0 CM IN DIAMETER), CHEST AND LOWER MIDLINE, BRUISE (2.5 CM X 1.5 CM); COLD TO TOUCH. 13944 13948 9 1/11 PUPS PALE; NO MILK IN STOMACH. 3 11/12 PUPS COLD TO TOUCH. 4 11/11 PUPS COLD TO TOUCH. NIPPLE EXAMINATIONS FOR ALL MALE PUPS APPEARED NORMAL. a. Tabulation restricted to adverse observations; all other pups appeared normal. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 1) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a ARGUS 418-020 Page 320 13801 13802 13803 13805 13806 13807 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13808 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13809 22 ALL PUPS EXAMINED APPEARED NORMAL. 13810 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 3 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13812 13813 13814 13815 13816 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13817 2 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 2) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a I (Cont .) 0 13818 2 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13819 1 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 8b ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13830 1 1 PUP: STILLBORN,. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C3 9) for external clinical observations confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. ARGUS 418-020 Page 321 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 3) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 322 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a II 1 13831 22 ALL PUPS EXAMINED APPEARED NORMAL. 13832 22 ALL PUPS EXAMINED APPEARED NORMAL. 13833 22 ALL PUPS EXAMINED APPEARED NORMAL. 13834 22 ALL PUPS EXAMINED APPEARED NORMAL. 13835 2 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 3 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13837 1 1 PUP: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13838 4 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13839 22 ALL PUPS EXAMINED APPEARED NORMAL. 13841 1 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13842 7 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13843 13844 22 ALL PUPS EXAMINED APPEARED NORMAL. 8 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13845 13846 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 4) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) II (Cont ) 1 LITTER NUMBER 13847 13848 13849 DAY POSTPARTUM 1 22 22 22 OBSERVATIONS a 7 PUPS: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ARGUS 418-020 Page 323 13850 1 1 PUP: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13852 13853 13854 lib ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13855 1 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 5 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13856 22 ALL PUPS EXAMINED APPEARED NORMAL. 13857 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13858 22 ALL PUPS EXAMINED APPEARED NORMAL. 13859 11 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13860 22 ALL PUPS EXAMINED APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 5) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 324 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a III 13861 22 ALL PUPS EXAMINED APPEARED NORMAL. 13863 22 ALL PUPS EXAMINED APPEARED NORMAL. 13864 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13865 1 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13866 8 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 15 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13867 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 6 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 7 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13868 22 ALL PUPS EXAMINED APPEARED NORMAL. 13869 4 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13870 13871 22 ALL PUPS EXAMINED APPEARED NORMAL. 3 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 4 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 20 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 6) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 325 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a III (Cont.) 13872 13873 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13874 2 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13875 22 ALL PUPS EXAMINED APPEARED NORMAL. 13876 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13877 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13878 13879 13880 13881 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13882 3 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13883 1 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13884 13886 13887 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13888 1 1 PUP: STILLBORN.' ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13889 13890 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 7) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a ARGUS 418-020 Page 326 13891 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13892 1 I PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13893 13894 13895 13896 13897 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13898 3 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13899 22 ALL PUPS EXAMINED APPEARED NORMAL. 13901 7 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13902 13903 13904 13905 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13906 1 2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 3 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 8 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13907 22 ALL PUPS EXAMINED APPEARED NORMAL. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 8): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a IV (Cont.) 10 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 13919 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13920 3 1 PUP: !FOUND DEAD. ALL TISSUES APPEARED NORMAL. 9 2 PUPS: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP : FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL, 22 ALL PUPS EXAMINED APPEARED NORMAL. a Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. ARGUS 418-020 Page 327 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 9) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a ARGUS 418-020 Page 328 13921 22 ALL PUPS EXAMINED APPEARED NORMAL. 13922 1 2 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13923 13924 13925 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13926 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13927 7 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13928 3 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 8 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13930 6 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 8 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13931 6 2 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 8 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13932 13933 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C40 (PAGE 10) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 329 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY POSTPARTUM OBSERVATIONS a V (Cont.) 30 13934 13935 13936 13937 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13938 2 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13939 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13940 22 ALL PUPS EXAMINED APPEARED NORMAL. 13941 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13942 13943 13944 13945 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13946 22 1 PUP: KIDNEYS, RIGHT, PELVIS, MODERATE DILATION. ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS APPEARED NORMAL. 13947 1 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 13948 1394 9 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13950 1 3 PUPS: STILLBORN . ALL TISSUES APPEARED NORMAL 2 1 PUP: FOUND DEAD'. ALL TISSUES APPEARED NORMAL 22 ALL PUPS EXAMINED APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C41 (PAGE 1) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 330 MATERNAL DOSAGE GROUP I 0 MG/KG/DAY RAT/ LITTER NUMBER 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 BRAIN MFT SPLEEN M FT THYMUS M FT 1.67 1.53 1.60 0.27 0.21 0.24 0.21 1.58 1.48 1.53 0.10 0.15 0.12 0.19 1.35 1.43 1.39 0.11 0.13 0.12 0.17 MORIBUND SACRIFICED ON DAY 68 OF STUDY 1.31 1.20 1.26 0.19 0.11 0.15 0.26 1.45 1.41 1.43 0.12 0.14 0.13 0.13 1.27 1.23 1.25 0.09 0.06 0.08 0.07 1.45 1.63 1.54 0.18 0.21 0.20 0.22 1.40 1.41 1.40 0.14 0.12 0.13 0.11 1.47 1.40 1.44 0.17 0.17 0.17 0.21 NOT PREGNANT 1.36 1.29 1.32 0.11 0.10 0.10 0.08 1.38 1.48 1.43 0.13 0.14 0.14 0.14 1.38 1.33 1.36 0.13 0.08 0.10 0.15 1.36 1.34 1.35 0.05 0.05 0.05 0.13 1.20 1.16 1.18 0.17 0.14 0.16 0.13 1.59 1.54 1.56 0.14 0.13 0.14 0.12 1.30 1.25 1.28 0.08 0.06 0.07 0.09 1.38 1.35 1.36 0.20 0.12 0.16 0.18 1.43 1.26 1.34 0.12 0.08 0.10 0.18 1.45 1.41 1.43 0.07 0.17 0.12 0.11 SACRIFICED ON DAY 8 OF LACTATION 1.51 1.49 1.50 0.34 0.22 0.28 0.28 1.48 1.41 1.44 0.14 0.11 0.12 0.16 -- 1.37 1.37 -- 0.07 0.07 -- 1.36 1.25 1.30 0.14 0.14 0.14 0.13 1.57 1.56 1.56 0.17 0.20 0.18 0.15 1.39 1.45 1.42 0.25 0.16 0.20 0.18 1.51 1.27 1.39 0.15 0.13 0.14 0.17 1.38 1.44 1.41 0.11 0.10 0.10 0.14 0.23 0.16 0.21 0.16 0.14 0.07 0.28 0.13 0.25 0.14 0.14 0.15 0.08 0.12 0.13 0.08 0.26 0.17 0.18 0.25 0.16 0.10 0.12 0.13 0.12 0.15 0.20 0.22 0.18 0.19 0.21 0.14 0.07 0.25 0.12 0.23 0.11 0.14 0.15 0.10 0.12 0.12 0.08 0.22 0.18 0.14 0.26 0.16 0.10 0.12 0.14 0.15 0.16 0.17 TERMINAL BODY WEIGHT M FT 44.6 43.0 a 42.5 41.3 a 43.6 42.2 a 46.6 32.1 a 40.9 35.9 43.4 41.0 31.4 a 39.8 33.8 43.1 43.8 31.8 a 40.4 34.8 43.2 43.2 43.9 38.8 33.8 32.8 37.9 25.8 30.6 26.1 35.0 40.1 44.0 32.5 28.4 27.3 36.7 26.5 27.8 21.8 39.6 41.6 44.0 35.6 31.1 30.0 37.3 26.2 29.2 24.0 37.3 52.0 38.4 -- 31.8 42.5 42.2 42.0 35.0 51.3 38.8 32.7 23.6 37.5 39.6 32.8 36.9 51.6 38.6 32.7 27.7 40.0 40.9 37.4 36.0 M = MALE F * FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Pup's identification was not recorded; therefore, terminal body weight could not be determined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C41 (PAGE 2) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 331 MATERNAL DOSAGE GROUP II 1 MG/KG/DAY RAT/ LITTER NUMBER BRAIN M FT SPLEEN M FT THYMUS M FT TERMINAL BODY WEIGHT M FT 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 1.47 1.47 1.47 0.11 0.14 0.12 0.12 1.65 1.49 1.57 0.15 0.12 0.14 0.14 1.51 1.49 1.50 0.12 0.12 0.12 0.17 1.52 1.47 1.50 0.07 0.08 0.08 0.18 1.52 1.44 1.48 0.10 0.14 0.12 0.11 MORIBUND SACRIFICED ON DAY 59 OF STUDY 1.66 1.49 1.58 0.19 0.17 0.18 0.26 1.45 1.40 1.42 0.11 0.09 0.10 0.16 1.42 1.45 1.44 0.14 0.13 0.14 0.17 NOT PREGNANT 1.34 1.33 1.34 0.15 0.15 0.15 0.15 1.49 1.40 1.44 0.17 0.12 0.14 0.14 1.33 1.29 1.31 0.11 0.11 0.11 0.13 1.39 1.29 1.34 0.12 0.06 0.09 0.15 1.43 1.49 1.46 0.11 0.16 0.14 0.13 1.41 1.45 1.43 0.16 0.08 0.12 0.17 1.53 1.49 1.51 0.21 0.21 0.21 0.21 1.32 1.34 1.33 0.11 0.04 Q .08 0.15 1.30 1.28 1.29 0.06 0.07 0.06 0.08 1.56 1.42 1.49 0.13 0.14 0.14 0.17 NOT PREGNANT SACRIFICED ON DAY 11 OF LACTATION 1.53 1.40 1.46 0.13 0.14 0.14 0.17 1.11 1.10 1.10 0.15 0.04 0.10 0.18 1.53 1.53 1.53 0.08 0.08 0.08 0.20 1.40 1.30 1.35 0.10 0.07 0.08 0.10 1.45 1.54 1.50 0.06 0.15 0.10 0.22 1.36 1.36 1.36 0.11 0.11 0.11 0.11 1.52 1.50 1.51 0.18 0.17 0.18 0.16 1.44 1.37 1.40 0.10 0.10 0.10 0.19 0.13 0.17 0.19 0.12 0.17 0.22 0.12 0.10 0.15 0.19 0.13 0.12 0.16 0.17 0.24 0.15 0.07 0.16 0.14 0.05 0.18 0.07 0.25 0.12 0.20 0.18 0.12 0.16 0.18 0.15 0.14 0.24 0.14 0.14 0.15 0.16 0.13 0.14 0.14 0.17 0.22 0.15 0.08 0.16 0.16 0.12 0.19 0.08 0.24 0.12 0.18 0.19 33.1 45.2 a 36.2 36.7 a 36.0 36.1 36.3 43.4 34.3 33.6 a 36.3 51.4 a 27.5 37.3 37.8 30.1 40.2 32.9 39.6 33.2 37.4 35.4 36.7 35.5 a 37.7 37.3 a 36.0 32.7 37.0 37.7 30.1 27.8 a 31.0 50.4 a 23.6 33.8 27.5 23.8 37.0 25.6 41.8 30.7 40.7 38.7 34.9 40.4 a 37.0 37.0 a 36.0 34.4 36.6 40.6 32.2 30.7 a 33.6 50.9 a 25.6 35.6 32.6 27.0 38.6 29.2 40.7 32.0 39.0 37.0 . M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Pup's identification was not recorded or appeared incorrectly recorded; determined. therefore, terminal body weight could not be PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C41 (PAGE 3) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 332 MATERNAL DOSAGE GROUP III 3 MG/KG/DAY RAT/ LITTER NUMBER BRAIN M FT SPLEEN M FT THYMUS M FT TERMINAL BODY WEIGHT M FT 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 1.34 --- 1.34 0.08 --- 0.08 PREGNANT; DID NOT DELIVER A LITTER 1.36 1.43 1.40 0.11 0.11 0.11 1.50 -- 1.50 0.28 -- 0.28 1.48 1.42 1.45 0.12 0.14 0.13 1.28 1.13 1.20 0.12 0.06 0.09 1.34 1.28 1.31 0.05 0.12 0.08 1.41 1.45 1.43 0.08 0.11 0.10 1.23 1.35 1.29 0.09 0.10 0.10 -- 1.25 1.25 -- 0.10 0.10 1.12 1.25 1.18 0.02 0.08 0.05 1.44 1.41 1.42 0.09 0.10 0.10 1.40 1.40 1.40 0.10 0.12 0.11 1.63 1.40 1.52 0.22 0.16 0.19 1.48 1.43 1.46 0.13 0.13 0.13 1.59 1.62 1.60 0.11 0.23 0.17 1.51 1.55 1.53 -- 1.54 1.54 0.16 0.14 0.15 -- 0.23 0.23 1.64 1.53 1.58 0.10 0.19 0.14 1.58 1.39 1.48 0.19 0.16 0.18 1.45 1.39 1.42 0.06 0.07 0.06 1.45 1.50 1.48 0.10 0.13 0.12 1.47 1.39 1.43 0.19 0.13 0.16 1.51 1.31 1.41 0.21 0.08 0.14 b 1.47 1.45 1.46 0.12 0.12 0.12 1.62 1.55 1.58 0.18 0.18 0.18 -- 1.31 1.31 -- 0.15 0.15 1.53 1.32 1.42 0.15 0.10 0.12 -- 1.37 1.37 -- 0.06 0.06 0.04 -- 0.04 0.11 0.23 0.08 0.11 0.10 0.13 0.07 -- 0.08 0.10 0.15 0.15 0.14 0.15 0.22 -- 0.16 0.21 0.11 0.11 0.22 0.18 0.11 -- 0.14 0.11 0.12 0.15 0.10 0.15 0.08 0.15 0.15 0.18 0.08 0.06 0.18 0.20 0.24 0.15 0.08 0.12 0.18 0.15 0.11 0.23 0.11 0.11 0.11 0.14 0.08 0.15 0.08 0.12 0.15 0.16 0.11 0.10 0.20 0.20 0.20 0.18 0.10 0.12 0.20 0.16 0.15 0.24 -- 0.16 -- 0.15 0.20 0.09 0.13 0.17 0.15 0.22 0.09 0.14 0.17 36.2 32.5 59.3 30.4 a 29.9 a 33.7 -- 26.8 29.8 35.3 49.1 40.1 45.3 45.8 -- 46.1 52.8 37.7 37.6 43.6 42.3 40.3 49.9 -- 35.8 -- -- 34.6 -- 28.6 a 28.2 a 29.8 36.3 29.1 30.0 35.6 43.4 42.9 47.0 42.5 51.8 47.7 42.9 37.2 44.5 48.0 27.4 40.6 45.3 25.9 32.1 38.8 36.2 33.6 59.3 29.5 a 29.0 a 31.8 36.3 28.0 29.9 35.4 46.2 41.S 46.2 44.2 51.8 46.9 47.8 37.4 41.0 45.8 34.8 40.4 47.6 25.9 34.0 38.'8 . M = MALE F > FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Pup's identification was not recorded; therefore, b. All pups were selected for continued observation. terminal body weight could not be determined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C41 (PAGE 4) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 333 MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY RAT/ LITTER NUMBER 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13 914 13915 13916 13917 13918 13919 13920 BRAIN MFT SPLEEN MFT 1.60 1.53 1.56 0.17 0.26 0.22 1.44 1.51 1.48 1.52 1.37 1.44 0.19 0.13 0.16 0.17 0.13 0.15 1.40 1.41 1.40 0.10 0.16 0.13 1.54 1.39 1.46 0.16 0.19 0.18 1.52 1.46 1.49 0.12 0.13 0.12 1.44 1.36 1.40 0.16 0.14 0.15 1.37 1.28 1.32 0.10 0.06 0.08 1.33 1.30 1.32 0.07 0.11 0.09 NOT PREGNANT; MATING NOT CONFIRMED 1.36 1.28 1.32 0.07 0.07 0.07 1.60 1.49 1.54 0.19 0.17 0.18 1.43 1.38 1.40 0.15 0.13 0.14 1.27 1.30 1.28 0.11 0.13 0.12 1.32 1.13 1.22 0.05 0.07 0.06 1.53 1.41 1.47 0.18 0.23 0.20 1.20 1.29 1.24 0.12 0.10 0.11 b 1.50 1.43 1.46 0.12 0.10 0.11 1.42 1.39 1.40 0.17 0.14 0.16 1.44 1.47 1.46 0.10 0.14 0.12 1.49 1.41 1.45 0.13 0.16 0.14 1.44 1.25 1.34 0.20 0.19 0.20 1.43 1.41 1.42 0.09 0.10 0.10 1.30 1.31 1.30 0.08 0.10 0.09 1.32 1.54 1.43 0.18 0.20 0.19 1.42 1.40 1.41 0.12 0.13 0.12 1.62 1.37 1.50 0.26 0.16 0.21 1.48 1.49 1.48 0.08 0.12 0.10 1.12 1.38 1.25 0.12 0.12 0.12 THYMUS MFT 0.17 0.19 0.22 0.17 0.22 0.13 0.27 0.11 0.20 0.22 0.15 0.16 0.20 0.14 0.14 0.26 0.10 0.15 0.20 0.17 0.19 0.18 0.18 0.14 0.26 0.10 0.18 0.08 0.16 0.20 0.12 0.10 0.20 0.10 0.06 0.21 0.14 0.14 0.09 0.24 0.12 0.07 0.18 0.17 0.13 0.10 0.22 0.11 0.14 0.18 0.23 0.18 0.27 0.18 0.13 0.22 0.16 0.19 0.11 0.23 0.11 0.16 0.23 0.15 0.23 0.13 0.15 0.20 0.17 0.15 0.09 0.19 0.12 0.17 0.23 0.16 0.25 0.16 0.14 0.21 0.16 0.17 0.10 0.21 TERMINAL BODY WEIGHT MFT 47.8 38.7 46.1 34.9 41.3 a 44.4 33.6 32.4 44.1 36.7 37.0 34.5 40.0 a 42.2 29.0 31.7 46.0 37.7 41.6 34.7 40.6 a 43.3 31.3 32.0 30.6 43.3 40.4 28.1 29.2 a 23.2 27.6 37.9 32.4 30.3 33.5 a 26.9 29.1 40.6 36.4 29.2 31.4 a 25.0 39.8 39.5 43.3 a 43.2 a 31.8 43.2 41.3 45.3 38.4 26.9 38.4 38.0 40.7 a 37.2 a 34.9 40.2 40.8 39.1 37.4 23.7 39.1 38.8 42.0 a 40.2 a 33.4 41.7 41.0 42.2 37.9 25.3 M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Pup's identification was not recorded or appeared determined. b. All pups were selected for continued observation. recorded; therefore, terminal body weight could not be PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE C41 (PAGE 5) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - FI GENERATION PUPS ARGUS 418-020 Page 334 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY RAT/ LITTER NUMBER BRAIN M FT SPLEEN M FT THYMUS M FT TERMINAL BODY WEIGHT M FT 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 1.53 1.29 1.52 1.49 1.35 1.39 1.19 1.49 -- 1.41 1.43 1.40 1.35 1.16 1.51 1.29 1.46 1.46 1.38 1.37 1.18 0.16 0.12 0.10 0.09 0.11 0.11 0.06 0.14 -- 0.09 0.08 0.13 0.12 0.07 0.15 0.12 0.10 0.08 0.12 0.12 0.06 0.18 0.10 0.15 0.14 0.16 0.16 0.07 0.10 -- 0.13 0.15 0.17 0.16 0.06 0.14 0.10 0.14 0.14 0.16 0.16 0.06 46.1 32.8 a 34.5 32.9 34.0 23.9 1.46 1.39 1.42 0.16 0.18 0.17 0.20 0.18 0.19 a NOT PREGNANT 1.28 1.33 1.30 0.08 0.10 0.09 0.06 0.06 0.06 25.3 1.13 1.15 1.14 0.07 0.07 0.07 0.09 0.10 0.10 24.9 1.32 1.30 1.31 0.11 0.14 0.12 0.05 0.12 0.08 31.5 1.17 1.19 1.18 0.06 0.10 0.08 0.06 0.08 0.07 a -- 1.26 1.26 -- 0.12 0.12 -- 0.15 0.15 -- 1.33 1.30 1.32 0.05 0.07 0.06 0.11 0.08 0.10 34.3 1.42 1.48 1.45 0.15 0.15 0.15 0.13 0.19 0.16 38.0 1.43 1.40 1.42 0.11 0.13 0.12 0.12 0.11 0.12 39.0 1.32 1.21 1.26 0.09 0.06 0.08 0.14 0.11 0.12 29.2 1.51 1.46 1.48 0.16 0.15 0.16 0.14 0.23 0.18 38.4 1.29 1.22 1.26 0.04 0.06 0.05 0.04 0.07 0.06 30.0 1.59 1.52 1.56 0.19 0.13 0.16 0.18 0.13 0.16 41.4 1.58 1.41 1.50 0.18 0.15 0.16 0.14 0.12 0.13 a -- 1.56 1.56 -- 0.24 0.24 -- 0.20 0.20 -- 1.39 1.35 1.37 0.13 0.12 0.12 0.16 0.18 0.17 35.1 1.41 1.35 1.38 0.09 0.11 0.10 0.12 0.14 0.13 a 1.35 1.26 1.30 0.11 0.14 0.12 0.16 0.17 0.16 43.2 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 1.46 1.38 1.42 0.14 0.14 0.14 0.18 0.15 0.16 43.4 1.52 1.45 1.48 0.12 0.12 0.12 0.19 0.18 0.18 40.9 1.64 1.48 1.56 0.18 0.17 0.18 0.28 0.21 0.24 47.4 40.6 ___ a 34.3 38.2 31.2 22.5 a 20.5 24.9 32.7 a 30.6 21.5 35.2 38.6 26.4 42.0 26.8 31.9 a a 34.7 a 42.3 42.4 38.3 42.0 43.4 32.8 a 34.4 35.6 32.6 23.2 a 22.9 24.9 32.1 a 30.6 27.9 36.6 38.8 27.8 40.2 28.4 36.6 a a 34.9 a 42.8 42.9 39.6 44.7 . M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Pup's identification was not recorded or appeared incorrectly recorded; determined. therefore, terminal body weight could not be ARGUS 418-020 APPENDIX D REPORT TABLES - Fl GENERATION MALE RATS Page 335 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-G889.G) TABLE D1 (PAGE 1) : CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 336 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 MAXIMUM POSSIBLE INCIDENCE 4563/ GO 4547/ 60 4576/ 60 4602/ 60 4473/ 60 MORTALITY FOUND DEAD a MORIBUND SACRIFICED a 3332 7 2331 6 100 1 1 ANNULAR CONSTRICTION OF THE TAIL 44/ 4 122/ 11* 69/ 7 122/ 11* 214/ 21** CHROMORHINORRHEA 12/ 9 18/ 9 22/ ii 10/ 4 26/ 12 ABDOMINAL DISTENTION 25/ 4 41/ 4 11/ i 73/ 5 124/ 10** URINE-STAINED ABDOMINAL FUR 11/ 1 2/ 2 13/ i 6/ 1 40/ 9** EMACIATION 0/ 0 1/ 1 2/ 2 15/ 3* 22/ 7** CHROMODACRYORRHEA 22/ 3 53/ 5 244/ 9 55/ 4 171/ 6 DECREASED MOTOR ACTIVITY COLD TO TOUCH 1/ 1 1/ 1 1/ 1 1/ 1 0/ 0 1/ 1 1/ 1 13/ 2 12/ 5** 11/ 5 INCISORS: TOTAL MISALIGNED MISSING/BROKEN 47/ 5 12/ 3 36/ 4 62/ 3 62/ 3 0/ 0 258/ 9 194/ 7 66/ 4 171/ 5 123/ 3 48/ 2 188/ 181/ 25/ 4 4 2 SCAB b 89/ 4 30/ 2 55/ 5 18/ 3 7/ 3 SOFT OR LIQUID FECES 22/ 11 14/ 11 6/ 5 7/ 7 3/ 3 MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS) /NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. - a. Refer to the individual clinical observations table (Table D14) for observations for rats that were found dead or moribund sacrificed. b. Located on neck, head, back, mouth, and behind left ear. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE DI (PAGE 2) : CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 337 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 MAXIMUM POSSIBLE INCIDENCE 4563/ 60 4547/ 60 4576/ 60 4602/ 60 4473/ 60 MORTALITY FOUND DEAD a MORIBUND SACRIFICED a 33327 23 3 1 6 10011 LOCALIZED ALOPECIA: TOTAL LIMBS BACK HEAD 30/ 1 30/ 1 0/ 0 0/ 0 56/ 1 56/ 1 0/ 0 0/ 0 36/ 3 31/ 1 3/ 1 2/ 1 10/ 1 0/ 0 10/ 1 0/ 0 7/ 2 7/ 2 0/ 0 0/ 0 RIGHT OR BOTH EYE(S): CORNEAL OPACITY 0/ 0 14/ 1 0/ 0 0/ 0 2/ 2 RALES 1/ 1 0/ 0 0/ 0 0/ 0 2/ 2 DEHYDRATION 0/ 0 0/ 0 0/ 0 19/ 2 14/ 1 LACRIMATION 0/ 0 0/ 0 34/ 1 0/ 0 6/ 1 RIGHT EYE : SWOLLEN 0/ 0 0/ 0 0/ 0 0/ 0 6/ 1 SNOUT : SWOLLEN PENIS : RED SUBSTANCE 3/ 1 0/ 0 2/ 1 0/ 0 32/ 2 0/ 0 6/ 1 1/ 1 4/ 1 4/ 1 EXCESS SALIVATION 4/ 4 2/ 2 3/ 3 1/ 1 1/ 1 RED, DRIED, SLIGHT PERINASAL SUBSTANCE 0/ 0 0/ 0 3/ 2 1/ 1 1/ 1 VOCALIZATION BOTH EARS : SWOLLEN 1/ 1 0/ 0 1/ 1 0/ 0 0/ 0 8/ 3 0/ 0 2/ 2 1/ 1 0/ 0 MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Refer to the individual clinical observations table (Table DI4) for observations for rats that were found dead or moribund sacrificed. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE D1 (PAGE 3): CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 MAXIMUM POSSIBLE INCIDENCE 4563/ 60 4547/ 60 4576/ 60 4602/ 60 4473/ 60 MORTALITY FOUND DEAD a MORIBUND SACRIFICED a 33327 23316 100 1 1 TIP OF TAIL MISSING 0/ 0 0/ 0 0/ 0 21/ 1 0/ 0 TIP OF TAIL BLACK 0/ 0 0/ 0 0/ 0 9/ 1 0/ 0 BACK: ULCERATION 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 RED, SLIGHT PERIORAL SUBSTANCE 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 PTOSIS 0/ 0 20/ 1 0/ 0 0/ 0 0/ 0 ENOPHTHALMOS 0/ 0 2/ 1 0/ 0 0/ 0 0/ 0 HEAD: ABRASION 18/ 2 0/ 0 0/ 0 0/ 0 0/ 0 RIGHT EYE: ENLARGED 102/ 1 0/ 0 0/ 0 0/ 0 0/ 0 MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS) /NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Refer to the individual clinical observations table (Table D14) for observations for rats that were found dead or moribund sacrificed. ARGUS 418-020 Page 338 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D2 (PAGE 1) : BODY WEIGHTS - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 339 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 BODY WEIGHT (G) DAY 1 MEANS.D. 42.7 6.9 41.0 6.8 43.8 9.7 44.6 6.6 40.4 8.4 DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 DAY 43 DAY 50 MEANS.D. MEANS.D . MEANS.D. MEANS.D. MEANS.D. MEANS.D . MEANS.D . 75.2 11.7 [ 59] a 124.1 15.9 [ 59] a 183.9 20.4 [ 59] a 241.0 23.1 ( 58] a 297.9 27.7 [ 47] a 342.4 28.8 l 30] a 383.2 33.7 [ 30] a 72.3 9.8 [ 58] a 118.8 13.3 ( 58] a 175.6 17.9 l 58] a 231.6 21.0 ( 58] a 288.2 28.3 l 54] a 327.8 25.9 [ 30] a 359.7 26.8* ( 29] a 77.3 15.2 ( 58] a 126.9 2 0 . 7 ( 571a 186.6 26.0 I 57] a 243.2 29.4 [ 57] a 299.7 29.7 ( 51] a 335.7 30.1 ( 31] a 369.7 31.9 [ 31] a 76.4 10.9 [ 59] a 122.6 15.8 ( 59] a 181.4 21.8 ( 59] a 233.0 27.6 C 59] a 280.1 40.0* [ 49] a 323.6 34.0* ( 30] a 355.3 40.2** ( 30] a 69.6 12.7* [ 55] a 109.2 17.6** [ 55] a 162.7 20.4** [ 55] a 211.1 25.2** ( 55] a 250.8 33.4** ( 48] a 291.3 32.5** [ 30] a 318.3 35.3** ( 30] a DAY = DAY POSTWEANING ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, * Significantly different from the Group I value (p^O.OS). ** Significantly different from the Group I value (p<0.01). found dead or moribund sacrificed. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D2 (PAGE 2) : BODY WEIGHTS - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 340 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 30a 29a 30a 30a 30a BODY WEIGHT (G) DAY 57 MEANS.D. 412.5 36.4 387.8 28.8* 398.7 33.0 380.1 43.8** 338.5 36.7** DAY 64 MEANS.D . 443.9 40.9 416.4 32.8* 424.1 34.8 404.5 49.3** 360.2 39.4** DAY 70b MEANS.D. 463.7 44.2 434.6 39.2* 442.2 36.6 420.9 51.1** 372.7 40.7** PRECOHABITATION c DAY 99d DAY 106 DAY 113 MEANS.D. MEANS.D . MEANS.D. MEANS.D . 488.1 46.5 521.9 54.0 539.0 55.5 554.8 57.6 ( 28] a 463.3 46.4 493.0 49.4* 504.6 t 52.0* 513.4 53.6* 468.2 39.9 497.4 40.9 506.9 45.4* 512.3 49.0* 443.8 53.9** 469.5 t 57.5** 481.8 60.8** 488.7 61.0** 391.0 42.0** 409.8 41.1** 416.1 48.0** 428.0 40.1** l 29] a DAY = DAY POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, found dead or moribund sacrificed. b. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. c. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. d. First weekly value recorded after cohabitation. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D3 (PAGE 1) : BODY WEIGHT CHANGES - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 341 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 59a 58a 58a 59a 55a BODY WEIGHT CHANGE (G) DAYS 1 - 8 MEANS.D. +32.3 7.0 +30.9 5.4 +33.0 7.1 +31.8 5.9 +27.9 6.4++ DAYS 8 - 1 5 DAYS 15 - 22 DAYS 2 2 - 2 9 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 MEANS.D. MEANS.D. MEANS.D . MEANS.D. MEANS.D . MEANS.D. +48.9 7.6 +59.8 6.0 +56.5 6.1 [ 58]a +56.8 6.8 [ 47] a +42.7 9.5 l 30] a +40.8 9.8 l 30] a +46.5 5.0 +56.8 7.0+ +55.9 5.2 +57.0 17.0 t 54] a +39.8 19.1 I 30] a +33.0 6.3+* l 29] a +49.2 6.9 [ 57] a +59.7 7.1 [ 57] a +56.6 5.6 l 57] a +56.5 6.5 [ 51] a +39.1 8.3 [ 31] a +34.0 8.1++ [ 31] a +46.2 6.6+ +58.8 8.2 +51.7 10.1+* +47.9 20.9++ [ 49] a +38.1 8.3 [ 30] a +31.7 9.2+* [ 30] a +39.6 6.6** +53.5 5.3*+ +48.4 12.6+* +40.7 13.2+* [ 48] a +35.4 1.1** ( 30] a +27.0 9.6++ ( 30] a DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a . Excludes values for rats that were sacrificed following sexual maturation. * Significantly different from the Group I value (p<0.05). * + Significantly different from the Group I value (p<0.01). found dead or moribund sacrificed. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D3 (PAGE 2) : BODY WEIGHT CHANGES - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 342 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 30a 29a 30a 30a 30a BODY WEIGHT CHANGE (G) DAYS 50 - 57 MEANS.D . +29.3 8.0 +28.1 6.2 +27.3 13.1 +24.8 7.3* +20.2 9.1** DAYS 57 - 64 MEANS.D . +31.4 8.3 +28.6 6.8 +25.3 6.4* +24.4 12.3 +21.7 6.6** DAYS 64 - 70b MEANlS.D . +19.8 6.2 +18.3 9.1 +18.2 5.3 +16.4 8.2 +12.5 6.8** DAY 1 PRECOHABITATION MEANS.D. +445.1 44.1 +422.3 44.5 +423.5 38.9 +399.7 50.8** +350.5 39.1** DAYS 99c-106 MEANiS.D. +17.1 t 33.5 +11.6 8.3 +9.6 12.4 +12.2 9.4 +6.3 26.5 DAYS 106- 113 DAYS 1 -113 MEANS.D. MEANS .D . +10.1 37.3 [ 28} a +511.6 55.0 [ 28] a +8.8 10.0 +472.5 52.3** +5.4 15.6 +467,6 49.6** +7.0 8.1 +444.6 58.3** +7.3 10.8 ( 29] a +387.8 37.4** [ 29] a DAY (S ) = DAY (S ) POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, found dead or moribund sacrificed. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time these rats were 92 to 106 days of age. c. First weekly value recorded after cohabitation. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). PROTOCOL 418 -020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D4 (PAGE 1) : ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 343 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED INCLUDED IN ANALYSES FEED CONSUMPTION (G/DAY) N N I 0 60 59a II III 13 60 60 58a 58a IV v 10 30 60 60 59a 55a DAYS 1 - 8 MEANS.D . 10.5 1.5 10.4 1.3 10.8 2.4 10.6 1.6 9.3 1.7** DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70c DAYS 1 - 70C MEANS.D. MEANfS.D. MEANS.D . MEANS.D. MEANS.D . MEANS.D . MEANS.D. MEANS.D . MEANS.D. MEANS.D. 18.1 2.0 ( 58] b 22.4 2.1 25.6 3.4 ( 58] a 28.1 2.4 [ 47] a 29.0 2.5 ( 30] a 29.2 3.2 [ 29]a ,b 29.9 2.8 [ 28] a ,b 30.0 3.8 [ 26] a ,b 29.2 3.8 ( 30]a 25.1 1.8 [ 30] a 17.4 1.8 21.6 t 2.0 24.7 2.2* 26.8 2.1* I 54]a 27.9 2.0 [ 29] a, b 27.0 2.1** ( 29] a, b 28.3 2.4 [ 26] a, b 28.2 2.7 l 27]a,b 27.6 3.3 [ 28]a,b 23.7 1.7** I 28]a,b 18.2 2.9 ( 57] a 22.3 2.7 [ 57] a 25.3 3.6 t 56]a,b 27.8 2.9 [ 50]a,b 28.7 2.5 [ 31] a 28.8 2.9 [ 29] a, b 29.9 3.2 [ 29] a, b 28.9 3.5 [ 28]a,b 28.5 2.6 ( 29] a, b 24.7 2.3 ( 29] a, b 17.6 2.8 21.6 2.4 25.7 2.5 [ 58]b 28.4 4.0 l 49] a 28.1 2.8 [ 29] a,b 28.3 3.0 [ 30] a 29.0 3.2 [ 29] a, b 28.5 3.4 t 30] a 27.7 3.8 ( 30] a 24.4 2.4 [ 30] a 16.0 3.0** 20.2 3.2** 24.5 3.1* 26.5 3.1** ( 47] a,b 27.9 3.8 [ 30] a 27.2 3.0* ( 28] a, b 27.6 3.3* [ 28]a,b 27.4 3.4 [ 30] a 26.8 3.8 ( 30] a 23.2 2.6** [ 30] a DAYS = DAYS POSTWEANING { ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, found dead or moribund.sacrificed. b. Excludes values that were associated with spillage, wet or soiled feed. c. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (piO.Ol). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D4 (PAGE 2) : ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 30a 28a, b 29a,b 30a 29a, b FEED CONSUMPTION (G/DAY) DAYS 99 -106 MEANS.D . 28.7 2.9 27.7 3.1 27.8 3.1 28.5 3.3 26.9 3.6 DAYS106 -113 DAYS 99 -113 MEANS.D . MEANS.D . 28.8 3.0 [ 24]b,c 28.8 3.0 [ 24]b,c 27.6 3.2 27.6 2.9 27.2 27.5 4.1 3.3 28.2 3.1 [ 28] b 28.2 3.0 l 28] b 26.9 3.4 [ 28] a, b 27.2 3.1 [ 28]a,b DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, b. Excludes values that were associated with spillage, wet or soiled feed. c. Excludes values for rats that were sacrificed before day 113 postweaning. found dead or moribund sacrificed. ARGUS 418-020 Page 344 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D5 (PAGE 1) : RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 345 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 59a 58a 58a 59a 55a FEED CONSUMPTION (G/KG/DAY) DAYS 1 - 8 MEANS.D . 179.2 23.9 183.8 19.4 177.8 25.7 176.6 19.9 168.3 25.0* DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70c DAYS 1 - 70c MEANS.D. MEANS .D . MEANS.D . MEANS.D . MEANS.D . MEANS.D. M E A N t S .D . MEANS.D . MEANS.D. MEANS.D . 182.9 19.5 [ 581b 146.3 12.2 121.0 15.8 [ 581a 104.6 7.6 I 47] a 90.7 6.8 [ 30] a 81.0 9.0 ( 29] a, b 75.6 6.6 [ 28}a,b 70.1 6.2 ( 26] a,b 64.4 6.6 [ 30] a 91.8 4.8 [ 30] a 182.6 15.9 147.3 10.4 121.7 8.8 103.8 7.6 1 54] a 91.3 7.7 [ 29] a,b 78.7 5.6 . ( 2 9] a, b 75.8 t 5.4 [ 26]a,b 70.0 5.2 [ 27] a, b 64.8 5.5 [ 28]a,b 91.8 4.5 [ 28]a,b 179.6 22.2 l 57] a 143.3 10.9 l 57] a 117.8 13.1 [ 56] a,b 102.5 5.6 [ 50) a, b 90.9 4.6 [ 31] a 82.1 5.5 [ 29] a, b 77.2 6.8 [ 29] a, b 70.0 7.3 [ 28]a,b 66.1 4.0 [ 29] a,b 92.4 4.5 [ 291a,b 177.3 22.4 142.6 12.9 124.0 11.4 ( 58] b 112.3 20.5* ( 49] a 92.0 5.8 [ 29] a, b 83.5 5.8 ( 30] a 79.2 6.0 [ 29] a, b 72.8 6.5 [ 30] a 67.2 i 6.4 [ 30] a 95.2 5.9* ( 30] a 181.0 25.6 149.4 17.7 131.9 16.4** 116.1 13.5** [ 47] a, b 102.0 8.0** [ 30] a 90.1 6.2** [ 28] a ,b 84.6 6.3** [ 28]a,b 78.6 6.3** [ 30] a 73.2 8.7** [ 30] a 101.0 5.3** t 30] a DAYS = DAYS POSTWEANING [ ) = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, found dead or moribund .sacrificed. b. Excludes values that were associated with spillage, wet or soiled feed. ` c. Because feed consumption was recorded at weekly intervals, based oneach rat's daypostweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngestrats inthis group. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D5 (PAGE 2) : RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 30a 28a, b 29a, b 30a 29a,b FEED CONSUMPTION (G/KG/DAY) DAYS 99 -106 MEANS.D. 54.4 4.6 55.7 5.0 55.3 5.5 60.4 8.8** 65.6 8.1** DAYS106 -113 DAYS 99 -113 MEANS.D . MEANS.D . 52.8 i 4.8 [ 24) b, c 53.7 4.4 [ 24]b,c 54.7 5.6 55.1 4.9 53.5 6.7 54.5 5.3 58.0 5.0** [ 28] b 58.6 5.0** [ 28] b 63.3 6.5** [ 28] a, b 64.8 6.6** [ 28] a,b DAYS = DAYS POSTWEANING ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, b. Excludes values that were associated with spillage, wet or soiled feed. c. Excludes values for rats that were sacrificed before day 113 postweaning. ** Significantly different from the Group I value (p<0.01). found dead or moribund sacrificed. ARGUS 418-020 Page 346 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D6 (PAGE 1): SEXUAL MATURATION - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 MALE RATS N 60 60 60 60 60 INCLUDED IN ANALYSES N 52a-d 58a 57a 58a 54a PREPUTIAL SEPARATION e MEANS.D . 48.5 2.0 49.5 2.7 49.4 3.4 49.7 3.1 52.2 3.1** a. Excludes values for rats that were found dead or.moribund sacrificed. b. Excludes values for rats in which testing was discontinued before the ratbecame sexually mature. c. Excludes values for rats that were not observed. d. Excludes values for rat 6555, which did not have preputial separation recordedon one day and was separated the following day. e. Average day postpartum that the prepuce was observed to be separated. ** Significantly different from the Group I value (p<0.01). ARGUS 418-020 Page 347 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-G889.6) TABLE D7 (PAGE 1) : MATING AND FERTILITY - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS IN COHABITATION N 30 29 30 DAYS IN COHABITATION a MEAN+S.D . 3.0 + 2.4 3.0 + 1.1 2.4 + 1.2 RATS THAT MATED b N (%) 29( 96.7) 29(100.0) 30(100.0) FERTILITY INDEX C N/N <%> 28/ 29 ( 96.6) 28/ 29 ( 96.6) 28/ 30 ( 93.3) RATS WITH CONFIRMED MATING DATES N 29 29 30 MATED WITH FEMALE d DAYS 1-7 N (%) 29(100.0) 29(100.0) 30(100.0) RATS PREGNANT/RATS IN COHABITATION N/N 28/ 30 (%) ( 93.3) 28/ 29 ( 96.6) 28/ 30 ( 93.3) ( ] = NUMBER OF VALUES AVERAGED a. Restricted to rats with a confirmed mating date and rats that did not mate. b. Includes only one mating for each male rat. c. Number of pregnancies/number of rats that mated. d. Restricted to rats with a confirmed mating date. IV 10 30 2.7 + 1.6 30(100.0) 28/ 30 ( 93.3) 30 30(100.0) 28/ 30 ( 93.3) V 30 30 2.5 + 1.2 30(100.0) 29/ 30 ( 96.7) 30 30(100.0) 29/ 30 ( 96.7) ARGUS 418-020 Page 348 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D8 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 349 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS EXAMINED a I 0 N 60 II III 13 60 60 IV V 10 30 60 60 MORTALITY a N3 3 3 2 7 FOUND DEAD N2 3 3 1 6 MORIBUND SACRIFICED N1 0 0 11 APPEARED NORMAL N 59 58 53 44** 49** LUNGS: ALL LOBES, MOTTLED DARK RED N 1 0 0 00 PROSTATE: SMALL N0 1 0 0 0 TESTES: LEFT, FLACCID, SMALL N 0 1 0 0 0 LEFT, LARGE N0 0 1 0 0 EPIDIDYMIDES: LEFT, SMALL N0 1 0 0 0 LIVER: LEFT LATERAL AND/OR MEDIAN LOBES, TAN AND/OR BLACK OR WHITE AREA(S) N0 0 6* 10** 9** LARGE N0 0 0 0 1 KIDNEYS: RIGHT, PELVIS, MODERATE OR SLIGHT DILATION N0 0 0 4 ** 1 a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy and for rats that were found dead or moribund sacrificed. * Significantly different from the Group I value (p0.05). ** Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D8 (PAGE 2): NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 350 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS EXAMINED a N 60 60 60 60 60 MORTALITY a N3 3 3 2 7 FOUND DEAD N2 3 3 1 6 MORIBUND SACRIFICED N1 0 0 11 INTESTINES : DISTENDED WITH GAS N0 0 0 10 THYMUS: SMALL N0 0 0 1 0 STOMACH: CARDIAC REGION, ULCERATIONS N 0 0 0 10 SPLEEN: TAN AREA EXTENDED INTO THE PARENCHYMA N0 0 0 1 0 SMALL N0 0 0 0 1 a. Refer to the individual clinical observations table (Table D14 ) for external observations confirmed at necropsy and for rats that were found dead or moribund sacrificed. ** Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D9 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 351 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 30 29 TERMINAL BODY WEIGHT MEANS.D . 559.9 59.8 527.2 54.8* EPIDIDYMIS LEFT MEANS.D . 0.6854 0.0589 0.6626 0.0821 CAUDA EPIDIDYMIS LEFT MEANS.D . 0.3333 0.0363 0.3177 0.0499 TESTIS LEFT MEANS.D . 1.7456 0.1501 1.7058 0.1844 LEFT TESTIS MINUS TUNICA ALBUGINEA MEANS.D. 1.6129 0.1426 1.5455 0.2513 SEMINAL VESICLES WITH FLUID MEANS.D. 1.8978 0.3480 2.0708 0.2430 SEMINAL VESICLES WITHOUT FLUID EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE MEANS.D. MEANS.D. MEANS.D. MEANS.D . 0.9878 0.1781 0.6982 0.0609 1.7324 0.1389 1.0374 0.2849 1.0380 0.1480 0.6870 0.0446 1.7227 0.1363 1.0825 0.2897 PITUITARY MEANS.D. 0.015 0.003 0.017 0.006 BRAIN MEANS.D. 2.34 0.13 2.28 0.16 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Excludes values for rats that had organs damaged (weight affected). * Significantly different from the Group I value (p<0.05). * * Significantly different from the Group I value (p<0.01). III 3 30 523.9 48.2* 0.6749 0.0573 0.3287 0.0301 1.8278 0.2751 1.6826 0.2590 1.9677 0.2768 1.0194 0.1240 0.6831 0.0458 1.7860 0.1539 1.0265 0.2336 0.016 0.006 2.31 0.12 IV 10 30 499.3 63.5** 0.6720 0.0589 0.3288 0.0395 1.7732 0.1254 V 30 29 437.6 41.6** 0.6503 0.0488 0.3169 0.0290 1.7284 0.1618 1.6259 0.1201 1.5914 0.1483 2.0598 0.3113 1.8930 0.3026 1.0701 0.1428 0.6881 0.0455 1.7677 0.1195 1.0455 0.2343 0.014 0.005 2.28 0.10 0.9493 0.1712 0.6693 0.0503 1.7432 0.1783 0.8724 0.1759* 0.013 0.006 [ 281a 2.18 0.14** PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D9 (PAGE 2) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 30 29 TERMINAL BODY WEIGHT MEANS.D. 559,9 59.8 527.2 54.8* LIVER MEANS.D . 21.65 3.22 24.57 4.04** KIDNEY LEFT MEANS.D. 2.21 0.20 2.35 0.26* KIDNEY RIGHT MEANS.D. 2.24 0.21 2.34 0.28 ADRENAL LEFT MEANS.D. 0.032 0.006 0.032 0.008 ADRENAL RIGHT SPLEEN MEANS.D. MEANS.D. 0.030 0.007 l 29) a 0.94 0.14 0.029 0.007 0.83 0.15* THYMUS MEANS.D. 0.51 0.12 0.46 0.12 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Excludes values for rats that had organs damaged (weight affected). * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). III 3 30 523.9 48.2* 28.24 4.22** 2.46 0.20** 2.48 t 0.24** 0.031 t 0.005 0.029 t 0.005 0.85 0.14* 0.44 0.15 IV 10 30 499.3 t 63.5** 29.28 4.09** 2.30 0.22 2.33 0.25 0.029 0.006 0.028 i 0.006 0.81 0.23** 0.38 0.11** V 30 29 437.6 41.6** 29.74 3.97** 2.03 0.22** 2.04 0.21** 0.028 0.006* 0.026 0.006 0.74 0.13** 0.39 0.15** ARGUS 418-020 Page 352 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D10 (PAGE 1) : RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY FI GENERATION MALE RATS ARGUS 418-020 Page 353 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 29 30 30 29 TERMINAL BODY WEIGHT MEANS.D. 559.9 59.8 527.2 54.8* 523.9 48.2* 499.3 t 63.5** 437.6 41.6** EPIDIDYMIS LEFT MEANS.D . 0.123 0.014 0.127 0.018 0.130 0.016 0.136 t 0.017** 0.149 0.017** CAUDA EPIDIDYMIS LEFT MEANS.D. 0.060 0.007 0.060 0.011 0.063 0.008 0.066 i 0.010* 0.072 0.010** TESTIS LEFT MEANS.D. 0.314 0.036 0.327 0.050 0.351 0.061** 0.360 t 0.048** 0.396 0.044* + LEFT TESTIS MINUS TUNICA ALBUGINEA MEANS.D. 0.290 0.034 0.296 0.057 0.324 0.057* 0.330 t 0.047** 0.366 0.041** SEMINAL VESICLES WITH FLUID MEANfS.D. 0.339 0.061 0.396 0.052** 0.377 0.049* 0.416 0.064** 0.436 0.082** SEMINAL VESICLES WITHOUT FLUID EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE PITUITARY a BRAIN MEANS.D. MEANS.D . MEANS.D. MEANS.D . MEANS.D. MEANS.D. 0.176 0.033 0.126 0.014 0.312 0.036 0.185 0.052 2.621 0.589 0.421 0.045 0.198 0.034* 0.131 0.011 0.329 0.040 0.203 0.050 3.181 1.203 0.435 0.040 0.196 0.028* 0.130 0.013 0.343 0.044* 0.197 0.046 3.071 1.054 0.443 0.041 0.217 0.032** 0.140 0.017** 0.358 0.049** 0.210 0.043 2.809 1.064 0.461 0.055** 0.218 0.046** 0.152 0.018** 0.401 0.050** 0.199 0.039 3.041 1.421 ( 28] b 0.502 0.043** ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value wa9 multiplied by 1000. b. Excludes values for rats that had organs damaged (weight affected). * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. - PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE DIO (PAGE 2) : RATIOS () OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 29 30 30 29 TERMINAL BODY WEIGHT MEANS.D . 559.9 59.8 527.2 54.8* 523.9 48.2* 499.3 63.5** 437.6 41.6** LIVER MEANS.D . 3.860 0.324 4.648 0.510** 5.408 0.754** 5.895 0.697** 6.787 0.550** KIDNEY LEFT MEANS.D. 0.396 0.031 0.446 0.042** 0.472 0.045** 0.464 0.046** 0.465 0.038** KIDNEY RIGHT MEANS.D. 0.402 0.034 0.446 0.041** 0.474 0.041** 0.469 0.050** 0.467 0.036** ADRENAL LEFT a MEANS.D. 5.693 1.124 6.016 1.402 5.999 1.124 5.837 1.282 6.332 1.366 ADRENAL RIGHT a SPLEEN MEANS.D. MEANS.D . 5.355 1.242 ( 29] b 0.169 0.024 5.517 1.251 0.157 0.023 5.494 1.007 0.161 0.021 5.697 1.076 0.166 0.063 5.899 1.426 0.171 0.027 THYMUS MEANS.D . 0.091 0.022 0.088 0.023 0.082 0.024 0.077 0.025 0.088 0.033 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. b. Excludes values for rats that had organs damaged (weight affected). * Significantly different from the Group I value (p<0.05). * * Significantly different from the Group I value (p<0.01). RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. ARGUS 418-020 Page 354 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Dll (PAGE 1) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - FI GENERATION MALE RATS ARGUS 418-020 Page 355 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 29 30 30 29 BRAIN WEIGHT MEANS.D . 2.34 0.13 2.28 0.16 2.31 0.12 2.28 0.10 2.18 0.14** EPIDIDYMIS LEFT MEANS.D . 29.33 2.23 29.11 3.84 29.28 2.70 29.57 2.64 29.91 2.74 CAUDA EPIDIDYMIS LEFT MEANS.D . 14.26 1.41 13.94 2.20 14.28 1.53 14.46 1.71 14.60 1.74 TESTIS LEFT MEANS.D. 74.71 5.90 74.92 8.24 79.23 11.56 78.03 6.10 79.31 6.62* LEFT TESTIS MINUS TUNICA ALBUGINEA MEANS.D . 69.03 i 5.56 67.86 11.31 72.93 10.86 71.56 5.80 73.09 6.81 SEMINAL VESICLES WITH FLUID MEANS .D . 81.16 13.80 90.84 9.80* 85.37 12.40 90.50 12.96* 87.40 16.74 SEMINAL VESICLES WITHOUT FLUID MEANS.D . 42.24 7.07 45.56 6.31 44.20 1 5.44 47.06 6.27 43.78 8.89 EPIDIDYMIS RIGHT MEANS.D . 29.88 2.19 30.20 2.42 29.63 2.13 30.27 2.06 30.80 3.04 TESTIS RIGHT MEANS.D . 74.15 5.37 75.66 6.05 77.43 6.43 77.76 5.38* 80.05 8.12** PROSTATE MEANS.D. 44.37 11.95 47.19 11.80 44.54 10.14 45.93 10.09 40.10 8.42 PITUITARY MEANS.D . 0.62 0.14 0.73 0.25 0.70 0.24 0.60 0.20 0.61 0.29 [ 28] a ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Excludes values for rats that had organs damaged (weight affected). * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D U (PAGE 2) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 30 29 30 30 29 BRAIN WEIGHT MEANS.D . 2.34 0.13 2.28 0.16 2.31 0.12 2.28 0.10 2.18 0.14** LIVER MEANS.D. 927.17 135.62 1074.98 149.66** 1224.30 178.78** 1285.40 159.24** 1363.79 165.99** KIDNEY LEFT MEANS.D . 94.77 7.87 102.81 7.56** 106.56 9.07** 100.98 t 7.93* 93.27 9.95 KIDNEY RIGHT MEANS.D . 95.87 9.05 102.62 7.68** 107.40 10.20** 102.29 9.81* 93.60 7.88 ADRENAL LEFT MEANS.D. 1.35 0.24 1.39 0.36 1.35 0.23 1.27 t 0.26 1.26 0.25 ADRENAL RIGHT SPLEEN MEANS.D . MEANS.D. 1.28 0.28 [ 29] a 40.39 5.51 1.28 0.31 36.24 4.69* 1.24 0.22 36.73 6.06* 1.24 t 0.24 35.91 10.99** 1.17 0.26 34.21 5.76** THYMUS MEANS.D. 21.84 5.64 20.35 5.61 19.15 6.53 16.77 4.95** 17.78 6.93* ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Excludes values for rats that had organs damaged (weight affected). * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. ARGUS 418-020 Page 356 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6089.6) TABLE D12 (PAGE 1): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED N I 0 30 II III 13 29 30 IV 10 30 V 30 29 INCLUDED IN ANALYSES N 30 28a 30 30 29 ARGUS 418-020 Page 357 NUMBER MOTILE MEANS.D. 250.1 t 71.1 266.4 i 95.2 271.6 74.2 258.9 73.0 257.2 86.6 MOTILE PERCENT MEANS.D. 83.1 8.8 83.7 t 6.8 83.9 i 6.9 82.6 7.0 80.1 10.9 STATIC COUNT (NONMOTILE) MEANS.D . 51.2 30.5 51.9 27.0 52.8 27.0 56.3 20.4 64.6 40.4 TOTAL COUNT b MEANtS.D. 301.3 t 77.8 318.4 i 108.6 324.4 87.4 315.2 88.9 321.8 104.1 SPERM COUNT c MEANS.D. 135.6 t 7.8 162.0 i 110.4 144.6 79.0 136.3 62.0 115.7 t 57.5 SPERM DENSITY d MEANS.D. 1194.3 t 632.1 1423.7 i 922.5 1248.5 686.5 1206.8 565.8 1052.7 a. Excludes values for rat 1082, which had less than 200 sperm per 20 fields. b. Sum of number motile and static count. Groups of five fields were evaluated until a sperm count of at least 200 was achieved or 20 fields were evaluated. c. Sperm count used in the calculation of sperm density. Ten fields were evaluated. d. The sperm density was calculated by dividing the sperm count by the volume in the image area (34.3 x 10"6 mL), multiplying by 2 (dilution factor) and multiplying by 10'6 to obtain the sperm concentration. The calculated sperm concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left cauda epididymis (see Table D20 for the weight of the left cauda epididymis) to obtain the sperm density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. 487.7 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER; T-6889.6) TABLE D12 (PAGE 2) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED N I 0 30 ii III 13 29 30 IV 10 30 V 30 29 INCLUDED IN ANALYSES N 30 28a 30 30 29 SPERMATID COUNT b MEANS.D. 45.3 13.1 40,4 i 15.1 39.3 15.4 40.2 15.7 42.7 16.2 SPERMATID DENSITY c MEANS.D. 82.6 25.4 73.8 26.5 67.8 25.1 71.4 27.4 77.1 a. Excludes values for rat 1082, which had less than 200 sperm per 20 fields. b. Spermatid count used in the calculation of spermatid density. Ten fields were evaluated. c. The spermatid density was calculated by dividing the spermatid count by the volume in the image area (34.3 x 10'* mL I , multiplying by 2 (dilution factor) and multiplying by 10'6 to obtain the spermatid concentration. The calculated spermatid concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left testis minus tunica albuginea (see Table D20 for the weight of the left testis minus tunica albuginea) to obtain the spermatid density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. t 27.3 ARGUS 418-020 Page 358 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D13 (PAGE 1) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS TESTED N 30 29 30 INCLUDED IN ANALYSES N 30 28a 30 NORMAL MEANS.D. 195.3 1.9 195.2 2.6 194.9 2.0 DETACHED HEAD MEANS.D . 2.7 1.6 3.2 1.8 3.0 1.7 NO HEAD MEANS.D. 1.4 1.0 1.4 1.2 1.7 1.1 BROKEN FLAGELLUM MEANS.D . 0.5 0.7 0.0 0.2* 0.3 0.5 NO HOOK MEANS.D. 0.0 0.0 0.1 0.3 0.0 0.2 COILED FLAGELLUM MEANfS.D. 0.0 0.2 0.0 0.0 0.1 0.3 BENT FLAGELLUM MEANS.D . 0.0 0.0 0.0 0.0 0.0 i 0.0 BENT FLAGELLUM TIP MEANS.D . 0.0 0.0 0.0 0.0 0.0 0.0 PERCENT ABNORMAL MEANS.D. 2.4 0.9 2.4 1.3 2.6 1.0 a. Excludes values for rat 1082, which had less than 200 sperm per 20 fields. * Significantly different from the Group I value (p<0.05). IV 10 30 30 195.3 2.1 3.0 1.8 1.2 1.2 0.3 0.6 0.0 0.2 0.0 i 0.2 0.0 0.2 0.0 0.0 2.4 1.0 V 30 29 29 194.1 2.6 3.1 1.4 2.0 1.6 0.6 0.8 0.0 0.0 0.0 0.2 0.0 0.2 0.0 0.2 2.9 1.3 Page 359 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE DI4 (PAGE 1) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 360 DOSAGE GROUP I 0 MG/KG/DAY RAT # DESCRIPTION 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 6553 6554 6555 1021 1022 1023 1024 1025 1026 DP ( 93- 94) DP ( 93- 94) DP ( 93- 97) D P (112-113) D P (114 -118) DP( 76 ) DP ( 24 ) DP ( 3 ) DP ( 4- 7) DP ( 4- 14) DP ( 22- 32) DP( 22- 32) DP ( 31- 35) DP ( 35- 37) DP ( 35- 37) DP ( 37- 59) DP( 27- 34) DP ( 35- 37) DP( 25 ) DP ( 36 ) DP( 17-118) DPI 36 ) NO ADVERSE FINDINGS CHROMORHINORRHEA SNOUT : SWOLLEN CHROMODACRYORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISALIGNED INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES ANNULAR CONSTRICTION OF THE TAIL NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES URINE-STAINED ABDOMINAL FUR ANNULAR CONSTRICTION OF THE TAIL NECK AND HEAD: SCAB (0.4 CM IN DIAMETER) ABDOMINAL DISTENTION a NO ADVERSE FINDINGS SNOUT: SWOLLEN INCISORS: MISSING/BROKEN NECK: SCAB (0.3 CM IN DIAMETER) HEAD: SCAB (0.5 CM IN DIAMETER) HEAD: ABRASION (1.0 CM IN DIAMETER) a NO ADVERSE FINDINGS FOUND DEAD CHROMORHINORRHEA RIGHT EYE: ENLARGED a EXCESS SALIVATION DP DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 361 DOSAGE GROUP I 0 MG/KG/DAY RAT # DESCRIPTION 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 DP ( 8- 9) DP ( 2 ) DP ( 8- 16) DP ( 23- 43) DP ( 2- 4) DP ( 4 ) DP ( 4 ) DP ( 4 ) DP ( DP ( DP ( DP ( DP ( 8- 16) 35 ) 74 ) 2) 35 ) DP ( 34 ) DP ( 34 ) DP ( 42 ) DP ( 77- 85) DP ( 8 ) DPI 15- 24) DP ( 30- 31) DP ( 32- 46) DP ( 33- 34) DP ( 33- 40) DP( 47- 54) DP ( 59- 85) DP ( 89-118) ABDOMINAL DISTENTION SOFT OR LIQUID FECES ABDOMINAL DISTENTION ANNULAR CONSTRICTION OF THE TAIL CHROMORHINORRHEA a DECREASED MOTOR ACTIVITY COLD TO TOUCH MORIBUND SACRIFICED NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION EXCESS SALIVATION SOFT OR LIQUID FECES CHROMORHINORRHEA EXCESS SALIVATION NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA VOCALIZATION FOUND DEAD INCISORS: MISALIGNED NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES BACK: SCAB (DID NOT EXCEED 0.5 CM IN DIAMETER) HEAD: SCAB (0.4 CM IN DIAMETER) HEAD: ABRASION (1.0 CM IN DIAMETER) CHROMODACRYORRHEA INCISORS: MISSING/BROKEN HEAD: SCAB (0.8 CM IN DIAMETER) BACK: SCAB (DID NOT EXCEED 1.0 CM X 0.5 CM) LOCALIZED ALOPECIA: LIMBS a DP = DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 3) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 362 DOSAGE GROUP I 0 MG/KG/DAY RAT # DESCRIPTION 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 DP ( 33- 34) DP ( 34 ) DP ( 34 ) DP ( 34 ) DP ( 2 ) DP ( 9- 13) DP ( 42 ) DP ( 93- 94) DP ( 20 ) DP ( 29 ) DP( 4 ) DP ( 18- 28) DP ( 90 ) DP ( 90 ) DP ( 90- 97) DP ( 90-109) DP (103 -10 9) DP ( 109 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES CHROMORHINORRHEA SOFT OR LIQUID FECES EXCESS SALIVATION CHROMORHINORRHEA SOFT OR LIQUID FECES SOFT OR LIQUID FECES SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES CHROMORHINORRHEA ANNULAR CONSTRICTION OF THE TAIL CHROMORHINORRHEA RALES CHROMODACRYORRHEA INCISORS: MISSING/BROKEN a CHROMODACRYORRHEA a INCISORS: MISALIGNED a NO ADVERSE FINDINGS DP = DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 4) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 363 DOSAGE GROUP II 1 MG/KG/DAY RAT # ioei 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 DP ( 28- 36) D P (104 -105) DP ( 5 ) DP ( 5 ) DP ( 6 ) DP ( 3 ) DP ( 38 ) DP ( 26- 36) DP( 25- 35) DP ( 29 ) DP ( 44- 45) DP ( 27 ) DP ( 25- 35) DP ( 37 ) DP ( 25- 35) DP ( 37 ) DP ( 37 ) DP ( 25- 35) DP ( 28- 37) DESCRIPTION NO ADVERSE FINDINGS ANNULAR CONSTRICTION OF THE TAIL CHROMODACRYORRHEA CHROMORHINORRHEA a URINE-STAINED ABDOMINAL FUR FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA ANNULAR CONSTRICTION OF THE TAIL ANNULAR CONSTRICTION OF THE TAIL SOFT OR LIQUID FECES SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS ANNULAR CONSTRICTION OF THE TAIL NO ADVERSE FINDINGS VOCALIZATION NO ADVERSE FINDINGS ANNULAR CONSTRICTION OF THE TAIL NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS EXCESS SALIVATION ANNULAR CONSTRICTION OF THE TAIL HEAD: SCAB (0.2 CM IN DIAMETER) DP = DAY POSTWEANING a. Observation confirmed at necropsy. . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 5) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 364 DOSAGE GROUP II 1 MG/KG/DAY RAT # DESCRIPTION 1086 1087 1088 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 DP ( 10- 17) DP ( 80 ) DP ( 80- 81) DP ( 80-115) DP ( 80-119) D P (102 -103) DP ( 45 ) DP ( 25- 38) DP ( 37 ) DP ( 37 ) DP ( 20 ) DP ( 32- 51) DP ( 42- 51) DP ( 50- 52) DP ( 3- 6) DP ( 24- 25) DP ( 35- 36) DPI 50- 51) DP ( 34 ) DP ( 34 ) DP ( 34- 36) DPI 34- 37) DPI 34- 37) ABDOMINAL DISTENTION CHROMORHINORRHEA SNOUT : SWOLLEN INCISORS: MISALIGNED CHROMODACRYORRHEA a CHROMORHINORRHEA FOUND DEAD NO ADVERSE FINDINGS RIGHT EYE: CORNEAL OPACITY SOFT OR LIQUID FECES EXCESS SALIVATION NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES PTOSIS ANNULAR CONSTRICTION OF THE TAIL CHROMODACRYORRHEA NO ADVERSE FINDINGS CHROMODACRYORRHEA ENOPHTHALMOS CHROMORHINORRHEA CHROMORHINORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS SNOUT: SWOLLEN URINE-STAINED ABDOMINAL FUR CHROMORHINORRHEA CHROMODACRYORRHEA a INCISORS: MISALIGNED a DP = DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 6) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 365 DOSAGE GROUP II 1 MG/KG/DAY RAT # DESCRIPTION 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 DP ( 36 ) DP ( 1 ) DP ( 1 ) DP ( 1 ) DP ( 2 > DP ( 8- 18) DP( 23- 35) DP ( 8- 18) DP(lOO-lOl) DP ( 23- 33) DP(lOO-lOl) DP ( 23- 33) DP ( 5 ) DP ( 35 ) DP ( 34 ) DP ( 7- 17) DP ( 22- 41) DP ( 34 ) DP ( 64-119) DP ( 22- 34) DP ( 34 ) DP ( 100 ) DP ( 34 ) DP ( 64- 85) NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS DECREASED MOTOR ACTIVITY COLD TO TOUCH EMACIATION FOUND DEAD ABDOMINAL DISTENTION ANNULAR CONSTRICTION OF THE TAIL ABDOMINAL DISTENTION SOFT OR LIQUID FECES ANNULAR CONSTRICTION OF THE TAIL CHROMORHINORRHEA ANNULAR CONSTRICTION OF THE TAIL NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA CHROMORHINORRHEA ABDOMINAL DISTENTION HEAD AND NECK: SCAB (DID NOT EXCEED 0.5 CM IN DIAMETER) SOFT OR LIQUID FECES LOCALIZED ALOPECIA: LIMBS a ANNULAR CONSTRICTION OF THE TAIL NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES SOFT OR LIQUID FECES INCISORS : MISALIGNED DP = DAY POSTWEANING a. Observation confirmed at necropsy. . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6B89.6) TABLE D14 (PAGE 7) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 366 DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 DP ( 5 ) DP ( 38 ) DP ( 45 ) DP ( 62- 67) DP ( 97- 98) DP ( 97-110) DP ( 97-118) D P (100-118) DP ( 118 ) DP ( 5- 9) DP( 25- 35) DP ( 27- 38) DP ( 35- 38) DP ( 25- 28) DP ( 27- 54) DP ( 25- 35) DP ( 25- 35) DP ( 64- 69) DP ( 2 ) DP ( 4- 5) DP ( 50 ) DP ( 30- 81) DP ( 30-118) DP ( 37 ) DP { 44- 77) DP( 82-118) DP ( 37 ) DP ( 25- 35) FOUND DEAD SOFT OR LIQUID FECES ANNULAR CONSTRICTIONS OF THE TAIL BACK: SCAB (DID NOT EXCEED 0.5 CM IN DIAMETER) CHROMORHINORRHEA CHROMODACRYORRHEA INCISORS: MISALIGNED a SNOUT: SWOLLEN a CHROMODACRYORRHEA a NO ADVERSE FINDINGS CHROMORHINORRHEA ANNULAR CONSTRICTIONS OF THE TAIL HEAD: SCABS (DID NOT EXCEED 0.5 CM IN DIAMETER) a NECK: SCAB (2.0 CM X 0.5 CM) a BACK: SCAB (0.4 CM IN DIAMETER) BEHIND LEFT EAR: SCAB (DID NOT EXCEED 0.5 CM IN DIAMETER) ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL INCISORS: MISSING/BROKEN FOUND DEAD CHROMORHINORRHEA RED, DRIED, SLIGHT PERINASAL SUBSTANCE INCISORS: MISALIGNED CHROMODACRYORRHEA a CHROMORHINORRHEA LACRIMATION INCISORS: MISSING/BROKEN a CHROMORHINORRHEA ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS DP = DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 8) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 367 DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 1151 1152 1153 D P (107-119) D P (107-119) D P (107-119) D P (109-110) DP ( 3 ) DP( 9 ) DP ( DP ( DP ( DP ( DP ( 2) 2) 3) 3- 15) 9- 19) D P (101-103) DP ( 36 ) DP ( 36 ) DP ( 76-103) DP ( 91-103) D P (105-110) D P (119-120) DP ( 24- 36) CHROMODACRYORRHEA a SNOUT: SWOLLEN a INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA EMACIATION FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS EMACIATION COLD TO TOUCH CHROMORHINORRHEA URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMODACRYORRHEA NO ADVERSE FINDINGS EXCESS SALIVATION NO ADVERSE FINDINGS SOFT OR LIQUID FECES INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA CHROMODACRYORRHEA a NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL DP = DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 9) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 368 DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 DP ( 35 ) DP( 59- 62) DP ( 63- 65) DP ( 35 ) DP ( 59 ) DP ( 59- 65) DP ( 92 ) D P (102-119) DP ( 35 ) DP ( 23- 33) DP ( 43- 44) DP ( 43- 54) DP ( 63- 93) DP ( 35 ) DP ( 1- 4) DP ( 38- 39) DP ( 24 ) DP ( 34 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED, SLIGHT PERIORAL SUBSTANCE BACK: SCAB (0.5 CM IN DIAMETER) LOCALIZED ALOPECIA: BACK CHROMORHINORRHEA CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA a NO ADVERSE FINDINGS SOFT OR LIQUID FECES ANNULAR CONSTRICTIONS OF THE TAIL CHROMODACRYORRHEA INCISORS: MISALIGNED NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS SOFT OR LIQUID FECES CHROMORHINORRHEA NO ADVERSE FINDINGS RED, DRIED, SLIGHT PERINASAL SUBSTANCE SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP = DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 10) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 1175 1176 1177 1178 1179 1180 D P ( 34 ) D P ( 56- 57) D P ( 56- 61) D P ( 56-108) D P ( 56-119) D P (109-118) D P (117-119) D P ( 103 ) D P (103 -119) DPU03-119) D P ( 18- 20) D P ( 21- 22) D P ( 30 ) EXCESS SALIVATION CHROMORHINORRHEA SNOUT: SWOLLEN INCISORS: MISALIGNED CHROMODACRYORRHEA a INCISORS: MISSING/BROKEN INCISORS: MISALIGNED a CHROMORHINORRHEA CHROMODACRYORRHEA a INCISORS: MISALIGNED a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS HEAD: SCAB (0.3 CM IN DIAMETER) LOCALIZED ALOPECIA: HEAD EXCESS SALIVATION DP = DAY POSTWEANING a. Observation confirmed at necropsy. Page 369 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 11) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 370 DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 DP ( 10- 20) DP ( 5 ) DP ( 10- 20) DP ( 25- 44) DP ( 25- 33) DP ( 82- 83) DP ( 82- 98) DP ( 102 ) DP ( 48- 55) DP ( 81- 86) DP ( 84-117) DP ( 24- 26) DP ( 60 ) DP ( 61- 65) DP ( 66- 75) DP ( 87 ) DP ( 8- 16) DP ( 17- 37) DP ( 24 ) DP ( 24- 40) DP ( 25- 40) DP ( 29- 32) DP ( 29- 40) DP ( 29- 40) DP ( 39- 40) DP ( 40 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION CHROMORHINORRHEA ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMODACRYORRHEA INCISORS: MISALIGNED SOFT OR LIQUID FECES INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN a MOUTH: SCAB (DID NOT EXCEED 0.5 CM X 0.5 CM) BACK: ULCERATION (1.0 CM X 0.5 CM) BACK: SCAB (1.0 CM X 0.5 CM) LOCALIZED ALOPECIA: BACK PENIS: RED SUBSTANCE NO ADVERSE FINDINGS NO ADVERSE FINDINGS TIP OF TAIL BLACK TIP OF TAIL MISSING a NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMODACRYORRHEA DEHYDRATION a ABDOMINAL DISTENTION a URINE-STAINED ABDOMINAL FUR EMACIATION a COLD TO TOUCH URINE-STAINED ABDOMINAL FUR MORIBUND SACRIFICED DP = DAY POSTWEANING a. Observation confirmed at necropsy. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 12) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 371 DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION . 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 DP ( 36 ) DP ( 69-118) DP ( 23- 33) DP ( 41- 42) DP ( 35 ) DP ( 47 ) DP ( 3 ) DP ( 3 ) DP ( 3 ) DP ( 4 ) DP ( 23- 32) DP ( 64 ) DP ( 35- 36) DP ( 35 ) DP ( 35 ) DP ( 31 ) DP ( 34 ) DP ( 34 ) DP ( 63- 64) DP ( 63- 68) DP ( 63- 68) DP ( 63- 68) DP ( 69-118) DP ( 74-118) SOFT OR LIQUID FECES NO ADVERSE FINDINGS INCISORS : MISALIGNED a ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS EXCESS SALIVATION RED, DRIED, SLIGHT PERINASAL SUBSTANCE DECREASED MOTOR ACTIVITY EMACIATION a COLD TO TOUCH FOUND DEAD HEAD: SCAB (DID NOT EXCEED 0.4 CM IN DIAMETER) SOFT OR LIQUID FECES NO ADVERSE FINDINGS DEHYDRATION a NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA SOFT OR LIQUID FECES NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA SOFT OR LIQUID FECES CHROMORHINORRHEA CHROMODACRYORRHEA SNOUT: SWOLLEN INCISORS: MISALIGNED INCISORS: MISALIGNED a CHROMODACRYORRHEA a DP - DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 13) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 372 DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION 1222 1223 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 DP ( 22- 32) DP ( 2- 6) DP ( 4- 5) DP ( 7- 24) DP ( 7- 23) DP ( 22- 34) DP ( 22- 32) DP ( 48- 49) DP ( 22- 32) DP ( 22- 32) DP ( 8 ) DP ( 22- 34) DP ( 61- 119) DP ( 22- 31) DP ( 80 ) ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS CHROMORHINORRHEA EMACIATION ABDOMINAL DISTENTION ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL SOFT OR LIQUID FECES ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL SOFT OR LIQUID FECES ANNULAR CONSTRICTIONS OF THE TAIL BOTH EARS: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS CHROMODACRYORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP = DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 14) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 373 DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 DP ( 26- 36) DP ( 26- 34) DP ( 38- 39) DP ( 25- 26) DP ( 25- 35) DP( 5- 7) DP ( 10- 18) DP ( 37 ) DP ( 10- 20) DP ( 25- 34) DP ( 10- 20) DP ( 29- 42) DP ( 37 ) DP ( 5- 6) DP ( 25- 38) DP ( 37 ) DP ( 37 ) DP ( 37 ) DP ( 37 ) DP ( 37 ) DP ( 38 ) DP ( 4 ) DP ( 10- 20) DP ( 25- 35) ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL HEAD: SCAB (0.2 CM IN DIAMETER) a NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION CHROMORHINORRHEA ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL EXCESS SALIVATION CHROMORHINORRHEA ANNULAR CONSTRICTIONS OF THE TAIL a CHROMORHINORRHEA VOCALIZATION ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL RALES EMACIATION CHROMORHINORRHEA ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL DP = DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 15) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 374 DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 DP ( 36 ) DP ( 36 ) DP ( 67 ) DP ( 83- 91) DP( 84 ) DP ( 87 ) DP ( 92- 96) DP( 93 ) DP ( 3- 4) DP( 8- 9) DP ( 24- 34) DP( 6 ) DP ( 9- 19) DP ( 3 ) DP ( 3 ) DP < 3 ) DP ( 4 ) DP ( 24- 37) DP ( 1 ) DP ( 1 ) DP ( 1 ) DP ( 1 ) DP ( 2 ) DP ( 1 ) DP ( 1 ) DP( 1 ) DP( 1 ) DPI 2 ) NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES PENIS: RED SUBSTANCE URINE-STAINED ABDOMINAL FUR PENIS : RED SUBSTANCE PENIS : RED SUBSTANCE UNGROOMED COAT PENIS : RED SUBSTANCE CHROMORHINORRHEA CHROMORHINORRHEA ANNULAR CONSTRICTIONS OF THE TAIL CHROMORHINORRHEA ABDOMINAL DISTENTION DECREASED MOTOR ACTIVITY COLD TO TOUCH URINE-STAINED ABDOMINAL FUR FOUND DEAD NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL a DECREASED MOTOR ACTIVITY BOTH EYES: CORNEAL OPACITY a EMACIATION a COLD TO TOUCH FOUND DEAD DECREASED MOTOR ACTIVITY BOTH EYES: CORNEAL OPACITY a EMACIATION COLD TO TOUCH FOUND DEAD DP = DAY POSTWEANING a. Observation confirmed at necropsy. ' . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 16) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 375 DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 1265 1266 1267 1268 1269 1270 1271 1272 1273 . 1274 1275 1276 1277 1278 D P ( 24- 34) D P ( 36- 39) D P ( 36 ) D P ( 11- 16) D P ( 11- 16) D P ( 36- 37) DPI 49 ) D P ( 76- 77) D P ( 26- 33) DP( 26- 39) D P ( 29- 39) D P ( 32- 39) DP( 32- 39) D P ( 33- 39) D P ( 39 ) DP ( 39 ) DP ( 5 ) DP( 2 - 3 ) DP ( 3 ) DP ( 3 ) DP ( 3 ) DP( 3 ) DP( 4 ) DPI 3- 15) DPI 5- 7) DPI 8- 16) DPI 23- 70) ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS NO ADVERSE FINDINGS LACRIMATION RIGHT EYE : SWOLLEN ANNULAR CONSTRICTIONS OF THE TAIL a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED, DRIED, SLIGHT PERINASAL SUBSTANCE CHROMODACRYORRHEA CHROMORHINORRHEA DEHYDRATED a EMACIATION a DECREASED MOTOR ACTIVITY URINE-STAINED ABDOMINAL FUR a COLD TO TOUCH a CHROMODACRYORRHEA a MORIBUND SACRIFICED URINE-STAINED ABDOMINAL FUR CHROMORHINORRHEA a DECREASED MOTOR ACTIVITY EMACIATION a COLD TO TOUCH URINE-STAINED ABDOMINAL FUR a FOUND DEAD URINE-STAINED ABDOMINAL FUR EMACIATION ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL DP = DAY POSTWEANING a. Observation confirmed at necropsy. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 17) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 376 DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 1279 1280 1281 1282 1283 1284 1285 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 DP ( 8- 18) DP ( 28- 35) DP ( 2 ) DP ( 3 ) DP( 16 ) DP ( 18- 21) DP ( 61- 69) DP ( 89 ) DP ( 89 ) DP ( 89- 91) DP ( 89-119) D P (102-104) DP(117-119) DP(118-119) D P C L18-119) DP ( 22- 32) DP ( 7- 23) DP ( 7- 23) DP ( 9- 10) DP ( 59- 61) DP ( 7- 23) DP ( 61- 64) DP ( 61-119) DP ( 61-119) DP ( 22- 23) DP ( 15 ) ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL CHROMORHINORRHEA FOUND DEAD LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS INCISORS: MISALIGNED CHROMORHINORRHEA SOFT OR LIQUID FECES CHROMODACRYORRHEA INCISORS: MISALIGNED a CHROMODACRYORRHEA CHROMODACRYORRHEA a INCISORS : MISSING/BROKEN a LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL ABDOMINAL DISTENTION ABDOMINAL DISTENTION CHROMORHINORRHEA BACK: SCAB (0.3 CM IN DIAMETER) ABDOMINAL DISTENTION SNOUT: SWOLLEN CHROMODACRYORRHEA a INCISORS : MISALIGNED a NECK: SCAB (0.5 CM IN DIAMETER) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP DAY POSTWEANING a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D14 (PAGE 18) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 1296 1297 1298 1299 1300 D P ( 100 ) D P (100-101) D P (100-106) D P (100-106) D P (103-106) D P (104 -106) D P ( 107 ) D P ( 20- 29) D P ( 20- 29) D P ( 25- 99) D P ( 25-117) D P ( 67 ) D P ( 72- 84) D P ( 91- 92) D P (111-117) RALES CHROMORHINORRHEA CHROMODACRYORRHEA a INCISORS: MISALIGNED a EMACIATION a URINE-STAINED ABDOMINAL FUR a FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL INCISORS: MISALIGNED CHROMODACRYORRHEA a INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN a DP = DAY POSTWEANING a. Observation confirmed at necropsy. Page 377 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE I) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 378 RAT # 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 6553 6554 6555 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 DOSAGE GROUP I 0 MG/KG/DAY DAY 1 8 15 22 29 36 43 50 36. 39. 45. 45. 38. 38. 42. 44 . 50. 41. 42. 49. 48. 46. 47. 48. 44 . 35. 45. 47. 53. 48. 31. 30. 35. 37. 38. 38. 31. 44. 54 . 69. 81. 75. 74. 67. 105. 118. 133. 122. 133. 116. 159. 176. 198. 178. 192. 173 . 218. 233 . 264. 231. 254. 227. 281. 289. 323. 292. 319. 286. 337. 368. 364. 387. 407 . 408. 78. 124. 181. 240. 293. 334 . 372 . 83 . 138. 194. 250. 304. 87. 148. 212. 270. 338. 69. 116. 169. 225. 279. 79. 132. 188. 252. 307. 350. 394. 84. 123. 175. 230. 282. 320. 387 . 77. 116. 176. 236. 300. 354. 401. 88. 147. 209. 274. 328. 359. 398. 91. 148. 222. 290 . 350. 90. 137. 201. 262. 322. 80. 129. 192 . 250. 300. 336. 365. 57. 97. 152. 200. 80. 131. 185. 227. 80. 128 . 189. 238 . 85. 131. 201. 259. 318. 367. 411. 56 . 135. 201. 268 . 338. 57. 104 . 164 . 215. 269. 319. 368. 62. 97. 153. FOUND DEAD ON DAY 25 POSTWEANING 66. 101. 163. 220. 271. 69. 115. 174 . 235. 286. 331. 368. 57. 106. 158. 210. 261. 62. 107. 161. 208. 260. 298. 329. MORIBUND SACRIFICED ON DAY 4 POSTWEANING 76. 130. 198. 255. 317. 57 424 . 439. 433 . 407. 417. 422 . 432. 416. 387. 449 . 412 . 403 . 343 . 64 461. 469. 465. 434 . 441. 460. 471. 445 . 421. 491. 451. 446. 379. 70a PRECOHABITATION b 487. 489. 487. 452. 524 . 523 . 525 . 487. 473. 485. 500. 459. 508. 537. 542 . 4 97. 435. 472. 520. 483 . 559 . 524 . 466. 398 . 500 . 420. DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 2) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 379 RAT # DOSAGE GROUP I 0 MG/KG/DAY 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 DAY 1 46. 45. 31. 28. 40. 40. 39. 48 . 44. 40. 37. 42. 50. 62. 58. 58. 55. 43. 39. 39. 46. 44. 46. 50. 45. 41. 36. 37. 39. 39. 8 79. 77. 55. 52 . 65. 71. 63. 81. 76. 70. 61. 77. 84. 102 . 90. 97 . 92. 77. 67. 70. 85. 87. 82 . 89 . 85. 90. 66. 70. 76. 68. 15 132. 126. 92. 89. 110. 124 . 108. 129. 121. 112. 101. 112. 138 . 155. 141. 150. 147. 126. 107. 108. 139. 144 . 133 . 139. 138 . 144 . 118 . 122 . 128 . 123 . 22 192 . 184. 144 . 150. 161. 186. 161. 188. 182 . 163. 150. 166. 199. 215. 201. 217. 214. 191. 162 . 161. 205 . 217. 194. 202 . 209. 220. 177. 178 . 187. 183. 29 253 . 240. 198 . 198 . 219. 240. 211. 245. 232. 215 . 198 . 221. 252 . 261. 256. 272 . 275. 256. 219. 213 . 270. 270. 247. 267. 270. 272. 240. 248. 246. 231. 36 315. 291. 249. 246. 267. 296. 262. 275. 256. 257. 305. 307. 346. 322. 276. 333 . 335. 331. 329. 306. 306. 279. 43 364 . 50 407. 289. 299 . 319. 313. 57 445 . 345 . 349 . 64 474 . 371. 372. 70a PRECOHABITATION b 491. 518. 385 . 385 . 395. 406. FOUND DEAD ON DAY 42 POSTWEANING 320. 365. 388.. 415. 297. 332. 351 . 379. 348. 392. 423 . 448. 348. 379. 406 . 422. 411. 368 . 458. 420 . 496 . 456 . 540. 504. 313 . 373. 365. 347. 427. 408 . 372 . 461 . 443 . 395. 491. 483. 365. 365. 412. 407. 429 . 419 . 451. 454 . 434 . 396. 464 . 432. 569. 520 . 405. 512 . 500. 477 . 470 . 457. 421. 496. 458. 598. 548 . 428. 545. 510. 505. 490 . 365. 340. 304 . 3 92. 378 . 344 . 424 . 407 . 376 . 462. 426. 395. 480 . 441. 415 . 493. 441. 415. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 3) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 380 RAT # DOSAGE GROUP I DAY 78 85 92 99a 106 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 6553 6554 6555 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 507. 509. 510. 474 . 504. 523. 523. 480. 537. 542. 547. 503. 530. 554 . 558. 508. 547. 580. 576. 525. 491. 518. 528. 488. 456. 504. 541. 533. 498. 473. 525. 560. 564. 510. 490. 536. 577. 574. 509. 489. 552. 595. 585. 535. 500 . 534 . 555. 573. 576. 607 . 506. 518. 540. 559. FOUND DEAD ON DAY 25 POSTWEANING 577. 491. 503. 531. 534. 562 . 410 . 422. 432. 441. 568. MORIBUND SACRIFICED ON DAY 4 POSTWEANING DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. First weekly value recorded after cohabitation. 113 556. 592. 567. 532. 565. 621. 605. 540. 518. 612. 593 . 573 . 452 . 0 MG/KG/DAY 120 PROTOCOL 4X8-020 ? ^ J G tVAGE) TW0'GENERATI0N <NE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 4) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 381 RAT # DOSAGE GROUP I DAY 78 85 92 99a 106 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 510. 533. 389. 402 . 413. 404. 546 . 547. 418 . 423 . 425. 432. 444 . 447. 509. FOUND DEAD ON DAY 42 POSTWEANING 450. 464. 489 . 496. 416. 433. 448 . 454. 492. 486. 506 . 525. 453. 461. 476 . 487. 596. 542. 593. 545. 621 . 582 . 641. 594. 421. 523 . 512. 427. 551. 513 . 450 . 573 . 525.. 462. 595. 540. 495. 483 . 514. 503 . 523 ,. 510,. 540. 532. 507. 473. 529. 484 . 667. 603. 473 . 615. 560. 545. 546. 497. 455. 436. 506. 470. 439. 526.. 436.. 451 . 537. 449. 455. 541. 440 . 478 . DAY - DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. First weekly value recorded after cohabitation. 113 581. 465. 456. 516. 477. 540. 496. 682. 624. 489. 642. 576. 555. 562. 548. q MG/KG/DAY PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 5) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 382 RAT # DOSAGE GROUP II 1 MG/KG/DAY 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 DAY 1 43. 44. 41. 37. 35. 35. 31. 40. 37. 46. 40. 41. 50. 40. 42 . 47. 44 . 48. 33. 48. 48. 41. 37. 37. 32. 33 . 43 . 42 . 35. 36. 8 IS 22 29 69. 112. 166. 223 . 73 . 71. 118. 122. 170 ., 159.. 225. 220. FOUND DEAD ON DAY 6 POSTWEANING 59. 97. 140.. 185. 59. 101. 150 . 203 . 51. 95. 145.. 204. 65. 109. 161.. 211. 59. 99. 146., 201. 78. 125. 187.. 245. 69. 112. 163 .. 221. 74. 124. 186.. 241. 86. 13 7. 206,. 264. 71. 116. 181.. 239. 74 . 128. 190.. 242. 83 . 132. 195., 258. 80 . 131. 195.. 252. 86. 148. 206 ,. 264 . 60. 97. 150,. 205. 78. 128. 193 ,. 245. 79. 130. 193 ,. 254. 72 . 116. 172 ,. 228. 66. 113 . 165 . 220. 67. 112 . 165 . 216. 55 . 95. 146 . 190. 60. 101. 152.. 196. 83. 132. 194 . 258. 81. 134 . 196 . 254 . 80. 127. 181 . 238. 64 . Ill. 152 . 201. 36 264 . 281. 273 . 239. 254 . 260. 273 . 253. 321. 279. 310. 325. 300. 312. 322. 313 . 332. 254 . 296 . 313 . 286. 280. 268. 245. 245. 322. 315. 300 . 246. 43 301. 317. 299. 311. 296. 318. 365. 347. 372. 350. 328. 322 . 282. 361. 349. 288. 50 332 . 358. 335. 344 . 321. 353. 390. 57 360. 394 . 357. 367. 343 . 378 . 419. 64 385 . 422 . 379 . 400 . 355 . 406 . 446 . 70a PRECOHABITATION b 400. 436. 438. 465. 394. 397. 356. 438. 464. 422. 439. 380. 477. 494 . 382 . 404 . 408 . 439. 443 . 474 . 467. 496. 490. 538 . 381. 366 . 347 . 397 . 404 . 387. 425 . 436 . 416 . 453. 462 . 442 . 481. 512. 477 . 306 . 328 . 345 . 357. FOUND DEAD ON DAY 45 POSTWEANING 378 . 410. 446 . 465. 323 . 355 . 387 . 400. 329. 494 . 452 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 6) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 383 RAT # DOSAGE GROUP II 1 MG/KG/DAY 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 DAY 1 39. 44 . 40. 36. 40. 39. 42. 37. 39. 56. 63. 45. 33. 23. 32. 30. 44 . 48. 45. 40. 38. 50. 49. 48. 35. 35. 47. 52 . 43 . 43. 8 15 22 29 70. 117. 178 . 233 . 78. 126. 186 . 246. 73. 125. 179 . 242. 71. 111. 168 . 226. 73. 123. 184 . 244. 69. 118. 178 . 234. 66. 108. 165 . 224. 75. 123. 178 . 239. 76. 125. 187 . 254. 94. 142. 196 . 248. 92. 142. 193 . 249. 78. 135. 195 . 257. 71. 128 . 190 . 245. FOUND DEAD ON DAY 2 POSTWEANING 57. 101. 151 . 210. 52. 92 . 136 . 184. 75. 118. 172 . 220. 79. 125. 184 . 231. 72. 120. 170 . 223. 62 . 107. 161 . 212. 59. 106. 173 . 230. 87. 137. 201 . 266. 86. 131. 202 . 265. 84 . 134. 194 . 257. 65. 102. 165.. 220. 67. 108. 165 . 224. 75. 118. 177 . 231. 84. 126. 188 . 242. 77. 120 . 184 . 232. 74 . 121. 182 . 239. 36 293. 303 . 294. 278. 310. 293. 272. 293 . 271. 295. 310. 313 . 302. 275. 229. 268. 281. 284. 262 . 286. 324. 307. 381. 265. 291. 43 334 . 330. 336. 332. 335. 345. 276. 307. 298 . 364. 353 . 330. 346. 342 . 50 372 . 370. 386. 366. 359. 388. 311. 337. 325. 396. 382. 369. 372 . 378. 57 395. 402. 422. 390. 379. 418. 348. 360. 343. 426. 409. 399. 402 . 408 . 64 419. 440 . 459. 412 . 402 . 450. 387. 381. 368 . 453 . 451. 424 . 432 . 432 . 70a PRECOHABITATION b 435. 464 . 470 . 491. 424 . 414 . 509. 521. 445 . 440. 469. 501. 404 . 393 . 438. 409. 373 . 487 . 479. 445 . 444 . 448 . 392 . 520 . 496 . 471. 477 . 467. DAY - DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 7) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 384 RAT # DOSAGE GROUP II DAY 78 85 92 99a 106 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 421. 438. 449. 459. 455. 465. 478. 490. FOUND DEAD ON DAY 6 POSTWEANING 406. 419. 423. 428. 428 . 448. 438. 451. 369. 370. 389. 399. 465. 473. 491. 512. 484 . 495. 505. 518. 468. 511. 455. 475. 416. 511. 520. 480. 518. 485. 555. 506 . 562 . 511. 579. 538 . 595. 469. 492 . 462. 476. 503. 462 . 489 . 530 . 479 . 501. 557. 492. 517. 569. 507. 375. 323. 364 . 386. FOUND DEAD ON DAY 45 ]POSTWEANING 480 . 497 . 505 . 526. 433 . 459. 478 . 496. 372 . 533. 496. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. First weekly value recorded after cohabitation. 113 478. 509. 466. 464 . 413 . 525. 525. 542. 625 . 528. 558. 521. 402 . 556. 516. 1 MG/KG/DAY 120 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 8) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 385 RAT # DOSAGE GROUP II DAY 78 85 92 99a 106 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 452. 460. 474 . 489. 494 . 500. 506. 438. 429. 509. 519. 440. 434 . 533. 543. 458 . 454. 554 . 566. 465. 471. 573. 582. 475. 479. 490. 503. 521. 535. FOUND DEAD ON DAY 2 POSTWEANING 432. 403. 436. 407. 456. 419. 479. 429. 551. 492 . 434 . 389. 513 . 496. 465. 472. 460. 396. 521. 499. 484. 478 . 463 . 400. 541. 518. 496. 488. 486. 409. 545. 531. 511. 503 . 496. 425. 559. 543 . 527. 511. 506 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. First weekly value recorded after cohabitation. 113 504 . 573. 603 . 474 . 485. 562 . 503. 440. 429. 571. 549. 541. 517. 511. 1 MG/KG/DAY 120 512. 594 . 632. 498 . 494 . 446. 437. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 9) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 386 RAT # DOSAGE GROUP III 3 MG/KG/DAY 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 DAY 1 35. 39. 39. 31. 33. 34. 35. 39. 36. 24. 32. 42. 45. 53 . 51. 40. 40. 46. 47. 37. 35. 32. 35. 34. 42. 56. S3. 56. 54. 46. 8 15 22 29 36 FOUND DEAD ON DAY 5 POSTWEANING 74. 120. 186. 247. 300. 78. 132. 195. 249. 309. 64. 112. 178. 239. 297. 56. 99. 154 . 208 . 274 . 60. 103 . 152. 205. 269. 58. 102 . 153. 205. 258. 72. 125. 191. 248 . 312. 62. 102. 167. 228. 288. FOUND DEAD ON DAY 2 POSTWEANING 56. 102. 160. 226. 287. 72. 117. 179. 233. 283 . 77. 116. 173 . 225 . 280. 88. 142. 213. 270. 340. 87. 140. 204 . 266. 317. 76. 129. 184. 233 . 288. 80. 131. 197. 252. 306. 85. 140. 204 . 273 . 328 . 78. 128. 192. 252. 305. 55. FOUND DEAD ON DAY 9 POSTWEANING 63 . 109. 164. 222 . 281. 58. 99. 151. 203 . 256. 67. 110. 168 . 225. 283. 52. 92. 146. 191. 248. 68. 110. 163 . 211. 245. 85. 136. 196. 257. 313. 85. 141. 194 . 250. 304 . 94 . 144 . 198. 251. 299. 96. 145. 201. 249. 304 . 77. 124. 182. 234. 277 . 43 50 337. 345. 376. ' 379. 303 . 325. 344 . 318. 367. 338. 326. 339. 360. 392. 354. 406. 362. 360. 327 . 322 . 298 . 352. 364. 331. 276. 335. 338. 297. 381. 371. 57 407. 419. 64 431. 452. 70a PRECOHABITATION b - -- 448 . 472. 480 . 517. 354 . 390. 427. 390. 438. 380. 386. 375. 422 . 457. 419. 467. 398. 406. 389. 436. 469. 441. 483 . 421. 418. 407. 473 . 495. 474 . 520. 450. 439. 377. 398. 352. 395. 426. 383 . 400. 451. 402. 417. 494 . 433 . 315. 413. 391. 339. 441. 417. 354 . 469. 432 . 376. 485. 458 . DAY a DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 10) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 387 RAT # DOSAGE GROUP Ill 3 MG/KG/DAY 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 DAY 1 54 . 52. 49. 63. 59. 36. 36. 36. 50. 48. 53. 46. 46. 50. 49. 30. 30. 36. 34 . 36. 36. 55. 46 . 58. 58. 47. 64. 65 . 42 . 45 . 8 100. 92. 86. 99. 98. 66. 73. 70. 94. 93. 96. 79. 77. 93. 87. 46. 49. 63. 59. 64. 66. 95. 87. 96. 98. 80. 103. 101. 72 . 80. 15 158. 145. 145. 160. 151. 121. 122 . 124 . 152. 147. 148. 126. 120. 152. 148 . 82. 86. 102 . 95. 104 . 108. 144 . 137. 161. 149. 125 . 156. 155 . 126. 135. 22 226. 207. 207. 228 . 216. 189. 186. 183 . 226. 215. 216. 177. 171. 222. 211. 120. 137. 159. 144 . 155. 164 . 204 . 190. 231. 213 . 177. 220. 220. 184 . 196. 29 293. 269. 261. 292 . 282 . 253 . 242 . 238. 291. 277. 277. 238. 231. 274 . 272. 172. 189. 215. 193 . 202 . 214 . 261. 241. 293 . 275. 225. 275. 274 . 239. 255. 36 338. 328. 317. 346. 345. 327. 300. 291. 345. 339. 339. 291. 288. 326. 336. 228 . 248 . 274 . 265 . 300 . 340. 279. 330. 312 . 43 384 . 355 . 389.. 328 . 385 . 332 . 359 . 280 . 298 . 325.. 294 . 342 . 385 . 324 . 371 . 356 . 50 418. 390. 429. 343. 419. 377. 392. 319. 338. 368. 313. 370. 414. 360. 3 92. 395. 57 455. 428. 456. 391. 448. 399. 417. 381. 399. 332. 407. 390. 391. 401. 430. 64 488. 453 . 482 . 70a PRECOHABITATION b 514 . 544 . 474 . 499. 495 . 514 . 422 . 471. 445. 489. 473 . 525. 421. 438. 446 . ' 458. 462 . 477 . 416 . 427 . 435. 452 . 467. 483 . 353 . 439. 396. 416 . 416. 368 . 451. 413 . 434 . 437. 384 . 477 . 432 . 461. 443 . 448 . 475. 490 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 11) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 388 RAT # DOSAGE GROUP III 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 DAY 78 85 92 99a FOUND DEAD ON DAY 5 POSTWEANING 462. 471. 491. 497. 505. 508. 535. 504 . 106 513 . 498. 399. 408 . 414 . 425. 450. 480. 505. 517. FOUND DEAD ON DAY 2 POSTWEANING 476. 492. 512. 517. 465. 476. 490. 507. 507. 440. 430. 512. 445 . 431. 530. 465. 451. 542. 482 . 456. 437. 536. 538. 524. 561. 489. 472 . 405. 412. 428. 436. FOUND DEAD ON DAY 9 POSTWEANING 476. 485. 510. 526 . 423. 422 . 443 . 460. 443 . 545. 475. 372 . 483 . 445 . 377. 477. 457. 383. 512. 474 . 394 . 520 . 487. 405. 530. 497 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. First weekly value recorded after cohabitation. 113 509. 503. 447. 557. 556. 540. 580. 505. 419. 453. 562. 489. 411. 494 . 501. 3 MG/KG/DAY 120 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE D15 (PAGE 12) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 389 RAT # DOSAGE GROUP Ill DAY 78 85 92 99a 106 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 530. 486 . 504. 532. 500. 511. 556. 505. 527. 560. 516. 542. 579. 516. 561. 456. 515. 475. 524. 456. 477. 455. 478. 459. 478. 486. 486. 377. 472 . 432 . 453 . 442 . 388. 481. 436. 465. 450. 480. 518. 490. 536. 512 . 551. 482 . 491. 496. 502. 507. 516. 526. 529. 405. 496. 451. 480. 463. 417. 512. 472. 491. 480. 541. 545. 514 . 566 . 512. 498. 541. 548. 427. 518. 478 . 460. 457. 570 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. First weekly value recorded after cohabitation. 113 576. 528. 567. 523. 573. 531. 509. 555. 554. 432 . 524. 469. 471. 466. 565. 3 MG/KG/DAY 120 588 . 539. 580. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D1S (PAGE 13) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 390 RAT # DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 8 15 22 29 36 43 50 57 64 70a PRECOHABITATION b 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 47. 46. 34. 35. 33 . 31. 46. 48. 43. 47. 45. 45. 50. 48. 47. 48. 55. 61. 43. 41. 45. 46 . 35. 44 . 43 . 36. 40. 53. 49. 41. 76. 121. 183 . 231. 77. 123. 189 .. 243. 58. 102. 158. 214. 60. 101. 161.. 221. 54. 90. 134 ., 181. 54. 92. 143 . 199. 80. 131. 190., 247. 82. 142. 204 . 244. 78. 130. 202.. 266. 88. 149. 218.. 288. 77. 124. 182 . 236. 79. 120. 183.. 238. 90. 135. 201 . 254. 84. 132. 198 . 262. 83. 125. 183 . 233. 78. 120. 179 . 233. 83. 125. 178 . 230. 100. 151. 218 . 282. 70. 109. 161 . 207. 71. 117 . 144 . 134. 95. 127. 183 . 235. 76 . 126. 187 . 242. 70 . 116. 178 . 238. 76. 116. 186 . 240. 70. 112. 176 . 227. 66. 109. 168 . 215. 66. 102. 158 . 207. 82. 137. 198 . 252. 83 . 135. 198 . 246. FOUND DEAD ON DAY 4 :POSTWEANING 283 . 292 . 255. 269. 227. 245. 296 . 293 . 338. 361. 282. 290. 303 . 311. 283 . 282. 280. 348 . 245. 116 . 285. 297. 282. 291. 288. 277. 263 . 315. 306. 324 . 308., 292.. 323.. 391.. 353 . 346. 330. 346. 435. 370. 374 . 354. 371. 454. 400. 401. 381. 383. 467. 410. 426. 407. 386. 490 . 434 . 472. 430. 401. 521. 322,. 354.. 320,. 364. 385 . 351. 390. 415. 377. 418. 440 . 399. 443 . 463. 415. 462. 490. 441. 404 . 450. 497 . 541. 573 . MORIBUND SACRIFICED ON DAY 40 POSTWEANING 607. 314 . 334 . 346. 354 . 372. 383 . 397 . 406. 402 . 413 . 422 . 433. 306 . 351 . 339. 381. 361. 414 . 393 . 447 . 413 . 463 . 444 . 478 . DAY DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 14): BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 391 RAT # DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 8 15 22 29 36 43 50 57 64 70a PRECOHABITATION b 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 38. 51. 52. 47. 43 . 42 . 42. 36. 35. 55. 52. 52. 50. 35. 35. 48. 48. 42. 39. 38. 35. 48. 55. 54 . 47 . 46. 39. 44 . 49. 51. 61. 89. 90. 83. 82. 76. 77. 63. 62. 84. 83. 88. 85. 52. 54 . 82. 80. 70. 68. 65. 77. 84 . 89. 93. 78. 77. 66. 75. 83. 85. 102 . 149. 143. 136. 135. 122. 128. 108. 104. 135. 126. 134. 132. 80. 92. 132. 130. 111. 110. 108. 127. 128. 140. 149. 125. 129. 104. 126. 132. 136. 161. 222. 204 . 200. 204 . 186. 183 . 166 . 150. 190. 177. 197. 198. 123 . 139. 199. 188. 157. 159. 155. 190 . 184 . 205 . 212. 179. 196. 158. 191. 193 . 194 . 204 . 280. 260. 255. 260. 236. 241. 214. 188. 242. 233 . 246. 256. 177 . 196. 256. 232. 204 . 202. 203 . 242 . 226. 259. 267. 236. 245. 207. 246. 246 . 246. 254 . 330. 193 . 306. 315. 291. 296. 269. 238. 273 . 302 . 221. 251. 305. 253 . 259. 319. 301. 253 . 293 . 287. 373. 351.. 334. 336., 274 ., 303 ,. 333 . 274 . 291 . 345 . 276 . 290 . 354 . 343 . 273 . 328 . 320. 416. 390. 370 . 372. 297. 334. 362. 301. 310. 369. 306. 298. 400. 383 . 288. 362. 336. 440 . 413 . 404 . 401. 309. 363 . 384. 332. 342. 387. 324 . 312. 421. 403 . 305 . 394 . 358. 473 . 439. 439. 428 . 326. 335. 404 . 364 . 370 . 406 . 346. 329. 462 . 432. 326 . 424 . 372 . 483 . 400. 497. 455. 449 . 436. 338. 373 . 414 . 389. 387. 422 . 476. 476. 459. 364 . 386. 432 . 424 . 399. 451. 365. 390. 336. 484 . 346. 508 . 442. 338 . 454 . 353 . 440 . 463 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE IS) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 392 RAT # DOSAGE GROUP IV DAY 78 85 92 99a 106 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 427. 450. 423 . 415. 506. 424 . 462 . 440. 391. 510. 440. 485. 453. 425. 532 . 438 . 501. 454 . 446 . 547. 445 . 509. 479. 457. 574. 452. 477. 435. 450. 494 . 446. 466. 507 . 466. 476. 513 . 480 . 492 . 523. 495. 595. 607. 633 . 638. 679. MORIBUND SACRIFICED ON DAY 40 POSTWEANING 411. 430. 428. 430. 441. 444 . 455. 451. 469. 473. 432 . 447. 461. 473 . 472 . 481. 494 . 504 . FOUND DEAD ON DAY 4 POSTWEANING 483 . 517. DAY DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. First weekly value recorded after cohabitation. 113 460. 533 . 488 . 470. 582 . 488. 534 . 498. 661. 483 . 473 . 489. 526. 10 MG/KG/DAY 120 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 16) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 393 RAT # DOSAGE GROUP IV DAY 78 85 92 99a 106 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 388. 491. 396. 497. 412. 510. 428. 538. 447. 542. 471. 471. 458. 357. 382. 427. 414. 393. 443 . 470. 468. 452. 346. 372. 446. 424. 396. 455. 480. 484. 472. 373. 403. 457. 450. 414 . 471. 4 92 . 500. 480. 382. 404 . 480 . 466. 429. 484 . 501. 507. 498. 400. 413 . 492 . 486. 424 . 489. 386. 392 . 392 . 402. 407 . 338 . 503 . 348. 509. 352. 526. 360. 545 . 365. 544 . 452. 350. 455. 341. 454 . 357. 464 . 367. 465. 386. 454 . 458. 468 . 489. 492 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. First weekly value recorded after cohabitation. 113 455. 561. 512. 522. 503. 402. 414. 502. 490. 429. 500. 411. 366. 556. 480. 381. 493 . 10 MG/KG/DAY 120 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 17) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 394 RAT # 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 1269 1270 DOSAGE GROUP V DAY 1 8 15 22 29 35. 34. 34. 36. 41. 36. 32. 28. 30. 43 . 38. 41. 45. 39. 48. 48. 43. 41. 26. 24 . 43. 45. 25. 24 . 40. 42. 42. 47. 47. 59. 60. 100 . 157 . 216. 61. 102. 158 . 216. 51. 91. 147 . 202. 68. 113. 176 . 237. 70. 119. 180 . 244. 65. 100. 156 . 216. 54 . 85. 136 . 190. 48. 80. 129 . 179. 46. 82. 132 . 177. 64. 101. 14 8 . 183. 77. 126. 172 . 213. 71. 118. 170 . 209. 70. 107. 160 . 204. 58. 92. 145 . 194. 85. 133. 187 . 241. 86. 132. 186 . 240. 71. 112 . 168 . 231. 61. 97. 146 . 182. 47. 69. 118 . 171. FOUND DEAD ON DAY 4 POSTWEANING 68. 103 . 151 . 199. 71. 109. 162 . 208. FOUND DEAD ON DAY 2 POSTWEANING FOUND DEAD ON DAY 2 POSTWEANING 66. 99. 150 . 198. 71. 107. 157 . 213. 73 . 113 . 165 . 219. 83. 120. 181 . 235. 86. 128. 197 . 255. 99. 142. 191 . 242. 36 269. 260 . 235. 289. 311. 262. 235. 222. 229. 211. 248 . 243 . 247. 229. 289. 290. 274 . 204 . 214. 232 . 248 . 242. 255. 269. 272 . 288 . 269. 30 MG/KG/DAY 43 50 330,. 369. 329.. 354 ,. 278 ,. 254.. 268 ,. 359. 397. 310. 278. 300. 272,. 258 . 330.. 309,. 253 . 260,. 281. 278. 365. 351. 290. 286. 282.. 306. 331.. 356. 57 397 . 64 432 . 70a PRECOHABITATION b 448. 465 . 374 . 407. 339. 305. 330. 402 . 421. 365. 317. 346. 422 . 428. 382. 324. 348. 446. 457 . 399. 336. 360. 304 . 288. 381. 381. 312. 322. 323 . 311. 401. 406. 337. 349. 340. 328. 410. 416. 353 . 359. 359. 350. 441. 420 . 371. 377. 321. 391. 340 . 352 . 369. 417. 418 . 442 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 18) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 41S-020 Page 395 RAT # DOSAGE GROUP V 30 MG/KG/DAY 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 1281 1282 1283 1284 1285 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 1296 1297 1298 1299 1300 DAY 1 60. 42. 39. 47. 42 . 45. 25. 27. 33. 34. 36. 50. 51. 46. 45. 32. 36. 29. 48. 47. 45. 50. 49. 49. 52 . 49. 38. 36. 44. 42. 8 15 22 29 100. 152. 205 . 256. 66. 102. 155 . 201. 63. 100. 147 . 199. 77. 127. 184 . 242. 69. 117. 162 . 145. 72. 111. 169 . 199. FOUND DEAD ON DAY 4 POSTWEANING 40. 67. 108 . 144. 52. 83. 130 . 187. FOUND DEAD ON DAY 3 POSTWEANING 70. 113. 167 . 214. 79. 122. 175 . 223. 81. 124. 171 . 232. 71. 108. 164 . 210. 70. 111. 170 . 188. 55. 85. 138 . 187. 56. 88. 137 . 181. 52. 85. 130 . 182. 77. 119. 180 . 234. 80. 125. 185 . 239. 76. 124. 178 . 224. 87. 134 . 185 . 232. 84. 114 . 167 . 224. 81. 112. 172 . 229. 79. 123. 182 . 237. 76. 119. 180 . 218. 67. 114. 167 . 220. 65. 106. 158 . 203. 75. 122. 182 . 239. 76. 120. 177 . 210. 36 298. 238. 239. 285. 116. 244 . 172 . 234. 261. 260. 276. 256. 238. 226. 278 . 284. 259. 270. 261. 242. 267. 43 50 57 64 70a PRECOHABITATION b 330,. 362. 388. 410 . 436. 469. 265 . 282. 299. 320 . 334 . 323,. 348. 376. 412 . 440. MORIBUND SACRIFICED ON DAY 39 POSTWEANING 355 . 456. 205 ,. 243. 261. 289 . 301. 324 . 294 . 287,. 283 ,. 320. 293. 302. 354. 298. 322 . 374 . 307 . 346 . 388. 323 . 359. 414 . 346. 389. 278 ,. 264 . 316,. 318.. 289,. 316. 286. 331. 336. 303. 338. 311. 350. 354 . 312. 359 . 323 . 376 . 374 . 329 . 372. 338 . 386. 390. 336. 376. 350. 388 . 392 . 353 . 310.. 304.. 264 . 300 ,. 344. 329. 294. 334 . 350. 349. 300. 341. 367 . 370 . 312 . 371 . 388. 376. 318. 368. 401. 394. 341. 391. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 19) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 396 RAT # 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 1269 DOSAGE GROUP V DAY 78 85 92 456. 457. 461. 99a 477. 106 476. 113 441. 30 MG/KG/DAY 120 432. 435. 3 94. 332. 355. 436. 449. 398. 338. 353. 466. 472. 413. 356. 364. 469. 477. 418 . 358. 372 . 486. 480. 427. 368. 383. 492. 490. 439. 377. 378. 354. 352. 365. 382. 343. 429. 346. 433. 361. 443. 366. 448 . 416. 378. 415. 427 . 365. 378. 384. 397 . FOUND DEAD ON DAY 4 POSTWEANING 370. 357. 378. 367. FOUND DEAD ON DAY 2 POSTWEANING FOUND DEAD ON DAY 2 POSTWEANING 366. 367. 380. 390. 396. 380. 462. 444 . 411. 384 . 403 . 403 . 401. 476. 446 . 422. 376. 423. 437. 445. 467. 477. 495. 498. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. First weekly value recorded after cohabitation. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D15 (PAGE 20) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 397 RAT # DOSAGE GROUP V DAY 78 85 92 99a 106 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 1281 1282 1283 1284 1285 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 1296 1297 1298 1299 1300 452. 457. 465. 465. 478. 350. 341. 356. 359. 372. 450 . 448. 469. 475 . 486 . MORIBUND SACRIFICED ON DAY 39 POSTWEANING FOUND DEAD ON DAY 4 POSTWEANING 323. 326. 334. 345 . 369. FOUND DEAD ON DAY 3 POSTWEANING 407 . 412. 423. 437. 334. 350. 355. 363 . 450. 362 . 384. 396. 406. 423 . 434 . 378. 341. 385. 391. 350. 373 . 355. 388. 388 . 359. 388. 360. 391. 393 . 372. 405 . 371. 412 . 403 . 386 . 413 . 382. 422 . 415 . 396. 405 . 391. 338. 391. 408. 394 . 344 . 386. 417. 402 . 352. 394. 433 . 414 . 378. 401. 435. 284 . 372. 419 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. First weekly value recorded after cohabitation. 113 491. 378. 490. 30 MG/KG/DAY 120 510. 394 . 507. 382 . 466. 383 . 435. 420 . 397. 428 . 427 . 397 . 440. FOUND DEAD ON DAY 107 POSTWEANING 383 . 434 . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE 1) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 398 RAT # 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 6553 6554 6555 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 DOSAGE GROUP I 0 MG/KG/DAY DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 60. 116. 163. 188 . 199. 72. 124. 165. 202. 195. 197. 183 . 88. 144 . 191. 215. 231. 233 . 207. 76. 135. 164 . 181. 200. 81. 140 . 178 . 205. 212. 222 . 204 . 74. 130. 161. 173 . 177. 78. 117. 151. 172. 180. 195. 188. 87. 130. 165. 183. 193 . 82. 143. 191. 197. 219. 69. 114. 145. 165. 178. 78. 129. 156. 172 . 189. 203. 208. 73. 156. 165. 169. 183. 201. 186. 68. 137. 150. 171. 203. 206. 218 . 96. 143. 171. 193 . 211. 199. 189. 97. 169. 194. 209 . 234 . 86. 147. 158. 176. 195. 70. 142. 162. 181. 192. 182 . 186. 50. 107. 131. 144 . 85. 143 . 155. 260 . 80. 135 . 151. 166 . 76. 132. 149. 169. 178. 193. 204 . 82. 151. 167. 191. 205. 68. 116. 147. 174. 193 . 205. 203 . 76. 129. 149 . FOUND DEAD ON DAY 25 POSTWEANING 69. 118. 143 . 179. 195. 66. 125. 140 . 166 . 181. 186. 182 . 78. 111. 123. 137 . 156. 66. 108. 139. 158. 176. 177. 168 . MORIBUND SACRIFICED ON DAY 4 POSTWEANING 71. 134 . 168 . 196. 205 . 194. 223 . 210 . 194 . 209. 202 . 223. 199. 193 . 224 . 205 . 200. 173 . 194 . 229. 203 . 197. 211. 209. 225. 197. c 225 . 212 . 200. 165. 159. 173. 175. 170 . 192. 173. 191. 164. 167. 186. 185. 173 . 143 . 159. 218 . 206. 197. 206. 211. 218 . 195. 186 . 223 . 208 . 205. 173 . 178. 213 . 191. 188. 219 . c c 202 . c 220 . c 214 . 147 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE 2) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 399 RAT # DOSAGE GROUP I 0 MG/KG/DAY DAY 1 - 8 8 - 1 5 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 76. 62. 62. 53 . 60. 76. 55. 80. 75 . 75. 46. 78. 66. 87. 74. 82. 69. 74. 65. 70. 71. 70. 71. 81. 81. 87. 72. 77. 82. 57. 115. 109. 106 . 110. d 122 . 100 . 112. 112. 121. 103. 118. 128. 143 . 124. 136. 135. 124. 119. 117. 128. 143 . 115. 129. 136. 141. 126. 133. 118. 111. 165. 158. 147. 142. 140. 163 . 136. 154 . 157. 147. 131. 136. 170. 162. 151. 158. 161. 159. 145. 138 . 166. 177. 149. 153 . 172 . 170. 161. 168. 163 . 163. 196. 191. 180. 174 . 171. 190. 155. 180. 181. 165. 147 . 157. 186. 173. 177. 175. 175. 182 . 172. 174 . 199. 189. 193 . 206. 201. 191. 72 . 192 . 191. 183 . 200. 199. 189. 187. 191. 188. 162. 207. 188 . 179. 183 . 190. 212 . 212 . 199. 237. 210 . 215. 216 . 214. 208. 187. 207. 203. 194 . 181. 185. 160. 213. 194. 182. c 188. 173 . FOUND DEAD ON DAY 42 POSTWEANING 183. 192. 177. 179. 181. 199. 198. 185. 218. 224. 249. 267. 198. 221. 227. 214 . 211. 221. 228. 244. 228. 243. 240. 246. 206. 254. 210 . 263. c 232. 240. c 242. c c 264 . 200. 201. 196. 200. 204. 204. 190. 196. 209. 237. 192 . 209. 237. 207. 201. c 206. 219. 241. 193 . 174 . 156. 133 . 144 . 149. 196. 156. 191. 185. 163. 215. 185. 176. 246 . 181. 201. 153 . 204. 193. 162. 187. 190. 232 . 187. 220. 216. 198. 259. 218. 188. 206. 207. 180 . 190 . 212. 200. 166 . 180. 195. 213 . 189. 224 . 212 . 194 . 246 . 217. 192 . 207 , 213 . DAY DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. d. Soiled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE 3) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 400 RAT # DOSAGE GROUP II 1 MG/KG/DAY 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 67. 120. 159. 168. 77. 125. 151. 169. 69. 123. 128. 164. FOUND DEAD ON DAY 6 POSTWEANING 66. 106. 134. 160. 64 . 106. 139. 155. 54 . 99. 145. 174 . 69. 119. 155. 176. 62. 108. 138. 162. 79. 121. 159. 176. 72. 117. 141. 161. 65. 130. 159. 181. 86. 146. 177. 189. 72. 123. 169. 191. 72. 145. 179. 200. 80. 132. 165. 185. 68. 132. 160. 173. 84. 151. 182. 192 . 70. 114. 146. 164. 84 . 128 . 150. 171. 74 . 124. 154. 168. 74 . 135. 144 . 167. 61. 121. 152. 173 . 72 . 119. 140. 158. 69. 110. 140. 156. 72. 117 . 135. 147. 87. 122. 172. 191. 90. 121. 167. 173. 92. 136. 158. 175. 78. 124. 136. 154 . 178. 185. 187. 180. 169. 190. 196. 192. 203. 179. 201. 201. 207. 213. 187. 191. 208. 172. 184. 181. 177. 192. 176. 178. 158. 203. 188. 191. 159. 175. 207 . 171. 200 . 200. 190. 199. 170. 180. 168. 177. 209. 174. 181. 180 . 183 . 169. 180. 140. 152. 182 . 186. 204. 174. 188. 167. 185 . 204. 176. 189. 142. 139. 158. c 162. 165 . 191. 168 . 187 . 176. 186 . 195. 184. 177. 182 . 165 . 189. 181. 171. 191. 231. 192 . 193 . 195 . 211. 213 . 198. 191. 190. 208 . 195. 243 . 204 . 239. 169. 207. 222. 241. 195. 180 . 175. 211. 184 . 188 . 215. 183 . 183 . 177. 159. 157. 204 . 193 . 184 . 161. c c 130. FOUND DEAD ON DAY 45 POSTWEANING 190 . c c 174 . 179 . 191. 179. 145. 131. 204 . c 189. 240 . 200. 182 . 183 . 171. 256 . 174 . DAY - DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last Interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE 4) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 401 RAT # DOSAGE1 GROUP II 1 MG/KG/DAY 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 70 . 115. 145. 171. 75. 120. 150. 170 . 65. 108. 149. 181. 74. 115. 157. 180. 80. 125. 167. 203. 66. 118. 147. 167. 66. 128. 143. 167. 70. 129. 153. 183. 84. 151. 170. 218. 96. 134. 160. 180. 90. 162. 154. 170. 65. 129. 170. 200. 74. 132. 168. 189. FOUND DEAD ON DAY 2 POSTWEANING 65. 115. 141. 174 . 59. 100. 120. 137. 75. 111. 135. 159. 75. 115. 149. 172 . 67. 118. 139. 168 . 72 . 109. 124. 164 . 59. 109. 148. 164 . 77. 120. 154. 186 . 82 . 120. 165. 196. 80. 128. 161. 183. 62. 108. 136. 162. 68. 101. 136. 148. 72. 112. 137. 146. 71. 117. 149. 167. 60. 112. 157. 175. 66. 117. 157. 185. 189. 189. 193 . 199. 228. 184. 187. 195. 175. 203. 183. 197. 205. 188 . 151. 167. 197. 176. 173. 173. 206. 200. 178. 193 . 202. 195. 215. 199. 198. 202. 201. 162. 178. 182 . c 197. 193. 183. 199. 198. 214 . 222 . 200. 184 . 199. 172 . 188. 180. 206. 188. 203 . 188. 198. 200. 223. 238. 210. 197. 207. 186. 184 . 192 . 208. 201. 205 . 198. c 195. 222. 236. 198. 200. 204 . 188 . 204 . 179. 223 . 207. 205. 199. 203 . 159. 193 . 207. 187. 156. 175. 165. 183 . 147. 184 . 177. 171. 154 . 165. 185. 221. 218 . 193 . 181. 198. 194 . 214. 165. 206 . 209. 212 . 182. 202 . 194 . c 238. 191. 187. 194 . 190 . 210 . 167 . 207 . 198. 209 . 197. 194 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE 5) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 402 RAT # 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 DOSAGE GROUP III 3 MG/KG/DAY DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 FOUND DEAD ON DAY 5 POSTWEANING 89. 131. 169. 61. 198. 90. 137. 171. 184 . 203 . 68. 114. 153 . 175. 189. 58. 114. 146. 173 . 181. 68. 104 . 137. 166. 175. 56. 101. 131. 154. 175. 64. 117. 165. 187. c 51. 112 . 157. 185. 199. FOUND DEAD ON DAY 2 POSTWEANING 59. 122 . 145. 170. 178. 81. 128. 164. 179. 161. 86. 138. 154. 167. 178. 83. 149. 176. 198. 210. 82. 143. 180. 205. 217 . 42. 99. 153. 165. 179. 73. 123 . 164. 181. 185. 92. 147 . 175. 191. 208 . 82. 129. 170. 208 . 195. 63. FOUND DEAD ON DAY 9 POSTWEANING 72 . 119. 146. 165. 176. 50. 102 . 131. c 170. 69. 138. 143. 170 . 190. 56. 109. 139. 157. 180. 62. 160. 137. 157. 171. 68. 177. 147. 175 . 194. 89. 159. 180. 173 . 195. 91. 14 9. 144 . 160. 173. 87. 135. 161. 169. 195. 81. 126. 155. 182. 198. 200. 213 . 195 . 198. 211. 189. 222. 207. 190. 203 . 198. 181. 165. 214 . 213 . 192. 199. 188 . 202. 219. 183 . 213. 189. 190. 192 . 189. 178. 172 . 212. c 189. 216. 192. 212 . 233 . 196. 218. 189. 203 . 197 . 194. 176. 172 . 211. 207. 181. 211. 190. 207. 226. 196. 212. 189. 201. 199. 190 . 177 . 164 . 209. 210 . 157. 178. 160. 185. 183 . 164 . c 169. 164 . 165 . 162 . 156. 144 . 185 . 164 . 176. 121. 193 . 229. 215. 200. 199. 210. 192 . c 199. 182 . 167 . 203 . 191. 183 . 136 . 184 . 231. 229. 202 . 197. 210. 113 . 183 . 204 . 191. 164 . 162 . 190 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE G) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 403 RAT # DOSAGE GROUP Ill 3 MG/KG/DAY 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 DAY 1 - 8 101. 82. 88. 96. 98. 74 . 75. 79. 122. 98. 92. 66. 70. 89. 83. 33. 42. 48. 56. 71. 68. 75. 85. 85. 90. 73 . 81. 87. 78. 81. 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 151. 162 . 149. 146. 147. 124. 119. 123. 146. 142. 129. 111. 112. 144 . 138. 69. 90. 99. 99. 113. 105. 133. 133 . 142. 136. 113. 139. 131. 122. 117. 181. 176. 176. 179. 181. 162. 150. 160. 185. 176. 164. 129. 132. 181. 177. 101. 121. 135. 125. 137. 129. 159. 152. 182. 175. 137. 166. 170. 168. 155. 210. 197. 185. 205. 203 . 195. 178. 182. 208. 193. 188. 170. 165. 195. 214 . 128 . 148. 159. 142 . 154 . 147 . 205 . 180. 213 . 206 . 149. 181. 183 . 190 . 184 . 225. 213 . 202. 219. 224 . 218. 195. 204 . 233. 220. 199. 190. 179. 216. 230. 149. 167. 187. 166. 195. 230 . 165. 204. 218. 228. 217. 217. 212. 222. 179. 209. 173 . 185 . 203 . 164 . 189. 227 . 182 . 206 . 212. 227. c 213. 202. 262. 183 . 209. 186. 218. 216. 167. 200 . 228 . 198 . 206 . 229. 235. 236. 225. 256. 269. 186. 220. 217 . 218. c 209. 176 . 203 . 208. 206. 223 . c 224 . 254. 235. 180. 212. 225. 216. c 211. 123 . 202 . 203. 194 . 194 . 193. 182. 198 . 202. 151. 177. 176. 177. 139. 167. 151. 167. 180. 168. 199. 205. 209. 207. 216 . 190. 194 . 224 . 218 . 168 . 193 . 199. 157. 186. 206. 211. c 210. 228. 210 . 200. 204 . 220. 201. 168 . 186 . 155. 145 . 213 . 200 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE 7) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 404 RAT # DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 - 8 8 - 1 5 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 76. 137 . 156. 190. 75. 119. 163 . 199. 58. 101. 134 . 159. 63 . 103 . 147. 174. 56. 110. 127 . 174. 64 . 107 . 135. 169. 78. 136. 160. 178 . 84. 134. 174. 184 . 80. 160. 164 . 201. 88. 194 . 180. 238. 84. 138. 157. 176. 87. 135. 155. 173 . 95. 140 . 166. 199. 85. 138. 164 . 190. 85. 143 . 155. 195. 81. 129. 137. 165. 59. 117. 131. 155. 91. 152 . 169. 192 . 72. 142 . 142. 177. 75 . 143 . 170 . d 86. 140 . 162. 178. 83. 126. 148. 174 . 75 . 155 . 168 . 205. 84. 123 . 161. 208 . 80. 127 . 157 . 203 . 79 . 123 . 146. 168 . 73. 112. 132. 161. 85. 137. 156. 183. 84 . 122 . 154 . 184. FOUND DEAD ON DAY 4 POSTWEANING 205. 211. 176. 189. 206. 179. 197. 200. 241. 265. 189. 203 . 223 . 219. 218. 184 . 183. 223 . 198 . 181. 208. 199. 216. 225. 239. 194 . 179. 206. 211. 212 . 195. 162. 201. 231. 198. 169. 178 . 187. 243 . 206. 181. 182. c 230. 213. 176. 182 . 199. 218. 172 . 159. 154. 155. 193 . 195. 196. 190. 208 . 239. 199. 218. 213 . 195. 213 . 196. 200. 221. 206. 193. 220. 192 . 167. 194. 163 . 198. 205. 199. 238 . 241. 260 . 257. 213 . MORIBUND SACRIFICED ON DAY 40 POSTWEANING 233 . 197. 211. 179. 198 . 190. 219. 178 . 213 . 141. 178 . 183. 240 . 189. 206 . 187 . 212 . 189. 212 . 182 . 215. 157 . 184 . 185 . 209. 194 . 204 . 188 . 207. 239. 191. 226 . 200 . 236. 187 . 229. 180 . 211. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. d. Wet feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE 8) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 405 RAT # DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 64 . 90. 86. 79. 76. 76. 86. 62. 59. 75. 67. 77. 75. 39. 39. 80. 70. 71. 66. 64. 76. 76. 76. 83 . 69. 69. 65. 72. 75. 74 . 106. 145. 132 . 125 . 121. 116. 125. 105. 80. 121. 112. 123. 117. 76. 83. 122 . 113. 110. 109 . 112. 121. 114 . 122 . 130. 107. 107. 104 . 120. 119. 118. 130. 185. 165. 161. 188 . 114 . 165. 132. 125. 145. 129. 149. 156. 112. 119. 159. 142. 136. 147. 145. 161. 135. 166. 166. 145. 148. 140. 169. 152. 151. 154. 212. 198 . 193. 204 . 155. 181. 162. 152. 165. 155. 183 . 179. 150. 174 . 176 . 161. 161. 177 . 171. 193 . 161. 191. 193 . 177 . 165. 173 . 202. 179. 194 . 167. 220 . 99. 201. 211. 170. 194. 179. 177. 164 . 193 . 169. 190. 197. 198. 166. 211. 178. 281. 217. 174 . 224. 206 . 184. 197. 186. 166. 191. 174. 192. 209. c 161. 208. 183 . 177 . 204 . 183 . 230. 200. 194. 217. 184 . 183 . 186. 178. 202 . 212 . 184 . 153 . 222 . 199. 188. 227 . 189. 229. 203 . 212. 232 . 190. 189. 188 . 177. 207. 212 . 184 . 146. 228 . 197 . 192 . 228 . 183. 221. 190. 216. 226. 176. 165. 185. 183 . 220 . 210 . 165. 145. 232 . 204 . 203 . 226 . 159. 188 . 164 . 181. 191. 157 . 109. 141. 149. 173. 180 . 143 . 124 . 202. 168. 165. 158. 197. 209. 178. 203 . 203. 184. 192. 188. 187 . 189. 206. 154 . 151. 221. 186. 260 . 193 . 200. 220. 181. c 193. 181. 206. 199. 177. 187. 199. 152. 145 . 214 . 191. c 190. DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D16 (PAGE 9) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 406 RAT # DOSAGE GROUP V 30 MG/KG/DAY 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 1269 1270 DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 52. 99. 137. 166 . 60. 107. 143. 180 . 47 . 94. 147. 180 . 70. 123. 177. 217 . 75. 127. 168. 211. 68. 108. 144. 171. 55. 92. 118. 150. 74 . 92 . 117. 142 . 49. 93 . 113. 149. 61. 100. 136. 152. 81. 132. 143. 167. 73. 129. 147. 161. 69. 114. 139. 170. 59. 106. 133. 174. 83. 126. 148. 174 . 83 . 123 . 142. 165. 70. 125. 137. 162. 58. 120. 128. 140. 50. 88. 118. 151. FOUND DEAD ON DAY 4 POSTWEANING 66. 133 . 129. 155 . 74 . 146. 134. 169. FOUND DEAD ON DAY 2 POSTWEANING FOUND DEAD ON DAY 2 POSTWEANING 69. 126. 139. 171. 75. 123 . 135. 157. 72 . 149. 143 . 174. 69. 197. 172. 205 . 81. 138. 187. 222. 91. 135. 242 . 172 . 185. 187. 176. 237. 248 . 188 . 168. 168. 176. 158. 184. 188. 184. 182. 194. 178. 185. 148. 167. 161. c 188. 176. 200. 215. 229. 194. 210. 250. 259. 182. 174 . 190. 196. 195. 197. 191. 178. 165. 180. 261. 193. 232. c 172 . 159. 167. 185. 174 . 199. 203. 176. 172 . 170. 230. 188. c 246. 184 . 169. 176. 200. 175. 196. 218 . 170 . 180. 170. 239. 210. 215. 239. 177. 158. 159. 189. 185. 187. 216. 166. 181. 167. 231. 64 - 70a 99b-106 106 -113 165. 178. 142 . 193 . 179. 159. 135. 118. c 230. 173 . 156. 152. 217 . 236 . 174 . 164 . 147 . 168. 161. 159. 180. 140 . 144 . 203 . 234. 181. 197. 171. 179. 185 . 191. 199. 198. 176 . 162. 144 . 182. 190. 222 . 192 . 226 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) ' TABLE D16 (PAGE 10) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 407 RAT # DOSAGE! GROUP V 30 MG/KG/DAY DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 106 -113 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 1281 1282 1283 1284 1285 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 1296 1297 1298 1299 1300 92. 136. 99. 202 . 63. 95. 128 . 157 . 67. 101. 128 . 165. 79. 116. 168 . 200. 70. 113 . 164 . 235. 49. 107 . 146. 145. FOUND DEAD ON DAY 4 POSTWEANING 29. 68 . 105. 128. 44. 81. 119. 159. FOUND DEAD ON DAY 3 POSTWEANING 70. 113 . 134 . 165. 67. 110. 136. 163 . 65. 111. 131. 180. 59. 102. 155. 182. 59. 111. 159. 205. 55. 88. 118 . 148. 56. 82. 121. 161. 55. 91. 117. 147. 68. 112. 146. 187. 73 . 113 . 150 . 195 . 60. 117. 144 . 167. 74 . 136. 168. 194 . 70. 107. 128 . 177. 57. 82 . 141. 188 . 67. 119. 154 . 185 . 59. 109. 141. 151. 55 . 108 . 134 . 157. 55. 100 . 132 . 159 . 63 . 109. 144 . 171. 63. 102 . 148. 164. 206. 163. 186. 213. 173. 169. 134. 177. 189. 173 . 188. 198. 185. 182. 203. 218. 169. 205. 167. 175. 203 . 221. 227. 231. 215. 190. 179. 166. 168. 167. 142 . 210 . 192. 199. 214. 178. MORIBUND SACRIFICED ON DAY 39 POSTWEANING 141. 157. 161. 165. 142. 181. 183 . 187. 197. 182. 180. 216. 171. 186. 201. 174. 173. 164. 149. 153. 184. 190. 205 . 209. 166. c 183 . 204 . 200 . 211. c 189. 216. 212. 168. 226. 178. 215. 207. 173. 228. 168. 172. 173 . 125. 211. 179. 177 . 210 . 213. 182. 189. 221. 197. 185. 185. 222. 194. 182. 167. 230. 162. 142. 137. 165. 203 . 169. 178. 180. 204 . 163. 203. 218. 189. 212. 202 . 167. 194 . 124 . 174 . 213 . 221. 162 . 181. 177. 206. 183 . 194 . 216. 191. 196. 199. 160 . 170 . d e 218 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value. d. Rat 1296 was found dead on day 107 postweaning. e. Wet feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D17 (PAGE 1) : SEXUAL MATURATION - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 408 DOSAGE GROUP - MG/KG/DAY I II III IV V 0 1 3 10 30 PREPUTIAL RAT # SEPARATION (DAY) PREPUTIAL PREPUTIAL PREPUTIAL PREPUTIAL RAT # SEPARATION (DAY) RAT # SEPARATION (DAY) RAT # SEPARATION (DAY) RAT # SEPARATION (DAY) 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 6553 6554 6555 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 52 49 49 49 48 49 47 7 46 47 45 51 48 46 47 49 48 b 46 52c 52 49 52 d 52 53 49 48 a 50 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 46 47 51 a 51 47 48 48 51 51 55 51 49 53 51 47 49 47 50 49 47 50 52 50 55 50 47 50 50 47 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 a 51 50 52 50 52 51 45 48 a 55 53 55 47 47 45 47 48 47 a 55 52 54 58 52 46 47 46 50 46 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 47 46 52 52 58 53 48 46 50 49 48 49 49 49 49 46 49 51 52 d 50 49 48 48 56 51 50 50' 48 a 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 , 1267 1268 1269 1270 56 57 59 52 55 56 58 53 55 50 50 53 49 53 49 54 49 54 58 a 51 49 a a 49 49 50 49 46 54 DAY = DAY POSTPARTUM a. Rat was found dead or moribund sacrificed before the start of sexual maturation evaluation. b. Sexual maturation testing was discontinued before rat became sexually mature. c. Rat did not have preputial separation recorded on one day and was separated the following day; value excluded from group averages and statistical analyses. d. Rat was found dead or moribund sacrificed. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D17 (PAGE 2) : SEXUAL MATURATION - INDIVIDUAL DATA - FI GENERATION MALE RATS DOSAGE GROUP - MG /KG/DAY I II III IV V 0 1 3 10 30 PREPUTIAL RAT # SEPARATION (DAY) PREPUTIAL PREPUTIAL PREPUTIAL PREPUTIAL RAT # SEPARATION (DAY) RAT # SEPARATION (DAY) RAT # SEPARATION (DAY) RAT # SEPARATION (DAY) 1031 48 1032 50 1033 48 1034 51 1035 48 1036 48 1037 51 1038 49 p 1039 49 OQ 1040 c CD .p. 1041 49 1042 47 1043 44 1044 47 1045 50 1046 47 1047 49 1048 50 1049 50 1050 47 1051 47 1052 c 1053 49 1054 48 1055 48 1056 44 1057 48 1058 49 1059 d 1060 d 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 49 52 55 52 51 48 49 46 49 45 49 50 51 b 56 53 48 45 48 48 50 48 50 47 55 52 48 47 47 44 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 44 49 49 46 49 50 46 50 44 46 46 47 51 48 46 58 53 50 52 53 52 52 52 45 45 50 46 46 49 49 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 51 48 48 48 48 49 50 53 53 47 44 54 47 58 59 48 45 50 52 52 49 49 48 49 50 45 53 5047 47 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 1281 1282 1283 1284 1285 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 1296 1297 1298 1299 1300 49 53 54 50 a 50 b 56 54 b 54 54 48 52 52 55 58 56 53 53 49 52 49 47 52 52 52 52 49 50 "~ DAY = DAY POSTPARTUM a . Rat was found dead or moribund sacrificed. b. Rat was found dead or moribund sacrificed before the start of sexual maturation evaluation. C . Sexual maturation testing was discontinued before rat became sexually mature. d . Sexual maturation was not observed on rats 1059 and 1060. ARGUS 418-020 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D18 (PAGE 1) : MATING AND FERTILITY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 410 DOSAGE GROUP I RAT # DAYS IN COHABITATION 1002 1003 1005 1007 1011 1012 1013 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 1052 1054 1055 1058 1059 1060 2 4 3 2 2 14 2 2 1 4 2 3 3 2 4 4 1 3 5 1 5 2 4 2 4 2 1 3 3 1 M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P m PREGNANT NP NOT PREGNANT 0 MG/KG/DAY MATING STATUS M M M M M DID NOT MATE M M M M M M M M M M M M M M M M M M M M M M M M MATING DATE C C C C C C c c c c c c c c c c c c c c c c c c c c c c c FEMALE PREGNANCY STATUS P (1341) P (1302) P (1335) P (1318) P (1308) -(1358) P (1334) P (1304) P (1346) P (1359) P (1350) P (1355) P (1336) P (1342) P (1328) P (1344) N P (1316) P (1330) P (1353) P (1348) P (1340) P (1338) P (13 31) P (1345) P (1306) P (1313 ) P (1312) P (1321) P (1310) P (1325) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D18 (PAGE 2) : MATING AND FERTILITY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 411 DOSAGE GROUP II RAT # DAYS IN COHABITATION 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 1112 1114 1116 1118 1120 1 3 3 4 3 4 3 3 4 3 2 4 6 2 4 4 2 2 3 4 2 3 2 3 4 2 1 2 4 M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P. = PREGNANT NP * NOT PREGNANT 1 MG/KG/DAY MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M IG DATE C C C C C C C C C C C C C C C C C C C C C C C C c c c c c FEMALE PREGNANCY STATUS P (1415) P (1410) P (1364) P (1362) P (1387) P (1392) P (1363) N P (1378) P (1371) P (1368) P (1418) P (1367) P (1409) P (1389) P (1404) P (1413) P (13 75) P (1397) P (1407) P (1376) P (1383) P (13 99) P (14 01) P (1382) P (1379) P (1384) P (1416) P (13 93) P (1381) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D18 (PAGE 3) : MATING AND FERTILITY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 412 DOSAGE GROUP III RAT # 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 1171 1173 1175 1176 1177 1180 DAYS IN COHABITATION 1 2 4 3 2 4 4 2 2 2 3 4 i 4 1 3 1 4 i 2 4 2 1 3 2 3 2 4 i i M = MATED ( ) = FEMALE RAT NUMBER C > CONFIRMED P = PREGNANT NP NOT PREGNANT 3 MG/KG/DAY MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M MATING DATE C C C C C C C C C C C C C C C C C C C C C C C C C C C C C c FEMALE PREGNANCY STATUS P (1456) P (1443) P (1476) P (1461) P (1474) P (1472) P (1455) P (1448) P (1430) P (1424) P (1450) N P (1446) P (1480) P (1437) P (1426) P (1439) P (1431) P (1477) P (1469) P (1452) P (1436) P (1459) NP (1458) P (1428) P (1465) P (1433) P (1463) P (1468) P (1421) P (1442) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D18 (PAGE 4) : MATING AND FERTILITY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 413 DOSAGE GROUP IV RAT # DAYS IN COHABITATION 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 1237 1240 3 4 4 2 4 7 i i 2 2 3 1 1 3 4 4 3 4 4 4 i 5 1 1 1 2 1 3 4 1 M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P = PREGNANT NP = NOT PREGNANT 10 MG/KG/DAY MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M MATING DATE C C C C C C C C C C C C C C C C C C C C C C C C C c c c c c FEMALE PREGNANCY STATUS P (1528) P (1523) P (1516) P (1513) P (1527) NP(1511) P (1519) P (1502) P (14 96) P (1491) P (1533) NP(1483) P (1488) P (1500) P (1521) P (1531) P (1505) P (1508) P (14 97) P (1494) P (1486) P (1539) P (1534) P (1517) P (1524) P (1514) P (1482) P (1537) P (1507) P (1490) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D18 (PAGE 5) : MATING AND FERTILITY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 414 DOSAGE GROUP V RAT # 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 1291 1294 1296 1298 1300 DAYS IN COHABITATION 3 2 2 1 4 4 4 3 2 4 2 4 3 1 4 3 3 3 3 3 2 5 1 1 1 1 1 2 1 3 M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P = PREGNANT NP NOT PREGNANT 30 MG/KG/DAY MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M MATING DATE C C C C C C C C C C C C C C C C C C C C C C C C C C C C c c FEMALE PREGNANCY STATUS P (1588) P (1565) P (1557) P (1560) P (1566) P (1555) P (1546) P (1548) P (1573) P (1586) P (1541) P (1598) P (1568) P (1558) P (1600) P (1589) P (1571) N P (1578) P (1545) P (1552) P (1591) P (1544) P (1584) P (1583) P (1593) P (1550) P (1576) P (157 9) P (1587) P (1564) - PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 1) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 415 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a I 0 1001 DP 39 38 ALL TISSUES APPEARED NORMAL. 1002 DP 119 118 ALL TISSUES APPEARED NORMAL. 1003 DP 119 118 ALL TISSUES APPEARED NORMAL. 1004 DP 39 38 ALL TISSUES APPEARED NORMAL. 1005 DP 118 117 ALL TISSUES APPEARED NORMAL. 1006 DP 38 37 ALL TISSUES APPEARED NORMAL. 1007 DP 118 117 ALL TISSUES APPEARED NORMAL. 1008 DP 38 37 ALL TISSUES APPEARED NORMAL. 1009 DP 38 37 ALL TISSUES APPEARED NORMAL. 1010 DP 38 37 ALL TISSUES APPEARED NORMAL. 1011 DP 118 117 ALL TISSUES APPEARED NORMAL. 1012 DP 117 116 ALL TISSUES APPEARED NORMAL. 1013 DP 117 116 ALL TISSUES APPEARED NORMAL. 1014 DP 117 116 ALL TISSUES APPEARED NORMAL. 1015 DP 37 36 ALL TISSUES APPEARED NORMAL. 1016 1017 DP 37 DP 118 36 117 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 6553 6554 DP 35 DP 35 34 34 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 6555 1021 1022 1023 DP 35 DP 118 DP 37 DP 118 34 117 36 117 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1024 DP 25 25 FOUND DEAD ON DAY 25 POSTWEANING (DEATH OCCURRED 56 MINUTES AFTER DOSAGE ADMINISTRATION) . LUNGS: ALL LOBES, MOTTLED, DARK RED. ALL OTHER TISSUES APPEARED NORMAL. 1025 1026 DP 37 DP 118 36 117 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. . DP * DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 416 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a I 0 CONT. 1027 1028 DP 37 DP 117 36 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1029 DP 4 4 MORIBUND SACRIFICED ON DAY 4 POSTWEANING. ALL TISSUES APPEARED NORMAL. 1030 1031 1032 1033 1034 1035 1036 1037 1038 DP 36 DP 117 DP 36 DP 36 DP 117 DP 119 DP 36 DP 36 DP 35 35 116 35 35 116 118 35 35 34 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1039 DP 42 42 FOUND DEAD ON DAY 42 POSTWEANING (DEATH OCCURRED 33 MINUTES AFTER DOSAGE ADMINISTRATION). ALL TISSUES APPEARED NORMAL. 1040 1041 1042 1043 1044 1045 1046 1047 1048 104 9 1050 1051 DP 118 DP 118 DP 35 DP 118 DP 35 DP 118 DP 35 DP 118 DP 118 DP 35 DP 118 DP 119 117 117 34 117 34 117 34 117 117 34 117 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL.' . DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 CD H Page 417 DOSAGE GROUP (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a I 0 CONT. 1052 1053 1054 1055 1056 1057 1058 1059 1060 DP 119 DP 34 DP 118 DP DP 34 DP 31 DP 115 DP 109 DP 109 118 33 117 117 33 30 114 108 108 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 4) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 418 DOSAGE GROUP DOSAGE (MG/KG/DAY) II 1 RAT NUMBER 1061 1062 1063 1064 DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a DP 119 DP 39 DP 119 DP 6 118 38 118 5 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. FOUND DEAD ON DAY 6 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1065 DP 39 38 ALL TISSUES APPEARED NORMAL. 1066 DP 119 118 PROSTATE: SMALL (0.2716 G) . ALL OTHER TISSUES APPEARED NORMAL. 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 DP 119 DP 39 DP 119 DP 38 DP 118 DP 38 DP 118 DP 38 DP 38 DP 38 DP 118 DP 119 DP 38 DP 38 DP 119 118 38 118 37 117 37 117 37 37 37 117 118 37 37 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. b ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1082 DP 119 118 TESTES: LEFT, FLACCID, SMALL (1.0590 G ) . EPIDIDYMIDES: LEFT, SMALL (0.3393 G ) . ALL OTHER TISSUES APPEARED NORMAL. . 1083 1084 1085 1086 DP 119 DP 38 DP 38 DP 119 118 37 37 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. b. Necropsy observations were not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 5) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 419 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER ' DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a II 1 CONT. 1087 DP 45 44 FOUND DEAD ON DAY 45 POSTWEANING (DEATH OCCURRED PRIOR TO DOSAGE ADMINISTRATION). ALL TISSUES APPEARED NORMAL. 1088 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 DP 119 DP 38 DP 119 DP 120 DP 37 DP 37 DP 120 DP 37 DP 120 DP 37 DP 120 DP 37 DP 120 DP 37 DP 36 DP 119 118 37 118 119 36 36 119 36 119 36 119 36 119 36 35 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1104 DP 2 i FOUND DEAD ON DAY 2 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1105 1106 1107 1108 1109 1110 DP 36 DP 119 DP 120 DP 36 DP 36 DP 120 35 118 119 35 35 119 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING ' a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 6) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a II 1 CONT. 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 DP 36 DP 119 DP 35 DP 119 DP 35 DP 119 DP 35 DP 119 DP 35 DP 119 35 118 34 118 34 118 34 118 34 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. ARGUS 418-020 Page 420 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 7) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 421 DOSAGE GROUP DOSAGE (MG/KG/DAY) III 3 RAT NUMBER 1121 DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a DP 5 4 FOUND DEAD ON DAY 5 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1122 1123 DP 119 DP 118 118 117 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1124 DP 38 37 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.3 CM) ALL OTHER TISSUES APPEARED NORMAL. 1125 DP 38 37 LIVER: LEFT LATERAL LOBE, FOUR TAN AREAS (PINPOINT TO 0.1 1CM) . ALL OTHER TISSUES APPEARED NORMAL. 1126 DP 38 37 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.2 CM) ALL OTHER TISSUES APPEARED NORMAL. 1127 DP 118 117 ALL TISSUES APPEARED NORMAL. 1128 DP 38 37 LIVER: LEFT LATERAL LOBE, TAN AREA (0.4 CM X 0.2 C M ) . ALL OTHER TISSUES APPEARED NORMAL. 1129 DP 118 117 ALL TISSUES APPEARED NORMAL. 1130 DP 2 1 FOUND DEAD ON DAY 2 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1131 1132 1133 1134 1135 1136 1137 1138 1139 DP 118 DP 118 DP 38 DP 118 DP 119 DP 119 DP 38 DP 38 DP 119 117 117 37 117 118 118 37 37 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL.' ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. . DP DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 8) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 422 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a III 3 CONT 1140 DP 9 8 FOUND DEAD ON DAY 9 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 1151 1152 DP 119 DP 118 DP 37 DP 37 DP 118 DP 37 DP 118 DP 37 DP 118 DP 37 DP 120 DP 37 118 117 36 36 117 36 117 36 117 36 119 36 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1153 DP 120 119 TESTES: LEFT, LARGE (3.0171 G ) . ALL OTHER TISSUES APPEARED NORMAL. 1154 1155 1156 DP 120 DP 37 DP 36 119 36 35 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. LIVER: LEFT LATERAL LOBE, SIX TAN AREAS (PINPOINT TO 0.3 CM) ALL OTHER TISSUES APPEARED NORMAL. 1157 1158 1159 1160 1161 1162 1163 1164 DP 36 DP 119 DP 119 DP 36 DP 36 DP 119 DP 36 DP 119 35 118 118 35 35 118 35 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL.' ALL TISSUES APPEARED NORMAL. . DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 9) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a III 3 CONT. 1165 DP 36 35 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.2 CM) ALL OTHER TISSUES APPEARED NORMAL. 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 DP 56 DP 119 DP 119 DP 35 DP 35 DP 119 DP 35 DP 119 DP 35 DP 119 DP 119 DP 118 DP 34 DP 31 DP 115 55 118 118 34 34 118 34 118 34 118 118 117 33 30 114 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. ARGUS 418-020 Page 423 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 10) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 424 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a IV 10 1181 DP 38 37 ALL TISSUES APPEARED NORMAL. 1182 DP 118 117 ALL TISSUES APPEARED NORMAL. 1183 DP 38 37 ALL TISSUES APPEARED NORMAL. 1184 DP 118 117 ALL TISSUES APPEARED NORMAL. 1185 DP 38 37 ALL TISSUES APPEARED NORMAL. 1186 DP 118 117 KIDNEYS: RIGHT, PELVIS, MODERATE DILATION. ALL OTHER TISSUES APPEARED NORMAL. 1187 1188 1189 DP 38 DP 118 DP 117 37 117 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1190 DP 37 36 LIVER: LEFT LATERAL AND MEDIAN LOBES, NUMEROUS TAN AREAS, (PINPOINT TO 0.2 CM ) . ALL OTHER TISSUES APPEARED NORMAL. 1191 DP 37 36 LIVER: LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.1 CM) . ALL OTHER TISSUES APPEARED NORMAL. 1192 DP 117 116 ALL TISSUES APPEARED NORMAL. 1193 DP 37 36 LIVER: LEFT LATERAL LOBE, FOUR TAN AREAS (PINPOINT TO 0.2 CM) . ALL OTHER TISSUES APPEARED NORMAL. 1194 1195 1196 1197 1198 1199 DP 117 DP 118 DP 37 DP 37 DP 118 DP 37 116 117 36 36 117 36 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. . DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 11) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 425 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a IV 10 CONT. 1200 DP 40 39 MORIBUND SACRIFICED ON DAY 40 POSTWEANING. INTESTINES: DISTENDED WITH GAS. THYMUS: SMALL, (0.02 G ) . STOMACH: TWO REGIONS OF THE CARDIAC REGION, FIRST REGION, NUMEROUS ULCERATIONS, (PINPOINT TO 0.1 CM IN DIAMETER), SECOND REGION, FIVE ULCERATIONS (PINPOINT). ALL OTHER TISSUES APPEARED NORMAL. 1201 1202 1203 1204 DP 37 DP 37 DP 118 DP 117 36 36 117 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1205 DP 36 35 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.5 CM) . ALL OTHER TISSUES APPEARED NORMAL. 1206 DP 36 35 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.5 CM X 0.1 CM ) . ALL OTHER TISSUES APPEARED NORMAL. 1207 1208 1209 DP 117 DP 36 DP 117 116 35 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1210 DP 4 3 FOUND DEAD ON DAY 4 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1211 1212 1213 1214 1215 1216 1217 DP 117 DP 117 DP 36 DP 36 DP 119 DP 119 DP 119 116 116 35 35 118 118 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL.' ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. . DP DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T- 6889.6) TABLE D19 (PAGE 12) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 426 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a IV 10 CONT. 1218 DP 36 35 LIVER: LEFT LATERAL LOBE, TAN AND BLACK AREA (0.2 CM X 0.2 CM); CAUDATE LOBE, TAN AREA (0.4 CM) . ALL OTHER TISSUES APPEARED NORMAL. 1219 1220 1221 1222 DP 119 DP 35 DP 118 DP 118 118 34 117 117 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1223 DP 35 34 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.2 CM IN DIAMETER). ALL OTHER TISSUES APPEARED NORMAL. 1224 DP 118 117 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 1225 1226 1227 1228 1229 DP 119 DP 119 DP 35 DP 35 DP 119 118 118 34 34 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. SPLEEN: TAN AREA EXTENDED INTO THE PARENCHYMA (2.0 CM X 1.5 CM) . ALL OTHER TISSUES APPEARED NORMAL. 1230 1231 DP 35 DP 35 34 34 ALL TISSUES APPEARED NORMAL. LIVER: LEFT LATERAL LOBE, FIVE TAN AREAS (PINPOINT TO 0.5 CM). ALL OTHER TISSUES APPEARED NORMAL. 1232 DP 119 118 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. . 1233 DP 119 118 ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 13) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) IV 10 CONT. RAT NUMBER 1234 DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a DP 35 34 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.7 CM); MEDIAN LOBE, ONE TAN AREA (0.2 CM ) . ALL OTHER TISSUES APPEARED NORMAL. 1235 DP 35 34 LIVER: LEFT LATERAL LOBE, 4 TO 5 TAN AREAS, (PINPOINT TO 0.1 CM); MEDIAN LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.3 C M ) . ALL OTHER TISSUES APPEARED NORMAL. 1236 1237 1238 1239 DP 119 DP 119 DP 35 DP 35 118 118 34 34 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1240 DP 119 118 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. ARGUS 418-020 Page 427 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 14) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 428 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a V 30 1241 DP 119 118 ALL TISSUES APPEARED NORMAL. 1242 DP 3 9 38 ALL TISSUES APPEARED NORMAL. 1243 DP 3 9 38 ALL TISSUES APPEARED NORMAL. 1244 DP 118 117 ALL TISSUES APPEARED NORMAL. 1245 DP 118 117 ALL TISSUES APPEARED NORMAL. 1246 DP 38 37 ALL TISSUES APPEARED NORMAL. 1247 DP 118 117 ALL TISSUES APPEARED NORMAL. 1248 DP 118 117 ALL TISSUES APPEARED NORMAL. 1249 DP 118 117 ALL TISSUES APPEARED NORMAL. 1250 DP 38 37 ALL TISSUES APPEARED NORMAL. 1251 DP 38 37 LIVER: LEFT LATERAL AND MEDIAN LOBES, NUMEROUS TAN AREAS, (PINPOINT TO 0.3 CM IN DIAMETER). ALL OTHER TISSUES APPEARED NORMAL. . 1252 1253 1254 1255 1256 DP 118 DP 38 DP 119 DP 118 DP 37 117 37 118 117 36 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. LIVER: LEFT LATERAL LOBE, TAN AREA (0.8 CM). ALL OTHER TISSUES APPEARED NORMAL. 1257 1258 1259 DP 118 DP 37 DP 118 117 36 117 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1260 DP 4 3 FOUND DEAD ON DAY 4 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1261 DP 118 117 ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING a . Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 15) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 429 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a V 30 CONT. 1262 DP 37 36 LIVER: LEFT LATERAL LOBE, SIX TAN AREAS (PINPOINT TO 1.0 CM); MEDIAN LOBE, FIVE TAN AREAS (PINPOINT TO 0.3 CM) . ALL OTHER TISSUES APPEARED NORMAL. 1263 DP 2 1 FOUND DEAD ON DAY 2 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1264 DP 2 1 FOUND DEAD ON DAY 2 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1265 1266 1267 DP 37 DP 118 DP 37 36 117 36 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1268 DP 37 36 LIVER: MEDIAN LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.4 CM X 0.2 CM). ALL OTHER TISSUES APPEARED NORMAL. 1269 1270 1271 1272 1273 1274 DP 118 DP 37 DP 120 DP 37 DP 120 DP 120 117 36 119 36 119 119 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1275 DP 39 38 MORIBUND SACRIFICED ON DAY 39 POSTWEANING. LIVER: MEDIAN LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.1 CM). SPLEEN: SMALL (0.04 G ) . ALL OTHER TISSUES APPEARED NORMAL. 1276 DP 37 36 LIVER: LARGE (26.64 G ) . ALL OTHER TISSUES APPEARED NORMAL. . 1277 DP 4 3 FOUND DEAD ON DAY 4 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1278 DP 119 118 ALL TISSUES APPEARED NORMAL. DP DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 16) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 430 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a V 30 CONT. 1279 DP 36 35 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.3 CM) . ALL OTHER TISSUES APPEARED NORMAL. 1280 DP 3 2 FOUND DEAD ON DAY 3 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1281 1282 DP 119 DP 119 118 118 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. 1283 DP 36 35 LIVER: LEFT LATERAL AND MEDIAN LOBES, NUMEROUS TAN AREAS, (PINPOINT TO 0.3 CM X 0.1 CM ) . ALL OTHER TISSUES APPEARED NORMAL. 1284 1285 1286 1287 1288 1289 1290 1291 1292 1293 DP 118 DP 35 DP 35 DP 118 DP 119 DP 119 DP 119 DP 119 DP 35 DP 35 117 34 34 117 118 118 118 118 34 34 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.5 C M ) . ALL OTHER TISSUES APPEARED NORMAL. 1294 1295 DP 119 DP 35 118 34 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. LIVER: LEFT LATERAL LOBE, FOUR TAN AND WHITE AREAS (PINPOINT TO 0.3 CM ) . . ALL OTHER TISSUES APPEARED NORMAL. DP DAY POSTWEANING a. Refer to the Individual clinical observations table (Table D14) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D19 (PAGE 17) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF DOSAGES NECROPSY ADMINISTERED OBSERVATIONS a V 30 1296 DP 107 106 FOUND DEAD ON DAY 107 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1297 1298 1299 1300 DP 34 DP 118 DP 33 DP 117 33 117 32 116 ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. ARGUS 418-020 Page 431 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 432 DOSAGE GROUP I 0 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS LEFT ABS . REL. W T . % TBW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. * TBW TESTIS LEFT ABS. REL. WT. % TBW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW 1002 1003 1005 1007 1011 1012 1013 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 1052 1054 1055 1058 1059 1060 567. 602 . 572. 546. 580. 633. 607. 557. 528. 623. 604. 581. 464 . 585. 465. 461. 537. 496. 537. 509. 700. 642 . 503 . 645. 580. 568 . 574. 565 . 468. 498. 0.7752 0.7726 0.6687 0.6686 0.6963 0.7115 0.6641 0.7869 0.6555 0.6987 0.6580 0.7822 0.6933 0.6753 0.6971 0.5600 0.6153 0.5846 0.6476 0.6937 0.7059 0.6579 0.6975 0.7675 0.7354 0.7518 0.6775 0.5881 0.6360 0.6379 0.14 0.13 0.12 0.12 0.12 0.11 0.11 0.14 0.12 0.11 0.11 0.13 0.15 0.12 0.15 0.12 0.11 0.12 0.12 0.14 0.10 0.10 0.14 0.12 0.13 0.13 0.12 0.10 0.14 0.13 0.3991 0.3611 0.3080 0.3350 0.3387 0.3373 0.3204 0.3583 0.2932 0.3482 0.3339 0.4020 0.3383 0.3248 0.3283 0.2757 0.2846 0.2599 0.3170 0.3335 0.3676 0.3233 0.3498 0.3806 0.3854 0.3819 0.3243 0.2814 0.2937 0.3128 0.07 0.06 0.05 0.06 0.06 0.05 0.05 0.06 0.06 0.06 0.06 0.07 0.07 0.06 0.07 0.06 0.05 0.05 0.06 0.06 0.05 0.05 0.07 0.06 0.07 0.07 0.06 0.05 0.06 0.06 1.9221 1.8125 1.6994 1.5619 1.5902 1.7682 1.6088 1.8831 1.7762 1.8218 1.7024 1.9518 1.7226 1.7995 1.5867 1.4438 1.5830 1.6181 1.8685 2.0197 1.7596 1.5749 1.6161 2.0003 1.9346 1.9560 1.7734 1.6935 1.7162 1.6027 0.34 0.30 0.30 0.29 0.27 0.28 0.26 0.34 0.34 0.29 0.28 0.34 0.37 0.31 0.34 0.31 0.29 0.33 0.35 0.40 0.25 0.24 0.32 0.31 0.33 0.34 0.31 0.30 0.37 0.32 1.7786 1.6880 1.5948 1.4691 1.4829 1.6627 1.5081 1.7555 1.6737 1.6868 1.5794 1.8349 1.6188 1.6663 1.4943 1.2926 1.5238 1.4797 1.6406 1.8917 1.6111 1.4321 1.4572 1.8134 1.7771 1.8014 1.6231 1.5125 1.6036 1.4347 0.31 0.28 0.28 0.27 0.26 0.26 0.25 0.32 0.32 0.27 0.26 0.32 0.35 0.28 0.32 0.28 0.28 0.30 0.30 0.37 0.23 0.22 0.29 0.28 0.31 0.32 0.28 0.27 0.34 0.29 1.6467 2.1281 1.7303 1.8008 1.7689 2.1506 2.2159 2.5406 1.6431 1.8339 1.6675 2.2373 1.5930 2.2558 2.0640 1.6995 2.0948 1.7416 1.4429 2.1573 1.3668 2.0222 1.7612 2.3132 2.0816 2.5943 2.0127 1.8827 1.1345 1.3529 0.29 0.35 0.30 0.33 0.30 0.34 0.36 0.46 0.31 0.29 0.28 0.38 0.34 0.38 0.44 0.37 0.39 0.35 0.27 0.42 0.20 0.31 0.35 0.36 0.36 0.46 0.35 0.33 0.24 0.27 0.8308 1.0361 0.8830 0.9282 0.9602 1.0488 1.2484 1.3229 0.9578 1.0077 0.7430 1.0835 0.9180 1.1674 0.8644 0.9306 0.9268 1.0356 0.8137 1.1610 0.7839 0.9460 0.7748 1.1160 1.1932 1.4246 1.1275 0.9591 0.7241 0.7172 0.15 0.17 0.15 0.17 0.16 0.16 0.20 0.24 0.18 0.16 0.12 0.19 0.20 0.20 0.18 0.20 0.17 0.21 0.15 0.23 0.11 0.15 0.15 0.17 0.20 0.25 0.20 0.17 0.15 0.14 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 2) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 433 DOSAGE GROUP I 0 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS RIGHT ABS. REL. W T . % TBW 1002 1003 1005 1007 1011 1012 1013 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 1052 1054 1055 1058 1059 1060 567. 602. 572. 546. 580. 633. 607. 557. 528. 623 . 604. 581. 464 . 585. 465. 461. 537. 496. 537. 509. 700. 642 . 503 . 645. 580 . 568. 574. 565. 468 . 498 . 0.7585 0.7227 0.6810 0.6742 0.6834 0.6799 0.6817 0.8172 0.6814 0.7343 0.6593 0.7373 0.6915 0.6714 0.6982 0.5628 0.6359 0.6364 0.6825 0.7169 0.7403 0.6381 0.7014 0.8552 0.8026 0.7438 0.7348 0.6267 0.6254 0.6724 0.13 0.12 0.12 0.12 0.12 0.11 0.11 0.15 0.13 0.12 0.11 0.13 0.15 0.11 0.15 0.12 0.12 0.13 0.13 0.14 0.10 0.10 0.14 0.13 0.14 0.13 0.13 0.11 0.13 0.14 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. TESTIS RIGHT ABS. REL. WT. % TBW PROSTATE ABS. WT. REL. % TBW PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW 1.8845 1.7920 1.6608 1.5845 1.5867 1.7336 1.6417 1.7921 1.7002 1.8175 1.6437 1.8810 1.6696 1.6776 1.5835 1.5086 1.6333 1.5862 1.8901 1.9229 1.7809 1.4826 1.5870 1.9756 1.9853 1.9381 1.8211 1.6947 1.7833 1.7323 0.33 0.30 0.29 0.29 0.27 0.27 0.27 0.32 0.32 0.29 0.27 0.32 0.36 0.29 0.34 0.33 0.30 0.32 0.35 0.38 0.25 0.23 0.32 0.31 0.34 0.34 0.32 0.30 0.38 0.35 0.4671 0.6059 0.5167 0.5157 0.7725 1.3440 1.0484 1.0938 1.3176 0.9022 1.2225 1.6240 1.2618 1.2276 1.2740 0.8117 1.1217 1.1027 0.8592 1.0457 1.4155 1.0329 1.0311 1.3585 1.1700 1.1579 1.1323 1.1133 0.7495 0.8267 0.08 0.10 0.09 0.09 0.13 0.21 0.17 0.20 0.25 0.14 0.20 0.28 0.27 0.21 0.27 0.18 0.21 0.22 0.16 0.20 0.20 0.16 0.20 0.21 0.20 0.20 0.20 0.20 0.16 0.17 0.015 0.014 0.011 0.014 0.011 0.014 0.014 0.012 0.013 0.013 0.015 0.015 0.015 0.016 0.013 0.009 0.011 0.011 0.019 0.015 0.014 0.023 0.010 0.020 0.013 0.020 0.021 0.018 0.018 0.012 2.64 2.32 1.92 2.56 1.90 2.21 2.31 2.15 2.46 2.09 2.48 2.58 3.23 2.74 2.80 1.95 2.05 2.22 3.54 2.95 2.00 3.58 1.99 3.10 2.24 3.52 3.66 3.18 3.85 2.41 2.27 2.40 2.36 2.23 2.22 2.32 2.29 2.51 2.30 2.27 2.25 2.52 2.17 2.45 2.25 2.25 2.39 2.25 2.40 2.28 2.42 2.40 2.20 2.62 2.47 2.46 2.43 1.94 2.44 2.40 0.40 0.40 0.41 0.41 0.38 0.37 0.38 0.45 0.44 0.36 0.37 0.43 0.47 0.42 0.48 0.49 0.44 0.45 0.45 0.45 0.34 0.37 0.44 0.41 0.42 0.43 0.42 0.34 0.52 0.48 21.20 25.00 19.70 21.20 24.75 24.99 21.79 22.01 17.05 25.08 23.69 22.31 18.86 21.65 17.02 16.86 20.38 23.82 21.30 18.32 29.20 27.26 21.29 25.09 24.34 20.05 21.35 20.17 16.10 17.81 3.74 4.15 3.44 3.88 4.27 3.95 3.59 3.95 3.23 4.02 3.92 3.84 4.06 3.70 3.66 3.66 3.80 4.80 3.97 3.60 4.17 4.25 4.23 3.89 4.20 3.53 3.72 3.57 3 .44 3.58 ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-S889.6) TABLE D20 (PAGE 3) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 434 DOSAGE GROUP I 0 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. TBW ADRENAL LEFT ABS. REL. WT. % TBW a ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. WT. REL. % TBW 1002 1003 1005 1007 1011 1012 1013 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 1052 1054 1055 1058 1059 1060 567. 602. 572. 546. 580. 633. 607. 557. 528. 623. 604 . 581. 464 . 585. 465. 461. 537. 496. 537. 509. 700. 642 . 503. 645. 580. 568. 574 . 565. 468 . 498 . 2.17 2.38 2.13 2.10 2.19 2.22 2.35 2.08 2.05 2.41 2.21 2.41 1.85 2.31 1.73 1.98 2.22 2.35 2.07 1.99 2.37 2.58 1.96 2.59 2.51 2.22 2.31 2.21 2.19 2.30 0.38 0.40 0.37 0.38 0.38 0.35 0.39 0.37 0.39 0.39 0.36 0.41 0.40 0.39 0.37 0.43 0.41 0.47 0.38 0.39 0.34 0.40 0.39 0.40 0.43 0.39 0.40 0.39 0.47 0.46 2.28 2.20 2.08 2.00 2.18 2.20 2.28 2.16 2.04 2.56 2.24 2.39 1.93 2.20 1.71 1.95 2.23 2.54 2.22 2.09 2.56 2.63 2.13 2.54 2.47 2.26 2.42 2.28 2.13 2.27 0.40 0.36 0.36 0.37 0.38 0.35 0.38 0.39 0.39 0.41 0.37 0.41 0.42 0.38 0.37 0.42 0.42 0.51 0.41 0.41 0.36 0.41 0.42 0.39 0.42 0.40 0.42 0.40 0.46 0.46 0.031 0.029 0.037 0.029 0.038 0.025 0.027 0.026 0.029 0.026 0.035 0.034 0.036 0.030 0.028 0.028 0.022 0.024 0.023 0.041 0.038 0.039 0.035 0.041 0.033 0.028 0.037 0.030 0.039 0.030 5.47 4.82 6.47 5.31 6.55 3.95 4.45 4.67 5.49 4.17 5.79 5.85 7.76 5.13 6.02 6.07 4.10 4.84 4.28 8.06 5.43 6.07 6.96 6.36 5.69 4.93 6.44 5.31 8.33 6.02 0.028 0.023 0.038 0.031 0.032 0.022 0.027 0.023 0.030 0.036 0.030 0.036 0.037 0.019 0.011bi 0.022 0.018 0.024 0.023 0.039 0.036 0.036 0.029 0.041 0.036 0.027 0.037 0.030 0.036 0.023 4.94 3.82 6.64 5.68 5.52 3.48 4.45 4.13 5.68 5.78 4.97 6.20 7.97 3.25 2.36b 4.77 3.35 4.84 4.28 7.66 5.14 5.61 5.76 6.36 6.21 4.75 6.44 5.3 i 7.69 4.62 0.96 1.02 1.00 ' 1.03 0.95 0.90 1.02 0.95 0.72 0.98 0.93 0.97 0.98 0.93 0.73 0.69 1.34 0.94 0.88 0.79 1.13 1.05 0.83 1.13 1.03 0.99 0.83 0.86 1.04 0.73 0.17 0.17 0.17 0.19 0.16 0.14 0.17 0.17 0.14 0.16 0.15 0.17 0.21 0.16 0.16 0.15 0.25 0.19 0.16 0.16 0.16 0.16 0.16 0.18 0.18 0.17 0.14 0.15 0.22 0.15 0.28 0.42 0.62 0.59 0.71 0.73 0.52 0.32 0.43 0.44 0.50 0.46 0.41 0.44 0.37 0.43 0.45 0.72 0.59 0.61 0.36 0.56 0.59 0.52 0.70 0.54 0.55 0.58 0.33 0.47 0.05 0.07 0.11 0.11 0.12 0.12 0.08 0.06 0.08 0.07 0.08 0.08 0.09 0.08 0.08 0.09 0.08 0.14 0.11 0.12 0.05 0.09 0.12 0.08 0.12 0.10 0.10 0.10 0.07 0.09 ALL WEIGHTS WERE RECORDED IN GRAMS (G),. a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. b. Damaged during processing (weight affected) ; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 4) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 435 DOSAGE GROUP II 1 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 1112 1114 1116 1118 1120 486. 522. 480. 485. 424 . 545. 541. 541. 627. 532. 582. 538. 415. 562. 529. 512 . 594 . 632 . 498 . 4 94 . 575. 526. 446. 437. 585. 563 . 552. 542. 525. EPIDIDYMIS LEFT ABS. REL. WT. % TBW 0.7660 0.7170 0.6338 0.6124 0.6531 0.6507 0.7059 0.7864 0.7598 0.7080 0.3393a 0.6435 0.5518 0.7257 0.6785 0.6134 0.6428 0.6912 0.7062 0.6344 0.6689 0.5997 0.6601 0.6219 0.6981 0.6757 0.6704 0.6492 0.7509 0.16 0.14 0.13 0.13 0.15 0.12 0.13 0.14 0.12 0.13 0.06 0.12 0.13 0.13 0.13 0.12 0.11 0.11 0.14 0.13 0.12 0.11 0.15 0.14 0.12 0.12 0.12 0.12 0.14 CAUDA EPIDIDYMIS LEFT ABS. REL. W T . t TBW 0.3553 0.3300 0.2762 0.2886 0.3027 0.3269 0.2707 0.4014 0.3979 0.3712 0.1461a 0.3460 0.2467 0.3524 0.3080 0.3012 0.3252 0.3288 0.3866 0.3308 0.3369 0.2759 0.3072 0.3101 0.3442 0.3169 0.2919 0.2958 0.3424 0.07 0.06 0.06 0.06 0.07 0.06 0.05 0.07 0.06 0.07 0.02 0.06 0.06 0.06 0.06 0.06 0.05 0.05 0.08 0.07 0.06 0.05 0.07 0.07 0.06 0.06 0.05 0.05 0.06 TESTIS LEFT ABS. REL. WT. % TBW 1.7863 1.8632 1.7790 1.5556 1.7625 1.6107 1.9881 1.8023 1.7878 1.7687 1.0590a 1.4745 1.6224 1.6645 1.6320 1.7090 1.6702 1.6920 1.9487 1.6819 1.7418 1.5584 1.6067 1.6555 1.8105 1.9848 1.5620 1.6885 2.0030 0.37 0.36 0.37 0.32 0.42 0.30 0.37 0.33 0.28 0.33 0.18 0.27 0.39 0.30 0.31 0.33 0.28 0.27 0.39 0.34 0.30 0.30 0.36 0.38 0.31 0.35 0.28 0.31 0.38 L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % TBW 1.6295 1.7520 1.6559 1.4453 1.6520 1.5115 1.8542 1.6513 1.6647 1.6044 0.4551a 1.3716 1.5186 1.5413 1.5236 1.3518 1.4565 1.5653 1.7580 1.5379 1.5524 1.4213 1.4424 1.5194 1.6908 1.8202 1.4146 1.5853 1.8717 0.34 0.34 0.34 0.30 0.39 0.28 0.34 0.30 0.26 0.30 0.08 0.25 0.36 0.27 0.29 0.26 0.24 0.25 0.35 0.31 0.27 0.27 0.32 0.35 0.29 0.32 0.26 0.25 0.36 1.9084 2.2839 2.2858 1.7391 2.0289 2.2645 2.1775 2.2437 1.9818 1.9950 2.0247 2.3555 1.7858 2.0530 1.8496 2.4316 2.2994 2.0056 2.4765 1.9311 1.7219 1.7814 1.5051 1.8402 2.1860 2.3440 2.0547 2.1617 2.3378 0.39 0.44 0.48 0.36 0.48 0.42 0.40 0.41 0.32 0.38 0.35 0.44 0.43 0.36 0.35 0.47 0.39 0.32 0.50 0.39 0.30 0.34 0.34 0.42 0.37 0.42 0.37 0.40 0.44 1.0157 1.1167 1.3449 0.9152 1.0798 1.1328 1.1732 1.0133 0.9239 0.9701 0.9927 0.9679 0.9166 0.9295 0.8012 1.3115 1.0829 1.0369 1.3095 0.9989 0.7884 1.0277 0.8120 0.8915 1.2293 1.2241 1.0185 1.0063 1.0701 0.21 0.21 0.28 0.19 0.25 0.21 0.22 0.19 0.15 0.18 0.17 0.18 0.22 0.16 0.15 0.26 0.18 0.16 0.26 0.20 0.14 0.20 0.18 0.20 0.21 0.22 0.18 0.18 0.20 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Rat 1082 had a small, left epididymis and cauda epididymis, small, flaccid left testis, and a fluid filled left testis minus tunica albuginea; values included in group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 5) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT * INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 436 DOSAGE GROUP II 1 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS RIGHT ABS. REL. W T . % TBW TESTIS RIGHT ABS. REL. W T . % TBW PROSTATE ABS. WT. REL. * TBW PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 109B 1100 1103 1106 1107 1110 1112 1114 1116 1118 1120 486. 522. 480. 485. 424 . 545. 541. 541. 627. 532. 582. 538. 415 . 562. 529. 512 . 594 . 632 . 498 . 494 . 575 . 526. 446. 437. 585. 563 . 552. 542 . 525 . 0.7284 0.7113 0.6396 0.6431 0.6310 0.6846 0.7456 0.7614 0.7545 0.7025 0.6989 0.6288 0.6170 0.6845 0.7019 0.6599 0.6911 0.7465 0.7631 0.6229 0.6993c 0.6575 0.6578 0.6330 0.6748 0.7494 0.6639 0.6786 0.6911 0.15 0.14 0.13 0.13 0.15 0.12 0.14 0.14 0.12 0.13 0.12 0.12 0.15 0.12 0.13 0.13 0.12 0.12 0.15 0.13 0.12 0.12 0.15 0.14 0.12 0.13 0.12 0.12 0.13 1.8528 1.8505 1.5745 1.5154 1.6782 1.5542 1.9825 1.8037 1.7230 1.7244 1.7261 1.4717 1.6474 1.6176 1.6796 1.7494 1.6621 1.7774 1.9639 1.6532 1.7282 1.6263 1.6277 1.6504 1.8656 1.9312 1.5988 1.7496 1.9723 0.38 0.35 0.33 0.31 0.40 0.28 0.37 0.33 0.27 0.32 0.30 0.27 0.40 0.29 0.32 0.34 0.28 0.28 0.39 0.33 0.30 0.31 0.36 0.38 0.32 0.34 0.29 0.32 0.38 0.4761 0.8821 0.2716b 0.5982 0.8284 1.3268 1.3308 0.8947 1.3800 1.3717 1.2924 1.3446 0.9942 1.5251 1.2761 1.1454 1.0867 1.0373 1.1216 1.1903 0.8336 1.2108 0.9999 0.9081 1.4610 1.1564 1.2054 1.0908 1.1517 0.10 0.17 0.06 0.12 0.20 0.24 0.24 0.16 0.22 0.26 0.22 0.25 0.24 0.27 0.24 0.22 0.18 0.16 0.22 0.24 0.14 0.23 0.22 0.21 0.25 0.20 0.22 0.20 0.22 0.011 0.012 0.011 0.012 0.011 0.012 0.016 0.011 0.014 0.014 0.016 0.014 0.012 0.014 0.017 0.014 0.025 0.016 0.015 0.024 0.013 0.013 0.033 0.015 0.018 0.023 0.026 0.023 0.028 2.26 2.30 2.29 2.47 2.59 2.20 2.96 2.03 2.23 2.63 2.75 2.60 2.89 2.49 3.21 2.73 4.21 2.53 3.01 4.86 2.26 2.47 7.40 3.43 3.08 4.08 4.71 4.24 5.33 2.16 2.26 2.10 1.98 2.04 2.37 2.26 2.08 2.25 2.35 2.17 2.30 2.07 2.33 2.24 2.45 2.28 2.47 2.38 2.33 2.35 2.13 2.15 2.33 2.64 2.55 2.36 . 2.37 2.43 0.44 0.43 0.44 0.41 0.48 0.43 0.42 0.38 0.36 0.44 0.37 0.43 0.50 0.41 0.42 0.48 0.38 0.39 0.48 0.47 0.41 0.40 0.48 0.53 0.45 0.45 0.43 0.44 0.46 20.77 26.60 20.80 20.97 21.61 26.35 27.94 25.28 30.05 22.81 24.34 23.15 15.51 29.13 21.48 27.07 29.60 32.95 30.37 22.79 27.76 22.68 19.46 20.50 28.97 27.29 21.37 22.51 22.49 4.27 5.10 4.33 4.32 5.10 4.83 5.16 4.67 4.79 4.29 4.18 4.30 3.74 5.18 4.06 5.29 4.98 5.21 6.10 4.61 4.83 4.31 4.36 4.69 4.95 4.85 3.87 4.15 4.28 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT,. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. b. Rat 1066 had a small prostate; values included in group averages and statistical analyses. c. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 6) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 437 DOSAGE GROUP II 1 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 1112 1114 1116 1118 1120 486. 522 . 480. 485. 424. 545. 541. 541. 627. 532. 582. 538. 415. 562 . 529. 512 . 594 . 632 . 498 . 494 . 575. 526. 446 . 437. 585. 563. 552. 542 . 525. KIDNEY LEFT ABS. REL. W T . % TBW 2.06 2.50 2.03 1.95 2.10 2.43 2.43 2.39 2.67 2.24 2.16 2.27 1.79 2.22 2.27 2.68 2.39 2.39 2.35 2.59 2.54 2.19 2.05 2.21 2.90 2.80 2.33 2.74 2.46 0.42 0.48 0.42 0.40 0.50 0.44 0.45 0.44 0.42 0.42 0.37 0.42 0.43 0.40 0.43 0.52 0.40 0.38 0.47 0.52 0.44 0.42 0.46 0.50 0.50 0.50 0.42 0.50 0.47 KIDNEY RIGHT ABS. REL. W T . % TBW 1.90 2.46 2.10 2.07 1.98 2.46 2.50 2.18 2.69 2.41 2.15 2.23 1.92 2.02 2.27 2.56 2.38 2.45 2.44 2.37 2.59 2.21 2.05 2.16 3.01 2.84 2.37 2.73 2.53 0.39 0.47 0.44 0.43 0.47 0.45 0.46 0.40 0.43 0.45 0.37 0.41 0.46 0.36 0.43 0.50 0.40 0.39 0.49 0.48 0.45 0.42 0.46 0.49 0.51 0.50 0.43 0.50 0.48 ADRENAL LEFT ABS. REL. WT. % TBW a 0.016 0.041 0.028 0.024 0.020 0.018 0.037 0.044 0.036 0.028 0.035 0.039 0.028 0.032 0.025 0.029 0.048 0.024 0.030 0.038 0.040 0.024 0.034 0.020 0.039 0.042 0.041 0.032 0.030 3.29 7.85 5.83 4.95 4.72 3.30 6.84 8.13 5.74 5.26 6.01 7.25 6.75 5.69 4.72 5.66 8.08 3.80 6.02 7.69 6.96 4.56 7.62 4.58 6.67 7.46 7.43 5.90 5.71 ADRENAL RIGHT ABS. REL. WT. % TBW a 0.023 0.034 0.022 0.027 0.009 0.024 0.037 0.041 0.032 0.028 0.031 0.030 0.026 0.027 0.024 0.030 0.041 0.024 0.028 0.033 0.036 0.023 0.035 0.019 0.043 0.037 0.027 0.029 0.026 4.73 6.51 4.58 5.57 2.12 4.40 6.84 7.58 5.10 5.26 5.33 5.58 6.26 4.80 4.54 5.86 6.90 3 .80 5.62 6.68 6.26 4.37 7.85 4.35 7.35 6.57 4.89 5.35 4.95 SPLEEN ABS. REL. W T . % TBW 0.76 0.84 0.64 0.65 0.72 0.84 0.68 0.58 0.92 0.83 0.86 0.75 0.74 0.85 0.75 0.89 1.00 0.95 0.80 0.82 0.92 0.75 0.60 0.73 1.24 1.03 0.90 1.06 1.00 0.16 0.16 0.13 0.13 0.17 0.15 0.12 0.11 0.15 0.16 0.15 0.14 0.18 0.15 0.14 0.17 0.17 0.15 0.16 0.16 0.16 0.14 0.13 0.17 0.21 0.18 0.16 0.20 0.19 THYMUS ABS. REL. WT. % TBW 0.60 0.61 0.64 0.46 0.39 0.42 0.22 0.57 0.42 0.37 0.46 0.37 0.29 0.40 0.31 0.55 0.53 0.69 0.61 0.55 0.65 0.58 0.36 0.44 0.35 0.48 0.32 0.41 0.36 0.12 0.12 0.13 0.09 0.09 0.08 0.04 0.10 0.07 0.07 0.08 0.07 0.07 0.07 0.06 0.11 0.09 0.11 0.12 0.11 0.11 0.11 0.08 0.10 0.06 0.08 0.06 0.08 0.07 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-S889.6) TABLE D20 (PAGE 7) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 438 DOSAGE GROUP III 3 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT 1122 1123 1127 1129 1131 1132 1134 113 S 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 1171 1173 1175 1176 1177 1180 518. 505. 452 . 568 . 564 . 529. 579. 505. 441. 457. 561. 506. 413 . 513 . 512. 588 . 539. 580. 550. 587 . 550. 523 . 566. 571. 453 . 530. 498. 4 94 . 480 . 586. EPIDIDYMIS LEFT ABS. REL. W T . % TBW 0.7208 0.6070 0.6614 0.7407 0.6952 0.6725 0.7615 0.6679 0.6855 0.6190 0.6450 0.6121 0.6915 0.7098 0.8130 0.6764 0.6843 0.5970 0.6503 0.7223 0.6669 0.7675 0.6801 0.6367 0.5776 0.6524 0.6272 0.5684 0.7391 0.6971 0.14 0.12 0.15 0.13 0.12 0.13 0.13 0.13 0.16 0.14 0.11 0.12 0.17 0.14 0.16 0.12 0.13 0.10 0.12 0.12 0.12 0.15 0.12 0.11 0.13 0.12 0.12 0.12 0.15 0.12 CAUDA EPIDIDYMIS LEFT ABS. REL. W T . % TBW 0.3470 0.2968 0.3302 0.3502 0.3581 0.3378 0.3358 0.3218 0.3406 0.3274 0.3546 0.2953 0.3255 0.3588 0.4132 0.3179 0.3349 0.2924 0.3024 0.3698 0.3101 0.3613 0.3252 0.2903 0.2903 0.3273 0.2745 0.2863 0.3494 0.3350 0.07 0.06 0.07 0.06 0.06 0.06 0.06 0.06 0.08 0.07 0.06 0.06 0.08 0.07 0.08 0.05 0.06 0.05 0.05 0.06 0.06 0.07 0.06 0.05 0.06 0.06 0.06 0.06 0.07 0.06 TESTIS LEFT ABS. REL. WT. t TBW 1.6159 1.8182 1.6347 1.9335 1.7682 1.7645 1.8988 1.7237 1.9009 1.6472 1.5627 1.6597 1.8607 1.6976 2.0462 1.8091 3.0171a 1.7007 1.7179 1.8480 1.7050 1.9198 1.7101 1.8227 1.5240 1.5741 1.7498 1.9718 2.2666 1.9639 0.31 0.36 0.36 0.34 0.31 0.33 0.33 0.34 0.43 0.36 0.28 0.33 0.45 0.33 0.40 0.31 0.56 0.29 0.31 0.31 0.31 0.37 0.30 0.32 0.34 0.30 0.35 0.40 0.47 0.34 L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. W T . % TBW SEMINAL VESICLES WITH FLUID ABS. REL. W T . t TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % TBW 1.5221 1.6922 1.5124 1.8129 1.6707 1.6362 1.7685 1.6026 1.6834 1.5631 1.4612 1.5318 1.7494 1.6060 1.9344 1.5925 2.7687a 1.4274 1.5439 1.6935 1.5581 1.7783 1.5089 1.6190 1.4063 1.4256 1.6409 1.8165 2.1025 1.8501 0.29 0.34 0.33 0.32 0.30 0.31 0.30 0.32 0.38 0.34 0.26 0.30 0.42 0.31 0.38 0.27 0.51 0.25 0.28 0.29 0.28 0.34 0.27 0.28 0.31 0.27 0.33 0.37 0.44 0.32 2.0470 2.3013 1.7196 2.1930 2.3326 2.3904 2.1383 1.8500 1.3217 1.7038 1.7528 2.0896 1.8492 1.7211 2.3386 2.2078 1.9461 1.8889 2.1813 2.3263 2.0033 1.9163 2.0326 1.5592 1.8020 2.1183 1.713 -2 1.4040 2.0790 2.1032 0.40 0.46 0.38 0.39 0.41 0.45 0.37 0.37 0.30 0.37 0.31 0.41 0.45 0.34 0.46 0.38 0.36 0.32 0.40 0.40 0.36 0.37 0.36 0.27 0.40 0.40 0.34 0.28 0.43 0.36 1.0874 1.2447 0.9666 1.1095 1.0857 1.2665 1.0924 0.9966 0.7638 0.9308 0.8441 0.9784 1.0012 0.9009 1.1584 0.9860 1.0849 0.8750 1.1530 1.1211 0.8661 0.8735 1.0820 0.9914 1.0915 1.0216 1.0295 0.8061 1.1398 1.0329 0.21 0.25 0.21 0.20 0.19 0.24 0.19 0.20 0.17 0.20 0.15 0.19 0.24 0.18 0.23 0.17 0.20 0.15 0.21 0.19 0.16 0.17 0.19 0.17 0.24 0.19 0.21 0.16 0.24 0.18 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT . = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Rat 1153 had a large, left testis and testis minus tunica albuginea; values included in group averages and statistical analyses PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 8) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 439 DOSAGE GROUP III 3 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 1171 1173 1175 1176 1177 1180 518. 505. 452. 568 . 564. 529. 579. 505. 441. 457. 561. 506. 413. 513 . 512 . 588 . 539. 580. 550. 587. 550. 523. 566. 571. 453 . 530 . 498 . 494 . 480 . 586 . EPIDIDYMIS RIGHT ABS. REL. W T . % TBW 0.6838 0.6106 0.6629 0.7111 0.6877 0.6987 0.7236 0.6703 0.6601 0.6262 0.6701b 0.6442 0.6614 0.6789 0.7538 0.6490 0.7007 0.6741 0.6996 0.7245 0.6761b 0.7592 0.7044 0.6950 0.5841 0.6720 0.6517 0.6153 0.7824 0.7608 0.13 0.12 0.15 0.12 0.12 0.13 0.12 0.13 0.15 0.14 0.12 0.13 0.16 0.13 0.15 0.11 0.13 0.12 0.13 0.12 0.12 0.14 0.12 0.12 0.13 0.13 0.13 0.12 0.16 0.13 TESTIS RIGHT ABS. REL. W T . % TBW 1.6035 1.7572 1.6197 1.8049 1.7444 1.7356 1.9533 1.6461 1.8638 1.7137 1.5828 1.6204 1.8248 1.7369 2.0918 1.7336 1.7874 1.7880 1.7801 1.8539 1.6565 1.9644 1.7935 1.9170 1.5517 1.6114 1.7506 1.9358 2.2229 1.9351 0.31 0.35 0.36 0.32 0.31 0.33 0.34 0.32 0.42 0.37 0.28 0.32 0.44 0.34 0.41 0.29 0.33 0.31 0.32 0.32 0.30 0.38 0.32 0.34 0.34 0.30 0.35 0.39 0.46 0.33 PROSTATE ABS. REL. WT. % TBW 0.4770 0.3938 0.4890 0.9503 0.9830 1.1426 1.0100 1.1130 0.8226 1.0147 1.2215 0.9640 1.0366 1.0363 1.3772 1.1726 1.2844 1.1087 0.8279 1.1479 1.2450 1.2929 1.1156 0.9715 1.0645 1.1758 1.1055 0.9663 1.2319 1.0538 0.09 0.08 0.11 0.17 0.17 0.22 0.17 0.22 0.19 0.22 0.22 0.19 0.25 0.20 0.27 0.20 0.24 0.19 0.15 0.20 0.23 0.25 0.20 0.17 0.23 0.22 0.22 0.20 0.26 0.18 PITUITARY ABS. WT. REL. % TBW a 0.010 0.013 0.012 0.016 0.010 0.016 0.011 0.014 0.011 0.011 0.012 0.013 0.014 0.010 0.015 0.017 0.013 0.023 0.019 0.025 0.014 0.013 0.018 0.021 0.020 0.028 0.012 0.032 0.015 0.025 1.93 2.57 2.65 2.82 1.77 3.02 1.90 2.77 2.49 2.41 2.14 2.57 3.39 1.95 2.93 2.89 2.41 3.96 3.45 4.26 2.54 2.48 3.18 3.68 4.42 5.28 2.41 6.48 3.12 4.27 BRAIN ABS. WT. REL. * TBW 2.40 2.40 2.20 2.29 2.23 2.22 2.40 2.17 2.16 2.29 2.17 2.16 2.04 2.33 2.36 2.41 2.35 2.23 2.28 2.24 2.31 2.41 2.23 2.51 2.31 2.41 2.53 2.33 2.43 2.47 0.46 0.48 0.49 0.40 0.40 0.42 0.41 0.43 0.49 0.50 0.39 0.43 0.49 0.45 0.46 0.41 0.44 0.38 0.41 0.38 0.42 0.46 0.39 0.44 0.51 0.45 0.51 0.47 0.51 0.42 LIVER ABS. REL. WT. % TBW 28.00 27.20 28.00 37.20 31.29 24.46 31.25 26.42 24.58 26.94 24.41 24.96 24.17 26.73 28.43 31.06 15.00 31.44 33 .93 28.29 31.33 30.89 33.05 31.60 25.18 27.19 26.00 25.54 34.48 28.35 5.40 5.39 6.19 6.55 5.55 4.62 5.40 5.23 5.57 5.89 4.35 4.93 5.85 5.21 5.55 5.28 2.78 5.42 6.17 4.82 5.70 5.91 5.84 5.53 5.56 5.13 5.22 5.17 7.18 4.84 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . W T . = ORGAN WEIGHT. a. Value was multiplied by 1000. b. Damaged during processing (weight not affected). REL. V TBW = (ORGAN WEIGHT /TERM INAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 9) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 440 DOSAGE GROUP III 3 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 1171 1173 1175 1176 1177 1180 518. 505., 452., 568.564. 529. 579., 505., 441. 457. 561, 506.. 413. 513. 512. 588 . 539. 580. 550 . 587. 550. 523. 566 . 571. 453. 530. 498 . 4 94 . 480. 586. KIDNEY LEFT ABS. REL. WT. % TBW 2.33 2.40 2.10 2.58 2.81 2.43 2.52 2.46 2.49 2.50 2.23 2.19 2.20 2.24 2.74 2.58 2.46 2.72 2.46 2.54 2.59 2.67 2.56 2.45 2.09 2.28 2.21 2.56 2.76 2.54 0.45 0.48 0.46 0.45 0.50 0 .46 0.44 0.49 0.56 0.55 0.40 0.43 0.53 0.44 0.54 0.44 0.46 0.47 0.45 0.43 0.47 0.51 0.45 0.43 0.46 0.43 0.44 0.52 0.58 0.43 KIDNEY RIGHT ABS. REL. W T . * TBW 2.31 2.40 2.11 2.78 2.67 2.49 2.63 2.35 2.41 2.48 2.24 2.16 2.02 2.17 2.50 2.78 2.55 2.71 2.57 2.92 2.71 2.62 2.56 2.43 1.95 2.37 2.45 2.69 2.79 2.51 0.44 0.48 0.47 0.49 0.47 0.47 0.45 0.46 0.55 0.54 0.40 0.43 0.49 0.42 0.49 0.47 0.47 0.47 0.47 0.50 0.49 0.50 0.45 0.42 0.43 0.45 0.49 0.54 0.58 0.43 ADRENAL LEFT ABS. REL. WT. % TBW a 0.024 0.030 0.024 0.036 0.024 0.039 0.037 0.026 0.039 0.037 0.030 0.029 0.028 0.032 0.034 0.027 0.024 0.030 0.029 0.042 0.027 0.035 0.029 0.029 0.031 0.028 0.029 0.036 0.034 0.036 4.63 5.94 5.31 6.34 4.26 7.37 6.39 5.15 8.84 8.10 5.35 5.73 6.78 6.24 6.64 4.59 4.45 5.17 5.27 7.16 4.91 6.69 5.12 5.08 6.84 5.28 5.82 7.29 7.08 6.14 ADRENAL RIGHT ABS. REL. WT. % TBW a 0.020 0.032 0.026 0.032 0.028 0.036 0.038 0.027 0.032 0.032 0.030 0.026 0.019 0.027 0.029 0.018 0.021 0.028 0.024 0.034 0.027 0.030 0.031 0.029 0.032 0.033 0.022 0.029 0.030 0.037 3.86 6.34 5.75 5.63 4.96 6.80 6.56 5.35 7.26 7.00 5.35 5.14 4.60 5.26 5.66 3.06 3.90 4.83 4.36 5.79 4.91 5.74 5.48 5.08 7.06 6.23 4.42 5.87 6.25 6.31 SPLEEN ABS. WT. REL. % TBW 1.02 0.80 0.75 0.83 0.95 0.59 0.95 0.75 0.72 0.56 0.94 0.65 0.69 0.86 0.77 0.91 0.93 1.01 0.86 1.08 0.78 0.80 1.17 0.94 0.77 0.73 0.94 . 0.76 0.89 1.05 0.20 0.16 0.16 0.15 0.17 0.11 0.16 0.15 0.16 0.12 0.17 0.13 0.17 0.17 0.15 0.15 0.17 0.17 0.16 0.18 0.14 0.15 0.21 0.16 0.17 0.14 0.19 0.15 0.18 0.18 THYMUS ABS. WT. REL. % TBW 0.49 0.29 0.28 0.72 0.59 0.37 0.66 0.33 0.46 0.24 0.34 0.48 0.18 0.27 0.30 0.73 0.55 0.67 0.49 0.44 0.35 0.44 0.73 0.40 0.40 0.51 0.35 0.44 0.36 0.40 0.09 0.06 0.06 0.13 0.10 0.07 0.11 0.06 0.10 0.05 0.06 0.09 0.04 0.05 0.06 0.12 0.10 0.12 0.09 0.07 0.06 0.08 0.13 0.07 0.09 0.10 0.07 0.09 0.08 0.07 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 10) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 441 DOSAGE GROUP IV RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS LEFT ABS. REL. WT. % TBW 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 1237 1240 458. 547. 498. 474. 591. 500. 549. 510. 682. 488. 476. 499. 536. 472. 572. 518. 534. 515. 418. 427. 520. 497. 440. 514. 408. 377. 585. 491. 393. 490. 0.5873 0.7364 0.6724 0.6851 0.7693 0.6944 0.7103 0.6484 0.7207 0.5748 0.7346 0.7013 0.6512 0.6746 0.7302 0.6593 0.6832 0.6969 0.5811 0.5729 0.6980 0.6952 0.6728 0.6327 0.6796 0.6882 0.5594 0.6243 0.6220 0.8036 0.13 0.13 0.14 0.14 0.13 0.14 0.13 0.13 0.10 0.12 0.15 0.14 0.12 0.14 0.13 0.13 0.13 0.14 0.14 0.13 0.13 0.14 0.15 0.12 0.17 0.18 0.10 0.13 0.16 0.16 ALL WEIGHTS WERE RECORDED IN GRAMS (G) io MG/KG/DAY CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % TBW TESTIS LEFT ABS. REL. WT. % TBW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW 0.2692 0.3508 0.3462 0.3285 0.4167 0.3106 0.3404 0.3165 0.3662 0.2920 0.3820 0.3523 0.3423 0.3294 0.3596 0.3135 0.3559 0.3209 0.2735 0.2820 0.3349 0.3592 0.3371 0.2997 0.3348 0.3264 0.2432 0.2962 0.2763 0.4063 0.06 0.06 0.07 0.07 0.07 0.06 0.06 0.06 0.05 0.06 0.08 0.07 0.06 0.07 0.06 0.06 0.07 0.06 0.06 0.07 0.06 0.07 0.08 0.06 0.08 0.09 0.04 0.06 0.07 0.08 1.6842 1.9148 1.5726 1.7130 1.8304 1.7946 1.7653 1.6721 1.9297 1.5606 1.7581 1.7531 1.7328 1.7361 1.9206 1.8977 1.7087 1.8089 1.6144 1.7055 2.0374 1.7559 1.6548 1.7194 1.8306 1.9365 1.7079 1.7320 1.6722 2.0756 0.37 0.35 0.32 0.36 0.31 0.36 0.32 0.33 0.28 0.32 0.37 0.35 0.32 0.37 0.34 0.37 0.32 0.35 0.39 0.40 0.39 0.35 0.38 0.33 0.45 0.51 0.29 0.35 0.42 0.42 1.5580 1.7769 1.4546 1.5980 1.5499 1.5264 1.6519 1.5753 1.7940 1.4555 1.6592 1.6424 1.5972 1.6305 1.8200 1.7249 1.4910 1.6898 1.4823 1.5490 1.8144 1.5914 1.5289 1.5668 1.6824 1.8148 1.5194 1.5580 1.5690 1.9055 0.34 0.32 0.29 0.34 0.26 0.30 0.30 0.31 0.26 0.30 0.35 0.33 0.30 0.34 0.32 0.33 0.28 0.33 0.35 0.36 0.35 0.32 0.35 0.30 0.41 0.48 0.26 0.32 0.40 0.39 2.1825 2.8035 1.6253 1.8294 2.0923 2.2638 2.2778 1.8174 2.2576 2.0476 2.1362 2.0554 2.0879 2.2509 2.5826 1.8533 2.0138 1.7647 2.0568 1.5690 2.1344 2.2735 2.2355 1.7349 1.3942 1.8359 2.3104 1.6820 2.0813 2.5458 0.48 0.51 0.33 0.38 0.35 0.45 0.41 0.36 0.33 0.42 0.45 0.41 0.39 0.48 0.45 0.36 0.38 0.34 0.49 0.37 0.41 0.46 0.51 0.34 0.34 0.49 0.39 0.34 0.53 0.52 1.0993 1.3573 0.7547 1.0218 0.9952 1.3117 1.1574 0.9382 1.1818 0.9225 1.0182 1.0792 1.0570 1.2076 1.1246 1.0642 1.0114 0.9204 1.1085 0.9655 1.1960 1.2959 1.0700 0.9698 0.8422 1.0507 1.3382 1.0255 0.9398 1.0793 0.24 0.25 0.15 0.22 0.17 0.26 0.21 0.18 0.17 0.19 0.21 0.22 0.20 0.26 0.20 0.20 0.19 0.18 0.26 0.23 0.23 0.26 0.24 0.19 0.21 0.28 0.23 0.21 0.24 0.22 ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 11) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 442 DOSAGE GROUP IV 10 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS RIGHT ABS. REL. WT. TBW TESTIS RIGHT ABS. :REL. WT. % TBW PROSTATE ABS. WT. REL. % TBW PITUITARY ABS. WT. REL. % TBW a 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 1237 1240 458. 547. 498. 474 . 591. 500. 549. 510. 682. 488. 476. 499. 536. 472. 572 . 518 . 534 . 515. 418 . 427. 520. 497. 440. 514 . 408 . 377. 585. 491. 393. 490. 0.6047 0.7559 0.6982 0.6993 0.7530 0.6947 0.7274 0.6028 0.7218 0.6076 0.7386 0.7052 0.6614 0.7154 0.7298 0.6595 0.6748 0.7102b 0.6257 0.6549 0.7082 0.7384 0.6937 0.6851 0.7064 0.6704 0.6843 0.6360 0.6242 0.7558 0.13 0.14 0.14 0.15 0.13 0.14 0.13 0.12 0.10 0.12 0.16 0.14 0.12 0.15 0.13 0.13 0.13 0.14 0.15 0.15 0.14 0.15 0.16 0.13 0.17 0.18 0.12 0.13 0.16 0.15 1.6680 1.8710 1.6171 1.6425 1.8294 1.7973 1.7765 1.6682 1.8638 1.6140 1.7777 1.6577 1.6149 1.7180 1.9154 1.9394 1.6544 1.7837 1.6034 1.7229 1.9675 1.8250 1.6822 1.7896 1.8647 1.8883 1.7895 1.7348 1.6814 2.0720 0.36 0.34 0.32 0.35 0.31 0.36 0.32 0.33 0.27 0.33 0.37 0.33 0.30 0.36 0.33 0.37 0.31 0.35 0.38 0.40 0.38 0.37 0.38 0.35 0.46 0.50 0.30 0.35 0.43 0.42 0.3623 0.7091 0.8461 1.0337 1.2066 0.8355 1.2309 1.0630 0.9586 1.2275 1.1547 1.3065 1.2231 1.0513 1.3466 0.9439 1.4602 1.3746 0.9941 0.9705 1.0687 1.0011 1.0253 1.1083 0.5994 0.9128 1.1748 1.1124 0.8318 1.2324 0.08 0.13 0.17 0.22 0.20 0.17 0.22 0.21 0.14 0.25 0.24 0.26 0.23 0.22 0.24 0.18 0.27 0.27 0.24 0.23 0.20 0.20 0.23 0.22 0.15 0.24 0.20 0.23 0.21 0.25 0.005 0.015 0.013 0.008 0.014 0.009 0.009 0.012 0.014 0.010 0.013 0.012 0.013 0.012 0.010 0.014 0.017 0.012 0.018 0.012 0.013 0.026 0.026 0.021 0.013 0.015 0.015 0.013 0.010 0.020 1.09 2.74 2.61 1.69 2.37 1.80 1.64 2.35 2.05 2.05 2.73 2.40 2.42 2.54 1.75 2.70 3.18 2.33 4.31 2.81 2.50 5.23 5.91 4.08 3.19 3.98 2.56 2.65 2.54 4.08 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT . = ORGAN WEIGHT. a. Value was multiplied by 1000. b. Damaged during processing (weight not affected). REL. % TBW = (ORGAN BRAIN ABS. WT. 1EL. TBW 2.23 2.30 2.16 2.20 2.40 2.22 2.22 2.16 2.36 2.22 2.30 2.24 2.22 2.28 2.44 2.49 2.30 2.32 2.09 2.21 2.07 2.39 2.32 2.44 2.15 2.22 2.40 2.23 2.37 2.32 0.49 0.42 0.43 0.46 0.41 0.44 0.40 0.42 0.35 0.45 0.48 0.45 0.41 0.48 0.43 0.48 0.43 0.45 0.50 0.52 0.40 0.48 0.53 0.47 0.53 0.59 0.41 0.45 0.60 0.47 LIVER ABS. WT. REL. % TBW 25.00 30.64 20.80 27.64 32.61 30.76 29.51 26.56 35.89 26.54 31.81 24.11 35.57 27.46 34.89 30.79 33.30 30.02 27.85 24.86 31.71 26.90 31.17 32.01 22.60 26.98 38.30 25.35 28.38 28.51 5.46 5.60 4.18 5.83 5.52 6.15 5.38 5.21 5.26 5.44 6.68 4.83 6.64 5.82 6.10 5.94 6.24 5.83 6.66 5.82 6.10 5.41 7.08 6.23 5.54 7.16 6.55 5.16 7.22 5.82 X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-68B9.6) TABLE D20 (PAGE 12) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 443 DOSAGE GROUP IV 10 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 1237 1240 458. 547. 498. 474. 591. 500. 549. 510. 682. 488. 476. 499. 536. 472. 572. 518. 534 . 515. 418. 427 . 520 . 497. 440. 514. 408. 377. 585. 491. 393 . 490. KIDNEY LEFT ABS. REL. W T . % TBW 1.96 2.40 2.00 2.25 2.52 2.16 2.32 2.25 2.65 2.32 2.56 2.37 2.23 2.27 2.49 2.51 1.98 2.17 2.07 1.94 2.26 2.42 2.28 2.58 2.11 2.12 2.77 2.48 2.00 2.53 0.43 0.44 0 .40 0.47 0.43 0.43 0.42 0.44 0.39 0.48 0.54 0.47 0.42 0.48 0.44 0.48 0.37 0.42 0.50 0.45 0.43 0.49 0.52 0.50 0.52 0.56 0.47 0.50 0.51 0.52 KIDNEY RIGHT ABS. REL. WT. % TBW 2.06 2.30 1. Bib 2.21 2.65 2.31 2.72 2.27 2.61 2.21 2.49 2.19 2.34 2.11 2.54 2.56 2.02 2.14 2.39 2.09 2.36 2.50c 2.18 2.60 2.13 2.07e 2.85 2.44 2.02 2.67 0.45 0.42 0.36 0.47 0.45 0.46 0.50 0.44 0.38 0.45 0.52 0.44 0.44 0.45 0.44 0.49 0.38 0.42 0.57 0.49 0.45 0.50 0.50 0.50 0.52 0.55 0.49 0.50 0.51 0.54 ADRENAL LEFT ABS. REL. WT. % TBW a 0.010 0.031 0.033 0.031 0.032 0.032 0.029 0.025 0.042 0.025 0.032 0.025 0.026 0.020 0.026 0.030 0.030 0.025 0.023 0.025 0.029 0.030 0.035 0.029 0.038 0.026 0.036 0.028 0.026 0.039 2.18 5.67 6.63 6.54 5.41 6.40 5.28 4.90 6.16 5.12 6.72 5.01 4.85 4.24 4.54 5.79 5.62 4.85 5.50 5.85 5.58 6.04 7.95 5.64 9.31 6.90 6.15 5.70 6.62 7.96 ADRENAL RIGHT ABS. REL. WT. ; TBW a 0.022 0.033 0.032 .016 .037 .032 .030 .028 .040 .025 .026 0.022 0.024 0.032 0.025 0.029 0.030 0.022 0.026 0.026 0.029 0.024 0.034 0.026 0.031 0.026 0.038 0.024 0.021 0.039 4.80 6.03 6.42 3.38 6.26 6.40 5.46 5.49 5.86 5.12 5.46 4.41 4.48 6.78 4.37 5.60 5.62 4.27 6.22 6.09 5.58 4.83 7.73 5.06 7.60 6.90 6.50 4.89 5.34 7.96 SPLEEN ABS. WT. REL. % TBW 0.67 0.72 0.69 0.78 0.85 0.92 0.81 0.76 0.81 0.81 0.71 0.65 0.76 0.69 0.76 0.84 0.79 0.70 0.63 0.79 0.76 0.82 0.76 0.92 1.95d 0.82 1.04 0.88 0.65 0.70 0.15 0.13 0.14 0.16 0.14 0.18 0.15 0.15 0.12 0.16 0.15 0.13 0.14 0.15 0.13 0.16 0.15 0.14 0.15 0.18 0.15 0.16 0.17 0.18 0.48 0.22 0.18 0.18 0.16 0.14 THYMUS ABS. WT. REL. % TBW 0.35 0.39 0.27 0.56 0.35 0.73 0.30 0.37 0.36 0.32 0.43 0.27 0.25 0.32 0.32 0.32 0.32 0.40 0.47 0.55 0.41 0.44 0.34 0.45 0.31 0.39 0.55 0.36 0.27 0.24 0.08 0.07 0.05 0.12 0.06 0.15 0.05 0.07 0.05 0.06 0.09 0.05 0.05 0.07 0.06 0.06 0.06 0.08 0.11 0.13 0.08 0.09 0.08 0.09 0.08 0.10 0.09 0.07 0.07 0.05 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. ORGAN WEIGHT. (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100 . b. Rat 1186 had moderate dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. c . Rat 1224 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. d. Rat 1229 had tan areas on the spleen that extended into the parenchyma; value included in group averages and statistical analysis. Rat 1232 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 13) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 444 DOSAGE GROUP V 30 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT EPIDIDYMIS LEFT ABS. REL. W T . % TBW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % TBW TESTIS LEFT ABS. REL. WT. % TBW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % TBW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 1291 1294 1298 1300 460. 485. 502. 442. 378. 376. 409. 414. 490. 457. 426. 388. 429. 514. 510. 394 . 507. 405. 472. 403 . 443 . 418. 407. 443 . 447. 399. 450. 385. 438. 0.6112 0.6273 0.6766 0.6881 0.6792 0.7319 0.6596 0.6469 0.6245 0.7072 0.6969 0.5900 0.6313 0.6429 0.6784 0.5963 0.6832 0.6289 0.6557 0.6104 0.6110 0.5705 0.5772 0.6419 0.6438 0.7084 0.7602 0.5738 0.7065 0.13 0.13 0.13 0.16 0.18 0.19 0.16 0.16 0.13 0.15 0.16 0.15 0.15 0.12 0.13 0.15 0.13 0.16 0.14 0.15 0.14 0.14 0.14 0.14 0.14 0.18 0.17 0.15 0.16 0.2998 0.3142 0.3187 0.3340 0.3129 0.3795 0.3158 0.3557 0.3120 0.3545 0.3539 0.2959 0.3086 0.3347 0.2913 0.2747 0.3324 0.2912 0.3389 0.2935 0.3077 0.2924 0.2718 0.3011 0.2949 0.3777 0.3415 0.2755 0.3154 0.06 0.06 0.06 0.08 0.08 0.10 0.08 0.08 0.06 0.08 0.08 0.08 0.07 0.06 0.06 0.07 0.06 0.07 0.07 0.07 0.07 0.07 0.07 0.07 0.06 0.09 0.08 0.07 0.07 1.5908 1.7212 1.7176 1.8326 1.6396 1.7786 1.4497 1.7510 1.7416 1.8200 1.7863 1.6848 1.6450 1.7958 1.9897 1.5513 1.8321 1.6986 1.5348 2.0059 1.7608 1.5426 1.4489 1.8533 1.8455 1.8660 2.0868 1.4615 1.6906 0.34 0.35 0.34 0.41 0.43 0.47 0.35 0.42 0.36 0.40 0.42 0.43 0.38 0.35 0.39 0.39 0.36 0.42 0.32 0.50 0.40 0.37 0.36 0.42 0.41 0.47 0.46 0.38 0.38 1.3979 1.5926 1.6080 1.6988 1.5464 1.6728 1.3774 1.6523 1.6095 1.7299 1.6566 1.5730 1.5233 1.6760 1.7853 1.4009 1.6903 1.6003 1.3779 1.8552 1.6309 1.4114 1.3122 1.7185 1.6862 1.5842 1.8566 1.3341 1.5934 0.30 0.33 0.32 0.38 0.41 0.44 0.34 0.40 0.33 0.38 0.39 0.40 0.36 0.33 0.35 0.36 0.33 0.40 0.29 0.46 0.37 0.34 0.32 0.39 0.38 0.40 0.4.1 0.35 0.36 1.8364 2.8798 2.1597 1.7738 2.5952 2.0331 1.8891 1.9214 1.6770 2.2625 2.0366 1.8242 1.9019 1.8292 1.8426 1.9182 1.6601 1.7792 1.8714 1.4607 1.6002 1.5734 2.0014 1.8222 1.6617 1.8949 1.3983 1.8111 1.9824 0.40 0.59 0.43 0.40 0.69 0.54 0.46 0.46 0.34 0.50 0.48 0.47 0.44 0.36 0.36 0.49 0.33 0.44 0.40 0.36 0.36 0.38 0.49 0.41 0.37 0.47 0.31 0.47 0.45 1.0081 1.4614 1.0569 1.0022 1.2934 1.0653 0.9906 0.8235 0.6609 1.0298 1.0283 0.8953 0.7353 0.8866 0.9089 0.9421 0.8003 0.8806 0.9200 0.7963 0.8986 0.7565 0.9903 1.0444 0.8188 0.9639 0.7453 0.8992 1.2279 0.22 0.30 0.21 0.23 0.34 0.28 0.24 0.20 0.13 0.22 0.24 0.23 0.17 0.17 0.18 0.24 0.16 0.22 0.19 0.20 0.20 0.18 0.24 0.24 0.18 0.24 0.16 0.23 0.28 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020; ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D20 (PAGE 14) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 445 DOSAGE GROUP V 30 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT 1241 1244 1245 1247 1248 124 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 1291 1294 1298 1300 460. 485. 502. 442. 378. 376. 409. 414 . 490. 457. 426. 388. 429. 514. 510. 3 94 . 507. 405. 472 . 403 . 443 . 418. 407. 443 . 447. 399. 450 . 385. 438 . EPIDIDYMIS RIGHT ABS. REL. WT. % TBW 0.6533 0.6699 0.6880 0.6936 0.7177 0.7145 0.5818 0.6693 0.6530 0.7350 0.7351 0.6319 0.6521 0.6597 0.6398 0.6096 0.6309 0.6590 0.6883 0.6620 0.6740 0.5821 0.5847 0.7166 0.6780 0.7411 0.7335 0.5936 0.7606 0.14 0.14 0.14 0.16 0.19 0.19 0.14 0.16 0.13 0.16 0.17 0.16 0.15 0.13 0.12 0.15 0.12 0.16 0.14 0.16 0.15 0.14 0.14 0.16 0.15 0.18 0.16 0.15 0.17 TESTIS RIGHT ABS. REL. WT. % TBW 1.6469 1.6944 1.7335 1.7629 1.7090 1.7860 1.3457 1.8852 1.7597 1.8935 1.8626 1.7525 1.5782 1.7311 1.9298 1.5443 1.8951 1.7218 1.5678 2.0764 1.8308 1.5509 1.3930 2.0066 1.8514 1.8543 1.9582 1.4529 1.7792 0.36 0.35 0.34 0.40 0.45 0.48 0.33 0.46 0.36 0.41 0.44 0.45 0.37 0.34 0.38 0.39 0.37 0.42 0.33 0.52 0.41 0.37 0.34 0.45 0.41 0.46 0.44 0.38 0.41 PROSTATE ABS. REL. W T . % TBW 0.7133 0.4297 0.6958 1.0837 0.8798 0.8470 0.7562 0.9728 1.0766 1.0167 1.1325 0.5891 1.1156 1.0011 1.0235 1.0554 1.0326 0.7614 0.7429 0.7483 1.0285 0.8656 0.8578 0.7964 0.7592 0.7997 0.9946 0.6132 0.9123 0.16 0.09 0.14 0.24 0.23 0.22 0.18 0.23 0.22 0.22 0.26 0.15 0.26 0.19 0.20 0.27 0.20 0.19 0.16 0.18 0.23 0.21 0.21 0.18 0.17 0.20 0.22 0.16 0.21 PITUITARY ABS. WT. REL. % TBW a 0.009 0.012 0.013 0.011 0.010 0.011 0.009 0.009 0.010 0.013 0.009 0.011 0.014 0.005 0.019 0.021b 0.015 0.024 0.032 0.010 0.012 0.010 0.026 0.010 0.014 0.008 0.026 0.011 0.010 1.96 2.47 2.59 2.49 2.64 2.92 2.20 2.17 2.04 2.84 2.11 2.84 3.26 0.97 3.72 5.33b 2.96 5.92 6.78 2.48 2.71 2.39 6.39 2.26 3.13 2.00 5.78 2.86 2.28 BRAIN ABS. WT. REL. % TBW 2.21 2.14 2.14 2.19 2.02 2.08 2.16 2.00 2.29 2.11 1.95 2.17 2.09 2.14 2.70 2.16 2.27 2.04 2.08 2.20 2.25 2.09 2.22 2.34 2.27 2.35 2.37 2.06 2.18 0.48 0.44 0.43 0.50 0.53 0.55 0.53 0.48 0.47 0.46 0.46 0.56 0.49 0.42 0.53 0.55 0.45 0.50 0.44 0.54 0.51 0.50 0.54 0.53 0.51 0.59 0.53 0.54 0.50 LIVER ABS. WT. ]REL. % TBW 33.90 37.00 35.80 30.46 23.36 22.66 29.14 24.07 32.45 29.80 25.93 24.08 29.42 32.70 30.75 27.46 34.70 26.59 30.95 29.72 30.21 26.56 25.71 33.07 34.68 26.73 33.81 27.51 33.29 7.37 7.63 7.13 6.89 6.18 6.03 7.12 5.81 6.62 6.52 6.09 6.21 6.86 6.36 6.03 6.97 6.84 6.56 6.56 7.37 6.82 6.3S 6.32 7.46 7.76 6.70 7.51 7.14 7.60 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . WT. = ORGAN WEIGHT. RE L . % TBW = (ORGAN WE IGHT/TERM INAL BODY WEIGHT) X 100. a. Value was multiplied by 1000. b. Damaged during processing (weight affected); values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-S889.6) TABLE D20 (PAGE 15) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 446 DOSAGE GROUP V 30 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 1291 1294 1298 1300 460. 485. 502. 442. 378. 376. 409. 414. 490. 457. 426. 388. 429. 514. 510. 394 . 507. 405. 472. 403 . 443 . 418. 407. 443 . 447. 399. 450. 385. 438. KIDNEY LEFT ABS. REL. WT. % TBW 2.30 2.60 2.60 1.85 1.90 1.94 1.78 1.91 2.13 1.89 1.90 1.75 1.90 1.93 2.21 1.90 2.29 1.74 2.10 1.92 2.16 2.16 1.96 2.02 1.99 2.09 2.07 1.85 2.06 0.50 0.54 0.52 0.42 0.50 0.52 0.44 0.46 0.43 0.41 0.45 0.45 0.44 0.38 0.43 0.48 0.45 0.43 0.44 0.48 0.49 0.52 0.48 0.46 0.44 0.52 0.46 0.48 0.47 KIDNEY RIGHT ABS. REL. W T . % TBW 2.28 2.41 2.40 1.67 1.94 1.94 1.78 1.88 2.23 1.87 1.79 1.93 2.00 2.12 2.50 1.86 2.35 1.81 2.04 2.01 1.99 2.06 2.12 1.97 2.08 2.05 2.26b 1.86 1.99 0.50 0.50 0.48 0.38 0.51 0.52 0.44 0.45 0.46 0.41 0.42 0.50 0.47 0.41 0.49 0.47 0.46 0.45 0.43 0.50 0.45 0.49 0.52 0.44 0.46 0.51 0.50 0.48 0.45 ADRENAL LEFT ABS. REL. WT. % TBW a 0.024 0.035 0.033 0.023 0.031 0.028 0.027 0.025 0.023 0.028 0.023 0.021 0.030 0.022 0.038 0.033 0.020 0.031 0.030 0.036 0.034 0.020 0.028 0.019 0.026 0.023 0.039 0.022 0.026 5.22 7.22 6.57 5.20 8.20 7.45 6.60 6.04 4.69 6.13 5.40 5.41 6.99 4.28 7.45 8.38 3.94 7.65 6.36 8.93 7.67 4.78 6.88 4.29 5.82 5.76 8.67 5.71 5.94 ADRENAL RIGHT ABS. REL. WT. % TBW a 0.031 0.030 0.024 0.016 0.029 0.024 0.024 0.022 0.019 0.030 0.016 0.025 0.028 0.023 0.037 0.029 0.022 0.026 0.030 0.038 0.032 0.020 0.022 0.015 0.030 0.024 0.035 0.019 0.024 6.74 6.18 4.78 3.62 7.67 6.38 5.87 5.31 3.88 6.56 3.76 6.44 6.53 4.47 7.25 7.36 4.34 6.42 6.36 9.43 7.22 4.78 5.40 3.39 6.71 6.02 7.78 4.94 5.48 SPLEEN ABS. WT. REL. % TBW 0.65 0.64 0.85 0.95 0.60 0.63 0.73 0.67 0.67 0.62 0.69 0.59 0.78 0.89 0.69 0.75 0.84 0.84 0.91 0.78 0.65 0.67 0.84 0.71 0.81 0.72 1.14 0.52 0.78 0.14 0.13 0.17 0.21 0.16 0.17 0.18 0.16 0.14 0.14 0.16 0.15 0.18 0.17 0.14 0.19 0.16 0.21 0.19 0.19 0.15 0.16 0.21 0.16 0.18 0.18 0.25 0.14 0.18 THYMUS ABS. WT. REL. % TBW 0.28 0.18 0.73 0.20 0.53 0.28 0.34 0.24 0.31 0.26 0.22 0.21 0.30 0.55 0.51 0.47 0.68 0.34 0.52 0.73 0.46 0.40 0.31 0.39 0.43 0.27 0.44 0.30 0.39 0.06 0.04 0.14 0.04 0.14 0.07 0.08 0.06 0.06 0.06 0.05 0.05 0.07 0.11 0.10 0.12 0.13 0.08 0.11 0.18 0.10 0.10 0.08 0.09 0.10 0.07 0.10 0.08 0.09 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT . = ORGAN WEIGHT . REL. % TBW := (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. b. Rat 1294 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 1) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 447 DOSAGE GROUP I 0 MG/KG/DAY RAT NUMBER BRAIN WEIGHT EPIDIDYMIS LEFT ABS. REL. W T . % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. W T . % BRW TESTIS LEFT ABS. REL. W T . BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. W T . % BRW SEMINAL VESICLES WITH FLUID ABS. REL. W T . % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % BRW 1002 1003 1005 1007 1011 1012 1013 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 1052 1054 1055 1058 1059 1060 2.27 2.40 2.36 2.23 2.22 2.32 2.29 2.51 2.30 2.27 2.25 2.52 2.17 2.45 2.25 2.25 2.39 2.25 2.40 2.28 2.42 2.40 2.20 2.62 2.47 2.46 2.43 1.94 2.44 2.40 0.7752 0.7726 0.6687 0.6686 0.6963 0.7115 0.6641 0.7869 0.6555 0.6987 0.6580 0.7822 0.6933 0.6753 0.6971 0.5600 0.6153 0.5846 0.6476 0.6937 0.7059 0.6579 0.6975 0.7675 0.7354 0.7518 0.6775 0.5881 0.6360 0.6379 34.15 32.19 28.33 29.98 31.36 30.67 29.00 31.35 28.50 30.78 29.24 31.04 31.95 27.56 30.98 24.89 25.74 25.98 26.98 30.42 29.17 27.41 31.70 29.29 29.77 30.56 27.88 30.31 26.06 26.58 0.3991 0.3611 0.3080 0.3350 0.3387 0.3373 0.3204 0.3583 0.2932 0.3482 0.3339 0.4020 0.3383 0.3248 0.3283 0.2757 0.2846 0.2599 0.3170 0.3335 0.3676 0.3233 0.3498 0.3806 0.3854 0.3819 0.3243 0.2814 0.2937 0.3128 17.58 15.04 13.05 15.02 15.26 14.54 13.99 14.27 12.75 15.34 14.84 15.95 15.59 13.26 14.59 12.25 11.91 11.55 13.21 14.63 15.19 13.47 15.90 14.53 15.60 15.52 13.34 14.50 12.04 13.03 1.9221 1.8125 1.6994 1.5619 1.5902 1.7682 1.6088 1.8831 1.7762 1.8218 1.7024 1.9518 1.7226 1.7995 1.5867 1.4438 1.5830 1.6181 1.8685 2.0197 1.7596 1.5749 1.6161 2.0003 1.9346 1.9560 1.7734 1.6935 1.7162 1.6027 84.67 75.52 72.01 70.04 71.63 76.22 70.25 75.02 77.23 80.26 75.66 77.45 79.38 73.45 70.52 64.17 66.23 71.92 77.85 88.58 72.71 65.62 73.46 76.35 78.32 79.51 72.98 87.29 70.34 66.78 1.7786 1.6880 1.5948 1.4691 1.4829 1.6627 1.5081 1.7555 1.6737 1.6868 1.5794 1.8349 1.6188 1.6663 1.4943 1.2926 1.5238 1.4797 1.6406 1.8917 1.6111 1.4321 1.4572 1.8134 1.7771 1.8014 1.6231 1.5125 1.6036 1.4347 78.35 70.33 67.58 65.88 66.80 71.67 65.86 69.94 72.77 74.31 70.20 72.81 74.60 68.01 66.41 57.45 63.76 65.76 68.36 82.97 66.57 59.67 66.24 69.21 71.95 73.23 66.79 77.96 65.72 59.78 1.6467 72.54 2.1281 88.67 1.7303 73.32 1'.8008 80.75 1.7689 79.68 2.1506 92.70 2.2159 96.76 2.5406 101.22 1.6431 71.44 1.8339 80.79 1.6675 74.11 2.2373 88.78 1.5930 73.41 2.2558 92.07 2.0640 91.73 1.6995 75.53 2.0948 87.65 1.7416 77.40 1.4429 60.12 2.1573 94.62 1.3668 56.48 2.0222 84.26 1.7612 80.05 2.3132 88.29 2.0816 84.28 2.5943 105.46 2.0127 82.83 1.8827 97.05 1.1345 46.50 1.3529 56.37 0.8308 1.0361 0.8830 0.9282 0.9602 1.0488 1.2484 1.3229 0.9578 1.0077 0.7430 1.0835 0.9180 1.1674 0.8644 0.9306 0.9268 1.0356 0.8137 1.1610 0.7839 0.9460 0.7748 1.1160 1.1932 1.4246 1.1275 0.9591 0.7241 0.7172 36.60 43.17 37.42 41.62 43.25 45.21 54.52 52.70 41.64 44.39 33.02 43.00 42.30 47.65 38.42 41.36 38.78 46.03 33.90 50.92 32.39 39.42 35.22 42.60 48.31 57.91 46.40 49.44 29.68 29.88 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 2) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 448 DOSAGE GROUP I 0 MG/KG/DAY RAT NUMBER BRAIN WEIGHT EPIDIDYMIS RIGHT ABS. REL. WT. % BRW 1002 1003 1005 1007 1011 1012 1013 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 1052 1054 1055 1058 1059 1060 2.27 2.40 2.36 2.23 2.22 2.32 2.29 2.51 2.30 2.27 2.25 2.52 2.17 2.45 2.25 2.25 2.39 2.25 2.40 2.28 2.42 2.40 2.20 2.62 2.47 2.46 2.43 1.94 2.44 2.40 0.7585 0.7227 6810 6742 6834 6799 6817 0.8172 0.6814 7343 6593 7373 6915 6714 6982 0.5628 0.6359 0.6364 6825 7169 7403 6381 7014 0.8552 0.8026 7438 7348 6267 6254 6724 33.41 30.11 28.86 30.23 30.78 29.31 29.77 32.56 29.63 32.35 29.30 29.26 31.87 27.40 31.03 25.01 26.61 28.28 28.44 31.44 30.59 26.59 31.88 32.64 32.49 30.24 30.24 32.30 25.63 28.02 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . TESTIS RIGHT ABS. REL. WT. % BRW PROSTATE ABS. WT. REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW 1.8845 1.7920 1.6608 1.5845 1.5867 1.7336 1.6417 1.7921 1.7002 1.8175 1.6437 1.8810 1.6696 1.6776 1.5835 1.5086 1.6333 1.5862 1.8901 1.9229 1.7809 1.4826 1.5870 1.9756 1.9853 1.9381 1.8211 1.6947 1.7833 1.7323 83.02 74.67 70.37 71.05 71.47 74.72 71.69 71.40 73.92 80.07 73.05 74.64 76.94 68.47 70.38 67.05 68.34 70.50 78.75 84.34 73.59 61.78 72.14 75.40 80.38 78.78 74.94 87.36 73.09 72.18 0.4671 0.6059 0.5167 0.5157 0.7725 1.3440 1.0484 1.0938 1.3176 0.9022 1.2225 1.6240 1.2618 1.2276 1.2740 0.8117 1.1217 1.1027 0.8592 1.0457 1.4155 1.0329 1.0311 1.3585 1.1700 1.1579 1.1323 1.1133 0.7495 0.8267 20.58 25.24 21.89 23.12 34.80 57.93 45.78 43.58 57.29 39.74 54.33 64.44 58.15 50.11 56.62 36.08 46.93 49.01 35.80 45.86 58.49 43.04 46.87 51.85 47.37 47.07 46.60 57.39 30.72 34.44 0.015 0.014 0.011 0.014 0.011 0.014 0.014 0.012 0.013 0.013 0.015 0.015 0.015 0.016 0.013 0.009 0.011 0.011 0.019 0.015 0.014 0.023 0.010 0.020 0.013 0.020 0.021 0.018 0.018 0.012 0.66 0.58 0.47 0.63 0.50 0.60 0.61 0.48 0.56 0.57 0.67 0.60 0.69 0.65 0.58 0.40 0.46 0.49 0.79 0.66 0.58 0.96 0.45 0.76 0.53 0.81 0.86 0.93 0.74 0.50 21.20 933.92 25.00 1041.67 19.70 834.74 21.20 950.67 24.75 1114.86 24.99 1077.16 21.79 951.53 22.01 876.89 17.05 741.30 25.08 1104.84 23.69 1052.89 22.31 885.32 18.86 869.12 21.65 883.67 17.02 756.44 16.86 749.33 20.38 852.72 23.82 1058.67 21.30 887.50 18.32 803.51 29.20 1206.61 27.26 1135.83 21.29 967.73 25.09 957.63 24.34 985.42 20.05 815.04 21.35 - 878.60 20.17 1039.69 16.10 659.84 17.81 742.08 2.17 2.38 2.13 2.10 2.19 2.22 2.35 2.08 2.05 2.41 2.21 2.41 1.85 2.31 1.73 1.98 2.22 2.35 2.07 1.99 2.37 2.58 1.96 2.59 2.51 2.22 2.31 2.21 2.19 2.30 95.59 99.17 90.25 94.17 98.65 95.69 102.62 82.87 89.13 106.17 98.22 95.63 85.25 94.28 76.89 88.00 92.89 104.44 86.25 87.28 97.93 107.50 89.09 98.85 101.62 90.24 95.06 113.92 89.75 95.83 ABS. WT. ORGAN WEIGHT REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 3) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 449 DOSAGE GROUP I 0 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1002 1003 1005 1007 1011 1012 1013 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 1052 1054 1055 1058 1059 1060 2.27 2.40 2.36 2.23 2.22 2.32 2.29 2.51 2.30 2.27 2.25 2.52 2.17 2.45 2.25 2.25 2.39 2.25 2.40 2.28 2.42 2.40 2.20 2.62 2.47 2.46 2.43 1.94 2.44 2.40 KIDNEY RIGHT ABS. REL. W T . % BRW 2.28 2.20 2.08 2.00 2.18 2.20 2.28 2.16 2.04 2.56 2.24 2.39 1.93 2.20 1.71 1.95 2.23 2.54 2.22 2.09 2.56 2.63 2.13 2.54 2.47 2.26 2.42 2.28 2.13 2.27 100.44 91.67 88.14 89.69 98.20 94.83 99.56 86.06 88.70 112.78 99.56 94.84 88.94 89.80 76.00 86.67 93.30 112.89 92.50 91.67 105.78 109.58 96.82 96.95 100.00 91.87 99.59 117.52 87.30 94.58 ADRENAL LEFT ABS. REL. WT. % BRW 0.031 0.029 0.037 0.029 0.038 0.025 0.027 0.026 0.029 0.026 0.035 0.034 0.036 0.030 0.028 0.028 0.022 0.024 0.023 0.041 0.038 0.039 0.035 0.041 0.033 0.028 0.037 0.030 0.039 0.030 1.36 1.21 1.57 1.30 1.71 1.08 1.18 1.04 1.26 1.14 1.56 1.35 1.66 1.22 1.24 1.24 0.92 1.07 0.96 1.80 1.57 1.62 1.59 1.56 1.34 1.14 1.52 1.55 1.60 1.25 ADRENAL RIGHT ABS. REL. WT. % BRW 0.028 0.023 0.038 0.031 0.032 0.022 0.027 0.023 0.030 0.036 0.030 0.036 0.037 0.019 0.011a 0.022 0.018 0.024 0.023 0.039 0.036 0.036 0.029 0.041 0.036 0.027 0.037 0.030 0.036 0.023 1.23 0.96 1.61 1.39 1.44 0.95 1.18 0.92 1.30 1.58 1.33 1.43 1.70 0.78 0.4 9a 0.98 0.75 1.07 0.96 1.71 1.49 1.50 1.32 1.56 1.46 1.10 1.52 1.55 1.48 0.96 SPLEEN ABS. WT. REL. BRW 0.96 1.02 1.00 1.03 0.95 0.90 1.02 0.95 0.72 0.98 0.93 0.97 0.98 0.93 0.73 0.69 1.34 0.94 0.88 0.79 1.13 1.05 0.83 1.13 1.03 0.99 0.83 0.86 1.04 0.73 42.29 42.50 42.37 46.19 42.79 38.79 44.54 37.85 31.30 43.17 41.33 38.49 45.16 37.96 32.44 30.67 56.07 41.78 36.67 34.65 46.69 43.75 37.73 43.13 41.70 40.24 34.16 44.33 42.62 30.42 THYMUS ABS. WT. 1 % 0.28 0.42 0.62 0.59 0.71 0.73 0.52 0.32 0.43 0.44 0.50 0.46 0.41 0.44 0.37 0.43 0.45 0.72 0.59 0.61 0.36 0.56 0.59 0.52 0.70 0.54 0.55 0.58 0.33 0.47 12.33 17.50 26.27 26.46 31.98 31.46 22.71 12.75 18.70 19.38 22.22 18.25 18.89 17.96 16.44 19.11 18.83 32.00 24.58 26.75 14.88 23.33 26.82 19.85 28.34 21.95 22.63 29.90 13.52 19.58 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Damaged during processing (weight affected); values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 4) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 450 DOSAGE GROUP II 1 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 1112 1114 1116 1118 1120 2.16 2.26 2.10 1.98 2.04 2.37 2.26 2.08 2.25 2.35 2.17 2.30 2.07 2.33 2.24 2.45 2.28 2.47 2.38 2.33 2.35 2.13 2.15 2.33 2.64 2.55 2.36 2.37 2.43 EPIDIDYMIS LEFT ABS. REL. WT. BRW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. BRW 0.7660 35.46 0.7170 31.72 0.6338 30.18 0.6124 30.93 0.6531 32.01 0.6507 27.46 0.7059 31.23 0.7864 37.81 0.7598 33.77 0.7080 30.13 0.3393a 15.64 0.6435 27.98 0.5518 26.66 0.7257 31.14 0.6785 30.29 0.6134 25.04 0.6428 28.19 0.6912 27.98 0.7062 29.67 0.6344 27.23 0.6689 28.46 0.5997 28.15 0.6601 30.70 0.6219 26.69 0.6981 26.44 0.6757 26.50 0.6704 28.41 0.6492 27.39 0.7509 30.90 0.3553 16.45 0.3300 14.60 0.2762 13.15 0.2886 14.58 0.3027 14.84 0.3269 13.79 0.2707 11.98 0.4014 19.30 0.3979 17.68 0.3712 15.80 0.1461a 6.73 0.3460 15.04 0.2467 11.92 0.3524 15.12 0.3080 13.75 0.3012 12.29 0.3252 14.26 0.3288 13.31 0.3866 16.24 0.3308 14.20 0.3369 14.34 0.2759 12.95 0.3072 14.29 0.3101 13.31 0.3442 13.04 0.3169 12.43 0.2919 12.37 0.2958 12.48 0.3424 14.09 TESTIS LEFT ABS. REL. WT. ' BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL VESICLES WITH FLUID ABS. REL. WT. * BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. BRW 1.7863 82.70 1.8632 82.44 1.7790 84.71 1.5556 78.56 1.7625 86.40 1.6107 67.96 1.9881 87.97 1.8023 86.65 1.7878 79.46 1.7687 75.26 1.0590a 48.80 1.4745 64.11 1.6224 78.38 1.6645 71.44 1.6320 72.86 1.7090 69.76 1.6702 73.25 1.6920 68.50 1.9487 81.88 1.6819 72.18 1.7418 74.12 1.5584 73.16 1.6067 74.73 1.6555 71.05 1.8105 68.58 1.9848 77.84 1.5620 66.19 1.6885 71.24 2.0030 82.43 1.6295 75.44 1.7520 77.52 1.6559 78.85 1.4453 72.99 1.6520 80.98 1.5115 63.78 1.8542 82.04 1.6513 79.39 1.6647 73.99 1.6044 68.27 0.4551a 20.97 1.3716 59.63 1.5186 73.36 1.5413 66.15 1.5236 68.02 1.3518 55.18 1.4565 63.88 1.5653 63.37 1.7580 73.86 1.5379 66.00 1.5524 66.06 1.4213 66.73 1.4424 67.09 1.5194 65.21 1.6908 64.04 1.8202 71.38 1.4146 59.94 1.5853 66.89 1.8717 77.02 1.9084 88.35 2.2839 101.06 2.2858 108.85 1.7391 87.83 2.0289 99.46 2.2645 95.55 2.1775 96.35 2.2437 107.87 1.9818 88.08 1.9950 84.89 2.0247 93.30 2.3555 102.41 1.7858 86.27 2.0530 88.11 1.8496 82.57 2.4316 99.25 2.2994 100.85 2.0056 81.20 2.4765 104.05 1.9311 82.88 1.7219 73.27 1.7814 83.63 1.5051 70.00 1.8402 78.98 2.1860 82.80 2.3440 91.92 2.0547 87.06 2.1617 91.21 2.3378 96.20 1.0157 1.1167 1.3449 0.9152 1.0798 1.1328 1.1732 1.0133 0.9239 0.9701 0.9927 0.9679 0.9166 0.9295 0.8012 1.3115 1.0829 1.0369 1.3095 0.9989 0.7884 1.0277 0.8120 0.8915 1.2293 1.2241 1.0185 1.0063 1.0701 47.02 49.41 64.04 46.22 52.93 47.80 51.91 48.72 41.06 41.28 45.75 42.08 44.28 39.89 35.77 53.53 47.50 41.98 55.02 42.87 33.55 48.25 37.77 38.26 46.56 48.00 43.16 42.46 44.04 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . WT. - ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 1082 had a small, left epididymis and cauda epididymis, small, flaccid left testis, and a fluid filled left testis minus tunica albuginea; values included in group averages and statistical analyses. PROTOCOL 418-020: ! ^ J G?VAGE) TM0-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 5) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 451 DOSAGE GROUP II 1 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 1112 1114 1116 1118 1120 2.16 2.26 2.10 1.98 2.04 2.37 2.26 2.08 2.25 2.35 2.17 2.30 2.07 2.33 2.24 2.45 2.28 2.47 2.38 2.33 2.35 2.13 2.15 2.33 2.64 2.55 2.36 2.37 2.43 EPIDIDYMIS RIGHT ABS. REL. WT. % BRW 0.7284 33.72 0.7113 31.47 0.6396 30.46 0.6431 32.48 0.6310 30.93 0.6846 28.89 0.7456 32.99 0.7614 36.60 0.7545 33.53 0.7025 29.89 0.6989 32.21 0.6288 27.34 0.6170 29.81 0.6845 29.38 0.7019 31.33 0.6599 26.93 0.6911 30.31 0.7465 30.22 0.7631 32.06 0.6229 26.73 0.6993b 29.76 0.6575 30.87 0.6578 30.60 0.6330 27.17 0.6748 25.56 0.7494 29.39 0.6639 28.13 0.6786 28.63 0.6911 28.44 TESTIS RIGHT ABS. REL. WT. % BRW 1.8528 1.8505 1.5745 1.5154 1.6782 1.5542 1.9825 1.8037 1.7230 1.7244 1.7261 1.4717 1.6474 1.6176 1.6796 1.7494 1.6621 1.7774 1.9639 1.6532 1.7282 1.6263 1.6277 1.6504 1.8656 1.9312 1.5988 1.7496 1.9723 85.78 81.88 74.98 76.54 82.26 65.58 87.72 86.72 76.58 73.38 79.54 63.99 79.58 69.42 74.98 71.40 72.90 71.96 82.52 70.95 73.54 76.35 75.71 70.83 70.67 75.73 67.74 73.82 81.16 PROSTATE ABS. REL. WT. % BRW 0.4761 22.04 0.8821 39.03 0.2716a 12.93 0.5982 30.21 0.8284 40.61 1.3268 55.98 1.3308 58.88 0.8947 43.01 1.3800 61.33 1.3717 58.37 1.2924 59.56 1.3446 58.46 0.9942 48.03 1.5251 65.45 1.2761 56.97 1.1454 46.75 1.0867 47.66 1.0373 42.00 1.1216 47.13 1.1903 51.08 0.8336 35.47 1.2108 56.84 0.9999 46.51 0.9081 38.97 1.4610 55.34 1.1564 45.35 1.2054 51.08 1.0908 46.02 1.1517 47.40 PITUITARY ABS. WT. REL. % BRW 0.011 0.012 0.011 0.012 0.011 0.012 0.016 0.011 0.014 0.014 0.016 0.014 0.012 0.014 0.017 0.014 0.025 0.016 0.015 0.024 0.013 0.013 0.033 0.015 0.018 0.023 0.026 0.023 0.028 0.51 0.53 0.52 0.61 0.54 0.51 0.71 0.53 0.62 0.60 0.74 0.61 0.58 0.60 0.76 0.57 1.10 0.65 0.63 1.03 0.55 0.61 1.53 0.64 0.68 0.90 1.10 0.97 1.15 LIVER ABS. REL. W T . % BRW 20.77 961.57 26.60 1176.99 20.80 990.48 20.97 1059.09 21.61 1059.31 ' 26.35 1111.81 27.94 1236.28 25.28 1215.38 30.05 1335.56 22.81 970.64 24.34 1121.66 23.15 1006.52 15.51 749.28 29.13 1250.21 21.48 958.93 27.07 1104.90 29.60 1298.24 32.95 1334.01 30.37 1276.05 22.79 978.11 27.76 1181.28 22.68 1064.79 19.46 905.12 20.50 879.83 28.97 1097.35 27.29 1070.20 21.37 905.51 22.51 949.79 22.49 925.51 KIDNEY LEFT ABS. REL. W T . t BRW 2.06 2.50 2.03 1.95 2.10 2.43 2.43 2.39 2.67 2.24 2.16 2.27 1.79 2.22 2.27 2.68 2.39 2.39 2.35 2.59 2.54 2.19 2.05 2.21 2.90 2.80 2.33 2.74 2.46 95.37 110.62 96.67 98.48 102.94 102.53 107.52 114.90 118.67 95.32 99.54 98.70 86.47 95.28 101.34 109.39 104.82 96.76 98.74 111.16 108.08 102.82 95.35 94.85 109.85 109.80 98.73 115.61 101.23 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 1066 had a small prostate; values included in group averages and statistical analyses. b. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 6) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 452 DOSAGE GROUP II 1 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 1112 1114 1116 1118 1120 2.16 2.26 2.10 1.98 2.04 2.37 2.26 2.08 2.25 2.35 2.17 2.30 2.07 2.33 2.24 2.45 2.28 2.47 2.38 2.33 2.35 2.13 2.15 2.33 2.64 2.55 2.36 2.37 2.43 KIDNEY RIGHT ABS. REL. W T . % BRW 1.90 2.46 2.10 2.07 1.98 2.46 2.50 2.18 2.69 2.41 2.15 2.23 1.92 2.02 2.27 2.56 2.38 2.45 2.44 2.37 2.59 2.21 2.05 2.16 3.01 2.84 2.37 2.73 2.53 87.96 108.85 100.00 104.54 97.06 103.80 110.62 104.81 119.56 102.55 99.08 96.96 92.75 86.70 101.34 104.49 104.38 99.19 102.52 101.72 110.21 103.76 95.35 92.70 114.02 111.37 100.42 115.19 104.12 ADRENAL LEFT ABS. REL. W T . % BRW 0.016 0.041 0.028 0.024 0.020 0.018 0.037 0.044 0.036 0.028 0.035 0.039 0.028 0.032 0.025 0.029 0.048 0.024 0.030 0.038 0.040 0.024 0.034 0.020 0.039 0.042 0.041 0.032 0.030 0.74 1.81 1.33 1.21 0.98 0.76 1.64 2.12 1.60 1.19 1.61 1.70 1.35 1.37 1.12 1.18 2.10 0.97 1.26 1.63 1.70 1.13 1.58 0.86 1.48 1.65 1.74 1.35 1.23 ADRENAL RIGHT ABS. REL. WT. t BRW 0.023 0.034 0.022 0.027 0.009 0.024 0.037 0.041 0.032 0.028 0.031 0.030 0.026 0.027 0.024 0.030 0.041 0.024 0.028 0.033 0.036 0.023 0.035 0.019 0.043 0.037 0.027 0.029 0.026 1.06 1.50 1.05 1.36 0.44 1.01 1.64 1.97 1.42 1.19 1.43 1.30 1.26 1.16 1.07 1.22 1.80 0.97 1.18 1.42 1.53 1.08 1.63 0.82 1.63 1.45 1.14 1.22 1.07 SPLEEN ABS. WT. REL. % BRW 0.76 0.84 0.64 0.65 0.72 0.84 0.68 0.58 0.92 0.83 0.86 0.75 0.74 0.85 0.75 0.89 1.00 0.95 0.80 0.82 0.92 0.75 0.60 0.73 1.24 1.03 0.90 1.06 1.00 35.18 37.17 30.48 32.83 35.29 35.44 30.09 27.88 40.89 35.32 39.63 32.61 35.75 36.48 33.48 36.33 43.86 38.46 33.61 35.19 39.15 35.21 27.91 31.33 46.97 40.39 38.14 44.72 41.15 THYMUS ABS. REL. WT. % BRW 0.60 0.61 0.64 0.46 0.39 0.42 0.22 0.57 0.42 0.37 0.46 0.37 0.29 0.40 0.31 0.55 0.53 0.69 0.61 0.55 0.65 0.58 0.36 0.44 0.35 0.48 0.32 0.41 0.36 27.78 26.99 30.48 23.23 19.12 17.72 9.73 27.40 18.67 15.74 21.20 16.09 14.01 17.17 13.84 22.45 23.24 27.94 25.63 23.60 27.66 27.23 16.74 18.88 13.26 18.82 13.56 17.30 14.81 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.G) TABLE D21 (PAGE 7) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 453 DOSAGE GROUP III 3 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 1171 1173 1175 1176 1177 1180 2.40 2.40 2.20 2.29 2.23 2.22 2.40 2.17 2.16 2.29 2.17 2.16 2.04 2.33 2.36 2.41 2.35 2.23 2.28 2.24 2.31 2.41 2.23 2.51 2.31 2.41 2.53 2.33 2.43 2.47 EPIDIDYMIS LEFT ABS. REL. WT. % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % BRW 0.7208 0.6070 0.6614 0.7407 0.6952 0.6725 0.7615 0.6679 0.6855 0.6190 0.6450 0.6121 0.6915 0.7098 0.8130 0.6764 0.6843 0.5970 0.6503 0.7223 0.6669 0.7675 0.6801 0.6367 0.5776 0.6524 0.6272 0.5684 0.7391 0.6971 30.03 25.29 30.06 32.34 31.17 30.29 31.73 30.78 31.74 27.03 29.72 28.34 33.90 30.46 34.45 28.07 29.12 26.77 28.52 32.24 28.87 31.85 30.50 25.37 25.00 27.07 24.79 24.39 30.42 28.22 0.3470 0.2968 0.3302 0.3502 0.3581 0.3378 0.3358 0.3218 0.3406 0.3274 0.3546 0.2953 0.3255 0.3588 0.4132 0.3179 0.3349 0.2924 0.3024 0.3698 0.3101 0.3613 0.3252 0.2903 0.2903 0.3273 0.2745 0.2863 0.3494 0.3350 14.46 12.37 15.01 15.29 16.06 15.22 13.99 14.83 15.77 14.30 16.34 13.67 15.96 15.40 17.51 13.19 14.25 13.11 13.26 16.51 13.42 14.99 14.58 11.56 12.57 13.58 10.85 12.29 14.38 13.56 TESTIS LEFT ABS. REL. WT. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL VESICLES WITH FLUID ABS. REL. WT. % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % BRW 1.6159 67.33 1.8182 75.76 1.6347 74.30 1.9335 84.43 1.7682 79.29 1.7645 79.48 1.8988 79.12 1.7237 79.43 1.9009 88.00 1.6472 71.93 1.5627 72.01 1.6597 76.84 1.8607 91.21 1.6976 72.86 2.0462 86.70 1.8091 75.07 3.0171al28.39 1.7007 76.26 1.7179 75.35 1.8480 82.50 1.7050 73.81 1.9198 79.66 1.7101 76.69 1.8227 72.62 1.5240 65.97 1.5741 65.32 1.7498 69.16 1.9718 84.63 2.2666 93.28 1.9639 79.51 1.5221 63.42 1.6922 70.51 1.5124 68.74 1.8129 79.16 1.6707 74.92 1.6362 73.70 1.7685 73.69 1.6026 73.85 1.6834 77.94 1.5631 68.26 1.4612 67.34 1.5318 70.92 1.7494 85.75 1.6060 68.93 1.9344 81.97 1.5925 66.08 2.7687all7.82 1.4274 64.01 1.5439 67.71 1.6935 75.60 1.5581 67.45 1.7783 73.79 1.5089 67.66 1.6190 64.50 1.4063 60.88 1.4256 59.15 1.6409 64.86 1.8165 77.96 2.1025 86.52 1.8501 74.90 2.0470 85.29 2.3013 95.89 1.7196 78.16 2.1930 95.76 2.3326 104.60 2.3904 107.68 2.1383 89.10 1.8500 85.25 1.3217 61.19 1.7038 74.40 1.7528 80.77 2.0896 96.74 1.8492 90.65 1.7211 73.87 2.3386 99.09 2.2078 91.61 1.9461 82.81 1.8889 84.70 2.1813 95.67 2.3263 103.85 2.0033 86.72 1.9163 79.51 2.0326 91.15 1.5592 62.12 1.8020 78.01 2.1183 87.90 1.7132 67.72 1.4040 60.26 2.0790 85.56 2.1032 85.15 1.0874 1.2447 0.9666 1.1095 1.0857 1.2665 1.0924 0.9966 0.7638 0.9308 0.8441 0.9784 1.0012 0.9009 1.1584 0.9860 1.0849 0.8750 1.1530 1.1211 0.8661 0.8735 1.0820 0.9914 1.0915 1.0216 1.0295 0.8061 1.1398 1.0329 45.31 51.86 43.94 48.45 48.69 57.05 45.52 45.93 35.36 40.65 38.90 45.30 49.08 38.66 49.08 40.91 46.16 39.24 50.57 50.05 37.49 36.24 48.52 39.50 47.25 42.39 40.69 34.60 46.90 41.82 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 1153 had a large, left testis and testis minus tunica albuginea; values included in group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 8) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA * FI GENERATION MALE RATS ARGUS 418-020 Page 454 DOSAGE GROUP III 3 MG/KG/DAY RAT NUMBER BRAIN WEIGHT EPIDIDYMIS RIGHT ABS. REL. WT. % BRW TESTIS RIGHT ABS. REL. WT. % BRW PROSTATE ABS. WT. REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 1171 1173 1175 1176 1177 1180 2.40 2.40 2.20 2.29 2.23 2.22 2.40 2.17 2.16 2.29 2.17 2.16 2.04 2.33 2.36 2.41 2.35 2.23 2.28 2.24 2.31 2.41 2.23 2.51 2.31 2.41 2.53 2.33 2.43 2.47 .6838 28.49 .6106 25.44 .6629 30.13 .7111 31.05 .6877 30.84 .6987 31.47 .7236 30.15 .6703 30.89 0.6601 30.56 0.6262 27.34 0.6701ai 30.88 0.6442 29.82 0.6614 32.42 0.6789 29.14 0.7538 31.94 0.6490 26.93 0.7007 29.82 0.6741 30.23 0.6996 30.68 0.7245 32.34 0.6761ai 29.27 0.7592 31.50 0.7044 31.59 0.6950 27.69 0.5841 25.28 0.6720 27.88 0.6517 25.76 0.6153 26.41 0.7824 32.20 0.7608 30.80 1.6035 1.7572 1.6197 1.8049 1.7444 1.7356 1.9533 1.6461 1.8638 1.7137 1.5828 1.6204 1.8248 1.7369 2.0918 1.7336 1.7874 1.7880 1.7801 1.8539 1.6565 1.9644 1.7935 1.9170 1.5517 1.6114 1.7506 1.9358 2.2229 1.9351 66.81 73.22 73.62 78.82 78.22 78.18 81.39 75.86 86.29 74.83 72.94 75.02 89.45 74.54 88.64 71.93 76.06 80.18 78.07 82.76 71.71 81.51 80.43 76.37 67.17 66.86 69.19 83.08 91.48 78.34 0.4770 0.3938 0.4890 0.9503 0.9830 1.1426 1.0100 1.1130 0.8226 1.0147 1.2215 0.9640 1.0366 1.0363 1.3772 1.1726 1.2844 1.1087 0.8279 1.1479 1.2450 1.2929 1.1156 0.9715 1.0645 1.1758 1.1055 0.9663 1.2319 1.0538 19.88 16.41 22.23 41.50 44.08 51.47 42.08 51.29 38.08 44.31 56.29 44.63 50.81 44.48 58.36 48.66 54.66 49.72 36.31 51.24 53.90 53.65 50.03 38.70 46.08 48.79 43.70 41.47 50.70 42.66 0.010 0.013 0.012 0.016 0.010 0.016 0.011 0.014 0.011 0.011 0.012 0.013 0.014 0.010 0.015 0.017 0.013 0.023 0.019 0.025 0.014 0.013 0.018 0.021 0.020 0.028 0.012 0.032 0.015 0.025 0.42 0.54 0.54 0.70 0.45 0.72 0.46 0.64 0.51 0.48 0.55 0.60 0.69 0.43 0.64 0.70 0.55 1.03 0.83 1.12 0.61 0.54 0.81 0.84 0.86 1.16 0.47 1.37 0.62 1.01 28.00 1166.67 27.20 1133.33 28.00 1272.73 37.20 1624.45 31.29 1403.14 24.46 1101.80 31.25 1302.08 26.42 1217.51 24.58 1137.96 26.94 1176.42 24.41 1124.88 24.96 1155.56 24.17 1184.80 26.73 1147.21 28.43 1204.66 31.06 1288.80 15.00 638.30 31.44 1409.86 33.93 1488.16 28.29 1262.95 31.33 1356.28 30.89 1281.74 33.05 1482.06 31.60 1258.96 25.18 1090.04 27.19 1128.22 26.00 . 1027.67 25.54 1096.14 34.48 1418.93 28.35 1147.77 2.33 2.40 2.10 2.58 2.81 2.43 2.52 2.46 2.49 2.50 2.23 2.19 2.20 2.24 2.74 2.58 2.46 2.72 2.46 2.54 2.59 2.67 2.56 2.45 2.09 2.28 2.21 2.56 2.76 2.54 97.08 100.00 95.45 112.66 126.01 109.46 105.00 113.36 115.28 109.17 102.76 101.39 107.84 96.14 116.10 107.05 104.68 121.97 107.89 113.39 112.12 110.79 114.80 97.61 90.48 94.60 87.35 109.87 113.58 102.83 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. W T . ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 9) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 455 DOSAGE GROUP III J MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 1171 1173 1175 1176 1177 1180 2.40 2.40 2.20 2.29 2.23 2.22 2.40 2.17 2.16 2.29 2.17 2.16 2.04 2.33 2.36 2.41 2.35 2.23 2.28 2.24 2.31 2.41 2.23 2.51 2.31 2.41 2.53 2.33 2.43 2.47 KIDNEY RIGHT ABS. REL. W T . % BRW 2.31 2.40 2.11 2.78 2.67 2.49 2.63 2.35 2.41 2.48 2.24 2.16 2.02 2.17 2.50 2.78 2.55 2.71 2.57 2.92 2.71 2.62 2.56 2.43 1.95 2.37 2.45 2.69 2.79 2.51 96.25 100.00 95.91 121.40 119.73 112.16 109.58 108.29 111.57 108.30 103.22 100.00 99.02 93.13 105.93 115.35 108.51 121.52 112.72 130.36 117.32 108.71 114.80 96.81 84.42 98.34 96.84 115.45 114.81 101.62 ADRENAL LEFT ABS. REL. W T . % BRW 0.024 0.030 0.024 0.036 0.024 0.039 0.037 0.026 0.039 0.037 0.030 0.029 0.028 0.032 0.034 0.027 0.024 0.030 0.029 0.042 0.027 0.035 0.029 0.029 0.031 0.028 0.029 0.036 0.034 0.036 1.00 1.25 1.09 1.57 1.08 1.76 1.54 1.20 1.80 1.62 1.38 1.34 1.37 1.37 1.44 1.12 1.02 1.34 1.27 1.88 1.17 1.45 1.30 1.16 1.34 1.16 1.15 1.54 1.40 1.46 ADRENAL RIGHT ABS. REL. W T . % BRW 0.020 0.032 0.026 0.032 0.028 0.036 0.038 0.027 0.032 0.032 0.030 0.026 0.019 0.027 0.029 0.018 0.021 0.028 0.024 0.034 0.027 0.030 0.031 0.029 0.032 0.033 0.022 0.029 0.030 0.037 0.83 1.33 1.18 1.40 1.26 1.62 1.58 1.24 1.48 1.40 1.38 1.20 0.93 1.16 1.23 0.75 0.89 1.26 1.05 1.52 1.17 1.24 1.39 1.16 1.38 1.37 0.87 1.24 1.23 1.50 SPLEEN ABS. REL. W T . % BRW 1.02 0.80 0.75 0.83 0.95 0.59 0.95 0.75 0.72 0.56 0.94 0.65 0.69 0.86 0.77 0.91 0.93 1.01 0.86 1.08 0.78 0.80 1.17 0.94 0.77 0.73 0.94 0.76 0.89 1.05 42.50 33.33 34.09 36.24 42.60 26.58 39.58 34.56 33.33 24.45 43.32 30.09 33.82 36.91 32.63 37.76 39.57 45.29 37.72 48.21 33.77 33.20 52.47 37.45 33.33 30.29 37.15 32.62 36.62 42.51 THYMUS ABS. WT. REL. % BRW 0.49 0.29 0.28 0.72 0.59 0.37 0.66 0.33 0.46 0.24 0.34 0.48 0.18 0.27 0.30 0.73 0.55 0.67 0.49 0.44 0.35 0.44 0.73 0.40 0.40 0.51 0.35 . 0.44 0.36 0.40 20.42 12.08 12.73 31.44 26.46 16.67 27.50 15.21 21.30 10.48 15.67 22.22 8.82 11.59 12.71 30.29 23.40 30.04 21.49 19.64 15.15 18.26 32.74 15.94 17.32 21.16 13.83 18.88 14.81 16.19 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 10) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 456 DOSAGE GROUP IV 10 MG/KG/DAY RAT NUMBER BRAIN WEIGHT EPIDIDYMIS LEFT ABS. REL. W T . % BRW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % BRW TESTIS LEFT ABS. REL. WT. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL VESICLES WITH FLUID ABS. REL. W T . % BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % BRW 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 1237 1240 2.23 2.30 2.16 2.20 2.40 2.22 2.22 2.16 2.36 2.22 2.30 2.24 2.22 2.28 2.44 2.49 2.30 2.32 2.09 2.21 2.07 2.39 2.32 2.44 2.15 2.22 2.40 2.23 2.37 2.32 0.5873 0.7364 0.6724 0.6851 0.7693 0.6944 0.7103 0.6484 0.7207 0.5748 0.7346 0.7013 0.6512 0.6746 0.7302 0.6593 0.6832 0.6969 0.5811 0.5729 0.6980 0.6952 0.6728 0.6327 0.6796 0.6882 0.5594 0.6243 0.6220 0.8036 26.34 32.02 31.13 31.14 32.05 31.28 32.00 30.02 30.54 25.89 31.94 31.31 29.33 29.59 29.93 26.48 29.70 30.04 27.80 25.92 33.72 29.09 29.00 25.93 31.61 31.00 23.31 28.00 26.24 34.64 0.2692 0.3508 0.3462 0.3285 0.4167 0.3106 0.3404 0.3165 0.3662 0.2920 0.3820 0.3523 0.3423 0.3294 0.3596 0.3135 0.3559 0.3209 0.2735 0.2820 0.3349 0.3592 0.3371 0.2997 0.3348 0.3264 0.2432 0.2962 0.2763 0.4063 12.07 15.25 16.03 14.93 17.36 13.99 15.33 14.65 15.52 13.15 16.61 15.73 15.42 14.45 14.74 12.59 15.47 13.83 13.09 12.76 16.18 15.03 14.53 12.28 15.57 14.70 10.13 13.28 11.66 17.51 1.6842 1.9148 1.5726 1.7130 1.8304 1.7946 1.7653 1.6721 1.9297 1.5606 1.7581 1.7531 1.7328 1.7361 1.9206 1.8977 1.7087 1.8089 1.6144 1.7055 2.0374 1.7559 1.6548 1.7194 1.8306 1.9365 1.7079 1.7320 1.6722 2.0756 75.52 83.25 72.80 77.86 76.27 80.84 79.52 77.41 81.77 70.30 76.44 78.26 78.05 76.14 78.71 76.21 74.29 77.97 77.24 77.17 98.42 73.47 71.33 70.47 85.14 87.23 71.16 77.67 70.56 89.46 1.5580 1.7769 1.4546 1.5980 1.5499 1.5264 1.6519 1.5753 1.7940 1.4555 1.6592 1.6424 1.5972 1.6305 1.8200 1.7249 1.4910 1.6898 1.4823 1.5490 1.8144 1.5914 1.5289 1.5668 1.6824 1.8148 1.5194 1.5580 1.5690 1.9055 69.86 77.26 67.34 72.64 64.58 68.76 74.41 72.93 76.02 65.56 72.14 73.32 71.94 71.51 74.59 69.27 64.83 72.84 70.92 70.09 87.65 66.58 65.90 64.21 78.25 81.75 63.31 69.86 66.20 82.13 2.1825 97.87 2.8035 121.89 1.6253 75.24 1.8294 83.15 2.0923 87.18 2.2638 101.97 2.2778 102.60 1.8174 84.14 2.2576 95.66 2.0476 92.23 2.1362 92.88 2.0554 91.76 2.0879 94.05 2.2509 98.72 2.5826 105.84 1.8533 74.43 2.0138 87.56 1.7647 76.06 2.0568 98.41 1.5690 71.00 2.1344 103.11 2.2735 95.12 2.2355 96.36 1.7349 71.10 1.3942 64.85 1.8359 82.70 2.310.4 96.27 1.6820 75.43 2.0813 87.82 2.5458 109.73 1.0993 1.3573 0.7547 1.0218 0.9952 1.3117 1.1574 0.9382 1.1818 0.9225 1.0182 1.0792 1.0570 1.2076 1.1246 1.0642 1.0114 0.9204 1.1085 0.9655 1.1960 1.2959 1.0700 0.9698 0.8422 1.0507 1.3382 1.0255 0.9398 1.0793 49.30 59.01 34.94 46.44 41.47 59.08 52.14 43.44 50.08 41.55 44.27 48.18 47.61 52.96 46.09 42.74 43.97 39.67 53.04 43.69 57.78 54.22 46.12 39.74 39.17 47.33 55.76 45.99 39.65 46.52 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 11) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 457 DOSAGE GROUP IV 10 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 1237 1240 2.23 2.30 2.16 2.20 2.40 2.22 2.22 2.16 2.36 2.22 2.30 2.24 2.22 2.28 2.44 2.49 2.30 2.32 2.09 2.21 2.07 2.39 2.32 2.44 2.15 2.22 2.40 2.23 2.37 2.32 EPIDIDYMIS RIGHT ABS. REL. WT. % BRW 0.6047 27.12 0.7559 32.86 0.6982 32.32 0.6993 31.79 0.7530 31.38 0.6947 31.29 0.7274 32.76 0.6028 27.91 0.7218 30.58 0.6076 27.37 0.7386 32.11 0.7052 31.48 0.6614 29.79 0.7154 31.38 0.7298 29.91 0.6595 26.48 0.6748 29.34 0.7102a 30.61 0.6257 29.94 0.6549 29.63 0.7082 34.21 0.7384 30.90 0.6937 29.90 0.6851 28.08 0.7064 32.86 0.6704 30.20 0.6843 28.51 0.6360 28.52 0.6242 26.34 0.7558 32.58 TESTIS RIGHT ABS. REL. WT. % BRW 1.6680 1.8710 1.6171 1.6425 1.8294 1.7973 1.7765 1.6682 1.8638 1.6140 1.7777 1.6577 1.6149 1.7180 1.9154 1.9394 1.6544 1.7837 1.6034 1.7229 1.9675 1.8250 1.6822 1.7896 1.8647 1.8883 1.7895 1.7348 1.6814 2.0720 74.80 81.35 74.86 74.66 76.22 80.96 80.02 77.23 78.97 72.70 77.29 74.00 72.74 75.35 78.50 77.89 71.93 76.88 76.72 77.96 95.05 76.36 72.51 73.34 86.73 85.06 74.56 77.79 70.94 89.31 PROSTATE ABS. WT. REL. % BRW 0.3623 0.7091 0.8461 1.0337 1.2066 0.8355 1.2309 1.0630 0.9586 1.2275 1.1547 1.3065 1.2231 1.0513 1.3466 0.9439 1.4602 1.3746 0.9941 0.9705 1.0687 1.0011 1.0253 1.1083 0.5994 0.9128 1.1748 1.1124 0.8318 1.2324 16.25 30.83 39.17 46.99 50.28 37.64 55.44 49.21 40.62 55.29 50.20 58.32 55.09 46.11 55.19 37.91 63.49 59.25 47.56 43.91 51.63 41.89 44.19 45.42 27.88 41.12 48.95 49.88 35.10 53.12 PITUITARY ABS. WT. REL. % BRW 0.005 0.015 0.013 0.008 0.014 0.009 0.009 0.012 0.014 0.010 0.013 0.012 0.013 0.012 0.010 0.014 0.017 0.012 0.018 0.012 0.013 0.026 0.026 0.021 0.013 0.015 0.015 0.013 0.010 0.020 0.22 0.65 0.60 0.36 0.58 0.40 0.40 0.56 0.59 0.45 0.56 0.54 0.58 0.53 0.41 0.56 0.74 0.52 0.86 0.54 0.63 1.09 1.12 0.86 0.60 0.68 0.62 0.58 0.42 0.86 LIVER ABS. WT. REL. % BRW 25.00 1121.08 30.64 1332.17 20.80 962.96 27.64 1256.36 32.61 1358.75 30.76 1385.58 29.51 1329.28 26.56 1229.63 35.89 1520.76 26.54 1195.50 31.81 1383.04 24.11 1076.34 35.57 1602.25 27.46 1204.39 34.89 1429.92 30.79 1236.55 33.30 1447.83 30.02 1293.96 27.85 1332.54 24.86 1124.89 31.71 1531.88 26.90 1125.52 31.17 1343.53 32.01 1311.88 22.60 1051.16 26.98 1215.32 38.30 1595.83 25.35 1136.77 28.38 1197.47 28.51 1228.88 KIDNEY LEFT ABS. REL. W T . % BRW 1.96 2.40 2.00 2.25 2.52 2.16 2.32 2.25 2.65 2.32 2.56 2.37 2.23 2.27 2.49 2.51 1.98 2.17 2.07 1.94 2.26 2.42 2.28 2.58 2.11 2.12 2.77 2.48 2.00 2.53 87.89 104.35 92.59 102.27 105.00 97.30 104.50 104.17 112.29 104.50 111.30 105.80 100.45 99.56 102.05 100.80 86.09 93.53 99.04 87.78 109.18 101.26 98.28 105.74 98.14 95.50 115.42 111.21 84.39 109.05 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 12) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 458 DOSAGE GROUP IV 10 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 1237 1240 2.23 2.30 2.16 2.20 2.40 2.22 2.22 2.16 2.36 2.22 2.30 2.24 2.22 2.28 2.44 2.49 2.30 2.32 2.09 2.21 2.07 2.39 2.32 2.44 2.15 2.22 2.40 2.23 2.37 2.32 KIDNEY RIGHT ABS. REL. WT. % BRW 2.06 92.38 2.30 100.00 1.81a 83.80 2.21 100.45 2.65 110.42 2.31 104.05 2.72 122.52 2.27 105.09 2.61 110.59 2.21 99.55 2.49 108.26 2.19 97.77 2.34 105.40 2.11 92.54 2.54 104.10 2.56 102.81 2.02 87.83 2.14 . 92.24 2.39 114.35 2.09 94.57 2.36 114.01 2.50b 104.60 2.18 93.96 2.60 106.56 2.13 99.07 2.07d 93.24 2.85 118.75 2.44 109.42 2.02 85.23 2.67 115.09 ADRENAL LEFT ABS. REL. WT. % BRW 0.010 0.031 0.033 0.031 0.032 0.032 0.029 0.025 0.042 0.025 0.032 0.025 0.026 0.020 0.026 0.030 0.030 0.025 0.023 0.025 0.029 0.030 0.035 0.029 0.038 0.026 0.036 0.028 0.026 0.039 0.45 1.35 1.53 1.41 1.33 1.44 1.31 1.16 1.78 1.13 1.39 1.12 1.17 0.88 1.06 1.20 1.30 1.08 1.10 1.13 1.40 1.26 1.51 1.19 1.77 1.17 1.50 1.26 1.10 1.68 ADRENAL RIGHT ABS. REL. WT. % BRW 0.022 0.033 0.032 0.016 0.037 0.032 0.030 0.028 0.040 0.025 0.026 0.022 0.024 0.032 0.025 0.029 0.030 0.022 0.026 0.026 0.029 0.024 0.034 0.026 0.031 0.026 0.038 0.024 0.021 0.039 0.99 1.43 1.48 0.73 1.54 1.44 1.35 1.30 1.69 1.13 1.13 0.98 1.08 1.40 1.02 1.16 1.30 0.95 1.24 1.18 1.40 1.00 1.46 1.06 1.44 1.17 1.58 1.08 0.89 1.68 SPLEEN ABS. WT. REL. % BRW 0.67 0.72 0.69 0.78 0.85 0.92 0.81 0.76 0.81 0.81 0.71 0.65 0.76 0.69 0.76 0.84 0.79 0.70 0.63 0.79 0.76 0.82 0.76 0.92 1.95c 0.82 1.04 0.88 0.65 0.70 30.04 31.30 31.94 35.45 35.42 41.44 36.49 35.18 34.32 36.49 30.87 29.02 34.23 30.26 31.15 33.73 34.35 30.17 30.14 35.75 36.71 34.31 32.76 37.70 90.70 36.94 43.33 39.46 27.43 30.17 THYMUS ABS. WT. 1 % 0.35 0.39 0.27 0.56 0.35 0.73 0.30 0.37 0.36 0.32 0.43 0.27 0.25 0.32 0.32 0.32 0.32 0.40 0.47 0.55 0.41 0.44 0.34 0.45 0.31 0.39 0.55 0.36 0.27 0.24 15.70 16.96 12.50 25.45 14.58 32.88 13.51 17.13 15.25 14.41 18.70 12.05 11.26 14.04 13.11 12.85 13.91 17.24 22.49 24.89 19.81 18.41 14.66 18.44 14.42 17.57 22.92 16.14 11.39 10.34 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S , WT. = ORGAN WEIGHT. R E L . % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 1186 had moderate dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. b. Rat 1224 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. c. Rat 1229 had tan areas on the spleen that extended into the parenchyma; value included in group averages and statistical analysis. d. Rat 1232 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-68B9.6) TABLE D21 (PAGE 13) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 459 DOSAGE GROUP V 30 MG/KG/DAY RAT NUMBER BRAIN WEIGHT EPIDIDYMIS LEFT ABS. REL. WT. : BRW CAUDA EPIDIDYMIS LEFT ABS. REL. WT. % BRW TESTIS LEFT ABS. REL. WT. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. BRW SEMINAL VESICLES WITH FLUID ABS. REL. W T . * BRW SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % BRW 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 1291 1294 1298 1300 2.21 2.14 2.14 2.19 2.02 2.08 2.16 2.00 2.29 2.11 1.95 2.17 2.09 2.14 2.70 2.16 2.27 2.04 2.08 2.20 2.25 2.09 2.22 2.34 2.27 2.35 2.37 2.06 2.18 0.6112 0.6273 0.6766 0.6881 0.6792 0.7319 0.6596 0.6469 0.6245 0.7072 0.6969 0.5900 0.6313 0.6429 0.6784 0.5963 0.6832 0.6289 0.6557 0.6104 0.6110 0.5705 0.5772 0.6419 0.6438 0.7084 0.7602 0.5738 0.7065 27.66 29.31 31.62 31.42 33.62 35.19 30.54 32.34 27.27 33.52 35.74 27.19 30.20 30.04 25.12 27.61 30.10 30.83 31.52 27.74 27.16 27.30 26.00 27.43 28.36 30.14 32.08 27.85 32.41 0.2998 0.3142 0.3187 0.3340 0.3129 0.3795 0.3158 0.3557 0.3120 0.3545 0.3539 0.2959 0.3086 0.3347 0.2913 0.2747 0.3324 0.2912 0.3389 0.2935 0.3077 0.2924 0.2718 0.3011 0.2949 0.3777 0.3415 0.2755 0.3154 13.56 14.68 14.89 15.25 15.49 18.24 14.62 17.78 13.62 16.80 18.15 13.64 14.76 15.64 10.79 12.72 14.64 14.27 16.29 13.34 13.68 13.99 12.24 12.87 12.99 16.07 14.41 13.37 14.47 1.5908 1.7212 1.7176 1.8326 1.6396 1.7786 1.4497 1.7510 1.7416 1.8200 1.7863 1.6848 1.6450 1.7958 1.9897 1.5513 1.8321 1.6986 1.5348 2.0059 1.7608 1.5426 1.4489 1.8533 1.8455 1.8660 2.0868 1.4615 1.6906 71.98 80.43 80.26 83.68 81.17 85.51 67.12 87.55 76.05 86.26 91.60 77.64 78.71 83.92 73.69 71.82 80.71 83.26 73.79 91.18 78.26 73.81 65.26 79.20 81.30 79.40 88.05 70.95 77.55 1.3979 1.5926 1.6080 1.6988 1.5464 1.6728 1.3774 1.6523 1.6095 1.7299 1.6566 1.5730 1.5233 1.6760 1.7853 1.4009 1.6903 1.6003 1.3779 1.8552 1.6309 1.4114 1.3122 1.7185 1.6862 1.5842 1.8566 1.3341 1.5934 63.25 74.42 75.14 77.57 76.55 80.42 63.77 82.62 70.28 81.98 84.95 72.49 72.88 78.32 66.12 64.86 74.46 78.45 66.24 84.33 72.48 67.53 59.11 73.44 74.28 67.41 78.34 64.76 73.09 1.8364 83.10 2.8798 134.57 2.1597 100.92 1.7738 81.00 .5952 128.48 .0331 97.74 .8891 87.46 .9214 96.07 .6770 73.23 .2625 107.23 .0366 104.44 .8242 84.06 .9019 91.00 1.8292 85.48 1.8426 68.24 1.9182 88.80 .6601 73.13 .7792 87.22 .8714 89.97 .4607 66.40 .6002 71.12 1.5734 75.28 2.0014 90.15 .8222 77.87 .6617 73.20 .8949 80.63 .3983 59.00 .8111 87.92 .9824 90.94 1.0081 1.4614 1.0569 1.0022 1.2934 1.0653 0.9906 0.8235 0.6609 1.0298 1.0283 0.8953 0.7353 0.8866 0.9089 0.9421 0.8003 0.8806 0.9200 0.7963 0.8986 0.7565 0.9903 1.0444 0.8188 0.9639 0.7453 0.8992 1.2279 45.62 68.29 49.39 45.76 64.03 51.22 45.86 41.18 28.86 48.80 52.73 41.26 35.18 41.43 33.66 43.62 35.26 43.17 44.23 36.20 39.94 36.20 44.61 44.63 36.07 41.02 31.45 43.65 56.32 ALL WEIGHTS WERE RECORDED IN GRAMISS (G) . ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE 14) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (t) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA * FI GENERATION MALE RATS ARGUS 418-020 Page 460 DOSAGE GROUP V 30 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 1291 1294 1298 1300 2.21 2.14 14 19 02 08 16 00 29 11 1.95 2.17 2.09 2.14 2.70 16 27 04 08 20 25 09 22 34 27 35 37 06 18 EPIDIDYMIS RIGHT ABS REL. WT. % BRW .6533 .6699 .6880 .6936 .7177 .7145 .5818 .6693 .6530 .7350 0.7351 0.6319 0.6521 0.6597 0.6398 0.6096 0.6309 0.6590 0.6883 0.6620 .6740 .5821 .5847 .7166 .6780 .7411 .7335 .5936 .7606 29.56 31.30 32.15 31.67 35.53 34.35 26.94 33.46 28.52 34.83 37.70 29.12 31.20 30.83 23.70 28.22 27.79 32.30 33.09 30.09 29.96 27.85 26.34 30.62 29.87 31.54 30.95 28.82 34.89 TESTIS RIGHT ABS. REL. WT. % BRW 1.6469 1.6944 1.7335 1.7629 1.7090 1.7860 1.3457 1.8852 1.7597 1.8935 1.8626 1.7525 1.5782 1.7311 1.9298 1.5443 1.8951 1.7218 1.5678 2.0764 1.8308 1.5509 1.3930 2.0066 1.8514 1.8543 1.9582 1.4529 1.7792 74.52 79.18 81.00 80.50 84.60 85.86 62.30 94.26 76.84 89.74 95.52 80.76 75.51 80.89 71.47 71.50 83.48 84.40 75.38 94.38 81.37 74.20 62.75 85.75 81.56 78.91 82.62 70.53 81.61 PROSTATE ABS. WT. REL. % BRW 0.7133 0.4297 0.6958 1.0837 0.8798 0.8470 0.7562 0.9728 1.0766 1.0167 1.1325 0.5891 1.1156 1.0011 1.0235 1.0554 1.0326 0.7614 0.7429 0.7483 1.0285 0.8656 0.8578 0.7964 0.7592 0.7997 0.9946 0.6132 0.9123 32.28 20.08 32.51 49.48 43.55 40.72 35.01 48.64 47.01 48.18 58.08 27.15 53.38 46.78 37.91 48.86 45.49 37.32 35.72 34.01 45.71 41.42 38.64 34.03 33.44 34.03 41.97 29.77 41.85 PITUITARY ABS. WT. REL. % BRW 0.009 0.012 0.013 0.011 0.010 0.011 0.009 0.009 0.010 0.013 0.009 0.011 0.014 0.005 0.019 0.021a 0.015 0.024 0.032 0.010 0.012 0.010 0.026 0.010 0.014 0.008 0.026 0.011 0.010 0.41 0.56 0.61 0.50 0.50 0.53 0.42 0.45 0.44 0.62 0.46 0.51 0.67 0.23 0.70 0.97a 0.66 1.18 1.54 0.45 0.53 0.48 1.17 0.43 0.62 0.34 1.10 0.53 0.46 LIVER ABS. WT. REL. % BRW 33.90 37.00 35.80 30.46 23.36 22.66 29.14 24.07 32.45 29.80 25.93 24.08 29.42 32.70 30.75 27.46 34.70 26.59 30.95 29.72 30.21 26.56 25.71 33.07 34.68 26.73 33.81 27.51 33.29 1533.94 1728.97 1672.90 1390.87 1156.44 1089.42 1349.07 1203.50 1417.03 1412.32 1329.74 1109.68 1407.66 1528.04 1138.89 1271.30 1528.63 1303.43 1487.98 1350.91 1342.67 1270.81 1158.11 1413.25 1527.75 1137.45 1426.58 1335.44 1527.06 AMS (G) . ABS. WT. = ORGAN WEIGHT., REL. % TBW = (ORGAN 1 a. Damaged during processing (weight affected); values excluded from group averages and statistical analyses. KIDNEY LEFT ABS. REL. W T . % BRW 2.30 2.60 2.60 1.85 1.90 1.94 1.78 1.91 2.13 1.89 1.90 1.75 1.90 1.93 2.21 1.90 2.29 1.74 2.10 1.92 2.16 2.16 1.96 2.02 1.99 2.09 2.07 1.85 2.06 104.07 121.50 121.50 84.47 94.06 93.27 82.41 95.50 93.01 89.57 97.44 80.64 90.91 90.19 81.85 87.96 100.88 85.29 100.96 87.27 96.00 103.35 88.29 86.32 87.66 88.94 87.34 89.80 94.50 X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D21 (PAGE IS) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION MALE RATS ARGUS 418-020 Page 461 DOSAGE GROUP V 30 MG/KG/DAY RAT NUMBER BRAIN WEIGHT 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 1291 1294 1298 1300 2.21 2.14 2.14 2.19 2.02 2.08 2.16 2.00 2.29 2.11 1.95 2.17 2.09 2.14 2.70 2.16 2.27 2.04 2.08 2.20 2.25 2.09 2.22 2.34 2.27 2.35 2.37 2.06 2.18 KIDNEY RIGHT ABS. REL. WT. % BRW 2.28 2.41 2.40 1.67 1.94 1.94 1.78 1.88 2.23 1.87 1.79 1.93 2.00 2.12 2.50 1.86 2.35 1.81 2.04 2.01 1.99 2.06 2.12 1.97 2.08 2.05 2.26a 1.86 1.99 103.17 112.62 112.15 76.26 96.04 93.27 82.41 94.00 97.38 88.62 91.79 88.94 95.69 99.06 92.59 86.11 103.52 88.72 98.08 91.36 88.44 98.56 95.50 84.19 91.63 87.23 95.36 90.29 91.28 ADRENAL LEFT ABS. REL. WT. % BRW 0.024 0.035 0.033 0.023 0.031 0.028 0.027 0.025 0.023 0.028 0.023 0.021 0.030 0.022 0.038 0.033 0.020 0.031 0.030 0.036 0.034 0.020 0.028 0.019 0.026 0.023 0.039 0.022 0.026 1.08 1.64 1.54 1.05 1.53 1.35 1.25 1.25 1.00 1.33 1.18 0.97 1.44 1.03 1.41 1.53 0.88 1.52 1.44 1.64 1.51 0.96 1.26 0.81 1.14 0.98 1.64 1.07 1.19 ADRENAL RIGHT ABS. REL. WT. % BRW 0.031 0.030 0.024 0.016 0.029 0.024 0.024 0.022 0.019 0.030 0.016 0.025 0.028 0.023 0.037 0.029 0.022 0.026 0.030 0.038 0.032 0.020 0.022 0.015 0.030 0.024 0.035 0.019 0.024 1.40 1.40 1.12 0.73 1.44 1.15 1.11 1.10 0.83 1.42 0.82 1.15 1.34 1.07 1.37 1.34 0.97 1.27 1.44 1.73 1.42 0.96 0.99 0.64 1.32 1.02 1.48 0.92 1.10 SPLEEN ABS. WT. REL. % BRW 0.65 0.64 0.85 0.95 0.60 0.63 0.73 0.67 0.67 0.62 0.69 0.59 0.78 0.89 0.69 0.75 0.84 0.84 0.91 0.78 0.65 0.67 0.84 0.71 0.81 0.72 1.14 0.52 0.78 29.41 29.91 3 9.72 43.38 29.70 30.29 33.80 33.50 29.26 29.38 35.38 27.19 37.32 41.59 25.56 34.72 37.00 41.18 43.75 35.45 28.89 32.06 37.84 30.34 35.68 30.64 48.10 25.24 35.78 THYMUS ABS. WT. REL. % BRW 0.28 0.18 0.73 0.20 0.53 0.28 0.34 0.24 0.31 0.26 0.22 0.21 0.30 0.55 0.51 0.47 0.68 0.34 0.52 0.73 0.46 0.40 0.31 0.39 0.43 0.27 0.44 . 0.30 0.39 12.67 8.41 34.11 9.13 26.24 13.46 15.74 12.00 13.54 12.32 11.28 9.68 14.35 25.70 18.89 21.76 29.96 16.67 25.00 33.18 20.44 19.14 13.96 16.67 18.94 11.49 18.56 14.56 17.89 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100 . a. Rat 1294 had slight dilation of the pelvis of the right kidney; value included in. group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE 022 (PAGE 1) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - FI GENERATION MALE RATS (See footnotes at the end of this table.) ARGUS 418-020 Page 462 DOSAGE GROUP I RAT NUMBER NUMBER MOTILE 1002 205 1003 220 1005 1007 216 198 1011 224 1012 229 1013 1014 1017 1021 217 383 191 226 1023 320 1026 1028 253 160 1031 204 1034 300 1035 1040 1041 1043 373 197 183 424 1045 370 1047 1048 314 256 1050 336 1051 244 1052 1054 1055 1058 295 218 179 202 1059 175 1060 191 MOTILE PERCENT 80 85 87 95 85 68 75 84 92 84 97 90 74 80 90 92 87 86 91 86 89 74 78 86 78 90 56 70 81 84 0 MG/KG/DAY STATIC COUNT (NONMOTILE) 50 40 31 11 40 110 71 71 17 43 10 29 56 51 35 31 29 31 42 60 40 09 96 39 85 25 141 88 40 36 TOTAL COUNT a 255 260 247 209 264 339 288 454 208 269 330 282 216 255 335 404 226 214 466 430 354 345 432 283 380 243 320 290 215 227 SPERM COUNT b 79 60 53 157 115 71 65 189 98 134 130 107 104 205 145 88 200 162 386 160 143 238 195 129 92 156 85 88 71 162 SPERM DENSITY C 572.6 480.6 497.8 1355.7 982.2 608.9 586.8 1525.9 966.9 1113.2 1126.2 770.0 889.3 1825.8 1277.6 923.3 2032.8 1803.1 3522.4 1387.8 1125.3 2129.5 1612.6 980.5 690.5 1181.6 758.2 904.6 699.3 1498.1 SPERMATID COUNT d 26 69 44 35 49 47 50 65 39 44 43 30 45 34 41 47 63 48 45 42 64 32 83 33 37 . 59 43 32 36 34 SPERMATID DENSITY e 42.3 118.2 79.8 68.9 95.6 81.8 95.9 107.1 67.4 75.5 78.8 47.3 80.4 59.0 79.4 105.2 119.6 93.8 79.3 71.4 114.9 71.8 164.8 52.6 60.2 94.7 76.6 61.2 64.9 68.6 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6B89.6) TABLE D22 (PAGE 2) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - FI GENERATION MALE RATS (See footnotes at the end of this table .) ARGUS 418-020 Page 463 DOSAGE GROUP II RAT NUMBER NUMBER MOTILE 1061 189 1063 165 1066 171 1067 267 1069 193 1071 232 1073 342 1077 327 1070 203 1081 337 1082 9 1083 213 1086 348 1088 238 1090 222 1091 255 1094 184 1096 203 1098 214 1100 312 1103 273 1106 346 1107 282 1110 381 1112 318 1114 265 1116 624 1118 189 1120 167 1 MG/KG/DAY MOTILE STATIC COUNT PERCENT {NONMOTILE) 76 61 77 48 75 57 70 77 67 94 78 66 80 83 76 104 87 30 94 20 31 20 88 28 90 40 94 16 83 44 89 31 88 25 91 21 91 21 87 47 81 62 88 47 79 74 83 80 75 108 90 28 89 79 86 30 84 33 TOTAL COUNT a 250 213 228 344 287 298 425 431 233 357 29 241 388 254 266 286 209 224 235 359 335 393 356 461 426 293 703 219 200 SPERM COUNT b 105 109 40 80 109 98 52 90 185 188 1 138 75 228 155 282 499 196 410 235 368 156 134 93 98 104 74 111 123 SPERM DENSITY c 854.9 955.5 418.9 801.9 1041.6 867.2 555.7 648.6 1344.9 1465.1 19.8 1153.7 079.4 1871.6 1455.7 2708.3 4438.7 1724.4 3067.8 2055.0 3159.7 1635.6 1261.8 867.5 823.6 949.3 733.3 1085.5 1039.1 SPERMATID COUNT d 28 . 57 16 31 22 48 58 58 42 37 6 24 34 38 36 46 54 61 68 55 60 40 26 23 61 27 21. 30 30 SPERMATID DENSITY e 49.7 94.1 28.0 62.0 38.5 91.9 90.5 101.6 73.0 66.7 38.1 50.6 64.8 71.3 68.3 98.4 107.2 112.7 111.9 103.5 111.0 81.4 52.1 43.8 104.4 42.9 42.9 54.7 46.4 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6B09.6) TABLE D22 (PAGE 3) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - FI GENERATION MALE RATS (See footnotes at the end of this table.) ARGUS 418-020 Page 464 DOSAGE GROUP III RAT NUMBER NUMBER MOTILE 1122 205 1123 198 1127 171 1129 186 1131 252 1132 244 1134 298 1135 292 1136 280 1139 182 1141 391 1142 298 1145 271 1147 183 1149 204 1151 271 1153 236 1154 232 1158 395 1159 231 1162 294 1164 406 1167 337 1168 311 1171 434 1173 282 1175 243 1176 254 1177 178 1180 390 MOTILE PERCENT 93 78 80 60 88 86 79 87 89 78 88 85 92 85 89 94 92 88 90 75 81 86 84 89 81 81 79 77 84 78 3 MG/KG/DAY * STATIC COUNT (NONMOTILE) 15 55 42 124 33 41 78 44 36 51 53 54 23 32 25 17 21 31 46 76 67 64 62 38 104 67 66 76 34 1Q8 TOTAL COUNT a 220 253 213 310 285 285 376 336 316 233 444 352 294 215 229 288 257 263 441 307 361 470 399 349 538 349 309 330 212 498 SPERM COUNT b 30 76 125 68 161 123 148 256 139 192 74 89 95 194 144 407 214 209 104 125 104 333 121 113 160 129 66 120 125 95 SPERM DENSITY c 250.1 740.7 1095.1 561.7 1300.5 1053.3 1274.9 2301.2 1180.5 1696.4 603.7 871.8 844.3 1564.1 1008-1 3703.5 1848.4 2067.6 994.8 977.8 970.1 2666.1 1076.3 1126.0 1594.3 1140.1 695.5 1212.5 ' 1034.9 820.3 SPERMATID COUNT d 34 21 24 50 45 39 16 36 36 68 29 43 31 29 72 62 67 45 55 61 40 44 33 33 21 35 20 27 41 21 SPERMATID DENSITY e 64.6 35.9 45.9 79.8 77.9 68.9 26.2 65.0 61.9 125.8 57,4 81.2 51.3 52.2 107.7 112.6 70.0 91.2 103.1 104.2 74.3 71.6 63.3 59.0 43.2 71.0 35.3 43.0 56.4 w 1M S PROTOCOL 418-020 : ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATB (APPO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D22 (PAGE 4) : CAUDA EPIDIDYMAL ;SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - FI GENERATION MALE RATS (See footnotes at the end of this table.) ARGUS 418-020 Page 465 DOSAGE GROUP IV RAT NUMBER NUMBER MOTILE 1182 288 1184 175 1166 188 1188 206 1189 338 1192 239 1194 286 1195 194 1198 192 1203 181 1204 200 1207 190 1209 221 1211 233 1212 194 1215 189 1216 252 1217 294 1219 338 1221 229 1222 263 1224 407 1225 319 1226 299 1229 264 1232 341 1233 292 1236 162 1237 340 1240 454 MOTILE PERCENT 80 81 85 87 84 72 89 91 91 83 68 73 85 78 90 87 95 83 80 83 71 86 75 77 79 92 90 73 89 81 10 MG/KG/DAY STATIC COUNT (NONMOTILE) 73 42 34 31 65 92 34 20 20 37 93 72 39 67 22 28 14 60 87 48 108 65 104 90 71 30 33 61 44 105 TOTAL COUNT a 361 217 222 237 403 331 320 214 212 218 293 262 260 300 216 217 266 354 425 277 371 472 423 389 335 371 325 223 384 559 SPERM COUNT b 99 46 189 72 143 110 88 157 105 148 224 146 99 123 213 238 233 205 108 290 103 94 184 94 113 165 40 70 116 74 SPERM DENSITY c 1063.8 379.3 1579.2 634.0 992.7 1024.5 747.8 1434.9 829.4 1466.2 1696.2 1198.8 836.6 1080.2 1713.4 2196.1 1893.8 1847.9 1142.3 2974.8 889.7 757.0 1578.9 907.3 976.3 1462.3 475.8 683.6 ' 1214.5 526.9 SPERMATID COUNT d 34 42 31 42 29 24 48 23 27 27 30 53 61 50 31 75 37 42 34 83 63 57 31 25 47 39 17 . 29 44 30 SPERMATID DENSITY e 63.1 68.4 61.6 76.0 54.1 45.5 84.1 42.2 43.5 53.7 52.3 93.3 110.5 88.7 49.3 125.8 71.8 71.9 66.4 155.0 100.4 103.6 58.7 46.2 80.8 62.2 32.4 53.8 81.1 45.5 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D22 (PAGE 5): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - FI GENERATION MALE RATS (See footnotes at the end of this table.) ARGUS 418-020 Page 466 DOSAGE GROUP V RAT NUMBER NUMBER MOTILE 1241 159 1244 330 1245 172 1247 287 1248 251 1249 470 1252 289 1254 219 1255 294 1257 91 1259 254 1261 231 1266 420 1269 192 1271 209 1273 279 1274 296 1278 451 1281 310 1282 256 1284 251 1287 159 1288 167 1289 326 1290 240 1291 250 1294 240 1298 184 1300 182 MOTILE PERCENT 75 77 80 84 86 82 60 92 87 45 91 91 83 64 95 83 93 84 85 66 81 75 83 84 86 77 71 88 76 30 MG/KG/DAY STATIC COUNT (NONMOTILE) 53 97 43 55 40 103 196 18 44 113 24 23 88 110 12 58 24 86 54 130 60 54 34 62 40 73 98 25 57 TOTAL COUNT a 212 427 215 342 291 573 485 237 338 204 278 254 508 302 221 337 320 537 364 386 311 213 201 388 280 323 338 209 239 SPERM COUNT b 68 60 68 104 78 45 52 163 128 168 253 136 125 108 82 110 130 73 279 67 174 100 61 111 201 73 147 96 96 SPERM DENSITY c 656.1 552.4 617.2 900.7 721.1 343.0 476.3 1325.6 1106.8 1370.9 2068.0 1329.5 1171.7 933.4 814.3 1158.3 1131.3 725.2 2381.4 660.3 1635.8 989.3 649.2 1066.4 1971.6 559.1 1245.2 1008.0 ` 880.5 SPERMATID COUNT d 20 37 60 39 10 36 56 38 57 51 29 37 26 83 80 32 50 44 44 53 43 53 23 34 44 40 50. 21 49 SPERMATID DENSITY e 41.4 67.2 107.9 66.4 18.7 62.3 117.6 66.5 102.4 85.3 50.6 68.0 49.4 143.3 129.6 66.1 85.6 79.5 92.4 82.6 76.3 108.6 50.7 57.2 75.5 73.0 77.9 45.5 89.0 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6809.6) TABLE D22 (PAGE 6) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - FI GENERATION MALE RATS FOOTNOTES ^_________________________________ _____ a. Sum of number motile and static count. Groups of five fields were evaluated until a sperm count of at least 200 was achieved or 20 fields were evaluated. b. Sperm count used in the calculation of sperm density. Ten fields were evaluated. c. The sperm density was calculated by dividing the sperm count by the volume in the image area (34.3 x 10"6 mL), multiplying by 2 (dilution factor) and multiplying by 10'6 to obtain the sperm concentration. The calculated sperm concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left cauda epididymis (see Table D20 for the weight of the left cauda epididymis) to obtain the sperm density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. d. Spermatid count used in the calculation of spermatid density. Ten fields were evaluated. e. The spermatid density was calculated by dividing the spermatid count by the volume in the image area (34.3 x 10* mL), multiplying by 2 (dilution factor) and multiplying by 10"6 to obtain the spermatid concentration. The calculated spermatid concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left testis minus tunica albuginea (see Table D20 for the weight of the left testis minus tunica albuginea) to obtain the spermatid density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. f. Rat 1082 had less than 200 sperm per 20 fields; values excluded from group averages and statistical analyses. ARGUS 418-020 Page 467 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D23 (PAGE 1) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 o (N Page 468 DOSAGE GROUP I RAT NUMBER 1002 1003 1005 1007 1011 1012 1013 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 1052 1054 1055 1058 1059 1060 NORMAL 198 196 193 195 197 196 192 195 196 194 191 197 197 196 196 195 198 193 194 196 193 193 197 198 196 193 198 195 196 195 DETACHED HEAD 1 3 6 2 2 2 6 4 1 3 5 1 2 2 3 3 1 5 4 2 4 4 2 2 1 5 1 2 1 2 0 MG/KG/DAY NO HEAD 1 1 1 3 1 2 2 1 1 1 2 1 0 1 0 1 0 2 2 0 2 3 1 0 2 2 0 3 3 3 BROKEN FLAGELLUM 0 0 0 0 0 0 0 0 2 2 2 1 1 1 1 1 1 0 0 2 1 0 0 0 1 0 0 0 0 0 NO HOOK 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 COILED FLAGELLUM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 BENT FLAGELLUM BENT FLAGELLUM TIP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 .o 0 0 o 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 1.0 20 35 25 15 2.0 4.0 2.5 2.0 3.0 4.5 X .5 1.5 2.0 2.5 1.0 3.5 3.0 2.0 3.5 3.5 1.5 1.0 2.0 3.5 1.0 2.5 2.0 2.5 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D23 (PAGE 2) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 in Page 469 DOSAGE GROUP II 1 MG/KG/DAY RAT NUMBER NORMAL DETACHED HEAD NO HEAD BROKEN FLAGELLUM NO HOOK COILED FLAGELLUM BENT FLAGELLUM BENT FLAGELLUM TIP 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082a 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 1112 1114 1116 1118 1120 194 197 195 196 198 195 193 196 191 193 0 196 190 196 197 194 196 196 196 195 191 197 198 190 199 199 193 197 198 24 21 32 31 20 41 61 31 53 52 00 30 64 31 21 33 40 31 31 50 63 12 20 73 10 10 42 21 02 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 10 00 00 00 00 00 10 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0 0 .0 0 a. Rat 1082 had less than 200 sperm per 20 fields; values excluded from group averages and statistical analyses. U1 O1 PERCENT ABNORMAL 1.5 2.5 2.0 1.0 2.5 2.0 4.5 3.5 100.0 2.0 5.0 2.0 1.5 3.0 2.0 2.0 2.0 2.5 4.5 1.5 1.0 5.0 0.5 0.5 3.5 1.5 1.0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D23 (PAGE 3) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 470 DOSAGE GROUP III RAT NUMBER 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 1171 1173 1175 1176 1177 1180 NORMAL 193 191 193 197 196 196 195 197 195 195 194 196 194 197 195 199 190 198 193 195 196 195 196 196 195 195 193 194 192 196 DETACHED HEAD 5 5 5 2 2 2 3 1 3 3 2 2 2 0 4 0 8 1 3 3 2 4 3 2 4 4 6 3 4 2 3 MG/KG/DAY NO HEAD 2 4 2 1 1 2 2 1 1 2 4 1 4 3 1 1 1 1 3 2 1 1 3 0 1 0 0 3 2 1 BROKEN FLAGELLUM 0 0 0 0 1 0 0 1 1 0 0 0 0 0 0 0 1 0 1 0 1 0 0 2 0 0 1 0 1 0 NO HOOK 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 COILED FLAGELLUM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 1 BENT FLAGELLUM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 BENT FLAGELLUM TIP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 3.5 4.5 3.5 1.5 2.0 2.0 2.5 1.5 2.5 2.5 3.0 2.0 3.0 1.5 2.5 0.5 5.0 1.0 3.5 2.5 2.0 2.5 3.0 2.0 2.5 2.5 3.5 3.0 4.0 2.0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D23 (PAGE 4) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 o <N Page 471 DOSAGE GROUP IV RAT NUMBER 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 1237 1240 NORMAL 196 196 195 195 196 197 198 195 197 193 193 196 192 194 192 194 193 196 195 199 195 193 197 197 198 198 198 191 197 193 DETACHED HEAD 1 2 4 2 2 3 2 3 1 4 6 4 8 3 7 4 5 3 4 1 3 4 2 2 1 1 0 4 2 3 10 MG/KG/DAY NO HEAD 1 1 0 1 2 0 0 2 1 3 1 0 0 3 1 2 1 1 1 0 0 3 1 1 0 1 1 5 1 3 BROKEN FLAGELLUM 2 1 1 2 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 1 0 0 1 NO HOOK 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 COILED FLAGELLUM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 BENT FLAGELLUM BENT FLAGELLUM TIP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 2.0 2.5 2.5 2.0 1.5 1.0 2.5 1.5 3.5 3.5 2.0 4.0 3.0 4.0 3.0 3.5 2.0 2.5 0.5 2.5 3.5 1.5 1.5 1.0 1.0 1.0 4.5 1.5 3.5 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE D23 (PAGE 5) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - FI GENERATION MALE RATS ARGUS 418-020 Page 472 DOSAGE GROUP V RAT NUMBER 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 1291 1294 1298 1300 NORMAL 191 197 196 193 196 197 189 195 195 196 197 193 196 196 198 195 194 193 192 191 196 196 194 188 192 192 197 194 191 DETACHED HEAD 6 2 3 3 2 2 6 4 2 2 2 3 1 3 2 4 4 3 5 4 2 2 1 6 3 3 3 3 5 30 MG/KG/DAY NO HEAD 2 1 1 3 1 1 5 1 2 1 1 3 2 0 0 0 2 4 1 5 0 1 4 4 3 5 0 1 3 BROKEN FLAGELLUM 1 0 0 0 1 0 0 0 1 0 0 1 1 1 0 1 0 0 2 0 2 1 1 2 2 0 0 2 0 NO HOOK 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 COILED FLAGELLUM 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 BENT FLAGELLUM 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 BENT FLAGELLUM TIP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 PERCENT ABNORMAL 4.5 1.5 2.0 32.. 05 1.5 5.5 2.5 2.5 2.0 1.5 3.5 2.0 2.0 1.0 2.5 3.0 3.5 4.0 4.5 2.0 2.0 3.0 6.0 4 .0 4 .0 1.5 3.0 4.5 ARGUS 418-020 APPENDIX E REPORT TABLES - FI GENERATION FEMALE RATS Page 473 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE El (PAGE 1) : CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 474 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION) MAXIMUM POSSIBLE INCIDENCE 3283/ 60 3306/ 60 3310/ 60 3281/ 60 FOUND DEAD 0 2b ,c Id le ABDOMINAL DISTENTION 47/ 6 56/ 7 29/ 4 39/ 5 URINE-STAINED ABDOMINAL FUR 8/ 2 48/ 5c 22/ 4d 14/ 4e COLD TO TOUCH 0/ 0 1/ lb 0/ 0 1/ le ANNULAR CONSTRICTION OF THE TAIL 0/ 0 16/ 2 0/ 0 0/ 0 CHROMORHINORRHEA 4/ 2 14/ 4b, c 17/ 7d 1/ 1 RALES 0/ 0 0/ 0 0/ 0 0/ 0 TIP OF TAIL MISSING 0/ 0 61/ 2b 0/ 0 70/ 1 BACK OR HEAD: SCAB 1/ 1 0/ 0 0/ 0 9/ 1 LOCALIZED ALOPECIA: TOTAL LIMBS NECK HEAD 19/ 2 4/ 1 0/ 0 15/ 1 22/ 1 22/ 1 0/ 0 0/ 0 42/ 2 42/ 2 0/ 0 0/ 0 18/ 2 15/ 1 3/ 1 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a . Ratsi 1562! and 1563 did not have clinical observations recorded on day 1 postweaning b. Rat 1365 was found dead on day 4 postweaning. c . Rat 1373 was found dead on day 51 postweaning. d. Rat 1432 was found dead on day 7 postweaning. e . Rat 1484 was found dead on day 3 postweaning. f . Rat 1549 was found dead on day 8 postweaning. g- Rat 1559 was found dead on day 6 postweaning. h. Rat 1562 was found dead on day 2 postweaning. i. Rat 1563 was found dead on day 2 postweaning. j- Rat 1574 was found dead on day 3 postweaning. k. Rat 1575 was found dead on day 3 postweaning. ** Significantly different from the Group I value (p<0.01). V 30 3171/ 60a 6* *f-k 72/ 10 21/ sf,g,j 8/ 3f,g, j 3/ 3 7/ 2f 2/ 2 18/ 1 6/ X 5/ 1 5/ 1 0/ 0 0/ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE El (PAGE 2) : CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 475 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II h i IV 0 1 3 10 PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION) MAXIMUM POSSIBLE INCIDENCE 3283/ 60 3306/ 60 3310/ 60 3281/ 60 FOUND DEAD 0 2b, c Id le DECREASED MOTOR ACTIVITY 0/ 0 7/ 2b, c 0/ 0 1/ le EMACIATION 4/ 1 16/ 1c 2/ 2d 1/ 1 TAIL BENT 0/ 0 0/ 0 0/ 0 0/ 0 INCISORS: TOTAL MISALIGNED MISSING/BROKEN 30/ 3 17/ 1 13/ 2 2/ l 0/ 0 2/ l 57/ 3 15/ 2 43/ 3 10/ 1 10/ 1 0/ 0 LACRIMATION 1/ 1 4/ 1 0/ 0 1/ 1 RIGHT OR LEFT EYE: SWOLLEN 0/ 0 4/ 1 0/ 0 1/ 1 LABORED BREATHING 0/ 0 0/ 0 0/ 0 1/ le SOFT OR LIQUID FECES 0/ 0 1/ 1 3/ 2 0/ 0 CHROMODACRYOERHEA 5/ 2 1/ lc 19/ 1 0/ 0 SWOLLEN EAR(S) 24/ 1 16/ l 3/ 1 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rats 1562 and 1563 did not have clinical observations recorded on day 1 postweaning. b. Rat 1365 was found dead on day 4 postweaning. c. Rat 1373 was found dead on day 51 postweaning. d. Rat 1432 was found dead on day 7 postweaning. e. Rat 1484 was found dead on day 3 postweaning. f. Rat 1549 was found dead on day 8 postweaning. g. Rat 1559 was found dead on day 6 postweaning. h. Rat 1562 was found dead on day 2 postweaning. i. Rat 1563 was found dead on day 2 postweaning. j. Rat 1574 was found dead on day 3 postweaning. k. Rat 1575 was found dead on day 3 postweaning. ** significantly different from the Group I value (p<0.0l). V 30 3171/ 60a 6*'*f-k 2/ If 1/ ig 1/ l 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE El (PAGE 3) : CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 476 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION) MAXIMUM POSSIBLE INCIDENCE 3283/ 60 3306/ 60 3310/ 60 3281/ 60 FOUND DEAD 0 2b, c Id le DEHYDRATION 5/ 1 23/ 2C 0/ 0 0/ 0 HEAD: SWOLLEN 0/ 0 1/ 1 0/ 0 0/ 0 SNOUT: SWOLLEN 0/ 0 1/ 1 0/ 0 0/ 0 PTOSIS 20/ 2 0/ 0 0/ 0 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS) /NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rats 1562 and 1563 did not have clinical observations recorded on day 1 postweaning. b. Rat 1365 was found dead on day 4 postweaning. c. Rat 1373 was found dead on day 51 postweaning. d. Rat 1432 was found dead on day 7 postweaning. e. Rat 1484 was found dead on day 3 postweaning. f. Rat 1549 was found dead on day 8 postweaning. g. Rat 1559 was found dead on day 6 postweaning. h. Rat 1562 was found dead on day 2 postweaning. i. Rat 1563 was found dead on day 2 postweaning. j. Rat 1574 was found dead on day 3 postweaning. k. Rat 1575 was found dead on day 3 postweaning. ** Significantly different from the Group I value (p<0.01). V 30 3171/ 60a 6 '**f-k 0/ 0 0/ 0 0/ 0 0/ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE El (PAGE 4) : CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page All DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 PRESUMED GESTATION: a MAXIMUM POSSIBLE INCIDENCE 644/ 29 644/ 29 669/ 30 670/ 30 MORTALITY 0000 LOCALIZED ALOPECIA: LIMBS 2/ 1 22/ 1 7/ 1 0/ 0 RIGHT AXILLA: MASS 0/ 0 0/ 0 0/ 0 0/ 0 TIP OF TAIL MISSING 0/ 0 22/ 1 0/ 0 17/ 1 CHROMODACRYORRHEA 0/ 0 0/ 0 22/ 1 0/ 0 SWOLLEN EAR(S) 65/ 4 23/ 2* 0/ o** 0/ 0** PTOSIS 22/ i 0/ 0 0/ 0 0/ 0 INCISORS: TOTAL MISALIGNED MISSING/BROKEN 29/ 2 29/ 2 0/ 0 0/ 0 0/ 0 0/ 0 28/ 2 0/ 0 28/ 2 3/ 1 3/ I 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION, a. Restricted to rats with a confirmed mating date. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). V 30 663/ 30 0 16/ 4 8/ i 0/ 0 0/ 0 0/ o** 0/ 0 0/ 0 0/ 0 0/ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE El (PAGE 5) : CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 478 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 LACTATION: MAXIMUM POSSIBLE INCIDENCE 616/ 28 616/ 28 616/ 28 616/ 28 MORTALITY 0000 LOCALIZED ALOPECIA: LIMBS 22/ 1 22/ 1 81/ 4 33/ 2 RIGHT AXILLA: MASS 0/ 0 0/ 0 0/ 0 0/ 0 SWOLLEN EAR(S) 88/ 4 22/ 1 0/ 0 0/ 0 RED PERIVAGINAL SUBSTANCE 0/ 0 0/ 0 4/ 4** 0/ 0 SOFT OR LIQUID FECES 0/ 0 0/ 0 5/ 3 6/ 2 URINE-STAINED ABDOMINAL FUR 0/ 0 0/ 0 0/ 0 3/ 2 INCISORS: TOTAL MISSING/BROKEN MISALIGNED 42/ 2 19/ 1 29/ 2 0/ 0 0/ 0 0/ 0 44/ 2 44/ 2 0/ 0 0/ 0 0/ 0 0/ 0 CHROMODACRYORRHEA 0/ 0 0/ 0 22/ 1 0/ 0 TIP OF TAIL MISSING 0/ 0 22/ 1 0/ 0 22/ 1 PTOSIS 22/ 1 0/ 0 0/ 0 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. ** Significantly different from the Group I value (p<0.01). . V 30 638/ 29 0 72/ 4 19/ 1 18/ i 1/ i 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E2 (PAGE 1) : BODY WEIGHTS - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 IV 10 RATS TESTED N 60 60 60 60 INCLUDED IN ANALYSES N 60 60 60 60 BODY WEIGHT (G) DAY 1 MEANS.D. 41.4 6.8 39.2 6.3 42.9 8.7 43.3 7.3 DAY 8 DAY 15 DAY 22 DAY 29 MEANS.D . MEANS.D. MEANS.D. MEANS.D. 71.7 9.9 111.3 13.0 148.9 1 4 . 2 [ 59]a 177.0 16.2 [ 47]a 66.8 8.5* [ 59] a 104.2 10.6** [ 59] a 142.9 11.1* [ 59] a 170.2 12.0* [ 53] a 73.5 12.6 [ 59] a 112.7 1 3 . 7 [ 59] a 151.1 12.3 ( 59] a 180.6 14.2 ( 51] a 72.1 11.5 [ 59] a 108.6 13.8 [ 59] a 146.8 15.1 [ 59] a 175.0 14.8 [ 48] a DAY DAY POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a . Excludes values for rats that were sacrificed following sexual maturation or found dead. Significantly different from the Group I value (p<0.05). Significantly different from the Group I value (p<0.01). V 30 60 58a 39.2 7.9 66.9 9.9* [ 54] a 102.8 13.2** ( 54) a 139.4 13.4** [ 54] a 167.9 16.0** [ 45] a ARGUS 418-020 Page 479 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E2 (PAGE 2) : BODY WEIGHTS - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 480 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 30a 30a 30a 30a 30a BODY WEIGHT (G) DAY 36 MEANS.D . 199.9 15.7 193.5 19.7 203.8 15.3 198.5 18.1 190.1 19.1 DAY 43 MEANS.D. 219.8 18.4 212.5 24.6 225.6 13.2 219.3 18.4 209.7 18.4 DAY 50 MEANS.D. 237.1 19.2 228.3 1 29.6 243.5 14.7 236.0 18.0 224.4 19.2* DAY 57 MEANS.D. 248.6 1 17.1 244.2 20.7 254.6 14.7 247.0 19.0 236.1 20.8* DAY 64 DAY 70b PRECOHAB ITATION C MEANS.D. MEANS.D . MEANS.D. 259.6 19.9 264.9 19.7 276.7 22.9 255.6 20.7 [ 29] a 263.4 20.7 [ 29] a 278.1 23.6 [ 29] a 266.9 16.7 274.2 16.4 287.4 18.1 259.4 21.9 266.2 21.0 277.0 22.1 248.7 22.1 254.5 21.8 263.7 23.0* DAY = DAY POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. b. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. c. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. * Significantly different from the Group I value (p<0.05). these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E3 (PAGE 1) : BODY WEIGHT CHANGES - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 013 RATS TESTED N 60 60 60 INCLUDED IN ANALYSES N 60 59a 59a BODY WEIGHT CHANGE (G) DAYS 1 - 8 MEANS.D . +30.3 4.6 +27.4 3.9** +30.4 5.6 DAYS 8 - 15 MEANS.D . +39.6 4.3 +37.4 3.8 + +3 9.2 4.5 DAYS 15 - 22 DAYS 22 - 29 M E A N S .D. MEANS.D . +37.6 1 5.2 [ 59) a +28.2 5.4 [ 47] a +38.7 4.4 +28.0 5.9 t 53) a +38.4 6.0 +28.7 6.7 [ 51] a DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. * Significantly different from the Group I value (p<0.05). *+ Significantly different from the Group I value (p<0.01). IV 10 60 59a +28.5 6.5 +36.5 5.3 ++ +38.2 5.5 +28.2 5.3 [ 48] a V 30 60 54a +26.6 4.2** +35.9 4.8++ +36.5 4.9 +28.6 5.3 [ 45] a ARGUS 418-020 Page 481 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E3 (PAGE 2) : BODY WEIGHT CHANGES - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 482 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 30a 30a 30a 30a 30a BODY WEIGHT CHANGE (G) DAYS 29 - 36 MEANS .D . +25.1 6.1 +23.3 9.8 +25.0 8.9 +23.9 4.2 +22.8 5.5 DAYS 36 - 43 MEANS .D . +19.9 7.9 +19.0 7.8 +21.8 8.4 +20.8 5.9 +19.6 4.7 DAYS 43 - 50 MEANS.D . +17.3 7.7 +15.8 7.9 +18.0 5.8 +16.6 4.5 +14.7 3.6 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70b DAYS 1 - 70b DAYS 1 PRECOHABITATION c MEANlS.D. MEANS.D . MEANS.D. MEANS.D. MEANS.D . +11.5 7.6 +11.0 5.9 +5.3 4.7 +223.3 18.0 +235.2 20.9 +11.8 6.5 [ 29] a +11.4 7.4 ( 29] a +7.8 7.3 [ 29] a +224.3 19.0 [ 29] a +239.0 22.6 [ 29] a +11.1 8.1 +12.3 5.2 +7.3 6.0 +231.3 18.8 +244,5 20.6 +11.1 6.0 +12.4 5.7 +6.8 4.9 +222.6 17.5 +233.4 19.1 +11.7 5.3 +12.7 3.4 +5.8 5.0 +215.1 19.3 +224.3 21.0* DAY (S ) = DAY (S ) POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. b. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. c. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. * Significantly different from the Group I value (p<0.05). , these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E4 (PAGE 1) : MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 30 29 PREGNANT N 28 28 MATERNAL BODY WEIGHT (G) DAY 0 MEANS.D. 274.8 20.9 275.4 2 3 . 6 DAY 7 MEANS.D. 304.0 23.0 303.4 25.5 DAY 10 MEANS.D . 316.8 23.9 317.0 26.8 DAY 14 MEANS.D. 333.9 24.5 333.2 28.4 DAY 18 MEANlS.D. 380.2 29.6 380.8 31.6 DAY 21 MEANS.D . 417.9 33.0 [ 27] a 418.0 32.9 [ 26] a DAY = DAY OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for dams that delivered. * Significantly different from the Group I value (p<0.05). III 3 30 28 285.4 17.6 312.2 19.4 326.1 20.2 343.1 22.2 394.8 27.7 427.8 31.3 [ 20] a IV V 10 30 30 30 28 29 275.0 2 3 . 2 303.3 24.3 314.0 24.0 331.4 24.6 380.6 2 8 . 9 415.1 31.1 ( 25]a 262.1 23.2* 287.4 22.6* 299.6 23.2* 316.1 25.4* 366.6 2 8 . 9 399.2 3 4 . 8 [ 24] a ARGUS 418-020 Page 483 PROTOCOL 418 020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E5 (PAGE 1) : MATERNAL BODY WEIGHT CHANGES - GESTATION - SUMMARY - FI GENERATION FEMALE RATS 1 1 1 1 1 1 1 U I O < 11 1 1 1 1 1 1 1 1 1 1 DOSAGE GROUP DOSAGE (MG/KG/DAY) I 0 RATS TESTED N 30 PREGNANT N 28 MATERNAL BODY WEIGHT CHANGE (G) DAYS 0 - 7 MEANS.D . +29.1 5.8 DAYS 7 - 10 MEANS.D. +12.8 4.2 DAYS 10 - 14 MEANS.D . +17.1 5.3 DAYS 14 - 18 MEANS.D . +46.2 11.5 DAYS 18 - 21 DAYS 0 - 21 MEANS .D . MEANS.D . +37.6 9.2 ( 27] a +142.8 19.6 [ 27] a DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for dams that delivered. ii i 29 28 +28.0 7.0 +13.6 6.7 +16.2 6.1 +47.6 10.2 +38.1 6.7 [ 26] a +143.6 17.9 t 26] a III 3 30 28 +26.8 6.4 +13.9 4.4 +17.0 5.6 +51.7 10.3 +32.5 6.2 [ 20] a +141.5 18.2 [ 20] a IV 10 30 30 28 29 +28.4 7.2 +10.6 3.8 +17.5 5.2 +4 9.2 11.6 +35.9 9.2 [ 25] a +141.2 16.8 [ 25] a +25.2 6.3 +12.2 3.8 +16.5 4.4 +50.6 10.6 +34.4 10.9 [ 24 ]a +138.4 20.5 ( 24] a ARGUS 418-020 Page 484 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E6 (PAGE 1) : MATERNAL BODY WEIGHTS - LACTATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 30 29 PREGNANT N 28 28 DELIVERED A LITTER N 28 28 MATERNAL BODY WEIGHT (G) DAY 1 MEANS.D . 313.6 24.6 314.8 t 25.8 DAY 5 MEANS.D . 320.2 25.2 321.7 21.1 DAY 8 MEANS.D . 328.8 26.7 333.3 21.6 DAY 11 MEANS.D. 335.5 25.8 340.9 22.7 DAY 15 MEANS.D. 336.9 23.4 338.1 21.9 DAY 22 MEANS.D . 322.9 23.4 321.7 24.2 DAY = DAY OF LACTATION * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). III 3 30 28 28 325.5 23.1 328.7 20.8 338.8 22.0 346.4 18.1 343.3 20.1 329.2 21.5 IV V 10 30 30 30 28 29 28 29 313.2 23.4 317.8 20.2 325.3 23.0 336.0 23.1 334.4 19.8 325.1 23.5 302.0 24.2 305.2 23.0* 309.9 23.5** 321.8 24.7* 323.6 26.6* 315.7 20.9 ARGUS 418-020 Page 485 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E7 (PAGE 1) : MATERNAL BODY WEIGHT CHANGES - LACTATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED N PREGNANT N DELIVERED A LITTER N MATERNAL BODY WEIGHT CHANGE (G) DAYS 1 - 5 MEANS.D. DAYS 5 - 8 MEANS.D . DAYS 8 - 11 MEANlS.D. DAYS 11 - 15 MEANS.D . DAYS 1 - 15 MEANS.D. DAYS 15 - 22 MEANS.D. DAYS 1 - 22 MEANS.D . DAYS = DAYS OF LACTATION I 0 30 28 28 +6.6 9.8 +8.5 9.2 +6.8 16.4 +1.4 19.0 +23.2 14.2 -14.0 15.3 + 9.2 18.9 II 1 29 28 28 +7.0 10.7 +11.6 7.1 +7.6 8.8 -2.8 13.4 +23.3 14.5 -16.4 13.1 +6.9 14.8 III 3 30 28 28 +3.1 10.0 +10.2 8.1 +7.5 1 13.9 -3.0 13.3 +17.8 16.5 -14.1 16.0 +3.6 23.2 IV V 10 30 30 30 28 29 28 29 +4.7 8.9 +7.4 9.9 +10.7 10.1 -1.6 14.6 +21.2 17.8 -9.3 15.4 +11.9 22.4 +3.1 11.0 +4.7 10.8 +11.9 11.9 +1.9 16.5 +21.6 14.2 -8.0 17.6 +13.6 19.0 ARGUS 418-020 Page 486 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E8 (PAGE 1) : ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 487 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 RATS TESTED N 60 60 60 60 INCLUDED IN ANALYSES N 60 59a 59a 59a FEED CONSUMPTION (G/DAY) DAYS 1 - 8 MEANS.D . 10.1 1.5 9.4 1.2** 10.0 1.6 10.0 1.7 DAYS 8 - 1 5 MEANS .D . 16.4 2.0 15.0 1.5** 16.2 1.9 15.8 1.8 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70c DAYS 1 - 70c MEANS.D . MEANlS.D. MEANS.D. MEANS.D . MEANS .D . MEANS.D . MEANS.D . MEANS.D . MEANS.D . 19.0 1.9 [ 58]a,b 19.4 2.4 [ 471a 20.0 2.2 ( 30] a 20.1 2.5 [ 29] a, b 21.6 3.4 [ 28]a,b 21.1 2.9 [ 28]a,b 20.6 2.8 ( 29]a,b 19.3 1.9 ( 29] a,b 18.6 1.7 [ 29] a, b 18.4 1.4 [ 57] b 19.0 2.2 [ 53]a,b 19.9 3.2 ( 30]a,b 19.6 1.9 [ 28] a,b 22.0 4.1 [ 29] a,b 20.2 2.8 [ 28]a,b 19.9 2.6 [ 28]a,b 19.7 3.1 [ 28] a,b 18.3 1.4 [ 28} a,b 19.1 2.0 [ 57] b 19.9 2.7 [ 50]a,b 20.5 4.4 [ 30] a, b 20.6 3.0 ( 29]a,b 22.3 3.6 [ 29] a,b 20.4 2.0 [ 26] a,b 21.0 3.4 [ 28]a,b 19.8 2.1 [ 30] a 18.9 1.8 t 30] a 18.8 2.0 19.6 2.5 [ 46] a ,b 19.2 1.7 [ 29] a,b 20.2 2.4 ( 301a 22.8 1 5.2 [ 26] a,b 20.9 2.7 [ 27la,b 20.6 2.8 ( 26] a, b 19.6 2.3 I 29] a,b 18.4 1.6 [ 29] a,b DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. b. Excludes values that were not recorded, as well as those associated with spillage, soiled or wet feed. c. Last weekly value recorded before cohabitation. ** Significantly different from the Group I value (p<0.01). V 30 60 55a 9.0 1.4** 14.7 1.5** l 54] a 18.0 2.0** [ 52]a,b 18.6 1.8 ( 44]a,b 18.8 2.3 [ 29] a, b 19.2 1.9 [ 29] a,b 22.2 6.2 [ 26]a,b 19.8 2.7 [ 271a,b 19.1 3.4 [ 28]a,b 19.0 2.8 ( 27]a,b 17.7 1.7 [ 27] a ,b PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E9 (PAGE 1) : RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS W1 O< 1 ARGUS 418-020 Page 488 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 RATS TESTED N 60 60 60 60 INCLUDED IN ANALYSES N 60 59a 59a 59a FEED CONSUMPTION (G/KG/DAY) DAYS 1 - 8 MEANS.D . 180.7 22.3 177.5 19.4 173.7 18.8 174.2 17.6 DAYS 8 - 15 MEANS.D . 180.6 16.1 176.3 16.5 174.6 15.6 176.9 17.3 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70c DAYS 1 - 70C MEANS.D. MEANS.D . MEANS.D. MEANS.D. MEANS.D . MEANS .D . MEANS.D. MEANS.D . MEANS.D. 146.5 13.1 [ 58]a,b 119.5 11.6 [ 47] a 106.8 9.1 I 30] a 96.0 8.4 [ 29] a,b 94.5 12.1 [ 28] a,b 86.9 8.9 [ 28] a,b 81.4 8.8 I 29] a, b 73.4 5.6 [ 29] a, b 103.7 6.0 [ 29] a,b 150.1 12.5 [ 57] b 121.9 15.5 [ 53]a,b 110.4 24.0 ( 30]a,b 98.2 16.3 [ 28]a,b 101.5 23.1 [ 29]a,b 85.0 10.9 [ 28] a, b 79.7 9.1 [ 28]a,b 76.2 13.3 [ 28]a,b 104.5 6.0 [ 28]a,b 146.2 14.2 ( 57] b 120.1 13.8 [ 50]a,b 107.5 24.7 ( 30]a,b 96.2 12.2 [ 29] a, b 95.2 16.2 [ 29]a,b 82.0 8.0 [ 26] a,b 80.1 11.4 [ 28] a,b 73.1 6.2 [ 30] a 102.6 7.7 ( 30] a 148.1 17.4 121.5 15.0 [ 46] a,b 103.1 7.1 ( 29] a, b 96.6 9.4 [ 30] a 99.6 23.5 ( 26] a,b 86.6 14.3 [ 27] a, b 80.6 11.6 [ 26]a,b 74.5 7.4 [ 29] a, b 103.0 7.3 [ 29] a,b DAYS = DAYS POSTWEANING ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. b. Excludes values that were not recorded, as well as those associated with spillage, soiled or wet feed. c. Last weekly value recorded before cohabitation. 60 55a 172.2 16.7 174.2 14.1 [ 54 ]a 149.3 16.4 [ 52]a,b 121.9 12.6 I 44]a,b 106.0 12.2 ( 29] a,b 96.7 10.2 1 29] a,b 103.4 31.6 ( 26]a,b 86.2 10.6 [ 27]a,b 79.2 13.2 [ 28]a,b 76.2 11.5 [ 27]a,b 104.6 9.5 [ 27] a,b PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E10 (PAGE 1) : MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - GESTATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED PREGNANT MATERNAL FEED CONSUMPTION (G/DAY) N N I 0 29 28 II III 13 29 30 28 28 IV 10 30 28 DAYS 0 - 7 DAYS 7 - 1 0 DAYS 10 - 14 MEANS.D . MEANS.D . MEANS.D. 22.8 2.5 [ 27] a 24.2 3.8 [ 27] a 24.4 3.0 22.7 3.0 [ 25] a 24.1 3.6 23.7 3.3 22.2 2.7 [ 25] a 24.1 2.9 ( 27] a 24.2 2.9 22.3 2.3 [ 27] a 22.8 2.5 [ 27] a 23.4 2.1 DAYS 14 - 18 MEANS.D . 24.1 3.0 24.0 2.7 25.1 2.6 23.9 2.4 DAYS 1 8 - 2 1 DAYS 0 - 2 1 MEANS .D . MEANS.D. 23.0 23.7 2.8 2.7 23.1 2.8 [ 27] a 23.2 2.5 [ 27] a 23.7 2.7 [ 25] a 23.7 2.4 [ 25] a 22.5 2.6 [ 27] a 23.0 1.9 [ 27] a DAYS = DAYS OF GESTATION [ ) = NUMBER OF VALUES AVERAGED a. Excludes values that were not recorded as well as those associated with spillage or wet feed. * Significantly different from the Group I value (p^O.OS). V 30 30 29 21.0 2.6 l 27] a 22.0 2.7* [ 28] a 22.8 2.6 24.2 2.6 23.2 2.3 [ 26] a 22.4 2.2 [ 26] a ARGUS 418-020 Page 489 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE Ell (PAGE 1) : MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - GESTATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED PREGNANT MATERNAL FEED CONSUMPTION (G/KG/DAY) N N I 0 29 28 II III 13 29 30 28 28 IV 10 30 28 DAYS 0 - 7 DAYS 7 - 10 DAYS 1 0 - 1 4 MEANS .D . MEANlS .D . MEANS.D. 79.3 7.3 [ 27] a 78.3 10.8 [ 27] a 74.8 6.9 78.3 8.1 [ 25] a 77.6 7.6 72.7 6.5 74.3 7.9 [ 25] a 75.4 6.9 [ 27] a 72.3 6.6 76.9 7.9 [ 27] a 74.0 7.8 ( 27] a 72.7 6.1 DAYS 14 - 18 MEANS.D . 67.4 6.3 67.2 5.3 68.2 5.4 67.2 6.3 DAYS 18 - 21 DAYS 0 - 21 MEANS.D . MEANS .D . 57.8 6.4 [ 27] a, b 70.0 6.0 [ 27]a,b 58.4 6.8 [ 26]a,b 68.8 5.0 ( 26]a,b 58.3 7.0 ( 20]a,b 68.0 5.8 [ 20]a,b 56.7 7.5 [ 25]a,b 68.8 5.8 [ 25]a,b DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values that were not recorded as well as those associated with spillage or wet feed. b. Excludes values for dams that delivered. V 30 30 29 76.6 9.8 ( 27]a 74.4 6.8 [ 28] a 74.2 7.7 71.0 7.3 61.1 5.9 [ 24]a,b 70.3 6.5 [ 24]a ,b ARGUS 418-020 Page 490 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E12 (PAGE 1) : MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - LACTATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED PREGNANT DELIVERED'A LITTER MATERNAL FEED CONSUMPTION (G/DAY) N N N I 0 28 28 28 II III 13 28 28 28 28 28 28 IV V 10 30 28 29 28 29 28 29 DAYS 1 - 5 DAYS 5 - 8 MEANS.D. MEANS.D . 30.3 6.8 l 27] a 48.1 8.3 30.6 48.5 5.9 7.0 28.6 4.2 [ 27] a 46.2 5.8 28.9 5.3 [ 26] a 46.7 8.7 29.2 44.6 4.9 6.7 DAYS 8 - 1 1 DAYS 11 - 15b DAYS 1 - 15b MEANS.D . MEANS.D . MEANS.D . 54.0 8.5 59.0 8.5 [ 27] a 48.0 6.1 [ 27] a 55.4 t 57.5 47.4 7.2 9.5 5.3 55.2 6.2 [ 27] a 57.3 7.2 46.5 4.4 52.3 8.1 56.3 12.4 46.0 6.7 50.4 52.2 43.6 7.7 9.5 5.5** DAYS = DAYS OF LACTATION ( ] = NUMBER OF VALUES AVERAGED a. Excludes values that were associated with spillage. b. Because it is presumed that the pups begin to consume maternal were not tabulated on days 15 to 22 of lactation. ** Significantly different from the Group I value (p<0.01). feed after day 15 of lactation, maternal feed consumption values ARGUS 418-020 Page 491 PROTOCOL 418 -020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER : T-6889.6) TABLE E13 (PAGE 1) : MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - LACTATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS TESTED N 28 28 28 28 29 PREGNANT N 28 28 28 28 29 DELIVERED1A LITTER N 28 28 28 28 29 MATERNAL FEED CONSUMPTION (G/KG/DAY) DAYS 1 - 5 DAYS 5 - 8 MEANS.D . MEANS.D . 95.7 18.4 [ 271 a 147.7 18.5 96.9 21.0 148.4 21.3 87.8 15.3 l 27] a 138.5 15.9 92.6 18.7 [ 26] a 145.3 26.9 96.5 16.9 144.8 18.2 DAYS 8 - 11 DAYS 11 - 15b DAYS 1 - 15b MEANS.D. MEANS.D. MEANS.D . 162.7 23.8 174.7 22.6 [ 27] a 146.1 15.4 [ 27J a 164.6 21.0 169.1 25.3 144.1 16.5 161.5 21.1 ( 27] a 166.2 19.3 138.5 15.0 158.7 26.1 168.2 37.1 141.9 21.8 159.5 21.8 161.7 25.9 139.7 15.6 DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values that were associated with spillage. b. Because it is presumed that the pups begin to consume maternal were not tabulated on days 15 to 22 of lactation. feed after day 15 of lactation, maternal feed consumption values ARGUS 418-020 Page 492 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E14 (PAGE 1) : SEXUAL MATURATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV 0 1 3 10 FEMALE RATS N 60 60 60 60 INCLUDED IN ANALYSES N 60 58a,b 58a,b 58a,b VAGINAL PATENCY c MEANS.D. 34.9 2.1 35.5 2.3 34.1 2.6 34.8 2.1 a. Excludes values for rats that were found dead. b. Excludes values for rats in which testing was discontinued before the rat became sexually mature. c. Average day postpartum that the vagina was observed to be patent. ** Significantly different from the Group I value (p<0.01). V 30 60 54a 36.6 2.4** Page 493 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E15 (PAGE 1) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 494 DOSAGE GROUP DOSAGE (MG/KG/DAY) I ii 0i ESTROUS CYCLING OBSERVATIONS PRECOHABITATION ESTROUS CYCLING RATS EVALUATED N 30 29a ESTROUS STAGES/ 21 DAYS MEAN+S.D . 4.7 + 0.9 5.0 + 0.9 RATS WITH 6 OR MORE CONSECUTIVE DAYS OF DIESTRUS N 1 0 RATS WITH 6 OR MORE CONSECUTIVE DAYS OF ESTRUS N 0 0 ESTROUS STAGE AT SACRIFICE RATS EVALUATED DIESTRUS PROESTRUS ESTRUS METESTRUS N N N N N 30 18 2 6 4 29 15 1 10 3 a. Excludes rat 1373, which was found dead prior to cohabitation. ** Significantly different from the Group I value (p<0.01). III 3 30 5.0 + 0.8 0 0 30 20 3 5 2 IV 10 30 5.0 + 1.1 1 0 30 21 2 6 1 V 30 30 5.4 + 0.7** 0 0 30 23 2 4 1 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E15 (PAGE 2) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - SUMMARY - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS IN COHABITATION DAYS IN COHABITATION b N MEAN+S.D . I 0 30 3.0 + 2.4 II 1 29a 3.0 + 1.1 III 3 30 2.4 + 1.2 IV 10 30 2.7 + 1.6 V 30 30 2.5 + 1.2 ARGUS 418-020 Page 495 RATS THAT MATED N (% ) 29( 96.7) 29(100.0) 30 (100.0) FERTILITY INDEX C N/N 28/ 29 <%> ( 96.6) 28/ 29 ( 96.6) 28/ 30 ( 93.3) RATS WITH CONFIRMED MATING DATES N 29 29 30 RATS MATING d DAYS 1-7 N (%) 29(100.0) 29(100.0) 30(100.0) RATS PREGNANT/RATS IN COHABITATION N/N 28/ 30 (%) ( 93.3) 28/ 29 ( 96.6) 28/ 30 ( 93.3) a. Excludes rat 1373, which was found dead prior to cohabitation, b. Restricted to rats with a confirmed mating date and rats that did not mate. c. Number of pregnancies/number of rats that mated. d. Restricted to rats with a confirmed mating date. 30(100.0) 28/ 30 ( 93.3) 30 30(100.0) 28/ 30 ( 93.3) 30(100.0) 29/ 30 ( 96.7) 30 30(100.0) 29/ 30 ( 96.7) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E16 (PAGE 1) : NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS i (See footnotes on the last page of this table.) ARGUS 418-020 Page 496 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS EXAMINED a N FOUND DEAD N INCLUDED IN ANALYSES N APPEARED NORMAL N LIVER: LEFT LATERAL LOBE, FIRM MASS CUT SURFACE REVEALED YELLOW AND DARK RED AREAS N CAUDATE LOBE ADHERED TO LEFT LATERAL LOBE N KIDNEYS : BILATERAL, PELVIS, SLIGHT DILATION N RIGHT, PELVIS, MODERATE DILATION N URINARY BLADDER: WALLS THICKENED N URETER: BILATERAL, MODERATE DILATION N ONE CALCULI LOCATED AT THE CAUDAL END N I 0 60 0 60 59 0 0 0 0 0 0 0 II 1 60 2b, c 59 1 57b . III 3 60 Id 60 59d 10 10 01 00 00 00 00 IV V 10 30 60 60 le 6f-k 60 60 60e S9f -k 00 00 00 01 01 01 0 1 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E16 (PAGE 2) : NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 497 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 RATS EXAMINED a N 60 60 60 60 60 FOUND DEAD N0 2b, c Id le 6f-k INCLUDED IN ANALYSES N 60 59 1 60 60 60 STOMACH: DISTENDED N0 lc 0 00 INTESTINES : DISTENDED N0 lc 0 00 LUNGS: DORSAL SURFACE, RIGHT APICAL LOBE, DEPRESSED WHITE AREA N 0 lc 0 00 SPLEEN: SMALL N1 0 0 0 0 a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. b. Rat 1365 was found dead on day 4 postweaning. c. Rat 1373 was found dead on day 51 postweaning. d. Rat 1432 was found dead on day 7 postweaning. e. Rat 1484 was found dead on day 3 postweaning. f. Rat 1549 was found dead on day 8 postweaning. g. Rat 1559 was found dead on day 6 postweaning. h. Rat 1562 was found dead on day 2 postweaning. i. Rat 1563 was found dead on day 2 postweaning. j. Rat 1574 was found dead on day 3 postweaning. k. Rat 1575 was found dead on day 3 postweaning. l. Excludes rat 1362, which did not have necropsy observations recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E17 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 498 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 28 28 TERMINAL BODY WEIGHT MEANS.D . 322.9 23.4 321.7 24.2 PITUITARY MEANS.D. 0.017 0.004 0.016 0.003 BRAIN MEANS.D. 2.07 0.09 2.09 0.12 LIVER MEANS.D . 16.57 1.58 15.96 1.76 KIDNEY LEFT MEANlS.D . 1.36 0.13 1.39 0.14 KIDNEY RIGHT MEANS.D . 1.38 0.12 1.41 0.14 ADRENAL LEFT MEANS.D. 0.043 0.008 0.044 0.007 ADRENAL RIGHT SPLEEN THYMUS OVARY LEFT MEANS .D . 0.040 0.007 MEANS.D . 0.60 0.07 MEANS.D . 0.20 0.06 MEANS.D . 0.050 0.012 0.041 0.007 0.61 0.12 0.19 0.05 0.054 0.012 OVARY RIGHT MEANS.D . 0.054 0.012 0.053 0.012 UTERUS NON-GRAVID MEANS.D . 0.54 0.16 0.56 0.16 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Excludes a value that appeared incorrectly recorded. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). III 3 28 329.2 21.5 0.015 0.003* 2.08 0.10 16.41 1.40 1.41 0.09 [ 27] a 1.42 0.10 0.044 0.006 0.041 0.006 0.60 0.06 0.21 0.07 0.051 0.012 0.049 0.010 0.57 0.18 IV 10 28 325.1 23.5 0.015 0.002* 2.10 0.12 16.68 1.70 1.38 0.14 1.42 0.16 0.046 0.006 0.042 0.006 0.59 0.09 0.20 0.08 0.049 0.010 0.051 0.011 0.56 0.12 V 30 29 315.7 20.9 0.015 0.003** 2.07 0.10 16.78 1.36 1.34 0.18 1.40 0.20 0.045 0.008 0.041 0.006 0.60 0.11 0.22 0.09 0.052 0.013 0.052 0.013 0.54 0.18 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E18 (PAGE 1) : RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - FI GENERATION FEMALE RATS 1 1 1 1 1 1 1 1 UJ 1 O< I ARGUS 418-020 Page 499 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 28 28 TERMINAL BODY WEIGHT PITUITARY a BRAIN LIVER KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT a ADRENAL RIGHT a SPLEEN THYMUS OVARY LEFT a OVARY RIGHT a UTERUS NON-GRAVID MEANS.D . 322.9 23.4 MEANS.D . 5.462 1.605 MEANS.D . 0.644 0.058 MEANS.D . 5.130 0.305 MEANS.D . 0.421 i 0.038 MEANS.D . 0.427 0.030 MEANS.D . 13.285 2.147 MEANS.D. 12.301 t 1.979 MEANS.D . 0.184 0.021 M E A N S .D . 0.062 0.020 MEANS.D . 15.652 3.706 MEANS.D . 16.754 4.015 MEANS.D. 0.167 0.050 321.7 24.2 4.976 t 0.861 0.653 t 0.054 4.958 i 0.340 0.432 0.040 0.438 0.037 13.551 i 1.994 12.743 2.192 0.189 0.041 0.058 0.017 16.844 3.672 16.742 4.266 0.176 0.058 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. b. Excludes a value that appeared incorrectly recorded. * Significantly different from the Group I value (p<0.05). III IV 3 10 28 28 29 329.2 21.5 4.648 0.860* 0.632 0.045 4.991 0.377 0.426 0.036 [ 27] b 0.432 0.034 325.1 23.5 4.715 0.898* 0.648 0.063 5.136 0.409 0.426 0.038 0.435 0.046 315.7 20.9 4.749 1.028* 0.659 0.044 5.326 0.455 0.426 0.055 0.444 0.058 13.581 2.048 14.046 1.831 14.209 2.762 12.600 1.834 12.881 1.981 13.191 2.177 0.184 0.019 0.183 0.027 0.191 0.034 0.064 0.023 0.061 0.025 0.070 0.029 15.616 3.778 15.235 3.166 16.364 4.200 14.955 3.246 15.235 3.016 16.496 4.132 0.175 0.059 0.173 0.044 0.171 0.058 RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E19 (PAGE 1) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 500 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II 01 RATS TESTED N 28 28 BRAIN WEIGHT MEANS .D . 2.07 0.09 2.09 0.12 PITUITARY MEANS.D . 0.84 0.21 0.76 0.14 LIVER MEANS.D . 802.60 85.59 764.62 81.65 KIDNEY LEFT MEANS.D . 65.77 6.04 66.51 6.49 KIDNEY RIGHT MEANS.D. 66.76 6.09 67.36 5.83 ADRENAL LEFT MEANS.D . 2.08 i 0.38 2.08 0.32 ADRENAL RIGHT MEANS.D. 1.93 0.37 1.96 0.34 SPLEEN MEANS.D . 28.89 3.82 29.10 5.58 THYMUS MEANS.D. 9.65 2.74 9.10 2.84 OVARY LEFT MEANS.D . 2.43 0.56 2.58 0.52 OVARY RIGHT MEANS.D. 2.60 0.59 2.56 0.58 UTERUS NON-GRAVID MEANS.D. 25.95 7.78 27.06 7.66 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Excludes a value that appeared incorrectly recorded. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). III IV V 3 10 30 28 28 29 2.08 0.10 2.10 0.12 2.07 0.10 0.74 0.14* 0.72 0.12* 0.72 0.16** 790.69 67.15 798.38 91.68 810.62 71.58 67.59 5.25 [ 27] a 66.44 6.23 66.10 6.57 67.61 7.12 64.85 8.48 67.57 9.54 2.14 0.30 2.18 0.30 2.16 0.39 2.00 0.29 2.00 0.32 2.00 0.30 29.08 2.59 28.35 4.31 29.28 5.67 10.23 3.44 9.69 4.04 10.69 4.48 2.46 0.57 2.36 0.50 2.48 0.63 2.37 0.52 2.44 0.54 2.50 0.62 27.58 8.91 26.76 6.12 26.02 8.40 RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E20 (PAGE 1) : NATURAL DELIVERY OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS ARGUS 418-020 Page 501 DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS ASSIGNED TO NATURAL DELIVERY N I 0 28 II III 13 28 28 IV V 10 30 28 29 PREGNANT DELIVERED A LITTER N N (%) 28 28(100.0) 28 28(100.0) 28 28(100.0) 28 28(100.0) 29 29(100.0) DURATION OF GESTATION a MEANS.D . 22.8 0.4 22.6 0.6 22.7 0.5 22.8 0.6 22.7 1 IMPLANTATION SITES N PER DELIVERED LITTER MEANS.D . 414 14.8 3.0 443 15.8 2.1 412 14.7 2.8 419 15.0 2.9 420 14.5 : DAMS WITH STILLBORN PUPS N (%) 3( 10.7) 4( 14.3) 3( 10.7) 5 ( 18.5) 2( 7.1) DAMS WITH NO LIVEBORN PUPS N(%) 0( 0.0) 0( 0.0) 0( 0.0) 0< 0.0) 0( 0.0) GESTATION INDEX b % N/N 100.0 28/ 28 100.0 28/ 28 100.0 28/ 28 100.0 27/ 27 100.0 28/ 28 DAMS WITH ALL PUPS DYING DAYS 1-4 POSTPARTUM N (%) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) DAMS WITH ALL PUPS DYING DAYS 5-21 POSTPARTUM N (%) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) a. Calculated as the time (in days) elapsed between confirmed mating (arbitrarily defined as day 0) and the time (in days) the first pup was delivered. b. Number of rats with live offspring/number of pregnant rats. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E21 (PAGE 1) : LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION PUPS ARGUS 418-020 Page 502 DOSAGE GROUP DOSAGE (MG/KG/DAY) I II III 0 13 DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS: N 28 28 28 PUPS DELIVERED (TOTAL) N MEANS.D. 386 13.8 2.9 388 13.8 2.5 394 14.1 3.0 LIVEBORN MEANS.D. N (%) 13.6 2.9 380( 98.4) 13.7 2.4 383 ( 98.7) 13.8 3.0 388( 98.5) STILLBORN MEANS.D . N (%) 0.2 0.5 5( 1.3) 0.2 0.5 5( 1.3) 0.2 0.6 6( 1.5) UNKNOWN VITAL STATUS N 1 0 0 PUPS FOUND DEAD OR PRESUMED CANNIBALIZED DAY 1 DAYS 2 - 5 DAYS 6 - 8 DAYS 9-15 DAYS 16-22 VIABILITY INDEX a N / N (%) N / N (%) N / N (%) N / N (%) N/N (%) % N/N 0/380( 2/380( 0/3781 3/378( 2/375( 0.0) 0.5) 0.0) 0.8) 0.5) 99.5 378/380 0/383( 5/383 ( 1/378( 2/377 ( 1/375( 0.0) 1.3) 0.3) 0.5) 0.3) 98.7 378/383 5/388 ( 5/383 ( 5/378 ( 0/373( 0/373( 1.3)** 1.3) 1.3) 0.0) 0.0) 97.4 378/388 LACTATION INDEX b % 98.7 N/N 373/378 98.9 374/378 98.7 373/378 D A Y (S ) = D A Y (S ) POSTPARTUM a. Number of live pups on day 5 postpartum/number of liveborn pups on day 1 postpartum. b. Number of live pups on day 22 postpartum/number of live pups on day 5 postpartum. ** Significantly different from the Group I value (p<0.01). IV V 10 30 28 385 13.8 3.1 13.5 3.1 378( 98.2) 0.2 0.5 6( 1.6) 1 29 389 13.4 2.8 13.3 2.8 387( 99.5) 0.1 0.2 2( 0.5) 0 4/3781 3/374( 1/371( 1/370( 1/369( 1.0)** 0.8) 0.3) 0.3) 0.3) 98.1 371/378 99.2 368/371 1/3 87 ( 3/386 ( 4/383( 0/3 79 ( 1/379( 0.2) 0.8) 1.0) 0.0) 0.3) 99.0 383/387 98.7 378/383 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E21 (PAGE 2) : LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION PUPS ARGUS 418-020 Page 503 DOSAGE GROUP DOSAGE (MG/KG/DAY) DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS SURVIVING PUPS/LITTER a N I 0 28 II III 13 28 28 DAY lb DAY 5 DAY 8 DAY 15 DAY 22 PERCENT MALE PUPS PER NUMBER OF PUPS SEXED MEANS.D . MEANS.D. MEANS.D . MEANS.D . MEANS.D. 13.6 2.9 13.5 2.8 13.5 2.8 13.4 2.8 13.3 2.7 13.7 2.4 13.5 2.3 13.5 2.3 13.4 2.2 13.4 2.2 13.8 3.0 13.5 2.9 13.3 2.9 13.3 2.9 13.3 2.9 DAY lb MEANS.D . 50.2 11.8 51.9 11.2 51.5 13.1 DAY 5 MEANS.D . 49.9 12.0 52.2 11.5 51.7 13.7 DAY 8 MEANS.D . 49.9 12.0 52.1 11.5 52.1 13.7 DAY 15 MEANS.D. 49.8 11.8 52.4 11.6 52.1 13.7 DAY 22 MEANS.D . 50.0 11.7 52.5 11.8 52.1 13.7 DAY = DAY POSTPARTUM a. Average number of live pups per litter, including litters with no surviving pups. b. Includes pups born alive, found dead day 1 postpartum. IV V 10 30 28 29 13.5 3.1 13.2 3.0 13.2 2.9 13.2 2.9 13.1 2.9 13.3 2.8 13.2 2.8 13.1 2.8 13.1 2.8 13.0 2.7 55.6 15.7 55.6 15.1 55.7 15.0 55.8 15.0 55.9 14.9 47.3 13.5 47.3 13.5 47.0 13.3 47.0 13.3 47.1 13.3 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E21 (PAGE 3) : LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION PUPS ARGUS 418-020 Page 504 DOSAGE GROUP DOSAGE (MG/KG/DAY) DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N LIVE LITTER SIZE AT WEIGHING DAY 1 MEANS.D. DAY 5 MEANS .D . DAY 8 MEANS.D . DAY 15 MEANS.D. DAY 22 MEANS.D . PUP WEIGHT/LITTER (GRAMS) DAY 1 MEANS.D . DAY 5 MEANS.D . DAY 8 MEANS.D. DAY 15 MEANS.D . DAY 22 MEANS.D . I 0 28 13.6 2.9 13.5 2.8 13.5 2.8 13.4 2.8 13.3 2.7 6.5 0.5 10.2 1.2 14.5 2.1 25.4 4.1 38.7 7.1 II 1 28 13.7 2.4 13.5 2.3 13.5 2.3 13.4 2.2 13.4 2.2 6.3 0.5 10.0 1.2 14.4 1.8 25.3 3.4 38.9 5.4 III 3 28 13.7 2.9 13.5 2.9 13.3 2.9 13.3 t 2.9 13.3 2.9 6.4 0.7 10.1 1.6 14.3 2.3 25.8 t 4.4 39.6 7.1 IV V 10 30 28 29 13.4 3.0 13.2 3.0 13.2 2.9 13.2 2.9 13.1 2.9 13.3 2.8 13.2 2.8 13.1 2.8 13.1 2.8 13.0 2.7 6.4 0.7 10.2 1.5 14.3 2.3 24.8 3.7 39.1 6.6 6.0 0.5 9.6 1.2 13.5 2.0 23.2 3.7 36.5 6.7 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E22 (PAGE 1) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - !SUMMARY F2 GENERATION PUPS ARGUS 418-020 Page 505 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTERS EXAMINED (N) I II III IV V 0 1 3 10 30 28 28 28 28 29 TRANSIENT CLINICAL OBSERVATIONS: a TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS COLD TO TOUCH 2/ 1 5/ 1 1/ 1 1/ 1 3/ 3 TAIL: ABRASION 0/ 0 0/ 0 0/ 0 0/ 0 10/ 2 NO TAIL PRESENT 0/ 0 0/ 0 0/ 0 0/ 0 22/ 1 TIP OF TAIL MISSING 0/ 0 0/ 0 0/ 0 0/ 0 12/ 1 TAIL: SCAB 0/ 0 0/ 0 0/ 0 0/ 0 9/ 1 MOUTH: MASS 0/ . 0 0/ 0 0/ 0 0/ 0 8/ 1 BACK: ABRASION BACK: SCAB 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 7/ 1 4/ 1 PALE IN APPEARANCE BASE OF TAIL: ABRASION 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 3/ 1 3/ 1 TIP OF TAIL BLACK EMACIATION DOMED HEAD DEHYDRATION 0/ 0 1/ 1 0/ 0 34/ 3 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 2/ 2 2/ 1 1/ 1 1/ 1 0/ 0 TAIL BENT 0/ 0 0/ 0 0/ 0 22/ 1 0/ 0 N/N = TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS. a. Tabulation restricted to adverse observations; all other pups appeared normal. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E22 (PAGE 2) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - SUMMARY - F2 GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTERS EXAMINED (N) I II III IV V 0 1 3 10 30 28 28 28 28 29 TRANSIENT CLINICAL OBSERVATIONS: a TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS RIGHT EYE: NOT PRESENT 0/ 0 0/ 0 0/ 0 3/ 1 0/ 0 THREAD-LIKE TAIL 0/ 0 22/ 1 0/ 0 0/ 0 0/ 0 NO ANAL OPENING PRESENT 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0 UNGROOMED COAT 16/ 1 0/ 0 0/ 0 0/ 0 0/ 0 NO MILK PRESENT IN STOMACH 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 N/N = TOTAL FREQUENCY (DAYS x PUPS)/LITTERS WITH OBSERVATIONS. a. Tabulation restricted to adverse observations; all other pups appeared normal. ARGUS 418-020 Page 506 PROTOCOL 418-020-. ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E23 (PAGE 1) : NECROPSY OBSERVATIONS - SUMMARY - F2 GENERATION PUPS ARGUS 418-020 Page 507 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 LITTERS EXAMINED N 28 28 28 28 29 TOTAL PUPS STILLBORN OR FOUND DEAD a STILLBORN N FOUND DEAD N 3 1 2 6 10 10 6 3 4 62 3 6 44 NO MILK IN STOMACH b N (%} 1( 50.0) PUPS SACRIFICED AND NECROPSIED ON DAY 22 POSTPARTUM 3(100.0) 5( 83.3) 3 ( 75.0) 3( 75.0) LITTERS EVALUATED PUPS EVALUATED N 28 N 168 28 28 28 29 168 167 164 170 APPEARED NORMAL LITTER INCIDENCE PUP INCIDENCE N (%) N(%) 27 ( 96.4) 167 ( 99.4) 27( 96.4) 167 ( 99.4) 26( 92.8) 165( 98.8) 27 ( 96.4) 163 ( 99.4) 29(100.0) 170(100.0) KIDNEYS: PELVIS SLIGHT OR MODERATE DILATION LITTER INCIDENCE PUP INCIDENCE N (t ) N(%) M 3.6) 1( 0.6) 1( 3.6) 1< 0.6) 2( 7.1) 2( 1.2) 0( 0.0) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) BRAIN: THIRD AND LATERAL VENTRICLES, MARKED DILATION LITTER INCIDENCE PUP INCIDENCE N (%) N (%) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 1( 3.6) 1< 0.6) 0( 0.0) 0( 0.0) a. Restricted to pups in which complete necropsies were performed. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. b. Analysis restricted to pups found dead and necropsied. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6B89.6) TABLE E24 (PAGE 1) : PUP ORGAN WEIGHTS - SUMMARY - F2 GENERATION PUPS ARGUS 418-020 Page 508 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 LITTERS EXAMINED N 28 28 28 28 29 TERMINAL BODY WEIGHT WEIGHT/LITTER MALE PUPS FEMALE PUPS MEAN+S.D. MEAN+S.D. MEAN+S.D. 39.10 + 7.23 40.01 + 7.43 38.38 + 7.37 ( 27] a 39.02 + 5.91 39.73 + 6.39 38.30 + 5.98 39.70 + 7.51 [ 27] a 39.95 + 8.48 [ 27] a 39.46 + 7.19 [ 27]a 40.06 + 6.88 41.15 + 6.82 38.24 + 6.47 [ 27] b 37.02 + 6.63 [ 28] a 37.60 + 7.28 [ 28] a 36.44 + 6.35 [ 28] a BRAIN WEIGHT/LITTER MALE PUPS FEMALE PUPS MEAN+S.D . MEAN+S.D . MEAN+S.D . 1.49 + 0.10 1.50 + 0.15 1.48 + 0.11 1.47 + 0.08 1.50 + 0.09 1.44 + 0.09 1.48 + 0.11 1.50 + 0.12 1.45 + 0.11 1.48 + 0.07 1.50 + 0.07 1.46 + 0.10 t 27] b 1.44 + 0.08 1.46 + 0.08 1.42 + 0.10 SPLEEN WEIGHT/LITTER MALE PUPS FEMALE PUPS MEAN+S.D . MEAN+S.D. MEAN+S .D . 0.1.5 + 0.04 0.14 + 0.04 0.15 + 0.05 0.14 + 0.04 0.14 + 0.04 0.15 + 0.04 0.14 + 0.04 0.14 + 0.05 0.14 + 0.04 0.15 + 0.04 0.15 + 0.04 0.14 + 0.04 [ 27] b 0.14 + 0.05 0 . 1 4 + 0.06 0.13 + 0.05 THYMUS WEIGHT/LITTER MALE PUPS FEMALE PUPS MEAN+S.D. MEAN+S.D . MEAN+S.D. 0.18 + 0.06 0.19 + 0.06 0.18 + 0.06 0.17 + 0.04 0.16 + 0.05 0.17 + 0.04 0.16 + 0.05 0.16 + 0.06 0.17 + 0.06 0.17 + 0.04 0.17 + 0.05 0.17 + 0.04 [ 27] b 0.16 + 0.05 0.16 + 0.06 0.16 + 0.05 ALL WEIGHTS WERE RECORDED IN GRAMS (G). [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for pups in which the terminal body weight could not be determined because pup identification appeared incorrectly recorded. b. Excludes values for litter(s) that had no female pups examined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E24 (PAGE 2) : PUP ORGAN WEIGHTS - SUMMARY - F2 GENERATION PUPS ARGUS 418-020 Page 509 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 LITTERS EXAMINED N 28 28 28 28 29 INCLUDED IN ANALYSES N 28 28 27a 28 28a RATIOS (%) OF BRAIN TO TERMINAL BODY WEIGHT WEIGHT/LITTER MEAN+S.D . 3.92 + 0.65 3.83 + 0.44 3.83 + 0.54 3.80 + 0.55 3.98 + 0.56 MALE PUPS MEAN+S.D . 3.86 + 0.69 3.83 + 0.46 3.89 + 0.70 3.73 + 0.50 3.98 + 0.57 FEMALE PUPS MEAN+S.D . 3.97 + 0.72 [ 27] a 3.82 + 0.48 3.77 + 0.50 3.92 + 0.68 [ 27] b 3.99 + 0.59 RATIOS (%) OF SPLEEN TO TERMINAL BODY WEIGHT WEIGHT/LITTER MEAN+S.D. 0.38 + 0.07 0.36 + 0.06 0.35 + 0.06 0.36 + 0.06 0.37 + 0.09 MALE PUPS MEAN+S.D . 0.36 + 0.08 0.34 + 0.08 0.34 + 0.08 0.36 + 0.07 0.37 + 0.10 FEMALE PUPS MEAN+S.D . 0.39 + 0.09 I 27] a 0.39 + 0.07 0.36 + 0.06 0.36 + 0.07 [ 27] b 0.37 + 0.10 RATIOS (%) OF THYMUS TO TERMINAL BODY WEIGHT WEIGHT/LITTER MEAN+S.D . 0.47 + 0.11 0.42 + 0.07 0.40 + 0.08 0.44 + 0.08 0.42 + 0.09 MALE PUPS MEAN+S.D . 0.46 + 0.11 0.41 + 0.10 0.40 + 0.09 0.42 + 0.10 0.42 + 0.10 FEMALE PUPS MEAN+S. D. 0.47 + 0.11 [ 27] a 0.43 + 0.06 0.41 + 0.09 0 ,4S + 0.09 [ 27] b 0.43 + 0.10 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for pups in which the terminal body weight could not be determined because pup identification appeared incorrectly recorded. b. Excludes values for litter(s) that had no female pups examined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E24 (PAGE 3) : PUP ORGAN WEIGHTS - SUMMARY - F2 GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I II III IV V 0 1 3 10 30 LITTERS EXAMINED N 28 28 28 28 29 RATIOS (%) OF SPLEEN TO BRAIN WEIGHT WEIGHT/LITTER MALE PUPS MEAN+S.D. MEAN+S.D. 9.93 2.44 9.66 + 2.62 9.70 2.39 9.04 + 2.70 9.44 + 2.38 9.06 + 2.72 9.81 + 2.51 9.97 + 2.67 9.46 + 3.18 9.46 + 3.42 FEMALE PUPS MEAN+S.D. 10.19 + 2.95 10.36 + 2.54 9.82 + 2.38 9.55 + 2.78 [ 27] b 9.44 + 3.31 RATIOS (%) OF THYMUS TO BRAIN WEIGHT WEIGHT/LITTER MEAN+S.D. 12.34 + 3.30 11.27 + 2.52 10.94 + 3.02 11.75 + 2.76 10.97 + 3.41 MALE PUPS MEAN+S.D . 12.41 + 3.62 10.98 + 3.22 10.53 + 3.32 11.51 + 3.22 11.05 + 3.95 FEMALE PUPS MEAN+S.D. 12.28 + 3.64 11.57 + 2.40 11.34 + 3.21 1 1 . 9 6 + 3.05 [ 27] b 10.90 + 3.38 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for pups in which the terminal body weight could not be determined because pup identification appeared incorrectly recorded. b. Excludes values for litter(s) that had no female pups examined. ARGUS 418-020 Page 510 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E25 (PAGE 1) : ANOGENITAL DISTANCE - SUMMARY - F2 GENERATION PUPS ARGUS 418-020 Page 511 DOSAGE GROUP DOSAGE (MG/KG/DAY) LITTERS WITH ONE OR MORE LIVE PUPS N I 0 28 II III 13 28 28 IV 10 28 DAY 1 POSTPARTUM: ANOGENITAL DISTANCE (MM) DISTANCE/ LITTER MALE PUPS FEMALE PUPS DAY 22 POSTPARTUM: MEANS .D . MEANlS.D. MEANS.D. 1.03 0 . 2 0 2.59 0.17 1.07 0.06 1 . 8 6 4 0.19 2.58 4 0.17 1.08 4 0 . 1 0 1.87 0.22 2.60 0 . 2 0 1 . 1 0 0.08 1.96 4 0.41 2.64 4 0.26 1.08 4 0.08 ( 27] a ANOGENITAL DISTANCE (MM) DISTANCE/ LITTER MEANS.D. MALE PUPS MEANS.D . FEMALE PUPS MEANS.D . 11.06 0.92 13.90 1 . 1 0 8.24 0.78 11.26 4 1.04 13.95 1 . 1 0 8.28 4 0.60 1 1 . 0 1 1.26 l 27] b 13.58 4 1.26 ( 27] b 8.33 4 0.86 [ 27]b 11.31 4 1.70 13.70 4 1.44 8.10 4 0.74 l 27] a [ ] = NUMBER OF VALUES AVERAGED a. Litter 1524 had no female pups. b. Excludes litter 1474, which did not have anogenital distances recorded on day 22 postpartum. V 30 29 1.83 4 0.24 2.63 4 0.17 1.12 4 0 . 1 0 10.55 4 1.46 13.31 4 1.34 8 . 0 2 4 0.85 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 1) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 512 DOSAGE GROUP I RAT # 0 MG/KG/DAY DESCRIPTION 1301 1302 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317 1318 19779 19780 1321 1322 1323 1324 1325 1326 1327 DP ( 62- 65) DG ( 19- 20) DL( 1- 22) DG ( 16- 22) DL( 1- 22) DP ( 61- 68) DP ( 24- 25) DP ( 24- 28) DP ( 25- 28) DP ( 26- 28) DP ( 27 ) DP ( 27- 28) DP ( 28 ) DP ( 41- 55) DP ( 27 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS : MISALIGNED INCISORS: MISALIGNED a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN NO ADVERSE FINDINGS CHROMORHINORRHEA DEHYDRATION a EMACIATION a URINE-STAINED ABDOMINAL FUR LACRIMATION PTOSIS CHROMODACRYORRHEA a LOCALIZED ALOPECIA: HEAD HEAD: SCAB (0.5 CM IN DIAMETER) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 513 DOSAGE GROUP I 0 MG/KG/DAY RAT # DESCRIPTION 1328 1329 1330 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 DP ( 3- 7) DP ( 8- 12) DG ( 14- 21) DL( 1- 22) DP ( 3- 4) DP ( 7- 10) DP ( 50- 54) DG ( 1- 21) DL( 1- 22) DP ( 6- 12) DP ( 6- 16) DP ( 6- 15) DG ( 8- 21) DL( 1- 22) DP ( 57- 81) DG ( 0- 21) DL( 1- 22) DP ( 64- 83) DG ( 0- 21) DL( 1- 6) DL( 4- 22) DL ( 22 ) DP ( 6- 15) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION SWOLLEN EAR (S) SWOLLEN EAR(S) a CHROMORHINORRHEA ABDOMINAL DISTENTION INCISORS : MISSING/BROKEN NO ADVERSE FINDINGS SWOLLEN EAR(S) SWOLLEN EAR(S) a ABDOMINAL DISTENTION ABDOMINAL DISTENTION ABDOMINAL DISTENTION SWOLLEN EAR(S) SWOLLEN EAR(S) a SWOLLEN EAR (S) SWOLLEN EAR (S) SWOLLEN EAR(S) a NO ADVERSE FINDINGS INCISORS : MISALIGNED INCISORS: MISALIGNED INCISORS : MISALIGNED INCISORS : MISSING/BROKEN a INCISORS : MISALIGNED a NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 3) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS DOSAGE GROUP I 0 MG/KG/DAY RAT # DESCRIPTION 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 DP ( 62- 81) DG ( 0- 21) DL( 1- 22) DP ( 1- 4) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS PTOSIS PTOSIS PTOSIS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMODACRYORRHEA NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL DAY OF LACTATION Page 514 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 4) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 515 DOSAGE GROUP II 1 MG/KG/DAY RAT # DESCRIPTION 1361 1362 1363 1364 1365 1366 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 DP ( 63- 64) DP ( 3- 5) DP ( 1- 3) DP ( 3 ) DP ( 3 ) DP ( 3 ) DP ( 4 ) DP ( 9- 14) DP ( 17 ) DP ( 17 ) DP ( 17- 20) DP ( 17- 20) DP ( 2 ) DP ( 28- 35) DP( 29- 50) DP ( 32- 50) DP ( 35 ) DP ( 35- 50) DP ( 45- 50) DP ( 51 ) DP { 26- 31) DP ( 26- 35) NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN CHROMORHINORRHEA TIP OF TAIL MISSING a DECREASED MOTOR ACTIVITY CHROMORHINORRHEA a COLD TO TOUCH FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION HEAD : SWOLLEN SNOUT: SWOLLEN LACRIMATION RIGHT EYE: SWOLLEN NO ADVERSE FINDINGS SOFT OR LIQUID FECES CHROMORHINORRHEA DEHYDRATION a URINE-STAINED ABDOMINAL FUR CHROMODACRYORRHEA EMACIATION a DECREASED MOTOR ACTIVITY FOUND DEAD ANNULAR CONSTRICTION OF THE TAIL ANNULAR CONSTRICTION OF THE TAIL NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 5) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 516 DOSAGE GROUP II RAT # 1377 1378 1379 1380 1381 1382 1383 1384 1385 1386 1387 1388 1389 1390 1391 1392 1393 13 94 1395 1396 1397 1398 1399 1400 1401 1402 1403 DP ( DP( DP ( DP ( 2) 2- 3) 2- 10) 9- 19) DG ( 6- 21) DL ( 1- 22) DP ( 9- 12) DP ( 67- 83) DG ( 0- 6) DP ( 8- 14) DP ( 1- 9) 1 MG/KG/DAY DESCRIPTION DEHYDRATION CHROMORHINORRHEA URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SWOLLEN EAR(S) SWOLLEN EAR (S) a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS SWOLLEN EAR (S) SWOLLEN EAR(S) ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropay. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 6) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 517 DOSAGE GROUP II 1 MG/KG/DAY RAT # DESCRIPTION 1404 1405 1406 1407 1408 1409 1410 1411 1412 1413 1413 1414 1415 1416 1417 1418 1419 1420 DPI 3- 6) DP ( 7- 13) DP ( 24- 83) DG ( 0- 21) DL( 1- 22) DP ( 6- 15) DP ( 59- 83) DG ( 0- 21) DL( 1- 22) DP ( 1- 7) DP ( 6- 16) NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS TIP OF TAIL MISSING TIP OF TAIL MISSING TIP OF TAIL MISSING a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION LOCALIZED ALOPECIA : LIMBS LOCALIZED ALOPECIA: LIMBS a LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 7) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 518 DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 1421 DL( 2 ) 1422 1423 1424 1425 1426 DPI 2- 3) DP ( 3- 5) 1427 DP ( 26 ) 1428 DL ( 13 ) 1429 1430 DP ( 59- 66) 1431 DP ( 4- 11) 1432 DP ( 4- 6) DP ( 4- 6) DP ( 6 ) DP ( 7 ) 1433 DP ( 23 ) 1434 DL ( 1 ) DP ( 2- 4) 1435 1436 DL ( 5- 21) 1437 1438 1439 DP ( 62- 79) DG ( 15- 21) DL ( 1- 22) 1440 1441 DP ( 3 ) DP ( 3- 10) DP ( 9- 13) 1442 1443 1444 DP ( 1 ) . 1445 RED PERIVAGINAL SUBSTANCE NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES URINE-STAINED ABDOMINAL FUR SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN URINE-STAINED ABDOMINAL FUR CHROMORHINORRHEA a URINE-STAINED ABDOMINAL FUR EMACIATION a FOUND DEAD CHROMORHINORRHEA RED PERIVAGINAL SUBSTANCE CHROMORHINORRHEA NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS EMACIATION URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. . ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 8) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 519 DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 1446 1447 1448 1449 1450 1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 1461 1462 1463 1464 1465 DL ( 2 ) DL( 17 ) DL( 19- 20) DP ( 37 ) DP ( 41- 64) DP ( 51- 53) DP ( 51- 82) DP ( 54 ) DP ( 54- 55) DP ( 65- 82) DG( 0- 21) DG ( 0- 21) DL ( 1- 22) DL( 1- 22) DL ( 1- 22) DL ( 3- 22) DP ( 1- 3) DP ( 6- 18) DP ( 14- 15) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED PERIVAGINAL SUBSTANCE SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMORHINOERHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS CHROMORHINOERHEA INCISORS: MISSING/BROKEN INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA CHROMODACRYORRHEA INCISORS: MISSING/BROKEN CHROMODACRYORRHEA a INCISORS: MISSING/BROKEN a LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS CHROMORHINORRHEA ABDOMINAL DISTENTION CHROMORHINORRHEA DP DAY POSTWEANING DG - DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 9) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS DOSAGE GROUP III 3 MG/KG/DAY RAT # DESCRIPTION 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 1476 1477 1478 1479 1480 DP ( 6- 12) DP ( 7- 10) DL( 22 ) DL( 2 ) DP ( 60- 63) DP ( 64- 77) DG ( 16- 21) DL( 1- 22) DP ( 57- 59) ABDOMINAL DISTENTION ABDOMINAL DISTENTION NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED PERIVAGINAL SUBSTANCE NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS : MISALIGNED INCISORS : MISSING/BROKEN INCISORS : MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SWOLLEN EAR(S) DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. ARGUS 418-020 Page 520 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 10) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 521 DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION 1481 1482 . 1483 1484 1485 I486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP( 2- 8) 3) 9- 18) 1- 2) 2) 2) 2) 3) DP ( 5- 8) DP ( 9- 20) DP ( 8- 10) DP ( 15- 17) DP ( 8- 9) DPI 13- 83) DG ( 0- 21) DL( 18 ) DL( 18- 22) DL( 1- 22) DP ( 30 ) DP( 30 ) DP ( DP ( 6) 6) NO ADVERSE FINDINGS NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR EMACIATION ABDOMINAL DISTENTION URINE-STAINED ABDOMINAL FUR DECREASED MOTOR ACTIVITY COLD TO TOUCH LABORED BREATHING FOUND DEAD NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION LOCALIZED ALOPECIA: NECK NO ADVERSE FINDINGS ABDOMINAL DISTENTION TIP OF TAIL MISSING TIP OF TAIL MISSING URINE-STAINED ABDOMINAL FUR SOFT OR LIQUID FECES TIP OF TAIL MISSING NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LACRIMAT ION LEFT EYE : SWOLLEN NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP = DAY POSTWEANING DG DAY OF PRESUMED GESTATION DL = DAY OF LACTATION PROTOCOL 418-020; ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 11) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 522 DOSAGE GROUP IV 10 MG/KG/DAY RAT # DESCRIPTION 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 DP ( 7- 18) DP ( 65- 79) DL ( 5- 22) DP ( 59- 67) DL ( 8- 22) DL ( 14 ) DL ( 15- 16) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION LOCALIZED ALOPECIA; LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS BACK: SCAB (DID NOT EXCEED 0.5 CM X 0.3 CM) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 12) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS DOSAGE GROUP IV 10 MG/KG/DAY RAT tt DESCRIPTION 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 D P ( 71- 83) DG( 0- 2) NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISALIGNED INCISORS: MISALIGNED NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION Page 523 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 13) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 524 DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553 1554 1555 1556 1557 1558 1559 1560 1561 1562 1563 1564 DP ( 10- 19) DP ( 10- 11) DP ( 61- 66) DP ( 62- 66) DP ( 56 ) DL( 2 ) DP ( 9- 13) DL ( 5- 22) DP ( 2- 3) DP ( 2- 7) DP ( 3- 7) DP ( 5- 7) DP ( 8 ) DP ( 9- 13) DP ( 40 ) DP ( 9- 14) DP ( 13 ) DP ( 14- 31) DG ( 17- 21) DL ( 1- 22) DP ( DP ( DP ( DP ( DP ( 8- 13) 3- 5) 5) 5) 6) DP ( DP ( 2) 2) ABDOMINAL DISTENTION ABDOMINAL DISTENTION NO ADVERSE FINDINGS BACK: SCAB (0.5 CM X 0.2 CM) LOCALIZED ALOPECIA: LIMBS CHROMORHINORRHEA RED PERIVAGINAL SUBSTANCE NO ADVERSE FINDINGS ABDOMINAL DISTENTION SWOLLEN EAR(S) a DECREASED MOTOR ACTIVITY CHROMORHINORRHEA a COLD TO TOUCH URINE-STAINED ABDOMINAL FUR FOUND DEAD ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL ABDOMINAL DISTENTION TAIL BENT TIP OF TAIL MISSING a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION URINE-STAINED ABDOMINAL FUR COLD TO TOUCH EMACIATION a FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS FOUND DEAD b FOUND DEAD b NO ADVERSE FINDINGS DP * DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. b. Clinical observations were not recorded on day 1 postweaning. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E2G (PAGE 14) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 525 DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 1565 1566 1567 1568 1569 1570 1571 1572 1573 1574 1575 1576 1577 1578 1579 1580 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 DP ( 39 ) DG ( 14- 21) DL( 1- 22) DG ( 21 ) DL( 1- 22) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 8- 19) 2- 3) 2- 3) 3) 3) 3- 8) 9- 13) 38 ) DG ( 14- 21) DL ( 1- 19) DP ( 24 ) DG ( 20- 21) DL ( 1- 6) ANNULAR CONSTRICTIONS OF THE TAIL LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION COLD TO TOUCH URINE-STAINED ABDOMINAL FUR FOUND DEAD FOUND DEAD URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RIGHT AXILLA: MASS (0.5 CM X 0.5 ffl X 0.5 CM) RIGHT AXILLA: MASS (DID NOT EXCEED 0.5 CM X 0.5 CM X 0,5 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS RALES NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E26 (PAGE 15) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS DOSAGE GROUP V 30 MG/KG/DAY RAT # DESCRIPTION 1592 1593 1594 1595 1596 1597 1598 1599 1600 D P ( 6- 12) D P ( 7- 15) DP ( 8 ) D P ( 5- 16) URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RALES ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION Page 526 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 1) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 527 RAT # DOSAGE GROUP I 0 MG/KG/DAY 1301 1302 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317 1318 19779 19780 1321 1322 1323 1324 1325 1326 1327 1328 1329 1330 DAY 1 39. 41. 40. 46. 53 . 31. 31. 47 . 44. 46. 40. 49. 45. 46. 50. 45. 48. 39. 32. 41. 46. 51. 47. 33. 35. 34 . 33. 35. 39. 34 . 8 71. 69. 69. 76. 86. 66. 59. 76. 74. 74. 71. 74 . 70. 83. 95. 87. 85. 72. 58. 71. 77. 84. 78 . 59. 60. 63. 61. 67. 67. 62. 15 107. 105. 109. 115 . 131. 107 . 99. 116. 115. 123. 108. 116. 104. 124. 144 . 134 . 132 . 119. 94. 108 . 116. 119. 117. 98 . 97 . 109. 102. 111. 103 . 96. 22 146. 137. 144. 144 . 176. 148 . 134 . 150. 151. 158. 145. 158. 140. 160. 191. 169. 169. 159. 136. 124 . 153. 156 . 160. 131. 133. 143 . 151. 146. 132. 133 . 29 176. 162 . 173. 172 . 201. 178 . 163 . 176. 180 . 190. 170. 192. 168. 196. 236. 196. 202. 192 . 183 . 188 . 182. 152. 159. 180 . 192. 181. 159. 162. 36 180. 194 . 208. 201. 220. 230. 194. 228. 228. 196. 191. 199. 184 . 43 196. 208. 219. 215. 239. 248. 211. 248 . 271. 242 . 203 . 225. 200. 50 206. 217. 236. 234. 249. 263 . 222. 254 . 271. 274 . 224 . 239. 222 . 57 219. 233. 252. 241. 267. 274. 242 . 276. 284 . 262 . 235. 254. 230. 64 220. 246. 260 . 253 . 285 . 295. 254 . 279 . 298 . 274 . 245. 268 . 239 . 70a PRECOHABITATION b 235. 246. 264. 256. 285. 304 . 258 . 237. 266. 276. 279. 306. 312. 268. 288. 305. 297 . 327. 280. 287. 253 . 267. 270. 246 . 279. 255. DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 2) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 528 RAT # DOSAGE GROUP I o MG/KG/DAY 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 1 44. 40. 28. 28. 40. 37. 47. 48. 32. 37. 40. 42. 53. 60. 47. 44. 36. 41. 40. 49. 45. 49. 38. 44 . 43 . 48. 35. 33 . 36. 37. 8 72 . 69. 52. 48 . 69. 66. 72. 77. 59. 58. 72. 73. 91. 91. 80. 76. 68. 68. 68. 86. 79. 85. 62. 74 . 80. 83. 60. 64. 65. 70. 15 112. 110. 88. 79. 102. 100. 107 . 115. 96. 93. 114. 110. 134. 138. 122. 118. 108. 102 . 106 . 133 . 123 . 125. 100 . 108 . 123. 124 . 99. 100. 99. 112. 22 151. 144 . 130. 120. 146. 136. 152. 152. 141. 137. 146. 144 . 173. 173 . 160 . 155. 148. 142. 144 . 172 . 158. 172 . 137. 140. 157. 167. 135. 137. 137. 29 183. 173. 155. 146. 171. 167. 181. 168. 174 . 170. 196. 186. 174. 168 . 191. 163 . 180. 154. 159. 36 201. 167. 194. 187. 204 . 200. 198. 200. 215. 213. 197. 190. 222 . 180. 209. 177. 189 . 43 223 . 187. 212. 212. 229. 220. 217. 222. 229. 232. 214 . 213 . 234 . 205. 226. 192 . 201. 50 238 . 201. 232. 226. 247. 258. 237. 237. 250. 255. 229. 234 . 263 . 223 . 251. 211. 210. 57 252 . 211. 250. 238. 254 . 250. 253 . 254 . 257. 268 . 237. 244 . 262 . 240. 263 . 228. 228 . 64 268 . 225. 253 . 243 . 272 . 272 . 266. 274 . 259. 280. 241. 259. 276 . 245. 273 . 232 . 234 . 70a PRECOHABITATION b 263 . 280. 227 . 268. 249. 278. 285. 263. 276. 261. 288 . 247. 264 . 275 . 238 . 275 . 262 . 303 . 279 . 291. 295 . 266. 295. 253 . 275 . 298. 256 . 279. 262 . 295. 238 . 239. 240. 239 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 3): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 529 RAT # DOSAGE GROUP II 1 MG/KG/DAY 1361 1362 1363 1364 1365 1366 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 1377 1378 1379 1380 13 81 1382 1383 13 84 1385 1386 1387 1388 1389 1390 DAY 1 40. 40. 35. 35. 31. 36. 29. 38. 41. 40. 37. 49. 44 . 41. 40. 37. 26. 47. 49. 40. 38. 31. 29. 40. 39. 36. 40. 42 . 44 . 38. 8 15 22 29 66. 100. 139. 169. 64. 92 . 124 . 152. 66. 103 . 148. 176. 59. 95. 143. 170. FOUND DEAD ON DAY 4 POSTWEANING 61. 98. 131. 163 . 48. 76. 112 . 140. 64. 102. 138. 162 . 70. 106. 137. 162. 66. 108. 151. 186. 65. 105. 14 6. 181. 80. 120. 156. 181. 73. 112. 151. 151. 70. 107. 147. 177. 66. 104 . 143 . 170. 62. 96. 127. 161. 43. 84 . 134. 172. 79. 121. 158. 188. 78. 118. 162. 187. 65. 98 . 135. 156 . 62 . 96. 136. 159. 58. 96. 133 . 160. 49. 85 . 124 . 153. 68. 110. 140. 156. 76. Ill. 150. 179. 65. 98. 132. 160. 69. 111. 158. 184. 70. 107. 149. 183 . 73. 113 . 154. 181. 73 . 113. 148 . 170. 36 172 . 201. 197. 158. 181. 210. 130. 201. 194 . 210. 213. 182 . 188. 178. 176. 221. 214 . 43 188. 216. 211. 177. 200. 236. 118. 221. 223 . 224 . 232. 202. 210. 202. 183. 240. 237 . 50 202 . 228. 230. 186. 213. 251. 107. 233. 236. 242. 259. 217. 229. 219. 202 . 254. 253 . 57 64 70a PRECOHABITATION b 212. 246. 241. 226 . 261. 257. 236. 264. 262. 245. 282. 272. 197. 230. 202 . 243 . 220. 247. 223 . 266. 260. 282. 281. 303. FOUND DEAD ON DAY 51 POSTWEANING 239. 267. 255. 284 . 265. 296 . 278. 316. 258. 267. 270 . 278 . 278 . 280. 288. 295. 228 . 239. 232 . 203 . 239. 249. 245. 219. 242 . 248 . 253 . 225. 256. 265. 274 . 236. 272 . 273 . 286 . 291. 286 . 291. 308. 302. DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats,- at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 4) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 530 RAT # DOSAGE GROUP II 1 MG/KG/DAY 13 91 13 92 13 93 13 94 1395 13 96 13 97 1398 13 99 1400 14 01 1402 14 03 1404 1405 14 06 1407 1408 1409 1410 1411 1412 1413 1414 1415 1416 1417 1418 1419 1420 DAY 1 36. 38. 39. 40. 34 . 42. 40. 31. 58. 57. 34. 38. 32. 31. 28. 44. 47. 42 . 41. 40 . 44. 49 . 40 . 35. 30. 46. 45. 41. 38. 42. 8 64. 73. 65. 68. 58. 74 . 72. S3 . 85. 82. 63. 68. 62. 57. 50. 72 . 75 . 65. 66. 72 . 74 . 84. 68. 63 . 58. 74 . 72 . 65. 69. 64 . 15 103 . 122. 101. 109. 95. 108. 116. 88. 121. 117. 98. 104 . 95. 94. 84. 105. 116. 101. 104 . 112 . 114 . 128 . 106. 98 . 89. 114. 112. 99. 108. 104 . 22 142. 158. 139. 153 . 131. 153 . 159. 132. 157. 150. 132. 138. 135. 134. 126. 136. 155 . 136. 142 . 157. 154 . 163 . 14 8. 135. 129 . 150. 151. 138. 14 9. 145. 29 174. 187 . 171. 186. 166. 182 . 189. 162 . 181. 177. 158. 164. 153. 165. 166. 164. 183. 162 . 174 . 189. 177. 157. 181. 163 . 36 213. 191. 206. 205 . 177. 188 . 210. 204 . 221. 195. 180. 203 . 186. 43 235. 214 . 233 . 231. 194. 212 . 229. 212 . 239. 216. 208 . 225. 206. 50 246. 230. 253. 244 . 208. 230 . 242 . 252. 266. 237. 222 . 239. 219. 57 269. 234 . 257. 251. 222. 242 . 259. 263. 275 . 245. 232 . 240. 230 . 64 258. 260. 261. 260. 230 . 258 . 263 . 258 . 285. 252 . 249. 248. 245. 70a PRECOHABITATION b 289. 267. 316. 279. 284. 275 . 235. 301. 288. 250. 263 . 285. 274 . 269. 294 . 277 . 280. 315. 264 . 250. 256. 246. 273 . 264 . 265. 262 . DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a< Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweanlng was the last day on which the youngest rats (in this group) had a body weight value recorded, b. Precohabitation body weights were recorded on the day cohabitation was begun Cor the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 5) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 531 RAT # DOSAGE GROUP Ill 3 MG/KG/DAY 1421 1422 1423 1424 1425 1426 1427 1428 1429 1430 1431 1432 1433 1434 1435 1436 1437 1438 1439 1440 1441 1442 1443 1444 1445 1446 1447 1448 1449 1450 DAY 1 31. 34. 33. 37. 32. 34 . 44 . 45. 42. 35. 31. 31. 40. 43. 51. 42 . 42 . 38. 47. 45 . 32 . 33 . 35. 37. 39. 41. 46. 52. 57. 56. 8 15 22 29 62. 97. 138 . 170. 62. 100. 143 . 167. 64. 106. 14 3 . 180. 72. 111. 150 . 177. 61. 104 . 145 . 177. 60. 97. 136 . 157. 74. 121. 163 . 191. 78. 119. 158 . 191. 76. 112. 150 . 177. 65. 110. 160 . 199. 52 . 86. 138 . 176. FOUND DEAD ON DAY 7 POSTWEANING 71. 112. 14 8 . 182. 52. 102. 14 7 . 183. 85. 128 . 169 . 199. 81. 124 . 162 . 189. 76. 114 . 145 . 168. 75. 113. 136 . 144. 76. 120. 160 . 184. 76. 122 . 162 . 189. 51. 90. 140 . 172. 61. 94 . 143 . 169. 62. 94. 136 . 166. 65 . 107. ISO . 179. 72. 108 . 150 . 166. 70. 103 . 137 . 173. 74 . 109. 14 5 . 191. 80. 117. 158 . 180. 93 . 135. 156 . 182. 90. 131. 159 . 180. 36 191. 211. 191. 213 . 233. 209. 212. 217. 192. 214 . 196. 194 . 189. 216. 200. 43 209. 223 . 223 . 233 . 258. 232. 234 . 228 . 206 . 233 . 229. 215. 207. 234 . 218 . 50 222 . 232 . 238. 249. 275. 257. 246. 244 . 227. 254 . 237. 240. 222 . 256. 233. 57 234 . 249. 266. 260. 283. 271. 263 . 259 . 248 . 271. 238 . 261. 231. 263 . 238 . 64 245 . 268. 276 . 280. 297. 282. 284 . 271. 255. 287. 248. 279. 246. 275 . 250 . 70a PRECOHABITATION b 251. 266. 267. 287. 289 . 308. 290. 282. 280. 299. 307. 329. 297. 303. 281. 255. 293 . 298. 264. 304 . 258 . 279. 278. 300. 253 . 287. 263 . 260. 302. 277. DAY DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 6) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 532 RAT # DOSAGE GROUP III 3 MG/KG/DAY DAY 1 8 15 22 29 36 43 50 57 64 70a PRECOHABITATION b 1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 1461 1462 1463 1464 1465 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 1476 1477 1478 1479 1480 56. 50. 54. 57. 46. 61. 39. 38. 52. 43 . 42. 46. 42. 53. 30. 32. 34. 36. 38. 33. 47. 46. 53. 50. 37. 46. 67. 57. 44 . 42. 93 . 82. 96. 93. 78. 96. 70. 69. 93. 77. 71. 76. 73. 92. 49. 53. 60. 60. 62. 58. 78. 75. 83. 81. 68. 76. 100. 91. 76. 71. 136. 119. 138. 133 . 116. 131. 108 . 113. 138. 117. 108. 112. 113. 139. 83 . 92. 101. 92. 97. 100. 114. 110. 126. 121. 103. 116. 125. 128. 120. 115. 176 . 151. 170. 168 . 151. 169. 143 . 154 . 172. 160. 152. 158. 149 . 178 . 128. 133 . 140. 130. 132. 135. 150. 144 . 156. 152 . 134 . 156. 173 . 166. 154 . 152. 208 . 179. 197. 189. 184. 192 . 162. 178. 207. 196. 188. 181. 176. 217. 164 . 157. 160. 170. 175. 188. 200. 185. 169. 211. 216 . 202. 243 . 211. 200 . 192. 178 . 196. 189. 195. 213. 216. 205. 224. 231. 231. 222 . 258 . 234 . 216 . 222 . 206. 217 . 214 . 213. 237. 242. 218 . 251. 246. 246. 232. 277. 250. 240. 242 . 230. 242 . 228. 220. 259. 269. 242. 254. 270. 250 . 243 . 290. 266. 253 . 254 . 239. 244 . 243 . 233. 265. 256. 244 . 264 . 288 . 265. 247. 300 . 273 . 265. 272 . 245 . 258. 253 . 231. 272 . 268. 263 . 272 . 290 . 287. 266. 265. 311. 287. 269. 278. 300. 279. 271. 323. 297 . 283 . 302. 261. 262 . 267. 272 . 251. 248 . 286. 267. 260. 265. 292 . 279. 273 . 278 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. precohabitation body weights were recorded on the day cohabitation, was begun for the FI generation rats; at that time these rats were 92 to 106 days of age. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 7) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 533 RAT # DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 8 15 22 29 36 43 50 57 64 70a PRECOHABITATION b 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 14 92 1493 1494 1495 14 96 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 48. 47. 29. 28. 30. 27. 46. 46. 39. 39. 43. 42. 46. 48. 44. 44. 64. 53. 43 . 39. 40. 42 . 43 . 39. 40. 34 . 40. 54 . 53. 43. 76. 116. 155. 184 . 75. 112. 149. 172. 48. 82. 124. 153 . FOUND DEAD ON DAY 3 POSTWEANING 53. 93. 134. 170. 36. 63. 99. 136. 78. 115. 146. 168. 78. 119. 153. 185. 70. 105. 142. 178. 64. 104. 150. 186. 73 . 102. 140. 169. 67. 104 . 138. 168. 82. 127. 171. 196. 89. 101. 161. 191. 78. 110. 144 . 164 . 78. 116. 154. 176. 98. 140. 182. 213. 55. 93 . 141. 182. 71. 107. 140. 169. 66. 100. 139. 167. 68. 102. 147. 181. 71. 110 . 156. 186. 72 . 104 . 143 . 173 . 67. 103 . 142. 174. 66. 99. 135. 161. 63. 97. 132. 162. 69. 103. 145. 173. 89. 130. 171. 202. 81. 112. 147. 167. 72 . 117. 154. 193 . 200. 183. 159. 209 . 206. 192. 217. 193. 233 . 184 . 210. 184 . 192. 230 . 215. 202 . 186. 241. 221. 219. 236. 217 . 252. 205 . 250. 208 . 210. 247. 231. 221. 202. 262. 225. 231. 248 . 235. 267. 216 . 256. 223 . 228. 264 . 243 . 231. 219. 280. 253. 240. 259. 240. 281. 230 . 255. 236. 233 . 271. 256. 247. 230. 300. 265. 246. 277. 250. 294 . 235 . 277. 247. 250 . 288. 270. 251. 279. 275. 232. 312. 268. 248 . 248. 329. 276. 261. 284 . 265. 293 . 290 . 271. 304 . 238 . 280. 254 . 304 . 258. 258. 296 . 273 . 259. 300 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 8) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 in Page 534 RAT # DOSAGE GROUP IV 10 MG/KG/DAY 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 38. 46. 43 . 53 . 47. 45 . 45 . 36. 34. 52. 50. 49. 36. 35. 52. 48. 40. 34. 50 . 47. 55. 56. 44 . 38. 42. 37. 36. 47. 44 . 64 . 75. 75. 90. 73. 84. 79. 64. 58. 81. 74 . 85. 72. 63 . 60. 88. 79. 70. 50. 83 . 76. 86. 92. 78. 72. 67. 58. 60. 73 . 71. 103 . 113 . 111. 131. 108. 121. 120 . 105. 95. 119. 107. 122. 102. 91. 91. 123 . 119. 103 . 85. 123 . 117. 132. 136. 118. 114 . 105. 94. 98. 112. 102 . 139. 157. 150. 172. 143. 152. 155. 14 9. 134. 159. 140. 157. 136. 133. 130. 164. 157. 125. 114 . 163 . 160. 170. 175. 154. 154. 133 . 127. 135. 153 . 138. 29 169. 182. 175. 196. 167. 181. 183. 182. 162. 159. 159. 161. 184. 142. 180. 199. 178. 158. 182 . 36 197. 201. 223 . 202. 208. 190 . 180. 175. 186. 201. 162. 208. 226. 206. 188. 210 . 43 222. 217. 241. 217. 234 . 211. 198 . 194. 211. 225. 179. 220 . 239. 226. 205 . 232 . 50 238. 233 . 256. 237. 250. 229. 216. 211. 233. 240. 197. 246. 258. 247 . 227 . 252 . 57 253. 247. 274 . 242. 268 . 242 . 225. 219. 234 . 251. 207. 252 . 274 . 251. 234 . 267. 64 276. 253 . 283 . 257. 293 . 247. 236. 227. 247. 268. 214 . 254 . 286. 259. 242. 278 . 70a PRECOHABITATION b 275 . 288. 256. 289. 268. 304 . 270 . 296. 274 . 311. 262 . 264. 248 . 251. 241. 257. 251. 255. 269. 219. 282. 233. 264. 289. 267. 272 . 305. 277. 251. 281. 262 . 291. DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time these rats were 92 to 106 days of age. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 9) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 535 RAT # DOSAGE GROUP V 30 MG/KG/DAY 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553 1554 1555 1556 1557 1558 1559 1560 1561 1562 1563 1564 1565 1566 1567 1568 1569 1570 DAY 1 34 . 34 . 35. 37. 33. 36. 34 . 34 . 28. 33. 42. 42. 38. 44 . 39. 43. 43 . 30. 22 . 43 . 39. c c 36. 40. 44 . 43 . 67. 58. 39. 8 15 22 29 53 . 84. 115. 144 . 62. 97. 139. 171. 56. 86. 114 . 136. 58. 93 . 143 . 179. 62. 104 . 140. 169. 65. 101. 142. 171. 58. 91. 135. 165. 58. 88. 124. 152. FOUND DEAD ON DAY 8 POSTWEANING 54. 80. 108 . 132. 68. 108. 150. 178. 70. 116. 142. 167. 59. 85. 119. 144 . 70. 108. 147. 172. 64. 94 . 133 . 164 . 72 . 106. 139. 166. 77. 113. 153. 186. 57. 91. 131. 163 . FOUND DEAD ON DAY 6 POSTWEANING 74 . 110 . 14 5. 171. 71. 109. 143 . 179. FOUND DEAD ON DAY 2 POSTWEANING FOUND DEAD ON DAY 2 POSTWEANING 63 . 97. 129. 156. 67. 100. 135. 167. 73 . 107 . 141. 176. 75. 116. 151. 182. 106. 152. 183 . 210. 89. 123 . 151. 168. 70 . 108. 146. 178. 36 165. 215. 199. 201. 174. 148. 196. 182 . 212. 180 . 186. 175. 178 . 207. 229. 43 181. 234. 218 . 217. 194. 171. 206. 201. 234 . 205. 200. 195. 198 . 226 . 250 . 50 191. 252. 232. 233. 205. 189. 215. 214 . 255. 225. 215 . 206. 212 . 240 . 265 . 57 205 . 270. 247. 250. 220. 201. 231. 221. 268. 236. 234 . 214. 219. 258 . 270. 64 220 . 285 . 263 . 263. 234 . 209. 245. 231. 275. 256. 241. 226. 226 . 272 . 281. 70a PRECOHABITATION b 228 . 247. 293. 265. 270. 233. 217. 239. 304. 282. 273. 251. 224. 252. 238. 290. 264. 248 . 250. 300. 272. 258 . 234 . 236 . 275 . 289. 239. 243. 252 . 290. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time these rats were 92 to 106 days of age. c. Value not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E27 (PAGE 10) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 536 RAT # DOSAGE GROUP V 30 MG/KG/DAY 1571 1572 1573 1574 1575 1576 1577 1578 1579 1580 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 1592 1593 1594 1595 1596 1597 1598 1599 1600 DAY 1 36. 44 . 42 . 23 . 23 . 25. 33. 35. 49. 46. 48. 39. 41. 33 . 33. 37. 39. 45. 39. 45 . 44 . 44. 46. 47 . 45. 46. 31. 36. 44 . 44 . 8 15 22 29 60. 89. 123 . 153. 68. 106 . 150 . 188. 71. 110. 156 . 190. FOUND DEAD ON DAY 3 POSTWEANING FOUND DEAD ON DAY 3 POSTWEANING 43 . 68. 108 . 140. 54. 85. 126 . 154. 61. 98. 135 . 161. 77. 120. 156 . 186. 73. 104. 145 . 180. 76. 112. 149 . 177. 57. 91. 125 64. 97. 140 . 164. 58. 94. 128 . 148. 57. 98. 134 62. 96 . 131 . 152. 64. 97. 134 . 157. 73 . 112 . 149 . 169. 76. 117. 156 . 176. 73 . 107 . 136 72 . 109. 143 . 169. 67. 103 . 140 78. 120. 152 . 195. 73 . 106. 139 74 . 115 . 148 71. 111. 147 59. 94 . 133 65. 106. 141 . 172. 69. 110 . 154 69. 110. 149 . 180. 36 176. 212. 163 . 186. 209. 182. 171. 168 . 176. 194 . 206 . 194 . 217. 195. 206. 43 198 . 234. 190. 207. 234. 204 . 200. 183. 196. 220. 216. 210. 228 . 215. 226. 50 212. 250. 208. 221. 247. 220. 215. 198. 209. 230. 236. 220. 239. 239. 239. 57 216. 265. 214. 226. 269. 64 229. 280. 228. 235. 285. 70a PRECOHABITATION b 241. 247 . 286. 302. 241. 246. 285. 250. 251. 303. 227. 222. 210. 220. 244 . 253. 233. 244 . 242 . 235. 217. 228. 259. 267. 246 . 259. 240. 245. 227. 231. 255. 274 . 246. 265 . 245. 251. 231. 236. 275. 291. 262 . 275. 240. 255. 252 . 273 . 257. 278 . 266. 290. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. b. Precohabitation body weights were recorded on the day cohabitation was begun for the FI generation rats; at that time rats were 92 to 106 days of age. these PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E28 (PAGE 1) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 537 RAT # DOSAGE GROUP I 0 MG/KG/DAY PREGNANCY STATUS DAY 0 7 10 1302 P 1304 P 1306 P 1308 P 1310 P 1312 P 1313 P 1316 NP 1318 P 1321 P 1325 P 1328 P 1330 P 1331 P 1334 P 1335 P 1336 P 1338 P 1340 P 1341 P 1342 P 1344 P 1345 P 1346 P 1348 P 1350 P 1353 P 1355 P 1358 NP 1359 P 236. 262. 269. 266. 294. 311. 273 . 306. 314 . 269. 291. 298. 303 . 332. 342 . 305. 327. 338. 264. 288 . 299. 299. 304 . 315. 322. 366. 379. 292. 325. 340. 264. 296. 312 . 284 . 313 . 322. 253 . 274. 285. 277 . 307. 319. 239. 258 . 271. 271. 309. 327. 264. 296. 321. 297. 324 . 336. 282 . 312. 324 . 286 . 314 . 328 . 281. 314 . 334 . 267. 298 . 313 . 293 . 311. 326 . 250 . 278. 291. 271. 306. 314. 292. 321. 329. 255. 293 . 302. 295. 324. 342. MATING NOT CONFIRMED 245. 273 . 284 . 14 287 . 324. 341. 321. 360. 360. 316. 314. 400. 349. 328. 344 . 298. 338 . 286. 333. 336. 354. 351. 345. 346 . 332. 346. 309. 325. 351. 322. 349. 299. 18 324 . 371. 391. 377. 417. 374. 363. 315. 456. 409. 367. 382 . 341. 376. 324 . 390. 396. 412 . 380. 390. 395. 373 . 408 . 344 . 382. 404 . 352. 404 . 343 . 21 366. 410. 441. 451. 385. 400. 308. 498. 454 . 398. 429. 382. 418. 351. 425. 428. 457. 425. 416. 422. 421. 450. 365. 430. 442 . 397. 441. 382. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E28 (PAGE 2) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 538 RAT # PREGNANCY STATUS DAY 0 1362 P 1363 P 1364 P 1367 P 1368 P 1371 P 1375 P 1376 P 1378 NP 1379 P 1381 P 1382 P 1383 P 1384 P 1387 P 1389 P 13 92 P 1393 P 13 97 P 1399 P 1401 P 1404 P 1407 P 1409 P 1410 P 1413 P 1415 P 1416 P 1418 P 248. 277. 272. 225. 246. 305. 277. 318. 292. 303. 255. 264. 275. 237. 300. 301. 322. 278. 290 . 271. 255. 282. 270. 280 . 298. 279. 262. 264. 256. DOSAGE GROUP II 7 268. 298. 299. 262. 289. 333 . 292. 354. 306. 339. 279. 283. 297. 261. 330. 328. 353. 308 . 314 . 297. 279. 320. 290. 306. 333. 310. 292. 303. 278. 10 275. 315. 311. 272. 294 . 355. 303 . 360. 304 . 353 . 277. 297. 310. 276 . 344 . 345. 367. 322 . 340. 307. 299. 334 . 306. 320. 346. 322. 302. 311. 312. 14 289. 327. 324. 292. 311. 376. 324. 378. 306. 370. 298. 310 . 323. 293 . 373. 359. 380. 336. 360. 324 . 309. 365. 320. 341. 361. 334 . 314. 329. 310. 18 309. 379. 376. 334 . 378. 422. 378. 440. 316. 406. 344 . 358 . 367. 347. 434. 418 . 429. 385. 402 . 377. 357. 401. 376. 374 . 415. 363 . 359. 377 . 358. 1 MG/KG/DAY 21 336. 422. 413 . 385. 413. 469. 419. 474 . 309. 440. 381. 400 . 395. 378. 477. 453 . 417. 432 . 415. 443 . 407. 423 . 466. 406. 395. 413 . 395. 25 314. P = PREGNANT NP NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E28 (PAGE 3) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 539 RAT # PREGNANCY STATUS DAY 0 1421 P 1424 P 1426 P 1428 P 1430 P 1431 P 1433 P 1436 P 1437 P 1439 P 1442 P 1443 P 1446 NP 1448 P 1450 P 1452 P 1455 P 1456 P 1458 NP 1459 P 1461 P 1463 P 1465 P 1468 P 1469 P 1472 P 1474 P 1476 P 1477 P 1480 P 264. 275 . 301. 298. 321. 296. 300. 301. 255. 296. 268. 301. 262. 292. 278. 282. 305. 274 . 270. 315. 293 . 274 . 296. 271. 265. 264. 257. 295. 283 . 271. DOSAGE GROUP III 7 282. 297. 342. 320. 348. 322. 324. 340. 285. 323. 303. 318. 287. 316. 297. 312. 338. 301. 297. 345. 315. 298. 318. 304 . 287. 293 . 284 . 330. 299. 300. 10 297. 320. 359. 339. 360. 344 . 335. 352. 299. 335. 314. 329. 293 . 327. 308. 331. 351. 315. 301. 359. 332. 314. 335. 316. 304 . 300. 301. 346. 303. 306. 14 320. 328. 371. 356. 387. 366. 362. 371. 314. 366. 327. 342. 301. 342. 320. 347. 370. 328. 316. 369. 344 . 336. 357. 335. 319. 315. 316. 364. 316. 318. 18 380. 390. 434 . 411. 458. 429. 432. 413 . 361. 424. 356. 390. 295. 406. 369. 395. 411. 365. 321. 420. 382. 396. 416. 379. 368. 356. 362. 411. 370. 370. 3 MG/KG/DAY 21 417. 465. 444 . 4 94 . 472 . 452. 450. 379. 427. 297. 445 . 406. 25 296. 385. 325. 448 . 417. 425. 438. 400. 390. 394 . 334. 407. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E28 (PAGE 4) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 540 RAT # PREGNANCY STATUS DAY 0 1482 P 1483 NP 1486 P 1488 P 1490 P 1491 P 1494 P 1496 P 1497 P 1500 P 1502 P 1505 P 1507 P 1508 P 1511 NP 1513 P 1514 P 1516 P 1517 P 1519 P 1521 P 1523 P 1524 P 1527 P 1528 P 1531 P 1533 P 1534 P 1537 P 1539 P 277. 275. 237. 326. 274 . 259. 296. 271. 304. 252. 296. 272. 262. 296. 296. 275. 294. 281. 310. 261. 242. 252 . 250. 284 . 230. 270. 291. 277. 260. 300. DOSAGE GROUP IV 7 321. 279. 266 . 354. 302. 280. 330. 293. 337. 271. 329. 289. 293. 327. 319. 295. 324 . 304 . 344 . 289. 269. 288. 290. 303 . 259. 306. 324 . 304 . 289. 313 . 10 332. 281. 285. 366. 310. 293 . 337. 308. 348. 286. 339. 299. 299. 344 . 329. 303. 336. 309. 350. 296. 276. 296. 299. 312 . 274 . 316. 339. 309. 304 . 326. 14 358. 284. 308. 381. 340. 304 . 353 . 322 . 365. 308. 351. 314 . 314. 358. 338. 316 . 348 . 334 . 368 . 313 . 289. 313 . 309. 335. 292. 335. 360. 319. 322 . 351. 18 414 . 288 . 352 . 444 . 395. 351. 385. 386. 391. 363. 393 . 366. 369. 399. 338. 372. 402 . 379. 430 . 375. 329. 347. 332. 387. 339. 381. 434 . 373. 371. 399. 10 MG/KG/DAY 21 449. 293. 389. 468. 437. 390. 431. 424 . 426. 400. 430. 399. 437. 339. 407. 437. 25 290. 335. 413. 373 . 384 . 342 . 434 . 360. 429. 459. 407 . 400 . 452 . P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E28 (PAGE 5) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 541 RAT # DOSAGE GROUP V 30 MG/KG/DAY PREGNANCY STATUS DAY 0 7 10 14 18 21 25 1541 P 1544 P 1545 P 1546 P 1548 P 1550 P 1552 P 1555 P 1557 P 1558 P 1560 P 1564 P 1565 P 1566 P 1568 P 1571 P 1573 P 1576 P 1578 NP 1579 P 1583 P 1584 P 1586 P 1587 P 1588 P 1589 P 1591 P 1593 P 1598 P 1600 P 247 . 300. 269. 277. 248. 224. 257. 254. 294. 268. 258. 240 . 237. 288. 280. 236. 299. 244 . 249. 299. 238. 247. 230. 230. 269. 282. 254 . 272 . 268 . 293 . 259. 330. 299. 304 . 274 . 247. 276. 277. 314. 302. 288. 256. 262. 306. 295. 265. 317. 276. 258. 321. 278 . 273 . 260. 260. 295. 315. 282. 292 . 292 . 319. 273. 345. 310. 311. 282. 265. 290. 286. 322. 319. 302. 272. 274 . 318. 308. 280. 334 . 282. 254 . 332. 283. 277. 269. 273. 309. 330. 293 . 308. 308. 332. 287. 371. 334 . 330. 296. 280. 303 . 298. 349. 341. 314. 286. 292. 337. 326. 291. 351. 305. 261. 344 . 301. 289. 284 . 287. 325. 348. 308. 323 . 318. 348. 347. 405. 408. 371. 354. 333 . 343. 338. 406. 393. 368. 338. 340. 384 . 390. 342 . 411. 360. 264 . 408. 356. 324 . 321. 340. 377. 404 . 361. 347. 359. 405. 370. 452. 455. 361. 381. 382. 435. 434 . 401. 373. 377. 427. 430 . 441. 394 . 260. 378 . 332. 359. 368. 401. 395. 366. 416. 453. 268. P - PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E29 (PAGE 1) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 542 RAT # DOSAGE GROUP I 0 MG/KG/DAY DAY 1 5 8 11 15 22 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 267. 284 . 299 . 303 . 304 . 324 . 331. 343. 324 . 338. 346. 363. 302 . 318. 329. 352. 342. 346. 345. 361. 334 . 329. 339. 333 . 292. 308 . 316. 289. NOT PREGNANT 370. 385. 396. 398. 326. 338. 352. 357. 308. 305. 315. 318. 326. 329. 349. 363. 265. 285. 258. 297. 322 . 323 . 330. 336. 276. 272 . 287. 285. 327. 331., 333. 327. 311. 341.. 349. 364. 350. 357., 359. 330. 321. 317,. 325. 357. 328. 331,. 329. 323 . 312. 326 . 325. 321. 314 . 310,, 328. 342. 323 . 338 . 351. 331. 301. 293 . 303. 308. 307. 305 . 321. 348. 329. 330 . 344. 348 . 296. 292 , 299. 328 . 334 . 332 . 349. 352. NOT PREGNANT,; MATING NOT CONFIRMED 271. 279 . 298. 318. 298 . 332. 341. 340. 335. 339. 318. 412. 345. 314. 356. 309. 322 . 307. 346. 331. 377. 354 . 341. 331. 330. 369. 314 . 331. 355. 322. 340. 324 . 284. 320. 335. 357. 331. 336. 298. 369. 329. 323 . 328. 280. 300 . 284 . 324. 331. 345. 338. 316. 294 . 333 . 364 . 325. 339. 339. 293 . 313. 313 . DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E29 (PAGE 2) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 543 RAT # DOSAGE GROUP II DAY 1 5 8 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 273. 277. 303. 323 . 309. 319. 276. 290. 287. 315. 337. 346. 303. 319. 359. 370. NOT PREGNANT 355. 341. 288. 289. 296. 312. 321. 328. 288. 306. 351. 355. 340. 340. 357. 346. 324. 332. 330. 334 . 310. 309. 278 . 305. 337. 341. 299. 316. 327 . 323. 338. 339. 322 . 312. 300. 304. 315. 311. 290. 306 . 284. 319. 326. 307. 339. 358. 328. 369. 362. 299. 323. 333. 313. 367. 363. 356. 338. 355. 322. 315. 344. 328. 333. 356. 336. 321. 319. 319. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). 11 298. 322. 329. 328 . 343 . 372. 332. 384. 385. 312. 336. 344 . 320 . 376. 353 . 362. 345. 345. 336. 306. 359. 335. 337. 359. 360. 320. 321. 326. 1 MG/KG/DAY 15 22 288. 329. 315. 328. 339. 360. 321. 359. 287. 308 . 323. 297. 310. 352. 299. 360. 367. 307. 310. 368 . 312. 358. 357. 361. 355. 365. 318. 310. 349. 344 . 340. 363. 343. 335. 336. 329. 355. 282. 308. 350. 262. 338. 344 . 347. 330. 331. 320. 297. 332. 325. 327. 344 . 320. 339. 303 . 317. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E29 (PAGE 3): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 544 RAT # DOSAGE GROUP III DAY 1 5 8 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 297 ., 312. 326. 321. 368., 364. 341. 338. 366.. 357. 348. 345. 350., 355. 347. 353 . 290.. 309. 340. 352. 309. 312. 327. 342. NOT PREGNANT 328. 326. 307., 313. 324 . 310. 351. 342. 328. 329. NOT PREGNANT 349. 363. 333 ., 349. 316.. 315. 324.. 330. 309. 315. 298. 296. 301. 303. 284.. 289. 348. 326. 297. 313. 309.. 324. 320. 321. 374. 353. 357. 364. 364. 357. 320. 371. 330. 341. 350. 316. 317. 358. 334. 380. 348. 326. 343. 316. 319. 317. 296 . 353. 317. 326. DAY DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . 11 331. 336. 371. 353. 367. 358. 350. 359. 306. 347. 338. 356. 361. 315. 327. 366. 333. 375. 362. 330. 348. 342. 341. 324 . 322. 370. 357. 353 . 3 MG/KG/DAY 15 22 313 . 330. 376. 358. 370. 379 . 337. 347. 314. 370. 338. 357. 326. 307 . 369. 334 . 308. 358. 314 . 341. 311. 361. 344. 336. 344 . 324. 313 . 335. 343 . 343 . 331. 301. 332. 329. 378. 351. 319. 337. 330. 353. 338. 320. 366. 333. 340. 368. 336. 302 . 297. 300. 317. 309. 310. 358. 335. 340. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E29 (PAGE 4) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 545 RAT # DOSAGE GROUP IV DAY 1 5 8 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 322.. 326. NOT PREGNANT 276. 291. 351. 350. 317., 327. 281. 292. 324 . 340. 313 . 310. 347. 342. 287. 300. 343. 344 . 296. 294 . 301.. 308. 353. 348. NOT PREGNANT 293 . 308. 320. 333. 309. 317. 357. 333. 295. 307. 280.. 276. 294 . 306. 321. 318. 325. 333. 282., 291. 319.. 328. 320. 327. 309. 305. 302., 303. 332. 343. 312. 300. 354. 331. 305. 341. 313. 378. 306. 348. 291. 309. 355. 323. 341. 327. 344 . 320. 294 . 319. 311. 328. 284. 341. 342. 318. 310. 363. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . 11 315. 308. 367. 353. 311. 374. 329. 385. 328. 350. 298 . 333. 353 . 341. 358. 347. 351. 328. 299. 327. 318. 355. 306. 349. 336. 313 . 318. 358. 10 MG/KG/DAY 15 22 331. 313. 317. 353. 356. 319. 369. 324. 375. 315. 341. 321. 334 . 332. 316. 359. 368. 316. 353. 319. 355. 302. 322. 318. 341. 338. 317. 343. 329. 346. 322. 314. 328 . 319. 326. 307. 362. 345. 343 . 303. 373 . 250. 325. 316. 325. 317. 312. 313 . 326. 315. 310. 350. 347. 316. 306. 355. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E29 (PAGE 5) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 546 RAT # DOSAGE GROUP V DAY 1 5 8 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 264 . 281. 360. 350. 318. 322. 300. 317. 296. 276. 265. 271. 284 . 302 . 276. 288 . 325. 324. 320. 336. 297. 320. 265. 277. 280. 280. 324. 312. 324. 322 . 292. 279. 341. 334 . 284 . 271. NOT PREGNANT 320 . 328. 306. 308. 296. 291. 270. 272 . 278., 290. 312., 322. 326 ., 317. 296.. 304. 314 . 322. 301,. 302. 325.. 332. 278. 348. 340. 279. 280. 280. 315. 294. 333 . 330. 325. 277. 294. 314. 336. 288. 344 . 288. 327. 319. 295. 286. 286. 321. 334. 310. 318. 303. 344. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . 11 294 . 376. 342. 310. 295 . 276 . 324 . 317. 348. 339. 313. 319. 291. 322 . 343 . 311. 350. 299. 329. 331. 295 . 303 . 282 . 340 . 339 . 322. 328. 320. 373 . 30 MG/KG/DAY 15 22 291. 371. 332. 338. 303 . 293. 310. 285. 329. 343 . 348. 306 . 307 . 320. 338. 289. 355. 303 . 296. 342. 298. 329. 306. 298. 319. 312. 319. 288. 325. 309. 275 . 324 . 339. 304 . 336. 292 . 356. 325. 302. 289. 290. 350. 364. 306. 346. 333 . 364 . 346. 303 . 294 . 294 . 300 . 322. 354 . 318. 342. 317 . 354. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 1) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 547 RAT # DOSAGE GROUP I 0 MG/KG/DAY STATUS DAY 1 - 8 1301 1302 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317 1318 19779 19780 1321 1322 1323 1324 1325 1326 1327 1328 1329 1330 63. 61. 70. 61. 89. 71. 68. 89. 73. 74. 76. 102. 64. 91. 98. 77. 56. 69. 61. 78. 72. 71. 63 . 64. 63 . 64 . 58. 48. 74 . 69. 8 - 1 5 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 110. 112. 115. 117 . 144 . 125. 123 . 115. 113 . 131. 110. 116. 106. 146. 155. 119. 140. 107. 97. 126. 123 . 106. 110. 104 . 96. 120. 102 . 110. 112 . 104 . 128. 125. 133 . 140 . 171. 135. 129. 124. 140. 147. 114. 143 . 123 . 147. 181. 137. 147. 154 . 129. 159. 136. 127. 130. 124 . 134 . 129. 144 . 131. c 126 . 129. 119. 127. 145. 197 . 133. 136. 137. 159. 154 . 120. 147. 126. 183. 174 . 136. 143 . 153. 126. 124 . 121. 112. 136. 134. 155. 132. 116. 146. 118. 132. 131. 131. 163. 180 . 127. 145. 157. 146. 146. 14 8. 122 . 119. 132. 131. 130. 167. 167. 125. 149. 189. 180. 145. 148. 121. 109. 127 . 138 . 193 . 161. 180. 126 . 151. 157. 210. 117. 138. 134 . 130. 193. 168. 129. 148. b 158. 115. 131. 128 . 134 . 162. 181. 127. 141. 169. 159. 102 . 107 . 112 . 109. 125. 141. 112 . 116. 128. 123 . 174 . 156. 130. 164 . 159. 118. 165. 167 . 120 . 106. 142. 108 . --- DAY = DAY POSTWEANING .' ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Soiled feed precluded the calculation of this value. c. Wet feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 2) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 548 RAT # DOSAGE GROUP I 0 MG/KG/DAY STATUS DAY 1 - 8 8 - 1 5 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 65. 57. 60. 55. 71. 64 . 70 . 77 . 62. 57. 72. 73. 77 . 77. 79. 80. 63 . 69. 70. 84 . 80. 80. 55. 76. 84 . 85. 67. 66. 74 . 80. 108 . 119. 104 . 101. 92 . 112 . 105. 118. 107. 106. 128. 107. 131. 129. 127. 124 . 109. 110. 114 . 137 . 136. 124 . 94 . 102 . 124 . 129. 106. 106. 87. 106. 118 . 129. 125. 127. 125. 116. 127. 125. 139. 126. 122. 114 . 142 . 140. 134 . 141. 128 . 123 . 129 . 147 . 148. 143 . Ill. 114 . 140 . 145 . 127. 119. 116 . 133 . 133 . 131. 139. 134 . 126 . 134. 134. 128. 115. 135. 136. 139. 124. 142 . 113. 140. 120. 127. 166. 129. 135. 128. 144 . 127. 135. 124. 145. 146. 146. 163. 139. 114 . 150. 132. 134. 129. 130. 140 . 138. 146. 120. 137. 132. c 151. 145. 125. 133 . 126. 151. 140. 138. b 142. 145. 132 . 171. 140 . 169. 139. b 182. 174. 133 . 160. 121. 154 . 130 . 127 . 137 . 120 . 145. 139. 168. 126. 158. 170. 152. 167. 162 . 132 . 178 . 140 . 167. 125. b 140. 122. 140. 136. 186 . 129. 157. 14 9. 137. b 166. 139. 175. 118. 136. 126. 139. 104 . 108. 130. b 122*. 117. 108. 108 . 99. 130 . 122 . 108. 119. 104 , 129 . 105. 110. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. c. Soiled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 3) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 549 RAT # DOSAGE GROUP II 1 MG/KG/DAY STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 1361 1362 1363 1364 136S 1366 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 1377 1378 1379 1380 1381 1382 1383 1384 1385 1386 1387 1388 1389 1390 63. 98. 117. 114 . 49. 88 . 109. 118. 61. 99. 136 . 127. 57. 91. 133 . 184 . FOUND DEAD ON DAY 4 POSTWEANING 63 . 79. 129. 109. 52. 85. 116. 116 . 69. 115. 142 . 131. 76. 122 . 141. 136. 63. 98. 129. 152. 65. 113. 130. 138 . 73 . 122. 132. 131. 68. 110. 139. 196. 75. 113 . 141. 141. 62. 103 . 130. 140. 66. 95. 105. 127. 44 . 92 . 131. 151. 75. 122. 141. 140 . 69. 116. 146. 136. 56. 104 . 136 . 139 . 62. 101. 124 . 117 . 66. 109. 126 . 141. 49. 94 . 126 . 147 . 54. 89. 118. 130. 80. 122 . 137. 133 . 54. 101. 119. 118. 70. 114 . 136. 134 . 74 . 108 . 131. 130. 71. 106 . c 127. 75. 116. c 130. 119. 133 . 194 . 109. 140. b 145. 221. 134 . 127 . 136. 141. 121. 134 . 131. Ill. 161. 150. 114 . 139. b 116. 144 . 159. 152. 130. 139. 137. 152. 128 . 135 . 133 . 115 . 153 . 151. 118 . 134 . b 109. 150. 175. 137. 132. 169. 148. 164 . 138. 189. 189. 133 . 200. 179. 113 . 136. b 124 . 134 . 157. 181. 116. 89. 108. 157. 108 . 174 . 98 . 148. 150. 157. 127. FOUND DEAD ON DAY 51 POSTWEANING 130. 152. 133 . 151. 113 . 126 . 134 . 156. 141. 157. 125. 129. 134 . 129. 133. 119. 128. 129 . 131. 129. 115. 100 . 108 . 101. 153 . 156. 157. 165. 126. 126 . DAY DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. c. Wet feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 4): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 550 RAT # DOSAGE GROUP II 1 MG/KG/DAY STATUS DAY 1 - 8 8 - 1 5 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 1391 1392 1393 1394 1395 1396 1397 1398 1399 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 1412 1413 1414 1415 1416 1417 1418 1419 1420 68. 61. 65. 64. 59. 72 . 81. 51. 77. 74. 79. 74 . 68. 68. 57. 69. 71. 67. 64 . 68 . 69. 73 . 67. 62. 60. 74 . 72 . 62. 64. 52. 101. 102 . 89. 105. 105. 93 . 126. 102. 118 . 109. 102 . 116. 106. 114 . 91. 106 . 125 . 99. 102 . 108 . 106 . 116 . 114 . 103 . 100. 110. 108 . 95. 102. 99. 129. 137 . 130. 138 . 129. 149. 152. 130 . 136. 129. 125. 126 . 128 . 133 . 123 . 126. 144 . 116. 113 . 132 . 117 . 126 . 143 . 116. 121. 130. 126 . 110. 124 . 120 . 132 . 126 . 127 . 135. 130. 127. 151. 130. 126. 123 . 137. 135. 121. 134 . 142. 123 . 116. 113 . 125. 134 . 147 . 126. 135. 112 . b 148 . 129. 150. 136. 123 . 147. 154. 133 . 140. 130. 133 . 133 . 117. b 127 . 161. 138. 129. 146. 157. 122 . 138. 129. 140. 143 . 120. 159. 122. 152. 142. 154 . 157 . 173 . 136. 144 . 136 . 150 . 137. 252 . 165. 108 . 139. 134. 124. 151. 154 . 151. 143 . 144 . 149. 146. 204 . 176. 129. 135. 126 . 116. 166. 141. 109. 127 . 138. 146. 128 . b 145 . 106. 125. 107 . 108. 123 . 129. b 116. 116. 105. 107. 96. DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 5) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 551 RAT # DOSAGE GROUP Ill 3 MG/KG/DAY STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 1421 1422 1423 1424 1425 1426 1427 1428 1429 1430 1431 1432 1433 1434 1435 1436 1437 1438 1439 1440 1441 1442 1443 1444 1445 1446 1447 1448 1449 1450 61. 99. 124 . 121. 67. 105. 125. 121. 67. 109. 130. 140 . 75. 114 . 131. 139. 66. 116. 149. 173 . 51. 82 . 110. 108 . 68. 120. 144 . 153. 73. 113 . 142. 180. 70. 111. 141. 161. 71. 131. 164 . 185. 51. 103 . 129. 147. FOUND DEAD ON DAY 7 POSTWEANING 73. 115. 129 . 138. 61. 108. 134 . 145. 84. 124 . 149. 170. 73. 129. 142 . 144 . 60. 115. 124. 130. 69. 117. 121. 110. 69. 115. 151. 14 9 . 74 . 127. 146 . 157. 45. 95. 126. 138. 67. 99. 130. 134. 61. 94. 118 . 123 . 49. 93 . 133 . 130. 70. 128 . 173 . 172 . 69. 112 . 120. 121. 64. 105. 125 . c 72. 106 . 134 . 135. 77. 125. c 161. 79. 124. c 124 . 123. 120. 124. 141. 175. 140. 140. 140. 128. 137. 135. 126. 132. 142. b 139. 121. 127. 138. 151. 174 . 145. 137. 130. 123. 215. 162. 129. 130. 145. 140 . 124 . 124 . 150. 149. 164. ISO. 145. 150. 163 . 153 . 158. 140. 235. 177. 135 . 126 . 127. 149. 153 . 162. 151. 149. 143 . 148 . 153 . 136. 137. b 128 . 124 . 127. 124 . 158. 154 . 172. 141. 155. 143 . 132. 177 . 138. 192. 124 . 130. 125. 106. 104 . 123 . 124 . 135. 123 . 117. 130. 108 . 134. 130. 114. 114 . 117. 103. DAY = DAY POSTWEANING ' ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. c. Wet feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 6) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 552 RAT # DOSAGE GROUP III 3 MG/KG/DAY STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 1461 1462 1463 1464 1465 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 1476 1477 1478 1479 1480 85. 70. 89. 74 . 84 . 85. 82. 82. 97. 80. 76. 72. 71. 86. 45. 49. 62. 59. 69. 64. 72 . 71. 80. 78. 62. 75 . 87. 73 . 73 . 67. 127 . 129. 133 . 126 . 129. 117 . 118. 121. 132. 101. 108. 100. 108. 131. 84. 96. 101. 97. 81. 103 . 125 . 120. 132 . 119. 103 . 118 . 123 . 130 . 121. 113 . 146. 133 . 143. 143 . 180. 128. 128 . 145. 145. 135. 131. 123 . 125. 142. 119. 127. 142. 117. 101. 125. 124 . 12 2 . 135. 126. 117 . 145. 131. 147. 136 . 136. 145. 135. 147 . 136. 167. 117 . 120. 145. 160 . 143. 148. 111. 128 . 148. 138. 116. 115. 121. 125. 144 . 135. 132. 276. 202 . 123. 137. 162. 139. 136. 145. 115. 136. 119. 126. 150. 160. 141. 163. 182. b 117. 132. 163 . 147. 138. 157 . 196. 123 . 127. 166 . 147. 156. 191. 125. 134 . 152. 14 9. 130. 1 b 127. 136. 153 . 180 . 162. 196. 158 . 134 . b b 110. 123 . 151. 14 7. 147. b 14 8 . 161. 170 . 146. 150. 157. 126. 205. 189. 122 . 111. 137. 129. 142. 168 . 145 . 159. b b 151. 146. 126. 122 . 153 . 96 . 109. 126 . 116. 129. 129. 109. 104 . 101. 108. 123 . 133 . 119. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). ,' a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 7) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 553 RAT # DOSAGE GROUP IV 10 MG/KG/DAY STATUS DAY 1 - 8 8 - 1 5 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1494 1495 14 96 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 71. 117. 129 . 144 . 83 . 117 . 144 . 140 . 45. 92 . 133 . 135. FOUND DEAD ON DAY 3 POSTWEANING 56. 110 . 145. 170 . 35. 74 . 107. 12 2 . 79. 127 . 138. 137. 73. 132. 140. 145. 67. 105. 139. 145. 64. 116. 147. 169. 73. 10 1. 133 . 120 . 69. 107 . 129. 131. 84. 123 . 150. 140 . 88. 109. 140 . 138. 89. 124 . 128. 125. 82. 116. 133 . 129. 89. 128 . 145 . 146. 36. 103 . 136. 150. 65. 104 . 127. 133 . 65. 91. 179. c 70. 115. 141. 138. 67. 116. 144 . 166 . 69. 104 . 113 . 122 . 76. 10 1. 124 . 134. 65. 110 . 136. 133 . 67. 108 . 111. 124 . 66. 93 . 123 . 130. 85. 127. 139. 152. 80. 103 . 118. 115. 75. 135. 178. 155. 125. 131. 123. 135. 157. 133. 138. 124 . 149. b 165. 131. 124 . 146. 127. 127. 127 . 156. 194. 146 . 168. 129. 149. 142. 177. 139. 126. 146. 130. 125. 128 . 163 . 292. 189. 128 . 131. 165. 187 . 206. 139. 132. 141. 132. 126. 130. 163 . 174. 150. 130. 123 . 149. 138. 149. 140 . 123 . 138. 125. 146 . 129. 168. 118. 146. 139. 124 . 138. 128. 173 . 135. 12 1. 136. 118. 104 . 108. 143 . b 122 . 116. 116. 120 . 109 . 163 . 123 . 104 . 109. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. c . Value was not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 8 ) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 554 RAT # DOSAGE GROUP IV 10 MG/KG/DAY STATUS DAY 1 - 8 8 - 15 15 - 2 2 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 55. 85. 71. 83 . 69. 91. 79. 68. 60. 70. 71. 82. 64. 62. 59. 78. 92. 68. 52. 75 . 71. 75. 81. 71. 68. 67. 58. 62. 69. 70. 105. 124 . 107. 117. 106 . 110 . 120 . 118. 10 1. 125. 95. 129. 10 0 . 76. 96. 116. 124 . 12 2 . 96. 113. 113 . 127. 132. 118. 113. 119. 102 . 110 . 111. 10 2. 119. 134 . 129. 128. 116. 124 . 133. 138. 124. 127. 119. 127. 109. 114. 114. 137. 142. 118. 109. 134 . 140. 142. 144 . 131. 129. 120 . 123. 132. 133. 119. 127. 136. 139. 133 . 115. 126 . 136. 147 . 135. 12 1. 108. 118. 144 . b 140. 129. 123 . 130. 209. 137. 137. 137. 137. 127. 125. 12 1. 115. 130. 138. 114. 145. 151. 133 . 132. 141. 142. 138. 140. 143. 136. 129. 124 . 124 . 137. 148. 116. 143 . 135. 128 . 134 . 165. 143 . 173. 190. 157. 142. 125. b b b b 151. 150. 152. 143. 199. 167. 140 . 161. 166. 146. 145. 130. 138. b b b 2 11. 144 . 153 . 142 . 143 . 166. 136. 177 . 145. 150. 142 . 116. b b 187. b b 137. 151. 148. 176 . 164 . 141. 115. 114 . 128. 119. 10 2. 116. 108. 109. 12 1. 92. 115 . 12 1. 10 1. 119. 127. DAY DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 9) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 555 RAT # DOSAGE GROUP V 30 MG/KG/DAY STATUS 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553 1554 1555 1556 1557 1558 1559 1560 1561 1562 1563 1564 1565 1566 1567 1568 1569 1570 DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 49. 85. 111. 120 . 114. 57. 10 1. 133 . 135. 56. 89. 108 . 110 . 58 . 10 2. 142. 157. 152. 66. 113. 130. 157. 192. 65. 95. 119. 119. 123. 65. 96. 124 . 138. 62. 95. 117 . 128 . 115. 15. FOUND DEAD ON DAY 8 POSTWEANING 57. 92. 107. 115. 104 . 62. 103 . 128. 137. 65. 107. 120 . 123 . 119. 58. 91. 110 . 122 . 66. 104 . 128 . 136. 64. 95. 124 . 138. 118. 70. 96. 110 . 112 . 79. 107. 124 . 124 . 138. 63 . 106. 137. 143 . 136. FOUND DEAD ON DAY 6 POSTWEANING 67. 118. 141. b 137. 72 . 116. 135. 144 . FOUND DEAD ON DAY 2 POSTWEANING FOUND DEAD ON DAY 2 POSTWEANING 65. 10 0 . c 125. 133 . 64. 95. c 123 . 115. 70. 113 . 123 . 131. b 70. 119. 138. 140. 83. 133 . 138. 134 . 138. 79. 118. 122 . 116. 62. 93. 130. 126. 105. 157. 169 . 130. 130. 126. 113. 131. 137. 146. 155. 130. 113 . 139. 143 . 108 . 158. 167. 142. 133 . 12 1. 116. 143 . 149. 248 . 291. 170. 113 . 137. 145. 113 . 168. 181. 141. 133 . 123 . 126. 113 . 133 . b 149. 136. 104 . 140 . 132 . 116. 165. 193. 137. 139. 127. 125. 120 . 130 . 141. 140 . 129. 107. 132. 129. 10 0 . 136. 128. 116. 111. 108. 99. 106. 118. 124 . b 114 . 95. 110 . 109. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. c. Wet feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E30 (PAGE 10) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 556 RAT # DOSAGE GROUP V 30 MG/KG/DAY STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 1571 1572 1573 1574 1575 1576 1577 1578 1579 1580 1581 1S82 1583 1584 1585 1586 1587 1588 1589 1590 1591 1592 1593 1594 1595 1596 1597 1598 1599 1600 60. 88. 110 . 113. 54 . 99. 140 . 146. 66. 116. 143 . 143 . FOUND DEAD ON DAY 3 POSTWEANING FOUND DEAD ON DAY 3 POSTWEANING 49. 82. 114. 123. 53. 94 . 116. 120 . 56. 104 . 12 2 . 143 . 66. 107. 124. 130. 63 . 99. 114. 1 2 1 . 71. 106. 130. 128 . 52. 90. 118. 62. 106. 120 . 115. 60. 94. 118. 126. 62. 106. 131. 61. 93. 113. 114 . 61. 106. 129. 135. 62. 103. 114. 113. 72. 127. 174. 144 . 68. 109. 141. 69. 108. 175. 164. 67. 105. 1 2 0 . 76. 103 . 12 2 . 138. 63 . 103. 112 . 70. 111. 120 . 59. 105. 126. 62. 89. 134. 72. 109. 130. 135. 63 . 108. 128. 68. 104. 119. 133 . 129. 146. 130. 139. 127. 137. 129. 117. 133. 118. 136. 144 . 140. 139. 125. 132. b 141. 125. 134. 136. 135. 12 1. 134 . 128 . 133 . 142 . 132 . 147. 129. 129. 153 . 144 . 148. 137. b 144 . 235. b b b 204 . 135. 149. 132. 12 2 . 155. 137. 107. 13 9. 159. 132. 140 . 153 . 137. b b 165. 156. 145. 51. 158. 129. 117. 128 . b 130. 140. 148. 125. b 156. 151. 146. 145. 175. 134. 111. 94 . b 97. 99. 103 . 113 . 98. b 107. 114 . 130. 126. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. b. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E31 (PAGE 1) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 557 RAT # DOSAGE GROUP I 0 MG/KG/DAY PREGNANCY STATUS DAYS 0 - 7 7 - 10 10 - 14 14 - 18 18 - 2 1 1302 P 1304 P 1306 P 1308 P 1310 P 1312 P 1313 P 1316 NP 1318 P 1321 P 1325 P 1328 P 1330 P 1331 P 1334 P 1335 P 1336 P 1338 P 1340 P 1341 P 1342 P 1344 P 1345 P 1346 P 1348 P 1350 P 1353 P 1355 P 1359 P 125. 156. 149. 156. 175. 167. 146. 141. a 193. 184. 154. 141. 148. 136. 183. 188. 159. 147. 165. 159. 138. 172 . 160. 153. 151. 154. 189. 158. 60. 71. 71. 68. 78. 77. 68. 64. a 93 . 79. 74 . 32. 75. 68. 85. 87. 68. 65 . 77. 72. 88. 73 . 68. 68. 68. 68. 87. 68. 76 . 91. 96. 95. 112 . 114. 92 . 83 . 126 . 112 . 116. 95. 82 . 97. 92 . 111. 114 . 94 . 88 . 89. 94 . 106. 99. 88. 90. 86. 86. 100 . 86. 77. 95. 91. 99. 112 . 105. 90. 63. 119 . 112 . 110 . 89. 76 . 92. 94 . 117. 107. 100 . 82. 98. 91. 95. 110 . 87. 92. 92. 79 . 107. 80. 62. 66. 71. 70. 73 . 74 . 67. 52. 82. 77. 84 . 66. 56. 59. 67. 79. 72 . 81. 56 . 64 . 55 . 69. 83 . 63 . 62. 66. 64 . 77. 70. P = PREGNANT NP = NOT :PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Spilled feed precluded the calculation of this value. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E31 (PAGE 2) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 558 RAT # DOSAGE GROUP II 1 MG/KG/DAY PREGNANCY STATUS DAYS 0 - 7 7 - 10 10 - 14 14 - 18 18 - 2 1 1382 P 1363 P 1364 P 1367 P 1368 P 1371 P 1375 P 1376 P 1378 NP 1379 P 1381 P 1382 P 1383 P 1384 P 1387 P 1389 P 1392 P 1393 P 1397 P 1399 P 1401 P 1404 P 1407 P 1409 P 1410 P 1413 P 1415 P 1416 P 1418 P 123 . a a 13 9. 183. 170. 135. 182. 149. 191. 136. a 144 . 148. 177. 194 . 191. 163. 157. 130. 170. 175. 154. 143. 158. 159. 142. 179. 133. 62. 68. 67. 70 . 78. 95. 59. 81. 55. 87. 58. 62. 67. 62. 83 . 86. 94. 71. 83 . 58. 73 . 85. 65. 71. 69. 73. 67. 74 . 59. 77. 90. 89. 88. 105. 117. 87. 110 . 81. 108. 86. 84. 88 . 80. 117. 108. 118. 88 . 99. 83 . 93 . 124 . 91. 88. 85. 89. 87. 93. 80. 79. 90. 99. 87. 112 . 120 . 84. 106 . 79. 105. 90. 90. 92 . 88. 110 . 109. 108. 93. 102 . 93 . 10 1. 106 . 97. 87. 90. 80. 88. 100 . 80. 70. 61. 52 . 67. 75. 89. 70. 69. 50. 62. 67. 69. 66. 68. 84. 80. b 67. 79. 66. 58. 70. 70. 79. 57. 67. 68. 77. 64 . P = PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. b. Value was not recorded. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E31 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 559 RAT # DOSAGE GROUP III 3 MG/KG/DAY PREGNANCY STATUS DAYS 0 - 7 1421 P 1424 P 1426 P 1428 P 1430 P 1431 P 1433 P 1436 P 1437 P 1439 P 1442 P 1443 P 1446 NP 1448 P 1450 P 1452 P 1455 P 1456 P 1458 NP 1459 P 1461 P 1463 P 1465 P 1468 P 1469 P 1472 P 1474 P 1476 P 1477 P 1480 P a 134. 178. a 173. 158. 159. 184. 146. 168. 193. 145. 136. 123. 128. 160. 183. 158. 152 . 160. 146. 156. a 168 . 129. 133. 135. 163. 147. 165. 7 - 10 10 - 14 14 - 18 18 - 2 1 60. 65. 85. 75. 81. 70. 68. 84. 70. 79. 79. 71. 66. 56. 58. 82. 90. 76. 61. 74. 68 . 73 . 78. a 65. 61. 71. 82. 67. 65. 84 . 82. 104 . 105. 110 . 10 1. 106. 111. 88. 123 . 108. 96. 85. 74 . 80. 100 . 113. 104 . 89. 93 . 92. 10 0 . 102 . 10 1. 87. 86. 86. 104 . 87. 87 . 86. 90. 115. 105. 126. 111. 107 . 93 . 90. 114 . 112 . 99. 73. 96. 89. 10 2. 107. 109. 83 . 99. 92. 112 . 106. 10 0 . 86. 88. 98. 95. 94. 94 . 68. b 87. 72. 79. 87. 75. 64. 61. 77. 82. 72 . 47. 70. 66. b 75. 80. 54. 80. 66. 64. 56. 64. 65. 69. 61. b 69. 70. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. b. Value was not recorded. . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E31 (PAGE 4) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 560 RAT # DOSAGE GROUP IV 10 MG/KG/DAY PREGNANCY STATUS DAYS 0 - 7 7 - 10 10 - 14 14 - 18 18 - 2 1 1482 P 1483 NP 1486 P 1488 P 1490 P 1491 P 1494 P 1496 P 1497 P 1500 P 1502 P 1505 P 1507 P 1508 P 1511 NP 1513 P 1514 P 1516 P 1517 P 1519 P 1521 P 1523 P 1524 P 1527 P 1528 P 1531 P 1533 P 1534 P 1537 P 1539 P 173. 128. a 175. 181. 165. 176. 144 . 168. 157. 192. 153. 136. 135. 143. 158. 150. 155. 159. 125. 132. 150. 164. 148. 145. 145. 150. 139. 175. 165. 75 . 54 . 66. 76. b 84 . 76. 68. 72. 63 . 81. 67. 64. 73 . 68. 70 . 68 . 67. 55 . 55. 58. 68 . 63 . 72 . 60. 73 . 70. 57. 69. 76. 10 1. 73 . 95. 102 . 109. 98. 95. 84 . 94 . 96. 107. 93 . 82 . 10 2. 88. 91. . 86. 97 . 91. 82 . 71. 91. 10 0 . 98. 88. 94 . 104 . 82 . 90 . 99 . 10 1. 72 . 96. 95. 112 . 97. 83. 93 . 89. 96. 117. 96. 82. 97. 77 . 102 . 91. 106 . 98 . 93 . 77. 82 . 95. 99. 85. 91. 105 . 86. 10 0 . 113. 64. 55. 66. 62 . 82 . 68. 61. 70. 61. 70. 78. 64 . b 63 . 52 . 75 . 60. 78. 65. 61. 61. 56. 76. 73 . 61. 81. 61. 63. 61. 84. P = PREGNANT NP = NOT :PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. b. Value was not recorded. . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E31 (PAGE 5) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 561 RAT # DOSAGE GROUP V 30 MG/KG/DAY PREGNANCY STATUS DAYS 0 - 7 1541 P 1544 P 1545 P 1546 P 1548 P 1550 P 1552 P 1555 P 1557 P 1558 P 1560 P 1564 P 1565 P 1566 P 1568 P 1571 P 1573 P 1576 P 1578 NP 1579 P 1583 P 1584 P 1586 P 1587 P 1588 P 1589 P 1591 P 1593 P 1598 P 1600 P 119. 171. 183 . 149. a 147. 143. 130. 135. 168. 170. 150. 12 1. 131. 115. 134. 157. 156. 104. 128. c 168. 136. 143. 136. 166. 158. 144 . 160. 162. 7 - 10 10 - 14 14 - 18 18 - 2 1 63 . 87. 79. 70. 57. a 57. 59. 62. 76. 67. 60. 57. 62. 58. 59. 75. 65. 37. 65. 62. 56. 60. 67. 57. 73 . 72 . 69. 76. 74. 79. 112 . 111. 92. 87. 94. 84 . 78. 83 . 96. 102 . 95. 74. 83 . 92. 84 . 95. 97. 57. 72 . 86. 81. 82 . 93 . 89. 106. 98 . 97 . 94 . 106. 87. 104 . 119. 91. 106 . 10 2. 79. 80. 92. 103. 111. 94 . 81. 86. 96. 96. 106. 104 . 57. 93 . 99. 86. 81. 104 . 92 . 111. 109. 98. 89. 106 . 60. 75. 76. 65. b 66. 58. 63 . 71. 74 . 75 . 75. 66. 60. 69. b 76. 78. 43 . 64 . 74. 62. 56. 78. 67. b 71. 72 . 78. 77. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Wet feed precluded the calculation of this value. b. Value was not recorded. c. Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E32 (PAGE 1) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 562 RAT # DOSAGE GROUP I 0 MG/KG/DAY 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 DAY 1 - 5 5 - 8 8 - 1 1 11 - 15a 118. 118. 145. 185. 125. 148 . 180 . 199. 149. 153. 176. 239. 185. 167. 193 . 255. b 170. 200. 234 . 84 . 10 1. 119. 158. 12 0 . 134 . 138. 186 . NOT PREGNANT 154. 184. 170. 270. 129. 180. 12 0 . 250. 104. 157. 170 . 272. 15. 141. 180 . 277. 90. 117. 163 . 232. 108. 127. 140. 198 . 83 . 107. 126. b 113. 138. 151. 225. 161. 168 . 192. 200 . 195. 190. 150. 254. 125. 132. 165. 306. 110 . 132. 117. 2 11. 113. 150. 133 . 214. 124. 155 . 174 . 244 . 131. 159. 184 . 271. 109. 128. 144 . 227. 103 . 156. 205. 244 . 103 . 151. 183. 245. 115. 98. 159. 273 . 113. 166 . 180. 246. NOT PREGNANT; MATING NOT CONFIRMED 96. 114. 177. 256. -- DAY = DAY OF' LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a . Because it isi presumed that the pups begin to consume maternal were not tabulated on days 15 to 22 of lactation. b. Spilled feed precluded the calculation of this value. feed after day 15 of . lactation, ' maternal feed consumption values PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E32 (PAGE 2) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 563 RAT # DOSAGE GROUP II \ MG/KG/DAY DAY 1 - 5 5-8 8 - 1 1 1 1 - 15a 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 13 92 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 90. 97. 122. 148. 127. 145. 137.. 152. 174. 194. 142. 171. 116. 139. 122. 138. NOT PREGNANT 99. 134. 125. 141. 151. 166. 112 . 148. 160. 123 . 125. 146. 161. 159. 94 . 129 . 97. 142 . 109. 163 . 10 2 . 121. 139. 146. 129. 113 . 161. 163 . 113 . 111. 12 1. 177. 93. 154 . 91. 141. 102 . 156. 118. 160 . 118. 177. 167. 171. 2 10 . 161. 155. 164. 168. 157. 215. 171. 164. 180. 159. 162. 170. 147. 145. 167. 159. 196. 145. 197. 190. 130. 154 . 156. 191 213 197 286 242 278 200 224 252 230 303 259 169 213 230 246 232 263 169 155 257 203 256 242 297 222 210 198 DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). ' a. Because it is presumed that the pups begin to consume maternal feed after day 15 of lactation, maternal feed consumption values were not tabulated on days 15 to 22 of lactation. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E32 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 564 RAT # DOSAGE GROUP III 3 MG/KG/DAY DAY 1 - 5 5 - 8 8 - 1 1 11 - 15a 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 122. 152. 109. 143. 93. 132. 113 . 154 . 108. 127. 133. 154 . 133 . 163 . 109. 117. 128. 152. 109. 148. 118. 121. 123. 155. NOT PREGNANT 107. 150. 99. 124. 80. 114. 110 . 139. 107. 121. NOT PREGNANT 123. 177 . 103 . 126. 110 . 135. 118. 161. 136. 114. b 130. 126. 136. 99. 128. 82. 140. 149. 110 . 147. 159. 186. 162. 157. 181. 160. 171. 169. 143 . 152 . 138. 152. 183 . 177. 141. 157. 167. 133 . 152 . 153 . 175. 179. b 176. 142 . 206. 196. 180. 187. 212 . 189. 230 . 221. 238. 268 . 230. 207. 230. 219. 205. 262. 196. 206. 171. 237 . 198 . 239. 239. 209. 210 . 243 . 256. 233. 246. 276. 307. 241. DAY = DAY OF' LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because it is presumed that the pups begin to consume maternal were not tabulated on days 15 to 22 Of lactation. b. Spilled feed precluded the calculation of this value. feed after day 15 of lactation, maternal feed consumption values PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E32 (PAGE 4) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 565 RAT # DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 - 5 5 8 8 - 1 1 11 - 15a 1482 1483 I486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 100. 121. NOT PREGNANT 134. 158. 102. 158. b 152. 157. 166. 127. 133 . 99. 90. 123. 152. 117. 133. b 149. 118. 130. 92. 169. 96. 122 . NOT PREGNANT 114. 153 . 117. 155. 152. 138., 87. 120 ., 115. 156., 103. 140 ,. 126. 145.. 79. 64.. 123 . 154.. 110. 8 6 ,. 145. 155,. 116. 158,. 82. 130 . 118. 157 . 154. 178 . 160. 178. 178. 176. 188. 154 . 166. 168. 178. 156. 113. 140. 135. 168. 190. 167. 172. 182. 159. 152. 79. 141. 153. 133. 155. 137. 178. 138. 185. 253. 205. 198. 273 . 309. 225 . 238. 252 . 228 . 249. 293 . 143 . 168 . 151. 231. 248 . 278 . 217 . 257 . 112. 153. 237. 274 . 261. 193 . 189 . 289. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED :[N GRAMS (G). a . Because it is presumed that the pups begin to consume maternal were not tabulated on days 15 to 22 Of lactation. b. Spilled feed precluded the calculation of this value. feed after day 15 of lactation, maternal feed consumption values PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E32 (PAGE 5) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 566 RAT # DOSAGE GROUP V 30 MG/KG/DAY DAY 1 - 5 5 - 8 8 - 11 11 - 15a 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 122 . 130. 130. 147. 140. 179. 128. 122 . 75. 113 . 141. 154 . 120. 137. 111. 119. 112. 131. 131. 181. 135. 151. 123 . 118. 110. 123. 101. 111. 121. 119. 84 . 123 . 120 . 148. 92. 116. NOT PREGNANT 108. 142. 127. 144 . 68. 87 . 123 . 129 . 113. 126 . 118. 137 . 91. 137. 140. 145. 129. 120 . 143. 128 . 133. 160. 152. 171. 186 . 112. 152 . 151. 158. 146. 162 . 184. 155. 152. 116. 115. 162 . 168 . 177 . 145 . 155 . 169 . 91. 164 . 128 . 132 . 143 . 182 . 131. 153 . 170 . 216. 289. 257. 205. 246. 203 . 181. 179. 207. 218. 241. 263 . 189. 224. 216. 174. 223 . 197. 194 . 167. 134 . 173 . 173 . 273 . 237. 192. 129. 225 . 234 . DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Because it is presumed that the pups begin to consume maternal were not tabulated on days 15 to 22 of lactation. feed after day 15 of lactation, ' maternal feed consumption values PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E33 (PAGE 1) : SEXUAL MATURATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 567 DOSAGE GROUP - MG/KG/DAY I II III 0 13 VAGINAL RAT # PATENCY (DAY) VAGINAL RAT # PATENCY (DAY) VAGINAL RAT # PATENCY (DAY) RAT # 1301 1302 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317 1318 19779 19780 1321 1322 1323 1324 1325 1326 1327 1328 1329 1330 37 37 36 38 36 35 36 36 35 34 36 36 35 31 29 31 34 34 36 36 31 31 31 35 36 35 34 34 36 36 1361 1362 1363 1364 1365 - 1366 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 1377 1378 1379 1380 1381 1382 1383 1384 1385 1386 1387 1388 1389 1390 35 37 37 37 a 35 35 35 34 37 35 36 36 38 38 38 38 36 34 37 37 38 39 36 33 34 36 32 31 36 1421 1422 1423 1424 1425 1426 1427 1428 1429 1430 1431 1432 1433 1434 1435 1436 1437 1438 1439 1440 1441 1442 1443 1444 1445 1446 1447 1448 1449 1450 37 36 33 34 35 35 33 34 35 36 38 C 35 36 33 33 33 33 35 33 37 36 40 35 34 35 35 33 32 34 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 DAY = DAY POSTPARTUM a. Rat was found dead before the start of sexual maturation evaluation. b. Sexual maturation testing was discontinued before rat became sexually mature. c. Rat was found dead. IV 10 VAGINAL PATENCY (DAY) 35 34 41 a 36 43 32 35 b 37 33 34 35 33 35 32 34 36 35 35 36 36 36 35 36 34 37 34 ' 33 34 RAT # 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553 1554 1555 1556 1557 1558 1559 1560 1561 1562 1563 1564 1565 1566 . 1567 1568 1569 1570 V 30 VAGINAL PATENCY (DAY) 42 37 40 36 36 35 38 35 c 37 39 36 43 38 40 35 36 36 c 34 36 a a 39 37 35 32 31 34 36 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E33 (PAGE 2) : SEXUAL MATURATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 568 DOSAGE GROUP - MG/KG/DAY I II III IV V 0 1 3 10 30 VAGINAL RAT # PATENCY (DAY) VAGINAL RAT # PATENCY (DAY) VAGINAL RAT # PATENCY (DAY) VAGINAL RAT # PATENCY (DAY) VAGINAL RAT # PATENCY (DAY) 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 38 36 36 40 35 34 35 35 36 35 34 36 33 34 38 34 36 36 37 31 34 33 33 34 35 32 36 37 37 36 1391 1392 1393 1394 1395 1396 1397 1398 1399 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 1412 1413 1414 1415 1416 1417 1418 1419 1420 36 35 39 35 35 32 32 38 34 35 38 33 32 35 43 37 30 38 b 34 33 34 36 37 37 35 34 35 35 34 1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 1461 1462 1463 1464 1465 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 1476 1477 1478 1479 1480 31 31 29 29 29 35 36 35 33 31 38 31 31 31 41 39 34 b 34 34 34 38 34 32 35 34 30 32 33 35 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 34 35 36 31 34 37 34 35 36 32 31 35 36 35 37 32 33 35 39 34 34 34 32 34 33 34 35 37 34 35 1571 1572 1573 1574 1575 1576 1577 1578 1579 1580 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 1592 1593 1594 1595 1596 1597 1598 1599 1600 37 36 36 a a 41 40 39 34 36 34 39 38 38 38 38 36 37 31 37 35 35 36 38 34 36 38 35 37 35 DAY - DAY POSTPARTUM a. Rat was found dead before the start of sexual maturation evaluation. b. Sexual maturation testing was discontinued before rat became sexually mature. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E34 (PAGE 1): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 569 DOSAGE GROUP I 0 MG/KG/DAY RAT # 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 ESTROUS STAGES/ 21 DAYS 6 5 6 5 5 4 3 5 3 4 6 6 5 3 5 5 5 5 3a 5 4 5 4 5 5 5 4 5 5 4 DAYS IN COHABITATION 4 2 4 2 3 1 2 1 2 3 1 4 3 4 2 3 3 2 5 2 2 4 2 1 1 2 5 3 14 4 MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M DID NOT MATE M MATING DATE C C C C C C C C C C C C C C C C c c c c c c c c c c c c - c M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS a. Six or more consecutive days of diestrus were observed. NP = NOT PREGNANT PREGNANCY STATUS P P P P P P P NP P P P P P P P P P P P P P P P P P P P P NP P ESTROUS STAGE AT SACRIFICE MET E D D E MET D D D E D E D D D D MET D D E E D D D MET D PRO D PRO D PROTOCOL 418-020: ORAL (GAVAGE) TWO -GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E34 (PAGE 2) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 570 DOSAGE GROUP II 1 MG/KG/DAY RAT # ESTROUS STAGES/ 21 DAYS DAYS IN COHABITATION MATING STATUS MATING DATE 1362 1363 1364 1367 1368 1371 1373 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 64 53 53 64 53 54 FOUND DEAD ON DAY 51 POSTWEANING 62 54 63 64 64 53 42 52 53 32 64 52 62 53 52 54 53 36 33 64 41 51 52 M M M M M M M M M M M M M M M M M M M M M M M M M M M M M C C C C C C C C C C C C C C C C C C c c c c c c c c c c c M = MATED C - CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP NOT PREGNANT PRO = PROESTRUS E ESTRUS MET = METESTRUS D = DIESTRUS PREGNANCY STATUS P P P P P P P P NP P P P P P P P P P P P P P P P P P P P P. ESTROUS STAGE AT SACRIFICE E E MET E D D D D E MET D D D E E D D E MET D E D D D E E D PRO D PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E34 (PAGE 3): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 571 DOSAGE GROUP III 3 MG/KG/DAY RAT # ESTROUS STAGES/ 21 DAYS DAYS IN COHABITATION 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 6 4 6 5 5 4 6 6 6 5 5 4 4 4 5 4 6 5 5 4 5 6 5 6 4 5 5 6 6 4 1 2 1 3 2 1 3 4 4 3 1 2 4 2 3 2 4 1 1 2 3 2 2 4 1 4 2 4 4 1 M = MATED C = CONFIRMED NC = NOT CONFIRMED PRO = PROESTRUS E ESTRUS MET = METESTRUS MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M P = PREGNANT D = DIESTRUS MATING DATE C C C C C C C c c c c c c c c c c c c c c c c c c c c c c c NP = NOT PREGNANT PREGNANCY STATUS P P P P P P P P P P P P NP P P P P P NP P P P P P P P P P P P. ESTROUS STAGE AT SACRIFICE D D D MET E D PRO D D MET D PRO D D D D D E D D D E D PRO E D D E D D PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E34 (PAGE 4) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 572 DOSAGE GROUP IV 10 MG/KG/DAY RAT # 1482 1483 1486 1488 1490 1491 1494 14 96 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 ESTROUS STAGES/ 21 DAYS 6 5 5 6 7 5 4 5 5 5 2a 5 6 6 3 3 5 6 6 5 6 6 6 5 5 4 5 5 5 4 DAYS IN COHABITATION 1 1 1 1 1 2 4 2 4 3 1 3 4 4 7 2 2 4 1 1 4 4 1 4 3 4 3 1 3 5 MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS a. Six or more consecutive days of diestrus were observed. MATING DATE C C C C C C C C C C C C C C C C C C C c c c c c c c c c c c NP = NOT PREGNANT PREGNANCY STATUS P NP P P P P P P P P P P P P NP P P P P P P P P P P P P P P P. ESTROUS STAGE AT SACRIFICE D E E D D E D PRO E D PRO D D D D D D D E D D MET E D D D D D D D PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E34 (PAGE 5): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 573 DOSAGE GROUP V 30 MG/KG/DAY RAT # 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 ESTROUS STAGES/ 21 DAYS 6 6 5 6 5 6 6 6 5 6 6 5 5 5 5 5 5 5 6 6 5 7 6 5 5 4 4 5 5 6 DAYS IN COHABITATION 2 5 3 4 3 1 3 4 2 1 1 3 2 4 3 3 2 1 3 2 1 1 4 i 3 3 2 1 4 4 MATING STATUS M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT PRO - PROESTRUS E = ESTRUS MET * METESTRUS D = DIESTRUS MATING DATE C C C C C C C C C C C C C C c c c c c c c c c c c c c c c c NP = NOT PREGNANT PREGNANCY STATUS P P P P P P P P P P P P P P P P P P NP P p p p p p p p p p p. ESTROUS STAGE AT SACRIFICE D MET D D D D E D D D D PRO D D D D E D E D D D D PRO D D D E D D PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 1) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a ARGUS 418-020 Page 574 1301 1302 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317 1318 19779 DP 32 DL 22 DP 32 DL 22 DP 32 DL 22 DP 31 DL 22 DP 31 DL 22 DP 31 DL 22 DL 22 DP 30 DP 30 DG 25 DP 30 DL 22 DP 28 - P - P P - P - P P P - - NP - P - 31 ALL TISSUES APPEARED NORMAL. 130 ALL TISSUES APPEARED NORMAL. 31 ALL TISSUES APPEARED NORMAL. 128 ALL TISSUES APPEARED NORMAL. 31 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 107 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 19780 DP 28 - 27 SPLEEN: SMALL (0.099 G ) . ALL OTHER TISSUES APPEARED NORMAL 1321 1322 1323 1324 1325 1326 1327 1328 1329 1330 DL 22 DP 30 DP 30 DP 30 DL 22 DP 30 DP 30 DL 22 DP 29 DL 22 P P P P 126 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 124 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 128 ALL TISSUES APPEARED NORMAL.. 28 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. DP DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Refer to the individual clinical observationa table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 575 DOSAGE GROUP DOSAGE (MG/KG/DAY) I 0 CONT. RAT NUMBER 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a DL 22 DP 29 DP 29 DL 22 DL 22 DL 22 DP 28 DL 22 DP 28 DL 22 DL 22 DL 22 DP 28 DL 22 DL 22 DL 22 DP 28 DL 22 DP 28 DL 22 DP 28 DP 27 DL 22 DP 27 DL 22 DP 27 DP 24 DP 114 DL 22 DP 18 P - - P P P - P - P P P - P P P - P - P - P - P - - NP P - 126 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 124 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 122 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 26 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 26 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 26 ALL TISSUES APPEARED NORMAL. 23 ALL TISSUES APPEARED NORMAL. 113 ALL TISSUES APPEARED NORMAL. 116 ALL TISSUES APPEARED NORMAL. 17 ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION ' a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 576 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a II 1 1361 DP 32 - 31 ALL TISSUES APPEARED NORMAL. 1362 DL 22 P 130 NECROPSY OBSERVATIONS! WERE NOT RECORDED. 1363 1364 DL 22 DL 22 P P 129 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEARED NORMAL. 1365 1366 1367 1368 1369 1370 1371 1372 DP 4 DP 32 DL 22 DL 22 DP 32 DP 31 DL 22 DP 31 - _ P P - P - 3 FOUND DEAD ON DAY 4 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 31 ALL TISSUES APPEARED NORMAL. 130 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEARED NORMAL. 31 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 128 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 1373 DP 51 - 1374 1375 1376 1377 1378 1379 1380 1381 1382 1383 1384 DP 31 DL 22 DL 22 DP 31 DG 25 DL 22 DP 31 DL 22 DL 22 DL 22 DL 22 _ P P - NP P - P P P P 50 FOUND DEAD ON DAY 51 POSTWEANING. STOMACH: DISTENDED. INTESTINES : DISTENDED. LUNGS: DORSAL SURFACE, RIGHT APICAL LOBE, DEPRESSED WHITE AREA (0.3 CM IN DIAMETER). ALL OTHER TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 128 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 110 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEALED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEARED NORMAL. 128 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. DP * DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 4) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 577 DOSAGE GROUP (MG/KG/DAY) II 1 CONT. RAT NUMBER 1385 1386 1387 1388 1389 1390 1391 1392 1393 1394 1395 1396 1397 1398 1399 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 1412 1413 1414 DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a DP 31 DP 31 DL 22 DP 30 DL 22 DP 30 DP 30 DL 22 DL 22 DP 30 DP 30 DP 30 DL 22 DP 30 DL 22 DP 30 DL 22 DP 29 DP 29 DL 22 DP 29 DP 29 DL 22 DP 29 DL 22 DL 22 DP 28 DP 28 DL 22 DP 28 P P " P P " P P P P * P P P P - 30 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 124 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 1415 DL 22 P 1 2 2 LIVER: LEFT LATERAL LOBE, FIRM MASS (2.0 CM X 1 .2 CM X 0 .4 CM) , CUT SURFACE REVEALED YELLOW AND DARK RED AREAS; CAUDATE LOBE ADHERED TO LEFT LATERAL LOBE. ALL OTHER TISSUES APPEARED NORMAL. DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL DAY OF LACTATION a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 5) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a II 1 CONT. 1416 1417 1418 1419 1420 DL 22 DP 28 DL 22 DP 28 DP 28 P - P - - 1 2 2 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL DP : DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a . Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. ARGUS 418-020 Page 578 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 6 ) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 579 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a III 1421 1422 1423 1424 1425 1426 1427 DL 2 2 DP 32 DP 31 DL 2 2 DP 31 DL 2 2 DP 31 P P P - 126 ALL TISSUES APPEARED NORMAL. 31 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 1428 DL 2 2 P 127 KIDNEYS: BILATERAL, PELVIS, SLIGHT DILATION ALL OTHER TISSUES APPEARED NORMAL. 1429 1430 1431 DP 31 DL 2 2 DL 2 2 - P P 30 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 1432 DP 7 " 6 FOUND DEAD ON DAY 7 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1433 1434 1435 1438 1437 1438 1439 1440 1441 1442 1443 1444 1445 1446 1447 1448 1449 DL 2 2 DP 31 DP 31 DL 2 2 DL 2 2 DP 31 DL 2 2 DP 31 DP 31 DL 2 2 DL 2 2 DP 30 DP 30 DG 25 DP 30 DL 2 2 DP 30 P P P P P P NP - P - 127 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEARED NORMAL. 128 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL.. 29 ALL TISSUES APPEARED NORMAL. 1 1 0 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. DP DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE E35 (PAGE 7) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 580 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a III 3 CONT. 1450 1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 1461 1462 1463 1464 1465 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 1476 1477 1478 1479 1480 DL 22 DP 30 DL 22 DP 30 DP 30 DL 22 DL 22 DP 29 DG 25 DL 22 DP 29 DL 22 DP 29 DL 22 DP 29 DL 22 DP 28 DP 28 DL 22 DL 22 DP 28 DP 28 DL 22 DP 28 DL 22 DP 28 DL 22 DL 22 DP 27 DP 24 DL 22 P P P P NP P P P P P P P P P P P 126 ALL TISSUES APPEARED NORMAL 29 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 29 ALL TISSUES APPEARED NORMAL 29 ALL TISSUES APPEARED NORMAL 127 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 28 ALL TISSUES APPEARED NORMAL 106 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 28 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 28 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 28 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 123 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 126 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 123 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 26 ALL TISSUES APPEARED NORMAL 23 ALL TISSUES APPEARED NORMAL 119 ALL TISSUES APPEARED NORMAL DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 8 ) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 581 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a IV 1481 1482 1483 DP 31 DL 2 2 DG 25 P NP 30 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 108 ALL TISSUES APPEARED NORMAL. 1484 DP 3 - 2 FOUND DEAD ON DAY 3 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1485 I486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508 DP 31 DL 2 2 DP 31 DL 2 2 DP 30 DL 2 2 DL 2 2 DP 30 DP 30 DL 2 2 DP 30 DL 2 2 DL 2 2 DP 30 DP 30 DL 2 2 DP 30 DL 2 2 DP 29 DP 29 DL 2 2 DP 29 DL 2 2 DL 2 2 - P - P P P P P P - - P P P - P P 30 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. DP DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a * Refer to the Individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 9) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 CD 00 CO c* Page 582 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a 10 CONT. 1509 1510 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 DP 29 DP 29 DG 25 DP 29 DL 2 2 DL 2 2 DP 29 DL 2 2 DL 2 2 DP 29 DL 2 2 DP DL 2 2 DP 28 DL 2 2 DL 2 2 DP 28 DP 28 DL 2 2 DL 2 2 DP 28 DP 28 DL 2 2 DP 28 DL 2 2 DL 2 2 DP DP DL 2 2 DP 28 DL 2 2 DP 28 NP P P P P P P P P P P P - P P P P - 28 ALL TISSUES APPEARED NORMAL 28 ALL TISSUES APPEARED NORMAL 1 1 2 ALL TISSUES APPEARED NORMAL 28 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 28 ALL TISSUES APPEARED NORMAL 126 ALL TISSUES APPEARED NORMAL 1 2 2 ALL TISSUES APPEARED NORMAL 28 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 126 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 125 ALL TISSUES APPEARED NORMAL 1 2 2 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 124 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL 127 ALL TISSUES APPEARED NORMAL 27 ALL TISSUES APPEARED NORMAL DP = DAY POSTWEANING DG DAY OF PRESUMED GESTATION DL = DAY OF LACTATION . Refer to the Individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 10) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a ARGUS 418-020 Page 583 1541 1542 1543 1544 1545 1546 1547 1548 DL 2 2 DP 32 DP 32 DL 2 2 DL 2 2 DL 2 2 DP 31 DL 2 2 P P P P P 128 ALL TISSUES APPEARED NORMAL. 31 ALL TISSUES APPEARED NORMAL. 31 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 128 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 1549 DP 8 - 7 FOUND DEAD ON DAY 8 POSTWEANING ALL TISSUES APPEARED NORMAL. 1550 1551 1552 1553 1554 1555 1556 1557 1558 DL 2 2 DP 31 DL 2 2 DP 31 DP 31 DL 2 2 DP 30 DL 2 2 DL 2 2 P P P P P 126 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 30 ALL TISSUES APPEARED NORMAL. 128 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 124 ALL TISSUES APPEARED NORMAL. 1559 DP 6 - 5 FOUND DEAD ON DAY 6 POSTWEANING ALL TISSUES APPEARED NORMAL. 1560 1561 DL 2 2 DP 30 P - 125 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 1562 DP 2 - 0 FOUND DEAD ON DAY 2 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1563 DP 2 - 0 FOUND DEAD ON DAY 2 POSTWEANING ALL TISSUES APPEARED NORMAL. 1564 1565 DL 2 2 DL 2 2 P P 127 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-68 89.6) TABLE E35 (PAGE 11) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 584 DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a V 30 CONT. 1566 1567 1568 1569 1570 1571 1572 1573 DL 22 DP 30 DL 22 DP 30 DP 30 DL 22 DP 30 DL 22 P - P - P - P 128 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 127 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 1574 DP 3 - 3 FOUND DEAD ON DAY 3 POSTWEANING (DEATH OCCURRED 67 MINUTES AFTER DOSAGE ADMINISTRATION) . ALL TISSUES APPEARED NORMAL. 1575 DP 3 - 2 FOUND DEAD ON DAY 3 POSTWEANING (DEATH OCCURRED OVERNIGHT) . ALL TISSUES APPEARED NORMAL. 1576 1577 1578 1579 1580 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 1592 DL 22 DP 29 DG 25 DL 22 DP 29 DP 29 DP 28 DL 22 DL 22 DP 28 DL 22 DL 22 DL 22 DL 22 DP 28 DL 22 DP 28 P - NP p - - p p - p p p p - p - 124 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 108 ALL TISSUES APPEARED NORMAL. 124 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 28 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 1 2 2 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 126 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL, 27 ALL TISSUES APPEARED NORMAL. 124 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING DG DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Refer to the Individual clinical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E35 (PAGE 12) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS DOSAGE GROUP DOSAGE (MG/KG/DAY) RAT NUMBER DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a V 30 CONT. 1593 DL 22 P 123 KIDNEYS: RIGHT, PELVIS, MODERATE DILATION. URINARY BLADDER: WALLS THICKENED. URETER: BILATERAL, MODERATE DILATION; ONE CALCULI LOCATED AT THE CAUDAL END (1.0 CM X 0.5 C M ) . ALL OTHER TISSUES APPEARED NORMAL. 1594 1595 1596 1597 1598 1599 1600 DP 28 DP 28 DP 28 DP 27 DL 22 DP 26 DL 22 - P - P 27 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 26 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 25 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. ARGUS 418-020 Page 585 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 586 DOSAGE GROUP I 0 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. TBW 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 284. 0.022 7.75 2.10 320. 0.021 6.56 2.10 335. 0.017 5.07 2.05 357. 0.018 5.04 2.01 331. 0.014 4.23 1.99 336. 0.022 6.55 2.15 298. 0.020 6.71 2.14 NOT PREGNANT 369. 0.017 4.61 2.06 329. 0.014 4.26 2.05 323 . 0.009 2.79 2.00 328. 0.015 4.57 2.09 280. 0.018 6.43 2.00 300. 0.018 6.00 2.33 284 . 0.016 5.63 1.96 324 . 0.012 3.70 1.93 331. 0.016 4.83 2.06 345. 0.022 6.38 2.10 338. 0.015 4.44 2.07 316. 0.029 9.18 2.06 294. 0.023 7.82 1.93 333 . 0.020 6.01 2.26 364 . 0.014 3.85 2.03 325. 0.018 5.54 2.03 339. 0.015 4.42 2.05 339. 0.016 4.72 2.03 293. 0.024 8.19 2.22 313. 0.007 2.24 2.04 NOT PREGNANT; MATING NOT CONFIRMED 313. 0.017 5.43 2.10 0.74 0.66 0.61 0.56 0.60 0.64 0.72 0.56 0.62 0.62 0.64 0.71 0.78 0.69 0.60 0.62 0.61 0.61 0.65 0.66 0.68 0.56 0.62 0.60 0.60 0.76 0.65 0.67 LIVER ABS. WT. REL. % TBW 14.52 17.50 17.30 18.06 18.04 14.95 15.73 5.11 5.47 5.16 5.06 5.45 4.45 5.28 17.38 18.67 17.15 17.40 12.61 14.43 15.10 15.81 17.19 18.61 16.97 16.15 14.09 17.38 17.73 17.30 18.89 18.24 15.33 16.3 9 4.71 5.67 5.31 5.30 4.50 4.81 5.32 4.88 5.19 5.39 5 .02 5.11 4.79 5.22 4.87 5.32 5.57 5.38 5.23 5.24 15.16 4.84 KIDNEY LEFT ABS. REL. WT. % TBW 1.30 1.38 1.45 1.29 1.30 1.24 1.26 0.46 0.43 0.43 0.36 0.39 0.37 0.42 1.53 1.36 1.35 1.41 1.22 1.11 1.26 1.28 1.42 1.56 1.60 1.17 1.22 1.61 1.28 1.35 1.46 1.37 1.54 1.40 0.41 0.41 0.42 0.43 0.44 0.37 0.44 0.40 0.43 0.45 0.47 0.37 0.41 0.48 0.35 0.42 0.43 0.40 0.52 0.45 1.35 0.43 KIDNEY RIGHT ABS. REL. W T . % TBW 1.38 1.40 1.55 1.32 1.33 1.36 1.28 0.48 0.44 0.46 0.37 0.40 0.40 0.43 1.43 1.46 1.39 1.47 1.17 1.26 1.22 1.40 1.46 1.53 1.65 1.18 1.25 1.41 1.32 1.41 1.57 1.42 1.31 1.38 0.39 0.44 0.43 0.45 0.42 0.42 0.43 0.43 0.44 0.44 0.49 0.37 0.42 0.42 0.36 0.43 0.46 0.42 0.45 0.44 1.31 0.42 ADRENAL LEFT ABS. REL. WT. % TBW , 0.027 0.044 0.050 0.041 0.040 0.036 0.036 9.51 13.75 14.92 11.48 12.08 10.71 12.08 0.039 0.047 0.044 0.044 0.047 0.041 0.036 0.036 0.046 0.051 0.043 0.039 0.039 0.053 0.047 0.052 0.055 0.063 0.038 0.037 10.57 14.28 13.62 13.41 16.78 13.67 12.68 11.11 13.90 14.78 12.72 12.34 13.26 15.92 12.91 16.00 16.22 18.58 12.97 11.82 0.031 9.90 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. A B S . WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 2) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 587 DOSAGE GROUP I 0 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. WT. REL. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. WT. % TBW 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 284. 0.028 9.86 0.63 320. 0.038 1 1 . 8 8 0.53 335. 0.037 11.04 0.59 357. 0.041 11.48 0.72 331. 0.047 14.20 0.66 336. 0.035 10.42 0.57 298. 0.030 10.07 0.62 NOT PREGNANT 369. 0.036 9.76 0.64 329. 0.041 12.46 0.71 323. 0.035 10.84 0.57 328. 0.047 14.33 0.61 280. 0.040 14.28 0.56 300. 0.037 12.33 0.56 284. 0.031 10.92 0.52 324. 0.037 11.42 0.56 331. 0.043 12.99 0.47 345. 0.047 13.62 0.65 338. 0.041 12.13 0.76 316. 0.037 11.71 0.55 294 . 0.036 12.24 0.60 333 . 0.048 14.41 0.64 364. 0.041 11.26 0.65 325. 0.047 14.46 0.52 339. 0.052 15.34 0.57 339. 0.062 18.29 0.66 293. 0.035 11.94 0.52 313. 0.031 9.90 0.43 NOT PREGNANT; MATING NOT CONFIRMED 313 . 0.034 1 0 . 8 6 0.64 0.22 0.16 0.18 0.20 0.20 0.17 0.21 0.17 0.22 0.18 0.18 0.20 0.19 0.18 0.17 0.14 0.19 0.22 0.17 0.20 0.19 0.18 0.16 0.17 0.19 0.18 0.14 0.20 0.13 0.26 0.21 0 .11 0.18 0.26 0.30 0.24 0.16 0.23 0.15 0.16 0.20 0.22 0.20 0.10 0.19 0.30 0.31 0.20 0.20 0.13 0.20 0.18 0.15 0.26 0.12 0.25 0.04 0.08 0.06 0.03 0.05 0.08 0.10 0.06 0.05 0.07 0.04 0.06 0.07 0.08 0.06 0.03 0.06 0.09 0.10 0.07 0.06 0.04 0.06 0.05 0.04 0.09 0.04 0.08 0.054 0.053 0.045 0.033 0.045 0.054 0.043 0.055 0.045 0.037 0.044 0.040 0.050 0.029 0.039 0.047 0.044 0.070 0.057 0.058 0.068 0.049 0.085 0.063 0.052 0.061 0.045 0.046 19.01 16.56 13.43 9.24 13.60 16.07 14.43 14.90 13.68 11.46 13.41 14.28 16.67 10.21 12.04 14.20 12.75 20.71 18.04 19.73 20.42 13.46 26.15 18.58 15.34 20.82 14 .38 14.70 0.068 0.063 .057 .042 .04 9 .054 .050 23.94 19.69 17.01 11.76 14.80 16.07 16.78 0.054 0.051 .032 .053 .046 .050 .033 .058 .055 .047 .092 .064 .034 0.042 0.055 0.061 0.062 0.060 0.075 0.050 14.63 15.50 9.91 16.16 16.43 16.67 11.62 17.90 16.62 13.62 27.22 20.25 11.56 12.61 15.11 18.77 18.29 17.70 25.60 15.97 0.053 16.93 0.48 0.80 0.65 0.34 0.70 0.45 0.58 49 38 78 87 33 66 0.40 0.48 39 30b 79 51 53 70 32b 42 60 43 52 42 0.74 0.17 0.25 0.19 0.10 0.21 0.13 0.19 0.13 0.12 0.24 0.26 0.12 0.22 0.14 0.15 0.12 09 23 16 18 21 09 13 0.18 0.13 0.18 0.13 0.24 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT . a . Value was multiplied by 1 0 0 0 . b. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION {ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 3) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 588 DOSAGE GROUP II RAT TERMINAL BODY NUMBER WEIGHT PITUITARY ABS. WT. REL. % TBW a 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 287. 0.015 308. 0.017 323. 0.019 297. 0.016 310. 0.014 352. 0.013 299. 0.017 360. 0.014 NOT PREGNANT 355. 0.021 282. 0.016 308. 0.017 350. 0.023 262. 0.014 338. 0.012 344. 0.017 347. 0.021 330. 0.013 331. 0.018 320. 0.013 297. 0.014 332. 0.017 325. 0.015 327. 0.015 344. 0.019 320. 0.015 339. 0.011 303. 0.018 317. 0.013 5.23 5.52 5.88 5.39 4.52 3.69 5.68 3.89 5.92 5.67 5.52 6.57 5.34 3.55 4.94 6.05 3.94 5.44 4.06 4.71 5.12 4.62 4.59 5.52 4.69 3.24 5.94 4.10 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. 1 MG/KG/DAY BRAIN ABS. WT. REL. TBW 2.09 2.13 2.10 1.98 1.95 2.34 2.00 2.05 0.73 0.69 0.65 0.67 0.63 0.66 0.67 0.57 2.32 2.13 2.06 1.97 1.94 2.06 2.04 2.23 2.02 2.10 2.26 1.95 2.03 2.07 2.06 2.05 2.29 1.92 2.23 2.15 0.65 0.76 0.67 0.56 0.74 0.61 0.59 0.64 0.61 0.63 0.71 0.66 0.61 0.64 0.63 0.60 0.72 0.57 0.74 0.68 LIVER ABS. WT. REL. % TBW 14.91 15.01 17.48 13.92 15.62 19.98 14.17 16.89 5.20 4.87 5.41 4.69 5.04 5.68 4.74 4.69 14.44 13.26 15.82 17.23 12.14 17.48 16.17 18.85 16.60 17.41 16.58 13.63 15.01 15.09 15.90 18.06 16.36 17.79 15.44 15.71 4.07 4.70 5.14 4.92 4.63 5.17 4.70 5.43 5.03 5.26 5.18 4.59 4.52 4.64 4.86 5.25 5.11 5.25 5.10 4.96 KIDNEY LEFT ABS. REL. WT. TBW 1.29 1.42 1.39 1.35 1.45 1.58 1.25 1.67 0.45 0.46 0.43 0.45 0.47 0.45 0.42 0.46 1.49 1.52 1.37 1.52 1.08 1.26 1.33 1.62 1.25 1.49 1.38 1.28 1.16 1.40 1.22 1.45 1.46 1.51 1.48 1.22 0.42 0.54 0.44 0.43 0.41 0.37 0.39 0.47 0.38 0.45 0.43 0.43 0.35 0.43 0.37 0.42 0.46 0.44 0.49 0.38 KIDNEY RIGHT ABS. REL. WT. % TBW 1.28 1.38 1.40 1.33 1.44 1.64 1.32 1.62 0.44 0.45 0.43 0.45 0.46 0.46 0.44 0.45 1.48 1.51 1.29 1.51 1.15 1.43 1.29 1.59 1.29 1.57 1.38 1.19 1.22 1.36 1.28 1.51 1.55 1.52 1.55 1.32 0.42 0.54 0.42 0.43 0.44 0.42 0.38 0.46 0.39 0.47 0.43 0.40 0.37 0.42 0.39 0.44 0.48 0.45 0.51 0.42 ADRENAL LEFT ABS. REL. WT. % TBW a 0.041 0.045 0.042 0.044 0.053 0.054 0.048 0.044 14.28 14.61 13.00 14.81 17.10 15.34 16.05 12.22 0.056 0.038 0.058 0.041 0.032 0.046 0.041 0.048 0.041 0.046 0.032 0.034 0.047 0.040 0.031 0.044 0.043 0.046 0.044 0.040 15.77 13.48 18.83 11.71 12.21 13.61 11.92 13.83 12.42 13.90 10.00 11.45 14.16 12.31 9.48 12.79 13.44 13.57 14.52 12.62 A B S . WT. = ORGAN WEIGHT. REL. TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 4) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 589 DOSAGE GROUP II 1 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT ADRENAL RIGHT ABS. REL. WT. % TBW a 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 287. 0.038 308. 0.049 323. 0.039 297. 0.041 310. 0.047 352. 0.046 299. 0.043 360. 0.042 NOT PREGNANT 355. 0.053 282. 0.036 308. 0.052 350. 0.031 262. 0.028 338. 0.042 344 . 0.047 347. 0.041 330. 0.041 331. 0.043 320. 0.031 297. 0.033 332. 0.039 325. 0.039 327. 0.028 344 . 0.035 320. 0.054 339. 0.052 303. 0.041 317. 0.035 13.24 15.91 12.07 13.80 15.16 13.07 14.38 11.67 14.93 12.76 16.88 8.86 10.69 12.43 13.66 11.82 12.42 12.99 9.69 11.11 11.75 12.00 8.56 10.17 16.88 15.34 13.53 11.04 SPLEEN ABS. WT. REL. % TBW 0.73 0.50 0.47 0.50 0.53 0.56 0.64 0.58 0.25 0.16 0.14 0.17 0.17 0.16 0.21 0.16 0.60 0.50 0.83 0.59 0.57 0.59 0.68 0.61 0.57 0.63 0.63 0.67 0.48 0.65 0.41 0.58 1.03 0.72 0.59 0.57 0.17 0.18 0.27 0.17 0.22 0.17 0.20 0.18 0.17 0.19 0.20 0.22 0.14 0.20 0.12 0.17 0.32 0.21 0.19 0.18 THYMUS ABS. WT. REL. % TBW 0.20 0.17 0.07 0.11 0.20 0.21 0.19 0.24 0.07 0.06 0.02 0.04 0.06 0.06 0.06 0.07 0.17 0.27 0.16 0.24 0.12 0.20 0.14 0.12 0.23 0.21 0.18 0.21 0.28 0.20 0.20 0.20 0.17 0.32 0.14 0.14 0.05 0.10 0.05 0.07 0.04 0.06 0.04 0.03 0.07 0.06 0.06 0.07 0.08 0.06 0.06 0.06 0.05 0.09 0.05 0.04 OVARY LEFT ABS. REL. WT. * TBW a 0.062 0.055 0.055 0.054 0.054 0.087 0.050 0.046 21.60 17.86 17.03 18.18 17.42 24.72 16.72 12.78 0.054 0.055 0.043 0.059 0.051 0.056 0.047 0.047 0.054 0.053 0.058 0.042 0.085 0.044 0.045 0.054 0.078 0.040 0.044 0.040 15.21 19.50 13.96 16.86 19.46 16.57 13.66 13.54 16.36 16.01 18.12 14.14 25.60 13.54 13.76 15.70 24.38 11.80 14.52 12.62 OVARY RIGHT ABS. WT. REL. % TBW a 0.064 0.076 0.061 0.058 0.054 0.032 0.040 0.056 22.30 24.68 18.88 19.53 17.42 9.09 13.38 15.56 0.068 0.076 0.046 0.066 0.060 0.056 0.058 0.056 0.035 0.060 0.053 0.045 0.061 0.036 0.041 0.051 0.048 0.038 0.038 0.062 19.15 26.95 14.94 18.86 22.90 16.57 16.86 16.14 10.61 18.13 16.56 15.15 18.37 11.08 12.54 14.82 15.00 11.21 12.54 19.56 UTERUS NON-GRAVID ABS. WT. REL. % TBW 0.80 0.68 0.46 0.62 0.50 0.55 0.67 0.38 0.28 0.22 0.14 0.21 0.16 0.16 0.22 0.10 0.69 0.63 0.53 0.57 0.83 0.55 0.74 0.38 0.37 0.46 0.47 0.57 0.42b 0.40 0.34 0.60 1.00 0.69 0.43 0.46 0.19 0.22 0.17 0.16 0.32 0.16 0.22 0.11 0.11 0.14 0.15 0.19 0.13 0.12 0.10 0.17 0.31 0.20 0.14 0.14 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. a. Value was multiplied by 1000. b. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 5) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 590 DOSAGE GROUP III 3 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT PITUITARY ABS. WT. REL. % TBW a 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 326. 0.009 307. 0.013 369. 0.019 334 . 0.016 308. 0.017 358. 0.015 314. 0.014 341. 0.018 311. 0.015 361. 0.017 344 . 0.016 336. 0.018 NOT PREGNANT 343. 0.015 331. 0.015 301. 0.016 332. 0.012 329. 0.017 NOT PREGNANT 368. 0.018 336. 0.017 302. 0.016 297. 0.006 300. 0.015 317. 0.016 309. 0.013 310. 0.014 358. 0.013 335. 0.021 340. 0.018 2.76 4.23 5.15 4.79 5.52 4.19 4.46 5.28 4.82 4.71 4.65 5.36 4.37 4.53 5.32 3.61 5.17 4.89 5.06 5.30 2.02 5.00 5.05 4.21 4.52 3.63 6.27 5.29 BRAIN ABS. WT. REL. % TBW 1.96 2.05 2.12 2.18 1.85 2.02 1.95 2.20 2.18 2.01 2.05 2.07 0.60 0.67 0.57 0.65 0.60 0.56 0.62 0.64 0.70 0.56 0.60 0.62 2.23 2.13 1.96 2.27 2.13 0.65 0.64 0.65 0.68 0.65 2.04 2.00 2.07 1.99 2.02 2.17 2.08 2.10 1.96 2.25 2.13 0.55 0.60 0.68 0.67 0.67 0.68 0.67 0.68 0.55 0.67 0.63 LIVER ABS. WT. :REL. % TBW 16.89 16.43 18.04 16.19 15.49 19.48 16.49 15.80 17.76 16.30 15.42 14.80 5.18 5.35 4.89 4.85 5.03 5.44 5.25 4.63 5.71 4.52 4.48 4.40 17.20 18.62 15.77 18.40 16.01 5.01 5.62 5.24 5.54 4.87 17.41 13.89 14.98 15.23 14.72 15.62 15.33 14.41 17.55 17.98 17.23 4.73 4.13 4.96 5.13 4.91 4.93 4.96 4.65 4.90 5.37 5.07 KIDNEY LEFT ABS. REL. W T . % TBW 1.44 1.42 1.37 1.50b 15.30c 1.49 1.36 1.28 1.41 1.48 1.35 1.28 0.44 0.46 0.37 0.45 4.97c 0.42 0.43 0.38 0.45 0.41 0.39 0.38 1.45 1.29 1.34 1.51 1.54 0.42 0.39 0.44 0.45 0.47 1.45 1.29 1.34 1.38 1.45 1.24 1.62 1.31 1.50 1.48 1.43 0.39 0.38 0.44 0.46 0.48 0.39 0.52 0.42 0.42 0.44 0.42 KIDNEY RIGHT ABS. REL. W T . % TBW 1.40 1.36 1.40 1.54b 1.63 1.63 1.42 1.30 1.47 1.43 1.38 1.33 0.43 0.44 0.38 0.46 0.53 0.46 0.45 0.38 0.47 0.40 0.40 0.40 1.50 1.36 1.38 1.44 1.55 0.44 0.41 0.46 0.43 0.47 1.48 1.32 1.32 1.25 1.45 1.26 1.32 1.37. 1.48 1.50 1.44 0.40 0.39 0.44 0.42 0.48 0.40 0.43 0.44 0.41 0.45 0.42 ADRENAL LEFT ABS. REL. WT. % TBW a 0.049 0.048 0.051 0.046 0.048 0.042 0.041 0.041 0.044 0.048 0.04 6 0.053 15.03 15.64 13.82 13.77 15.58 11.73 13.06 12.02 14.15 13.30 13.37 15.77 0.040 0.041 0.043 0.041 0.032 11.66 12.39 14.28 12.35 9.73 0.04 3 0.037 0.043 0.041 0.046 0.051 0.036 0.050 0.033 0.055 0.058 11.68 11.01 14.24 13.80 15.33 16.09 11.65 16.13 9.22 16.42 17.06 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. b. Rat 1428 had slight dilation of the pelvis in both kidneys. c. Value was presumed incorrectly recorded; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE E36 (PAGE 6) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 591 DOSAGE GROUP III 3 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT ADRENAL RIGHT ABS. REL. WT. TBW a 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 326. 0.043 307. 0.046 369. 0.046 334. 0.047 308. 0.042 358. 0.043 314. 0.050 341. 0.039 311. 0.039 361. 0.044 344 . 0.042 336. 0.052 NOT PREGNANT 343.. 0.037 331.. 0.039 301., 0.037 332. 0.028 329., 0.042 NOT PREGNANT 368., 0.036 336.. 0.033 302 . 0.041 297.. 0.036 300., 0.033 317., 0.039 309. 0.043 310.. 0.042 358.. 0.038 335.. 0.053 340.. 0.048 13.19 14.98 12.47 14.07 13.64 12.01 15.92 11.44 12.54 12.19 12.21 15.48 10.79 11.78 12.29 8.43 12.76 9.78 9.82 13.58 12.12 11.00 12.30 13.92 13.55 10.61 15.82 14.12 SPLEEN ABS. WT. REL. % TBW 0.58 0.64 0.61 0.62 0.58 0.71 0.55 0.64 0.58 0.52 0.73 0.60 0.18 0.21 0.16 0.18 0.19 0.20 0.18 0.19 0.19 0.14 0.21 0.18 0.70 0.58 0.62 0.67 0.70 0.20 0.18 0.20 0.20 0.21 0.57 0.55 0.57 0.51 0.55 0.56 0.61 0.62 0.51 0.63 0.60 0.15 0.16 0.19 0.17 0.18 0.18 0.20 0.20 0.14 0.19 0.18 THYMUS ABS. WT. REL. % TBW 0.23 0.20 0.21 0.14 0.20 0.29 0.28 0.26 0.07 0.23 0.11 0.22 0.07 0.06 0.06 0.04 0.06 0.08 0.09 0.08 0.02 0.06 0.03 0.06 0.20 0.21 0.23 0.35 0.29 0.06 0.06 0.08 0.10 0.09 0.12 0.18 0.18 0.22 0.18 0.17 0.40 0.24 0.19 0.10 0.23 0.03 0.05 0.06 0.07 0.06 0.05 0.13 0.08 0.05 0.03 0.07 OVARY LEFT ABS. REL. WT. t TBW a 0.034 0.057 0.047 0.059 0.056 0.075 0.055 0.068 0.037 0.042 0.062 0.045 10.43 18.57 12.74 17.66 18.18 20.95 17.52 19.94 11.90 11.63 18.02 13.39 0.042 0.033 0.047 0.069 0.052 12.24 9.97 15.61 20.78 15.80 0.038 0.038 0.046 0.056 0.071 0.054 0.064 0.043 0.050 0.040 0.051 10.33 11.31 15.23 18.86 23.67 17.03 20.71 13.87 13.97 11.94 15.00 OVARY RIGHT ABS. REL. WT. % TBW a 0.035 0.031 0.053 0.055 0.064 0.056 0.043 0.034 0.044 0.056 0.057 0.041 10.74 10.10 14.36 16.47 20.78 15.64 13.69 9.97 14.15 15.51 16.57 12.20 0.045 0.044 0.043 0.062 0.068 13.12 13.29 14.28 18.67 20.67 0.045 0.035 0.046 0.056 0.057 0.056 0.062 0.037 0.059 0.039 0.051 12.23 10.42 15.23 18.86 19.00 17.66 20.06 11.94 16.48 11.64 15.00 UTERUS NON-GRAVID ABS. REL. WT. % TBW 0.34 0.64 0.49 0.47 0.62 0.59 1.18 0.83 0.46 0.37 0.51 0.54 0.10 0.21 0.13 0.14 0.20 0.16 0.38 0.24 0.15 0.10 0.15 0.16 0.50b 0.42 0.45 0.75 0.67 0.14 0.13 0.15 0.22 0.20 0.28 0.56 0.60 0.49 0.58 0.51 0.83 0.72 0.56 0.50 0.54 0.08 0.17 0.20 0.16 0.19 0.16 0.27 0.23 0.16 0.15 0.16 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT . = ORGAN WEIGHT. a. Value was multiplied by 1000. b. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 7) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 592 DOSAGE GROUP IV RAT TERMINAL BODY NUMBER WEIGHT PITUITARY ABS. WT. REL. % TBW a 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 313. 0.015 NOT PREGNANT 316. 0.017 359. 0.013 368. 0.015 316. 0.014 353. 0.016 319. 0.015 355. 0.016 302. 0.018 322. 0.014 318. 0.015 341. 0.015 338 . 0.013 NOT PREGNANT 250. 0.017 325. 0.016 316. 0.014 325. 0.013 317. 0.017 312. 0.016 313 . 0.011 326. 0.010 315. 0.023 310. 0.015 350. 0.014 347. 0.017 316. 0.015 306. 0.015 355. 0.017 4.79 5.38 3.62 4.08 4.43 4.53 4.70 4.51 5.96 4.35 4.72 4.40 3.85 6.80 4.92 4.43 4.00 5.36 5.13 3.51 3.07 7.30 4.84 4.00 4.90 4.75 4.90 4.79 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Value was multiplied by 1000. 10 MG/KG/DAY BRAIN ABS. WT. REL. % TBW 2.23 0.71 1.90 2.06 2.12 2.05 2.12 1.76 2.23 1.97 2.05 2.05 2.21 2.20 0.60 0.57 0.58 0.65 0.60 0.55 0.63 0.65 0.64 0.64 0.65 0.65 2.24 2.19 2.15 2.03 2.08 2.18 2.02 1.98 2.14 2.11 2.15 2.11 2.20 1.93 2.22 0.90 0.67 0.68 0.62 0.66 0.70 0.64 0.61 0.68 0.68 0.61 0.61 0.70 0.63 0.62 LIVER ABS. WT. REL. % TBW 15.34 4.90 18.55 17.62 20.37 16.20 16.00 16.62 15.83 16.39 14.76 16.77 18.65 16.98 5.87 4.91 5.54 5.13 4.53 5.21 4.46 5.43 4.58 5.27 5.47 5.02 13.67 15.60 15.89 17.35 17.52 15.27 15.78 13.46 18.04 15.96 18.68 19.96 16.16 15.08 18.63 5.47 4.80 5.03 5.34 5.53 4.89 5.04 4.13 5.73 5.15 5.34 5.75 5.11 4.93 5.25 KIDNEY LEFT ABS. REL. WT. * TBW 1.26 0.40 1.37 1.33 1.65 1.24 1.52 1.33 1.50 1.48 1.18 1.51 1.46 1.39 0.43 0.37 0.45 0.39 0.43 0.42 0.42 0.49 0.37 0.47 0.43 0.41 1.28 1.32 1.28 1.13 1.45 1.35 1.32 1.24 1.35 1.46 1.49 1.56 1.38 1.21 1.69 0.51 0.41 0.40 0.35 0.46 0.43 0.42 0.38 0.43 0.47 0.42 0.45 0.44 0.40 0.48 KIDNEY RIGHT ABS. REL. WT. t TBW 1.25 0.40 1.31 1.41 1.56 1.28 1.49 1.28 1.48 1.49 1.22 1.68 1.51 1.46 0.41 0.39 0.42 0.40 0.42 0.40 0.42 0.49 0.38 0.53 0.44 0.43 1.30 1.38 1.27 1.13 1.56 1.42 1.38 1.21 1.42 1.53 1.58 1.61 1.37 1.25 1.81 0.52 0.42 0.40 0.35 0.49 0.46 0.44 0.37 0.45 0.49 0.45 0.46 0.43 0.41 0.51 ADRENAL LEFT ABS. REL. WT. % TBW a 0.045 14.38 0.054 0.042 0.052 0.044 0.042 0.047 0.044 0.042 0.041 0.046 0.051 0.041 17.09 11.70 14.13 13.92 11.90 14.73 12.39 13.91 12.73 14.46 14.96 12.13 0.043 0.053 0.036 0.043 0.047 0.046 0.041 0.030 0.051 0.044 0.054 0.053 0.041 0.046 0.056 17.20 16.31 11.39 13.23 14.83 14.74 13.10 9.20 16.19 14.19 15.43 15.27 12.97 15.03 15.77 A B S . WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 8) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 593 DOSAGE GROUP IV RAT TERMINAL BODY NUMBER WEIGHT ADRENAL RIGHT ABS. WT. REL. % TBW a 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 313 . 0.035 NOT PREGNANT 316. 0.047 359. 0.043 368. 0.045 316. 0.040 353. 0.042 319. 0.047 355. 0.040 302. 0.041 322. 0.042 318. 0.040 341. 0.050 338. 0.042 NOT PREGNANT 250. 0.044 325. 0.043 316. 0.033 325. 0.041 317. 0.041 312. 0.045 313. 0.040 326. 0.026 315. 0.042 310. 0.035 350. 0.049 347. 0.041 316. 0.031 306. 0.051 355. 0.052 11.18 14.87 11.98 12.23 12.66 11.90 14.73 11.27 13.58 13.04 12.58 14.66 12.43 17.60 13.23 10.44 12.62 12.93 14.42 12.78 7.98 13.33 11.29 14.00 11.82 9.81 16.67 14.65 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value waa multiplied by 1000. 10 MG/KG/DAY SPLEEN ABS. WT. REL. % TBW 0.53 0.17 0.58 0.61 0.66 0.56 0.46 0.57 0.68 0.48 0.48 0.70 0.54 0.64 0.18 0.17 0.18 0.18 0.13 0.18 0.19 0.16 0.15 0.22 0.16 0.19 0.51 0.67 0.55 0.58 0.52 0.60 0.54 0.74 0.82 0.67 0.67 0.66 0.50 0.51 0.57 0.20 0.21 0.17 0.18 0.16 0.19 0.17 0.23 0.26 0.22 0.19 0.19 0.16 0.17 0.16 THYMUS ABS. WT. REL. % TBW 0.29 0.09 0.11 0.33 0.26 0.10 0.12 0.15 0.26 0.24 0.13 0.23 0.21 0.13 0.03 0.09 0.07 0.03 0.03 0.05 0.07 0.08 0.04 0.07 0.06 0.04 0.10 0.16 0.18 0.10 0.17 0.08 0.35 0.38 0.23 0.26 0.30 0.20 0.17 0.15 0.29 0.04 0.05 0.06 0.03 0.05 0.02 0.11 0.12 0.07 0.08 0.08 0.06 0.05 0.05 0.08 OVARY LEFT ABS. REL. WT. % TBW a 0.046 14.70 0.065 0.041 0.076 0.031 0.039 0.045 0.065 0.046 0.063 0.048 0.040 0.048 20.57 11.42 20.65 9.81 11.05 14.11 18.31 15.23 19.56 15.09 11.73 14.20 0.048 0.042 0.064 0.041 0.044 0.045 0.051 0.050 0.056 0.037 0.042 0.045 0.060 0.044 0.061 19.20 12.92 20.25 12.62 13.88 14.42 16.29 15.34 17.78 11.94 12.00 12.97 18.99 14.38 17.18 OVARY RIGHT ABS. REL. WT. % TBW a 0.044 14.06 0.049 0.033 0.068 0.04 9 0.059 0.063 0.070 0.054 0.066 0.045 0.056 0.044 15.51 9.19 18.48 15.51 16.71 19.75 19.72 17.88 20.5ft, 14 .life 16.4** 13.02 0.048 0.046 0.045 0.051 0.056 0.040 0.039 0.057 0.035 0.052 0.049 0.053 0.035 0.043 0.075 19.20 14.15 14.24 15.69 17.66 12.82 12.46 17.48 11.11 16.77 14.00 15.27 11.08 14.05 21.13 UTERUS NON- GRAVID ABS. REL. WT. % TBW 0.68 0.22 0.57 0.44 0.53 0.67 0.60 0.56 0.84 0.69 0.42 0.41 0.42 0.74 0.18 0.12 0.14 0.21 0.17 0.18 0.24 0.23 0.13 0.13 0.12 0.22 0.62 0.50 0.54 0.65 0.51 0.49 0.84 0.47 0.68 0.43 0.53 0.52 0.42 0.49 0.40 0.25 0.15 0.17 0.20 0.16 0.16 0.27 0.14 0.22 0.14 0.15 0.15 0.13 0.16 0.11 ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 9) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 594 DOSAGE GROUP V 30 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT PITUITARY ABS. WT. REL. t TBW a 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 296. 0.022 342. 0.016 298. 0.012 329. 0.019 306. 0.017 298. 0.016 319. 0.018 312. 0.009 319. 0.018 288. 0.011 325. 0.015 309. 0.012 275. 0.013 324 . 0.010 339. 0.018 304. 0.010 336. 0.015 292. 0.015 NOT PREGNANTr 346. 0.013 303. 0.014 294. 0.016 294. 0.015 300. 0.014 322. 0.016 354 . 0.015 318. 0.015 342. 0.023 317. 0.015 354 . 0.012 7.43 4.68 4.03 5.78 5.56 5.37 5.64 2.88 5.64 3.82 4.62 3.88 4.73 3.09 5.31 3.29 4.46 5.14 3.76 4.62 5.44 5.10 4.67 4.97 4.24 4.72 6.72 4.73 3.39 BRAIN ABS. WT. REL. % TBW 2.00 2.12 2.13 2.04 2.02 2.05 2.19 2.03 2.20 2.01 2.21 2.00 2.03 2.13 2.21 1.91 2.03 1.78 0.68 0.62 0.71 0.62 0.66 0.69 0.69 0.65 0.69 0.70 0.68 0.65 0.74 0.66 0.65 0.63 0.60 0.61 1.99 2.11 2.13 2.15 2.02 2.10 2.02 2.11 2.04 2.18 2.18 0.58 0.70 0.72 0.73 0.67 0.65 0.57 0.66 0.60 0.69 0.62 LIVER ABS. WT. REL. % TBW 14.69 16.14 17.89 17.75 18.02 19.33 16.81 15.58 15.27 17.49 18.14 17.80 14.42 17.00 15.50 15.97 17.15 15.62 4.96 4.72 6.00 5.40 5.89 6.49 5.27 4.99 4.79 6.07 5.58 5.76 5.24 5.25 4.57 5.25 5.10 5.35 17.26 16.59 13.71 15.78 15.72 17.39 17.58 18.89 17.20 17.75 18.06 4.99 5.48 4.66 5.37 5.24 5.40 4.97 5.94 5.03 5.60 5.10 KIDNEY LEFT ABS. REL. WT. % TBW 1.11 1.57 1.40 1.32 1.49 1.29 1.43 1.21 1.30 1.50 1.37 1.37 1.11 1.30 1.24 1.14 1.20 1.20 0.38 0.46 0.47 0.40 0.49 0.43 0.45 0.39 0.41 0.52 0.42 0.44 0.40 0.40 0.36 0.38 0.36 0.41 1.37 1.38 1.19 1.49 1.23 1.34 1.21 1.38 1.98 1.59 1.25 0.40 0.46 0.40 0.51 0.41 0.42 0.34 0.43 0.58 0.50 0.35 KIDNEY RIGHT ABS. REL. WT. % TBW 1.20 1.65 1.47 1.45 1.50 1.33 1.56 1.25 1.24 1.55 1.57 1.39 1.22 1.28 1.27 1.23 1.20 1.29 0.40 0.48 0.49 0.44 0.49 0.45 0.49 0.40 0.39 0.54 0.48 0.45 0.44 0.40 0.37 0.40 0.36 0.44 1.37 1.42 1.19 1.40 1.35 1.35 1.30 1.40 2.18b 1.52 1.45 0.40 0.47 0.40 0.48 0.45 0.42 0.37 0.44 0.64 0.48 0.41 ADRENAL LEFT ABS. REL. WT. % TBW a 0.050 0.040 0.065 0.032 0.053 0.055 0.042 0.045 0.039 0.042 0.041 0.044 0.042 0.053 0.040 0.043 0.033 0.043 16.89 11.70 21.81 9.73 17.32 18.46 13.17 14.42 12.22 14.58 12.62 14.24 15.27 16.36 11.80 14.14 9.82 14.73 0.044 0.044 0.024 0.050 0.041 0.047 0.046 0.047 0.046 0.045 0.059 12.72 14.52 8.16 17.01 13.67 14.60 12.99 14.78 13.45 14.20 16.67 D IN GRAMS (G) . ABS. WT. - ORGAN WEIGHT,. a. by 1000. b. Rat 1593 had moderate dilation of the pelvis in the right kidney. REL. % TBW = (ORGAN WEIGHT/TERM INAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E36 (PAGE 10) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION FEMALE RATS ARGUS 418-020 Page 595 DOSAGE GROUP V 30 MG/KG/DAY RAT TERMINAL BODY NUMBER WEIGHT ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. WT. REL. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. WT. % TBW 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 15B3 1584 1586 1587 1588 1589 1591 1593 1598 1600 296. 0.043 342. 0.050 298. 0.054 329. 0.044 306. 0.049 298. 0.053 319. 0.039 312. 0.040 319. 0.034 288. 0.039 325. 0.043 309. 0.048 275. 0.044 324 . 0.035 339. 0.034 304 . 0.044 336 . 0.030 292. 0.039 NOT PREGNANT 346. 0.037 303. 0.036 294 . 0.039 294. 0.040 300. 0.034 322 . 0.046 354 . 0.042 318. 0.043 342. 0.041 317. 0.037 354. 0.044 14.53 14.62 18.12 13.37 16.01 17.78 12.22 12.82 10.66 13.54 13.23 15.53 16.00 10.80 10.03 14.47 8.93 13.36 10.69 11.88 13.26 13.60 11.33 14.28 11.86 13.52 11.99 11.67 12.43 0.50 0.76 0.64 0.59 0.80 0.60 0.57 0.52 0.48 0.74 0.65 0.65 0.64 0.56 0.56 0.56 0.47 0.62 0.69 0.48 0.51 0.50 0.52 0.58 0.59 0.64 0.95 0.51 0.66 0.17 0.22 0.21 0.18 0.26 0.20 0.18 0.17 0.15 0.26 0.20 0.21 0.23 0.17 0.16 0.18 0.14 0.21 0.20 0.16 0.17 0.17 0.17 0.18 0.17 0.20 0.28 0.16 0.19 0.20 0.44 0.23 0.25 0.21 0.14 0.11 0.21 0.12 0.24 0.29 0.24 0.26 0.19 0.19 0.12 0.20 0.17 0.13 0.16 0.33 0.12 0.26 0.37 0.16 0.22 0.50 0.20 0.16 0.07 0.13 0.08 0.08 0.07 0.05 0.03 0.07 0.04 0.08 0.09 0.08 0.09 0.06 0.06 0.04 0.06 0.06 0.04 0.05 0.11 0.04 0.09 0.11 0.04 0.07 0.15 0.06 0.04 0.037 0.098 0.038 0.058 0.062 0.050 0.058 0.040 0.044 0.058 0.038 0.051 0.064 0.045 0.046 0.032 0.043 0.043 0.051 0.068 0.052 0.043 0.060 0.043 0.043 0.049 0.069 0.065 0.046 12.50 28.65 12.75 17.63 20.26 16.78 18.18 12.82 13.79 20.14 11.69 16.50 23.27 13.89 13.57 10.53 12.80 14.73 14.74 22.44 17.69 14.62 20.00 13.35 12.15 15.41 20.18 20.50 12.99 0.049 0.089 0.068 0.065 0.049 0.049 0.055 0.031 0.043 0.058 0.068 0.068 .054 .043 .052 .035 .042 0.054 0.041 0.040 0.066 0.035 0.055 0.045 0.045 0 .041 0.069 0.051 0.045 16.55 26.02 22.82 19.76 16.01 16.44 17.24 9.94 13.48 20.14 20.92 22.01 19.64 13.27 15.34 11.51 12.50 18.49 11.85 13.20 22.45 11.90 18.33 13.98 12.71 12.89 20.18 16.09 12.71 0.56 0.82 0.39 0.37 82 27 94 49 36 71 82 45 67 46b 42 31 39 34 66 38 51 45 59 83 45 56 0.61 0.60 0.44 19 24 13 11 27 09 29 0.16 0.11 0.25 0.25 0.14 0.24 0.14 0.12 0.10 0.12 0.12 0.19 0.12 0.17 0.15 0.20 0.26 0.13 0.18 0.18 0.19 0.12 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT . = ORGAN WEIGHT,. a. Value was multiplied by 1 0 0 0 . b. Damaged during processing (weight not affected) REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 1) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 596 DOSAGE GROUP I 0 MG/KG/DAY RAT NUMBER 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 BRAIN WEIGHT PITUITARY ABS. WT. REL. * BRW LIVER ABS. WT. REL. BRW 2.10 0.022 1.05 14.52 2.10 0.021 1.00 17.50 2.05 0.017 0.83 17.30 2.01 0.018 0.90 18.06 1.99 0.014 0.70 18.04 2.15 0.022 1.02 14.95 2.14 0.020 0.93 15.73 NOT PREGNANT 2.06 0.017 0.82 17.38 2.05 0.014 0.68 18.67 2.00 0.009 0.45 17.15 2.09 0.015 0.72 17.40 2.00 0.018 0.90 12.61 2.33 0.018 0.77 14.43 1.96 0.016 0.82 15.10 1.93 0.012 0.62 15.81 2.06 0.016 0.78 17.19 2.10 0.022 1.05 18.61 2.07 0.015 0.72 16.97 2.06 0.029 1.41 16.15 1.93 0.023 1.19 14.09 2.26 0.020 0.88 17.38 2.03 0.014 0.69 17.73 2.03 0.018 0.89 17.30 2.05 0.015 0.73 18.89 2.03 0.016 0.79 18.24 2.22 0.024 1.08 15.33 2.04 0.007 0.34 16.39 NOT PREGNANT; MATING NOT CONFIRMED 2.10 0.017 0.81 15.16 691.43 833.33 843.90 898.51 906.53 695.35 735.05 843.69 910.73 857.50 832.54 630.50 619.31 770.41 819.17 834.47 886.19 819.81 783.98 730.05 769.03 873.40 852.22 921.46 898.52 690.54 803.43 721.90 KIDNEY LEFT ABS. REL. W T . % BRW 1.30 1.38 1.45 1.29 1.30 1.24 1.26 61.90 65.71 70.73 64.18 65.33 57.67 58.88 1.53 1.36 1.35 1.41 1.22 1.11 1.26 1.28 1.42 1.56 1.60 1.17 1.22 1.61 1.28 1.35 1.46 1.37 1.54 1.40 74.27 66.34 67.50 67.46 61.00 47.64 64.28 66.32 68.93 74.28 77.29 56.80 63.21 71.24 63.05 66.50 71.22 67.49 69.37 68.63 1.35 64.28 KIDNEY RIGHT ABS. REL. WT. % BRW 1.38 1.40 1.55 1.32 1.33 1.36 1.28 65.71 66.67 75.61 65.67 66.83 63.26 59.81 1.43 1.46 1.39 1.47 1.17 1.26 1.22 1.40 1.46 1.53 1.65 1.18 1.25 1.41 1.32 1.41 1.57 1.42 1.31 1.38 69.42 71.22 69.50 70.33 58.50 54.08 62.24 72.54 70.87 72.86 79.71 57.28 64.77 62.39 65.02 69.46 76.58 69.95 59.01 67.65 1.31 62.38 ADRENAL LEFT ABS. REL. W T . % BRW 0.027 0.044 0.050 0.041 0.040 0.036 0.036 1.28 2.10 2.44 2.04 2.01 1.67 1.68 0.039 0.047 0.044 0.044 0.047 0.041 0.036 0.036 0.046 0.051 0.043 0.039 0.039 0.053 0.047 0.052 0.055 0.063 0.038 0.037 1.89 2.29 2.20 2.10 2.35 1.76 1.84 1.86 2.23 2.43 2.08 1.89 2.02 2.34 2.32 2.56 2.68 3.10 1.71 1.81 0.031 1.48 ADRENAL RIGHT ABS. :REL. WT. % BRW 0.028 0.038 0.037 0.041 0.047 0.035 0.030 1.33 1.81 1.80 2.04 2.36 1.63 1.40 0.036 0.041 0.035 0.047 0.040 0.037 0.031 0.037 0.043 0.047 0.041 0.037 0.036 0.048 0.041 0.047 0.052 0.062 0.035 0.031 1.75 2.00 1.75 2.25 2.00 1.59 1.58 1.92 2.09 2.24 1.98 1.80 1.86 2.12 2.02 2.32 2.54 3.05 1.58 1.52 0.034 1.62 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. t TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 2) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 597 DOSAGE GROUP I 0 MG/KG/DAY RAT NUMBER BRAIN WEIGHT SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL. % BRW OVARY LEFT ABS. REL. WT. % BRW OVARY RIGHT ABS. REL. WT. % BRW UTERUS NON-GRAVID ABS. REL. W T . % BRW 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 2.10 0.63 30.00 0.13 2.10 0.53 25.24 0.26 2.05 0.59 28.78 0.21 2.01 0.72 35.82 0.11 1.99 0.66 33.16 0.18 2.15 0.57 26.51 0.26 2.14 0.62 28.97 0.30 NOT PREGNANT 2.06 0.64 31.07 0.24 2.05 0.71 34.63 0.16 2.00 0.57 28.50 0.23 2.09 0.61 29.19 0.15 2.00 0.56 28.00 0.16 2.33 0.56 24.03 0.20 1.96 0.52 26.53 0.22 1.93 0.56 29.02 0.20 2.06 0.47 22.82 0.10 2.10 0.65 30.95 0.19 2.07 0.76 36.71 0.30 2.06 0.55 26.70 0.31 1.93 0.60 31.09 0.20 2.26 0.64 28.32 0.20 2.03 0.65 32.02 0.13 2.03 0.52 25.62 0.20 2.05 0.57 27.80 0.18 2.03 0.66 32.51 0.15 2.22 0.52 23.42 0.26 2.04 0.43 21.08 0.12 NOT PREGNANT; MATING NOT CONFIRMED 2.10 0.64 30.48 0.25 6.19 12.38 10.24 5.47 9.04 12.09 14.02 11.65 7.80 11.50 7.18 8.00 8.58 11.22 10.36 4.85 9.05 14.49 15.05 10.36 8.85 6.40 9.85 8.78 7.39 11.71 5.88 11.90 0.054 0.053 0.045 0.033 0.045 0.054 0.043 0.055 0.045 0.037 0.044 0.040 0.050 0.029 0.039 0.047 0.044 0.070 0.057 0.058 0.068 0.049 0.085 0.063 0.052 0.061 0.045 0.046 2.57 2.52 2.20 1.64 2.26 2.51 2.01 2.67 2.20 1.85 2.10 2.00 2.14 1.48 2.02 2.28 2.10 3.38 2.77 3.00 3.01 2.41 4.19 3.07 2.56 2.75 2.20 2.19 0.068 0.063 0.057 0.042 0.049 0.054 0.050 0.054 0.051 0.032 0.053 0.046 0.050 0.033 0.058 0.055 0.047 0.092 0.064 0.034 0.042 0.055 0.061 0.062 0.060 0.075 0.050 0.053 3.24 3.00 2.78 2.09 2.46 2.51 2.34 2.62 2.49 1.60 2.54 2.30 2.14 1.68 3.00 2.67 2.24 4.44 3.11 1.76 1.86 2.71 3.00 3.02 2.96 3.38 2.'45 2.52 0.48 0.80 0.65 0.34 0.70 0.45 0.58 0.49 0.38 0.78 0.87 0.33 0.66 0.40 0.48 0.39 0.3 0a 0.79 0.51 0.53 0.70 0.32a 0.42 0.60 0.43 0.5? 0.42 0.74 22.86 38.10 31.71 16.92 35.18 20.93 27.10 23.79 18.54 39.00 41.63 16.50 28.33 20.41 24.87 18.93 14.28 38.16 24.76 27.46 30.97 15.76 20.69 29.27 21.18 23.42 20.59 35.24 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . A B S . WT. = ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 3) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 598 DOSAGE GROUP II 1 MG/KG/DAY RAT NUMBER BRAIN WEIGHT PITUITARY ABS. WT. REL. BRW 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 13 92 1393 1397 1399 1401 14 04 1407 1409 1410 1413 1415 1416 1418 2.09 0.015 2.13 0.017 2.10 0.019 1.98 0.016 1.95 0.014 2.34 0.013 2.00 0.017 2.05 0.014 NOT PREGNANT 2.32 0.021 2.13 0.016 2.06 0.017 1.97 0.023 1.94 0.014 2.06 0.012 2.04 0.017 2.23 0.021 2.02 0.013 2.10 0.018 2.26 0.013 1.95 0.014 2.03 0.017 2.07 0.015 2.06 0.015 2.05 0.019 2.29 0.015 1.92 0.011 2.23 0.018 2.15 0.013 0.72 0.80 0.90 0.81 0.72 0.56 0.85 0.68 0.90 0.75 0.82 1.17 0.72 0.58 0.83 0.94 0.64 0.86 0.58 0.72 0.84 0.72 0.73 0.93 0.66 0.57 0.81 0.60 ALL WEIGHTS WERE RECORDED IN GRAMS (G). LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW ADRENAL RIGHT ABS. REL. WT. % BRW 14.91 15.01 17.48 13.92 15.62 19.98 14.17 16.89 713.40 704.69 832.38 703.03 801.02 853.85 708.50 823.90 1.29 1.42 1.39 1.35 1.45 1.58 1.25 1.67 61.72 66.67 66.19 68.18 74.36 67.52 62.50 81.46 1.28 1.38 1.40 1.33 1.44 1.64 1.32 1.62 61.24 64.79 66.67 67.17 73.85 70.08 66.00 79.02 0.041 0.045 0.042 0.044 0.053 0.054 0.048 0.044 1.96 2.11 2.00 2.22 2.72 2.31 2.40 2.15 0.038 0.049 0.039 0.041 0.047 0.046 0.043 0.042 1.82 2.30 1.86 2.07 2.41 1.96 2.15 2.05 14.44 13.26 15.82 17.23 12.14 17.48 16.17 18.85 16.60 17.41 16.58 13.63 15.01 15.09 15.90 18.06 16.36 17.79 15.44 15.71 622.41 622.54 767.96 874.62 625.77 848.54 792.65 845.29 821.78 829.05 733.63 698.97 739.41 728.98 771.84 880.98 714.41 926.56 692.38 730.70 1.49 1.52 1.37 1.52 1.08 1.26 1.33 1.62 1.25 1.49 1.38 1.28 1.16 1.40 1.22 1.45 1.46 1.51 1.48 1.22 64.22 71.36 66.50 77.16 55.67 61.16 65.20 72.64 61.88 70.95 61.06 65.64 57.14 67.63 59.22 70.73 63.76 78.64 66.37 56.74 1.48 1.51 1.29 1.51 1.15 1.43 1.29 1.59 1.29 1.57 1.38 1.19 1.22 1.36 1.28 1.51 1.55 1.52 1.55 1.32 63.79 70.89 62.62 76.65 59.28 69.42 63.24 71.30 63.86 74.76 61.06 61.02 60.10 65.70 62.14 73.66 67.68 79.17 69.51 61.40 0.056 0.038 0.058 0.041 0.032 0.046 0.041 0.048 0.041 0.046 0.032 0.034 0.047 0.040 0.031 0.044 0.043 0.046 0.044 0.040 2.41 1.78 2.82 2.08 1.65 2.23 2.01 2.15 2.03 2.19 1.42 1.74 2.32 1.93 1.50 2.15 1.88 2.40 1.97 1.86 0.053 0.036 0.052 0.031 0.028 0.042 0.047 0.041 0.041 0.043 0.031 0.033 0.039 0.039 0.028 0.035 0.054 0.052 0.041 0.035 2.28 1.69 2.52 1.57 1.44 2.04 2.30 1.84 2.03 2.05 1.37 1.69 1.92 1.88 1.36 1.71 2.36 2.71 1.84 1.63 ABS. WT. * ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 4) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 599 DOSAGE GROUP II l MG/KG/DAY RAT NUMBER 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 BRAIN WEIGHT SPLEEN ABS. WT. REL. % BRW 2.09 0.73 2.13 0.50 2.10 0.47 1.98 0.50 1.95 0.53 2.34 0.56 2.00 0.64 2.05 0.58 NOT PREGNANT 2.32 0.60 2.13 0.50 2.06 0.83 1.97 0.59 1.94 0.57 2.06 0.59 2.04 0.68 2.23 0.61 2.02 0.57 2.10 0.63 2.26 0.63 1.95 0.67 2.03 0.48 2.07 0.65 2.06 0.41 2.05 0.58 2.29 1.03 1.92 0.72 2.23 0.59 2.15 0.57 34.93 23.47 22.38 25.25 27.18 23.93 32.00 28.29 25.86 23.47 40.29 29.95 29.38 28.64 33.33 27.35 28.22 30.00 27.88 34.36 23.64 31.40 19.90 28.29 44.98 37.50 26.46 26.51 THYMUS ABS. WT. REL. % BRW 0.20 0.17 0.07 0.11 0.20 0.21 0.19 0.24 9.57 7.98 3.33 5.56 10.26 8.97 9.50 11.71 0.17 0.27 0.16 0.24 0.12 0.20 0.14 0.12 0.23 0.21 0.18 0.21 0.28 0.20 0.20 0.20 0.17 0.32 0.14 0.14 7.33 12.68 7.77 12.18 6.18 9.71 6.86 5.38 11.39 10.00 7.96 10.77 13.79 9.66 9.71 9.76 7.42 16.67 6.28 6.51 OVARY LEFT ABS. REL. WT. % BRW 0.062 0.055 0.055 0.054 0.054 0.087 0.050 0.046 2.97 2.58 2.62 2.73 2.77 3.72 2.50 2.24 0.054 0.055 0.043 0.059 0.051 0.056 0.047 0.047 0.054 0.053 0.058 0.042 0.085 0.044 0.045 0.054 0.078 0.040 0.044 0.040 2.33 2.58 2.09 2.99 2.63 2.72 2.30 2.11 2.67 2.52 2.57 2.15 4.19 2.12 2.18 2.63 3.41 2.08 1.97 1.86 OVARY RIGHT ABS. REL. WT. t BRW 0.064 0.076 0.061 0.058 0.054 0.032 0.040 0.056 3.06 3.57 2.90 2.93 2.77 1.37 2.00 2.73 0.068 0.076 0.046 0.066 0.060 0.056 0.058 0.056 0.035 0.060 0.053 0.045 0.061 0.036 0.041 0.051 0.048 0.038 0.038 0.062 2.93 3.57 2.23 3.35 3.09 2.72 2.84 2.51 1.73 2.86 2.34 2.31 3.00 1.74 1.99 2.49 2.10 1.98 1.70 2.88 UTERUS NON-GRAVID ABS. REL. WT. % BRW 0.80 0.68 0.46 0.62 0.50 0.55 0.67 0.38 38.28 31.92 21.90 31.31 25.64 23.50 33.50 18.54 0.69 0.63 0.53 0.57 0.83 0.55 0.74 0.38 0.37 0.46 0.47 0.57 0.42a 0.40 0.34 0.60 1.00 0.69. 0.43 0.46 29.74 29.58 25.73 28.93 42.78 26.70 36.27 17.04 18.32 21.90 20.80 29.23 20.69 19.32 16.50 29.27 43.67 35.94 19.28 21.40 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 5) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 600 DOSAGE GROUP III 3 MG/KG/DAY RAT NUMBER BRAIN WEIGHT PITUITARY ABS. WT. REL. % BRW 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 1.96 0 .009 2.05 0 ,.013 2.12 0 ,.019 2.18 0 ,.016 1.85 0 ,.017 2.02 0 ,.015 1.95 0 ,.014 2.20 0 ,.018 2.18 0 .015 2.01 0 ,.017 2.05 0 .016 2.07 0 .018 NOT PREGNANT 2.23 0 .015 2.13 0 .015 1.96 0 .016 2.27 0 .,012 2.13 0 .,017 NOT PREGNANT 2.04 0 .,018 2.00 0 .,017 2.07 0 .,016 1.99 0 .006 2.02 0 .015 2.17 0 .016 2.08 0 .,013 2.10 0 .,014 1.96 0 .013 2.25 0 .021 2.13 0 .,018 0 ,.46 0 ,.63 0 ,.90 0 ,.73 0 .92 0 ,.74 0 ,.72 0 ..82 0 ..69 0 ..84 0 ..78 0 ..87 0 ..67 0 .,70 0 ..82 0 ..53 0 .,80 0 .,88 0 ..85 0 .,77 0 ..30 0 ..74 0 .,74 0 ..62 0 ..67 0 ..66 0 ..93 0 .84 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Rat 1428 had slight dilation of the b. Value appeared incorrectly recorded, LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. W T . % BRW KIDNEY RIGHT ABS. REL. W T . % BRW ADRENAL LEFT ABS. REL. W T . % BRW ADRENAL RIGHT ABS. REL. W T . % BRW 16.89 16.43 18.04 16.19 15.49 19.48 16.49 15.80 17.76 16.30 15.42 14.80 861.73 801.46 850.94 742.66 837.30 964.36 845.64 718.18 814.68 810.94 752.20 714.98 44 42 37 50a 15.30b 49 36 28 41 1.48 1.35 1.28 73.47 69.27 64.62 68.81 827.03b 73.76 69.74 58.18 64.68 73.63 65.85 61.84 1.40 1.36 1.40 1.54a 1.63 1.63 1.42 1.30 1.47 1.43 1.38 1.33 71.43 66.34 66.04 70.64 88.11 80.69 72.82 59.09 67.43 71.14 67.32 64.25 0.049 0.048 0.051 0.046 0.048 0.042 0.041 0.041 0.044 0.048 0.046 0.053 2.50 2.34 2.40 2.11 2.59 2.08 2.10 1.86 2.02 2.39 2.24 2.56 0.043 0.046 0.046 0.047 0.042 0.043 0.050 0.039 0.039 0.044 0.042 0.052 2.19 2.24 2.17 2.16 2.27 2.13 2.56 1.77 1.79 2.19 2.05 2.51 17.20 18.62 15.77 18.40 16.01 771.30 874.18 804.59 810.57 751.64 1.45 1.29 1.34 1.51 1.54 65.02 60.56 68.37 66.52 72.30 1.50 1.36 1.38 1.44 1.55 67.26 63.85 70.41 63.44 72.77 0.040 0.041 0.043 0.041 0.032 1.79 1.92 2.19 1.81 1.50 0.037 0.039 0.037 0.028 0.042 1.66 1.83 1.89 1.23 1.97 17.41 13.89 14.98 15.23 14.72 15.62 15.33 14.41 17.55 17.98 17.23 853.43 694.50 723.67 765.33 728.71 719.82 737.02 686.19 895.41 799.11 808.92 45 71.08 29 64.50 34 64.73 38 69.35 45 71.78 24 57.14 62 77.88 31 62.38 50 76.53 48 65.78 43 67.14 1.48 1.32 1.32 1.25 1.45 1.26 1.32 1.37 1.48 1.50 1.44 72.55 66.00 63.77 62.81 71.78 58.06 63.46 65.24 75.51 66.67 67.60 0.043 0.037 0.043 0.041 0.046 0.051 0.036 0.050 0.033 0.055 0.058 2.11 1.85 2.08 2.06 2.28 2.35 1.73 2.38 1.68 2.44 2.72 0.036 0.033 0.041 0.036 0.033 0.039 0.043 0.042 0.038 0.053 0.048 1.76 1.65 1.98 1.81 1.63 1.80 2.07 2.00 1.94 2.36 2.25 ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100 . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 6): BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 601 DOSAGE GROUP III 3 MG/KG/DAY RAT NUMBER 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 BRAIN WEIGHT SPLEEN ABS. WT. REL. % BRW 1.96 0.58 2.05 0.64 2.12 0.61 2.18 0.62 1.85 0.58 2.02 0.71 1.95 0.55 2.20 0.64 2.18 0.58 2.01 0.52 2.05 0.73 2.07 0.60 NOT PREGNANT 2.23 0.70 2.13 0.58 1.96 0.62 2.27 0.67 2.13 0.70 NOT PREGNANT 2.04 0.57 2.00 0.55 2.07 0.57 1.99 0.51 2.02 0.55 2.17 0.56 2.08 0.61 2.10 0.62 1.96 0.51 2.25 0.63 2.13 0.60 29.59 31.22 28.77 28.44 31.35 35.15 28.20 29.09 26.60 25.87 35.61 28.98 31.39 27.23 31.63 29.52 32.86 27.94 27.50 27.54 25.63 27.23 25.81 29.33 29.52 26.02 28.00 28.17 THYMUS ABS. WT. REL. % BRW 0.23 0.20 0.21 0.14 0.20 0.29 0.28 0.26 0.07 0.23 0.11 0.22 11.73 9.76 9.90 6.42 10.81 14.36 14.36 11.82 3.21 11.44 5.36 10.63 0.20 0.21 0.23 0.35 0.29 8.97 9.86 11.73 15.42 13.62 0.12 0.18 0.18 0.22 0.18 0.17 0.40 0.24 0.19 0.10 0.23 5.88 9.00 8.70 11.06 8.91 7.83 19.23 11.43 9.69 4.44 10.80 OVARY LEFT ABS. REL. WT. % BRW 0.034 0.057 0.047 0.059 0.056 0.075 0.055 0.068 0.037 0.042 0.062 0.045 1.73 2.78 2.22 2.71 3.03 3.71 2.82 3.09 1.70 2.09 3.02 2.17 0.042 0.033 0.047 0.069 0.052 1.88 1.55 2.40 3.04 2.44 0.038 0.038 0.046 0.056 0.071 0.054 0.064 0.043 0.050 0.040 0.051 1.86 1.90 2.22 2.81 3.51 2.49 3.08 2.05 2.55 1.78 2.39 OVARY RIGHT ABS. REL. WT. % BRW 0.035 0.031 0.053 0.055 0.064 0.056 0.043 0.034 0.044 0.056 0.057 0.041 1.78 1.51 2.50 2.52 3.46 2.77 2.20 1.54 2.02 2.79 2.78 1.98 0.045 0.044 0.043 0.062 0.068 2.02 2.06 2.19 2.73 3.19 0.045 0.035 0.046 0.056 0.057 0.056 0.062 0.037 0.059 0.039 0.051 2.20 1.75 2.22 2.81 2.82 2.58 2.98 1.76 3.01 1.73 2.39 UTERUS NON-GRAVID ABS. REL. W T . % BRW 0.34 0.64 0.49 0.47 0.62 0,59 1.18 0.83 0.46 0.37 0.51 0.54 17.35 31.22 23.11 21.56 33.51 29.21 60.51 37.73 21.10 18.41 24.88 26.09 0.50a 0.42 0.45 0.75 0.67 22.42 19.72 22.96 33.04 31.46 0.28 0.56 0.60 0.49 0.58 0.51 0.83 0.72 0.56' 0.50 0.54 13.72 28.00 28.98 24.62 28.71 23.50 39.90 34.28 28.57 22.22 25.35 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. a. Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 7) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 602 DOSAGE GROUP IV 10 MG/KG/DAY RAT NUMBER BRAIN WEIGHT PITUITARY ABS. WT. REL. % BRW 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 2.23 0.015 NOT PREGNANT 1.90 0.017 2.06 0.013 2.12 0.015 2.05 0.014 2.12 0.016 1.76 0.015 2.23 0.016 1.97 0.018 2.05 0.014 2.05 0.015 2.21 0.015 2.20 0.013 NOT PREGNANT 2.24 0.017 2.19 0.016 2.15 0.014 2.03 0.013 2.08 0.017 2.18 0.016 2.02 0.011 1.98 0.010 2.14 0.023 2.11 0.015 2.15 0.014 2.11 0.017 2.20 0.015 1.93 0.015 2.22 0.017 0.67 0.89 0.63 0.71 0.68 0.75 0.85 0.72 0.91 0.68 0.73 0.68 0.59 0.76 0.73 0.65 0.64 0.82 0.73 0.54 0.50 1.07 0.71 0.65 0.80 0.68 0.78 0.76 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. !: BRW KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. BRW ADRENAL RIGHT ABS. REL. WT. % BRW 15.34 687.89 1.26 56.50 1.25 56.05 0.045 2.02 0.035 1.57 18.55 17.62 20.37 16.20 16.00 16.62 15.83 16.39 14.76 16.77 18.65 16.98 976.32 855.34 960.85 790.24 754.72 944.32 709.86 831.98 720.00 818.05 843.89 771.82 37 33 65 24 52 33 50 48 18 51 1.46 1.39 72.10 64.56 77.83 60.49 71.70 75.57 67.26 75.13 57.56 73.66 66.06 63.18 1.31 1.41 1.56 1.28 1.49 1.28 1.48 1.49 1.22 1.68 1.51 1.46 68.95 68.45 73.58 62.44 70.28 72.73 66.37 75.63 59.51 81.95 68.32 66.36 0.054 0.042 0.052 0.044 0.042 0.047 0.044 0.042 0.041 0.046 0.051 0.041 2.84 2.04 2.45 2.15 1.98 2.67 1.97 2.13 2.00 2.24 2.31 1.86 0.047 0.043 0.045 0.040 0.042 0.047 0.040 0.041 0.042 0.040 0.050 0.042 2.47 2.09 2.12 1.95 1.98 2.67 1.79 2.08 2.05 1.95 2.26 1.91 13.67 15.60 15.89 17.35 17.52 15.27 15.78 13.46 18.04 15.96 18.68 19.96 16.16 15.08 18.63 610.27 712.33 739.07 854.68 842.31 700.46 781.19 679.80 842.99 756.40 868.84 945.97 734.54 781.35 839.19 1.28 1.32 1.28 1.13 1.45 1.35 1.32 1.24 1.35 1.46 1.49 1.56 1.38 1.21 1.69 57.14 60.27 59.53 55.66 69.71 61.93 65.35 62.63 63.08 69.19 69.30 73.93 62.73 62.69 76.13 1.30 1.38 1.27 1.13 1.56 1.42 1.38 1.21 1.42 1.53 1.58 1.61 1.37 1.25 1.81 58.04 63.01 59.07 55.66 75.00 65.14 68.32 61.11 66.36 72.51 73.49 76.30 62.27 64.77 81.53 0.043 0.053 0.036 0.043 0.047 0.04 6 0.041 0.030 0.051 0.044 0.054 0.053 0.041 0.046 0.056 1.92 2.42 1.67 2.12 2.26 2.11 2.03 1.52 2.38 2.08 2.51 2.51 1.86 2.38 2.52 0.044 0.043 0.033 0.041 0.041 0.045 0.040 0.026 0.042 0.035 0.049 0.041 0.031 0.051 0.052 1.96 1.96 1.53 2.02 1.97 2.06 1.98 1.31 1.96 1.66 2.28 1.94 1.41 2.64 2.34 ABS. WT. ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 8) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 603 DOSAGE GROUP IV RAT NUMBER BRAIN WEIGHT SPLEEN ABS. REL. W T . % BRW 1482 1483 I486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 2.23 0.53 NOT PREGNANT 1.90 0.58 2.06 0.61 2.12 0.66 2.05 0.56 2.12 0.46 1.76 0.57 2.23 0.68 1.97 0.48 2.05 0.48 2.05 0.70 2.21 0.54 2.20 0.64 NOT PREGNANT 2.24 0.51 2.19 0.67 2.15 0.55 2.03 0.58 2.08 0.52 2.18 0.60 2.02 0.54 1.98 0.74 2.14 0.82 2.11 0.67 2.15 0.67 2.11 0.66 2.20 0.50 1.93 0.51 2.22 0.57 23.77 30.53 29.61 31.13 27.32 21.70 32.39 30.49 24.36 23.41 34.15 24.43 29.09 22.77 30.59 25.58 28.57 25.00 27.52 26.73 37.37 38.32 31.75 31.16 31.28 22.73 26.42 25.68 ALL WEIGHTS WERE RECORDED IN GRAMS (G). 10 MG/KG/DAY THYMUS ABS. WT. REL. % BRW OVARY LEFT ABS. REL. WT. % BRW OVARY RIGHT ABS. REL. WT. % BRW UTERUS NON-GRAVID ABS. REL. W T . % BRW 0.29 13.00 0.046 2.06 0.044 1.97 0.68 30.49 0.11 0.33 0.26 0.10 0.12 0.15 0.26 0.24 0.13 0.23 0.21 0.13 5.79 16.02 12.26 4.88 5.66 8.52 11.66 12.18 6.34 11.22 9.50 5.91 0.065 0.041 0.076 0.031 0.039 0.045 0.065 0.046 0.063 0.048 0.040 0.048 3.42 1.99 3.58 1.51 1.84 2.56 2.91 2.34 3.07 2.34 1.81 2.18 0.049 0.033 0.068 0.049 0.059 0.063 0.070 0.054 0.066 0.045 0.056 0.044 2.58 1.60 3.21 2.39 2.78 3.58 3.14 2.74 3.22 2.20 2.53 2.00 0.57 0.44 0.53 0.67 0.60 0.56 0.84 0.69 0.42 0.41 0.42 0.74 30.00 21.36 25.00 32.68 28.30 31.82 37.67 35.02 20.49 20.00 19.00 33.64 0.10 0.16 0.18 0.10 0.17 0.08 0.35 0.38 0.23 0.26 0.30 0.20 0.17 0.15 0.29 4.46 7.30 8.37 4.93 8.17 3.67 17.33 19.19 10.75 12.32 13.95 9.48 7.73 7.77 13.06 0.048 0.042 0.064 0.041 0.044 0.045 0.051 0.050 0.056 0.037 0.042 0.045 0.060 0.044 0.061 2.14 1.92 2.98 2.02 2.12 2.06 2.52 2.52 2.62 1.75 1.95 2.13 2.73 2.28 2.75 0.048 0.046 0.045 0.051 0.056 0.040 0.039 0.057 0.035 0.052 0.049 0.053 0.035 0.043 0.075 2.14 2.10 2.09 2.51 2.69 1.83 1.93 2.88 1.64 2.46 2.28 2.51 1.59 2.23 3.38 0.62 0.50 0.54 0.65 0.51 0.49 0.84 0.47 0.68 0.43 0.53 0.52 0.42 0.49 0.40 27.68 22.83 25.12 32.02 24.52 22.48 41.58 23.74 31.78 20.38 24.65 24.64 19.09 25.39 18.02 ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 9) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 604 DOSAGE GROUP V 30 MG/KG/DAY RAT NUMBER 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 BRAIN WEIGHT PITUITARY ABS. WT. REL. % BRW 2.00 0.022 2.12 0.016 2.13 0.012 2.04 0.019 2.02 0.017 2.05 0.016 2.19 0.018 2.03 0.009 2.20 0.018 2.01 0.011 2.21 0.015 2.00 0.012 2.03 0.013 2.13 0.010 2.21 0.018 1.91 0.010 2.03 0.015 1.78 0.015 NOT PREGNANT 1.99 0.013 2.11 0.014 2.13 0.016 2.15 0.015 2.02 0.014 2.10 0.016 2.02 0.015 2.11 0.015 2.04 0.023 2.18 0.015 2.18 0.012 1.10 0.75 0.56 0.93 0.84 0.78 0.82 0.44 0.82 0.55 0.68 0.60 0.64 0.47 0.81 0.52 0.74 0.84 0.65 0.66 0.75 0.70 0.69 0.76 0.74 0.71 1.13 0.69 0.55 LIVER ABS. WT. REL. % BRW 14.69 16.14 17.89 17.75 18.02 19.33 16.81 15.58 15.27 17.49 18.14 17.80 14.42 17.00 15.50 15.97 17.15 15.62 734.50 761.32 839.91 870.10 892.08 942.93 767.58 767.49 694.09 870.15 820.81 890.00 710.34 798.12 701.36 836.12 844.83 877.53 17.26 16.59 13.71 15.78 15.72 17.39 17.58 18.89 17.20 17.75 18.06 867.34 786.26 643.66 733.95 778.22 828.10 870.30 895.26 843.14 814.22 828.44 KIDNEY LEFT ABS. REL. WT. t BRW 1.11 1.57 1.40 1.32 1.49 1.29 1.43 1.21 1.30 1.50 1.37 1.37 1.11 1.30 1.24 1.14 1.20 1.20 55.50 74.06 65.73 64.70 73.76 62.93 65.30 59.60 59.09 74.63 61.99 68.50 54.68 61.03 56.11 59.68 59.11 67.42 1.37 1.38 1.19 1.49 1.23 1.34 1.21 1.38 1.98 1.59 1.25 68.84 65.40 55.87 69.30 60.89 63.81 59.90 65.40 97.06 72.94 57.34 KIDNEY RIGHT ABS. REL. W T . % BRW 1.20 1.65 1.47 1.45 1.50 1.33 1.56 1.25 1.24 1.55 1.57 1.39 1.22 1.28 1.27 1.23 1.20 1.29 60.00 77.83 69.01 71.08 74.26 64.88 71.23 61.58 56.36 77.11 71.04 69.50 60.10 60.09 57.47 64.40 59.11 72.47 1.37 1.42 1.19 1.40 1.35 1.35 1.30 1.40 2.18a 1.52 1.45 68.84 67.30 55.87 65.12 66.83 64.28 64.36 66.35 106.86 69.72 66.51 ADRENAL LEFT ABS. REL. W T . % BRW 0.050 0.040 0.065 0.032 0.053 0.055 0.042 0.045 0.039 0.042 0.041 0.044 0.042 0.053 0.040 0.043 0.033 0.043 2.50 1.89 3.05 1.57 2.62 2.68 1.92 2.22 1.77 2.09 1.86 2.20 2.07 2.49 1.81 2.25 1.62 2.42 0.044 0.044 0.024 0.050 0.041 0.047 0.04 6 0.04.7 0.046 0.045 0.059 2.21 2.08 1.13 2.32 2.03 2.24 2.28 2.23 2.25 2.06 2.71 ADRENAL RIGHT ABS. REL. W T . % BRW 0.043 0.050 0.054 0.044 0.049 0.053 0.039 0.040 0.034 0.039 0.043 0.048 0.044 0.035 0.034 0.044 0.030 0.039 2.15 2.36 2.54 2.16 2.42 2.58 1.78 1.97 1.54 1.94 1.94 2.40 2.17 1.64 1.54 2.30 1.48 2.19 0.037 0.036 0.039 0.040 0.034 0.046 0.042 0.043 0.041 0.037 0.044 1.86 1.71 1.83 1.86 1.68 2.19 2.08 2.04 2.01 1.70 2.02 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT, a. Rat 1593 had moderate dilation of the pelvis in the right kidney. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E37 (PAGE 10) : BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA FI GENERATION FEMALE RATS ARGUS 418-020 Page 605 DOSAGE GROUP V 30 MG/KG/DAY RAT NUMBER BRAIN WEIGHT SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL. % BRW OVARY LEFT ABS. REL. WT. % BRW OVARY RIGHT ABS. REL. WT. % BRW UTERUS NON-GRAVID ABS. REL. W T . V BRW 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 2.00 0.50 2.12 0.76 2.13 0.64 2.04 0.59 2.02 0.80 2.05 0.60 2.19 0.57 2.03 0.52 2.20 0.48 2.01 0.74 2.21 0.65 2.00 0.65 2.03 0.64 2.13 0.56 2.21 0.56 1.91 0.56 2.03 0.47 1.78 0.62 NOT PREGNANT 1.99 0.69 2.11 0.48 2.13 0.51 2.15 0.50 2.02 0.52 2.10 0.58 2.02 0.59 2.11 0.64 2.04 0.95 2.18 0.51 2.18 0.66 25.00 35.85 30.05 28.92 39.60 29.27 26.03 25.62 21.82 36.82 29.41 32.50 31.53 26.29 25.34 29.32 23.15 34.83 34.67 22.75 23.94 23.26 25.74 27.62 29.21 30.33 46.57 23.39 30.28 0.20 0.44 0.23 0.25 0.21 0.14 0.11 0.21 0.12 0.24 0.29 0.24 0.26 0.19 0.19 0.12 0.20 0.17 0.13 0.16 0.33 0.12 0.26 0.37 0.16 0.22 0.50 0.20 0.16 10.00 20.75 10.80 12.25 10.40 6.83 5.02 10.34 5.45 11.94 13.12 12.00 12.81 8.92 8.60 6.28 9.85 9.55 6.53 7.58 15.49 5.58 12.87 17.62 7.92 10.43 24.51 9.17 7.34 0.037 0.098 0.038 0.058 0.062 0.050 0.058 0.040 0.044 0.058 0.038 0.051 0.064 0.045 0.046 0.032 0.043 0.043 0.051 0.068 0.052 0.043 0.060 0.043 0.043 0.049 0.069 0.065 0.046 1.85 4.62 1.78 2.84 3.07 2.44 2.65 1.97 2.00 2.88 1.72 2.55 3.15 2.11 2.08 1.68 2.12 2.42 2.56 3.22 2.44 2.00 2.97 2.05 2.13 2.32 3.38 2.98 2.11 0.049 0.089 0.068 0.065 0.049 0.049 0.055 0.031 0.043 0.058 0.068 0.068 0.054 0.043 0.052 0.035 0.042 0.054 0.041 0.040 0.066 0.035 0.055 0.045 0.045 0.041 0.069 0.051 0.045 2.45 4.20 3.19 3.19 2.42 2.39 2.51 1.53 1.95 2.88 3.08 23.. 6460 2 . 02 2 . 35 1 .83 2 . 07 3 .03 2 . 06 1 .90 3 .10 1 .63 2 . 72 2 . 14 2.23 1.94 3.38 2.34 2.06 0.56 0.82 0.39 0.37 0.82 0.27 0.94 0.49 0.36 0.71 0.82 0.45 0.67 0.46a 0.42 0.31 0.39 0.34 0.66 0.38 0.51 0.45 0.59 0.83 0.45 0.56. 0.61 0.60 0.44 28.00 38.68 18.31 18.14 40.59 13.17 42.92 24.14 16.36 35.32 37.10 22.50 33.00 21.60 19.00 16.23 19.21 19.10 33.16 18.01 23.94 20.93 29.21 39.52 22.28 26.54 29.90 27.52 20.18 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT., Damaged during processing (weight not affected). REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E38 (PAGE 1) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - FI GENERATION FEMALE RATS/F2 GENERATION LITTERS ARGUS 418-020 Page 606 DOSAGE GROUP I 0 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL TOTAL BORN BORN BORN NNN 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 22 11 0 11 23 12 0 12 22 16 0 16 22 16 0 16 23 14 0 14 23 4 0 4 23 13 0 13 NOT PREGNANT 23 15 0 15 23 17 0 17 23 11 0 11 22 13 0 13 23 16 0 16 23 16 0 16 23 9 0 9 23 12 0 12 23 15 0 15 23 17 0 17 22 14 0 14 23 12 0 12 23 16 0 16 23 15 0 15 23 14 2 16 23 10 0 10 23 14 2 16 23 17 0 17 22 13 0 14 [1] 23 15 0 15 NOT PREGNANT; MATING NOT CONFIRMED 23 13 1 14 1 MF 56 66 88 6 10 95 22 58 96 89 56 76 79 12 4 63 66 78 89 86 48 97 78 59 64 86 13 4 67 4 11 58 NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 56 66 88 6 10 95 22 58 56 66 88 6 10 95 22 58 56 66 88 6 10 95 22 58 56 66 88 6 10 95 22 57 86 89 56 76 79 12 4 63 66 78 89 86 48 97 78 49 64 86 13 4 67 4 11 86 89 56 76 79 12 4 63 66 78 89 86 48 97 78 49 64 86 13 4 67 4 11 86 78 56 76 79 11 4 63 66 78 89 86 48 97 78 49 64 86 13 4 67 4 il 86 78 56 76 79 il 4 63 66 78 88 86 48 97 78 49 64 86 13 4 67 4 11 58 58 58 58 M = MALE F = FEMALE [ ] = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. TOTAL IMPLANTATIONS N 13 14 17 17 15 4 15 16 17 12 16 16 16 10 13 16 18 16 14 16 16 16 10 18 18 15 16 14 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E38 (PAGE 2) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - FI GENERATION FEMALE RATS/F2 GENERATION LITTERS ARGUS 418-020 Page 607 DOSAGE GROUP II RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 23 22 22 22 23 23 22 23 NOT PREGNANT 23 23 23 23 22 23 22 22 23 23 23 22 23 23 23 21 23 23 23 23 M = MALE F = FEMALE LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 7 07 17 1 18 15 0 15 13 0 13 15 0 15 17 0 17 14 0 14 15 2 17 12 0 12 12 0 12 13 0 13 11 0 11 13 0 13 16 1 17 16 0 16 17 0 17 11 1 12 12 0 12 10 0 10 12 0 12 15 0 15 15 0 15 12 0 12 17 0 17 13 0 13 13 0 13 14 0 14 16 0 16 1 MG/KG/DAY 1 MF NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 MF 8 MF 15 MF 22 MF 43 7 10 78 85 87 11 6 95 10 5 43 79 78 85 87 11 6 95 10 5 43 79 78 85 87 11 6 95 10 5 43 79 78 85 87 11 5 95 10 5 43 79 78 85 87 11 5 94 10 5 66 66 58 65 67 97 88 98 56 75 46 57 10 5 78 75 13 4 76 76 3 11 6 10 66 66 58 65 57 97 88 98 56 75 46 57 10 5 78 75 13 3 76 76 3 11 68 66 66 58 65 57 97 78 98 56 75 46 57 10 5 78 75 13 3 76 76 3 11 68 66 66 58 65 57 97 78 98 56 75 46 57 10 5 78 75 13 3 76 76 3 11 67 6 6 5 6 5 9 7 9 5 7 4 5 10 7 7 13 7 7 '3 6 6 6 8 5 7 7 8 8 6 5 6 7 5 8 5 3 6 6 11 7 TOTAL IMPLAN TATIONS N 12 20 17 14 18 18 14 17 16 13 16 20 15 17 16 18 14 15 16 15 16 17 12 18 14 13 16 16 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E38 (PAGE 3) : NATURAL DELIVERY, IMPIANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - FI GENERATION FEMALE RATS/F2 GENERATION LITTERS ARGUS 418-020 Page 608 DOSAGE GROUP III 3 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 23 22 23 23 23 23 22 23 22 23 23 23 NOT PREGNANT 23 23 22 22 23 NOT PREGNANT 23 23 23 23 22 23 23 23 22 22 23 LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 17(2) 17 13 15 17 16(1) 18 12 16 1 0 (1) 7 14 0 0 0 0 0 0 0 0 0 2 0 0 17 17 13 15 17 16 18 12 16 12 7 14 14 2 16 14 0 14 14 0 14 15 0 15 6 06 14 11 13 16 16 12 10 14 17(1) 17 13 0 0 2 0 0 0 0 0 0 0 0 14 11 15 16 16 12 10 14 17 17 13 1 MF 10 5 98 76 69 6 11 96 10 8 84 97 63 43 86 68 4 10 86 87 42 95 47 76 6 10 5 11 93 55 10 4 79 89 3 10 NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 10 5 98 76 69 6 11 95 10 8 84 97 63 43 86 10 5 98 76 69 6 11 95 10 7 84 97 63 43 86 10 5 98 76 69 6 11 95 10 7 84 97 63 43 86 10 5 98 76 69 6 11 95 10 7 84 97 63 43 86 68 4 10 85 67 42 68 4 10 85 55 42 68 4 10 85 55 42 68 4 10 85 55 42 85 47 76 6 10 5 11 93 55 10 4 79 89 3 10 85 47 76 6 10 5 11 93 55 10 4 79 88 3 10 85 47 76 6 10 5 11 93 55 10 4 79 88 3 10 8 4 7 6 5 9 5 10 '7 8 3 5 7 6 10 11 3 5 4 9 8 10 . M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. TOTAL IMPLAN TATIONS N 17 17 14 16 17 16 19 14 16 14 7 14 16 16 15 16 7 15 12 16 16 16 12 11 15 17 17 14 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E38 (PAGE 4) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - FI GENERATION FEMALE RATS/F2 GENERATION LITTERS ARGUS 418-020 Page 609 DOSAGE GROUP IV 10 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 1 MF NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 23 NOT PREGNANT 23 23 23 22 23 22 23 23 23 23 22 23 NOT PREGNANT 23 23 22 22 23 23 22 25 23 23 23 22 23 23 23 15(1) 15 15 10 14 14(1) 13 11 14 13 16 16 13 13 17 13 15 16 12 1 2 (1) 2 17 10 13 19(1) 12 14 14 1 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 2 0 0 1 0 16 15 15 10 15(1] 14 13 11 15 13 16 16 13 14 17 13 15 16 12 12 2 17 10 15 19 12 15 14 68 96 87 73 4 10 85 76 47 95 49 79 97 49 94 98 94 87 88 75 74 211 6 64 85 6 12 66 10 4 95 68 96 87 73 4 10 85 76 47 95 48 79 97 48 94 98 94 87 88 75 74 210 6 64 85 6 12 66 10 4 95 68 96 87 73 4 10 85 76 47 95 48 79 97 48 94 98 94 87 88 75 74 2 10 6 64 85 6 11 66 10 4 95 68 96 87 73 4 10 85 76 47 95 48 79 97 48 94 97 94 87 88 75 74 210 6 64 85 6 11 66 10 4 95 68 96 87 73 4 10 85 76 47 95 48 79 97 48 94 97 94 87 87 75 74 210 6 64 85 6 11 '6 6 10 4 95 . M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. I ] = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. TOTAL IMPLAN TATIONS N 16 15 15 16 15 17 15 11 20 16 16 16 15 15 17 15 15 16 12 14 4 17 11 15 20 14 15 16 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E38 (PAGE 5) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - FI GENERATION FEMALE RATS/F2 GENERATION LITTERS ARGUS 418-020 Page 610 DOSAGE GROUP V 30 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF GESTATION (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN N NN 1 MF NUMBER OF LIVE PUPS AT COMPLETION OF DAY POSTPARTUM 5 8 15 MF MF MF 22 MF 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 23 23 23 22 22 22 23 23 23 23 23 23 23 23 23 22 23 22 NOT PREGNANT 22 22 23 23 22 23 22 23 23 23 23 14 13 19 15 13 12 14 15 13 16 15 13 12 15 13 13 15 13 15 12 4 13 11 13 14 14 6 17 15(1) 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 14 14 19 15 14 12 14 15 13 16 15 13 12 15 13 13 15 13 15 12 4 13 11 13 14 14 6 17 15 4 10 67 9 10 87 49 57 77 78 58 10 6 78 67 66 2 13 76 67 78 85 87 57 31 76 56 49 68 10 4 24 7 10 10 4 4 10 66 99 87 49 57 77 78 58 10 6 78 67 66 2 13 76 67 78 85 87 47 31 76 56 49 68 10 4 24 7 10 10 4 4 10 66 99 87 49 57 77 77 58 10 6 68 67 66 2 13 76 67 78 65 87 47 31 76 56 49 68 10 4 24 7 10 10 4 4 10 66 99 87 49 57 77 77 58 10 6 68 67 66 2 13 76 67 78 65 4 10 66 98 87 49 57 77 77 58 10 6 68 67 66 2 13 76 67 78 65 87 47 31 76 56 49 68 10 4 24 7 10 10 4 8 4 3 7 5 4 6 10 '2 7 10 7 7 1 6 6 9 8 4 4 10 4 M = MALE F = FEMALE ( ) NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. TOTAL IMPLAN TATIONS N IS 15 19 17 14 14 16 15 14 17 15 15 16 15 17 15 16 13 15 12 5 13 13 14 16 14 6 17 17 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE E39 (PAGE 1) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 611 MATERNAL DOSAGE GROUP I 0 MG/KG/DAY RAT/ LITTER NUMBER 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 DAY 1 MFT DAY 5 MFT 6.9 6.3 6.6 11.7 10.4 11.0 6.5 6.1 6.3 11.6 10.5 11.1 6.2 5.9 6.1 9.7 9.9 9.8 6.2 6.1 6.1 8.3 8.6 8.4 6.8 6.1 6.5 10.7 10.2 10.5 8.4 8.0 8.2 13.8 14.2 14.0 6.7 6.2 6.4 10.8 10.5 10.6 NOT PREGNANT 7.3 7.0 7.2 12.3 12.2 12.2 6.4 6.2 6.3 8.8 8.6 8.7 6.8 6.6 6.7 10.7 10.6 10.7 6.2 6.0 6.1 9.8 9.5 9.6 6.6 6.3 6.5 8.8 8.3 8.5 6.1 6.0 6.1 8.8 8.2 8.6 7.2 6.5 7.0 11.1 10.4 10.9 6.6 6.0 6.3 9.8 9.4 9.6 7.1 6.9 7.0 10.4 10.4 10.4 6.4 6.3 6.3 10.4 10.0 10.2 6.4 5.9 6.2 10.9 10.2 10.6 7.2 6.7 6.9 11.3 10.7 10.9 6.3 5.8 6.1 10.3 9.5 10.0 7.0 6.6 6.8 10.7 9.9 10.3 7.3 6.5 6.8 10.6 9.9 10.1 6.2 5.8 6.0 11.1 10.6 10.9 6.3 6.0 6.2 9.1 8.7 9.0 6.1 5.7 6.0 8.6 8.0 8.4 6.3 6.1 6.2 11.0 10.5 10.7 6.8 6.5 6.6 9.9 9.8 9.8 NOT PREGNANT; MATING NOT CONFIRMED 6.3 6.0 6.1 9.3 9.2 9.3 DAY 8 MFT 16.2 17.2 14.0 12.0 15.9 21.2 15.5 15.0 15.6 13.4 11.6 14.9 21.8 14.8 15.6 16.4 13.7 11.7 15.6 21.5 15.0 17.7 12.7 15.4 14.9 11.5 11.8 15.3 14.8 15.6 15.0 14.6 16.2 14.6 14.5 15.7 16.8 13.4 12.1 13.0 14.4 17.6 12.3 15.3 14.3 10.9 11.0 14.7 14.2 15.8 14.6 13.8 15.7 13.2 14.0 14.9 16.2 12.9 11.2 12.4 13.8 17.6 12.5 15.3 14.6 11.2 11.6 15.1 14.5 15.7 14.8 14.3 15.8 14.0 14.2 15.1 16.5 13.2 11.9 1 2 .7 14.0 12.3 12.0 12.1 DAY 15 MFT 28.4 28.6 23.2 22.1 27.8 36.9 24.4 26.5 26.3 22.5 22.4 25.0 39.2 22.0 27.4 27.4 22.8 22.3 26.8 38.0 23.0 28.4 18.9 28.6 29.1 21.3 22.0 28.4 25.4 24.8 20.2 27.0 28.7 23.6 25.0 29.4 31.8 26.4 21.3 24.4 26.5 28.2 16.4 28.2 27.9 19.0 20.0 28.2 25.0 25.5 17.7 25.1 27.6 19.8 24.3 28.3 30.8 25.4 19.6 23.7 25.5 28.3 17.6 28.4 28.5 20.0 21.5 28.3 25.2 25.2 18.9 26.2 28.0 21.9 24.7 28.6 31.4 26.0 20.9 24.0 25.8 25.2 24.0 24.4 DAY 22 MFT 47.4 45.6 34.2 27.6 44.6 53.0 40.7 44.1 43.3 34.0 28.5 40.0 53.3 38.4 45.6 44.4 34.1 28.2 43.0 53.2 39.4 48.3 31.2 36.5 48.9 27.9 30.8 38.7 41.6 40.9 29.0 42.5 47.6 38.2 43.8 40.0 42.2 37.1 25.8 41.4 41.3 48.1 27.4 36.2 45.4 23.4 28.0 38.3 39.9 41.2 27.9 40.6 45.4 33.6 42.4 39.4 40.7 35.4 24.2 40.5 39.8 48.2 29.2 36.3 47.3 25.4 30.0 38.5 40.7 41.1 28.4 41.7 46.1 36.2 43.1 39.6 41.6 36.3 25.4 40.9 40.2 41.9 39.7 40.5 M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO -GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE E39 (PAGE 2) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 612 MATERNAL DOSAGE GROUP II 1 MG/KG/DAY RAT/ LITTER NUMBER 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 DAY 1 MFT 6.6 6.2 6.4 6.0 5.7 5.8 5.4 5.1 5.3 6.9 6.6 6.8 6.5 5.9 6.2 6.6 6.4 6.5 6.6 6.0 6.4 6.2 6.1 6.1 NOT PREGNANT 6.6 6.4 6.5 7.6 6.8 7.2 6.3 5.7 5.9 6.4 6.1 6.2 7.1 6.5 6.8 6.9 6.4 6.7 6.0 5.3 5.6 5.9 5.6 5.7 6.6 6.1 6.4 7.5 7.4 7.5 7.0 6.7 6.8 6.8 6.6 6.6 6.1 5.8 6.0 6.5 6.1 6.3 6.0 5.8 5.9 6.0 5.5 5.9 6.5 5.9 6.2 6.6 6.0 6.4 6.3 6.5 6.4 6.4 6.0 6.2 DAY 5 M FT 12.0 8.6 9.1 11.1 10.9 8.9 10.2 9.1 11.5 8.5 8.7 10.8 10.2 9.0 9.1 9.2 11.7 8.6 8.9 11.0 10.6 8.9 9.8 9.2 11.0 12.3 10.2 10.7 11.9 10.4 8.3 8.6 11.2 12.1 12.4 11.4 10.1 8.7 10.1 9.6 9.4 9.4 9.3 9.0 10.0 11.1 9.1 10.4 11.2 9.9 8.0 7.7 10.4 12.3 11.8 11.2 10 .0 8.7 10.0 9.2 8.5 8.8 9.2 8.0 10.5 11.7 9.5 10.6 11.5 10.2 8.2 8.2 10.8 12.2 12.0 11.3 10.1 8.7 10.1 9.5 9.0 9.1 9.2 8.4 DAY 8 M FT 17.6 12.8 13.5 16.0 15.8 12.0 14.6 12.9 17.1 12.4 12.8 15.5 15.1 12.1 12.8 13.0 17.4 12.6 13.1 15.8 15.5 12.0 14.0 12.9 16.0 16.9 15.7 15.9 17.5 14.6 12.3 12.3 17.1 17.9 17.3 15.9 12.9 13.0 14.1 14.0 12.8 13.2 1 2 .9 13.9 14.8 15.2 14.1 15.8 16.7 14.3 11.6 11.2 16.1 17.4 16.3 15.9 12.5 13.1 14.0 13.0 12.2 12.5 13.2 11.4 15.4 16.0 14.7 15.8 17.0 14.5 11.9 11.8 16.5 17.7 16.7 15.9 12.8 13.0 14.0 13.8 12.5 12.9 13.1 12.5 DAY IS M FT 33.8 21.8 23.0 28.8 24.9 21.3 26.1 22.4 32.8 20.7 21.5 27.4 24.0 22.5 22.2 22.2 33.3 21.2 22 .2 28.3 24.4 21.7 24.7 22.3 28.9 29.3 31.0 29.9 28.3 24.4 23.0 22.8 32.4 26.7 27.9 24.7 23.4 21.4 27.7 24.2 26.1 22.6 21.9 23.2 27.2 27.0 28.5 29.8 27.6 24.7 21.3 21.7 31.1 26.0 26.2 24.3 21.9 21.6 27.0 22.0 25.7 21.4 21.9 20.6 28.0 28.2 29.5 29.9 27.9 24.5 22.1 22.3 31.7 26.4 26.9 24.5 22.9 21.6 27.4 23.8 25.9 22.1 21.9 21.8 DAY 22 MFT 42.7 32.5 32.9 37.4 42.2 33.7 34.5 36.7 42.3 32.1 30.6 35.8 38.8 36.2 30.5 36.0 42.5 32.3 31.7 36.7 40.6 34.5 33.3 36.4 38.8 50.9 38.3 46.8 41.8 36.0 36.8 30.2 44.4 49.5 47.4 44.3 37.2 34.5 47.5 39.5 45.2 37.8 35.3 36.2 36.0 47.3 35.1 47.1 41.5 36.4 34.7 28.6 43.0 47.1 45.0 41.5 33.4 35.7 45.2 36.2 43.6 36.6 35.4 32.7 37.4 49.1 36.3 46.9 41.7 36.2 35.7 29.4 43.6 48.5 46.0 42.6 35.9 35.1 46.6 38.9 44.5 37.2 35.4 34.3 M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E3 9 (PAGE 3): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 613 MATERNAL DOSAGE GROUP III 3 MG/KG/DAY RAT/ LITTER NUMBER DAY 1 M FT DAY 5 M FT DAY 8 MFT DAY 15 MFT DAY 22 MFT 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 6.7 6.3 6.6 5.5 5.2 5.3 6.7 6.2 6.5 6.9 6.2 6.5 6.7 6.1 6.3 6.3 6.5 6.4 6.1 5.9 6.0 6.4 5.8 6.2 6.0 5.9 6.0 6.8 6.5 6.7 8.3 7.9 8.1 6.3 6.2 6.2 NOT PREGNANT 6.8 6.3 6.5 6.1 6.0 6.0 5.6 5.0 5.3 6.0 5.6 5.8 7.1 6.8 7.0 NOT PREGNANT 6.3 5.9 6.2 6.8 6.7 6.7 6.5 6.0 6.3 6.9 6.7 6.8 5.9 5.5 5.6 6.4 6.5 6.4 8.3 7.9 8.1 6.5 6.4 6.5 6.0 5.7 5.8 5.5 5.5 5.5 7.7 7.4 7.4 9.8 8.3 10.2 10.4 9.4 10.3 9.4 10.4 9.4 11.3 14.3 10.0 9.6 7.8 9.5 9.7 8.7 10.3 9.0 9.8 9.2 10.8 14.1 10.0 9.8 8.1 9.9 10.0 9.0 10.3 9.2 10.2 9.3 11.2 14.2 10.0 10.8 8.6 8.5 9.5 13.2 9.2 8.6 7.9 8.6 12.7 9.9 8.6 8.2 9.0 13.0 1 0 .9 9.9 10.4 10.9 10.0 9.9 14.2 10.2 8.1 8.5 12.1 10.7 10.6 9.8 10.7 9.1 9.8 13.0 9.7 7.5 8.3 11.6 10.8 10.4 10.1 10.8 9.4 9.8 13.6 10.0 7.8 8.4 11.7 13.9 12.2 14.0 15.1 12.3 14.7 13.6 15.3 13.4 17.4 20.6 14.5 13.2 11.4 13.4 14.1 11.4 14.6 13.8 14.3 13.0 16.5 20.0 14.4 13.6 11.8 13.7 14.5 11.7 14.7 13.7 14.9 13.2 17.1 20.3 14.5 14.6 12.6 12.7 15.2 19.4 13.0 12.5 11.8 14.2 18.0 13.7 12.5 12.4 14.7 18.9 16.5 14.8 14.5 14.8 13.0 13.5 19.0 13.8 11.3 10.0 17.1 16.3 16.1 13.4 14.8 11.9 13.8 17.1 13.9 10.4 10.2 16.4 16.4 15.6 14.0 14.8 12.2 13.6 18.0 13.8 10.8 10.1 16.5 24.5 20.0 27.5 24.6 21.8 26.9 23.4 27.7 23.7 32.6 37.4 26.6 22.6 19.2 25.6 22.5 19.7 26.2 24.2 25.9 21.5 29.9 36.8 26.2 23.8 19.6 26.6 23.3 20.4 26.6 23.7 27.1 22.8 31.7 37.2 26.4 25.9 24.1 22.3 32.2 36.8 23.6 23.5 21.2 29.5 36.6 24.6 23.7 21.8 30.9 36.7 25.9 28.4 25.0 25.6 20.1 27.5 28.8 24.9 23.4 18.8 28.2 25.6 30.2 24.0 24.3 20.8 27.1 26.8 24.8 23.2 20.9 28.4 25.8 29.5 24.5 24.8 20.6 27.4 27.8 24.8 23.3 19.8 28.3 31.6 27.5 35.7 39.6 32.9 43.3 37.1 37.8 39.1 54.2 52.0 40.3 30.0 27.2 33.8 37.2 30.2 43.0 38.8 35.8 36.8 50.7 53.1 40.0 31.0 27.4 34.8 38.2 31.1 43.2 37.8 37.2 38.1 53.0 52.4 40.2 42.3 31.4 34.1 49.0 50.1 37.8 29.7 32.9 45.1 49.4 39.8 30.2 33.6 47.0 49.9 44.8 49.1 37.3 43.7 32.4 36.1 49.9 40.9 36.5 29.9 4'6 .1 44.4 49.9 37.7 40.8 31.6 35.1 46.5 39.8 35.4 34.7 44.6 44.6 49.6 37.5 41.9 31.9 35.8 48.2 40.6 35.9 .32.3 45.0 M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E39 (PAGE 4) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 614 MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY RAT/ LITTER NUMBER 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 DAY 1 M FT 7.1 6.8 6.9 NOT PREGNANT 7.1 6.8 7.0 6.5 6.0 6.3 7.9 7.1 7.7 6.0 5.7 5.8 6.7 6.0 6.4 6.3 6.3 6.3 7.0 6.9 6.9 6.1 6.2 6.2 6.4 5.8 6.0 6.3 6.1 6.2 5.5 5.4 5.4 6.5 5.7 6.0 NOT PREGNANT 6.8 6.7 6.8 6.3 6.1 6.2 6.8 6.8 6.8 5.8 5.6 5.7 6.3 5.7 6.0 7.1 6.9 7.0 6.1 5.8 6.0 8.6 -- 8.6 6.3 5.9 6.2 7.1 6.5 6.8 6.7 5.8 6.3 5.6 5.3 5.4 7.3 6.9 7.1 6.4 5.8 6.2 6.4 6.4 6.4 DAY 5 M FT 10.8 10.1 10.4 10.4 10.8 14.1 10.0 10.2 9.2 11.4 9.0 11.4 9.3 7.7 11.1 9.9 9.8 13.1 9.2 9.4 9.7 11.0 8.8 10.4 8.6 7.6 10.0 10.2 10.3 13.8 9.4 9.8 9.4 11.2 9.0 10.8 8.9 7.7 10.4 10.1 9.2 11.4 9.8 9.8 10.7 10.6 15.0 9.3 11.0 10.8 8.9 10.1 10.0 11.2 10.2 8.8 11.1 9.3 8.4 10.4 10.1 -- 8.6 10.2 9.7 8.4 9.6 8.6 11.2 10.1 9.0 11.3 9.6 9.1 10.6 10.4 15.0 9.0 10.7 10.4 8.6 9.8 9.6 11.2 DAY 8 M FT 14.3 12.8 13.4 14.6 15.6 19.8 14.3 14.0 11.3 17.2 12.4 16.6 12.1 10.8 16.0 14.1 14.2 18.3 13.2 13.0 11.2 17.0 12.7 15.5 11.9 10.4 15.0 14.4 15.0 19.4 13.5 13.6 11.2 17.1 12.5 15.9 12.0 10.6 15.3 14.7 13.3 16.3 14.2 13.3 14.5 15.8 21.5 13.2 13.0 15.7 12.6 13.8 14.1 16.3 13.7 12.1 15.7 13.2 11.9 14.1 14.7 -- 12.0 12.1 13.9 12.9 13.2 12.2 16.3 14.4 12.8 16.1 13.7 12.6 14.3 15.4 21.5 12.7 12.6 15.0 12.8 13.5 13.6 16.3 DAY 15 M FT 23.6 21.4 22.4 25.7 26.9 31.0 27.3 24.7 22.1 30.2 24.6 31.1 19.4 22.6 29.4 25.2 24.3 28.7 25.7 23.6 22.0 30.3 24.2 28.4 19.4 21.1 27.7 25.5 25.7 30.4 26.1 24.3 22.0 30.3 24.5 29.3 19.4 22.0 28.2 23.7 20.7 28.6 26.8 23.1 24.7 30.1 33.6 18.7 26.4 24.4 21.1 22.5 22.6 25.4 22.4 19.4 27.2 25.8 19.8 23.3 27.0 -- 16.8 24.3 2 2 .9 21.9 22.2 20.6 24.8 23.3 20.1 28.2 26.4 21.4 24.1 29.0 33.6 18.0 25.6 23.8 21.6 22.4 22.0 25.2 DAY 22 MFT 37.9 34.5 35.9 33.1 39.4 52.2 34.1 43.3 37.7 52.4 40.1 47.9 29.3 33.6 40.8 34.4 36.1 49.3 31.8 40.1 37.7 48.3 40.7 45.9 29.3 31.4 39.9 33.6 37.9 51.4 32.4 42.1 37.7 49.8 40.3 46.5 29.3 32.7 40.2 38.3 32.4 46.2 35.0 36.4 43.2 46.8 54.4 28.5 44.1 40.0 35.2 39.4 34.9 40.6 36.6 31.0 43.8 31.9 33.2 41.3 44.3 _____ 25.4 40.5 37.4 36.0 37.8 33.2 40.7 37.8 31.8 45.4 33.6 34.9 42.4 45.9 54.4 27.3 42.6 39.0 35.7 38.6 ?4.4 40.6 M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E3 9 (PAGE 5) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 615 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY RAT/ LITTER NUMBER DAY 1 M FT DAY 5 M FT DAY 8 M FT DAY 15 M FT DAY 22 MFT 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 6.0 5.6 5.7 6.4 6.4 6.4 6.3 6.1 6.2 5.6 5.4 5.5 5.3 5.2 5.2 6.6 6.0 6.2 6.3 6.0 6.2 6.3 5.4 5.8 6.8 6.5 6.6 6.5 6.5 6.5 5.8 5.5 5.7 6.2 5.8 6.0 6.2 5.8 6.0 6.2 5.9 5.9 6.8 6.5 6.7 5.6 5.2 5.3 6.5 6.0 6.3 5.8 5.8 5.8 NOT PREGNANT 6.4 6.0 6.2 5.4 5.2 5.3 6.8 6.5 6.8 5.7 5.4 5.6 5.8 5.6 5.6 6.4 6.0 6.2 5.7 5.4 5.5 6.1 5.9 6.0 7.0 7.1 7.1 5.9 5.8 5.8 6.3 5.7 6.1 10.4 11.1 9.5 9.4 8.7 10.5 9.0 9.0 11.3 9.9 7.4 10.2 11.0 9.4 10.4 8.0 10.3 7.3 9.6 10.9 8.7 9.1 8.6 9.6 8.6 8.3 11.1 10.2 7.0 9.2 9.9 8.4 10.3 7.4 9.5 7.4 9.8 11.0 9.1 9.2 8.6 10.0 8.8 8.7 11.1 10.0 7.2 9.7 10.5 8.5 10.3 7.6 9.9 7.3 10.4 10.1 12.3 9.3 9.8 9.2 8.4 9.9 12.4 9.3 10.4 10.1 9.6 10.9 9.0 9.3 9.5 7.8 9.6 12.9 8.8 9.6 10.3 9.8 12.0 9.2 9.5 9.4 8.1 9.8 12.7 9.0 10.2 14.4 15.7 13.8 13.0 12.6 14.9 12.6 12.8 15.5 13.9 10.6 13.0 15.4 12.4 14.3 11.3 14.2 1 0 .5 13.4 15.0 12.4 12.3 12.4 13.8 12.6 11.9 15.3 13.9 10.0 12.3 13.9 11.4 14.4 10.4 13.9 10.8 13.6 15.3 13.1 12.7 12.4 14.2 12.6 12.4 15.4 13.9 10.2 12.6 14.6 11.5 14.4 10.8 14.1 10.7 14.0 15.5 18.6 13.1 13.9 13.1 11.4 13.7 19.0 11.6 14.6 13.5 14.6 17.4 12.7 13.9 13.5 10.8 14.0 19.6 11.0 13.5 13.8 14.9 18.3 12.9 13.9 13.4 11.1 13.8 19.4 11.3 14.3 25.1 30.3 21.8 18.7 24.3 24.0 21.1 21.7 27.3 23.3 20.3 22.9 24.6 21.7 25.7 21.3 24.2 20.3 23.8 29.7 19.9 17.8 23.9 22.3 21.1 20.2 27.3 22.9 18.1 21.6 23.0 19.2 25.7 19.8 23.4 20.5 24.2 30.0 20.9 18.3 24.0 23.0 21.1 20.9 27.3 23.1 19.0 22.2 23.8 19.5 25.7 20.5 23.8 20.4 21.7 25.2 35.5 21.3 23.7 23.8 21.0 22.1 30.1 19.8 23.4 20.9 24.4 32.0 20.4 22.6 24.4 20.7 22.0 31.3 18.5 21.8 21.3 24.7 34.6 20.9 23.1 24.2 20.8 22.1 30.9 19.0 23.0 33.2 45.0 33.4 32.0 37.0 41.0 34.0 31.4 33.5 34.5 33.4 38.7 38.9 37.8 43.5 31.2 37.6 32.2 33.3 45.0 32.5 31.3 36.5 37.3 33.5 28.4 33.8 34.8 29.9 35.3 38.1 33.5 45.4 29.2 36.8 32.9 33.3 45.0 33.0 31.7 36.7 38.9 33.7 29.9 33.7 34.6 31.4 36.9 38.5 34.0 44.4 30.1 37.2 32.5 34.1 40.0 58.2 37.8 39.5 39.3 25.6 35.5 51.6 27.8 38.1 32.8 40.8 50.7 36.6 37.6 39.6 25.9 35.4 53.8 26.2 36.0 33.5 40.5 56.4 37.2 38.4 39.5 25.8 35.5 53.1 .26.9 37.5 m = Ma l e f = female t =. t o t a l (s u m o f p u p w e i g h t s /n u m b e r o f l i v e p u p s ) day = day postpartum ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 1) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 616 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 1 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 7.0 6.9 6.9 7.2 6.5 5.8 6.9 6.3 6.7 6.0 6.2 6.3 6.5 7.2 6.8 6.4 5.7 6.4 5.8 5.8 6.5 5.6 6.4 6.4 6.2 6.4 6.4 6.6 5.6 6.3 6.0 5.8 6.1 5.6 5.4 5.8 5.9 6.2 6.3 5.9 6.5 6.3 6.3 6.2 6.2 6.5 6.1 6.1 5.8 6.1 6.3 5.9 5.7 6.6 5.8 6.5 6.9 7.1 7.3 6.7 6.7 6.7 6.3 6.8 6.5 6.2 6.4 5.9 5.5 8.1 8.6 8.4 7.5 6.8 6.4 6.8 6.8 6.8 6.7 6.6 6.3 5.9 6.1 5.9 6.1 6.4 NOT PREGNANT 7.5 7.8 7.7 7 .4 6.9 7.2 6.7 7.6 6.8 5.8 7.2 7.3 6.9 7.4 7.2 6.2 6.7 6.6 6.7 6.2 6.0 6.4 6.4 6.3 6.2 6.1 6.5 6.1 6.0 6.5 5.7 6.3 6.4 7.1 6.7 7.5 6.0 6.6 6.9 6.0 7.3 6.5 6.1 6.2 6.6 6.2 6.1 5.6 6.5 6.1 5.8 6.1 5.8 6.0 6.1 6.7 6.8 6.5 6.8 6.3 6.9 6.3 6.3 6.2 6.2 6.0 6.5 6.4 6.7 6.5 6.3 6.8 5.4 6.1 6.0 5.7 6.1 6.7 5.9 6.7 6.0 6.1 6.2 5.6 6.4 6.2 5.8 7.2 7.3 7.3 7.1 7.3 7.1 6.9 6.5 6.2 6.9 6.1 6.9 6.6 6.6 6.2 5.9 5.9 6.2 6.0 6 .1 6.0 6.8 7.4 7.4 6.5 7.1 7.0 7.6 7.1 7.2 6.7 6.5 6.5 7.2 7.2 6.8 6.6 6.4 6.3 5.8 6.4 6.7 6.2 6.6 6.5 6.3 6.6 5.9 6.8 6.5 6.3 5.7 6.7 6.0 6.3 5.8 6.6 7.0 6.5 6.5 6.5 5.3 6.0 5.8 5.5 6.3 7.1 7.1 7.5 7.3 6.7 6.8 6.6 6.0 7.0 6.6 7.0 6.9 6.6 6.4 6.2 6 .1 6.1 6.2 6.7 6.1 6.3 5.7 5.7 5.7 5.6 5.9 6.2 5.8 7.1 7.4 6.9 6.8 6.7 7.1 7.3 6.3 6.6 6.7 6.4 7.2 7.1 6.8 5.6 7.6 6.5 7.3 7.6 7.5 MS 6.7 6.8 6.3 7.2 7.0 6.2 6.1 5.8 6.7 FS 6.4 6.3 6.2 6.2 6.2 6.0 5.6 6.1 5.7 5.8 5.9 6.8 5.7 5.9 6.5 6.8 MS 6.2 6.7 5.8 6.8 6.7 4.9 5.5 6.4 FS 6.1 6.0 6.7 6.1 5.3 5.4 5.9 7.0 6.9 6.5 4.8 6.0 6.8 6.8 5.5 4.9 6.0 6.5 7.4 6.7 5.5 5.5 6.1 6.1 6.2 6.4 6.0 5.7 6.1 FU 6.6 6.7 7.0 6.9 6.7 6.5 6.4 6.3 6.5 6.3 6.3 6.8 6.4 6.4 6.7 NOT PREGNANT; MATING NOT CONFIRMED 6.4 6.7 5.7 6.2 6.5 6.3 6.1 5.9 6.1 6.0 6.2 5.7 6.1 FS ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.G) TABLE E40 (PAGE 2) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 617 PUP # 1 2 3 4 5 G 7 8 9 10 11 12 13 14 15 1G 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 1 13G2 1363 13G4 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 6.8 6.4 6.7 5.7 6.3 6.3 5.5 5.6 5.1 6.6 7.4 7.0 6.6 5.7 6.7 6.3 7.2 6.5 6.4 6.9 7.2 6.4 6.6 6.2 NOT PREGNANT 6.4 6.2 6.6 7.6 7.9 7.0 6.1 6.0 6.0 5.4 6.3 7.0 7.3 6.9 7.1 6.3 6.0 6.2 5.5 5.6 6.5 7.0 7.3 6.5 7.8 7.5 7.3 7.1 7.2 7.1 6.9 6.9 6.2 5.7 6.2 6.4 6.5 6.2 6.1 6.2 6.1 5.9 5.7 6.0 5.9 6.5 6.4 6.6 6.5 6.4 6.7 6.2 6.7 6.1 6.6 6.6 6.4 6.3 6.3 5.6 7.4 7.1 6.4 6.7 6.7 7.0 8.2 6.9 6.6 6.7 6.3 6.2 6.4 8.1 6.7 7.0 6.4 6.5 6.0 5.7 6.4 6.6 6.4 6.0 6.5 5.6 5.0 6.6 6.7 6.7 6.4 6.2 6.8 7.1 6.3 6.2 6.6 6.0 6.1 6.0 6.8 6.5 7.0 6.8 6.3 6.2 6.0 6.9 6.7 6.0 6.6 5.9 6.0 5.3 6.7 6.6 6.4 6.6 6.0 6.5 7.6 5.7 6.8 7.0 5.2 6.1 MS 7.6 6.8 7.1 5.0 6.8 6.0 6.0 6.7 6.9 6.6 6.0 6.1 6.1 5.9 7.0 6.5 6.5 6.4 5.8 5.9 7.4 5.8 6.1 6.8 6.1 5.8 6.4 7.7 7.3 6.0 5.7 7.2 5.8 6.7 6.3 6.6 6.6 5.9 5.5 5.1 6.8 6.0 6.7 6.6 6.2 6.8 6.8 5.8 6.0 6.7 5.6 5.7 6.5 7.1 7.3 6.1 6.4 6.6 5.8 5.7 6.0 5.8 6.4 6.0 5.6 5.5 6.4 5.8 6.6 6.5 5.8 6.3 6.5 5.9 5.7 6.9 5.2 5.8 6.6 7.4 6.1 6.7 6.0 5.6 5.4 6.2 5.9 6.0 6.5 6.1 6.2 5.2 6.7 5.2 6.6 6.4 5.8 6.7 6.8 5.6 6.7 6.1 5.2 5.5 6.6 7.4 6.4 6.9 6.2 6.3 5.8 6.2 6.1 5.8 6.5 6.2 4.7 5.3 6.6 6.0 6.6 6.1 MS 6.5 6.5 5.5 6.0 6.3 5.7 5.6 5.4 8.1 6.5 6.4 6.0 5.7 6.2 5.5 5.9 6.8 5.8 5.0 4.5 6.2 6.3 6.3 5.5 MS 6.4 6.7 5.6 7.2 5.4 5.9 5.3 6.9 6.6 5.6 6.4 6.3 5.2 6.5 6.8 6.5 6.0 6.6 5.1 7.0 5.4 6.1 5.5 6.6 5.9 6.8 5.0 5.1 5.4 6.1 6.3 5.4 6.0 6.8 6.3 5.6 5.0 5.7 6.3 6.3 5.9 6.4 5.3 5.8 6.0 5.8 5.8 6.3 6.2 6.0 5.4 7.2 6.7 6.3 6.1 5.4 5.7 5.7 6.3 6.2 5.7 6.1 6.4 6.1 6.0 5.4 5.4 5.4 6.0 5.6 6.4 5.4 FS 5.4 4.5 FS ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE ' SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 3) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 618 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 1 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 7.3 6.3 6.6 5.9 5.8 5.4 6.8 6.5 6.7 7.0 6.3 7.2 6.2 7.2 6.7 6.4 6.6 5.6 6.2 6.1 6.1 5.8 6.5 6.6 6.4 5.9 5.5 6.7 6.9 7.1 8.7 8.2 8.0 6.4 6.4 6.3 NOT PREGNANT 6.6 7.4 6.8 5.8 6.6 5.7 5.8 5.4 5.7 6.2 5.7 5.9 7.2 6.9 7.1 NOT PREGNANT 6.8 6.0 6.0 7.0 6.5 7.2 6.4 6.5 6.0 6.6 7.3 6.9 5.9 5.9 6.1 6.3 6.5 6.8 8.7 8.8 8.5 6.7 6.3 6.0 6.0 5.7 5.6 5.9 5.8 5.0 8.0 7.6 7.5 6.8 5.4 6.9 6.8 6.7 6.8 5.6 6.4 6.2 6.7 8.3 6.6 6.6 6.3 5.5 5.8 7.1 6.1 6.6 6.5 6.6 5.7 6.0 7.7 6.5 6.2 5.0 8.0 6.6 6.8 5.4 5.1 7.1 6.7 7.0 6.9 6.6 7.0 6.3 6.4 5.9 5.4 6.8 6.9 6.4 6.0 6.6 6.5 8.3 8.0 6.4 6.5 7.3 6 .1 6.2 6.4 5.8 5.5 5.9 6.1 6.9 6.6 6.2 6.4 7.2 6.0 6.9 6.5 6.7 7.1 6.0 4.7 5.9 5.9 7.8 8.5 7.0 6.7 6.0 6.4 6.1 4.9 7.7 7.4 7.1 6.5 6.8 6.6 5.4 5.3 5.6 5.4 6.3 6.2 5.9 6.1 5.8 5.6 6.1 6.8 5.7 6.1 6.0 6.2 6.6 6.5 5.9 MD 1 6.4 6.2 6.7 6.7 6.2 6.0 5.8 5.8 6.2 6.7 5.1 6.1 6.2 6.4 6.9 FD 1 7.4 6.8 5.1 6.1 6.4 MS MS 6.4 6.1 5.6 5.6 6.3 5.9 5.3 5.4 5.5 4.5 6.0 6.4 5.4 5.2 6.2 6.8 6.3 5.9 6.7 6.7 7.1 6.6 6.9 MS 5.9 5.9 6.8 6.4 7.1 7.0 5.7 5.3 5.4 5.5 6.3 7.0 6.6 6.3 7.6 7.6 7.7 8.2 6.0 6.5 6.5 6.8 6.1 MD 1 6.0 5.4 5.1 6.2 5.9 4.8 7.2 7.3 7.5 7.1 6.2 5.4 6.4 6.0 7.0 6.6 6.0 5.9 6.2 FS 6.5 6.0 6.6 5.4 5.9 6.4 6.6 5.9 6.5 5.7 6.3 6.4 5.3 6.1 7.4 6.9 5.2 6.6 6.7 5.8 6.6 6.0 5.6 6.0 FS 6.1 6.0 5.9 5.2 5.5 6.0 6.5 6.3 5.8 6.8 6.3 6.1 5.9 7.6 5.9 4.9 6.2 6.4 6.1 6.1 5.5 6.1 6.0 5.9 6.0 4.7 5.2 5.5 5.9 6.9 5.6 6.5 6.1 4.9 6.5 6.2 4.9 6.6 5.9 6.4 6.2 5.7 6.0 6.5 5.8 4.9 5.8 5.9 5.9 6.1 5.8 6.6 5.3 5.7 6.4 FD 1 FD 1 5.0 5.1 5.3 6.2 6.5 6.4 5.6 6.2 6.9 5.8 5.8 6.0 5.5 5.8 6.7 6.5 5.9 FS 7.0 6.7 5.5 5.8 5.9 5.7 5.3 5.2 5.3 5.5 5.6 * ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE :PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020 ? ! ^ J GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 4) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 CO 00 in in Page 619 PUP # RAT/ LITTER # 12 34 5 MATERNAL DOSAGE GROUP IV 6 7 8 9 10 11 12 13 14 15 16 17 18 19 10 MG/KG/DAY ............... .............. ......... POSTPARTUM DAY 1 1482 1483 1486 1488 1490 1491 14 94 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 7.2 7.2 7.1 7.3 NOT PREGNANT 7.0 6.9 6.3 5.9 6.9 7.3 7.1 7.1 6.9 6.7 FD 1 FS 7.1 7.3 7.7 6.8 7.4 7.4 6.5 7.2 6.5 6.7 7.3 6.7 6.2 7.1 6.7 6.1 7.2 6.3 6.0 6.0 6.7 6.5 7.2 6.1 6.5 6.2 6.2 5.7 6.1 5.6 8.5 7.5 8.1 8.9 7.1 6.6 8.5 7.5 6.2 7.7 5.9 6.1 5.9 6.0 5.7 5.9 4.8 6.2 5.9 5.6 6.0 5.9 4.9 UU 6.2 6.6 6.9 6.6 7.0 6.7 6.6 6.9 MD 1 6.4 5.6 6.7 4.9 6.2 6.6 5.7 6.7 6.4 6.2 6.8 5.9 6.0 6.3 6.5 6.3 6.1 6.5 6.9 7.2 6.9 7.0 6.8 6.8 6.6 7.3 6.8 6.5 7.4 6.3 6.0 6.5 6.8 5.9 5.2 5.9 6.3 6.3 6.3 6.1 6.2 6.4 6.0 FS 6.3 6.6 6.7 6.2 5.5 5.6 6.0 5.8 6.5 5.7 5.7 6.2 5.5 6.6 6.1 6.2 6.1 6.7 6.6 6.0 6.3 6.1 6.1 5.7 6.0 5.9 6.6 5.7 6.3 5.9 5.6 5.3 5.4 5.6 5.4 5.4 5.7 4.9 5.8 5.5 4.8 5.3 5.5 5.4 5.5 6.2 7.0 6.4 6.4 5.6 5.4 5.9 5.6 5.6 5.3 5.4 6.8 5.9 NOT PREGNANT 7.0 6.5 6.7 7.3 6.0 7.2 7.1 6.8 6.9 6.7 6.4 6.6 7.0 MS 6.7 6.5 6.5 6.8 6.0 6.6 6.0 5.6 6.2 5.7 5.9 6.0 6.3 6.3 5.7 6.4 6.2 6.8 7.1 7.0 6.9 6.7 7.1 6.3 6.4 7.4 7.2 6.8 6.7 6.7 6.3 6.0 5.5 5.4 5.5 6.0 5.9 6.1 5.8 5.6 5.6 5.9 5.6 5.5 5.4 5.9 6.3 6.7 6.4 5.8 6.4 6.4 6.2 6.5 5.5 5.0 6.1 6.3 5.3 5.6 5.3 7.0 7.7 6.3 7.4 7.5 7.0 6.7 6.6 7.2 6.7 7.1 6.8 6.4 6.3 6.6 6.2 6.3 6.6 4.6 MD 1 4.6 5.9 6.2 6.6 8.4 8.9 6.5 6.9 6.5 6.7 6.3 6.3 6.8 6.3 4.4 6.6 6.5 5.7 5.6 6.4 6.0 5.5 6.0 7.1 7.6 6.6 7.0 7.3 7.0 6.3 6.6 6.5 6.5 6.6 7.2 6.5 6.2 7.0 6.3 6.7 6.9 MS 4.9 6.2 5.8 5.9 6.3 FS 5.0 5.5 5.7 6.2 5.7 5.5 5.4 5.3 5.9 5.4 5.8 5.7 2.9 5.3 5.3 5.9 5.0 5.7 FD 1 6.9 7.2 7.8 7.6 6.8 7.4 7.3 7.2 7.0 6.6 6.5 6.8 6.2 6.6 6.9 5.6 6.4 6 .7 6.3 6.6 6.6 6.5 6.1 4.9 6.3 FS 6.9 6.6 6.1 6.7 6.4 6.4 6.4 6.7 5.8 6.5 6.3 6.4 6.5 6.5 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 5) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 620 PUP # RAT/ LITTER # 1541 1544 1545 1546 154B 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 1 5.8 5.8 6.2 6.4 5.7 5.7 5.2 6.1 5.6 5.4 5.4 5.8 5.7 5.3 5.1 7.3 6.6 6.7 6.1 6.3 6.3 6.4 6.2 6.4 6.2 6.5 6.6 FS 6.2 6.6 5.3 6.3 6.6 6.6 6.5 6.5 5.8 7.0 5.0 6.0 4.6 6.3 6.1 6.2 6.2 5.9 5.6 5.7 4.9 5.9 5.5 6.0 5.1 5.0 5.2 5.9 5.4 5.3 5.3 5.7 5.5 5.4 5.1 5.2 5.1 5.2 5.7 5.6 5.0 5.0 5.0 5.4 5.0 FS 6.3 6.6 6.6 6.9 6.8 5.8 6.4 6.4 6.0 5.7 5.6 5.9 5.6 6.8 5.5 6.4 5.9 7.4 6.7 6.4 5.9 6.0 5.4 6.2 6.0 5.9 6.9 6.1 6.0 6.2 5.4 7.0 6.5 5.8 5.3 5.6 5.4 5.4 5.8 4.9 5.3 7.0 6.6 7.0 6.4 6.8 6.3 6.4 6.4 6.7 6.8 6.3 6.4 6.6 6.8 6.4 6.2 6.9 6.8 6.2 6.8 6.6 6.3 6.1 6.5 6.8 6.4 6.4 6.5 6.6 5.8 5.7 5.5 6.0 5.9 6.1 6.0 5.7 5.8 5.3 5.3 5.7 5.2 5.7 5.3 6.2 6.1 6.8 6.6 5.4 6.0 6.2 6.1 5.1 5.7 5.5 5.8 5.9 6.3 5.7 6.3 6.3 6.2 6.4 5.5 5.6 6.0 5.6 5.8 6.0 6.6 6.6 6.2 6.2 5.6 5.7 5.5 6.2 6.5 6.2 6.1 5.9 5.6 5.6 5.3 6.2 6.1 7.3 4.7 7.5 7.2 7.9 7.1 5.8 6.9 6.7 6.5 6.9 6.2 5.9 5.6 5.8 5.0 5.1 5.9 5.9 5.3 5.3 4.8 5.1 5.3 5.1 5.3 6.2 7.1 6.1 6.2 6.8 6.7 6.5 6.6 6.0 5.6 6.3 5.8 5.7 6.3 6.1 6.6 5.8 5.8 5.6 5.5 5.6 5.6 5.9 6.1 5.3 5.7 5.9 5.8 NOT PREGNANT 6.5 6.6 6.3 5.8 6.4 6.9 6.2 6.7 6.7 6.3 6.1 5.8 5.4 6.0 6.1 5.7 5.2 5.7 5.1 5.4 4.8 5.2 5.0 5.4 5.1 5.4 5.2 6.9 6.9 6.7 6.5 5.4 5.9 4.9 5.8 5.8 6.2 6.0 5.4 5.0 5.7 5.6 5.2 5.7 6.2 5.6 5.3 6.2 5.5 5.7 5.4 5.5 5.6 5.5 5.7 6.3 5.9 6.7 6.7 6.3 6.3 6.0 6.5 5.7 5.8 6.6 5.8 5.5 5.7 5.7 5.5 5.9 5.6 5.8 5.4 5.0 5.2 5.0 5.3 6.0 5.1 6 . 0 6.3 6.4 6.0 6.1 6.2 4.9 6.1 6.5 6.3 6.0 6.1 6.0 6.7 4.7 7.0 7.0 7.6 6.5 7.8 6.6 5.9 5.6 6.3 6.0 6.1 6.0 5.6 6.0 6.0 5.9 5.4 6.2 5.6 5.4 5.5 5.8 6.2 6.2 7.1 5.9 6.3 6.6 6.3 6.5 6.0 6.1 6.0 MD 1 6.0 5.5 5.6 5.8 . ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 6) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 621 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 IS 16 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 5 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 11.6 1 2 .9 11.5 11.0 11.7 11.2 11.4 12.2 11.6 10.3 12.6 11.8 11.3 10.7 9.5 10.3 9.0 9.5 10.4 9.6 9.7 8.4 7.8 8.1 9.0 8.2 8.1 8.3 10.6 10.9 10.8 10.3 10.1 10.4 11.0 14.2 13.5 13.6 14.9 11.2 10.3 11.2 11.0 10.5 10.1 11.1 NOT PREGNANT 12.0 11.0 11.9 12.5 13.3 13.5 11.4 8.3 9.0 8.5 9.5 9.2 7.4 9.6 9.9 10.3 11.0 11.6 10.7 11.5 10.2 9.9 9.4 10.3 9.9 8.9 9.8 10.3 8.6 9.1 9.0 9.0 8.4 9.1 8.1 10.3 9.5 9.2 8.4 8.6 7.4 8.8 10.3 11.4 11.2 11.2 11.3 11.4 10.0 10.0 9.7 10.0 9.8 9.3 10.1 9.5 10.5 10.7 10.4 10.8 10.0 10.2 10.6 10.1 11.2 10.2 9.2 10.3 11.2 10.3 10.8 11.1 10.4 11.2 11.4 10.7 10.5 12.3 10.8 11.0 11.2 9.8 11.3 10.8 10.6 10.9 9.5 10.9 9.6 10.9 11.0 10.7 11.5 10.3 10.8 10.9 10.9 10.0 10.3 11.0 11.1 10.2 MD 4 MS 8.8 11.1 12.1 10.7 11.0 10.7 11.0 10.3 8.8 8.7 9.3 8.6 9.7 9.1 MS 8.7 9.1 8.8 8.5 7.6 9.4 8.3 10.4 12.3 11.4 9.8 10.6 11.2 11.6 10.6 10.0 9.7 9.4 9.9 9.8 10.6 NOT PREGNANT; MATING NOT CONFIRMED 9.1 9.5 10.0 9.5 8.6 9.6 9.2 11.2 8.3 9.8 9.3 10.9 10.5 12.8 8.9 9.7 10.2 8.1 8.4 10.5 9.5 10.6 10.9 10.8 10.0 10.1 9.3 9.5 9.9 9.8 9.5 9.4 10.4 9.4 10.9 11.5 11.0 8.3 11.2 10.6 MM 2 8.0 11.3 9.4 9.0 9.1 10.7 9.4 10.2 11.4 10.8 11.2 9.2 10.0 9.4 10.4 9.1 9.3 10.5 9.8 9.0 10.6 10.6 9.9 8.1 9.5 9.9 12.1 8.2 10.9 9.0 8.7 8.6 9.6 10.0 10.2 9.3 10.8 9.6 9.5 11.0 11.7 9.7 8.5 10.8 9.0 9.2 7.4 10.2 10.2 8.7 9.5 10.4 13.0 9.0 10.2 9.4 7.3 9.4 9.4 10.7 9.1 10.6 9.9 9.6 11.1 10.3 10.0 7.6 10.6 9.4 8.9 11.7 8.8 7.9 10.8 10.7 13.0 8.4 9.5 8.1 7.8 8.9 11.3 9.9 10.2 12.1 9.6 10.5 10.2 10.0 8.1 10.8 9.7 9.5 8.8 9.2 10.4 11.0 10.6 8.8 9.4 8.6 8.2 10.7 9.1 10.6 9.2 10.3 9.5 6.9 8.4 10.0 9.6 9.2 10.2 7.8 10.6 12.0 8.5 8.2 8.2 10.9 9.3 9.5 8.6 10.1 10.3 8.3 7.2 FU 10.2 FS 9.9 9.4 12.2 8.4 7.9 7.7 8.8 10.5 9.7 8.4 10.2 7.5 7.8 9.4 10.2 8.6 9.1 9.0 8.8 11.1 10.5 FS FS 8.9 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 7) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 622 PUP # RAT/ LITTER # 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 5 11.4 12.1 12.1 8.3 9.0 8.0 8.1 9.3 9.2 10.6 10.9 11.2 10.8 11.0 10.5 7.0 8.5 7.6 10.0 10.6 10.0 9.5 9.1 9.3 NOT PREGNANT 11.6 11.8 10.9 11.8 12.6 11.7 11.4 9.8 10.2 11.1 9.0 11.1 12.8 11.5 11.7 11.2 9.8 9.5 8.3 7.2 8.0 7.6 9.7 8.0 11.2 12.0 10.8 11.3 12.2 12.0 12.5 12.6 11.9 11.7 12.0 10.8 10.5 10.3 10.4 9.2 7.4 9.5 10.5 10.1 9.8 10.4 9.9 9.5 9.0 9.9 9.7 8.9 9.8 9.1 9.7 8.5 9.7 7.2 8.6 9.6 12.2 8.8 9.7 11.2 11.5 8.0 10.1 9.7 10.9 11.8 9.4 10.4 11.7 10.8 7.2 9.5 10.4 13.4 12.6 11.2 9.0 8.8 10.1 9.1 9.0 9.7 8.9 9.1 10.9 8.8 9.8 11.6 10.8 8.7 10.1 8.4 11.5 9.0 8.8 11.2 9.9 9.8 10.9 8.3 10.7 12.6 10.0 11.3 11.9 10.4 9.6 8.5 11.7 11.8 11.1 11.2 10.8 9.6 9.9 8.7 9.3 9.3 9.4 9.8 10.1 13.2 9.4 11.2 MM 4 10.1 8.4 8.4 MS 12.5 12.2 12.0 9.4 9.0 10.5 10.4 9.3 9.6 8.9 9.7 12.0 8.0 8.9 11.7 12.2 9.3 9.9 9.7 9.8 11.0 9.8 9.7 11.3 10.9 8.8 8.0 11.1 11.3 12.9 10.4 9.8 7.4 9.7 9.5 9.5 9.4 8.8 7.0 9.3 9.2 10.5 10.5 10.1 10.1 9.5 10.0 11.1 8.7 10.5 11.4 10.3 9.0 9.3 9.4 11.7 11.8 11.2 9.7 9.6 9.9 8.1 8.9 8.5 8.9 7.9 8.3 9.2 10.3 9.6 10.0 10.5 9.1 10.5 11.4 9.0 9.8 10.9 10.5 8.5 8.7 11.0 11.5 11.1 10.2 10.4 6.2 9.9 9.8 8.1 9.1 9.2 8.1 9.2 7.6 11.2 9.9 8.9 9.2 8.7 9.8 10.1 9.4 11.3 11.0 10.3 8.3 7.1 11.3 12.4 11.5 11.7 10.9 9.2 9.6 9.5 8.4 8.8 10.5 6.4 9.7 9.4 10.8 8.9 9.6 8.5 MS 9.9 12.1 8.5 10.8 10.9 9.5 8.0 7.6 9.8 12.7 11.2 10.7 8.8 10.4 9.9 8.0 8.9 8.0 6.8 7.2 9.2 10.7 9.9 9.3 10.2 MS 10.1 11.1 9.9 11.5 10.2 7.5 8.0 9.8 13.2 11.6 9.8 8.3 10.4 10.4 8.6 8.8 9.9 8.9 9.3 8.5 10.9 11.7 9.0 9.8 9.3 8.4 11.2 8.7 7.6 8.1 10.2 9.6 9.5 8.9 8.5 10.0 9.5 7.8 8.8 10.6 8.3 7.6 8.5 9.5 8.2 8.1 10.4 8.9 8.6 9.0 9.2 7.3 7.7 11.1 10.2 10.1 10.6 8.2 7.4 8.7 8.7 9.7 FD 3 8.8 9.1 8.5 10.3 7.7 7.7 9.4 FM 3 FD 4 8.1 9.7 FS 7.5 FM 5 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 8) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 623 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 5 VO CD 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 11.0 9.3 7.8 8.0 8.9 10.2 10.5 10.7 10.9 10.7 10.8 9.0 9.3 9.4 10.7 11.5 10.5 10.1 9.7 10.1 10.3 10.6 10.9 9.4 9.8 9.6 11.3 11.1 11.5 14.9 14.2 13.2 10.3 10.4 10.3 NOT PREGNANT 11.1 11.3 11.1 8.9 7.5 9.2 8.4 8.5 8.9 10.1 10.4 6.5 12.8 12.9 13.3 NOT PREGNANT 11.5 11.1 9.7 8.9 10.3 9.8 11.2 10.3 10.9 11.2 11.6 10.6 10.2 10.4 10.2 9.9 9.4 9.3 14.0 14.5 13.9 9.9 11.0 10.0 7.6 7.5 7.8 8.2 8.5 8.8 12.0 12.1 12.2 9.5 7.6 10.2 9.6 9.1 10.0 8.8 9.9 10.8 11.2 15.0 9.5 9.4 8.9 8.8 10.6 13.6 10.4 10.7 10.4 10.0 9.6 9.7 13.9 9.4 8.9 7.0 11.5 9.7 8.5 9.8 10.6 9.5 10.6 10.5 9.8 7.9 11.2 14.1 10.3 11.1 9.4 8.8 9.4 13.0 11.0 10.9 8.9 10.4 9.7 10.1 14.5 10.1 8.9 9.4 12.3 10.1 7.8 9.4 10.0 10.0 9.9 9.6 10.3 9.5 11.7 14.6 8.1 10.7 8.8 8.6 9.9 12.4 11.7 10.0 10.1 11.8 9.9 11.0 12.6 10.2 7.7 10.0 12.6 10.0 8.0 10.5 9.6 8.1 10.9 9.1 10.4 8.9 11.1 13.7 10.4 MS 8.4 7.1 MD 5 10.5 10.5 10.7 10.9 8.9 9.1 12.6 9.8 8.2 7.4 10.9 10.3 8.9 9.8 10.4 8.3 10.1 8.7 11.0 10.5 10.8 10.0 9.1 8.5 9.3 8.9 8.3 9.1 9.8 8.7 10.5 10.5 9.9 MS 8.1 8.9 MM 3 9.1 9.2 7.1 6.6 11.0 11.1 MS 9.4 9.2 9.8 13.3 11.2 MD 1 8.7 10.4 MD 2 11.0 9.8 10.5 9.2 10.5 13.3 9.8 8.2 7.7 11.2 8.7 7.9 10.3 8.9 8.9 MD 1 8.3 9.8 9.1 FD 1 10.5 9.6 8.1 8.1 9.3 11.4 9.3 10.4 11.1 8.9 9.3 13.0 10.1 6.9 9.0 12.5 9.1 8.0 8.6 9.7 8 .7 10.9 9.5 9.7 9.5 FS 9.2 9.5 8.4 7.4 6.5 10.8 11.7 10.0 9.4 9.7 10.7 10.0 7.9 8.6 11.1 9.8 8.0 9.2 9.5 9.2 10.8 9.1 10.0 8.3 FS 9.5 8.4 10.6 10.4 8.1 9.8 9.7 9.5 10.3 10.0 8.8 8.4 9.5 7.9 7.6 9.1 9.5 9.1 9.9 10.1 9.4 10.4 6.5 9.5 9.8 10.6 8.7 9.1 8.1 8 .7 12.0 9.6 7.2 8.8 11.1 9.9 7.7 10.0 9.5 9.9 8.2 9.1 10.0 10.4 8.6 FM 2 9.6 11.2 9.4 11.6 8.7 10.2 7.7 7.9 , 9.8 7.9 9.8 8.5 10.2 8.3 9.5 9.5 9.6 FS 11.9 10.4 7.0 7.9 FD 1 7.1 9.1 FM 2 9.2 9.4 8.5 11.0 10.1 6.9 6.9 FD 1 7.7 8.8 7.5 7.9 9.1 10.6 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 19 20 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 9) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 624 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 5 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 10.7 10.3 11.5 NOT PREGNANT 9.3 9.8 11.0 10.7 11.9 11.0 14.8 15.3 15.0 10.4 9.2 10.8 10.3 10.4 10.9 9.6 9.1 10.3 10.8 11.9 11.2 9.1 9.9 10.3 11.4 11.8 11.0 9.4 9.0 9.4 7.1 7.4 8.8 11.6 8.9 12.2 NOT PREGNANT 10.3 9.9 9.9 9.5 9.6 9.3 11.6 11.7 12.9 10.2 9.7 9.0 9.5 9.8 10.5 10.7 10.6 10.2 10.9 11.4 11.3 14.8 15.2 9.6 9.6 8.4 11.5 10.4 10.5 10.9 11.1 10.8 8.3 8.5 9.2 10.5 10.2 10.1 10.0 10.2 9.7 11.3 10.9 11.9 10.7 10.0 10.6 13.5 9.7 9.8 8.1 11.6 8.7 11.3 10.1 7.4 11.6 10.2 8.8 11.4 10.2 9.8 10.8 10.6 9.2 11.9 10.7 9.6 9.7 10.3 10.3 10.8 10.9 11.1 10.7 15.4 9.4 9.6 9.6 10.8 9.2 10.2 8.7 8.5 7.8 10.8 10.1 12.8 6.9 9.3 9.6 11.6 7.5 11.2 8.5 7.3 10.2 10.2 7.4 10.9 10.1 9.9 10.4 7.6 10.4 10.5 11.4 10.2 9.4 11.0 11.1 9.5 10.8 11.2 7.9 10.5 10.0 10.5 8.8 10.8 11.2 9.7 9.4 9.6 10.9 10.1 11.1 11.8 11.7 7.7 10.2 8.5 11.6 7.8 10.8 9.9 7.5 10.8 9.0 8.9 10.2 8.7 9.6 11.1 11.1 10.1 9.9 10.0 9.3 8.9 10.4 11.4 9.4 9.4 9.2 11.5 10.3 10.7 9.9 12.0 9.3 11.1 8.0 7.8 10.6 10.7 10.2 12.1 10.5 9.8 11.1 MD 1 10.2 10.6 10.3 8.1 8.3 10.2 11.2 10.4 11.1 10.5 13.9 10.2 MD 1 9.4 10.4 9.5 10.4 9.5 7.9 11.7 10.4 8.4 10.4 8 .9 8.7 9.6 10.7 8.9 9.6 MS 9.0 7.7 10.4 12.3 10.0 8.9 9.8 14.0 9.4 9.9 10.7 10.7 8.3 10.2 8.9 7.3 10.0 9.2 7.6 11.1 9.2 7.6 10.3 7.5 8.9 10.9 10.6 9.0 11.6 8.8 10.4 9.5 10.2 10.2 9.9 9.5 10.1 10.3 8.9 9.5 8.4 7.9 9.7 10.6 9.4 12.0 10.0 9.9 10.7 11.6 MM 5 11.0 8.6 10.3 8.8 11.8 9.9 9.9 9.6 8.8 9.8 9.1 9.2 10.1 8.4 7.3 9.1 10.3 8.0 10.2 9.9 8.1 10.1 10.6 9.1 9.7 4.0 10.6 9.1 10.9 11.0 9.3 9.6 10.0 9.6 8.9 8.7 FD 2 8.6 8.0 FD 2 10.7 9.1 11.2 9.8 9.4 8.7 10.1 9.5 7.5 11.0 10.3 11.0 10.5 9.1 8.0 9.0 8.6 7.8 MS 8.7 9.0 8.3 8.1 7.3 9.1 9.0 11.9 FD 1 10.3 8.6 UU FS 8.8 6.7 8.8 8.3 7.4 9.0 FS 9.5 FS ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 16 FS 8.3 8.2 9.4 8.1 8.3 8.7 17 9.2 8.4 8.7 18 19 7.8 FD 1 20 PROTOCOL 418-020: TM - GENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 10) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 625 PUP # 10 11 1 2 13 14 15 16 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 5 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 10.4 12.2 10.4 10.2 10 .1 10.8 9.9 10.0 10.6 8.6 10.7 10.2 10 11 9 10 9.5 11.5 9.6 8.8 9.9 12.3 10. 9. 8. 11. 8. 8. 9.0 11.1 9.0 8.5 9.7 108.. 24 9.0 9. 9 1 1 .1 9. 0 9. 4 9.8 10.8 7 8 10.0 10.7 9.3 8.9 9.6 FM 2 6.7 9.5 9.7 FS 8.8 9.0 9.8 9.5 8.5 9.4 9.1 FD 3 9.1 8.9 9.0 7 8.4 8 7 . 8.5 8.6 8 . 5 8 8.9 9.2 FS 1 1 . 8 9.8 10.4 10 10.2 9 10.2 10.2 9.8 9. 5 8 9.6 9.8 9.3 8.3 9 8.4 8 9.3 8.6 8.9 7. 8 9 8.3 8.4 8 . 6 8 . 6 10.3 8 . 8 7 9.5 9.2 9.0 7.8 7.5 8 . 1 8 9.5 8 . 2 9.2 8.4 11.5 11.3 11.3 11.4 10.8 10.9 11.3 10.9 10.9 1 0 .9 11 1 1 . 2 11.3 1 0 . 8 1 0 . 1 10.7 7.7 7.6 6.9 9.8 8.1 9.8 6.7 9.6 8 9.5 6.3 9.3 5 9.3 7.1 1 0 .4 7. 9 106 10.6 7.8 9.6 10.4 7.2 7.2 9.8 10.2 7.1 1 0 . 2 9.8 9.2 10.0 11.1 10 1 1 . 1 1 1 . 6 1 1 . 2 11.1 10.6 10 9.3 10.2 9 9 9.6 1 0 .1 8.9 9.1 9.6 8 . 8 10.5 10.3 8.3 9.2 9.5 7.4 9.1 8.5 8 8 9.0 8.5 7.8 9.2 8.4 8.5 8.4 11.3 7.4 1 1 . 8 10.6 11.7 10.8 10 10.6 10.4 9.5 10.7 1 0 . 0 8 . 1 7.3 7.9 8.2 8.3 6.7 7 7.5 7.4 7.6 7.3 7.3 11.9 1 0 . 0 1 0 . 6 8.9 10.4 10.6 9 9.5 9.9 9.0 9.6 8 . 8 9.9 1 0 . 2 6 . 8 7.1 6 . 8 7.6 7.7 7.5 7 7.6 7.7. 7.2 7.0 7.4 NOT PREGNANT 10.2 9.6 12.6 11.2 10.2 12.4 11.2 9.8 11.9 11.0 10.7 10.9 9.8 9.5 MM 3 1 0 . 0 10.9 8.1 9.6 10.5 9.3 10.7 10.2 1 1 . 1 1 0 . 2 9.9 9.6 9.3 9.7 8.7 10.4 9.0 9.6 8 . 8 9. 8.7 9.9 1 0 . 0 9.5 8.6 9.4 8.4 8 . 6 9.4 10.4 8 . 1 10.7 9. 10.8 9.3 9.1 9.2 9.6 9.2 9.3 8 . 8 9.3 8.9 9. 8 . 6 8.4 8 . 2 8 . 9.7 9.9 9.3 10.4 9.6 9.5 8.4 9.3 9.1 8 . 8 8.2 8.4 7.5 7.0 8.8 8.1 7.8 7.6 7.6 10.5 9.3 1 0 . 8 9. 9.9 9.5 7.6 10.7 10.7 9.8 8.5 10.5 9.6 9.9 12.5 12.3 14.3 1 2 . 13. 11.6 9.4 9.4 8.5 9.7 9. 9.7 9.2 9.0 7.6 8.4 8 . 9.4 8.5 9.9 8 . 0 9.6 8.6 1 0 . 0 1 1 . 6 1 1 . 2 10.1 10.3 10.9 10.3 10.6 10.3 9.1 MD 1 0 . 0 9.9 8.5 1 0 . 1 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 11) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 626 PUP # 1 2 3 4 5 6 7 8 9 1 0 1 1 12 13 14 15 16 17 18 19 2 0 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 8 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 16.1 17.5 15.8 15.4 16.4 16.0 14.8 16.9 16.9 18.6 18.4 15.4 16.9 16.0 16.0 14.5 15.3 13.2 13.1 13.2 12.5 1 2 . 1 1 2 . 2 1 2 . 2 1 1 . 0 13.2 11.3 12.7 14.5 17.2 17.0 15.6 16.0 15.5 15.9 20.4 2 2 . 0 22.5 2 1 . 0 15.9 16.2 15.8 15.6 14.1 14.6 14.8 NOT PREGNANT 18.8 17.5 18.9 16.2 17.5 19.1 18.0 11.4 12.9 12.7 13.6 1 2 . 8 1 1 . 2 14.5 16.0 16.6 15.0 14.5 14.7 15.0 15.7 14.1 15.0 13.4 16.0 15.7 14.6 15.4 11.4 1 2 . 1 1 1 . 2 1 0 . 0 12.3 11.5 1 2 . 1 1 1 . 8 1 2 . 1 13.7 12.7 1 1 . 1 1 2 . 8 11.4 14.3 16.1 14.6 15.9 15.1 15.7 14.8 14.4 14.2 14.9 15.5 14.9 15.1 14.1 15.7 14.7 16.1 15.9 15.4 15.1 16.0 13.0 14.8 16.9 13.9 15.5 14.2 16.8 14.2 14.4 14.6 14.9 14.9 14.5 15.2 15.5 15.3 16.4 17.5 16.3 16.0 16.5 15.1 13.2 15.4 13.0 14.4 15.4 14.4 14.7 13.3 15.5 13.4 14.8 14.1 15.7 15.7 16.1 15.5 15.5 MD 4 MS 1 2 . 8 16.5 16.2 18.2 16.6 16.1 16.9 15.8 1 2 . 0 13.5 13.3 13.9 1 2 . 8 14.3 MS 1 2 . 8 11.3 12.9 10.4 1 2 . 0 13.3 13.2 13.2 14.8 11.7 13.4 1 2 . 6 1 2 . 6 11.3 15.2 13.5 14.1 14.7 13.4 14.8 14.3 NOT PREGNANT; MATING NOT CONFIRMED 1 2 . 6 12.9 12.4 12.3 11.5 1 2 . 6 1 1 . 6 11.2 17.2 14.6 10.5 15.7 14.6 15.5 12.7 14.6 13.2 12.0 12.5 14.5 14.1 16.7 15.0 14.3 13.9 15.5 14.5 14.4 15.7 13.6 13.8 12.4 14.2 12.2 15.6 13.0 13.4 12.2 16.1 14.7 MM 2 12.0 15.8 13.7 10.8 10.4 14.9 14.6 15.7 13.6 14.7 15.5 15.0 15.0 15.4 17.5 14.1 12.8 12.2 14.6 11.9 16.2 16.4 14.0 11.6 15.8 14.5 17.8 10.5 16.4 13.7 11.4 9.6 14.8 13.6 15.6 13.1 15.9 13.3 14.6 16.0 15.7 14.8 11.2 13.3 14.2 11.6 16.3 14.8 11.9 11.5 15.4 14.8 17.3 13.0 14.5 15.0 10.9 9.0 14.6 16.5 12.8 14.1 14.8 10.8 16.1 15.0 13.7 10 .1 12.4 11.7 11.7 16.1 13.8 11.9 14.0 15.4 18.7 12.9 15.1 10.8 14.0 13.3 15.5 17.0 14.0 16.7 13.8 14.3 16.0 14.2 11.5 12.8 15.8 11.7 13.6 10.7 13.9 14.6 15.7 13.0 15.0 10.7 10.4 16.0 13.5 13.2 13.9 14.1 15.1 11.9 12.4 12.7 13.5 12.4 14.1 10.9 15.2 17.4 10.8 10.3 11.2 16.1 13.8 13.7 14.1 11.2 14.4 12.8 10.3 FU 12.4 FS 12.9 10.9 18.8 13.0 11.7 10.8 16.5 16.1 12.3 12.5 14.8 10.2 10 .1 13.4 13.2 12.6 11.9 9.8 11.4 13.8 13.9 FS FS 10.2 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE E40 (PAGE 12) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 627 p u p # :1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 8 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 18 . 2 17 . 6 17,.9 1 2 .3 1 2 .9 1 2 .9 13 .3 13 . 6 13..7 16 . 6 16 . 1 15..6 14 . 2 IS .5 17..0 13 .9 13 . 0 1 0 .. 1 14 . 1 14 .4 15.. 1 13 . 6 13 .9 1 2 ,.3 NOT PREGNANT 17 . 2 16 . 1 16..3 16 .3 17 . 0 17.. 1 15 .4 15 .5 15..5 16 .7 16 . 0 13..8 18 .3 17 .5 17..3 13 .9 15 .0 15.. 2 1 1 .5 8 .4 13.. 1 1 2 .4 1 1 .4 1 1 .7 17 .7 17 .3 17..9 16 . 8 18 .8 17..9 17 .7 17 .4 16.,6 14 . 6 16 . 1 16.,3 13 . 8 13 . 0 15..0 1 2 . 6 15 . 0 14 .. 2 14 .3 14 . 6 14.. 1 14 . 0 13 .9 13..7 1 2 . 6 13 .5 1 2 ..6 1 2 .5 14 .0 13.,3 13 .5 1 2 . 1 13 .,0 13 .4 13 . 6 15..0 16 .5 1 2 .9 14 .5 16 .5 15,.9 13 .1 13 . 0 13 . 1 14 .6 15,.5 17,. 1 15,,7 18,.3 15 .7 1 2 .9 13 .0 16,. 2 18,.3 17..4 16..5 12 .2 12 .1 14 .6 14 .3 13,. 1 13,.5 13..3 15,. 2 16,.1 1 2 ..6 13.. 6 16.. 8 16.. 2 1 1 .. 1 15,. 1 1 2 .. 1 17.,5 13 .,6 14 .4 15. 3 15.,7 1 0 .9 15.. 2 13 .8 17 .8 1 2 .3 1 1 .4 16 .3 15,.5 1 1 .3 14 .6 13 . 0 14 ,.5 1 1 ,.4 15.. 2 16 .. 1 9.. 8 15 .0 1 2 .9 15.. 6 17..4 14.. 8 16..4 16.. 1 14..9 1 2 ..9 1 1 ..0 16..4 18..4 15..4 16 .,1 1 1 ,.7 1 2 ,.7 13 ,.8 1 2 ,. 2 1 2 .5 1 2 ..9 1 2 .8 15.. 2 16., 1 17.,9 14 .,9 16.,7 MM 4 13..5 13.,9 13. 8 MS 17. 0 15. 1 15. 9 1 2 ..6 1 1 ..0 13 .,7 14 .,3 1 2 .8 13.,9 13. 1 1 0 .9 15 . 1 15 .6 14 .3 14 .9 16,. 8 15 .9 13,.4 1 2 .7 15..4 18.. 0 15..9 16,. 0 12 .1 13 . 2 13 .5 IS .5 12 .2 1 2 ,.5 14,. 6 14,.4 15..4 13.. 1 14 ,.3 15,. 6 16.. 8 14 .. 2 MD 7 1 1 .9 16,.9 15.. 8 17..4 16.. 1 13.. 8 13.. 2 13 ,.6 13 ,. 1 1 2 .. 2 1 2 .9 13 .4 14..4 1 2 ..9 13..7 15.. 1 14.,3 1 2 ..2 14 ..6 1 1 .5 14 ..8 15..4 13.. 0 16..3 16..3 13 ., 1 1 2 .,1 1 2 ..8 17., 0 18 ..0 16..5 15.. 1 1 1 ,.8 1 2 ,.3 13 ,.5 1 2 ..8 1 2 ..0 1 2 .7 14. 4 13 .,3 1 1 ..8 1 1 .7 14 .9 15.. 6 13.. 0 13 .8 1 2 .7 14 ,.8 15,. 1 14 ,.9 17.. 0 16..7 15..3 1 1 .3 1 1 .9 17.,1 19., 0 17. 4 14 .,7 13 .3 14 ,. 2 13 .9 13 ,.1 1 1 ,.6 1 2 ,.5 13..3 1 1 ,.6 1 1 .,3 1 2 .9 16., 0 14.,9 13 .8 13 .7 MS 14.. 1 16..7 13.. 0 15.. 1 17.,3 15. 4 1 2 ..6 1 0 .8 14 .,6 17., 1 17 ..2 1 2 ..0 14 .3 15.. 0 15,. 1 1 2 .5 1 2 ,.0 1 2 .. 1 8 .4 13.1 13.3 15.3 15.7 10 .1 14.5 MS 14.8 15.6 13.4 16.8 13.2 11.4 11.3 15.5 17.1 16.3 13.3 11.9 14.1 14.8 12.7 12.5 12.3 7.5 13.7 12.2 16.0 14.3 11.5 12.1 13.3 15.2 16.3 14.6 12.6 10.9 12.4 10.5 14.6 12.2 12.2 13.4 12.1 8.3 12.6 14.1 13.8 10 .1 12.9 13.5 9.9 12.9 11.3 14.6 11.8 12.1 9.6 13.9 14.4 17.0 12.8 14.0 14.7 13.2 11.0 13.7 13.6 13.1 FD 3 11.8 13.7 12.3 13.7 10.0 10.4 14.1 FM 3 FD 4 10.8 12.3 FS 10.3 FM 5 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 13) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 628 PUP # 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 13 14 15 16 17 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 8 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 13.5 13.9 14.2 10.5 13.7 1 1 . 2 14.5 14.2 12.9 14.7 15.2 13.9 1 1 . 8 13.2 12.7 1 2 . 1 15.6 14.2 15.8 13.3 16.8 15.8 15.7 16.0 13.0 14.7 11.7 17.7 17.1 16.6 20.7 2 1 . 0 19.2 15.2 15.1 14.2 NOT PREGNANT 15.8 14.2 15.4 13.7 13.1 13.0 13.4 12.4 13.3 16.6 13.7 16.1 19.8 19.8 19.6 NOT PREGNANT 15.4 17.5 15.9 15.3 15.8 15.2 13.7 15.5 15.7 14.2 16.5 15.2 13.7 13.7 12.3 12.7 1 2 . 8 15.0 19.0 18.6 18.7 14.6 15.3 13.1 1 0 . 2 10.7 12.4 10.8 1 1 . 1 10 .1 17.2 16.9 17.2 13.8 10.5 12.8 15.5 12.3 15.0 11.2 15.5 14.0 17.7 21.3 15.3 15.3 10.8 10.7 15.0 18.2 17.4 13.1 15.8 13.3 12.3 14.3 19.2 13.8 12.0 9.6 15.9 14.6 12.3 14.7 15.6 12.8 15.6 11.4 14.9 10.7 17.6 20.1 14.4 12.7 12.1 14.7 15.8 11.1 15.3 13.5 13.9 14.2 17.9 19.9 11.9 12.9 12.5 12.6 14.8 18.6 14.3 12.1 13.5 MM 6 17.5 16.2 17.4 13.9 14.6 12.8 14.0 19.4 13.8 10.7 9.0 15.4 15.9 16.6 14.8 15.2 12.3 12.6 17.5 12.9 11.9 9.2 15.9 14.0 12.8 14.1 14.5 10.2 14.2 14.6 15.6 15.6 16.4 20.0 14.6 MS 12.4 14.3 MD 5 17.1 14.1 12.3 14.7 11.9 12.8 17.7 14.7 11.4 10.6 18.2 13.9 13.0 13.8 13.5 11.4 14.6 15.8 14.8 13.3 16.9 12.7 14.1 13.5 15.2 12.8 16.0 12.0 14.6 13.8 16.2 15.3 14.8 MS 11.0 11.7 MM 3 11.4 13.2 13.1 13.9 16.4 16.0 MS 16.0 12.9 13 .6 17.1 13.0 MD 1 9.7 16.9 MD 2 16.7 12.8 15.1 12.7 13.7 16.6 14.1 10 .1 9.9 16.2 15.6 12.0 15.2 12.8 11.0 MD 1 11.7 14.1 12.2 FD 1 13.6 12.8 13.0 11.1 13.9 16.7 15.4 13.3 12.1 8.3 13.2 16.6 12.4 11.4 9.4 17.4 14.2 11.4 12.4 14.4 11.7 14.9 17.2 14.1 13.6 FS 14.4 14.1 13.3 11.7 14.4 17.6 16.6 13.5 13.0 13.2 14.4 14.2 10.4 11.1 15.2 10.7 10.8 11.7 13.8 10.3 14.6 14.7 14.3 12.7 FS 14.7 15.0 10.3 10.9 14.2 16.4 13.5 15.8 12.6 13.9 12.7 9.3 10.5 16.8 13.8 11.0 13.7 14.7 12.1 13.9 13.4 12.4 14.7 11.6 14.5 12.1 14.5 15.4 13.4 14.9 11.8 14.3 10.2 10.3 15.9 13.7 9.6 14.3 11.1 15.1 10.7 13.4 14.5 13.1 12.3 FM 2 FM 6 15.6 13.6 14.2 11.3 14.4 10 .1 10.2 13.4 11.4 14.0 12.1 14.3 14.6 13.2 13.0 FD 6 FS 16.3 12.8 8.9 9.8 FD 1 12.9 11.2 FM 2 13.1 13.6 12.8 15.5 11.0 11.1 10.8 FD 1 11.9 11.4 13.1 11.9 FD 6 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 14) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 629 PUP # RAT/ LITTER # 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 13 14 15 16 17 18 19 MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 8 14.5 14.4 14.9 NOT PREGNANT 16.1 15.8 14.9 15.5 13.5 15.9 20.5 2 0 . 8 16.4 13.5 16.3 12.5 14.2 13.3 14.9 12.5 1 1 . 6 10.7 17.8 16.6 17.3 13.7 1 2 . 6 11.3 16.9 15.9 16.7 13.0 13.4 1 1 . 6 1 0 . 8 10.7 1 0 . 6 18.1 11.9 16.6 NOT PREGNANT 15.2 14.5 14.1 1 2 . 2 14.2 13.9 16.9 15.2 14.9 14.3 15.0 14.2 13.1 12.9 13.5 14.6 13.8 14.8 17.1 16.5 16.9 21.4 2 1 . 6 13.7 13.2 12.3 13.0 13.0 12.7 15.7 16.3 15.9 10.9 13.2 1 1 . 2 12.4 14.3 14.0 13.9 15.2 11.3 16.3 14.9 15.8 13.9 14.7 16.1 21.5 15.0 14.2 10.5 16.9 14.1 17.1 13.3 10.8 17.3 14.5 15.2 17.5 15.3 14.5 13.7 15.9 12.5 13.8 14.9 14.1 13.8 15.1 18.7 15.2 13.1 15.3 19.5 14.4 14.9 12.7 16.6 12.8 16.0 11.3 10.8 15.7 15.3 12.2 16.1 13.2 12.2 14.8 11.2 13.1 12.5 16.3 13.0 14.2 14.2 15.4 12.7 14.7 15.6 18.4 11.4 13.2 10.5 17.5 12.2 16.6 11.7 9.5 16.5 14.4 11.3 17.4 13.7 12.8 14.7 17.1 12.6 13.0 16.8 13.5 14.2 14.3 17.5 11.5 12.9 16.4 21.6 14.8 13.5 10.6 17.6 12.6 15.0 10.6 10.7 16.2 16.1 13.3 16.4 13.0 13.0 14.9 16.2 13.8 12.1 14.3 13.8 14.4 14.2 16.8 12.5 13.8 14.6 14.5 16.8 16.7 13.2 14.2 11.3 16.5 10.2 15.2 11.4 11.5 13.3 14.8 14.7 18.5 9.1 MD 1 10.2 16.4 12.0 14.9 11.6 12.1 12.1 14.6 14.2 19.7 15.7 13.9 12.7 17.6 13.5 14.6 10.6 10.4 18.0 13.3 13.3 16.3 14.7 14.5 12.3 MD 1 14.7 14.4 15.9 13.9 13.1 14.3 15.3 14.3 12.1 15.5 14.9 10.3 14.7 11.3 11.8 12.2 15.4 14.1 12.1 14.2 16.4 14.3 12.5 MS 13.7 13.7 14.1 15.2 14.2 11.6 14.0 13.8 12.6 14.5 15.5 11.0 15.3 14.2 11.2 11.1 11.6 16.9 12.4 15.3 11.6 11.2 14.0 14.5 12.6 17.3 13.7 11.4 14.7 16.6 MM 5 10 .1 13.9 14.6 10.2 16.9 13.5 13.0 14.6 13.9 13.4 10.5 11.9 16.7 12.5 11.0 14.4 13.6 14.3 13.9 12.3 10.8 14.3 15.6 11.7 15.4 12.0 11.5 12.4 16.1 13.5 1 1 . 8 14.9 12.4 13.7 13.8 14.0 13.8 10.9 14.6 12.8 13.0 FD 2 12.3 9.3 FD 2 12.6 11.1 10.5 12.4 12.1 16.0 12.1 11.1 MS 11.8 12.3 14.6 11.6 12.6 15.1 14.8 13.7 14.3 13.6 1 2 .7 17.5 15.5 FD 1 FS 14.2 14.3 UU FS 13.4 12.4 1 0 . 2 10.4 8.9 13.4 13.2 13.2 10.7 1 2 . 0 11.3 FS 9.6 11.0 FS 11.7 13.1 11.7 FM 6 FD 1 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 20 PROTOCOL 418 020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 15) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 630 PUP # RAT/ LITTER # 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 1 2 3 4 5 6 7 8 9 1 0 11 12 13 14 15 16 17 18 19 MATERNAL DOSAGE GROUP V 14.0 14.7 14.2 15.7 16.6 16.5 14.6 13.9 15.4 14.8 12.4 13.4 13.4 13.1 1 2 . 1 16.8 14.8 14.1 12.3 12.4 14.2 13.0 1 2 . 6 14.6 15.8 16.2 15.7 13.4 13.9 14.3 1 0 . 8 11.7 1 1 . 6 13.7 1 1 . 8 1 2 . 8 15.5 15.1 14.6 12.3 12.5 1 2 . 1 16.1 14.2 15.8 10.4 1 1 . 8 10.9 13.9 14.5 13.5 1 0 . 8 9.6 10.3 NOT PREGNANT 14.3 13.2 14.6 16.4 15.1 15.6 18.3 18.4 19.0 1 1 . 8 14.1 13.1 15.4 13.0 14.5 13.4 13.9 1 2 . 1 12.4 1 1 . 1 1 0 . 8 13.9 15.2 13.7 19.0 18.9 21.4 12.3 12.7 1 2 . 1 12.7 15.4 13.8 14.6 16.0 12.0 11.9 11.7 14.1 11.4 12.9 14.9 13.9 9.3 13.8 16.1 11.6 16.1 12.0 14.9 10.6 13.9 14.8 17.4 13.1 15.3 13.0 10.5 14.0 19.7 10.7 14.9 13.2 12.0 12.6 12.1 12.8 14.7 12.5 11.5 15.0 13.5 10.6 13.1 15.4 10 .1 14.4 11.0 14.8 10.9 14.0 MM 3 12.9 11.3 13.1 11.3 14.1 19.8 10.2 15.3 12.3 17.3 11.2 13.4 12.2 13.8 12.3 12.1 15.1 13.1 9.6 12.7 15.6 10.7 12.3 11.5 13.5 11.0 14.7 13.2 13.0 13.4 13.1 12.3 14.5 17.5 12.3 15.4 30 MG/KG/DAY 13.4 15.8 13.7 13.8 12.0 14.3 13.0 13.0 14.7 13.2 MD 7 12.5 12.2 12.6 11.3 10.9 14.7 MM 8 12.8 15.9 15.7 12.1 12.9 14.2 13.3 12.3 15.8 15.3 11.1 12.7 14.8 10.9 15.4 9.6 14.0 MD 7 13.3 14.0 15.3 12.4 12.6 14.1 12.0 11.1 15.8 13.8 8.3 10.4 13.6 12.0 14.6 9.9 13.0 10.6 13.1 14.3 13.9 14.9 14.7 14.9 13.9 13.9 13.0 10.9 10.3 13.0 13.9 13.2 10.3 13.1 12.9 14.1 13.4 10.3 14.0 10.9 10.9 1 0 . 8 15.1 15.4 15.1 14.2 14.9 13.2 12.3 12.8 11.9 13.0 12.7 16.0 14.8 8.1 11.8 14.3 10.4 13.5 9.6 14.5 11.6 14.0 15.0 12.9 14.1 14.7 10.4 14.4 10.7 12.8 POSTPARTUM DAY 8 13.9 14.9 11.8 12.6 12.5 14.0 12.3 11.5 15.0 13.8 10.4 13.5 14.2 13.0 15.4 11.1 13.6 11.2 13.7 14.3 13.7 13.2 12.7 14.0 13.2 11.6 15.6 12.6 9.7 12.2 14.4 11.0 13.4 10.4 13.3 10 .1 12.7 FM 2 12.5 12.9 10.8 11.6 11.2 14.3 13.3 10.4 12.8 10.3 14.2 11.0 14.5 10.6 14.0 FS 11.9 11.5 FS 12.8 12.8 14.9 10.8 11.3 14.3 8.6 11.5 FD 6 15.0 10.8 12.1 14.2 14.5 1 2 . 6 14.3 14.0 1 1 . 2 15.1 14.7 12.0 13.8 14.1 12.0 14.6 1 2 .9 14.4 11.6 14.2 12.6 12.2 10.4 1 2 .5 10.8 14.7 10.3 1 1 . 0 11.4 11.5 1 2 . 1 MD 1 3 .4 1 2 . 0 14.4 14.2 13.6 13.9 9.6 12.9 12.2 13.3 FD 3 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 20 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 16) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 631 PUP # 1 2 34 56 7 8 91 1 0 1 1 1 2 13 14 15 16 17 18 19 2 0 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 15 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 28. 1 29. 4 28. 3 27. 4 28. 7 26. 7 27. 5 25. 6 28. 7 28. 9 31. 2 28. 0 29. 0 28. 7 26. 3 25. 1 2 2 .3 2 0 .7 24. 0 2 2 .7 2 2 .2 2 2 .9 2 0 .7 23. 4 2 1 .7 2 1 .1 2 2 .8 2 1 .6 28. 3 27. 3 28. 4 25. 9 27. 2 27. 5 28. 1 38. 8 35. 0 39. 1 39. 3 24. 2 24. 8 23. 3 24. 9 25. 0 2 2 .7 15. 7 NOT PREGNANT 29. 1 28. 4 26.,6 26..0 30.,5 29. 4 26..7 15. 4 19. 0 17. 8 2 0 .4 2 0 .9 18. 6 2 0 .3 30.,0 27. 7 27. 2 29. 8 28., 1 27. 9 27. 4 27.,7 31. 6 30., 2 28.,5 27. 8 30. 0 27.,7 2 2 .5 2 1 .,5 2 2 ,. 1 2 1 ..3 2 2 ..2 2 0 .0 19. 8 2 0 ..6 24.,7 2 2 ..0 19..5 23..3 2 1 .5 24 .9 28..4 28. 1 29.. 1 28..3 27..4 29. 1 28..8 25.. 1 27.,0 23 .1 25,.9 25..3 26. 2 25.. 1 2 1 .8 24..4 25 . 2 23 .7 25,.7 27. 1 25..5 18 .4 2 2 .9 18 .4 2 1 .4 18 .8 18.,2 18 .8 27 . 2 27 . 2 27 .3 26 .5 29 .4 27.,9 25 . 2 27 .9 29,.1 28 .9 28 .8 28 .9 28 .. 2 25 . 2 25 . 2 25 .7 2 2 .4 25 .7 2 1 .5 19..7 2 2 .7 29 .1 27 . 0 25 . 6 24 . 1 25 .5 2 1 .. 2 2 2 .9 29 .5 30 . 6 28 .5 28 .9 MD 4 MS 30 .4 30 .5 32 .7 32 .7 30 .5 33 .9 30 .5 30 . 2 27 .7 27 .3 26 .9 27 . 2 25 .9 26 .5 MS 20 . 2 24 .5 18 .4 2 2 .7 2 2 .4 22 .9 19 .4 23 . 1 24 . 2 25 . 6 23 . 6 24 . 0 25 . 6 25 . 1 26 .5 25 .4 25 .9 28 . 2 26 .7 26 . 2 26 .3 NOT PREGNANT; MATING NOT 1CONFIRMED 25 .0 25 .8 25 .9 24 .8 24 .4 24 .3 24 .0 28. 1 25. 9 2 2 .1 19. 8 27. 9 27. 7 24 .7 19. 7 23 .1 29. 4 2 0 .9 25. 7 24 .4 19. 1 25. 7 28. 1 26. 7 23. 6 2 2 .3 24 .4 26. 1 2 2 .8 2 2 .9 24 .5 2 0 .8 23. 3 23 .9 23. 8 2 1 .8 30. 3 MM11 29. 7 26. 2 2 0 .1 2 0 .6 27.,9 24. 4 23. 6 24.,7 25..3 30,. 0 25..3 23 . 1 28 .4 30 .0 25 . 8 2 1 .5 23 .5 26 .4 MM 2 16. 4 27. 4 27. 6 2 0 .,0 23 .4 27 ,.8 24 ..2 27.. 1 18,. 8 23 .7 26 .5 24 . 2 23 .9 28 .7 30 .4 24 . 0 20 .4 23 . 8 27 . 0 28. 5 16. 0 29. 6 26. 9 18. 3 2 1 .8 26. 5 28., 1 2 0 .,5 27.. 2 26 ,.6 2 0 ,.7 25..1 28 .5 32 .7 26 . 1 24 . 6 22 .8 24 . 8 28. 5 15., 0 27.. 2 29.,7 2 0 .,6 2 0 ,.0 24.. 6 25 ,.8 2 0 ,. 2 24 . 6 28 .3 16 .4 28 . 0 27 . 1 25 .5 23 . 8 24 .5 28 .4 29. 4 18. 1 28. 5 19. 2 MM12 25. 3 26. 1 15 .3 24 .4 27.,1 2 0 ,. 2 24.,5 29.. 8 25 .3 16 .4 22 .8 23 . 0 23 .3 24 .9 23 .7 23 .9 25 . 0 2 2 .5 23. 7 26. 3 24 .3 27. 6 15. 9 28. 6 19..9 2 0 .,5 24 .,5 15.. 6 26.. 6 20 .2 21 .6 25 .5 20 .5 2 0 .3 23 . 2 2 2 .4 2 2 .5 19. 5 25. 9 24 .0 26. 5 16. 9 18 .7 19. 0 25. 4 18.,7 24 ..0 19..4 24 ,.5 27,. 6 26 .9 19 .3 FU 26 .5 FS 24 .0 25 .7 28.,6 2 0 .,7 17,, 0 2 0 ,.0 23 .4 15 .8 20 .0 24 . 0 28 . 6 28 . 0 17 . 1 22 .8 23.3 19.8 12.4 17.0 20.4 18.4 21.6 FS FS 18.6 FDIO 16.2 23.3 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 17) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 632 PUP # 1 2 3 4 5 6 7 8 9 1 0 1 1 12 13 14 15 16 17 18 19 2 0 RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 15 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 13 92 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 34.2 34.2 33.0 21.8 21.6 21.6 23.5 24.1 2 2 . 8 30.9 28.3 30.8 23.6 25.8 23.9 2 0 . 1 2 2 . 2 21.5 26.0 26.6 25.7 21.7 21.3 2 2 . 6 NOT PREGNANT 26.1 28.7 29.1 29.2 28.5 30.2 30.4 31.6 33.0 30.3 29.8 31.1 27.5 28.8 27.9 25.2 19.3 23.7 17.7 24.6 24.5 26.8 25.5 19.2 32.2 33.6 32.2 26.8 27.3 25.7 28.8 25.9 28.4 23.9 24.2 24.3 23.6 23.3 2 0 . 1 23.9 23.1 2 1 . 0 28.1 28.7 27.0 24.0 23.3 24.3 26.7 26.1 26.0 21.4 21.7 23.5 2 1 . 0 23.7 2 1 . 1 24.3 24.4 19.9 33.6 20.2 23.2 29.5 24.2 17.1 26.6 23.5 31.0 28.5 30.7 27.8 29.8 24.7 19.7 23.6 32.2 28.1 28.6 25.1 24.0 18.0 26.2 24.6 27.4 22.7 23.4 24.4 33.9 22.1 22.1 29.2 23.5 24.0 26.5 20.4 28.6 28.3 29.3 30.5 27.5 25.1 24.0 19.8 31.7 26.7 26.7 26.1 24.8 21.3 29.4 24.4 23.6 23.6 22.4 23.5 31.1 22.1 21.4 26.5 26.6 21.1 26.7 22.9 30.0 31.0 28.5 30.0 MM 4 26.5 25.6 22.4 MS 26.4 26.6 24.8 23.5 22.4 26.7 24.4 28.1 22.9 21.2 23.0 33.4 23.5 23.8 27.8 25.1 23.8 27.2 22.1 27.2 27.4 26.7 28.2 27.3 23.4 24.9 22.8 29.8 25.9 27.0 23.6 21.4 20.5 27.6 27.2 24.9 22.5 22.0 24.3 20.9 22.1 27.5 26.3 21.9 23.6 21.8 26.4 27.4 31.6 28.2 28.3 24.7 MD 7 23.4 29.3 25.0 27.7 23.3 23.9 23.2 27.2 24.1 25.8 22.1 21.3 18.1 22.3 22.5 27.7 23.2 23.1 25.9 22.9 26.3 30.6 27.7 29.6 27.0 26.9 21.6 21.9 32.9 25.2 25.6 24.3 24.5 19.9 27.6 25.1 24.1 20.3 21.4 16.2 22.8 22.4 28.5 21.8 21.9 24.4 24.7 28.1 27.0 27.7 30.8 26.4 24.7 19.1 25.9 30.3 28.0 23.6 24.6 25.0 18.5 26.5 23.0 26.7 21.4 21.7 23.6 19.7 19.6 28.2 23.8 18.1 13.9 MS 27.7 26.4 30.3 32.3 28.4 25.6 20.8 22.6 32.7 26.1 24.5 24.2 22.8 27.4 23.1 25.9 21.9 20.0 15.5 21.5 23.2 24.3 22.8 26.1 25.3 MS 27.3 23.5 26.9 27.9 24.1 22.5 22.1 31.5 25.5 25.1 25.2 19.5 26.1 24.7 25.7 21.2 21.3 24.2 18.8 20.8 28.4 23.9 22.8 23.5 20.6 28.9 27.7 26.6 23.6 23.6 21.6 21.6 23.1 26.0 21.6 22.9 22.3 24.8 23.2 26.6 18.3 23.7 22.1 24.8 21.8 23.3 18.1 23.2 23.1 23.3 FM14 14.3 2 1 . 0 18.0 25.6 2 2 . 8 22.3 24 .4 2 2 . 1 23.0 21.5 18.1 24.1 19.8 19.0 20.2 24.5 2 1 . 2 21.7 FD 3 FM 3 FD 4 FD 9 22.0 FS 18.9 FM 5 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 18) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 633 PUP # RAT/ LITTER # 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 10 11 12 13 14 15 16 17 18 MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 15 24.3 23.9 26.1 23.3 17.1 18.8 28.5 27.1 27.7 23.6 26.5 24.2 24.0 2 2 . 8 2 1 . 0 28.0 29.0 28.4 23.1 25.7 25.1 26.8 26.0 28.6 27.7 23.6 24.0 34.2 32.8 33.4 39.5 35.5 36.9 28.1 27.1 23.1 NOT PREGNANT 27.9 27.2 24.5 25.2 26.2 25.1 20.3 22.4 22.3 35.1 30.4 32.8 37.3 34.2 39.2 NOT PREGNANT 27.6 26.6 26.8 28.0 30.1 25.8 25.5 25.2 2 2 . 6 29.6 24.6 25.0 22.9 16.0 2 2 . 1 26.4 27.4 29.2 29.6 28.0 29.7 24.5 26.0 24.0 24.4 24.5 25.1 21.5 2 1 . 8 14.6 27.2 28.2 29.1 26.1 22.4 27.7 25.0 20.7 26.8 19.0 26.2 19.3 30.8 37.8 28.9 23.0 19.9 23.8 32.5 36.3 24.2 29.8 26.6 22.6 18.9 28.1 29.0 24.0 22.5 17.4 31.7 25.4 20.2 27.2 25.4 18.9 29.2 26.0 27.8 24.1 33.4 37.2 25.9 24.9 20.4 28.6 23.0 23.1 22.5 18.7 29.6 24.7 31.1 37.2 27.8 26.3 22.5 21.6 30.3 37.5 26.5 19.4 22.7 MM 6 35.8 27.2 27.8 25.1 27.1 20.5 27.9 27.8 25.4 19.4 23.0 27.8 25.3 30.7 26.3 24.6 21.5 27.2 27.3 24.3 27.5 19.8 28.0 23.5 20.3 25.8 22.5 20.4 24.4 26.3 28.8 25.0 31.3 36.0 26.6 MS 23.5 21.8 MD 5 23.6 28.8 23.7 27.1 14.9 27.2 27.4 23.9 20.7 17.2 28.0 23.3 20.5 24.6 24.4 20.9 25.1 24.2 27.5 19.9 29.6 25.1 MS 25.6 23.4 MM 3 25.8 30.1 MS 27.3 21.9 27.6 27.0 25.5 MD 1 14.7 26.0 24.4 16.9 27.4 23.9 20.4 28.5 24.5 25.3 25.0 28.9 26.2 24.8 25.5 21.0 30.0 MD 2 31.0 24.7 26.0 22.6 26.9 27.0 23.7 27.1 21.0 30.1 22.8 19.4 26.3 23.6 19.8 MD 1 21.4 27.4 20.1 FD 1 26.7 25.1 22.9 21.5 29.1 26.0 30.6 23.6 23.8 22.2 27.5 25.5 27.5 22.8 20.8 30.6 25.5 20.2 26.4 22.4 19.7 24.9 18.3 26.4 22.1 FS 26.6 23.6 25.5 22.4 29.8 25.4 32.1 23.3 23.4 20.2 25.8 24.4 21.7 20.5 29.4 24.6 19.3 23.8 21.6 15.7 27.3 25.1 24.6 21.0 FS 25.4 2 1.1 20.7 20.4 27.8 25.4 24.8 27.4 25.2 28.0 23.7 22.4 22.8 24.8 21.9 19.4 25.1 18.9 18.0 25.5 21.3 2 1.1 26.8 24.6 24.8 20.5 30.8 24.5 22.9 22.4 17.0 25.1 24.5 20.5 27.6 19.7 20.9 24.4 18.9 26.5 28.2 19.9 25.6 20.8 24.6 FM 2 FM 6 26.7 24.7 23.9 23.1 25.8 25.6 23.3 2 1.1 19.8 20.6 20.0 26.6 24.5 22.8 26.8 FD 6 FS 18.8 18.6 21.3 17.9 FD 1 16.0 22.1 FM 2 24.8 23.8 22.3 23.0 22.2 2 1 .9 20.4 FD 1 19.0 21.3 26.9 22.0 FD 6 FD 8 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 19 20 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 19) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 634 pup # RAT/ LITTER # 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 :L 2 3 4 5 6 7 8 9 1 0 1 1 1 2 13 14 15 16 17 18 19 MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 15 2 2 .4 2 2 .3 25 .5 NOT PREGNANT 24 .7 23 .3 25 .0 26 .9 25 .6 27 .3 32 . 8 28 . 2 31 . 1 30 .4 24 .4 27 .9 26 .3 25.. 1 25 .6 17 .3 2 2 . 1 2 0 .7 32 . 6 29 .7 29 . 2 24 . 8 23 .4 28 . 1 30 .9 31 .0 32 .9 19 .5 2 1 .7 18 .6 2 1 .5 24..3 2 2 .6 30 . 1 25.. 2 30,.8 NOT PREGNANT 24 .9 24 . 1 24 . 1 2 2 . 1 2 1 .. 1 2 1 .0 26 .3 28 .5 29 .7 26 . 6 28,.0 26 . 6 23 .3 2 2 .. 1 24 .4 25 .3 23.,7 24 .9 31 . 1 32 .6 30..3 31 .3 35,.9 18 .7 2 0 .. 2 2 0 .3 28 . 1 29..8 24 .3 23 .7 28..4 2 0 .5 2 0 . 2 24,.9 2 1 ,.5 2 2 .5 2 1 ,.5 23 .4 23 .9 23 .3 2 2 .5 25 .9 26 . 2 26,.8 23 .5 29.. 0 27,.7 33 .8 26..4 24..9 25 .0 29..4 24..3 29..7 13..3 2 2 ..0 31. 4 25.. 6 19.. 6 28,.9 25..4 2 2 ,,9 23..9 2 2 ..8 18. 4 27,. 0 23.. 1 2 1 ..8 2 2 .. 1 2 2 ..8 24 .4 24 .8 23 .4 24..3 29,.9 30,.5 25.. 0 24.. 0 2 2 ,.3 31.,7 26..5 27..9 2 1 .4 23..7 28.. 2 28,. 0 25 .9 28,.7 25..5 23 .4 2 1 ,.8 30,. 8 25.. 1 29 .5 19.. 0 23..9 25..5 2 1 .. 1 19. 6 28.. 8 25..3 2 1 .,3 27.. 8 30..4 2 1 .9 23..4 31..5 28.. 6 23..5 24 .9 31..4 17.,5 2 2 .3 25..1 2 1 .4 2 2 ..6 2 2 ,.6 25. 6 19..9 27.. 2 26.. 8 16..9 2 2 ..8 23.. 6 25.. 2 23 .7 2 1 .9 2 0 .4 18 .3 2 0 . 8 2 2 .3 25 .7 32 .3 27 .7 24 . 2 25 .3 30 .4 24 .5 27 .9 22 .1 2 0 .. 1 28 .8 26.. 6 26..3 30..3 24 .3 24 ,. 2 24..7 28.. 6 24.. 2 27.. 1 14..9 23 .,0 29.. 2 28..4 25..3 26., 6 28.,0 MD 1 2 1 .,5 28.,5 2 1 .0 28.,9 19..9 2 2 .5 26..8 22 .1 24 . 2 29 . 2 28,.3 23 .6 2 2 .4 32.. 8 24.. 0 29..5 2 0 .3 2 0 ..7 27,. 1 25.5 22.4 24.1 25.5 20.2 29.4 23.5 27.4 19.4 21.0 25.1 24 . 2 17,.7 27 .9 25 .6 23 .4 2 2 .7 32 .0 2 1 .. 1 2 0 .3 27.,9 28..6 24.. 1 23.. 2 MD 1 26. 1 2 1 .7 28. 3 26. 7 24 .4 23. 3 2 2 ..3 2 1 .,7 16.. 2 24 .9 24., 2 19.,7 2 2 ..6 27 ,.7 23.6 20.7 28.3 26.4 10.5 23.3 27.6 17,. 8 24 . 6 27 .6 23,. 0 24 . 1 24 . 1 24,. 8 18. 7 2 0 .,9 2 0 ..2 18. 4 2 1 .,7 17.,5 24. 4 18. 5 26.,5 MS 23. 6 2 1 .4 2 1 .9 25. 1 17. 4 25.. 2 28.. 2 24 .8 2 0 ..6 23..5 26..4 MM 5 24.4 22.4 23.2 21.8 25.0 21.8 27.6 24.9 25.0 24.0 22.7 24.7 29.0 21.2 22.8 30.6 21.7 18.2 29.3 24.1 19.6 24.0 30.5 19.5 22.3 17.6 22.4 22.3 25.3 22.5 24.9 23.7 29.4 24.1 20.3 25.0 FD 2 20.1 21.9 FD 2 22.4 20.6 26.1 26.8 19.0 17.1 13.4 24.0 17.1 23.8 21.7 23.3 24.5 19.3 20.7 23.9 22.0 19.4 MS 19.4 26.8 22.0 16.4 26.2 23.0 21.4 23.5 FD 1 27.7 25.2 UU FS 17.7 21.0 19.2 25.6 20.8 16.6 FS 22.6 FS FS 19.5 21.0 21.5 22.1 16.6 20.3 FD12 14.7 21.2 FM 6 FD 1 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 20 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.S) TABLE E40 (PAGE 20) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 635 PUP # RAT/ LITTER # 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 10 11 12 13 14 15 16 17 18 19 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 15 26.0 25.1 24.5 31.2 31.8 30.1 2 2 . 8 17.5 23.0 19.8 18.5 16.7 25.6 25.1 24.2 23.9 25.9 23.7 20.9 2 0 . 1 24.2 2 2 . 0 21.4 2 1 . 2 27.5 27.2 27.3 22.7 23.1 24.2 19.6 2 1 . 1 18.5 22.9 23.4 23.0 23.3 24.9 25.6 2 2 . 8 2 0 . 6 17.8 27.5 27.6 24.6 21.9 20.3 19.6 2 2 . 8 24.7 23.7 2 1 . 0 20.7 20.4 NOT PREGNANT 21.5 2 2 . 6 2 0 . 6 25.8 26.1 23.8 37.1 35.5 33.9 22.7 2 2 . 8 20.7 2 2 . 6 23.5 25.0 23.0 24.3 24.8 22.4 2 0 . 6 2 2 . 0 23.4 24.2 18.1 29.7 30.5 28.9 2 1 . 2 2 0 . 8 17.8 23.7 24.1 24.8 24.8 25.4 24.0 18.0 22.4 23.9 21.6 22.9 27.6 22.9 21.2 22.7 23.7 20.4 27.4 22.3 22.5 18.5 22.8 25.1 32.0 19.1 26.3 23.3 21.5 21.9 33.3 20.4 23.4 24 . 6 31 . 1 23 .7 18 .9 19 . 6 2 2 .7 18,.9 2 1 .. 2 27 . 1 2 2 .3 2 1 .9 23..4 25.. 2 17,. 2 26,, 1 2 1 .,7 26. 2 2 0 ., 1 23 .4 32 .4 2 2 .9 18 . 8 25 .9 22 .8 2 1 .9 2 2 .7 27 .9 2 2 .5 19,.5 2 1 ,.8 25 . 2 2 1 ,. 2 2 2 ,.5 2 1 ,.9 24..4 2 1 ,. 2 23 .7 31 .9 19 .6 19,.5 23,.4 23 . 1 2 0 .4 2 0 .5 28,. 2 24..4 MD 7 2 1 ,.7 24 .,0 19., 8 24 ..2 18 .2 25.,5 MM 8 24 . 2 29 . 1 17 . 8 19 . 6 24 .5 2 2 .3 2 1 .0 20 .1 25,.9 26,. 1 13,.9 2 2 .3 2 2 .7 17,.5 27,. 6 2 1 ..6 24 ,.5 MD 7 2 2 ,.7 31..5 25 . 2 18,. 2 23 .8 19,.8 2 0 .4 2 0 .. 2 27,.9 2 2 .1 19..3 2 2 .. 2 23.. 6 15. 8 24..5 19.,5 2 2 ., 1 2 1 .,1 2 2 .7 30 . 1 2 1 .3 17 .0 23 .0 22 .0 20 .3 19..4 26,. 6 2 2 ,.5 16,.4 2 1 ,. 2 2 2 ..8 19,. 1 26..5 18..7 23..7 2 0 .. 1 24 .4 29 . 0 22 .2 16 .9 24 .8 23 . 1 22 .0 20 .0 27 .5 19 . 1 20 .2 22 .0 2 1 .3 19 .0 26,.3 2 2 ,.0 24 .5 2 0 ,.6 2 1 ..5 19.. 2 2 2 .,0 23..6 2 2 ..7 2 1 ..5 2 0 .5 MM 3 24..6 25..0 24 .,3 2 1 .4 25..3 24 .6 2 1 ., 1 2 1 .2 23., 2 2 0 .8 2 1 .7 32.,7 2 0 .6 2 2 .6 2 1 .,1 2 2 .9 24 .,7 18..9 2 1 .4 30., 2 19..4 23 .,5 2 1 .7 23 .. 1 24 .,7 23 ., 1 23 .2 18. 3 24. 9 2 1 ,4 19..9 25.. 0 2 0 ..8 23., 0 17.,9 23 .,6 2 0 .8 23 .1 24 .,1 2 0 ..1 2 2 .4 19..4 2 2 .,6 18.. 2 23. 2 23.. 1 2 0 ..0 2 1 ..9 18.,8 2 1 ., 1 2 0 ,.3 23 ,.6 25,.7 19..9 2 2 .,7 2 0 .5 MD 1 22 .0 26 .5 22 .2 19 . 2 24 .9 23 .0 20 .0 2 1 .7 27 .6 24 .3 17,. 2 2 0 ,. 1 23 ,7 2 1 ..0 25.. 2 18,.5 23 ..2 2 0 ..8 25,.3 FM 2 2 0 ,.9 17,. 2 24 .9 2 1 .4 19..5 26.. 6 23..4 2 0 .7 2 1 .7 2 0 ,.2 24 ..0 2 0 .,1 2 2 .9 19. 8 25..4 FS 9., 0 18., 0 FS 2 2 .,4 2 0 .3 2 0 .1 2 0 .2 2 0 .7 2 1 .7 23.8 18.3 FD 6 25.9 16.9 19.8 24.4 18.4 24.4 19,.8 2 2 .,4 2 0 .8 18.5 25..5 2 0 .7 2 1 .,1 24..3 2 1 .4 2 0 .,6 24.,4 2 1 .3 2 2 .0 18. 7 2 2 .5 19.,7 17. 3 17 .5 19.3 16.0 23. 2 19. 2 2 2 .5 22.4 23.0 18.5 18.6 FD 3 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 20 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 21) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 636 PUP # 1 2 3 4 5 S 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY POSTPARTUM DAY 22 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 45.1 46.2 48.1 47.4 50.4 47.2 47.4 45.5 43.9 52.5 46.4 44.2 41.0 40.1 42.0 35.9 30.7 40.3 31.9 33.0 28.8 28.7 27.7 26.7 28.5 28.7 25.6 27.3 45.5 47.7 43.6 41.7 44.7 42.6 43.3 54.7 51.3 53.2 53.4 39.4 40.3 41.5 41.3 41.0 36.9 36.5 NOT PREGNANT 51.8 46.9 44.4 48.2 52.6 49.0 45.4 33.4 34.9 30.1 33.3 31.5 31.3 24.1 35.8 37.2 38.6 36.0 34.7 35.2 38.1 50.0 46.5 43.2 49.4 53.2 52.8 47.5 28.9 26.6 29.5 32.3 23.7 28.8 25.7 28.7 35.8 26.9 33.8 27.6 31.1 32.6 39.1 38.3 39.1 36.2 38.9 40.4 38.7 44.9 41.0 36.9 42.4 42.4 41.8 38.1 40.8 41.1 41.9 45.0 34.1 40.3 42.9 35.6 29.9 26.2 34.2 19.9 29.1 29.5 41.2 37.5 44.9 39.7 45.0 44.4 45.1 50.4 46.4 45.8 47.7 45.0 46.3 45.4 41.0 41.7 38.4 39.9 37.3 40.1 41.6 49.9 44.3 45.3 41.2 37.9 41.9 46.1 39.9 39.7 41.7 38.8 MD 4 MS 37.2 43.5 40.8 43.3 43.5 41.7 40.7 43.5 34.7 39.6 37.4 32.9 39.2 37.2 MS 25.6 22.6 29.5 29.0 24.3 27.4 27.3 43.4 44.9 39.1 38.9 41.0 41.4 43.0 38.7 42.2 43.9 40.4 41.7 37.0 41.7 NOT PREGNANT; MATING NOT CONFIRMED 43.1 43.2 38.4 43.4 41.5 38.5 40.0 44.1 39.8 31.4 28.4 46.0 39.1 47.8 MM11 35.5 41.8 24.3 27.5 38.8 44.2 41.8 27.4 42.4 47.5 33.1 44.8 40.4 39.8 37.4 21.1 40.1 41.2 37.7 44.0 47.2 34.3 24.4 46.0 38.0 MM 2 30.1 38.2 47.0 23.4 31.1 37.4 38.7 37.8 20.2 43.4 42.6 30.8 38.9 40.9 40.1 38.2 26.2 42.3 36.5 38.1 46.9 44.3 34.0 31.1 44.9 38.4 46.2 31.8 36.1 46.7 26.9 28.5 40.0 43.4 30.0 43.3 44.7 33.7 40.8 42.5 39.5 35.8 27.3 37.3 43.6 42.3 34.8 43.2 30.9 32.3 41.4 39.0 49.1 27.0 34.3 47.7 24.0 34.8 37.4 42.7 29.0 40.3 45.8 36.2 38.6 37.2 38.0 23.4 39.2 40.3 38.9 45.1 37.1 28.6 41.2 41.2 48.4 28.3 44.7 22.5 MM12 41.1 41.7 32.8 37.0 46.0 35.9 42.8 40.9 38.1 25.3 41.2 39.9 41.6 33.1 31.5 35.1 FD17 48.5 26.4 44.8 23.5 26.8 36.9 30.9 39.6 33.5 45.7 39.0 35.5 26.3 40.2 38.2 40.2 37.7 26.7 37.6 48.1 27.6 21.9 28.9 43.1 27.2 40.2 25.8 46.3 41.3 30.0 23.8 FU 39.2 FS 30.4 26.0 48.2 28.1 24.5 28.9 42.4 29.2 34.0 41.7 35.4 34.8 20.9 38.4 34.3 28.4 20.1 19.5 27.2 23.9 36.3 FS FS 23.0 FD10 FD16 29.1 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 22) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 637 p u p # :L 2 3 4 5 6 7 8 () 10 11 12 13 14 15 IS 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY POSTPARTUM DAY 22 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 42 .5 42..4 43 .3 31 .4 36..0 31 .0 32 .3 32..3 32 .7 38 .9 39 .5 39 .5 45 .5 38..3 40 .1 41 .9 31,.3 35 .9 35 .4 34..5 36 .3 36 .8 37..6 42 .0 NOT PREGNANT 34 .6 39..4 39 .7 48 .6 49..1 49 .7 36 .3 39..1 38 .1 48 .8 47..9 43 .2 43 .0 44..8 41,.4 33 .6 32. 4 35 .4 38 .9 32..0 41 .4 28 .6 33..1 30 .9 43 .3 43..9 45..8 50 .7 48 .4 48 .8 49 .6 50..3 49 .3 45 .8 42..8 42..3 39 .5 34..2 38..2 29 .3 38..0 34 .4 46 .7 48..3 50..2 40 .3 42..4 40,.3 47 .2 42.,3 42,.6 39 .1 36,.2 41 .1 39 .2 34 ,.9 31..7 37 .6 38..8 36..6 42 .6 34 .4 40,.8 40 .0 44 .2 36,.0 34,.9 32 .3 40..1 54 .7 37 .8 46 .3 43 ,.3 34 .7 36..7 24 .9 45,.5 46 .1 40,.4 45 ,.5 39,.2 35..6 48,.0 40..1 45..4 34..5 36,.9 30,.8 43..6 27..1 28.,1 36,.4 45,.2 39..8 33.,5 37..7 43 .8 34 .1 31..5 37,.1 37,.2 29..5 35.,0 36..3 39..1 53..9 40..1 48..1 36.,7 35..9 40..2 28.,3 43.,6 49..8 46..4 45. 0 32.,1 31.,1 46..0 38..2 48..3 38..7 36..8 37.,9 39.,7 49..5 38..5 46..4 MM 4 37..5 40..6 29. 8 MS 50..1 48..4 45..0 40. 2 39..6 45.,0 40.,6 41..9 36..4 33 .3 35. 6 39..6 33 .6 32..5 33 ,.5 42 .7 31..9 34..3 37,.7 34..5 52 .3 36..6 49..5 41.,7 40..9 27 ,.8 28..6 41.,5 52 ,.4 45..6 41..9 38..6 33 ,.3 48..2 40..8 48 ..8 38 ,.3 32..9 37..0 34 .0 32 .0 33,.9 44 ,.3 35,.2 32 .0 34 .5 37,.6 46,.7 33,.4 46..5 41..6 38..9 MD 7 35, 4 44 ..3 44 .9 48..5 35,.2 37..2 36..3 43 ,.4 45..1 42..9 36..2 34,.7 38..1 35 .7 33 .2 36 .3 41 .0 28 .4 35 .0 37 .9 34 .4 47 .4 35 .3 45..0 40,.6 34 .8 34 .7 31,.9 40,.5 45 .3 39,,i 39,.4 35,.7 31 .8 44 .6 32 .7 45 ,.0 37 .6 35 .4 35..5 37.7 31.2 36.5 36.4 34.7 31.1 34.1 36.0 42.7 33.3 49.9 43.2 36.4 35.0 32.4 45.1 52.8 42.1 44.9 37.3 42.4 48.0 36.3 41.9 35.7 34.1 37.7 28.1 32.7 32.8 40.7 26.2 30.4 MS 37.8 50.1 33.4 44.7 39.6 32.9 35.0 30.5 41.5 46.8 39.6 28.7 31.6 44.6 35.0 44.4 36.9 35.2 27.8 33.6 27.6 37.5 39.3 33.9 29.3 MS 36.0 44.4 35.7 42.4 34.2 39.9 27.6 45.1 45.7 44.5 35.9 37.6 45.6 42.0 42.9 35.4 38.1 26.2 35.2 25.1 35.7 38.8 29.9 31.2 38.1 34.7 41.7 38.4 25.8 30.9 37.9 36.7 40.2 44.4 37.7 38.0 26.8 34.9 32.2 39.1 38.3 FD17 40.2 36.6 36.9 31.9 32.7 38.1 37.9 33.9 FM14 27.5 30.8 36.0 39.3 28.6 43.1 39.3 25.7 31.6 31.2 33.5 FD 3 22.1 39.5 36.7 33.3 31.1 25.1 37.2 FM 3 FD 4 FD 9 36.2 FS 24.9 FM 5 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 23) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 638 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 22 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 34.3 33.3 30.2 28.8 26.1 27.9 36.0 33.1 36.6 37.2 40.9 40.9 37.6 34.4 32.6 45.1 40.3 37.5 42.4 39.6 41.2 37.7 39.5 37.4 40.5 41.5 34.0 54.6 54.5 52.4 53.5 52.8 52.8 41.0 43.7 41.8 NOT PREGNANT 43.9 43.6 39.3 31.6 27.7 32.3 34.7 35.4 35.9 48.7 50.8 46.8 52.1 50.0 50.2 NOT PREGNANT 42.0 44.5 47.0 50.3 44.7 51.1 37.2 38.8 36.2 38.5 47.9 41.4 33.8 35.8 26.2 37.6 36.3 39.5 50.3 49.5 51.1 38.4 43.3 42.1 41.3 39.8 38.5 37.4 36.6 26.8 45.0 46.5 46.9 32.5 32.2 36.4 40.1 29.0 40.6 37.2 37.9 39.4 51.3 48.7 39.7 41.2 34.2 34.9 53.1 48.1 44.8 50.2 41.1 49.8 30.2 35.0 49.5 41.6 28.8 19.5 43.9 33.3 25.5 35.3 37.4 26.3 43.6 30.0 35.9 42.4 58.9 50.8 40.2 45.4 30.8 34.9 45.4 51.0 43.3 47.9 39.5 43.3 36.0 33.9 49.2 37.8 40.4 27.1 43.0 31.5 28.3 36.6 41.0 37.4 45.9 34.8 40.5 39.2 53.3 53.9 34.7 40.3 31.4 31.2 MM 6 47.8 43.4 51.0 35.3 41.2 31.0 35.1 48.6 41.0 35.1 35.9 41.8 27.9 30.1 35.8 34.3 31.4 48.1 40.6 35.0 41.9 50.7 54.6 43.5 MS 27.8 33.7 MD 5 46.8 52.4 33.1 44.1 35.5 36.2 47.6 42.3 31.6 34.5 47.1 30.0 27.0 34.9 37.7 33.8 42.6 38.3 38.6 38.6 53.2 37.6 MS 28.8 32.3 MM 3 46.6 45.5 MS 43.9 36.2 35.5 41.3 39.4 MD 1 21.3 41.8 28.8 21.8 31.2 41.5 31.3 46.2 36.2 37.0 34.8 48.3 41.4 37.7 26.2 33.0 41.9 MD 2 50.1 37.2 45.9 34.3 35.7 44.7 42.4 40.2 32.6 44.7 33.9 24.4 32.9 34.1 30.7 MD 1 31.0 35.3 39.1 FD 1 39.2 40.2 30.5 31.6 46.9 48.7 50.7 37.8 41.9 35.3 35.9 50.3 40.8 39.6 39.7 45.8 33.6 28.1 34.1 40.9 24.2 43.8 35.0 35.6 37.6 FS 40.9 35.5 32.1 32.0 45.5 44.3 51.9 39.0 32.5 32.6 35.6 41.9 33.3 38.1 46.7 27.9 28.6 34.2 36.8 24.7 40.3 38.8 35.5 36.8 FS 37.0 36.3 31.5 36.3 47.6 44.1 41.2 38.8 34.3 33.8 39.9 34.5 33.4 47.1 34.0 27.3 35.7 39.4 32.2 40.9 39.2 34.7 38.5 43.1 29.5 31.5 43.5 42.3 36.2 38.9 26.3 38.8 33.5 39.6 44.1 25.5 27.1 35.5 33.8 44.2 41.9 37.5 43.0 32.2 28.5 FM 2 FM 6 42.7 35.0 37.3 29.8 38.8 36.9 33.5 28.8 28.6 34.6 30.2 45.9 32.1 34.1 36.5 FD 6 FS 41.1 21.4 37.7 26.2 FD 1 28.2 31.3 FM 2 41.4 38.0 41.3 43.6 31.3 32.2 34.3 FD 1 25.6 28.4 43.6 31.0 FD 6 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E40 (PAGE 24) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 639 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 22 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 38.1 33.8 38.4 NOT PREGNANT 37.1 31.1 35.8 37.4 41.7 40.1 48.3 52.3 49.3 36.3 36.3 31.3 45.4 40.1 46.5 38.8 42.1 31.4 43.0 55.2 54.0 32.7 40.5 40.4 50.2 47.1 49.3 28.3 34.2 30.8 35.4 37.7 30.9 39.5 42.9 40.5 NOT PREGNANT 34.5 39.2 40.0 34.9 35.4 34.3 43.3 47.3 44.4 36.8 36.9 36.3 36.3 40.8 37.2 43.4 42.2 42.7 48.2 50.4 50.1 58.4 50.5 32.6 28.0 25.3 47.6 42.2 47.3 41.6 46.2 36.3 36.6 42.1 38.2 39.0 37.7 41.4 37.4 37.3 39.2 41.5 39.9 39.6 43.5 32.1 39.7 52.7 32.4 45.6 35.3 57.5 45.7 44.9 19.7 36.2 40.4 37.4 37.8 44.5 34.8 33.5 47.5 47.7 33.3 49.0 41.9 26.6 40.0 33.0 39.5 39.1 34.3 33.5 37.3 33.7 36.5 38.4 55.9 30.2 39.5 44.4 50.7 38.2 47.6 29.1 34.5 43.0 31.6 38.8 51.9 35.0 42.2 36.1 49.5 43.1 45.5 32.6 33.8 38.7 32.6 39.9 55.1 36.2 44.4 35.9 49.0 40.8 49.0 30.4 33.1 39.6 32.7 39.1 52.7 30.1 42.6 37.4 54.6 40.8 44.2 31.9 30.2 38.2 28.2 35.7 50.0 29.7 MD 1 34.5 43.1 38.7 45.6 31.8 30.8 41.5 39.6 27.5 48.3 36.6 35.4 42.0 31.4 36.0 32.6 46.0 33.0 36.3 40.2 48.5 37.9 30.6 43.4 32.4 33.6 44.4 51.1 38.6 32.0 46.8 33.6 38.4 38.7 MD 1 41.7 27.0 51.6 31.7 38.9 43.1 47.0 26.1 37.2 38.1 36.9 42.0 38.4 41.5 32.3 41.1 34.5 31.0 36.1 36.4 41.8 29.5 41.2 46.6 37.3 37.1 24.4 42.4 27.8 43.7 34.5 38.0 36.8 35.5 39.6 26.7 41.5 MS 40.7 35.4 31.1 39.3 34.0 31.5 37.1 45.3 29.4 39.6 38.5 47.0 42.8 46.0 25.4 30.4 40.2 34.8 29.8 43.7 33.0 30.3 44.2 47.0 23.4 35.6 43.9 28.9 43.0 36.2 43.6 35.8 33.6 34.4 37.2 36.9 34.3 36.8 38.0 34.6 29.9 44.0 41.6 44.4 40.8 44.8 34.2 32.3 39.3 36.2 45.0 39.1 39.2 44.3 29.8 29.7 38.4 36.1 29.0 35.2 38.9 FD 2 26.5 33.2 FD 2 38.1 33.5 46.8 31.8 35.0 40.8 34.6 36.1 34.0 41.1 31.1 29.8 39.9 48.6 37.3 34.2 43.7 32.5 30.6 MM 5 24.8 30.5 40.5 37.2 39.9 36.8 40.6 42.6 31.2 34.3 35.5 41.0 21.9 37.4 36.1 37.2 33.4 FD 1 34.0 32.6 37.0 33.8 24.8 UU 43.1 42.0 FS 31.2 31.1 32.6 30.2 MS 29.2 33.2 30.7 32.4 36.8 30.8 23.2 21.6 38.3 FS 39.8 36.1 24.5 FS 41.1 FS 21.9 31.7 23.1 FD18 27.2 32.9 FD12 25.2 36.1 FM 6 FD 1 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E4 0 (PAGE 25) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 640 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY POSTPARTUM DAY 22 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 34.1 33.2 33.8 47.2 44.8 35.6 34.7 39.2 35.5 34.9 30.6 31.8 33.7 38.4 37.6 40.2 40.1 45.5 33.9 34.0 40.6 27.9 32.8 32.6 34.4 34.5 33.0 37.1 39.3 35.8 33.3 33.0 36.3 38.8 35.1 37.4 39.7 37.3 39.1 35.0 40.5 36.4 43.9 45.3 44.9 33.6 31.6 32.5 39.4 35.4 38.1 32.7 32.8 33.4 NOT PREGNANT 36.5 36.1 36.1 39.0 42.4 38.1 60.9 58.7 55.1 34.9 39.5 37.2 42.3 41.9 46.2 38.9 39.6 39.5 26.5 24.8 26.3 36.0 36.8 37.4 51.2 51.9 50.6 31.2 27.4 23.4 38.7 40.8 40.6 31.8 49.5 28.7 31.6 38.4 38.1 33.6 29.7 33.6 35.0 29.8 41.4 40.5 33.5 37.6 29.3 37.9 30.8 33.4 45.9 45.0 35.8 34.7 41.1 33.4 32.8 32.1 33.7 36.3 39.6 36.1 26.7 40.6 30.5 38.1 32.7 32.0 47.1 32.5 31.0 39.0 38.3 30.9 34.0 32.9 35.9 31.9 39.9 40.5 36.6 46.8 29.8 37.4 30.5 36.2 40.7 50.7 41.2 33.6 39.2 23.4 39.4 52.4 29.3 39.9 33.1 MM 3 37.2 33.3 40.8 26.7 35.9 56.3 29.4 42.1 34.1 40.4 40.3 37.2 37.7 25.9 37.5 56.1 25.0 37.5 34.5 44.6 35.1 32.1 38.3 37.1 31.3 30.0 34.3 33.8 MD 7 37.0 35.9 32.5 45.2 32.2 37.1 MM 8 33.0 44.8 27.2 27.8 36.3 39.6 34.6 28.6 34.5 31.6 32.9 31.3 39.1 30.9 44.7 29.7 35.9 MD 7 31.6 46.6 22.4 31.9 34.9 33.0 32.2 30.2 33.6 31.1 32.0 36.6 35.3 30.9 44.6 28.7 35.9 33.3 27.2 33.6 33.9 46.4 41.3 42.1 34.0 40.5 40.2 28.3 36.8 37.7 37.6 41.6 25.9 27.8 37.6 37.7 39.3 25.6 35.0 29.3 23.7 26.7 35.7 34.9 33.2 31.8 40.8 34.5 34.7 38.9 39.3 33.6 29.3 33.7 31.3 28.5 34.4 38.2 36.1 47.9 27.6 39.4 31.7 36.3 40.0 31.6 37.0 39.7 28.6 32.7 29.0 37.6 33.3 47.2 32.9 28.5 31.1 38.0 31.9 29.1 31.0 37.6 33.1 35.5 40.8 34.6 47.1 27.3 37.9 33.1 35.1 46.0 35.3 30.8 38.1 36.1 36.5 29.7 35.2 37.0 36.2 35.8 39.3 34.5 45.6 28.5 34.2 34.3 31.6 34.5 41.5 33.9 38.3 35.5 39.1 24.5 38.7 37.4 36.5 24.6 32.4 23.8 29.0 MD 1 38.2 34.8 FM 2 37.4 32.9 37.3 33.5 25.8 35.6 34.1 24.8 36.5 35.9 42.8 30.3 37.2 32.0 32.5 36.8 39.3 24.9 35.8 27.5 38.6 33.3 FS 29.7 29.6 FS 32.1 26.0 39.4 26.1 36.3 35.6 26.9 25.0 34.9 27.9 36.9 31.3 31.0 FD 6 28.3 25.6 30.2 38.0 33.6 22.1 30.3 28.9 32.3 27.7 30.1 24.8 FD16 FD 3 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 20 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E41 (PAGE 1) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 641 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 M A M A M A M A M A FA FA F A FA M A M A M A M A M A M A FA F A F A M A M A M A M A M A MA MA MA FA M A M A M A M A M A M A FA F A F A M A M A M A M A M A M A MA M A M A MA MA FA FA M A M A M A M A M A FA FA F A FA NOT PREGNANT M A M A M A M A M A M A M A M A MM 2 M A M A M A M A M A M A M A MM11 F A M A M A M A M A M A F A FA F A F A M A M A M A M A MA M A MA FA FA M A M A M A M A M A M A MA FA FA M A M A M A M A M A M A MA M A M A M A M A M A M A M A M A FA F A F A M A M A M A M A M A M A FA FA FA M A M A M A M A M A M A MA FA FA M A M A M A M A M A M A MA M A FA M A M A M A M A M A M A MA M A FA M A M A M A M A F A F A FA F A F A M A M A M A M A M A M A MA M A M A M A M A M A M A M A M A MA F A FA M A M A M A M A MD 4 M S F A F A F A M A M A M A M A M A M A FA F A F A MA MA MA MA MA MA MS MA MA MA M A M A M A M A MA MA M A MA M A M A M A M A M A M A FA F A FA M A M A M A M A F A FA FA F A FA NOT PREGNANT; MATING NOT CONFIRMED M A M A M A M A M A F A FA F A F A FA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A FD17 FA FA FA FA FA FA FA FA FA M A MM12 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA MA MA MA FA FA FA FA FA FA FA F A FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FU FA FS FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD10 FA FA F A FD16 FA FS FS FA FA FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E41 (PAGE 2) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 642 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA NOT PREGNANT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA FA FA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA M A MM 4 MA MA MA MA MA MA MA MS MA MA FA FA MA FA MA MA MA MA MA MA MA MA MA MA MA MA FA FA MA MA FA MA FA MA F A MA M A MA M A MA M A MA M A MA M A FA F A FA FA FA F A FA F A FA FA MA M A M A MD 7 MA M A FA F A MA FA FA F A FA F A MA M A MA FA MA FA MA M A MA FA MA FA FA F A FA F A FA FA FA FA MA MA MA FA FA FA FA FA MA FA MA FA FA FA FA MA FA FA MA FA FA FA FA FA FA FA FA MA FA MA FA FA FA FA FA FA FA FA FA FA FA FA MA FA FA MA FA FA FA FA FA FA FA FA MA FA MS FA FA FA FA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA MS FA FA FA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA F A F A F A F A FD 4 FA FA FA FA FA FA FA F A F A F A F A FD 9 F A FD17 FA FA FA FA FA FA FA FA FA FA FA FS FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA M A F A F A F A FM 5 FA FA FA FA F A FM14 FD 3 FM 3 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE ' SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E41 (PAGE 3) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 643 PUP # 12 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA NOT PREGNANT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA NOT PREGNANT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA M A M A MA M A M A MA MA MA MA MA MA FA M A MA MA FA FA FA M A M A FA F A F A F A M A M A FA FA FA FA M A M A M A M A M A MD 1 M A MA MA MA MA MA MA M A MA MA FA FA MA MA MA MA MA FA M A M A F A F A F A FD 1 FA FA FA MA MA MA M A FA FA MA MA MS MS FA FA F A F A FA F A F A FA M A M A MA M A FA FA M A MM 6 MD 5 MM 3 F A F A FA FA MA FA MA MA MA MA MA MA MA MA FA MA FA MA MA FA MA FA MA MA MA FA M A M A MD 2 FA FA FA MA M S FA FA FA FA FA F A FA MA M A MA FA F A FA MA MA MA M A MD 1 F A MA MA FA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FS FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FS FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A F A FD 1 FD 1 FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A F A FM 2 F A F A F A F A F A FD 8 FA FA FA FA FA FA FA FA FA FA FA F A FM 2 F A FM 6 FD 6 FA FA FA FA FA FS FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A F A F A FD 6 FA FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE E41 (PAGE 4) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 644 PUP # 12 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY 1482 1483 1486 1488 1490 1491 14 94 1496 1497 1 S00 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 MA MA MA NOT PREGNANT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA NOT PREGNANT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA FA MA FA MA MA FA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA FA MA FA MA MA FA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA F A FA MA M A M A MA M A FA MA F A FA FA F A F A M A M A MD 1 MA FA FA FA F A F A MA M A M A FA F A F A MA FA FA MA M A M A FA F A F A MA M A MA M A MA M A MA M A MA M A MA F A M A MD 1 MA MA MA FA FA FA FA MA M A M A FA F A FA MA M A M S FA F A FA FA F A FA MA MA MA MA MA M A FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA M A MM 5 FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 2 FA FA FA FA F A FD 2 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 1 F S FA FA FA FA FA UU FA FA FS FA FA FA FA FA FA MS F A F A F A FD12 FA FA F A F A FD18 FA FA FA FA FA FS F A F A F A F A FM 6 FD 1 FA FS FA FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E41 (PAGE 5) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 645 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 15B4 1586 15B7 1588 1589 1591 1593 1598 1600 M A M A M A M A F A F A FA F A F A F A F A F A F A F A M A M A M A M A M A M A F A F A F A F A F A F A FM 2 F S M A M A M A M A M A M A M A M A M A F A F A F A F A F A F A F A F A FD16 FD 3 M A MA MA MA MA M A MA M A FA FA FA FA FA FA FA M A M A M A M A F A F A FA F A F A F A F A F A F A F S M A M A M A M A M A F A FA F A F A F A FA F A MA M A M A MA M A MA MA FA FA FA FA FA FA FA M A M A M A M A M A M A M A F A F A F A F A F A F A F A FD 6 M A M A M A M A M A F A FA F A F A F A FA FA FA M A M A M A M A M A M A MA M A M A M A FA FA FA FA FA FA M A M A M A M A M A M A MD 7 F A F A F A F A F A F A F A F A M A M A M A M A M A M A FA F A F A F A FA F A F A M A M A M A M A M A M A FA FA F A F A FA FA M A M A F A F A F A F A FA F A F A F A F A FA F A F A F A M A M A M A MA M A MA MA FA FA FA FA FA FA M A M A M A M A M A M A FA FA F A F A FA FA F A MA M A M A M A MA M A MA FA FA FA FA FA FA FA FA M A M A M A M A M A M A MM 8 MD 7 F A F A F A F A F A NOT PREGNANT M A MA M A M A M A M A MA M A FA FA FA F A F A F A F A M A M A M A M A MM 3 F A F A F A F A F A F A F A MA MA MA FA M A MA MA MA M A MA MA FA FA FA FA FA FA M A M A M A M A M A F A FA F A F A F A FA M A M A M A M A F A F A FA F A F A F A FA F A F A M A M A M A M A M A M A FA F A F A F A FA F A F A F A M A M A M A M A M A MA MA M A MA MA FA FA FA FA MA MA FA FA FA FA M A M A M A M A M A M A M A F A F A F A F A F A F A F A F A FA FA M A M A M A M A M A M A M A M A M A M A MD 1 F A F A F A F A FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E42 (PAGE 1) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 646 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY (S) POSTPARTUM OBSERVATIONS a I 0 1308 22 16/16 PUPS: DEHYDRATION; UNGROOMED COAT.b 1313 16 1/13 PUPS: DEHYDRATION. 1321 10 1/17 PUPS: EMACIATION; NO MILK PRESENT IN STOMACH. 1348 3 2/14 PUPS: COLD TO TOUCH. 1350 21 17/17 PUPS: DEHYDRATION. II 1 1404 1-22 1/15 PUPS THREAD-LIKE TAIL; NO ANAL OPENING PRESENT. 2-22 1/15 PUPS THREAD-LIKE TAIL. 1418 2 12 12 4/16 PUPS 1/14 PUPS 1/14 PUPS COLD TO TOUCH. COLD TO TOUCH; DEHYDRATION. DEHYDRATION. III 3 1424 4 1/17 PUPS COLD TO TOUCH. IV 10 1517 1 1/15 PUPS COLD TO TOUCH. 1519 16 17 1/16 PUPS EMACIATION. 1/16 PUPS DEHYDRATION. 1523 1 2-22 20-22 22 1/12 PUPS 1/11 PUPS 1/11 PUPS 1/11 PUPS TAIL BENT (0.7 CM FROM BASE).b TAIL BENT (DID NOT EXCEED 3.2 CM FROM BASE RIGHT EYE: NOT PRESENT.b DOMED HEAD.b . 1527 22 1/16 PUPS DEHYDRATION. Tabulation restricted to adverse observations; all other pups appeared normal. b. Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E42 (PAGE 2) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY (S) POSTPARTUM OBSERVATIONS a ARGUS 418-020 Page 647 1545 15 1/18 PUPS: EMACIATION. 1548 1 1/14 PUPS: COLD TO TOUCH. 1550 1-22 1/12 PUPS: NO TAIL PRESENT. 1557 8-15 1/13 PUPS: MOUTH: MASS (DID NOT EXCEED 0.5 CM X 0.2 CM X 0.2 CM) 1565 2 3 4-7 1/12 PUPS: 1/12 PUPS: 1/12 PUPS: BACK: ABRASION (0.5 CM X 0.2 CM); COLD TO TOUCH. BACK: ABRASION (0.5 CM X 0.2 CM); COLD TO TOUCH. BACK: SCAB (0.5 CM X 0.2 CM). 1568 1-7 1/13 PUPS: TAIL: ABRASION (0.3 CM FROM BASE). 1573 5 1/15 PUPS: COLD TO TOUCH. 1583 5-7 8-10 11-12 13-21 22 1/11 PUPS: 1/11 PUPS : 1/11 PUPS: 1/11 PUPS: 1/11 PUPS: BASE OF TAIL: ABRASION (0.5 CM X 0.3 CM) TAIL: ABRASION (2.5 CM X 0.5 CM). TIP OF TAIL BLACK; TIP OF TAIL MISSING. TIP OF TAIL MISSING; TAIL: SCAB (0.2 CM X 0.2 C M ) . TIP OF TAIL MISSING. 1600 1 2-3 1/15 PUPS: PALE IN APPEARANCE. 1/14 PUPS: PALE IN APPEARANCE. a. Tabulation restricted to adverse observations; all other pups appeared normal. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-S889.6) TABLE E43 (PAGE 1) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 648 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I 0 LITTER NUMBER 1302 1304 1306 1308 1310 1312 1313 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 DAY (S) POSTPARTUM 22 22 22 22 22 22 17 22 22 10 22 22 22 22 22 22 22 22 16 22 22 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: KIDNEY: PELVIS, DILATED, SLIGHT. ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-688 9.6) TABLE E43 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) I 0 CONT LITTER NUMBER 1342 1344 1345 1346 1348 1350 1353 1355 1359 DAY (S) POSTPARTUM 22 22 1 4 22 22 1 22 22 22 22 1 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 2 PUPS: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 2 PUPS: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ARGUS 418-020 Page 649 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E43 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTER NUMBER DAY (S) POSTPARTUM OBSERVATIONS ARGUS 418-020 Page 650 1362 1363 1364 1367 1368 1371 1375 1376 1379 1381 1382 1383 1384 1387 22 1 4 22 22 22 22 9 22 17 22 1 22 22 22 22 22 22 1 22 ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: KIDNEY: RIGHT, PELVIS, MODERATE DILATION. ALL OTHER TISSUES APPEARED NORMAL. 5 PUPS: APPEARED NORMAL. ALL OTHER PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E43 (PAGE 4) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) II 1 CONT. LITTER NUMBER 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 DAY (S) POSTPARTUM 7 22 22 1 22 22 22 22 22 22 22 22 22 22 22 3 22 OBSERVATIONS 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN,. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ARGUS 418-020 Page 651 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E43 (PAGE 5) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 652 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) III 3 LITTER NUMBER 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1448 1450 1452 1455 DAY (S) POSTPARTUM 1 22 22 22 22 22 1 22 8 22 22 22 1 22 22 22 1 22 22 22 5 6 22 OBSERVATIONS 2 PUPS: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 2 PUPS: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. CANNIBALIZATION PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E43 (PAGE 6) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 653 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) III 3 CONT. LITTER NUMBER 1456 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 DAY (S) POSTPARTUM 22 2 22 22 1 22 22 22 22 22 22 1 22 6 22 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP: KIDNEYS: BILATERAL, PELVIS, MODERATE DILATION. ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: KIDNEY: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E43 (PAGE 7): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 654 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) IV 10 LITTER NUMBER 1482 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1513 1514 1516 1517 DAY (S) POSTPARTUM 1 22 22 22 22 22 1 22 22 22 1 22 22 22 22 2 22 1 22 12 22 22 22 OBSERVATIONS 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E43 (PAGE 8) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 655 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) IV 10 CONT. LITTER NUMBER 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 DAY (S) POSTPARTUM 18 22 22 1 22 22 22 22 1 22 1 22 22 1 22 22 OBSERVATIONS 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP: BRAIN: THIRD AND LATERAL VENTRICLES, MARKED DILATION. ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E43 (PAGE 9) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 656 MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) V 30 LITTER NUMBER 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 DAY (S) POSTPARTUM 22 1 22 3 16 22 22 1 22 22 22 6 22 22 22 7 22 22 22 22 22 22 22 7 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E43 (PAGE 10): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) V 30 CONT. LITTER NUMBER 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 DAY (S) POSTPARTUM 22 22 22 22 22 22 22 22 22 22 1 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ARGUS 418-020 Page 657 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E44 (PAGE 1) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 658 MATERNAL DOSAGE GROUP I 0 MG/KG/DAY RAT/ LITTER NUMBER 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 BRAIN M FT SPLEEN M FT 1.72 1.61 1.66 0.20 0.21 0.20 1.59 1.55 1.57 0.16 0.15 0.16 1.42 1.32 1.37 0.16 0.11 0.14 1.29 1.35 1.32 0.09 0.15 0.12 1.58 1.48 1.53 0.22 0.30 0.26 1.75 1.67 1.71 0.20 0.17 0.18 1.48 1.39 1.44 0.15 0.17 0.16 NOT PREGNANT 1.69 1.56 1.62 0.24 0.19 0.22 1.45 1.48 1.46 0.13 0.14 0.14 1.56 1.45 1.50 0.18 0.11 0.14 1.56 1.54 1.55 0.17 0.16 0.16 1.44 1.41 1.42 0.11 0.08 0.10 1.58 1.46 1.52 0.14 0.09 0.12 1.53 1.50 1.52 0.10 0.12 0.11 1.52 1.46 1.49 0.14 0.14 0.14 1.56 1.54 1.55 0.19 0.23 0.21 1.23 1.30 1.26 0.13 0.14 0.14 1.05 1.80 1.42 0.15 0.16 0.16 1.58 1.55 1.56 0.15 0.20 0.18 1.44 1.36 1.40 0.10 0.09 0.10 1.56 1.47 1.52 0.15 0.15 0.15 1.53 1.47 1.50 0.08 0.15 0.12 1.57 1.52 1.54 0.09 0.14 0.12 1.50 1.41 1.46 0.13 0.15 0.14 1.34 1.26 1.30 0.07 0.08 0.08 1.44 1.52 1.48 0.11 0.15 0.13 1.63 1.51 1.57 0.14 0.14 0.14 NOT PREGNANT; MATING NOT CONFIRMED 1.53 1.46 1.50 0.20 0.17 0.18 THYMUS M FT 0.31 0.20 0.13 0.09 0.20 0.31 0.21 0.30 0.17 0.08 0.09 0.19 0.26 0.26 0.30 0.18 0.10 0.09 0.20 0.28 0.24 0.26 0.24 0.12 0.20 0.15 0.15 0.16 0.22 0.24 0.14 0.20 0.25 0.12 0.14 0.14 0.22 0.18 0.06 0.16 0.24 0.24 0.18 0.14 0.23 0.10 0.08 0.18 0.23 0.22 0.16 0.17 0.24 0.12 0.16 0.21 0.22 0.19 0.09 0.21 0.23 0.25 0.21 0.13 0.22 0.12 0.12 0.17 0.22 0.23 0.15 0.18 0.24 0.12 0.15 0.18 0.22 0.18 0.08 0.18 0.24 0.22 0.18 0.20 TERMINAL BODY WEIGHT M FT 48.1 45.5 42.0 28.5 45.5 54.7 39.4 44.0 39.8 34.3 28.4 44.9 53.2 36.5 46.0 42.6 38.2 28.4 45.2 54.0 38.0 52.6 33.4 35.8 43.2 26.6 33.8 39.1 44.9 45.0 29.9 41.2 46.4 38.4 44.3 39.9 43.5 34.7 22.6 41.0 38.7 46.2 a 35.5 41.8 23.4 26.8 38.7 44.2 43.4 27.2 40.2 46.3 33.5 42.8 40.9 39.8 35.8 23.8 43.0 41.7 49.4 33.4 35.6 42.5 25.0 30.3 38.9 44.6 44.2 28.6 40.7 46.4 36.0 43.6 40.4 41.6 35.2 23.2 42.0 40.2 41.5 40.2 40'. 8 M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Pup's identification appeared incorrectly recorded; therefore, terminal body weight could not be determined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E44 (PAGE 2) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 659 MATERNAL DOSAGE GROUP II 1 MG/KG/DAY RAT/ LITTER NUMBER BRAIN SPLEEN THYMUS MFTMFTMFT 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 1.54 1.45 1.50 1.43 1.29 1.36 1.42 1.35 1.38 1.60 1.57 1.58 1.42 1.42 1.42 1.30 1.35 1.32 1.39 1.34 1.36 1.48 1.53 1.50 NOT PREGNANT 1.57 1.41 1.49 1.56 1.62 1.59 1.39 1.31 1.35 1.64 1.59 1.62 1.54 1.44 1.49 1.56 1.39 1.48 1.45 1.38 1.42 1.41 1.42 1.42 1.54 1.49 1.52 1.55 1.55 1.55 1.67 1.61 1.64 1.48 1.40 1.44 1.43 1.48 1.46 1.37 1.34 1.36 1.50 1.46 1.48 1.56 1.40 1.48 1.64 1.48 1.56 1.52 1.39 1.46 1.42 1.46 1.44 1.49 1.38 1.44 0.13 0.09 0.11 0.10 0.15 0.09 0.07 0.09 0.15 0.10 0.11 0.10 0.17 0.14 0.10 0.11 0.14 0.10 0.11 0.10 0.16 0.12 0.08 0.10 0.17 0.14 0.10 0.15 0.23 0.14 0.12 0.06 0.14 0.19 0.17 0.20 0.13 0.15 0.19 0.14 0.20 0.18 0.08 0.10 0.15 0.18 0.12 0.19 0.19 0.20 0.11 0.12 0.17 0.23 0.18 0.21 0.17 0.12 0.15 0.08 0.20 0.15 0.12 0.17 0.16 0.16 0.11 0.17 0.21 0.17 0.12 0.09 0.16 0.21 0.18 0.20 0.15 0.14 0.17 0.11 0.20 0.16 0.10 0.14 0.17 0.11 0.13 0.12 0.20 0.13 0.05 0.12 0.18 0.10 0.11 0.15 0.19 0.15 0.11 0.16 0.18 0.10 0.12 0.14 0.20 0.14 0.08 0.14 0.19 0.25 0.14 0.19 0.24 0.14 0.16 0.13 0.15 0.23 0.23 0.22 0.12 0.14 0.19 0.28 0.22 0.12 0.11 0.15 0.21 0.22 0.16 0.19 0.20 0.16 0.19 0.11 0.16 0.18 0.24 0.22 0.15 0.14 0.23 0.13 0.19 0.17 0.12 0.16 0.20 0.24 0.15 0.19 0.22 0.15 0.18 0.12 0.16 0.20 0.24 0.22 0.14 0.14 0.21 0.20 0.20 0.14 0.12 0.16 M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G). TERMINAL BODY WEIGHT M FT 42.5 34.1 32.7 39.5 38.3 29.5 36.3 36.3 43.6 27.5 33.2 36.3 41.0 33.9 30.4 38.1 43.0 30.8 33.0 37.9 39.6 31.7 33.4 37.2 39.7 49.7 36.3 47.9 41.4 38.9 32.0 28.6 43.3 48.4 50.3 45.8 37.2 34.4 48.3 45.1 48.3 38.3 31.7 37.6 34.5 46.7 33.3 49.5 43.2 38.4 35.0 27.6 41.5 44.9 46.4 45.0 37.9 31.8 44.6 33.5 44.4 35.4 36.8 38.1 37.1 48.2 34.8 48.7 42.3 38.6 33.5 28.1 42.4 46.6 48.4 45.4 37.6 33.1 46.4 39.3 46.4 36.8 34.2 37.8 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E44 (PAGE 3) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 660 MATERNAL DOSAGE GROUP III 3 MG/KG/DAY RAT/ LITTER NUMBER BRAIN M FT SPLEEN M FT THYMUS M FT TERMINAL BODY WEIGHT M FT 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 1.44 1.37 1.40 1.28 1.32 1.30 1.50 1.39 1.44 1.57 1.44 1.50 1.38 1.32 1.35 1.44 1.47 1.46 1.49 1.49 1.49 1.56 1.45 1.50 1.59 1.47 1.53 1.53 1.50 1.52 1.82 1.83 1.82 1.58 1.43 1.50 NOT PREGNANT 1.52 1.36 1.44 1.43 1.25 1.34 1.51 1.32 1.42 1.51 1.49 1.50 1.67 1.56 1.62 NOT PREGNANT 1.56 1.50 1.53 1.57 1.53 1.55 1.57 1.49 1.53 1.45 1.60 1.52 1.30 1.38 1.34 1.38 1.41 1.40 1.55 1.56 1.56 1.51 1.48 1.50 1.55 1.45 1.50 1.22 1.33 1.28 1.58 1.54 1.56 0.09 0.11 0.10 0.11 0.10 0.09 0.11 0.10 0.13 0.20 0.24 0.18 0.10 0.10 0.08 0.13 0.12 0.12 0.13 0.11 0.13 0.20 0.23 0.17 0.10 0.10 0.09 0.12 0.11 0.10 0.12 0.10 0.13 0.20 0.24 0.18 0.14 0.10 0.09 0.16 0.23 0.17 0.08 0.12 0.19 0.22 0.16 0.09 0.10 0.18 0.22 0.17 0.17 0.12 0.21 0.10 0.08 0.16 0.17 0.15 0.06 0.19 0.17 0.19 0.13 0.16 0.10 0.15 0.15 0.14 0.13 0.10 0.22 0.17 0.18 0.12 0.18 0.10 0.12 0.16 0.16 0.14 0.08 0.20 0.11 0.09 0.15 0.14 0.09 0.15 0.22 0.16 0.12 0.25 0.30 0.17 0.08 0.06 0.14 0.17 0.16 0.23 0.19 0.15 0.15 0.23 0.32 0.17 0.10 0.08 0.14 0.16 0.12 0.19 0.20 0.16 0.14 0.24 0.31 0.17 0.18 0.10 0.20 0.22 0.19 0.12 0.08 0.15 0.22 0.24 0.15 0.09 0.18 0.22 0.22 0.17 0.24 0.16 0.15 0.12 0.12 0.22 0.11 0.14 0.03 0.20 0.16 0.24 0.16 0.21 0.13 0.13 0.22 0.17 0.11 0.11 0.19 0.16 0.24 0.16 0.18 0.12 0.12 0.22 0.14 0.12 0.07 0.20 34.3 27.9 36.4 37.2 34.4 37.5 40.6 39.5 41.5 54.6 52.8 39.7 43.9 31.6 34.7 50.8 50.0 42.0 51.1 38.8 38.5 26.2 36.3 51.1 a 41.3 19.5 46.5 27.9 27.1 34.9 40.9 31.4 40.3 41.9 37.0 39.1 50.7 50.8 41.4 40.2 27.8 31.6 46.9 51.0 44.3 50.7 37.8 43.9 35.3 35.9 44.7 a 34.5 33.4 43.9 31.1 27.5 35.6 39.0 32.9 38.9 41.2 38.2 40.3 52.6 51.8 40.6 42.0 29.7 33.2 48.8 50.5 43.2 50.9 38.3 41.2 30.8 36.1 47.9 a 37.9 26.4 45.2 . M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Pup's identification appeared incorrectly recorded; therefore, terminal body weight could not be determined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E44 (PAGE 4) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 661 MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY RAT/ LITTER NUMBER BRAIN M FT SPLEEN M FT THYMUS MFT 1482 1483 I486 1488 1490 1491 14 94 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 1.50 1.41 1.46 NOT PREGNANT 1.42 1.42 1.42 1.51 1.43 1.47 1.52 1.48 1.50 1.42 1.78 1.60 1.56 1.42 1.49 1.54 1.45 1.50 1.49 1.48 1.48 1.45 1.41 1.43 1.63 1.53 1.58 1.44 1.38 1.41 1.39 1.29 1.34 1.54 1.57 1.56 NOT PREGNANT 1.63 1.49 1.56 1.39 1.39 1.39 1.48 1.44 1.46 1.57 1.44 1.50 1.52 1.46 1.49 1.60 1.54 1.57 1.53 1.44 1.48 1.65 -- 1.65 1.39 1.28 1.34 1.49 1.53 1.51 1.57 1.51 1.54 1.45 1.44 1.44 1.50 1.49 1.50 1.45 1.35 1.40 1.46 1.55 1.50 0 . 1 0 0.13 0 . 1 2 0.11 0.14 0.25 0.10 0.15 0.10 0.17 0.14 0.16 0.15 0.08 0.22 0.11 0.11 0.27 0.10 0.14 0.16 0.21 0.17 0.14 0.10 0.10 0.18 0.11 0.12 0.26 0.10 0.14 0.13 0.19 0.16 0.15 0.12 0.09 0.20 0.17 0.16 0.21 0.11 0.12 0.16 0.13 0.20 0.11 0.21 0.20 0.16 0.12 0.14 0.14 0.17 0.10 0.17 0.09 0.11 0.14 0.15 -- 0.08 0.18 0.16 0.16 0.11 0.10 0.13 0.17 0.13 0.19 0.10 0.12 0.15 0.14 0.20 0.10 0.20 0.18 0.16 0.12 0.12 0.14 0 . 2 0 0.19 0 . 2 0 0.06 0.22 0.29 0.13 0.19 0.15 0.15 0.18 0.25 0.11 0.21 0.20 0.11 0.16 0.26 0.09 0.17 0.20 0.21 0.24 0.19 0.21 0.19 0.23 0.08 0.19 0.28 0.11 0.18 0.18 0.18 0.21 0.22 0.16 0.20 0.22 0.14 0.14 0.18 0.14 0.10 0.18 0.23 0.21 0.12 0.25 0.20 0.15 0.14 0.16 0.18 0.15 0.11 0.20 0.15 0.14 0.19 0.22 -- 0.08 0.18 0.19 0.18 0.16 0.14 0.16 0.14 0.12 0.19 0.14 0.12 0.18 0.22 0.21 0.10 0.22 0.20 0.16 0.15 0.15 0.17 M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G). TERMINAL BODY WEIGHT M FT 38.1 34.0 36.0 32.6 40.1 52.3 36.3 45.4 35.3 43.0 40.5 50.2 30.8 30.9 42.9 36.9 34.6 52.7 29.7 44.0 34.5 49.0 42.8 45.5 34.2 29.7 38.7 34.8 37.4 52.5 33.0 44.7 34.9 46.0 41.6 47.8 32.5 30.3 40.8 39.2 35.4 48.3 36.8 36.3 42.2 50.4 58.4 32.6 47.6 46.2 42.1 41.4 37.4 39.6 34.8 29.8 43.7 31.8 38.9 38.7 47.0 -- 24.8 41.2 40.5 40.7 37.1 36.1 41.1 37.0 32.6 46.0 34.3 37.6 40.4 48.7 58.4 28.7 44.4 43.4 41.4 39.2 36.8 40.4 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E44 (PAGE 5) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 662 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY RAT/ LITTER NUMBER BRAIN M FT SPLEEN M FT THYMUS M FT TERMINAL BODY WEIGHT M FT 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1593 1.39 1.44 1.42 1.56 1.63 1.60 1.58 1.48 1.53 1.38 1.40 1.39 1.48 1.40 1.44 1.54 1.49 1.52 1.44 1.39 1.42 1.39 1.35 1.37 1.49 1.46 1.48 1.48 1.55 1.52 1.40 1.36 1.38 1.42 1.46 1.44 1.44 1.27 1.36 1.46 1.42 1.44 1.45 1.52 1.48 1.46 1.44 1.45 1.40 1.37 1.38 1.31 1.08 1.20 NOT PREGNANT 1.48 1.41 1.44 1.61 1.51 1.56 1 . 6 6 1.48 1.57 1.43 1.43 1.43 1.61 1.53 1.57 1.38 1.37 1.38 1.39 1.36 1.38 1.52 1.50 1.51 1.45 1.41 1.43 1.38 1.37 1.38 1.41 1.43 1.42 0.13 0.17 0.13 0.12 0.21 0.16 0.12 0.09 0.09 0.16 0.13 0.12 0.12 0.12 0.17 0.07 0.08 0.11 0.11 0.15 0.12 0.09 0.17 0.11 0.13 0.09 0.10 0.18 0.09 0.15 0.10 0.16 0.15 0.07 0.09 0.14 0.12 0.16 0.12 0.10 0.19 0.14 0.12 0.09 0.10 0.17 0.11 0.14 0.11 0.14 0.16 0.07 0.08 0.12 0.09 0.19 0.28 0.10 0.21 0.11 0.15 0.17 0.28 0.05 0.12 0.14 0.15 0.26 0.12 0.16 0.15 0.13 0.10 0.28 0.07 0.14 0.12 0.17 0.27 0.11 0.18 0.13 0.14 0.14 0.28 0.06 0.13 0.16 0.22 0.19 0.10 0.21 0.18 0.17 0.09 0.10 0.14 0.16 0.15 0.17 0.17 0.24 0.11 0.13 0.12 0.15 0.17 0.12 0.14 0.19 0.17 0.14 0.11 0.10 0.20 0.13 0.17 0.16 0.09 0.18 0.10 0.10 0.13 0.16 0.20 0.16 0.12 0.20 0.18 0.16 0.10 0.10 0.17 0.14 0.16 0.16 0.13 0.21 0.10 0.12 0.12 0.13 0.25 0.33 0.11 0.19 0.14 0.09 0.14 0.33 0.08 0.13 0.16 0.22 0.23 0.18 0.20 0.11 0.16 0.16 0.32 0.08 0.14 0.14 0.24 0.28 0.14 0.20 0.12 0.12 0.15 0.32 0.08 0.14 33.2 44.8 a 30.6 38.4 40.2 33.9 32.8 34.4 35.8 33.0 35.1 39.1 35.0 46.8 31.6 38.1 30.8 36.2 39.0 60.9 34.9 46.2 39.2 26.7 36.8 51.2 27.4 40.6 34.8 47.2 a 31.9 31.1 37.1 33.6 29.1 34.5 39.4 32.0 37.0 35.9 30.9 44.6 28.7 34.2 31.7 36.3 40.4 50.7 37.6 40.5 39.3 25.0 38.7 50.6 29.0 38.6 34.0 46.0 a 31.2 34.8 38.6 33.8 31.0 34.4 37.6 32.5 36.0 37.5 33.0 45.7 30.2 36.2 31.2 36.2 39.7 55.8 36.2 43.4 39.2 25.8 37.8 50.9 28.2 39.6 M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Pup's identification appeared incorrectly recorded; therefore, terminal body weight could not be determined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE I) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 663 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY DAY 1 POSTPARTUM 1302 1304 1306 1308 1310 1312 1313 1316 / MA MA MA MA MA FA FA FA FA FA FA 1 . 8 3.1 2 . 8 2 . 6 2 . 6 2.3 0.9 1 . 1 1 . 1 1 . 0 1.3 1 . 0 / MA MA MA MA MA MA FA FA FA FA FA FA 1 . 8 2 . 6 2.4 2 . 6 2.5 2.4 2.4 1 . 2 1 . 1 1 . 1 1 . 0 1 . 0 1.3 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1 . 8 2.5 2.4 2.4 2.4 2 . 6 2.3 2.5 2.5 1 . 0 1 . 0 1 . 1 1 . 1 1 . 0 1 . 1 1 . 1 1 . 0 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1 . 6 2.5 2.5 2.5 2 .5 2.5 2.7 1 . 0 1 . 0 1 . 1 1 . 0 0.9 1 . 1 1 . 1 1 . 0 1 . 0 1 . 0 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA 1.9 2.5 2 . 6 2.7 2.3 2.5 2.5 2 . 2 2.3 2.5 1 . 1 1 . 0 1 . 0 1 . 0 1 . 0 / MA MA FA FA 2 . 2 3.0 3.2 1 . 1 1.3 / MA MA MA MA MA FA FA FA FA FA FA FA FA 1.5 2 . 2 2 . 1 2.5 2 . 6 2.3 1 . 0 1 . 0 1 . 1 1 . 0 1 . 1 1 . 1 1 . 0 1 . 1 NOT PREGNANT 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 2 . 1 3.0 3.0 3.0 2.7 2 . 8 2 . 8 2.5 3.0 2.7 1 . 1 1 . 1 1 . 1 1 . 1 1 . 0 1 . 0 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 1 . 8 2.4 2.5 2.4 2.5 2.4 3.0 2.5 2.5 1 . 0 1 . 0 1 . 1 1 . 0 1 . 1 1 . 2 1 . 1 1 . 0 1 . 1 / MA MA MA MA MA FA FA FA FA FA FA 1.7 2 . 8 2.4 2 . 6 2.4 2.5 1 . 0 1 . 1 1 . 1 1 . 1 1 . 0 1 . 0 / MA MA MA MA MA MA MA FA FA FA FA FA FA 1.9 2.5 3.2 2.5 2 . 6 2 . 6 2.5 2.5 1 . 1 1 . 0 1 . 1 1.4 1 . 0 1 . 2 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 1.7 2.5 2.5 2.3 2.7 2 . 6 2 . 6 2.7 1 . 1 1 . 0 1 . 0 1 . 2 1 . 1 1 . 1 1 . 1 1 . 2 1 . 0 / MA MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA 2 . 0 2.3 2.7 2.3 2.5 2 . 2 2.5 2 . 1 2.5 2 . 6 2.4 2 . 1 2.3 1 . 1 1 . 0 1 . 0 1 . 0 / MA MA MA MA MA MA FA FA FA 2 . 0 2.7 2.5 2 . 6 2.5 2 . 6 2.3 0.7 1 . 0 1 . 0 / MA MA MA MA MA MA FA FA FA FA FA FA 2 . 0 3.2 2 . 6 2.9 3.0 2 . 6 2.7 1 . 2 1 . 0 1 . 0 1 . 2 1.3 1 . 0 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1 . 8 2.5 2.4 2 . 8 2.7 2.5 2.7 2 . 6 1 . 1 1 . 2 1 . 1 1 . 1 1 . 0 1 . 1 1 . 1 1 . 1 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 1 . 6 2.5 2.5 2 . 6 2.3 2.4 2 . 6 2.4 1 . 2 1 . 1 1 . 0 1 . 0 1 . 0 1 . 2 1 . 1 1 . 0 1 . 2 1 . 1 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 2) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 664 PUP # 12 3 4 5 6 7 8 9 10 11 1 2 13 14 15 16 17 18 19 20 2 1 2 2 23 RAT MEAN DOSAGE GROUP I 0 MG/KG/DAY DAY 1 POSTPARTUM 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA 2 . 0 2 . 6 2.7 2 . 8 2.5 2 . 6 2.7 2.7 2.9 1 . 1 1 . 0 1 . 2 1 . 1 1 . 2 1 . 1 / MA MA MA MA FA FA FA FA FA FA FA FA 1.5 2 . 6 2.4 2 . 2 2.5 1.3 1 . 0 1 . 0 1 . 0 1 . 2 1 . 1 1 . 0 1 . 0 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.9 2.7 2.5 2.5 2.3 2.5 2.5 2.7 2.5 2 . 2 1 . 2 1 . 0 1 . 1 1 . 0 1 . 0 1 . 0 1 . 2 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1 . 8 2.7 2.7 2 . 6 2.5 2.4 2 . 6 2.5 1 . 1 1 . 1 1 . 0 1 . 0 1 . 1 1 . 1 1 . 0 1 . 0 / MA MA MA MA MA MS FA FA FA FA FA FA FA FA FA FS 1.7 2 . 8 3.0 2.7 3.0 2 . 8 1.0 1.0 1.1 1.0 1.0 1.2 1.1 1.0 1.2 / MA MA MA MA MA MA FA FA FA FA 2 . 0 2.9 2.9 2.5 2 . 6 2 . 6 2.4 0.9 0.9 1 . 0 1 . 0 / MA MA MA MA MA MA MS MA MA FA FA FA FA FA FA FS 2 . 0 2.7 3.3 2.7 2 . 8 2.5 2.7 2.5 2.4 1.3 1 . 2 1 . 2 1 . 1 1 . 1 1 . 1 / MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA 2.3 2 . 6 3.0 2 . 6 2.5 2 . 6 2.5 2.5 3.0 2.5 2.4 3.4 2.5 2.5 .i 1 . 2 1 . 2 1 . 1 / MA MA MA MA MA MA FA FA FA FA FA FA FA FU 1 . 8 2 . 2 2.7 2 . 8 2 . 8 2.4 2.4 1 . 2 1 . 0 1 . 1 1 . 1 1 . 0 1 . 0 1 . 1 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA 1.5 2.5 2.7 2.4 2.7 1 . 1 1 . 0 1 . 1 1 . 1 1 . 2 1 . 0 1 . 1 1 . 0 1 . 1 1 . 1 1 . 1 NOT PREGNANT; MATING NOT CONFIRMED 1359 / MA MA MA MA MA FA FA FA FA FA FA FA FA FS 1 . 6 2 . 6 2.4 2.4 2.7 2 . 8 0.9 0.9 1 . 1 1 . 0 1 . 1 1 . 0 1 . 0 1 . 2 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . M "OTC01 ^ :T S k nssssiis ^ s s f' SeSrTM" '"'"" o TABLE E45 (PAGE 3) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 665 PUP # 1 2 3 4 5 6 7 8 9 10 1 1 1 2 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP II 1 MG/KG/DAY DAY 1 POSTPARTUM 1362 1363 1364 1367 1368 1371 1375 1376 1378 / MA MA MA MA FA FA FA 2 . 1 3.1 2.9 2.7 2.7 1 . 1 1 . 0 1 . 1 / MA MA MA 1 .6 2 .5 2 .2 2 . 2 / MA MA MA 1 .7 2 .b 2.5 2.5 / MA MA MA 2 .1 2 . 6 3.0 2.9 / MA MA MA 1 . 8 2 .7 2.5 2 . 8 / MA MA MA 2 .0 2.5 2.7 2.3 / MA MA MA 2.3 2.9 2.9 2.9 / MA MA MA 2 .0 2.3 2.4 2.5 NOT PREGNANT MA 2.5 MA 2.6 MA 2.9 MA 2.6 MA 2.6 MA 3.1 MA 2.6 MA 2.6 MA 2.5 MA 2.7 MA 2.5 MA 2.3 MA 2.6 MA 2.4 MA 2.5 MA 2.3 MA 2.4 MA 2.8 MA 2.7 MA 3.0 MA 2.6 MA 2.5 MA 2.3 MA 2.6 MA 2.5 MA 2.6 MA 2.9 MA 2.5 FA 1.1 FA 1.0 MA 2.5 MA 2.5 MA 2.9 MA 3.1 MA 2.6 FA 1.0 FA 1.1 FA 1.2 FA 0.9 MA 2.6 MA 3.1 MA 2.5 FA 1.0 FA 1.0 FA 1.1 FA 1.0 MA 2.7 FA 1.0 MA 2.3 FA 0.9 FA 1.0 FA 1.1 FA 0.9 MA 2.6 FA 1.1 MS FA 0.9 FA 0.9 FA 0.9 FA 1.0 FA 1.0 FA 1.1 MS FA 1.0 FA 0.8 FA 1 .3 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1 .0 FA 1.1 FA 1.1 FA 1.0 FA 1 .1 FA 1.2 FA 09 FA 1.0 FA 1.1 FA 1.2 FA i j) FA 1 .1 FA 1 .1 FA 1n FA 4J n FA in FS 1379 1381 1382 1383 1384 1387 1389 1392 1393 / MA MA MA MA MA MA FA FA FA FA FA FA 1 . 8 2.5 2.5 2 . 6 2 .7 2.4 2 . 6 1 . 1 1 . 1 1 . 0 1 . 0 0.9 1.3 / MA MA MA MA MA MA FA FA FA FA FA FA 2 . 0 2.7 2.9 3.0 3.1 2.9 2 . 8 1 . 2 1 . 1 1 . 2 1.3 1 . 2 1 . 2 / MA MA MA MA MA FA FA FA FA FA FA FA FA 1.7 2.3 2.5 2 . 8 2 . 8 2.7 1 . 1 1 . 2 1 . 0 1 . 0 1 . 0 1 . 2 1 . 1 1 . 2 / MA MA MA MA MA MA FA FA FA FA FA 1.9 2.5 2.4 2.3 2.5 2.5 3.2 1 . 0 1 . 0 1 . 0 1 . 0 1 . 1 / MA MA MA 1 . 8 2.5 3.1 2 . 6 MA MA MA 2.4 2.7 2 . 8 FA 1.1 FA 1.1 FA 1.2 FA 1.0 FA 1.2 FA 1.1 FA 1.0 / MA MA MA MA MA MA MA MA MA FA FA FA FA 1 .9 2.5 2 . 6 2.7 2.5 2 . 6 2.7 2 . 8 2.7 2.5 1 . 1 1 . 0 1 . 1 1 , 0 / MA MA MA MA MA MA MA MA FA FA FA FA FA 1.7 2.3 2.5 2 . 6 2.4 2 . 6 2.4 2.3 2 . 2 0.9 1 . 1 1 . 0 1 . 0 1 . 0 / MA MA MA 1 .8 2.5 2.4 2 . 6 MA 2.6 MA MA 2.5 2 . 2 MA MA MA FA FA 2.4 2.5 2.5- 0.9 1 . 0 FA 1.0 FA 1.1 / MA MA MA MA MA MS FA FA FA FA FA FA 1.7 2 . 6 2.5 2.4 2.5 2.7 1.0 1.0 1.0 1.2 1.1 1.2 FA FA FA FS 1 . 1 1 . 0 1 .0 FA FA FA 0.9 1 .0' 1 .1 FA FA FA FA 0.9 1 . 0 1 . 0 1 .0 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) , X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES HERE RECORDED IN MILLIMETERS (MM) . ' PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 4): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 666 PUP # 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP II 1 MG/KG/DAY DAY 1 POSTPARTUM 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 / MA MA MA MA MA MA MA FA FA FA FA FA 2 . 0 2.7 2.5 2 . 6 2 . 8 2 . 6 2.7 2 . 8 1 . 1 1 . 0 1 . 1 1.4 1.4 / MA MA MA MA FA FA FA FA FA FA 1.9 2.7 3.1 2.9 2.7 1 . 1 1 . 2 1.3 1 . 2 1 . 2 1 . 2 / MA MA MA MA MA FA FA FA FA FA FA FA 1 . 8 2 . 8 2 . 8 3.1 2 . 8 2 . 8 1 . 1 1 . 0 1 . 0 1 . 1 1 . 0 1 . 1 1 . 2 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA 2 . 1 2 . 2 2.5 2.3 2.5 2.5 2 . 2 2 . 2 2.4 2.5 2 . 6 2.5 1 . 2 1.3 1 . 2 1 . 1 t MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.7 2 . 6 2.4 2.3 2.5 2.5 2.3 2 . 6 1 . 1 1 . 0 1 . 0 1 . 0 1 . 1 0.9 1 . 0 1 . 2 / MA MA MA MA MA MA MA FA FA FA FA FA 1 . 8 2.4 2 . 2 2.4 2 . 6 2.5 2.5 2.5 1 . 0 1 . 2 1 . 0 1 . 0 1 . 0 / MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA 2 . 0 2.5 2.3 2.5 2.3 2.4 2.3 2.5 2.3 2 . 2 2.3 2 . 2 2.5 2.5 1 . 2 1 . 0 1 . 0 1 . 0 / MA MA MA MA MA MA MA FA FA FA FA FA FA 1 . 8 2 . 2 2.4 2 . 2 2.4 2.5 2 . 6 2.3 1 . 0 1 . 0 1 . 1 0.9 1.3 0.9 / MA MA MA MA MA MA MA FA FA FA FA FA FA 1.9 2.3 2.4 2.5 2.5 2.5 2 . 8 2 . 6 1 . 2 1 . 1 1 . 2 1 . 0 1 . 0 1 . 2 / MA MA MA FA FA FA FA FA FA FA FA FA FA FA 1.4 2.4 2.3 2.4 1 . 2 1 . 0 1 . 1 1 . 2 1 . 0 1 . 1 1 . 1 1 . 1 1 . 1 1.3 1 . 0 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1 . 6 2 .8 2 . 6 2.3 2 . 2 2.5 2 . 6 1 . 0 1 . 0 1 . 2 1 . 0 1 . 2 1 . 1 1 . 0 1 . 2 1 . 0 1 . 1 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 5) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 667 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP III 3 MG/KG/DAY DAY 1 POSTPARTUM 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 / MA MA MA 2.0 2.7 2.5 2.3 / MA MA MA 1.8 2.5 2.5 2.2 / MA MA MA 1.8 2.3 2.2 2.5 / MA MA MA 1.7 2.7 2.5 2.6 / MA MA MA 1.6 2.6 2.6 2.5 / MA MA MA 2.0 2.4 2.5 2.4 / MA MA MA 1.8 2.7 2.7 2.7 / MA MA MA 2.1 2.9 2.6 2.6 / MA MA MA 2.0 2.7 2.7 2.3 / MA MA MA 2.2 2.7 2.8 2.8 / MA MA MA 2.3 3.5 2.8 3.2 / MA MA MA 2.1 2.8 2.7 3.2 NOT PREGNANT MA 2.3 MA 2.7 MA 2.6 MA 2.5 MA 2.7 MA 2.9 MA 2.2 MA 2.7 MA 2.6 MA 2.5 MA 3.2 MA 2.5 MA 2.4 MA 2.4 MA 2.7 MA 2.8 MA 2.6 MA 2.7 MA 2.2 MA 2.7 MA 2.5 MA 3.0 FA 1.2 MA 2.5 MA 2.6 MA 2.5 MA 2.4 MA 2.5 MA 2.7 MA 2.8 MA 2.3 MA 2.5 MA 2.6 MA 2.5 FA 1.2 MA 2.7 MA 2.3 MA 2.5 MA 2.5 FA 1.1 FA 1.2 MA 2.5 MA 2.6 MA 2.4 MA 2.7 FA 1.2 FA 0.9 MA 2.7 MA 2.5 MA 2.8 FA 0.9 FA 1.0 FA 1.0 MA 2.7 MA 2.5 MA 2.5 MA 2.9 FA 1.0 MA 2.6 MA 2.3 MA 2.4 FA 0.9 FA 1.3 FA 1.0 MA 2.5 MA 2.8 FA 1.1 MA 2.5 FA 1.1 MA 2.6 FA 1.0 FA 1.2 FA 1.2 FA 1.2 MD1 MA 2.2 FA 1.0 FA 1.1 FD1 FA FA 1.1 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.2 FA 1.0 FA 1.2 FA 1.0 FA 1.0 FA 1.1 FS FA 1.1 FA 1.2 FA 1.0 FA 1.1 FA 1.1 FA 1.1 FA 1.1 FA 1.0 FA 1.1 FA 1.1 FS FA 1.6 FA 1.0 FA 1.0 FA 1.2 FA 1.2 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.2 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.3 FA 1.0 FA 1.0 FA 1.3 FA 1.0 FA 1.1 FA 0.9 FA 1.2 FD1 FA 1.0 FA 1.2 FA 1.1 FA 1.1 FA 1.2 FD1 FA 0.9 FA 1.2 FA 1.1 1448 1450 1452 1455 1456 / MA MA MA MA MA MA MS MS FA FA FA FA FA FA FA FA 1.7 2.2 2.8 2.6 2.5 2.5 2.3 1.2 1.1 1.0 1.3 1.0 1.0 1.0 1.0 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1.5 2.5 2.3 2.6 2.8 1.2 1.1 1.0 1.1 1.0 0.9 1.0 1.1 0.9 1.0 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA 1.8 2.4 2.4 2.5 2.3 2.2 2.2 2.5 2.4 1.0 1.0 1.0 1.0 0.9 1.0 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.9 2.7 2.5 2.5 2.7 2.5 2.4 2.6 2.8 1.1 1.2 0.9 1.0 1.2 1.0 1.1 / MA MA MA MA FA FA 2.1 2.5 2.7 2.5 2.8 1.2 1.0 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 6) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 668 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP III 3 MG/KG/DAY DAY 1 POSTPARTUM 1458 NOT PREGNANT 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA 2.0 2.7 2.2 2.7 2.5 2.5 2.4 2.4 2.2 2.5 1.3 1.4 1.3 1.2 1.4 / MA MA MA MA FA FA FA FA FA FA FA 1.6 2.7 2.5 2.4 2.5 1.2 1.1 1.4 1.2 1.1 1.0 1.1 / MA MA MA MA MA MA MA MS FA FA FA FA FA FA FS 1.7 2.5 2.1 2.3 2.5 2.2 2.1 2.2 1.0 1.0 0.9 1.0 1.0 1.0 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1.8 3.0 w O 3.1 3.0 3.1 2.5 1.1 1.2 1.1 1.1 1.1 1.1 1.2 1.0 1.0 1.3 / MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA 1.6 2.8 2.5 2.8 2.5 2.7 1.1 1.1 1.0 1.0 1.2 1.0 1.1 1.0 1.1 1.0 1.0 / MA MA MA MA MA MA MA MA MA FA FA FA 2.2 2.6 2.5 2.5 2.5 2.4 2.6 2.5 2.7 2.3 1.0 1.1 1.1 / MA MA MA MA MA FA FA FA FA FA 2.0 3.0 2.9 3.0 2.7 2.7 1.3 1.1 1.1 1.2 1.2 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA 2.1 2.5 2.4 2.4 2.7 2.7 2.5 2.4 2.5 2.5 2.5 1.1 1.0 1.2 1.0 / MA MA MA MA MA MA MA MD1 FA FA FA FA FA FA FA FA 1.6 2.2 2.3 2.5 2.2 2.5 2.6 2.3 1.1 1.0 0.9 1.1 1.2 1.0 1.1 1.0 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.8 2.4 2.6 2.5 2.4 2.9 2.4 2.5 2.6 1.2 1.0 1.1 1.3 0.8 1.0 1.1 1.1 / MA MA MA FA FA FA FA FA FA FA FA FA FA 1.6 2.9 2.9 3.2 1.4 1.3 1.2 1.2 1.2 1.2 1.2 1.2 1.3 1.3 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 7) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 669 PUP # 12 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 POSTPARTUM 1482 1483 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FD1 FS 1.7 2.6 2.7 2.8 2.4 2.5 2.7 1.0 1.1 1.0 1.2 1.0 1.0 1.0 1.0 NOT PREGNANT 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 2.1 2.8 2.9 3.0 3.0 2.9 2.9 2.7 2.8 2.5 1.1 1.1 1.3 1.0 1.2 1.0 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.9 2.8 2.8 2.5 2.3 2.7 2.5 2.4 2.8 1.0 1.2 1.1 1.2 1.0 1.1 1.0 / MA MA MA MA MA MA MA FA FA FA 2.6 3.2 3.0 3.6 3.5 3.0 2.7 3.1 1.2 1.3 1.2 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA UU 1.4 2.4 2.4 2.5 2.5 1.2 1.0 1.0 1.1 1.0 1.0 1.1 1.1 1.0 1.0 / MA MA MA MA MA MA MA MA MD1 FA FA FA FA FA 1.9 2.4 2.4 2.6 2.6 2.5 2.4 2.7 2.6 1.1 1.0 1.1 0.9 0.9 / MA MA MA MA MA MA MA FA FA FA FA FA FA 1.9 2.8 2.7 3.0 2.6 2.9 2.6 2.5 0.9 1.0 1.1 1.0 1.0 1.2 / MA MA MA MA FA FA FA FA FA FA FA 1.6 2.5 2.6 2.7 2.7 1.0 1.1 1.1 1.2 1.2 1.1 1.0 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FS 1.9 2.7 2.3 2.6 2.4 2.5 2.2 2.2 2.2 2.4 1.1 1.0 1.0 0.9 1 .1 / MA MA MA MA FA FA FA FA FA FA FA FA FA 1.4 2.3 2.2 2.5 2.6 1.0 1.0 1.0 1.0 1.1 1.0 1.1 1.0 1.0 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 1.7 2.4 2.5 2.5 2.3 2.6 2.5 2.5 1.1 1.2 1.1 1.1 1.1 1.0 1.0 1.1 1.2 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.8 2.5 2.7 2.4 2.4 2.1 2.4 2.3 2.5 2.4 0.9 1.0 1.0 0.9 1.0 0.9 1.1 / MA MA MA MA FA FA FA FA FA FA FA FA FA 1.5 2.6 2.8 2.4 2.5 1.1 1.0 1.1 0.9 1.0 1.2 0.9 1.1 1.1 NOT PREGNANT 1513 1514 1516 / MA MA MA MA MA MA MA MA MA FA FA FA FA MS 2.1 3.0 2.5 2.5 2.5 2.6 2.4 2.5 2.5 2.9 1.1 1.1 1.0 1.1 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 2 .1 2.9 2.7 2.8 3.1 3.1 2.8 2.9 2.9 2.7 1.2 1.2 1.2 1.0 1.2 1.4 1.0 1.0 / MA MA MA MA MA MA MA MA MA FA FA FA FA 2.2 2.3 2.7 2.7 2.6 2.5 2.5 2.5 2.6 2.6 1.4 1.1 1.4 1.4 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 8) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 670 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 POSTPARTUM 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 2.0 4.1 2.6 2.6 2.4 2.4 2.9 2.6 2.8 1.3 0.8 1.1 0.9 1.0 1.0 1.2 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.9 2.8 2.7 2.7 2.3 2 .9 2.5 2.8 2.9 1.2 1.0 1.2 1.1 1.0 1.0 1.0 1.1 / MA MA MA MA MA MA MA FA FA FA FA FA 2.0 2.6 2.5 2.3 2.5 2.5 2.7 2.7 1.3 1.2 1.2 1.1 1 .1 / MA MA MA MA MA MA MA MD1 FA FA FA FA 1.9 2.6 2.4 2.5 2.5 2.4 2.2 2.2 1.0 1.1 1.3 1.0 / MA MA 3.6 3.6 3.7 / MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 1.9 2.5 2.5 2.2 2.8 2.7 2.4 2.7 2.1 2.0 2.4 2.7 1.0 0.9 1.0 1.0 1.1 1.1 / MA MA MA MA MA MA FA FA FA FA 1.9 2.6 2.4 2.7 2.4 2.6 2.4 1.0 1.0 1.0 1.1 / MA MA MA MA MA MA MA MA MS FA FA FA FA FA FS 1.9 2.4 2.4 2.5 2.6 2.7 2.2 2.4 2.6 1.0 1.1 1.1 1.0 1.2 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA FA FD1 1.6 2.8 2.5 2.8 2.6 2.9 2.5 1.1 1.1 1.0 1.1 1.1 1.0 0.9 1.0 1.0 1.0 1.0 1.0 / MA MA MA MA MA MA FA FA FA FA FA FA 2.0 2.7 2.9 2.9 2.8 2.6 2.8 1.0 1.3 1.0 1.0 1.2 1.2 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA FS 2.1 2.7 2.5 2.6 2.7 2.5 2.5 2.8 2.5 2.5 2.5 1.0 1.0 1.0 1.0 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA 2.1 2.7 2.5 2.7 2.6 2.5 2.6 2.5 2.6 2.9 1.1 1.1 1.1 1.0 1.1 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 9) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 671 PUP ft 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP V 30 MG/KG/DAY DAY 1 POSTPARTUM 1541 1544 1545 1546 1548 1550 1552 1555 557 1558 1560 1564 1565 1566 1568 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1.5 2.5 2.9 2.4 2.5 1.1 1.1 1.1 1.0 1.2 1.2 1.1 1.1 1.0 1.0 / MA MA MA MA MA MA FA FA FA FA FA FA FA FS 1.7 2.7 2.7 2.3 2.5 2.4 2.5 1.2 1.0 1.1 1.2 1.0 1.1 1.0 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1.8 2.5 3.1 2.3 2.7 2.9 2.7 2.4 2.5 2.5 1.1 1.0 1.1 1.0 1.1 1.2 1.1 1.2 1.1 1.2 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.9 2.5 2.5 3.1 2.5 2.7 2.5 2.7 2.5 1.2 1.0 1.1 1.1 1.1 1.1 1.0 / MA MA MA MA FA FA FA FA FA FA FA FA FA FS 1.4 2.4 2.4 2.4 2.5 1.0 1.0 1.0 1.1 1.0 1.0 1.0 1.0 1.1 / MA MA MA MA MA FA FA FA FA FA FA FA 1.8 2.9 3.1 2.7 2.3 2.4 1.1 1.6 1.1 1.2 1.1 1.2 1.3 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.8 2.2 2.6 2.7 2.8 2.3 2.7 2.7 1.0 1.0 1.1 0.9 1.0 1.0 1.0 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.7 2.4 2.6 2.3 2 .1 2.4 2.6 2.7 1.0 0.9 1.1 1.0 1.1 1.1 1.1 1.0 / MA MA MA MA MA FA FA FA FA FA FA FA FA 1.6 2.7 2.8 2.7 2.5 2.2 1.1 1.1 1.0 1.0 1.1 1.1 1.0 1.1 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 2.1 3.2 2.5 2.6 2.8 2.6 2.7 2.4 2.8 2.5 2.7 1.4 1.2 1.3 1.2 1.1 1 .0 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.8 2.5 2.6 2.5 2.7 2.2 2.5 2 .6 1.2 1.0 .i 1.2 .i 1.2 1 .1 1.0 / MA MA MA MA MA MA FA FA FA FA FA FA FA 1.8 2.5 2.5 2.6 2.3 2.5 2.9 1.2 1.0 1.0 1.0 1.2 1.1 1.2 / MA MA MA MA MA MA FA FA FA FA FA FA 1.7 2.2 2.2 2.4 2.4 2.5 2.3 1.0 1.1 0.9 1.1 1.2 1.0 / MA MA FA FA FA FA FA FA FA FA FA FA FA FA FA 1.4 2.6 2.9 1.1 1.1 1.1 1.3 1.2 1.2 1.1 1.3 1.0 1.1 1.0 1.2 1.1 / MA MA MA MA MA MA MA FA FA FA FA FA FA 2.2 3.3 2.5 3.2 3.1 3.2 3.1 2.6 1.3 1.5 1.4 1.4 1.2 1.2 FIRST LETTER -- 1M-MALE, F-FEMALE, U- SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U- UNCERTAIN, D-DIED, M -MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 10) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 672 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP V 30 MG/KG/DAY DAY 1 POSTPARTUM 1571 1573 1576 1578 / MA MA MA MA MA MA FA FA FA FA FA FA FA 1.8 2.6 2.5 2.3 2.5 2.8 2.6 1.4 1.3 1.2 1.2 1.4 1.1 1.2 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.9 2.7 2.8 2.6 2.4 3.2 2.8 2.8 1.2 1.3 1.0 1.2 1.1 1.1 1.2 1.1 / MA MA MA MA MA MA MA MA FA FA FA FA FA 2.0 2.5 2.2 2.9 2.6 2.3 2.5 2.7 2.5 1.0 1.0 1 .3 1.0 1.0 NOT PREGNANT 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 2.0 3.0 2.7 2.6 2.8 2.9 2.8 2.8 2.9 1.1 1.0 1.1 1.1 1.1 1.0 1.0 / MA MA MA MA MA FA FA FA FA FA FA FA 1.7 2.8 2.7 2.4 2.3 2.7 1.2 1.0 1.2 1.1 1.1 1.2 1.0 / MA MA MA FA 2.5 2.8 3.0 2.9 1.2 / MA MA MA MA MA MA MA FA FA FA FA FA FA 1.9 2.5 2.6 2.4 2.6 2.7 2.6 2.5 1.2 1.0 1.2 1.1 1.1 1.1 / MA MA MA MA MA FA FA FA FA FA FA 1.7 2.8 2.4 2.5 2.6 2.6 1.0 1.0 1.0 1.0 0.9 1.0 / MA MA MA MA FA FA FA FA FA FA FA FA FA 1.5 2.5 2.8 2.8 2.4 1.1 1.0 1.0 1.1 1.1 1 .1 1.2 1 .1 0.9 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.7 2.5 2.5 2.5 2.6 2.6 2.4 1.2 1.0 1.1 1.0 1.0 1.2 1.2 1.4 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA 2.0 2.6 2.8 3.2 2.3 2.4 2.0 2.4 2.2 2.5 2.2 1.1 1.0 1 .0 1.1 / MA MA FA FA FA FA 2.0 3.3 3.0 1.5 1.4 1.6 1.5 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1.8 3.0 2.8 2.7 2.7 2.5 2.7 2.5 1.1 1.2 1.0 1.0 1.1 1.3 1.4 1.2 1.1 1.2 / MA MA MA MA MA MA MA MA MA MA MD1 FA FA FA FA 2.2 2.5 2.6 2.6 2.4 2.3 2.7 2.6 2.8 2.6 2.9 1.1 1.1 1.1 1.2 FIRST LETTER -- M-MALE, F- FEMALE, U- SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U--UNCERTAIN, D-DIED, M -MISSING (PRESUMED CANNIBALIZED) , X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 11) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 673 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY DAY 22 POSTPARTUM 1302 / MA MA MA MA MA FA FA FA FA FA FA 1 1 .2 13.6 13.5 14.5 15.1 15.2 8.5 7.9 8.7 8.1 9.1 8.8 1304 / MA MA MA MA MA MA FA FA FA FA FA FA 1 1 .9 15.9 15.2 14.9 14.5 15.2 13.2 8.1 8.3 9.2 10.0 9.0 9.5 1306 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1 0 .5 14.0 13.5 12.4 13.6 13.0 12.6 13.5 12.8 8.0 7.3 7.5 7.8 8.0 8.6 7.7 7.8 1308 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 9. 0 12.8 12.0 11.9 11.8 12.7 11.6 7.8 6.6 6.4 7.0 7.9 6.2 7.8 6.8 7.6 7.3 1310 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA 1 1 .7 14.6 13.3 13.0 13.4 13.4 14.3 12.9 13.3 13.8 8.6 8.0 8.2 8.6 8.7 1312 / MA MA FA FA 1 2 ,5 14.8 15.0 10.3 9.8 1313 / MA MA MA MA MA FA FA FA FA FA FA FA FD17 1 1 .3 13.3 14.0 15.0 15.6 16.0 9.1 9.3 9.9 7.1 8.1 9.1 9.2 1316 NOT PREGNANT 1318 / MA MA MA MA MA MA MA MA MM2 FA FA FA FA FA FA 1 2 ,3 16.3 14.6 13.5 14.7 14.9 15.0 15.5 16.3 8.6 9.2 8.2 8.5 8.7 7.9 1321 / MA MA MA MA MA MA MA MM11 FA FA FA FA FA FA FA FA FD10 9 .8 13.6 13.9 12.8 13.7 12.0 12.6 11.8 7.0 7.1 6.8 7.2 6.9 7.2 7.6 6.6 1325 / MA MA MA MA MA FA FA FA FA FA FA 9 .6 11.7 14.1 12.0 11.3 11.2 7.2 7.5 8.4 7.9 7.2 7.6 1328 / MA MA MA MA MA MA MA FA FA FA FA FA FA 11 .7 14.6 15.1 12.9 14.1 14.4 15.3 14.2 7.8 9.8 8.1 8.6 8.6 8.4 1330 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 9 .0 12.0 12.6 12.2 11.8 11.5 11.6 11.7 6.9 7.0 6.9 7.4 6.3 6.8 6.2 6.9 6.8 1331 / MA MA MA MA MA MA MA MA MA MA MA MM12 FA FA FA FA 11 .4 12.5 13.0 12.0 13.2 12.7 12.7 11.9 11.9 12.4 13.3 13.2 7.1 8 .3 7.9 8.2 1334 / MA MA MA MA MA MA FA FA FA 12 .3 15.2 13.9 13.8 14.9 15.2 13.5 7.8 8.5 7.8 1335 / MA MA MA MA MA MA FA FA FA FA FA FA 11 .5 15.6 14.2 14.6 13.0 14.2 14.0 9.0 8.3 8.8 8.6 8.3 9.1 1336 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 11 .6 15.0 14.0 14.3 14.9 13.8 14.5 15.5 9.2 8.7 9.2 9.4 8.7 8.2 9.4 9.1 1338 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FD16 10 .3 13.7 12.4 10.7 14.0 14.1 12.4 12.4 12.9 6.4 8.7 7.9 8.4 8.4 7.2 8.4 7.0 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 12) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 674 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY DAY 22 POSTPARTUM 1340 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA 12.2 13.2 13.1 15.5 14.9 15.4 13.3 15.6 15.2 8.6 9.9 8.9 8.7 9.0 9.0 1341 / MA MA MA MA FA FA FA FA FA FA FA FA 11.4 16.0 15.9 15.6 16.0 9.0 9.9 9.4 10.2 8.6 9.4 8.1 9.0 1342 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 11.6 14.4 15.2 15.1 15.0 14.0 15.8 14.5 13.8 12.6 8.5 8.1 9.0 7.5 6.8 7.8 8.4 1344 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 10.9 15.2 14.7 14.5 14.6 13.2 13.2 13.5 8.0 7.2 8.4 7.5 9.3 8.0 8.4 8.0 1345 / MA MA MA MA MD4 MS FA FA FA FA FA FA FA FA FA FS 10.8 15.6 15.4 14.6 15.1 8.5 9.4 8.6 9.3 8.2 9.2 9.1 8.8 8.3 1346 / MA MA MA MA MA MA FA FA FA FA 11.6 13.6 13.0 14.4 14.0 14.5 14.1 8.5 7.5 9.2 7.4 1348 / MA MA MA MA MA MA MS MA MA FA FA FA FA FA FA FS 11.2 13.3 14.1 14.6 13.2 14.3 13.4 14.2 14.7 7.7 7.9 7.2 8.8 7.2 6.9 1350 / MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA 10.5 12.8 11.6 12.2 12.7 11.5 12.5 11.1 9.8 10.9 12.8 11.4 11.3 12.2 6.3 6.2 6.3 7.7 1353 / MA MA MA MA MA MA FA FA FA FA FA FA FA FU 10.6 14.9 13.9 13.0 12.5 13.5 13.3 7.9 8.0 8.6 7.9 7.7 8.7 8.6 1355 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA 10.4 14.6 15.2 14.6 15.1 8.7 8.6 8.6 8.8 8.2 9.0 9.1 8.4 9.3 8.7 8.4 1358 NOT PREGNANT,- MATING NOT CONFIRMED 1359 / MA MA MA MA MA FA FA FA FA FA FA FA FA FS 10.8 14.4 14.5 13.3 14.9 13.6 8.5 8 .5 9.0 8.6 9.2 7.8 8.8 8.8 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 13) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 675 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 RAT # MEAN DOSAGE GROUP II 1 MG/KG/DAY DAY 22 POSTPARTUM 1362 / MA MA MA MA FA FA FA 11.9 14.4 14.9 14.7 13.6 8.8 8.5 8.5 1363 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FD4 FS 10.4 13.1 13.5 12.9 15.6 12.7 13.5 12.6 8.7 8.9 8.3 8.1 7.8 8.3 7.6 8.7 6.9 1364 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 10.4 14.1 14.0 13.1 13.3 12.5 13.5 13.0 7.6 8.7 8.1 8.1 7.2 7.7 7.9 7.5 1367 / MA MA MA MA MA MA MA MA FA FA FA FA FA 11.6 13.3 13.5 13.7 14.4 14.3 14.4 13.4 13.3 8.8 8.5 7.6 8.2 7.6 1368 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 11.5 15.4 13.6 13.5 14.9 15.3 13.4 14.0 14.1 8.6 8.1 8.3 8.7 9.2 7.7 8.3 1371 / MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FD9 11.2 13.3 12.5 13.6 13.0 13.3 12.1 12.2 12.7 11.3 13.6 11.9 7.7 8.1 7.4 8.9 7.8 137S / MA MA MA MA MA MA MA MA MA FA FA FA FA FD17 12.2 15.4 14.1 13.0 14.6 14.3 14.6 14.3 13.2 13.8 8.9 7.9 6.4 8.6 1376 / MA MA MA MA MA MA MA MA MA MA MS MS FA FA FA FA FA 11.5 13.0 12.9 13.9 12.7 13.5 13.0 12.4 12.9 13.6 12.6 7.8 8.3 8.7 8.9 8.5 1378 NOT PREGNANT 1379 / MA MA MA MA MA MA FA FA FA FA FA FA 10.5 12.6 14.1 12.6 13.4 13.2 13.7 7.8 7.9 6.8 8.3 8.0 7.4 1381 / MA MA MA MA MA NA FA FA FA FA FA FA 12.3 16.1 15.4 15.0 15.2 16.0 16.1 8.1 9.2 9.7 9.4 8.6 9.0 1382 / MA MA MA MA MA FA FA FA FA FA FA FA FA 10.7 14.5 13.5 14.3 13.8 14.9 9.2 8.4 8.4 8.8 8.0 8.3 8.6 8.8 1383 / MA MA MA MA MA MA FA FA FA FA FA 11.9 14.7 15.2 15.5 14.1 13.8 14.9 8.5 7.6 8.5 9.4 9.0 1384 / MA MA MA MA MA MM4 FA FA FA FA FA FA FA 10.6 14.2 14.2 15.0 14.6 13.0 8.3 7.7 8.0 7.2 7.4 9.0 8.0 1387 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FS 11.3 13.7 13.6 13.4 12.9 13.0 14.3 13.1 14.7 14.3 8.5 8.5 8.3 8.1 8.1 8.7 8.2 1389 / MA MA MA MA MA MA MA MD7 FA FA FA FA FA FA FA FA 10.0 12.2 13.0 13.9 13.0 15.1 13.4 11.5 7.7 7.0 7.3 7.8 6.8 7.1 8.0 6.8 1392 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 9.6 10.8 11.6 11.8 11.8 11.8 11.6 11.3 12.5 12.4 7.5 7.4 7.2 7.2 7.8 7.0 7.0 6.5 1393 / MA MA MA MA MA MS FA FA FA FA FA FA 11.3 14.7 15.0 14.8 15.5 15.4 8.0 8.1 7.6 9.0 8.1 8.3 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020; ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 14) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS PUP ft 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1G 17 18 19 20 21 22 23 RAT ft MEAN DOSAGE GROUP II 1 MG/KG/DAY DAY 22 POSTPARTUM 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 / MA MA MA MA MA MA MA FA FA FA FA FA 13.2 16.0 15.0 15.6 15.5 16.3 16.9 15.6 9.9 9.6 9.7 9.1 9.3 / MA MA MA MA FA FA FA FA FA FA 12.1 16.5 16.6 17.1 14.4 9.7 9.8 9.3 9.4 9.0 9.6 / MA MA MA MA MA FA FA FA FA FA FA FA 10.9 14.0 15.0 13.4 15.7 14.6 8.4 8.4 8.0 7.2 8.8 8.5 9.2 / MA MA MA MA MA MA MA MA MA MA MA FA FA 11.6 13.5 12.1 12.8 13.4 12.1 13.6 13.6 15.0 13.0 13.5 8.7 8.2 9.2 / MA MA MA MA MA MA MA FA FA FA FA FA FA 10.4 12.0 13.3 12.9 13.1 12.1 13.5 12.2 8.7 7.7 8.8 8.4 8.7 8.1 / MA MA MA MA MA MA MA FA FA FA FA FA 13.3 15.9 16.6 15.0 15.5 16.3 15.8 8.9 9.8 9.4 9.6 10.0 / MA MA MA MA MA MA MA MA MA MA MA MA MA 12.9 14.8 14.1 13.3 14.8 13.8 14.2 14.0 16.2 13.0 13.9 13.0 13.8 14.4 / MA MA MA MA MA MA MA FA FA FA FA FA FA 11.7 14.8 13.8 14.3 12.2 15.3 13.8 14.5 8.8 8.0 8.1 9.4 9.3 9.3 / MA MA MA MA MA MA MA FA FA FA FA FA FA 10.2 12.5 12.7 12.6 11.9 12.7 12.2 11.5 8.0 6.8 8.0 8.5 7.3 7.7 / MA MA MA FA FA FA FA FA FA FA FA FA FA 9.1 14.4 12.8 13.0 8.1 8.1 8.0 7.3 8.1 7.6 8.5 7.9 8.0 8.0 / MA MA MA MA MA MA FA FA FA FA FA FA FA 10.4 13.6 15.5 13.6 11.5 15.4 13.0 8.8 8.2 7.8 7.3 7.1 6 .1 7.6 FA FA 7.2 8.4 FA FA 8.3 8.8 FA FA 7.9 8.0 FA 7.8 FM14 FD3 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSINGr SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . ARGUS 418-020 oe tret Page 676 PROTOCOL 41B-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 15) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 677 PUP # 10 11 12 13 14 15 16 17 18 19 2 0 21 2 2 RAT # MEAN DOSAGE GROUP III 3 MG/KG/DAY DAY 22 POSTPARTUM 1421 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FD1 FD1 10.5 11.9 12.8 11.4 12.5 11.9 12.3 11.6 11.8 11.7 12.5 8.1 6.7 8.3 7.0 7.5 1424 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 9.0 10.6 10.6 11.2 12.5 10.8 10.9 12.0 10.1 10.2 6.6 6.5 6.7 6.6 6.8 7.4 7.1 6.7 1426 / MA MA MA MA MA MA MA FA FA FA FA FA FA 10 .4 11.3 12.6 12.5 14.4 12.6 13.4 12.3 7.6 6.9 8.4 7.1 8.7 7.7 1428 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 10.6 13.8 14.6 13.3 14.7 15.0 12.6 7.8 8.8 8.2 7.8 8.6 7.7 8.8 8.6 8.6 1430 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA 9.5 13.3 13.2 13.8 12.8 11.9 13.6 6.7 8.6 8.4 7.4 6.9 6.7 8.9 7.7 6.5 7.7 7.3 1431 / MA MA MA MA MA MA MA MA MA MD1 FA FA FA FA FA FM2 12.8 16.2 14.8 15.2 15.0 14.9 15.4 16.5 14.9 13.9 7.9 7.8 9.4 9.1 8.7 1433 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FD8 11.4 14.6 14.4 13.3 13.8 13.1 13.8 13.5 12.7 14.1 13.1 8.0 8.6 9.0 8.7 8.2 7.5 8.3 1436 / MA MA MA MA MA MA MA MA FA FA FA FA 11.7 12.5 13.4 13.9 12.7 13.6 13.3 12.4 13.5 8.8 8.8 8.4 8.7 1437 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 10.6 13.3 13.5 12.1 13.2 14.3 12.9 13.7 13.0 12.7 6.6 8.0 8.8 6.8 6.4 6.2 8.6 1439 / MA MA MA MA MA MA FA FA FA FD1 FS FS 13.9 15.4 15.8 16.7 15.8 16.3 14.9 10.6 9.9 9.5 1442 / MA MA MA MA FA FA FA 13.0 17.0 15.4 15.6 14.2 10.7 9.0 9.0 1443 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA 11.4 13.8 14.6 14.2 13.9 14.3 13.1 15.1 12.0 7.5 8.6 7.4 8.9 8.7 8.0 1446 NOT PREGNANT 23 1448 / MA MA MA MA MA MA MS MS FA FA FA FA FA FA FA FA 10.2 13.8 13.5 14.5 13.1 13.7 12.8 7.1 8.8 8.1 7.6 8.3 6.8 8.1 7.0 1450 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA 9.3 12.8 12.1 12.4 13.6 7.9 8.4 8.1 7.7 7.3 7.7 8.8 8.2 7.4 7.4 1452 / MA MA MA MA MA MA MA MA FA FA FA FA FA FM 2 10.6 10.9 11.6 12.4 12.9 11.8 12.5 12.6 11.6 9.4 8.0 8.5 7.9 7.2 1455 / MA MA MA MA MA MM6 MD5 MM3 FA FA FA FA FA FM 6 FD6 10.9 13.5 13.8 13.8 14.6 12.7 8.0 8.6 7.9 7.8 8.3 1456 / MA MA MA MA FA FA 12.2 12.6 12.3 14.2 15.9 9.1 9.4 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E4 5 (PAGE 16) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 678 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP III 3 MG/KG/DAY DAY 22 POSTPARTUM 1458 NOT PREGNANT 1459 / MA MA MA MA MA MA MA MA MD2 FA FA FA FA FA 12.1 13.6 14.7 14.7 15.0 14.1 14.3 15.9 14.0 10.0 9.0 7.7 7.0 7.0 1461 / MA MA MA MA FA FA FA FA FA FA FA 12.1 15.1 15.5 15.8 14.6 10.0 10.4 10.2 10.1 10.1 10.2 10.9 1463 / MA MA MA MA MA MA MA MS FA FA FA FA FA FA FS 10.8 13.4 14.1 12.4 13.2 13.6 13.5 14.0 8.4 8.0 7.3 7.1 8.2 7.3 1465 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 11.1 14.1 16.1 14.5 15.4 14.0 15.5 9.3 9.5 9.0 8.0 8.8 8.7 8.7 8.5 8.5 9.3 1468 / MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA 9.2 12.7 13.3 11.4 12.7 13.4 6.3 8.5 8.3 7.7 8.6 7.7 7.9 7.2 7.5 6.1 7.5 1469 / MA MA MA MA MA MA MA MA MA FA FA FA 11.8 13.8 13.2 14.2 12.6 12.0 12.4 11.6 12.6 13.0 8.6 8.3 9.0 1472 / MA MA MA MA MA FA FA FA FA FA 12.4 14.6 16.1 15.0 14.5 15.1 9.8 10.2 9.7 8.3 11.2 1474a 1476 / MA MA MA MA MA MA MA MD1 FA FA FA FA FA FA FA FA 9.9 11.9 13.6 12.9 11.3 13.3 12.4 12.0 8.6 8.0 7.7 8.0 7.7 8.7 8.2 7.0 1477 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 9.6 14.3 12.9 1 0 .3 9.2 11.3 11.8 12.6 10.2 7.2 7.3 7.4 7.7 8.3 8.0 6.5 8.3 1480 / MA MA MA FA FA FA FA FA FA FA FA FA FA 10.1 14.1 14.4 16.0 8.8 9.1 8.8 8.7 7.9 7.6 8.4 9.0 9.1 9.0 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . a. Anogenital distances for litter 1474 were not recorded. M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 17): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 679 PUP # 12 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP IV 10 MG/KG/DAY DAY 22 POSTPARTUM 1482 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FD1 FS 10.4 13.4 12.6 12.9 13.4 14.4 12.6 8.0 8.9 9.1 7.8 8.5 7.8 8.6 7.3 1483 NOT PREGNANT 1486 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 11.5 13.3 12.2 14.8 13.2 14.9 12.8 14.1 13.6 12.4 8.9 8.2 7.9 8.9 9.1 8.4 1488 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 12.7 15.2 15.5 15.0 16.8 16.6 15.1 16.9 12.6 9.6 9.4 10.0 8.7 9.4 10.0 10.4 1490 / MA MA MA MA MA MA MA FA FA FA 14.4 16.1 15.4 15.5 17.7 17.6 16.6 17.3 9.5 9.3 8.6 1491 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA UU 9.4 13.9 13.8 12.1 12.2 7.5 8.3 8.4 7.7 8.1 8.5 7.8 8.8 7.7 6.9 1494 / MA MA MA MA MA MA MA MA MD1 FA FA FA FA FA 11.9 14.6 13.0 14.9 13.7 15.8 14.1 14.1 12.7 8.5 8.3 8.8 7.0 8.8 1496 / MA MA MA MA MA MA MA FA FA FA FA FA FA 11.0 13.8 13.6 12.9 13.6 15.1 13.9 12.8 8.5 7.8 7.1 8.3 8.4 7.2 1497 / MA MA MA MA FA FA FA FA FA FA FA 11.3 12.9 14.7 14.6 16.3 9.2 9.9 10.0 9.5 9.3 8.7 9.0 1500 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FS 11.9 12.5 13.3 14.3 13.8 13.7 15.0 13.1 14.4 14.8 9.0 8.1 8.3 8.1 7.8 1502 / MA MA MA MA FA FA FA FA FA FA FA FA FD2 11.0 14.7 15.7 16.2 16.0 8.9 7.5 9.4 9.3 9.2 7.5 8.1 8.9 1505 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 9.1 11.0 12.6 11.5 9.0 11.0 12.0 11.3 7.7 7.8 6.2 8.3 7.6 7.2 7.7 7.7 6.6 1507 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 10.2 12.9 12.3 11.7 12.4 13.4 11.9 12.5 12.0 11.6 7.5 7.9 8.0 7.3 8.3 7.0 7.2 1508 / MA MA MA MA FA FA FA FA FA FA FA FA FD2 9.9 12.7 14.3 13.0 14.4 8.2 8.5 7.4 8.2 7.9 9.0 7.9 7.7 1511 NOT PREGNANT 1513 ! MA MA MA MA MA MA MA MA MA FA FA FA FA MS 11.9 12.5 13.7 14.3 13.3 13.7 13.6 13.0 13.5 14.0 7.0 8.8 8.7 8.5 1514 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FD12 11.3 14.8 15.0 13.8 14.0 13.1 14.4 13.6 13.3 12.0 7.3 8.6 8.5 9.1 7.4 8 .1 7.5 1516 / MA MA MA MA MA MA MA MA MA FA FA FA FA 12.3 13.4 14.5 13.0 14.3 13.9 15.2 14.4 13.4 14.6 7.8 8.7 9.0 8.3 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 18) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 680 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP IV 10 MG/KG/DAY DAY 22 POSTPARTUM 1517 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 9. 6 12.4 11.7 11.8 11.6 12.9 11.5 10.9 10.6 7.2 6.9 8.0 7.0 7.2 6.9 6.9 1519 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FD18 1 0 .6 13.7 14.5 13.5 14.1 11.8 14.2 13.6 13.4 8.0 6.3 8.0 7.1 7.0 8.2 6.4 1521 / MA MA MA MA MA MA MA FA FA FA FA FA 1 1 ..0 12.7 13.0 14.0 13.6 12.0 13.0 12.5 8.8 8.6 8.3 7.7 8.4 1523 / MA MA MA MA MA MA MA MD1 FA FA FA FA 1 2 .4 14.8 14.9 15.2 14.3 12.1 15.0 15.5 9.4 8.4 8.0 8.8 1524 / MA MA 17. 5 18.4 16.6 1527 / MA MA MA MA MA MA MA MA MA MA MM5 FA FA FA FA FA FA 9..2 11.1 11.3 10.8 12.4 11.3 11.6 11.6 12.7 10.0 9.2 6.5 6.8 5.5 5.1 6.4 5.7 1528 / MA MA MA MA MA MA FA FA FA FA 1 1 ,.6 14.4 14.1 15.0 14.0 13.5 13.1 8.2 7.8 8.2 8.0 1531 / MA MA MA MA MA MA MA MA MS FA FA FA FA FA FS 11 .8 13.3 14.4 15.0 14.8 13.4 12.9 13.7 13.9 9.3 8.3 9.0 5.9 9.2 1533 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA FM6 FD1 9 .9 13.7 14.6 13.8 11.0 12.9 12.0 8.6 8.0 8.0 6.9 9.1 8.1 8.9 7.3 7.5 8 .6 9.0 1534 / MA MA MA MA MA MA FA FA FA FA FA FA 10 .2 12.6 12.7 14.4 12.7 12.7 12.4 8.0 7.1 7.3 7.5 7.9 7.5 1537 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA FS 10 .6 11.8 12.0 12.1 11.6 12.9 13.4 10.5 12.0 11.6 12.4 7.5 7.3 7.7 6.1 1539 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA 12 .0 14.8 14.0 14.9 14.1 13.6 14.3 15.2 13.3 13.1 8.1 8.1 7.9 8.3 8.9 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 19) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 681 PUP # 12 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP V 30 MG/KG/DAY DAY 22 POSTPARTUM 1541 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA 9.7 12.4 13.9 13.8 13.6 9.0 8.0 7.8 8.3 8.3 8.1 8.1 7.8 8.2 8.8 1544 / MA MA MA MA MA MA FA FA FA FA FA FA FM2 FS 11.4 14.6 12.4 13.9 16.0 12.5 15.0 9.1 8.9 8.3 8.7 9.1 8.7 1545 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FD16 FD3 9.8 12.0 11.8 12.7 11.4 14.3 12.8 12.3 10.6 10.0 7.6 7.8 7.0 7.6 6.8 8.2 6.3 7.3 1546 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 9.6 12.4 11.7 12.3 11.8 12.6 12.2 12.3 10.8 7.3 7.1 7.2 6.8 6.6 6.3 6.9 1548 / MA MA MA MA FA FA FA FA FA FA FA FA FA FS 9.6 12.3 14.5 13.3 13.9 7.8 8.1 8.1 8.6 7.7 7.9 7.5 7.2 8.3 1550 ! MA MA MA MA MA FA FA FA FA FA FA FA 10.5 13.4 13.1 14.4 14.0 14.0 9.3 8.6 8.6 7.1 8.7 7.4 7.9 1552 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA 10.2 13.0 13.2 13.4 13.4 12.6 11.6 12.0 7.9 7.7 8.1 7.7 6.8 7.9 6.8 1555 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FD6 9.5 11.5 12.3 11.8 11.7 11.6 12.2 12.5 7.3 7.1 6.7 7.6 7.2 7.0 6.2 1557 / MA MA MA MA MA FA FA FA FA FA FA FA FA 10.3 14.0 13.8 13.1 13.5 12.7 8.6 8.3 8.2 8.0 8.3 8.0 8.7 9.2 1558 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 11.4 13.1 13.8 14.4 13.4 12.9 14.2 13.4 13.9 12.5 14.2 9.0 8.1 7.2 8.7 7.1 7.0 1560 / MA MA MA MA MA MA MD7 FA FA FA FA FA FA FA FA 9.2 12.6 11.7 12.0 11.8 12.5 11.8 7.0 8.0 6.4 7.0 8.8 6.3 6.3 6.0 1564 / MA MA MA MA MA MA FA FA FA FA FA FA FA 10.3 13.1 13.0 13.3 12.4 13.0 13.3 8.1 7.2 8.1 7.9 8.3 8.2 7.5 1565 / MA MA MA MA MA MA FA FA FA FA FA FA 11.8 14.9 14.0 14.2 14.5 13.8 14.9 9.6 9.4 8.5 9.1 9.1 9.4 1566 / MA MA FA FA FA FA FA FA FA FA FA FA FA FA FA 8.3 13.1 12.2 8.1 7.9 7.4 7.5 7.8 7.2 7.4 8.2 8.3 7.1 7.8 8.3 6.9 1568 / MA MA MA MA MA MA MA FA FA FA FA FA FA 11.9 14.3 15.0 14.7 13.0 14.2 15.6 14.2 8.8 8.9 8.5 9.0 9.4 9.7 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TABLE E45 (PAGE 20) : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 682 PUP # 12 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP V 30 MG/KG/DAY DAY 22 POSTPARTUM 1571 / MA MA MA MA MA MA FA FA FA FA FA FA FA 9.7 12.2 11.9 13.4 11.6 13.0 12.5 7.2 8.0 7.0 7.9 6.8 6.7 7.7 1573 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 11.0 15.1 13.3 13.6 14.4 14.3 14.8 13.3 8.5 7.3 8.1 8.7 8.1 8.2 9.2 8.7 1576 / MA MA MA MA MA MA MM8 MD7 FA FA FA FA FA 10.2 12.0 12.4 13.0 11.7 12.4 12.0 7.0 7.4 8.5 8.2 7.5 1578 NOT PREGNANT 1579 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 10.5 14.0 12.7 14.5 13.0 12.8 13.7 11.5 13.6 8.2 7.1 7.4 7.5 8.1 5.9 7.3 1583 / MA MA MA MA MM3 FA FA FA FA FA FA FA 10.7 14.0 14.1 14.6 14.7 8.4 9.0 8.8 8.8 9.0 8.5 8.0 1584 / MA MA MA FA 16.3 18.4 17.9 18.9 10.1 1586 / MA MA MA MA MA MA MA FA FA FA FA FA FA 11.4 13.7 15.0 12.4 13.3 12.9 14.9 12.3 8.2 8.4 8.8 9.1 9.4 9.3 1587 / MA MA MA MA MA FA FA FA FA FA FA 10.7 14.0 13.9 14.1 12.8 12.2 9.5 8.9 9.0 8.3 7.6 7.8 1588 / MA MA MA MA FA FA FA FA FA FA FA FA FA 10.1 12.9 13.5 13.9 12.5 9.3 8.6 7.9 9.2 8.4 8.0 8.9 9.0 8.7 1589 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA 9.0 11.0 11.2 11.8 11.2 12.4 12.0 8.1 7.0 6.7 7.6 6.9 7.0 6.4 6.3 1591 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA 11.6 12.5 13.2 13.2 13.2 14.6 13.0 12.1 12.7 13.4 12.3 8.0 6.9 7.7 9.0 1593 / MA MA FA FA FA FA 11.3 15.2 15.0 9.8 8.6 9.3 9.8 1598 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 8.7 11.8 11.5 10.7 12.0 11.6 11.6 11.8 5.9 7.4 7.6 6.6 6.6 6.8 7.2 5.9 1600 / MA MA MA MA MA MA MA MA MA MA MD1 FA FA FA FA 11.2 13.6 13.4 14.0 13.8 12.8 12.7 12.2 12.2 11.3 12.1 8.2 7.1 6.6 6.9 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE .' SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM) . ARGUS 418-020 APPENDIX F PROTOCOL AND AMENDMENTS Page 683 ARGUS 418-020 OPrimedica Argus Research Laboratories, lnc. 905 Sheehv Drive. Building A Horsham. PA 19044 Telephone: (2151443-8710 Telefax: (215)443-8587 P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 STUDY TITLE: Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO) in Rats PURPOSE: The purpose of this study is to provide information concerning the effects of Ammonium Perfluorooctanoate (APFO) on the male and female reproductive systems in C rl:C D (SD )IG S B R VAF/Plus rats, including gonadal function, estrous cycles, mating behavior, conception, parturition, lactation, weaning and the growth and development of offspring. The study is also designed to provide information about effects on neonatal morbidity, mortality and preliminary data on potential prenatal developmental toxicity, a s well a s to serve a s a guide for use in the design of subsequent tests. For further information on functional deficiencies and development, additional study segments can be incorporated into the protocol based on the guidelines for developmental toxicity and developmental neurotoxicity. TESTING FACILITY: Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A Horsham, Pennsylvania 19044-1297 Telephone: (215) 443-8710 Telefax: (215)443-8587 STUDY DIRECTO R: Raymond G. York, Ph.D., D A B T Associate Director of Research raymond.york @ primedica.com SPONSOR: 3M Corporate Toxicology 3M Center, Building 220-2E-02 St. Paul, Minnesota 55144-1000 Page 684 ARGUS 418-020 STUDY MONITOR. John Butenhoff, Ph.D., DABT, CIH 3M Corporate Toxicology 3M Medical Department Telephone: (651) 733-1962 Telefax: (651)733-1773 Protocol 418-020 Page 2 REGULATORY CITATIONS. U.S. Environmental Protection Agency (1998). Health Effects Test Guidelines; Reproduction and Fertility Effects. Office of Prevention. Pesticides and Toxic Substances (O P P T S) 870.3800, August, 1998. U.S. Environmental Protection Agency (1997). Toxic Substances Control Act (T SCA ) Test Guidelines; Final Rule. Reproduction and Fertility Effects, 799.9380 (crossreferenced to O P P T S 870.3800). Federal Register, August 15, 1997. U.S. Environmental Protection Agency. Federal Insecticide. Fungicide and Rodenticide Act/Toxic Substances Control Act (FIFRA/TSCA); Good Laboratory Practice Standards; Final Rule. 40 C F R Part 160/Part 792. Organization for Economic Cooperation and Development (1998). The Revised O E C D Principles of Good Laboratory Practices [C(97)186/Final]. REGULATORY CO M PLIAN CE: This study will be conducted in compliance with the Good Laboratory Practice (GLP) regulations cited above. All changes or revisions of this protocol shall be documented, signed by the Study Director and the Sponsor, dated and maintained with the protocol. The Testing Facility's Quality Assurance Unit (QAU) will audit the protocol, the raw data and the report, and will inspect critical phases of those portions of the study conducted at the Testing Facility in accordance with the Standard Operating Procedures of Argus Research Laboratories, Inc. Should any portion of the study be conducted by a subcontractor or by the Sponsor, the Q AU for that facility will conduct critical phase inspections and audit respective results and reports for that study portion according to the S O P s of that facility. Such critical phase inspection reports and report audits will be submitted by that facility to the Study Director. The dates of the inspections and report submissions will be incorporated into a Q A U Statement generated by that facility and provided to the Testing Facility for inclusion in the final report. The final report will include a compliance statement signed by the Study Director that the report accurately reflects the raw data obtained during the performance of the study Page 685 ARGUS 418-020 Protocol 418-020 Page 3 and that all applicable G L P regulations were followed in the conduct of the study. Should significant deviations from G L P regulations occur, each will be described in detail, together with how the deviation might affect the quality or integrity of the study. SCHEM ATIC OF STUDY D ESIG N AND STUDY SCHEDULE: See A T T A C H M E N T 1 to the protocol. T E ST SU B ST A N C E AND VEHICLE: Identification: Test Substance: Ammonium Perfluorooctanoate (APFO), Lot 332. The Sponsor will provide to the Testing Facility documentation or certification of the identity, composition, method of synthesis, strength and purity of the test substance. Vehicle: Reverse O sm osis Membrane Processed Deionized Water (R.O. deionized water). Neither the Sponsor nor the Study Director is aware of any potential contaminants likely to be present in the vehicle that would interfere with the results of this study. Therefore, no analyses other than those mentioned in this protocol will be conducted. Safety Precautions: Gloves, dust-mist/HEPA-filtered mask, appropriate eye protection and uniform/lab coat to be worn during formulation preparation and dosage. In addition, Tyvek sleeves and a half-face respirator will be worn and preparation will be conducted in a chemical fume hood when using the bulk test substance. The Material Safety Data Sheet (M S D S ) is attached to the protocol (A T T A C H M E N T 2). Storage: Bulk Test Substance: Vehicle: Prepared Formulations: Room temperature. Room temperature. Refrigerated, protected from light. All test substance shipments should be addressed to the attention of Julian Gulbinski, Manager of Formulations, at the previously cited Testing Facility address and telephone number. Shipments should include information concerning storage conditions and shipping Page 686 ARGUS 418-020 Protocol 418-020 Page 4 cartons should be labeled appropriately. The recipient should be notified in advance of shipment. FORM ULATION: Frequency of Preparation: Formulations (solutions) are prepared weekly at the Testing Facility. Detailed preparation procedures are attached to this protocol (A T T A C H M EN T 3). Adjustment for Purity: The test substance will be considered 100% pure for the purpose of dosage calculations. Testing Facility Reserve Sa m p le s: The Testing Facility will reserve a 1 g sample of each lot of bulk test substance and a 5 mL sample of vehicle used during the course of the study. Sam ples will be stored under the previously cited conditions. ANALYSES: Results of required analyses will be provided to the Testing Facility for inclusion in the study report. Sam ples additional to those described below may be taken if deemed necessary during the course of the study. Bulk Test Substance Sam pling: A sample (1g) of the test substance will be taken on the last day of treatment and sent (ambient conditions) to the Sponsor for analysis. Page 687 ARGUS 418-020 Protocol 418-020 Page 5 This sample will be sent to: Kris J. Hansen, Ph.D. 3M Environmental Technology & Safety Services 935 Bush Avenue Building 2-3E-09 St. Paul, Minnesota 55133-3331 Telephone: (651) 778-6018 Telefax: (651)778-6176 The recipient will be notified in advance of sample shipment. Analyses of Prepared Formulations: Concentration: Concentration of the prepared formulations will be verified during the course of this study. Duplicate samples will be taken from each concentration on the first and last days of preparation. One sample of each duplicate set will be shipped for analysis; the remaining samples will be retained a s backup samples. Backup sam ples will be stored under the previously cited conditions and discarded at the Testing Facility upon the request of the Sponsor. Stability: Stability of the prepared formulations will be documented during this study. Two sets of duplicate samples (2 mL each) from each concentration will be taken on the first day of preparation. One sample of each duplicate set will be shipped on the day of preparation. These sam ples will be analyzed at the following time points: a s soon after preparation a s possible and ten days after the first analysis. The remaining samples will be retained at the Testing Facility a s backup samples. Backup samples will be stored under the previously cited conditions and discarded at the Testing Facility upon the request of the Sponsor. Shipping Instructions: Sam ples to be analyzed will be shipped (on cold packs, protected from light) to Kris J. Hansen, Ph.D., at the previously cited address. The recipient will be notified in advance of sample shipment. Page 688 ARGUS 418-020 Protocol 418-020 Page 6 D ISP O SIT IO N : Prepared formulations will be discarded at the Testing Facility. All remaining bulk test substance will be returned to: Nelda Marecki, Ph.D. 3M SM M G EHS&R 3M Center Building 236-1B-10 St. Paul, MN 55144-1000 TEST SYSTEM: Species/Strain and Reason for Selection: The C rl:C D (SD )IG S B R VAF/Plus rat w as selected as the Test System because: 1) this strain of rat has been demonstrated to be sensitive to reproductive and developmental toxins and has been widely used throughout industry for reproductive and developmental toxicity evaluations; 2) historical data and experience exist at the Testing Facility0'31; and 3) the test article is pharmacologically active in the species and strain. Number: P Generation: Initial population acclimated: 165 virgin male rats and 165 virgin female rats. Population selected for study: 150 virgin male rats and 150 virgin female rats (30 per sex per group). F1 Generation: 150 male rats and 150 female rats, 30 rats per sex per group, will be selected for continued evaluation. An attempt will be made to select F1 generation rats to avoid over-representation of any P generation parental pair into the F2 generation. Body Weight and Age: P generation rats will be ordered to weigh from 100 g to 125 g each at receipt, at which time they will be expected to be at least 35 days of age. Actual body weights recorded will be recorded the day after receipt and will be documented in the raw data. The weight range will be included in the final report. Page 689 ARGUS 418-020 Sex: Protocol 418-020 Page 7 Both male and female rats will be evaluated. Source: P Generation: Charles River Laboratories, Inc. The rats will be shipped in filtered cartons by air freight and/or truck from Charles River Laboratories, Inc., to the Testing Facility. F1 and F2 Generations: Offspring will be delivered at the Testing Facility by the pregnant P or F1 generation dam s in this study. Identification: P Generation: Rats are permanently identified using Monel self-piercing ear tags (Gey Band and T ag Co., Inc., No. M S P T 20101). Male and female rats will be assigned temporary numbers at receipt and given unique permanent identification numbers when assigned to the study before administration of the first dosage of the test substance. F1 and F2 Generations: Pups will not be individually identified during the postpartum period; all parameters will be evaluated in terms of the litter. At weaning, each F1 generation rat selected for continued observation will be identified with a Monel self-piercing ear tag. ANIMAL HUSBANDRY: All cage sizes and housing conditions are in compliance with the Guide for the Care and Use of Laboratory A n im a te . Page 690 ARGUS 418-020 Protocol 418*020 Page 8 Housing: P Generation Rats/F1 Generation Litters: P generation rats will be individually housed in stainless steel, wire-bottomed cages except during the cohabitation and postpartum periods. During cohabitation, each pair of rats will be housed in the male rat's cage. Beginning no later than day 20 of presumed gestation, female rats will be individually housed in nesting boxes. Each dam and delivered litter will be housed in a common nesting box during the postpartum period. F1 Generation Rats/F2 Generation Litters: After weaning, the F1 generation rats will be individually housed before cohabitation, housed in pairs (one male rat per female rat) during cohabitation, and individually housed after cohabitation. The sam e type of caging will be used a s described for the P generation rats. Beginning no later than day 20 of presumed gestation, female rats will be individually housed in nesting boxes. Each dam and delivered litter will be housed in a common nesting box during the postpartum period. Nesting Material: Nesting material (bed-o'cobs) will be provided. Bedding will be changed as often as necessary to keep the animals dry and clean. Analyses for possible contamination are conducted semi-annually and documented in the raw data. Room Air. Temperature and Humidity: The animal room is independently supplied with at least ten changes per hour of 100% fresh air that has been passed through 99.97% H EP A filters. Room temperature will be maintained at 64F to 79F (18C to 26C) and monitored constantly. Room humidity will also be monitored constantly and maintained at 3 0 % to 70%. An automatically controlled 12-hour light: 12-hour dark fluorescent light cycle will be maintained. Each dark period will begin at 1900 hours EST. Diet: Rats will be given Certified Rodent Diet #5002 (PM I Nutrition International), available a d libitum from individual feeders. Page 691 ARGUS 418-020 Water: Protocol 418-020 Page 9 Water will be available a d libitum from individual bottles attached to the cages or from an automatic watering access system. All water will be from a local source and passed through a reverse osm osis membrane before use. Chlorine will be added to the processed water a s a bacteriostat; processed water is expected to contain no more than 1.2 ppm chlorine at the time of analysis. Water is analyzed monthly for possible bacterial contamination and twice annually for possible chemical contamination. Contaminants: Neither the Sponsor nor the Study Director is aware of any potential contaminants likely to be present in the certified diet, the drinking water or the nesting material at levels that would interfere with the results of this study. Therefore, no analyses other than those routinely performed by the feed supplier or those mentioned in this protocol will be conducted. DAY NUMBERING SYSTEM : Gestation day 0 is defined a s the day spermatozoa are observed in a smear of the vaginal contents and/or a copulatory plug observed in situ. The day of birth is designated lactation day 0 (postpartum day 0) in the Health Effects Test Guidelines - Reproduction and Fertility Effects (Office of Prevention, Pesticides and Toxic Substances 870.3800, August, 1998). This same day is designated day 1 postpartum (day 1 of lactation) in the Standard Operating Procedures of the Testing Facility. Throughout this protocol, the day of birth will be designated day 1 postpartum (day 1 of lactation) and all subsequent ages of the F1 generation rats and days of the lactation period will be determined and cited accordingly. RANDOMIZATION AND COHABITATION: Upon arrival, P generation rats will be assigned to individual housing on the basis of computer-generated random units. After acclimation, rats will be selected for study on the basis of physical appearance and body weight. The rats will be assigned to dosage groups based on computer-generated (weight-ordered) randomization procedures. Within each dosage group, consecutive order will be used to assign P generation rats to cohabitation, one male rat per female rat. A computer-generated randomization procedure or a table of random units will be used to assign F1 generation rats to cohabitation, one male rat per female rat. If random assignment to cohabitation results in the pairing of F1 generation siblings, an alternate assignment will be made. The cohabitation period (P and F1 generation rats) will consist of a maximum of 14 days. Female rats with spermatozoa observed in a smear of the vaginal contents and/or a copulatory plug observed in situ will be considered to be at day 0 of presumed Page 692 ARGUS 418-020 Protocol 418-020 Page 10 gestation and assigned to individual housing, if a female rat has not been mated after two weeks, the pair of rats will be separated without further opportunity for mating. Day 1 of lactation (postpartum) is defined a s the day of birth and is also the first day on which all pups in a litter are individually weighed (pup body weights will be recorded after all pups in a litter are delivered and groomed by the dam). Litters will not be culled during the lactation period, because random selection of. pups for culling could result in potential biases in pup viabilities and body weight gains during this period. All F1 generation rats will be weaned at the sam e age, based on observed growth and viability of these pups, on either day 22 postpartum, or if required, day 29 postpartum. Should it be necessary to extend the lactation period to day 29 postpartum, all affected observational intervals will be adjusted accordingly. At weaning, a table of random units or a computer-generated randomization procedure will be used to select 30 male and 30 female F1 generation pups per group, resulting in a total of 300 rats (150 rats per sex) chosen for continued evaluation. At least one male pup and one female pup per litter, when possible, will be selected. If results warrant that the study be extended to include a third generation, the procedures previously described for the F1 generation will be used for selection of F2 generation pups continued on study. If study results should warrant (e.g., poor reproduction performance in the control group or treatment-related alterations in litter size), parental pairs may be remated to produce F1b or F2b litters. If production of a second litter is deemed necessary, the second cohabitation period will be scheduled approximately one to two weeks following weaning of the F1 a or F2a litters. A D M IN IST R A T IO N : Route and Reason for Choice: The oral (gavage) route w as selected for use because: 1) in comparison with the dietary route, the exact dosage can be accurately administered; and 2) it is one possible route of human exposure. Method and Frequency: P Generation: Male and female rats will be given the test substance once daily, beginning at approximately six weeks of age (at least 70 days before cohabitation) and continuing until the day before sacrifice. D o sage s will be adjusted based on the most recently recorded body weight and given at approximately the sam e time each day. Page 693 ARGUS 418-020 Protocol 418-020 Page 11 F1 Generation: F1 generation pups may be exposed to the test substance during maternal gestation (in utero exposure) or via maternal milk during the postpartum period. F1 generation rats will be given the sam e dosage level of the test substance a s their respective P generation sires and dams. D o sage s will be given once daily, beginning at weaning (approximately 70 days before cohabitation) and continuing until the day before sacrifice. D osages will be adjusted at least weekly for body weight changes and given at approximately the sam e time each day. F2 Generation: Pups may be exposed in utero during gestation or via maternal milk during the lactation period. Rationale for Dosage Selection: D o sage s were selected on the basis of prior dietary and gavage studies in rats performed by the Sponsor. Concentrations may be adjusted if toxicity observed in the P or F1 generation rats indicates that it is required. The highest dosage is expected to produce some toxicity. The intermediate dosage level is expected to produce minimal observable toxic effects, while the lowest dosage level is expected to produce no evidence of either systemic or reproductive toxicity [no observable-adverse-effect level (NOAEL)]. Dosage Levels. Concentrations and Volumes: Dosage Group Number of Rats Dosage per Sex (mcj/kQ/dav! Concentration Dosage Volume (m q/m L) (m|_/kq) l I" I 1,1 IV 30 30 30 30 00 1 0.2 3 0.6 10 2 5 5 5 5 V 30 30 6 5 The test substance will be considered 100% pure ot the purpose ot dosage calculations. Arqus Batch Number | | B -4 1 8-020-A (D ay.M onth.Y ear) B -4 18-020-B(D ay. M onth. Year) B -418-020-C (D ay .M onth.Year) B -418-020-D (D ay.M onth. Year) B-418-020-E {D ay.M onth.Y ear) Page 694 ARGUS 418-020 TESTS. AN ALYSES AND M EA SU REM EN TS - P GEN ERATIO N: Protocol 418-020 Page 12 Viability - Maie and Female R a ts: Ali Periods: At least twice daily. Clinical Observations and/or General Appearance - Male and Female R a ts: Acclimation Period: Weekly. Dosage/Exposure Period: Daily before dosage. Postdosage observations will be recorded approximately 60 10 minutes after administration. Maternal Behavior: D ays 1, 5, 8, 15 and 22 postpartum. Observed abnormal behavior recorded daily. Clinical observations may be recorded more frequently than cited above if deemed appropriate by the Study Director and/or Study Monitor. Body W eights - Male R ats: Acclimation Period: Weekly. Dosage/Exposure Period: Weekly. Day of Sacrifice: Prior to sacrifice. Body W eights - Female R ats: Acclimation Period: Weekly. Precohabitation Period: Weekly. Cohabitation Period: Weekly. Gestation Period: Postpartum Period: D ays 0, 7, 10, 14, 18, 21 and 25 (if required). D ays 1, 5, 8, 11, 15 and 22 (terminal body weight recorded). Feed Consum ption V alu e s - Male R a ts (recorded and tabulated): Dosage/Exposure Period: Weekly. Page 695 ARGUS 418-020 Feed Consum ption V alue s - Fem ale R a ts (recorded and tabulated): Protocol 418-020 Page 13 Precohabitation Period: Weekly. Gestation Period: D ays 0, 7, 10, 14, 18, 21 and 25 (if necessary). Postpartum Period: D ays 1,5, 8, 11 and 15. Feed consumption not tabulated after day 15 postpartum, when it is expected that pups will begin to consume maternal feed. Feed Consum ption Values - Male and Female R a ts: Feed consumption values may be recorded more frequently than cited above if it is necessary to replenish the feed. During cohabitation, when two rats occupy the sam e cage with one feed jar, replenishment of the feed jars will be documented. Individual values will not be recorded or tabulated. Estrous Cycling and Mating: Estrous cycling will be evaluated daily by examination of vaginal cytology beginning 21 days before the scheduled cohabitation period and continuing until spermatozoa are observed in a smear of the vaginal contents and/or a copulatory plug is observed in situ during the cohabitation period. On the day of scheduled sacrifice, an examination of vaginal cytology will be performed to determine the stage of estrous cycle. Duration of Gestation: The duration of gestation is calculated from day 0 of presumed gestation to the day the first pup is observed. Litter O bservations: Litters will be examined after delivery to identify the number and sex of pups, stillbirths, live births and gross alterations. Fertility Param eters: Fertility Index (percentage of matings that result in pregnancies). Reported for each sex. Gestation Index (percentage of pregnancies that result in birth of live litters). Number and sex of offspring per litter (live and dead pups). Page 696 ARGUS 418-020 Protocol 418-020 Page 14 Number of implantation sites. General condition of dam and litter during the postpartum period. Litter Data: Litter size and viability [tabulated at birth (day 1) and on days 5. 8, 15 and 22 postpartum]. Viability Indices (percentages of pups bom that survive to days 1 and 5 postpartum. Lactation Index (percentage of pups that survive from day 8 to day 22 postpartum). Percent Survival and Sex Ratio [tabulated at birth (day 1) and on days 5, 8. 15 and 22 postpartum]. TESTS. ANALYSES AND M EASUREM ENTS - FI GENERATION: Viability: Preweaning Period: Litters will be observed for dead pups at least twice daily. The pups in each litter will be counted once daily. Postweaning Period: Twice daily. Clinical Observations and/or General Appearance - Male and Female Rats: Preweaning Period: Daily. Postweaning Period: Daily before dosage.Postdosage observations will be recorded approximately 60 10 minutes after administration. Maternal Behavior: D ays 1, 5, 8, 15 and 22 postpartum. Observed abnormal behavior recorded daily. Clinical observations may be recorded more frequently than cited above if deemed appropriate by the Study Director and/or Study Monitor. Body Weights - Male and Female Rats: Preweaning Period: D ays 1 (livebom pups), 5, 8,15 and 22 postpartum. Postweaning Period: Weekly. Page 697 ARGUS 418-020 Protocol 418-020 Page 15 Presumed Gestation Period (Female Rats): D ays 0, 7, 10, 14, 18, 21 and 25 (if required). Lactation Period (Female Rats): D ays 1,5, 8,11,15 and 22. Day of Sacrifice: Prior to sacrifice. Feed Consumption Values - Male and Female Rats: Postweaning to Cohabitation: Weekly. Postcohabitation Period (Male Rats): Weekly until sacrifice. Gestation Period (Female Rats): D ays 0, 7, 10, 14, 18. 21 and 25 (if required). Lactation Period (Female Rats): D ays 1,5, 8, 11 and 15. Feed consumption values not tabulated after day 15 postpartum, when it is expected that pups will begin to consume maternal feed. Feed consumption values may be recorded more frequently than cited above if it is necessary to replenish the feed. During cohabitation, when two rats occupy the same cage with one feed jar, replenishment of the feed will be documented. Individual values will not be recorded or tabulated. Postweaning Developmental Observations: Sexual Maturation: Female rats will be evaluated for the age of vaginal patency, beginning on day 28 postpartum. Male rats will be evaluated for the age of preputial separation, beginning on day 39 postpartum. Estrous Cycling and Mating: Estrous cycling will be evaluated daily by examination of vaginal cytology beginning 21 days before the scheduled cohabitation period and continuing until spermatozoa are observed in a smear of the vaginal contents and/or a copulatory plug is observed in situ during the cohabitation period. On the day of scheduled sacrifice, an examination of vaginal cytology will be performed Page 698 ARGUS 418-020 to determine the stage of estrous cycle. Protocol 418-020 Page 16 Duration of Gestation: A s cited above for P generation rats. Litter Observations: A s cited above for P generation rats. Fertility Parameters: A s cited above for P generation rats. Litter Data: A s cited above for P generation rats. TESTS. A N A L Y SE S AND M E A S U R E M E N T S - F2 G E N E R A T IO N : Viability: Preweaning Period: Litters will be observed for dead pups at least twice daily. The pups in each litter will be counted once daily. Clinical Observations and/or General Appearance: Preweaning Period: Body Weights: Daily. Preweaning Period: D ays 1.5, 8, 15 and 22. Preweaning Developmental Observations: If treatment-related effects are observed in sex ratio and/or sexual maturation of the F1 generation, anogenital distance will be measured for all live F2 generation pups on days 1 and 22 postpartum. METHOD OF SACRIFICE: Rats and pups will be sacrificed by carbon dioxide asphyxiation. Page 699 ARGUS 418-020 G RO SS NECROPSY AND H1STOPATHOLOGY: Protocol 418-020 Page 17 Adult P and F1 generation rats will be necropsied and examined for gross lesions. G ross lesions will be retained in neutral buffered 10% formalin and examined histologically. Tissue trimming and histopathoiogy will be performed under the supervision of or by a Board Certified Veterinary Pathologist. At scheduled sacrifice after completion of the cohabitation period (male rats) and on day 22 postpartum (female rats) blood sam ples (approximately 4 mL per rat) will be collected from the inferior vena cava into serum separator tubes and centrifuged. The resulting serum will be immediately frozen on dry ice and maintained frozen (<-70C) until shipment to the Sponsor for analysis. The liver will be excised, weighed, and a sample section (lateral lobe) frozen and retained at <-70C until shipment to the Sponsor for analysis. After completion of sample collection, serum and liver section sam ples will be shipped (frozen on dry ice) to Kris J. Hansen, Ph.D., at the previously cited address. Both the recipient and the Study Monitor will be notified in advance of sample shipment. G ross necropsy will include an initial physical examination of external surfaces and all orifices, a s well a s an internal examination of tissues and organs in situ. The following will be examined: external and internal portions of all hollow organs; the external surfaces of the brain and spinal column, the nasal cavity and neck with associated organs and tissues; the thoracic, abdominal and pelvic cavities with associated organs and tissues; and the musculo/skeletal carcass. The lungs will be perfused with neutral buffered 10% formalin. For all postweaning rats, the urinary bladder and lungs will be inflated with neutral buffered 10% formalin. See A T T A C H M E N T 4 for additional tissues to be weighed and retained, and histological evaluations to be conducted; all other tissues will be discarded. Adult Rats Found Dead or Moribund - P and F1 Generation R ats: Rats that die or are sacrificed because of moribund condition, abortion or premature delivery will be examined for the cause of death or moribund condition on the day the observation is made. The rats will be examined for gross lesions. Pregnancy status and uterine contents of female rats will be recorded (when appropriate). Aborted fetuses, delivered pups and/or concepti in uteri will be examined to the extent possible. Uteri of apparently nonpregnant rats will be examined while being pressed between glass plates to confirm the absence of implantation sites. See A T T A C H M E N T 4 for tissues to be weighed and retained, and histological evaluations to be conducted; all other tissues will be discarded. Page 700 ARGUS 418-020 Protocol 418-020 Page 18 Should postmortem autolysis preclude these evaluations, it will be noted in the necropsy data. Scheduled Sacrifice and Sperm Evaluations - P and F1 Generation Male R ats: After completion of the cohabitation period, adult male rats will be sacrificed, and a gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. To a sse ss the potential toxicity of the test substance on the male reproductive system, the following endpoints will be evaluated: Sperm Evaluations: A portion of the left cauda epididymis will be used for evaluation of cauda epididymal sperm concentration and motility using computer-assisted sperm analysis (CASA). Motility will be evaluated by the Hamilton Thome IV O S by collection of a sample from the left cauda epididymis. The remaining left cauda epididymis will be used to manually evaluate sperm morphology and to prepare a homogenate to be evaluated by the Hamilton Thome IV O S for a determination of sperm concentration (sperm per gram of tissue weight). Sperm morphology evaluations will include the following: 1) determination of the percentage of normal sperm in a sample of at least 200; and 2) qualitative evaluation of abnormal sperm, including such categories as abnormal head, abnormal tail, and abnormal head and tail. Organ Weights: The following organs will be individually weighed: right testis, left testis, left epididymis (whole and cauda), right epididymis, seminal vesicles (with and without fluid) and prostate. Histopatholoav; The remaining portion of the left epididymis, the right epididymis, prostate and seminal vesicles will be fixed in neutral buffered 10% formalin for possible histopathological evaluation. The testes will be fixed in Bouin's solution for 48 to 96 hours and then retained in neutral buffered 10% formalin for possible histopathological evaluation (see A T T A C H M E N T 4). Should a second litter be deemed necessary, male rats will not be sacrificed until after the cohabitation period for the second litter, extending the study by approximately 14 weeks. Scheduled Sacrifice - P and F1 Generation Female R ats: Female rats will be sacrificed after completion of the 22-day postpartum period (should a second litter not be required). The number and distribution of implantation sites will be recorded. Rats that do not deliver a litter will be sacrificed on day 25 of presumed Page 701 ARGUS 418-020 Protocol 418-020 Page 19 gestation and examined for pregnancy status. Uteri of apparently nonpregnant rats will be examined while being pressed between glass plates to confirm the absence of implantation sites. A gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. Female rats without a confirmed mating date that do not deliver a litter will be sacrificed on an estimated day 25 of presumed gestation. Dam s with No Surviving Pups - P and F1 Generation Female R a ts: Dam s with no surviving pups will be sacrificed after the last pup is found dead, missing or presumed cannibalized. A gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. F1/F2 Generation Puds Found Dead on Day 1 Postpartum: Pups that die before examination of the litter for pup viability will be evaluated for vital status at birth. The lungs will be removed and immersed in water. Pups with lungs that sink will be identified a s stillborn; pups with lungs that float will be identified a s iivebom, and to have died shortly after birth. Pups with gross lesions will be preserved in Bouin's solution for possible future evaluation. Should postmortem autolysis preclude these evaluations, it will be noted in the necropsy data. F1/F2 Generation Pups Found Dead or Moribund on Days 2 to 22 Postpartum: Pups found dead or sacrificed due to moribund condition will be examined for gross lesions and for the cause of the moribund condition or death. Pups with gross lesions found on days 2 to 5 postpartum will be preserved in Bouin's solution for possible future evaluation; gross lesions of pups found on days 6 to 22 postpartum will be preserved in neutral buffered 10% formalin. Should postmortem autolysis preclude these evaluations it will be noted in the necropsy data. F1/F2 Generation Pups Not Selected for Continued Observation: All pups culled on day 22 postpartum will be sacrificed, and three pups per sex per litter will be randomly selected and examined for gross lesions; gross lesions will be preserved in neutral buffered 10% formalin. Necropsy will include a single cross section of the head at the level of the frontal-parietal suture and examination of the cross-sectioned brain for apparent hydrocephaly. Tissues (see A T T A C H M E N T 4) from the three selected pups per sex per litter will be weighed and retained in neutral buffered 10% formalin for possible histological evaluation. All remaining pups will be discarded without further examination. Page 702 ARGUS 418-020 P R O P O S E D ST A T IST IC A L M ETHODS*5'11): Protocol 418-020 Page 20 Averages and percentages will be calculated. Litter values will be used where appropriate. Additional procedures and/or analyses may be performed, if appropnate. Type of Test3 I. Parametric II. Nonparametricb A. Bartlett's Testc A. Kruskal-Wallis Test (<75% ties) Significant at p<0.001 Not Significant Significant at p<,0.05 Not Signi' icant Nonparametric Analysis of Variance Dunn's Test Significant at p s 0.05 Not Significant B. Fisher's Exact Test (>75% ties) Dunnett's Test III. Test for Proportion Data Variance Test for Homogeneity of the Binomial Distribution a. Statistically significant probabilities are reported a s either p s 0.05 or psO.01. b. Proportion data are not included in this category. c. Test for homogeneity of variance. Page 703 ARGUS 418-020 DATA ACQUISITION. VERIFICATION AND ST O RA G E: Protocol 418-020 Page 21 Data generated during the course of this study will be recorded either by hand or using the Primedica Argus Autom ated Data Collection and M anagem ent System, the Vivarium Temperature and Relative Humidity Monitoring System and the Hamilton Thome IVOS. All data will be tabulated, summarized and/or statistically analyzed using the Primedica Argus Autom ated Data Collection and Managem ent System, the Vivarium Temperature and Relative Humidity Monitoring System, M icrosoft Excel [part of Microsoft Office 97 (version SR-2)] and/or The SAS System (version 6.12). Records will be reviewed by the Study Director and/or appropriate management personnel within 21 days after generation. All original records will be stored in the archives of the Testing Facility. All original data will be bound and indexed. A copy of all raw data will be supplied to the Sponsor upon request. Preserved tissues will be stored at the Testing Facility at no charge for one year after mailing of the draft final report, after which time the Sponsor will be contacted to determine the disposition of these materials. R E C O R D S TO BE MAINTAINED: Protocol and Amendments. Test Substance, Vehicle and/or Reagent Receipt, Preparation and Use. Animal Acquisition. Randomization Schedules. Mating History. Treatment (if prescribed by Staff Veterinarian). General Comments. Clinical Observations and/or General Appearance. Blood Sample Collection, Processing and Shipment. Body Weights. Feed Consumption Values. Gestation Length. Litter Observations. Gross Necropsy Observations. Sperm Evaluation (motility, concentration and morphology). Organ Weights. Histological Observations. Study Maintenance (room and environmental records). Feed and Water Analyses. Packing and/or Shipment Lists. Page 704 ARGUS 418-020 Protocol 418-020 Page 22 KEY PERSONNEL: Executive Director of Research: Mildred S. Christian, Ph.D., Fellow, A T S Director of Research: Alan M. Hobenman, Ph.D., D A BT Associate Director of Research and Study Director: Raymond G. York, Ph.D., D A B T Director of Operations and Compliance: Barbara J. Patterson, B.A. Director of Laboratory Operations: John F. Barnett, B.S. Director of Study Management: Valerie A. Sharper, M.S. Manager of Animal Operations and Chairperson, Institutional Animal Care and Use Committee: Dena C. Lebo, V.M.D. Consultant, Veterinary Pathology: W. Ray Brown, D.V.M., Ph.D., A C V P REPORTS: The Study Director will provide periodic updates of study progress to the Sponsor. Draft summary tables of unaudited computer-recorded data may accompany these updates. Statistical analyses will not be performed on these interim data. A comprehensive draft final report will be prepared on completion of the study and will be finalized following consultation with the Sponsor. The report will include the following: Summary and Conclusion. Experimental Design and Method. Evaluation of Test Results. Appendices: Figures, Summary and Individual Tables Summarizing the Above Data, Protocol and Associated Amendments and Deviations, Study Director's G L P Compliance Statement, Reports of Supporting Data (if appropriate) and Q AU Statement. An interim summary report covering the period from initiation of test diet exposure through weaning of the F1 generation will also be issued. This report will be identical in format to the final report with the exception of inclusion of histopathological findings. The Sponsor will receive one copy of the draft report and two copies of the final report. INSTITUTIONAL ANIMAL C A R E AND U SE CO M M ITTEE STATEM EN T: The procedures described in this protocol have been reviewed by the Testing Facility's Institutional Animal Care and Use Committee. All procedures described in this protocol that involve study animals will be conducted in a manner to avoid or minimize discomfort, distress or pain to the animals. Page 705 ARGUS 418-020 Protocol 418-020 Page 23 The Sponsor's signature below documents the fact that information concerning the necessity for conducting this study and the fact that this is not an unnecessarily duplicative study may be obtained from the Sponsor. No alternative (in vitro) procedures were available for meeting the stated purposes of the study. REFERENCES: 1. Christian, M.S. and Voytek, P.E. (1982). In Vivo Reproductive and Mutagenicity Tests. Environmental Protection Agency, Washington, D.C. National Technical Information Service, U.S. Department of Commerce, Springfield, V A 22161. 2. Christian, M.S. (1984). Reproductive toxicity and teratology evaluations of. naltrexone (Proceedings of Naltrexone Symposium, New York Academy of Sciences, November 7, 1983), J. Clin. Psychiat. 45(9):7-10. 3. Lang, P.L. (1988). Embryo a n d Fetal Developmental Toxicity (Teratology) Control Data in the Charles R iver Crl:CDBR Rat. Charles River Laboratories, Inc., Wilmington, M A 01887-0630. (Data base provided by Argus Research Laboratories, Inc.) 4. Institute of Laboratory Animal Resources (1996). Guide for the Care and Use o f Laboratory Animals. National Academy Press, Washington, D.C. 5. Snedecor, G.W. and Cochran, W .G. (1967). Variance test for homogeneity of the binomial distribution. Statistical Methods. 6th Edition, Iowa State University Press, Ames, pp. 240-241. 6. Sokal, R.R. and Rohlf, F.J. (1969). Bartlett's test of homogeneity of variances. Biometry, W.H. Freeman and Co., San Francisco, pp. 370-371. 7. Snedecor, G.W. and Cochran, W .G. (1967). Analysis of Variance. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 258-275. 8. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc. 50:1096-1121. 9. Sokal, R.R. and Rohlf, F.J. (1969). Kruskal-Wallis Test. Biometry, W.H. Freeman and Co., San Francisco, pp. 388-389. 10. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6(3):241-252. 11. Siegel, S. (1956). Nonparam etric Statistics for the Behavioral Sciences, McGraw-Hill, New York, pp. 96-104. Page 706 PROTOCOL APPROVAL FOR THE TESTING FACILITY n Alan M. Hoberman, Ph.D., D A B T Director of Research ARGUS 418-020 Protocol 418-020 Page 24 C "?- Slu. ' / -<-c' Date C\ J L {j r ~T ? C ______ [D^na C. Lebo, V.M.D. Chairperson, Institutional Animal Care and Use Committee FOR THE SPONSOR John Butenhoff, Ph.D., DABT, C IH Study Monitor Sponsor's Representative 0 7- Date g A W " Date Page 707 ARGUS 418-020 ATTACHMENT 1 SCHEMATIC OF STUDY DESIGN AND STUDY SCHEDULE Page 708 ARGUS 418-020 ATTACHMENT 1 Protocol 418-020 Page 1 of 3 TWO-GENERATION REPRODUCTION STUDY3 First Day of Test Substance Exposure - P Generation I Premating P Generation Male Rats 10 weeks P Generation Female Rats 10 weeks Cohabitation11 Last Day of Test Substance Exposure P Generation 2 weeks Presumed Gestation Natural Delivery I Lactation 3 weeks 3 weeks F1 Generation Rats I Postweaning j F1 Generation Rats Postpartum 3 weeks Day 22 Postpartum Weaning' Presumed Cohabitation* | Gestation Last Day of Test Substance Exposure F1 Generation" Lactation 10 weeks 2 weeks 3 weeks F2 Generation Rats Postpartum I 3 weeks Day 22 Postpartum" Dosage Period a. For additional details see "Tests, Analyses and Measurements" section of the protocol. b. Male rats sacrificed after determination of sufficient number of pregnancies; sperm evaluation. c. P generation female rats and F1 generation rats not selected for continuation on study sacrificed. d. F1 generation dam s and F2 generation litters sacrificed. Page 709 ARGUS 418-020 ATTACHMENT 1 Protocol 418-020 Page 2 of 3 SCH ED U LE10" 07 NO V 00 P Generation Animal Receipt - Acclimation Begins 13 N O V 00 Start of Test Substance Exposure P Generation Rats 21 JAN 01 P M - 04 F E B 01 A M P Generation Cohabitation Period (After at least 70 days of test substance exposure). 22 JAN 01 04 F E B 01 First Possible Day 0 of Presumed Gestation. Last Possible Day 0 of Presumed Gestation. 12 F E B 01 01 M A R 01 First Possible Delivery - F1 Generation Litters (Day 21 of presumed gestation). Last Possible Delivery - F1 Generation Litters (Day 25 of presumed gestation). 16 F E B 01 01 M A R 01 First Possible Day 25 of Presumed Gestation Female Rat Sacrifice. Last Possible Day 25 of Presumed Gestation Female Rat Sacrifice. 12 F E B 01 Scheduled Sacrifice - P Generation Male Rats (Earliest possible date). 05 M A R 01 22 M A R 01 First Possible Day-22 Postpartum W eaning (Sacrifice of P generation dams and F1 generation pups not selected for continued observation). Last Possible Day-22 Postpartum Weaning. 06 M A R 01 F1 Generation Postweaning Observations Begin (Details of tests cited in protocol). a. The study initiation date is the day the Study Director signs the protocol. b. The day of birth is designated postnatal day 0 (day 0 of lactation) in Addendum 10 to the Pesticide Assessm ent Guidelines of the U.S. Environmental Protection Agency (EPA). This sam e day is designated day 1 postpartum (day 1 of lactation) in the Standard Operating Procedures of the Test Facility. Throughout this protocol, the day of birth will be designated day 1 postpartum (day 1 of lactation) and all subsequent a ge s of the F1 generation rats and days of the lactation period will be determined and cited accordingly. c. The in-life portion of the study will require approximately 42 weeks. If results warrant, this study may be extended to include a third generation; such a study extension would be conducted according to the procedures described previously for the F1 and F2 generations. Page 710 ARGUS 418-020 ATTACHMENT 1 Protocol 418-020 Page 3 of 3 31 JUL01 Interim Status Report - Draft Mail Date. Estimated Dates3 06 M A R 01 Start of Test Substance Exposure F1 Generation Rats 28 M A Y 01 PM -1 8 JUN 01 A M F1 Generation Cohabitation Period (After at least 70 days of test substance exposure). 29 M A Y 01 18 JUN 01 First Possible Day 0 of Presumed Gestation. Last Possible Day 0 of Presumed Gestation. 19 JUN 01 13 JUL01 First Possible Delivery - F2 Generation Litters (Day 21 of presumed gestation). Last Possible Delivery - F2 Generation Litters (Day 25 of presumed gestation). 23 JUN 01 13 JUL01 First Possible Day 25 of Presumed Gestation Female Rat Sacrifice. Last Possible Day 25 of Presumed Gestation Female Rat Sacrifice. 26 JUN 01 F1 Generation Male Rats Sacrificed after Day 21 of Cohabitation Period - Earliest Approximate Date. 10 JUL01 03 A U G 01 First Possible Day 22 Postpartum (FI generation dams and F2 generation litters sacrificed). Last Possible Day 22 Postpartum. 12 D E C 01 Draft Final Report (Including histopathology). a. All of these dates are not possible to accurately schedule because they are dependent upon the timing of mating of the P generation and the times litters are delivered and weaned. Page 711 ARGUS 418-020 ATTACHMENT 2 MATERIAL SAFETY DATA SHEET Page 712 31 --O C T -- 2000 09:14 3M Fax Message ARGUS 418-020 Page 2/17 MATERIAL SAFETY DATA SHEET 3M 3M Cantor St. Paul, Minnesota 55144-1000 1-800-364-3577 or (651) 737-6501 (24 hours) Copyright, 2000, Minnesota Mining and Manufacturing company. All rights reserved. Copying and/or downloading of this information for the purpose of properly utilizing 3M products is allowed provided that: 1) the information is copied in full with no changes unless prior agreement is obtained from 3M, and 2) neither the copy nor the original is resold or otherwise distributed with the intention of earning a profit thereon. DIVISION: 3M SPECIALTY MATERIALS TRADE NAME: FC-143 FLUORAD Brand Fluorochemical Surfactant ID NUMBER/U.P .C .: 9B-0211-000B-0 00-51135-09138-8 98-0211-0891-9 98-0211-5489-7 00-51135-02941-1 98-0211-6581-0 98-0211-7394-7 00-51135-10762-1 2F-0002-0378-4 ISSUED: August 25, 2000 SUPERSEDES: July 28, 2000 DOCUMENT: 10-3808-2 00-51135-09365-8 00-51135-10405-7 --- 1. INGREDIENT C.A.S. NO. PERCENT AMMONIUM PERFLUOROOCTANOATE............ AMMONIUM PERFLU0R0HEXAN0ATE............ AMMONIUM PERFLUOROHEPTANOATE........... HEPTADECAFLU0R0N0NAN0IC ACID, AMMONIUM SALT................................. 3825-26-1 21615-47-4 6130-43-4 4149-60-4 96.5 0 0 0 - 100 - 1.5 -1 -1 The components of this product are in compliance with the chemical notification requirements of TSCA. All applicable chemical ingredients in this material are listed on the European Inventory of Existing Chemical Substances (EINECS), or are exempt polymers whose monomers are listed on EINECS. 2. PHYSICAL DATA BOILING POINT:..... VAPOR PRESSURE:.... VAPOR DENSITY:..... EVAPORATION RATE:... SOLUBILITY IN WATER: SPECIFIC GRAVITY:... PERCENT VOLATILE:... P H : ....................... VISCOSITY:......... N/A N/A N/A N/A apprec. 0.4 - 0.5 Water-1 (Bulk) N/A 4-7 (2% aqueous solution) N/A Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 713 31-OCT-2000 09:14 3M Fax Message ARGUS 418-020 Fage 3/rj USDS: FC-143 FLUORAD Brand Fluorochemical Surfactant. August 25, 2000 PAGE 2 2. PHYSICAL DATA (continued) MELTING POINT:................ N/A .... APPEARANCE AND ODOR: Solid, Light colored powder; slight odor. 3. FIRE AND EXPLOSION HAZARD DATA FLASH POINT:.................. Non-flammable FLAMMABLE LIMITS - LEL:...... N/A FLAMMABLE LIMITS - UEL:...... N/A AUTOIGNITION TEMPERATURE:..... N/A EXTINGUISHING MEDIA: Hater, Carbon dioxide, Dry chemical, Foam SPECIAL FIRE FIGHTING PROCEDURES: Hear full protective clothing, including helmet, self-contained, positive pressure or pressure demand breathing apparatus, bunker coat and pants, bands around arms, waist and legs, face mask, and protective covering for exposed areas of the head. UNUSUAL FIRE AND EXPLOSION HAZARDS: See Hazardous Decomposition section for products of combustion. 4. REACTIVITY DATA STABILITY: Stable INCOMPATIBILITY - MATERIALS/CONDITIONS TO AVOID: Not Applicable HAZARDOUS POLYMERIZATION: Hazardous polymerization will not occur. HAZARDOUS DECOMPOSITION PRODUCTS: Carbon Monoxide and Carbon Dioxide, Oxides of Nitrogen, Hydrogen Fluor ide, Ammon ia. 5. ENVIRONMENTAL INFORMATION SPILL RESPONSE: observe precautions from other sections. Collect spilled material. Use wet sweeping compound or water to avoid dusting. Clean up residue. Place in a closed container. Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 714 31--O C T --2000 09 :14 3M Fax Message ARGUS 418-020 Page 4/1/ USDS: FC-143 FLUORAD Brand Fluorochemical Surfactant August 25, 2000 5. ENVIRONMENTAL INFORMATION (continued) PAGE 3 RECOMMENDED DISPOSAL: Incinerate in an industrial or commercial facility in the presence of a combustible material. Combustion products will include HF. Do not dispose of in a sanitary landfill. Disposal alternative: Dispose of waste product in a facility permitted to accept chemical waste. ENVIRONMENTAL DATA: SUPPORTING DATA: BIODEGRADATION: Theoretical Oxygen Demand (ThOD): 0.320 g/g Chemical Oxygen Demand (COD): 0.0007 g/g 20-Day Biochemical Oxygen Demand (B0D20): Nil AQUATIC TOXICITY: Fathead minnow (Pimephales promelas) 96-hr LC50: 766 mg/L Hater flea (Daphnia magna) 48-hr EC50: 632 mg/L Blueglll sunfish (Lapomis macrochirus) 96-hr EC50: 569 mg/L Green Algae (Selenastrum capricornutum) 14-Day EC50: >1000 mg/L Microtox (Photobacterium phosphoreum) 30-min EC50: 730 mg/L BIONCONCENTRATION: BCF - 1.8 REGULATORY INFORMATION: Volatile Organic Compounds: N/A. VOC Less H20 & Exempt Solvents: N/A. Since regulations vary, consult applicable regulations or authorities before disposal. U.S. EPA Hazardous Haste Number = None (Not U.S. EPA Hazardous). The components of this product are in compliance with the chemical registration requirements of TSCA, EINECS, CDSL, AICS, MITI, KECI and PICCS. OTHER ENVIRONMENTAL INFORMATION: This substance has minimal toxicity to aquatic organisms (100 mg/L < Lowest LC50, EC50, or IC50 < or - 1000 mg/L). No data are available on the toxicity effects of this substance on wastewater treatment system organisms. This product can potentially generate Perfluorooctanoate anion, either through dissociation or metabolism, which has the potential to resist degradation and persist in the environment. EPCRA HAZARD CLASS: Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately 31-OCT-2000 09:14 3M Pax Message ARGUS 418-020 Page 5/17 USDS: FC-143 FLUORAD Brand Fluorochenical Surfactant August 25, 2000 PAGE 4 5. ENVIRONMENTAL INFORMATION (continued) FIRE HAZARD: No PRESSURE: No REACTIVITY: No ACUTE: Yes CHRONIC: Yes 6. SUGGESTED FIRST AID ' EYE CONTACT: Immediately flush eyes with large amounts of water for at least 15 minutes. Get immediate medical attention. ' SKIN CONTACT: Flush skin with large amounts of water. If irritation persists, get medical attention. INHALATION: If signs/symptoms occur, remove person to fresh air. If signs/symptoms continue, call a physician. IF SHALLOWED: Do not induce vomiting. Drink two glasses of water. Call a physician. 7. PRECAUTIONARY INFORMATION EYE PROTECTION: Avoid eye contact. Hear vented goggles. SKIN PROTECTION: Avoid skin contact. Hear appropriate gloves when handling this material. A pair of gloves made from the following material(s) are recommended: butyl rubber. Use one or more of the following personal protection items as necessary to prevent skin contact: head covering, coveralls. Protective garments (other than gloves) should be made of either of the following materials: polyethylene/polyvinylidene chloride (Saranex) Use disposable shoe/boot covering or rubber boots. Disposable fabric is preferable for all protective garments. RECOMMENDED VENTILATION: Use with appropriate local exhaust ventilation. Provide sufficient ventilation to maintain emissions below recommended exposure limits. If exhaust ventilation is not adequate, use appropriate respiratory protection. RESPIRATORY PROTECTION: Avoid breathing of airborne material. Select one of the following NIOSH approved respirators based on airborne concentration of contaminants and in accordance with OSHA regulations: full-face high- Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 716 31--OCT--2000 09:14 Ja jfax Message ARGUS 418-020 i-age o/j./ USDS: FC-143 FLUOKAD Brand Fluorochemical Surfactant. August 25, 2000 PAGE 5 7. PRECAUTIONARY INFORMATION (continued) efficiency filter respirator, full-face supplied air respirator. PREVENTION OF ACCIDENTAL INGESTION: Do not eat., drinJt or smoke when using this product. Hash exposed ' areas thoroughly with soap and water. Hash hands after handling and before eating. RECOMMENDED STORAGE: Store away from areas where product may come into contact with food ' or pharmaceuticals. Store at room temperature. Keep container closed when not in use. *"PREVENT MOISTURE CONTAMINATION TO KEEP POWDER FREE FLOWING.** FIRE AND EXPLOSION AVOIDANCE: Nonflammable. OTHER PRECAUTIONARY INFORMATION: No smoking: Smoking while using this product can result in contamination of the tobacco and/or smoke and lead to the formation of the hazardous decomposition products mentioned in the Reactivity Data section of this MSDS. Store work clothes separately from other clothing, food and tobacco products. Hash contaminated clothing thoroughly before re-use. Discard contaminated leather clothing. Decontaminate work surfaces frequently to avoid exposure by contact. HMIS HAZARD RATINGS: HEALTH: 3 FLAMMABILITY: 0 REACTIVITY: 0 PERSONAL PROTECTION: X (See precautions, section 7.) EXPOSURE LIMITS INGREDIENT VALUE UNIT TYPE AUTH SKIN* AMMONIUM PERFLUOROOCTANOATE........ .. AMMONIUM PERFLUOROHEXANOATE........ ,. AMMONIUM PERFLUOROHEPTANOATE....... . HEPTADECAFLUORONONANOIC ACID, AMMONIUM SALT.................... . 0.01 0.1 0.1 NONE MG/M3 MG/M3 MG/M3 NONE TWA TWA TWA NONE ACGIH 3M 3M NONE Y Y Y * SKIN NOTATION: Listed substances indicated with 'Y' under SKIN refer to the potential contribution to the overall exposure by the cutaneous route including mucous membrane and eye, either by airborne or, more particularly, by direct contact with the substance. Vehicles can alter skin absorption. SOURCE OF EXPOSURE LIMIT DATA: - 3M: 3M Recommended Exposure Guidelines - ACGIH: American Conference of Governmental Industrial Hygienists - NONE: None Established Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 717 31--OCT--2000 09:14 3a Fax aessaie ARGUS 418-020 r a g e //x/ MSDS: FC-143 FLUOEAD Brand Fluorochemical Surfactant. August. 25, 2000 PAGE 6 8. HEALTH HAZARD DATA EYE CONTACT: Moderate Eye Irritation: signs/symptoms can include redness, swelling, pain, tearing, and hazy vision. SKIN CONTACT: Mild Skin Irritation (after prolonged or repeated contact): signs/symptoms can include redness, swelling, and itching. May be absorbed through the skin and produce effects similiar to those caused by inhalation and/or ingestion. - INHALATION: Illness requiring medical attention may result from a single exposure by Inhalation to moderate quantities of this material. May be absorbed by inhalation and persist in the body for an extended time. Single overexposure, above recommended guidelines, may cause: Irritation (upper respiratory): signs/symptoms can include soreness of the nose and throat, coughing and sneezing. Prolonged or repeated overexposure, above recommended guidelines, may cause: Liver Effects: signs/symptoms can Include yellow skin(jaundice) and tenderness of upper abdomen. IF SWALLOWED: This product can potentially generate Perfluorooctanoate anion, either through dissociation or metabolism. Animal studies conducted on Perfluorooctanoate anion indicate effects including liver disturbances, weight loss, loss of appetite, adrenal and hematologic effects, and benign tumors of the liver, pancreas and testes of male rats. There are no known human health effects from anticipated exposure to this Perfluorooctanoate anion when used as Intended and instructed. Illness may result from a single swallowing of a moderate quantity of this material. CANCER: A mixture of ammonium perfluorooctanoate, ammonium perfluoroheptanoate, ammonium perfluoropentanoate and ammonium perfluorohexanoate, that was 93 to 97% AMMONIUM PERFLUOROOCTANOATE (3825-26-1) was fed to albino rats for 2 years, no compound induced carcinogenicity was found in the study. There were statistically significant compound related benign testicular tumors. In a second _ two-year study there were statistically significant compound related Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 718 31-OCT-2000 09 :14 3tt P a x Message ARGUS 418-020 Page a fl/ USDS: FC-143 FLUORAD Brand Fluorochemical Surfactant August 25, 2000 PAGE 7 8. HEALTH HAZARD DATA (continued) benign tumors in the liver, pancreas, and testis when compared to ad libitum and pair-fed controls. Based on the current knowledge, these findings have no human health implications. (3825-26-1) (1983 and 1993 studies conducted jointly by 3H and DuPont). ' MUTAGENICITY: Not mutagenic in invitro mutagenicity assays. Did not cause cell transformation in a mammalian cell transformation assay. REPRODUCTIVE/DEVELOPMENTAL TOXINS: Not teratogenic in rabbits by oral administration. Not teratogenic to rats by gavage or inhalation exposures. OTHER HEALTH HAZARD INFORMATION: A Product Toxicity Summary Sheet is available. The presence of organic fluorochemicals in the blood of the general population and subpopulations, such as workers, has been published dating back to the 1970's. 3M's epidemiological study of its own workers indicates no adverse effects. This product can potentially generate Perfluorooctanoate anion, either through dissociation or metabolism. Perfluorooctanoate anion has the potential to be absorbed and remain in the body for long periods of time and may accumulate with repeated exposures. There are no known human health effects from anticipated exposure to this Perfluorooctanoate anion when used as intended and instructed. SECTION CHANGE DATES INGREDIENTS SECTION CHANGED SINCE July 28, 2000 ISSUE Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 719 31--O C T --2000 09:14 3M Tax Message MSDS: FC-143 FLUORAD Brand Fluorochemical Surfactant August 25, 2000 ARGUS 418-020 r a g e s/j./ PAGE 8 The information in this Material Safety Data Sheet (MSDS) is believed to be correct as of the date issued. 3M MAKES NO WARRANTIES, EXPRESSED OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR COURSE OF . PERFORMANCE OR USAGE OF TRADE. User is responsible for determining whether the 3M product is fit for a particular purpose and suitable for user's method of use or application. Given the variety of factors that can affect the use and application of a 3M product, some of which are uniquely within the user's knowledge and control, it is essential that, the user evaluate the 3M product to determine whether it is fit for a particular purpose and suitable for user's method of use or application. 3M provides information in electronic form as a service to its customers. Due to the remote possibility that electronic transfer may have resulted in errors, omissions or alterations in this information, 3M makes no representations as to its completeness or accuracy. In addition, information obtained from a database may not be as current as the information in the MSDS available directly from 3M. Page 720 31-OCT-2000 09:14 3B Fax Bassaget ARGUS 418-020 vage lu/i> MATERIAL SAFETY DATA SHEET 3M 3M Cantor St. Paul, Minnesota 55144-1000 1-BOO-364-3577 or (651) 737-6501 (24 hours) Copyright, 2000, Minnesota Mining and Manufacturing Company. All rights reserved. Copying and/or downloading of this information for the purpose of properly utilizing 3M products is allowed provided that: 1) the information is copied in full with no changes unless prior agreement is obtained from 3M, and 2) neither the copy nor the original is resold or otherwise distributed with the intention of earning a profit thereon. DIVISION: 3M SPECIALTY MATERIALS TRADE NAME: FC-143 FLUORAD Brand Fluorochemical Surfactant ID NUMBER/U.P .C .: 98-0211-0008-0 00-51135-09138-8 98-0211-0891-9 98-0211-5489-7 00-51135-02941-1 98-0211-6581-0 98-0211-7394-7 00-51135-10762-1 ZF-0002-037B-4 ISSUED: August 25, 2000 SUPERSEDES: July 28, 2000 DOCUMENT: 10-3808-2 00-51135-09365-8 00-51135-10405-7 1. INGREDIENT C .A .S . NO . PERCENT AMMONIUM PERFLU0R00CTAN0ATE.......... AMMONIUM PERFLU0R0HEXAN0ATE.......... AMMONIUM PERFLUOROHEPTANOATE......... HEPTADECAFLUORONONANOIC ACID, AMMONIUM SALT............................... 3825-26-1 21615-47-4 6130-43-4 4149-60-4 96.5 0 0 0 - 100 - 1.5 -1 -1 The components of this product are in compliance with the chemical notification requirements of TSCA. All applicable chemical ingredients in this material are listed on the European inventory of Existing Chemical Substances (EINECS), or are exempt polymers whose monomers are listed on EINECS. 2. PHYSICAL DATA BOILING POINT:..... VAPOR PRESSURE:.... VAPOR DENSITY:..... EVAPORATION RATE:... SOLUBILITY IN WATER: SPECIFIC GRAVITY:... PERCENT VOLATILE:... P H :......................................... VISCOSITY:......... N/A N/A N/A N/A apprec. 0.4 - 0.5 Uater^l (Bulk) N/A 4-7 (2% aqueous solution) N/A Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 721 31--OCT--2000 09:14 3M Fax Message ARGUS 418-020 Fage n/i/ USDS: FC-143 FLUORAD Brand Fluorochemical Surfactant. August 25, 2000 PAGE 2 2. PHYSICAL DATA (continued) MELTING POINT:................ N/A APPEARANCE AND ODOR: Solid, Light colored powder; slight odor. 3. FIRE AND EXPLOSION HAZARD DATA FLASH POINT:.................. Non-flammable FLAMMABLE LIMITS - LEL:...... N/A FLAMMABLE LIMITS - UEL:...... N/A AUTOIGNITION TEMPERATURE:..... N/A EXTINGUISHING MEDIA: Hater, Carbon dioxide, Dry chemical, Foam SPECIAL FIRE FIGHTING PROCEDURES: Hear full protective clothing, including helmet, self-contained, positive pressure or pressure demand breathing apparatus, bunker coat and pants, bands around arms, waist and legs, face mask, and protective covering for exposed areas of the head. UNUSUAL FIRE AND EXPLOSION HAZARDS: See Hazardous Decomposition section for products of combustion. 4. REACTIVITY DATA STABILITY: Stable INCOMPATIBILITY - MATERIALS/CONDITIONS TO AVOID: Not Applicable HAZARDOUS POLYMERIZATION: Hazardous polymerization will not occur. HAZARDOUS DECOMPOSITION PRODUCTS: Carbon Monoxide and Carbon Dioxide, Oxides of Nitrogen, Hydrogen Fluoride, Ammonia. 5. ENVIRONMENTAL INFORMATION SPILL RESPONSE: Observe precautions from other sections. Collect spilled material. Use wet sweeping compound or water to avoid dusting. Clean up residue. Place in a closed container. Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 722 31--OCT--2000 09:14 311 P a x M essaie ARGUS 418-020 Page 12/1> USDS: FC-143 FLUORAD Brand Fluorocheaical Surfactant August 25, 2000 5. ENVIRONMENTAL INFORMATION (continued) PAGE 3 RECOMMENDED DISPOSAL: Incinerate in an industrial or commercial facility in the presence of a combustible material. Combustion products will include HF. Do not dispose of in a sanitary landfill. Disposal alternative: Dispose of waste product in a facility permitted to accept chemical waste. ENVIRONMENTAL DATA: SUPPORTING DATA: BIODEGRADATION: Theoretical Oxygen Demand (ThOD): 0.320 g/g Chemical Oxygen Demand (COD): 0.0007 g/g 20-Day Biochemical Oxygen Demand (B0D20): Nil AQUATIC TOXICITY: Fathead minnow (Pimephales promelas) 96-hr LC50: 766 mg/L Hater flea (Daphnia magna) 48-hr EC50: 632 mg/L Bluegill sunfish (Lepomis macrochirus) 96-hr EC50: 569 mg/L Green Algae (Selenastrum capricornutum) 14-Day EC50: >1000 mg/L Microtox (Photobacterium phosphoreum) 30-min EC50: 730 mg/L BIONCONCENTRATION: BCF - 1.8 REGULATORY INFORMATION: Volatile Organic Compounds: N/A. VOC Less H20 A Exempt Solvents: N/A. Since regulations vary, consult, applic a b l e regulations or aut h o r i t i e s before disposal. U.S. EPA Hazardous Haste Number = None (Not U.S. EPA Hazardous). The components of this product are in compliance with the chemical registration requirements of TSCA, EINECS, CDSL, AICS, MITI, KECI and PICCS. OTHER ENVIRONMENTAL INFORMATION: This substance has minimal toxicity to aquatic organisms (100 mg/L < Lowest LC50, EC50, or IC50 < or - 1000 mg/L). No data are available on the toxicity effects of this substance on wastewater treatment system organisms. This product can potentially generate Perfluorooctanoate anion, either through dissociation or metabolism, which has the potential to resist degradation and persist in the environment. EPCRA HAZARD CLASS: Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 723 31-OCT--2000 09:14 3U fax Message ARGUS 418-020 fage u/i. MSDS: FC-143 FLUORAD Brand Fluorochemical Surfactant August, 25, 2000 PAGE 4 5. ENVIRONMENTAL INFORMATION (continued) FIRE HAZARD: No PRESSURE: No REACTIVITY: No ACUTE: Yes CHRONIC: Yes 6. SUGGESTED FIRST AID EYE CONTACT: Immediately flush eyes with large amounts of water for at least 15 minutes. Get immediate medical attention. SKIN CONTACT: Flush skin with large amounts of water. If irritation persists, get medical attention. INHALATION: Xf signs/symptoms occur, remove person to fresh air. If signs/symptoms continue, call a physician. IF SHALLOWED: Do not induce vomiting. Drink two glasses of water. Call a physician. 7. PRECAUTIONARY INFORMATION EYE PROTECTION: Avoid eye contact. Hear vented goggles. SKIN PROTECTION: Avoid skin contact. Hear appropriate gloves when handling this material. A p a i r of g l o v e s m a d e f r o m the f o l l o w i n g m a t e r i a l (s ) a r e recommended: butyl rubber. Use one or more of the following personal protection items as necessary to prevent skin contact: head covering, coveralls. Protective garments (other than gloves) should be made of either of the following materials: polyethylene/polyvinylidene chloride (Saranex) Use disposable shoe/boot covering or rubber boots. Disposable fabric is preferable for all protective garments. RECOMMENDED VENTILATION; Use with appropriate local exhaust ventilation. Provide sufficient ventilation to maintain emissions below recommended exposure limits. If exhaust ventilation is not adequate, use appropriate respiratory protection. RESPIRATORY PROTECTION: Avoid breathing of airborne material. Select one of the following NI0SH approved respirators based on airborne concentration of contaminants and in accordance with OSHA regulations: full-face high- Abbraviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 724 31--OCT--2000 09:14 3B Tax Bossage ARGUS 418-020 Page 14/1 USDS: FC-143 FLUORAD Brand Fluorochemical Surfactant August. 25, 2000 PAGE 5 7. PRECAUTIONARY INFORMATION (continued) efficiency filter respirator, full-face supplied air respirator. PREVENTION OF ACCIDENTAL INGESTION: Do not eat, drink or smoke when using this product. Hash exposed areas thoroughly with soap and water. Hash hands after handling and before eating. RECOMMENDED STORAGE: Store away from areas where product may come into contact with food or pharmaceuticals. Store at room temperature. Keep container closed when not in use. PREVENT MOISTURE CONTAMINATION TO KEEP POWDER FREE FLOWING. FIRE AND EXPLOSION AVOIDANCE: Nonflammable. OTHER PRECAUTIONARY INFORMATION: No smoking: Smoking while using this product can result in contamination of the tobacco and/or smoke and lead to the formation of the hazardous decomposition products mentioned in the Reactivity Data section of this MSDS. Store work clothes separately from other clothing, food and tobacco products. Wash contaminated clothing thoroughly before re-use. Discard contaminated leather clothing. Decontaminate work surfaces frequently to avoid exposure by contact. HMIS HAZARD RATINGS: HEALTH: 3 FLAMMABILITY: 0 REACTIVITY: 0 PERSONAL PROTECTION: X (See precautions, section 7.) INGREDIENT EXPOSURE LIMITS VALUE UNIT TYPE AUTH SKIN* AMMONIUM PERFLUOROOCTANOATE........ .. AMMONIUM PEEFLUOROHEXANOATE........ .. AMMONIUM PERFLUOROHEPTANOATE....... . HEFTADECAFLUORONONANOIC ACID, AMMONIUM SALT.................... .. 0.01 0.1 0.1 NONE MG/M3 MG/M3 MG/M3 NONE TWA TWA TWA NONE ACGIH 3M 3M NONE Y Y Y * SKIN NOTATION: Listed substances Indicated with 'Y' under SKIN refer to the potential contribution to the overall exposure by the cutaneous route including mucous membrane and eye, either by airborne or, more particularly, by direct contact with the substance. Vehicles can alter skin absorption. SOURCE OF EXPOSURE LIMIT DATA: - 3M: 3M Recommended Exposure Guidelines - ACGIH: American Conference of Governmental Industrial Hygienists - NONE: None Established Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 725 31--OCT--2000 09:14 3M Fax Message ARGUS 418-020 Page 13/1. USDS: FC-143 FLUORAD Brand Fluorochemical Surfactant. August 25, 2000 PAGE 6 B. HEALTH HAZARD DATA EYE CONTACT: Moderate Eye Irritation: signs/symptoms can include redness, swelling, pain, tearing, and hazy vision. SKIN CONTACT: Mild Skin Irritation (after prolonged or repeated contact): signs/symptoms can include redness, swelling, and itching. May be absorbed through the skin and produce effects similiar to those caused by inhalation and/or ingestion. INHALATION: Illness requiring medical attention may result from a single exposure by Inhalation to moderate quantities of this material. May be absorbed by inhalation and persist in the body for an extended time. Single overexposure, above recommended guidelines, may cause: Irritation (upper respiratory): signs/symptoms can include soreness of the nose and throat, coughing and sneezing. Prolonged or repeated overexposure, above recommended guidelines, may cause: Liver Effects: signs/symptoms can include yellow skin(jaundice) and tenderness of upper abdomen. IF SWALLOWED: This product can potentially generate P e r f l u o r o o c t a n o a t e anion, either through dissociation or metabolism. Animal studies conducted on Perfluorooctanoate anion indicate effects including liver disturbances, weight loss, loss of appetite, adrenal and hematologic effects, and benign tumors of the liver, pancreas and testes of male rats. There are no known human health effects from anticipated exposure to this Perfluorooctanoate anion whan used as intended and instructed. Illness may result from a single swallowing of a moderate quantity of this material. CANCEB: A mixture of ammonium perfluorooctanoate, ammonium perfluoroheptanoate, ammonium perfluoropantanoate and ammonium perfluorohexanoate, that was 93 to 97% AMMONIUM PERFLUOROOCTANOATE (3825-26-1) was fed to albino rats for 2 years, no compound induced carcinogenicity was found in the study. There were statistically significant compound related benign testicular tumors. In a second two-year study there were statistically significant compound related Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 726 31--OCT--2000 09:14 3M Tax Message ARGUS 418-020 Tage lb/17 USDS: FC-143 FLUORAD Brand Fluorochemical Surfactant August 25, 2000 PAGE 7 8. HEALTH HAZARD DATA (continued) benign tumors in the liver, pancreas, and testis when compared to ad libitum and pair-fed controls. Based on the current knowledge, these findings have no human health implications. (3825-26-1) (1983 and 1993 studies conducted jointly by 3M and DuPont). ' MUTAGENICITY: Not mutagenic in invitro mutagenicity assays. Did not cause cell transformation in a mammalian cell transformation assay. REPRODUCTIVE/DEVELOPMENTAL TOXINS: Not teratogenic in rabbits by oral administration. Not teratogenic to rats by gavage or inhalation exposures. OTHER HEALTH HAZARD INFORMATION: A Product Toxicity Summary Sheet is available. The presence of organic fluorochemicals in the blood of the general population and subpopulations, such as workers, has been published dating back to the 1970's. 3M's epidemiological study of its own workers indicates no adverse effects. This product can potentially generate Perfluorooctanoate anion, either through dissociation or metabolism. Perfluorooctanoate anion has the potential to be absorbed and remain in the body for long periods of time and may accumulate with repeated exposures. There are no known human health effects from anticipated exposure to this Perfluorooctanoate anion when used as intended and instructed. SECTION CHANGE DATES INGREDIENTS SECTION CHANGED SINCE July 28, 2000 ISSUE Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately 31--OCT-2000 09:14 3M Fax Message MSDS: FC-143 FLUORAD Brand Fluorochemical Surfactant August 25, 2000 ARGUS 418-020 Page iv/i/ PAGE 8 The information in this Material Safety Data Sheet (MSDS) is believed to be correct as of the date issued. 3M MAKES NO WARRANTIES, EXPRESSED OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, ANT IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR COURSE OF PERFORMANCE OR USAGE OF TRADE. User is responsible for determining whether the 3M product is fit for a particular purpose and suitable for user's method of use or application. Given the variety of factors that can affect the use and application of a 3M product, some of which are uniquely within the user's knowledge and control, it is essential that the user evaluate the 3M product to determine whether it is fit for a ' particular purpose and suitable for user's method of use or application. 3M provides information in electronic form as a service to its customers. Due to the remote possibility that electronic transfer may have resulted in errors, omissions or alterations in this information, 3M makes no representations as to its completeness or accuracy. In addition, information obtained from a database may not be as current as the information in the MSDS available directly from 3M. Page 728 ARGUS 418-020 ATTACHMENT 3 T EST SU B ST A N C E PREPARATION PR O C ED U R E Page 729 ATTACHMENT 4 ARGUS 418-020 Protocol 418-020 Version: 418-020(04 NOV 00) Page 1 of 2 TEST SU BST A N CE PREPARATION PR O C ED U R E Test Substance: Vehicle : Ammonium Perfluorooctanoate (APFO) R.O. deionized water A. Purpose: The purpose of this procedure is to provide a method for the preparation of dosage solutions of A P F O for oral (gavage) administration to rats on Primedica Argus Research Laboratories, Inc., Study number 418-020. B. General Information: 1. All solution containers will be labeled and color coded. Each label will specify the protocol number, test substance identification, Argus batch number, concentration, dosage level, preparation date, expiration date and storage conditions. 2. Solutions will be prepared: ___ Daily X Weekly ___ Once prior to dosing __For _ days of use __ By Sponsor 3. Solutions will be administered at a final dosage volume of _5_ mL/kg/day. 4. Safety: X Gloves, uniform/lab coat, goggles or safety glasse s and faceshield X Dust-Mist Respirator (for solution preparation and dosing) __ Half-Face Respirator __ Full-Face Respirator/Positive Pressure Hood X Tyvek sleeves (when using the bulk material) _X Work in a chemical fume hood and use a half-face respirator when using the bulk TA/S only 5. D osage solutions adjusted for % Activity/Purity or Correction Factor ___ Y es __ X No (Calculations based on 100%) ___ Activity ____ % Purity ___ Correction Factor 6. Sampling requirements: Cited in protocol. 7. Storage: Cited in protocol. Page 730 ATTACHMENT 4 ARGUS 418-020 Protocol 41B-020 Version: 418-020f04 NOV 001 Page 2 ot 2 TE ST SU BSTAN CE PREPARATION PR O CED U R E C. D osage Solution Preparation: 1. W eigh out the required amount of the test substance in an appropriately sized, labeled container (see P R E P A R A T IO N CA LC U LA T IO N S). 2. Add approximately 8 0 % of the required amount of vehicle to the container and mix with a stir bar and magnetic stir plate (see P R E P A R A T IO N C A L C U L A T IO N S ). 3. Once the test substance is completely dissolved, transfer the solution to an appropriately sized graduated cylinder. Q S ad with vehicle to the required volume (see P R E P A R A T IO N C A LC U LA T IO N S). 4. Stopper the graduated cylinder or cover with parafilm and mix by inversion several times to ensure proper mixing. Return the solution to the labeled container with the stir bar. Place on a magnetic stir plate and agitate prior to and during aliquotting, dosage administration and/or sampling. 5. Repeat steps (1) through (4) for each concentration. Written By: U Page 731 ARGUS 418-020 ATTACHMENT 4 NECROPSY, ORGAN W EIGHTS AND HISTOPATHOLOGICAL EVALUATION Page 732 ATTACHMENT 4 ARGUS 418-020 Protocol 418-020 Page 1 of 2 NECROPSY, ORGAN W EIGHTS AND HISTOPATHOLOGICAL EVALUATION Organ W eights The following organs will be individually weighed and organ-to-body weight and organ-to-brain weight ratios will be calculated for all P and F1 parental rats. brain kidneys spleen ovaries testes thym u s target organs (if identified by amendment) liver adrenal glands pituitary uterus with oviducts and cervix epididym ides prostate seminal vesicles (with coagulating glands and fluid) For F1 and F2 generation weanlings, the following organs will be weighed from one randomly selected pup per sex per litter: brain spleen thym u s Tissue Retention The following tissues will be collected from all P and F l generation parental male and fem ale rats at necropsy and retained in neutral buffered 10% form alin for possible histological evaluation: pituitary target organs (if identified by amendment) Female Rats adrenal glands gross lesions (including tissue masses) vagina uterus with oviducts, cervix and ovaries Male Rats testis (right) seminal vesicles (with coagulating gland) epididym is (right) prostate Note: Testes will be fixed in Bouin's solution for 48 to 96 hours before being retained in neutral buffered 10% form alin. Page 733 ARGUS 418-020 ATTACHMENT 4 Protocol 418-020 Page 2 of 2 The following tissues will be collected from all F1 and F2 generation weanling rats and retained in neutral buffered 10% form alin for possible histological evaluation: target organs (if identified by amendment) gross lesions (including tissue masses) Histological Evaluation Histological examination will be performed on tissues from 10 randomly selected rats per sex from the control and high dosage groups. If lesions attributed to the test substance are observed in the rats from the high dosage groups, the same organs will be examined histologically for the remaining rats in the control and high dosage groups and for the rats in the low and interm ediate groups. All gross lesions will be examined histologically3. In addition to gross lesions such as atrophy or tumors, testicular histopathological examination should be conducted to identify treatm ent-related effects such as retained spermatids, missing germ cell layers or types, m ultinucleated giant cells or sloughing of spermatogenic cells into the lumen . Examination of the intact epididymis should include the caput, corpus and cauda (accomplished by evaluation of a longitudinal section) and conducted in order to identify such lesions as sperm granulomas, leukocytic infiltration (inflammation), aberrant cell types within the lumen, or the absence of clear cells in the cauda epididymal epithelium. The postlactional ovary should contain prim ordial and growing follicles as well as the large corpora ltea of lactation. Histopathological examination should detect qualitative depletion of the primordial follicle population. A quantitative evaluation of primordial follicles should be conducted for F1 fem ale rats; the number of rats, ovarian section selection and section sample size should be statistically appropriate for the evaluation procedure used. Examination should include enumeration of the number of prim ordial follicles, which can be combined with small growing follicles, for comparison of ovaries of rats assigned to treated and control groups. Additionally, reproductive organs of the low and interm ediate dosage group rats suspected of reduced fertility (e.g., those rats that failed to mate, conceive, sire or delivery healthy offspring, or for which estrous cyclicity or sperm number, m otility or morphology were affected, should be subjected to histological evaluation3. a. Should results warrant examination of the remaining control and high dosage group rats and the rats in the low and interm ediate dosage groups and conduct of the quantitative evaluation, or additional evaluations of low and intermediate dosage groups rats suspected of reduced fertility, scheduled report dates will be adjusted accordingly. Additional costs will be incurred should these evaluations be required.Novem ber 7, 2000 Page 734 `PrIMEDICA ARGUS 418-020 Argus Research Laboratories. Ine. 905 Sheehy Drive. Building A Horsham. PA 19044 Telephone: (215) 443-8710 Telefax: (215)443-8587 PROTOCOL 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSOR'S STUDY NUMBER: T-6889.6 Amendment 1-18 December 2000 1. Bodv Weight and Age (page 6 of the protocol): Actual body weights will be recorded the day after receipt and will be documented in the raw data. Reason for Change: This change corrects a typographical error. 2. Randomization and Cohabitation (page 9 of the protocol): At weaning, a table of random units or a computer-generated randomization procedure will be used to select two FI generation pups per sex per litter per group (60 male and 60 female pups per group), resulting in a total of 600 rats (300 rats per sex) chosen for continued evaluation, rather than 30 male and 30 female (1 per sex per litter) F 1generation pups per group, resulting in a total of 300 rats (150 rats per sex) chosen for continued evaluation. At least two male pups and two female pups, rather than one male pup and one female pup, per litter when possible, will be selected. The body weights will be recorded when rats reach sexual maturation. Following sexual maturation, a table of random units or a computer-generated randomization procedure will be used to select one male and one female FI generation rat per litter per group for continuation through mating to produce the F2 generation. If results warrant that the study be extended to include a third generation, the procedures previously described for the FI generation will be used for selection of F2 generation pups continued on study. ANY REVISIONS TO THIS FINALIZED AMENDMENT MUST BE MADE BY SUBSEQUENT AMENDMENT. Page 735 Reason for Change: ARGUS 418-020 Protocol 41S-020 Amendment 1 Page 2 The Sponsor requested that sexual maturation be measured for two pups per sex per litter per group. 3. Rationale for Dosage Selection (page 11 of the protocol): The intermediate dosage levels are expected to produce minimal observable toxic effects, rather than the intermediate dosage level is expected to produce minimal observable toxic effects. ' Reason for Change: This change corrects the protocol because there are two intermediate dosage levels rather than one intermediate dosage level. 4. Postweanine Developmental Observations (page 15 of the protocol). Nipple Examination: On day 12 postpartum, all pups will be examined for the presence of nipples. The criterion is met when there is a nipple present. Reason for Change: The addition was requested by the Sponsor. 5. Sperm Evaluations (page 18 of the protocol): The left testis will be used for evaluation of testicular spermatid concentration using computer-assisted sperm analysis (CASA). The left testis will be weighed (both before and after removal of the tunica albuginea) and then homogenized. A sample from the resulting homogenate will be stained with an 1DENT Stain Kit from Hamilton Thome Research and a slide will be prepared for analysis by the Hamilton Thome IVOS. Ten fields will be analyzed to determine testicular spermatid concentration (spermatids per gram of tissue weight). All images produced during analysis will be retained as raw data. Reason for Change: This change was added in order to comply with U.S. Environmental Protection Agency Health Effects Test Guidelines (OPPTS 870.3800), August, 1998. ANY REVISIONS TO THIS FINALIZED AMENDMENT MUST BE MADE BY SUBSEQUENT AMENDMENT. Page 736 ARGUS 418-020 Protocol 418-020 Amendment 1 Pase 3 6. F1/F2 Generation Pups Not Selected for Continued Observation (page 19 of the protocol): Tissues from one of the three selected pups per sex per litter, rather than from all three selected pups per sex per litter, will be weighed. Tissues from the three selected pups per sex per litter will be retained in neutral buffered 10% formalin for possible histological evaluation. Reason for Change: This change clarifies the protocol. 7. F1/F2 Generation Pups Not Selected for Continued Observation (page 19 of the protocol): All pups not selected for continued observation following continued observations for sexual maturation will be sacrificed and a limited necropsy will be performed. The thoracic, abdominal and pelvic cavities will be examined for gross lesions; gross lesions will be preserved in neutral buffered 10% formalin. All other tissues and the carcass will be discarded. Reason for Change: This addition provides for the sacrifice and necropsy of rats not selected for continued observation following continued observations for sexual maturation. 8. Tissue Retention (pages 1and 2 of ATTACHMENT 4 to the protocol): The following tissues will be collected from the three selected FI and F2 generation weanling rats per sex per litter, rather than from all FI and F2 generation weanling rats, and retained in neutral buffered 10% formalin for possible histological evaluation: target organs (if identified by amendment) gross lesions (including tissue masses) ANY REVISIONS TO THIS FINALIZED AMENDMENT MUST BE MADE BY SUBSEQUENT AMENDMENT. Page 737 Reason for Change: This change clarifies the protocol. ARGUS 418-020 Protocol 4 18-020 Amendment 1 Page 4 Alan M. Hoberman. Ph.D., DABT Date Director of Research 'G. York, ?ty Director of 'Director BT Date jk^**** Z / T 7frJ o / ; Jena C. Lebo, V.M.D. Date John Butenhoff. Ph.D., DABT, CIH Date Chairperson, Institutional Animal Care Study Monitor and Use Committee Sponsor's Representative ANY REVISIONS TO THIS FINALIZED AMENDMENT MUST BE MADE BY SUBSEQUENT AMENDMENT. Page 738 OPrimedica ARGUS 418-020 Argus Research Laboratories. Inc 905 Sheehy Drive. Building A Horsham. PA 19044 Telephone: (215) 443-8710 Telefax: (215)443-8587 PROTOCOL 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSOR'S STUDY NUMBER: T-6889.6 Amendment 2 -8 February 2001 1. Nipple Examination (page 2 of Amendment 1): [Effective Date: 1 February 2001] On day 12 postpartum, all male pups will be examined for the presence of nipples. The criterion of passing is met when no nipples are present. Reason for Change: This change clarifies the criterion and sex of pups to be examined. A /* Alan M. Hoberman, Ph.D., DABT Date Director o f Research f&A of Theresa H. Woodard, D.V.M. Date Chairperson, Institutional Animal Care and Use Committee John Butenhoff, Ph.D., DABT, CIH Date Study Monitor and Sponsor's Representative Any revisions to this finalized amendment must be made by subsequent amendment. Page 739 OPrimedica ARGUS 418-020 Argus Research Laboratories. Ine. 905 Sheehy Drive. Building A Horsham. PA I944 Telephone: (215) 443-8710 Telefax: (215)443-8587 PROTOCOL 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSOR'S STUDY NUMBER: T-6889.6 Amendment 3-20 July 2001 1. Gross Necropsy and Histonathology (page 17 of the protocol): Tissues will be shipped (ambient conditions) for embedding to: W. Ray Brown. D.V.M.. Ph.D., ACVP Veterinary Pathologist Research Pathology Services, Inc. 438 E. Butler Avenue New Britain. Pennsylvania 18901 Telephone: (215) 345-7070 Fax: (215)345-4326 The recipient will be notified in advance of sample shipment. Reason for Change: This change adds the address for tissue shipment to the protocol. ^A lan M. Hoberman. Ph.D.. DABT ' Director of Research uAuz.&Al 2J)jSu[L 0 1 Date Valerie A. Sharper, M.S. Director of Study Management for Raymond G. York, Ph.D., DABT Associate Director of Research and Study Director Date ikltn n irJ ic wuu Theresa H. Woodard, D.V.M. Date John Butenhoff, Ph.D., DABT, CIH Chairperson. Institutional Animal Care Study Monitor and Use Committee Date Any revisions to this finalized amendment must be made by subsequent amendment or Tage 740 ARGUS 418-020 905 Sheehy Drive Bldg. A Horshcm PA 19044 Tephone (215) 443-8710 Telefax: (215)443-8587 A RG U S RESEARCH C h a le s River Lcb orctories Discovery e n d Developm ent Serviaes PROTOCOL 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSOR'S STUDY NUMBER: T-6889.6 Amendment 4-19 November 2001 1. Litter Data (page 14 of the protocol): [Effective Date: 6 August 2001] Lactation Index will be calculated as the percentage of pups that survive from day 5 to day 22 postpartum, rather than day 8 to day 22 postpartum. Reason for Change: This change was made to account for survival of pups for entire period following the calculation of viability index (percentage of pups bom that survive to days 1and 5 postpartum). /9st/V - V Alan M. Hoberman, Ph.D., DABT Date Director of Research *J(u/ 2co! 3ABT Date l l (jJ r r J t* Theresa H. Woodard, D.V.M. Date Chairperson, Institutional Animal Care and Use Committee John Butenhoff, Ph.D., DABT, CIH Study Monitor Date Any revisions to this finalized amendment must be made by subsequent amendment Page 741 ARGUS 418-020 APPENDIX G DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FAdLITY Page 742 ARGUS 418-020 DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY 1. On 22 February 2001, the following P generation female rats were not weighed and potentially received the incorrect dosage volumes based on the previous body weight. Dosage Dosage Day of Group (mg/kg/day) Study4 Rat Numbers I 0 DL 8 13814, 13817, 13818, 13830 DL 11 13806, 13808 DG 18 13809 II 1 DL 8 13831, 13849, 13859, 13860 m DL 11 3 DL 8 13837, 13850, 13853, 13858 13868, 13874, 13877, 13882 DL 11 13889 IV 10 DL 8 13892, 13899, 13913, 13914, 13916, 13917, 13919, 13920 DL 21 13907 V 30 DL 5 13945 DL 8 13931, 13932, 13950 DL 11 13923 a. DL is used as an abbreviation for day of lactation. DG is used as an abbreviation for day of gestation. These deviations did not adversely affect the outcome or interpretation of the study because it was a single event and all rats were administered a dosage very similar to the dosage they should have received. 2. On 1 December 2000, DS 19, the P generation male and female rats in all dosage groups were administered the appropriate vehicle or test article approximately two hours and fifteen minutes late and three hours early, respectively. This deviation did not adversely affect the outcome or interpretation of the study because it was a single event and all rats received the appropriate vehicle or test article. 3. Body weights were not recorded and predosage and postdosage observations were not recorded for the following rats. It is presumed that the rats were not dosed. Generation FI Dosage Group V Dosage (mg/kg/day) 30 Date 08 MAR 01 08 MAR 01 Day of Study DS 1 DS 1 Sex Female Female Rat Number 1562 1563 These deviations did not adversely affect the outcome or interpretation of the study because it was a single event of a missed dosage and sufficient data were available to evaluate these parameters. Page 743 ARGUS 418-020 4. On 13 April 2001, day 35 of study (DS 35), FI generation male rat 1166 in the 3 mg/kg/day dosage group received 0.94 mL of the test substance rather than 0.86 mL. This deviation did not adversely affect the outcome or interpretation of the study because it was a single event and the amount of overage was small (0.08 mL). 5. On 15 April 2001, FI generation female rats in the 30 mg/kg/day dosage group received the incorrect dosage volume. Day of Study DS 41 DS 40 DS 40 DS 40 DS 40 DS 40 DS 40 DS 40 DS 39 DS 39 DS 39 DS 39 DS 39 DS 39 DS 39 DS 39 DS 39 DS 38 DS 38 DS 38 DS 37 DS 37 DS 37 DS 37 DS 37 DS 37 DS 37 DS 37 Rat Number 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 1593 Correct Volume (mL) 0.82 1.1 1 1 0.87 0.74 0.98 0.91 1.1 0.9 0.93 0.88 0.89 1 1.1 0.88 1.1 0.82 0.93 1 0.91 0.86 0.84 0.88 0.97 1 0.97 1.1 Dosage Volume Amount Received (mL) 1.3 1.4 1.6 1.2 1.1 1.1 1.2 1.1 1.4 1.4 1.1 1.2 1.3 1.4 1.5 1.2 1.4 0.86 1.3 1.3 1.3 1.2 1.1 1.4 1.4 1.3 1.4 1.3 Amount Deviated (mL) 0.48 0.3 0.6 0.2 0.23 0.36 0.22 0.19 0.3 0.5 0.17 0.32 0.41 0.4 0.4 0.32 0.3 0.04 0.37 0.3 0.39 0.34 0.26 0.32 0.43 0.3 0.43 0.2 These deviations did not adversely affect the outcome or interpretation of the study because it was a single event for each of the rats; they received more rather than less of the test substance and the amount and the overage was small. Page 744 ARGUS 418-020 6. Postdosage observations were performed out of the range of 60 10 minutes on the following dates. Dosage Group I Dosage (mg/kg/day) 0 II 1 III 3 IV 10 V 30 Date 18 NOV 00 04 DEC 00 28 DEC 00 06 JAN 01 18 FEB 01 13 MAR 01 15 MAR 01 15 NOV 00 18 NOV 00 01 DEC 00 04 DEC 00 06 DEC 00 09 DEC 00 18 NOV 00 06 DEC 00 18 JAN 01 02 FEB 01 27 FEB 01 18 NOV 00 05 DEC 00 01 FEB 01 11 FEB 01 12 FEB 01 13 FEB 01 22 FEB 01 27 FEB 01 11 DEC 00 25 DEC 00 05 JAN 01 02 FEB 01 07 FEB 01 13 FEB 01 23 FEB 01 26 FEB 01 27 FEB 01 Number of P Generation Rats Male Rats Female Rats 10 04 02 10 50 01 01 10 14 0 01 14 0 01 20 16 0 03 2 14 03 01 17 0 40 0 0 2 1 01 20 20 01 02 17 0 10 02 01 10 0 0 11 02 01 Range of Time Deviated (minutes) +1 +1 to +3 +1 +1 + 1 to +2 +4 +14 +52 +1 to +10 +329 +1 to +6 +1 +1 +1 to +8 + 1 to +2 +1 to +5 +1 to +2 -1 +1 to +8 +1 -1 +80 -1 +1 to +2. +1 to +2 -1 +1 +1 to +5 +229 -1 +4 +1 to +7 -4 to -1 -1 -1 Page 745 ARGUS 418-020 Dosage Group I II m IV Dosage (mg/kg/day) 0 1 3 10 Date 09 MAR 01 15 MAR 01 25 MAR 01 10 APR 01 15 APR 01 17 APR 01 21 APR 01 23 APR 01 23 JUN01 02 JUL 01 12 MAR 01 13 MAR 01 15 MAR 01 24 MAR 01 27 MAR 01 02 APR 01 05 APR 01 09 APR 01 12 APR 01 29 APR 01 06 JUNO 1 12 JUN 01 19 JUN01 27 JUN 01 23 MAR 01 12 APR 01 18 APR 01 20 APR 01 04 MAY 01 05 MAY 01 31 MAY 01 14 JUN 01 29 JUN 01 07 JUL 01 14 MAR 01 25 MAR 01 02 APR 01 09 APR 01 12 APR 01 19 APR 01 06 JUN 01 18 JUN 01 Number of FI Generation Rats Male Rats Female Rats 30 36 0 40 0 11 20 10 12 0 40 01 10 02 0 22 01 02 03 21 0 10 10 0 42 0 01 03 02 03 0 28 05 57 0 10 40 02 0 0 2 1 0 0 2 1 03 0 0 2 1 10 0 01 42 0 01 13 0 09 Range of Time Deviated (minutes) +1 + 1 to +17 + 1 to +3 + 1 to +6 +1 +5 + 1 to +3 + 1 to +3 +1 . +1 -1 -4 to -1 -2 +1 ' +1 +1 to +3 -1 -5 to -1 +1 to +10 +1 +1 +1 +1 to +2 +26 to +40 +1 to +2 +8 to +16 -1 +1 +1 to +2 +1 +63 +1 +1 +1 -1 +1 +4 to +7 -1 +8 to +15 -1 +1 to +4 +1 to +3 Page 746 ARGUS 418-020 Dosage Group V Dosage (mg/kg/day) 30 Date 08 MAR 01 15 MAR 01 17 MAR 01 19 MAR 01 30 MAR 01 02 APR 01 03 APR 01 08 APR 01 10 APR 01 12 APR 01 20 APR 01 16 MAY 01 09 JUN 01 12 JUN 01 01 JUL 01 Number of FI Generation Rats Male Rats Female Rats 21 10 60 55 0 01 20 50 30 10 54 0 0 15 0 10 03 01 06 Range of Time Deviated (minutes) -1 to +5 +41 + 1 to +2 +67 to +79 +29 + 1 to +12 -1 +1 -I +5 to +20 + 1 to +5 -2 to -1 -2 to -1 . +1 + 1 to +3 These deviations did not adversely affect the outcome or interpretation of the study because, except for fifteen incidents, the extent of the deviation was ten minutes or less. 7. Postdosage observations were not recorded for the following rats. Generation P FI Dosage Group II IV V I III IV V Dosage (mg/kg/day) 1 10 30 0 3 10 30 Date 18 JAN 01 18 JAN 01 15 DEC 00 22 MAR 01 26 MAR 01 21 MAY 01 05 JUL 01 31 MAR 01 12 APR 01 12 APR 01 12 APR 01 12 APR 01 12 APR 01 12 APR 01 Day of Study DS 67 DS 67 DS 33 DS 14 DS 19 DS 76 DL 15 DS 25 DS 34 DS 34 DS 34 DS 34 DS 34 DS 34 Sex Male Male Male Male Male Male Female Male Male Male Male Male Male Male Rat Number 13656 13712 13741 1034 1154 1132 1448 1186 1224 1225 1236 1237 1238 1246 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. Page 747 ARGUS 418-020 8. The estrous cycle evaluation was not recorded for the following rat. Generation P Dosage Group m Dosage (mg/kg/day) 3 Date 19 JAN 01 Day of Study DS 68 Sex Female Rat Number 13882 This deviation did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. Page 748 ARGUS 418-020 9. Observations for maternal behavior were not recorded for the following P generation female rats. Dosage Group I Dosage (mg/kg/day) 0 Day of Study DL 1 Date 16 FEB 01 DL 22 05 MAR 01 DL 22 06 MAR 01 DL 22 07 MAR 01 DL 22 08 MAR 01 DL 22 09 MAR 01 DL 22 10 MAR 01 DL 22 13 MAR 01 DL 22 19 MAR 01 II 1 DL 1 14 FEB 01 DL 22 05 MAR 01 DL 22 06 MAR 01 DL 22 07 MAR 01 DL 22 08 MAR 01 DL 22 09 MAR 01 III 3 DL 22 05 MAR 01 DL 22 06 MAR 01 DL 22 07 MAR 01 DL 22 08 MAR 01 DL 22 09 MAR 01 DL 22 10 MAR 01 DL 22 13 MAR 01 IV 10 DL 1 14 FEB 01 DL 1 15 FEB 01 DL 22 06 MAR 01 DL 22 07 MAR 01 DL 22 08 MAR 01 DL 22 09 MAR 01 V 30 DL 1 14 FEB 01 DL 1 16 FEB 01 DL 22 05 MAR 01 DL 22 06 MAR 01 DL 22 07 MAR 01 DL 22 08 MAR 01 DL 22 09 MAR 01 DL 22 10 MAR 01 DL 22 11 MAR 01 a. Behavior observation not recorded 1 - postpartum grooming 2 - removal of pup amniotic sac 3 - removal of pup placenta/umbilical cord 4 - normal nesting activity 5 - normal nursing activity Number of P Generation Female Rats 1 2 3 3 4 7 1 1 1 1 4 9 5 4 4 1 9 7 4 6 1 1 2 1 4 7 8 10 1 1 1 5 10 3 7 1 1 Behavior Observation Not Recorded3 1,2, 3, 4, 5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 1,2, 3,4, 5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 1,2, 3 ,4,5 1,2, 3, 4 4,5 4,5 4,5 4,5 1.2, 3 ,4,5 1.2, 3. 4 ,5 4,5 4,5 4,5 4,5 4,5 4,5 4,5 Number of Pups Affected 1 female all all all all all all all all 1 female all all all all all all all all all all all all 1 male 1 female all all all all 1 female 1 male all all all all all all all These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were collected to evaluate this parameter. Page 749 ARGUS 418-020 Observations for pups were not recorded for the following litters. Generation FI Dosage Group in V Dosage (mg/kg/day) 3 30 Date 10 MAR 01 10 MAR 01 Day of Study DL 22 DL 22 Litter Number 13864 13940 Number of Pups 6 15 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. Predosage observations and dosage volume were not recorded for the following rat. Generation FI Dosage Group I Dosage (mg/kg/day) 0 Date 22 MAR 01 Day of Study DS 14 Sex Female. Rat Number 1030 This deviation did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. Predosage observations, dosage volumes and postdosage observations were not recorded for the following rats. Generation FI Dosage Group m IV Dosage (mg/kg/day) 3 10 Date 12 APR 01 12 APR 01 12 APR 01 12 APR 01 12 APR 01 Day of Study DS 34 DS 34 DS 34 DS 34 DS 34 Sex Male Male Male Male Male Rat Number 1166 1225 1227-1235 1239 1240 These deviations did not adversely affect the outcome or interpretation of the study because sufficient observations were available to evaluate theses parameters. There was no discrepancy in the chemistry data, therefore it is presumed that the rats were dosed appropriately. Terminal body weights were not recorded for the following rat. Generation FI Dosage Group V Dosage (mg/kg/day) 30 Date 06 APR 01 Day of Study DS 28 Sex Female Rat Number 1596 This deviation did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. ARGUS 418-020 14. On 29 May 2001, DG 0, FI generation female rat 1486 in the 10 mg/kg/day dosage group was not removed from cohabitation and remained in cohabitation until DG 1. As a result of not being removed from cohabitation until DG 1, the feed consumption value for the interval DG 0 to DG 7 was not recorded. This deviation did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate feed consumption. 15. Feed left values were not recorded for the following rats. Generation FI Dosage Group II IV V Dosage (mg/kg/day) 1 10 30 Date 09 MAR 01 26 APR 01 09 MAR 01 05 APR 01 09 MAR 01 09 MAR 01 06 APR 01 Day of Study DS 4 DS 51 DS 3 DS 29 DS 2 DS 2 DS 28 Sex Female Female Female Female Female Female Female Rat Number 1365 1373 1484 1500 1562 1563 1596 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. 16. Vaginal patency was not evaluated until observed for the following rats. Generation FI Dosage Group II III IV Dosage (mg/kg/day) 1 3 10 Date of Last Evaluation 23 MAR 01 23 MAR 01 23 MAR 01 Day of Study DS 15 DS 14 DS 16 Sex Female Female Female Rat Number 1409 1468 1489 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. 17. Preputial separation was not evaluated until observed for the following rats. Generation FI Dosage Group I Dosage (mg/kg/day) 0 Date of Last Evaluation 03 APR 01 03 APR 01 03 APR 01 Day of Study DS 25 DS 25 DS 25 Sex Male Male Male Rat Number 1040 1052 6553 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. Page 751 ARGUS 418-020 Observations for sexual maturation were not recorded for the following rats. Generation FI Dosage Group I IV Dosage (mg/kg/day) 0 10 Date 05 APR 01 05 APR 01 08 APR 01 07 APR 01 08 APR 01 Day of Study DS 39 DS 39 DS 30 DS 29 DS 30 Sex Male Male Male Male Male Rat Number 1059 1060 6555 1222 1222 These deviations did not adversely affect the outcome or interpretation of the study because these sufficient data were available to evaluate this parameter. Maternal observations were not recorded for the following rats. Generation FI Dosage Group I IV Dosage (mg/kg/day) 0 10 V 30 Date 14 JUL01 25 JUN01 07 JUL 01 21 JUN01 23 JUN01 25 JUN 01 28 JUN01 Day of Study DL 22 DL 5 DL 15 DL 1 DL 1 DL 5 DL 8 Rat . Number 1328 1490 1523 1548 1568 1573 1557 Number of Pups all all 1 1 1 1 1 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. Clinical observations were not recorded for the following pups. Generation FI Dosage Group V Dosage (mg/kg/day) 30 Date 25 JUN 01 26 JUN 01 Day of Study DL 3 DL 4 Litter Number 1568 1568 Number of Pups 12 12 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. Anogenital distance measurements were not recorded for the following rat. Generation FI Dosage Group II Dosage (mg/kg/day) 3 Date 12 JUL 01 Day of Study DL 22 Sex Female Rat Number 1474 This deviation did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. ARGUS 418-020 22. The terminal blood sample was not taken for the following rat. Generation P Dosage Group I Dosage (mg/kg/day) 0 Date 19 MAR 01 Day of Study DL 22 Sex Female Rat Number 13809 This deviation did not adversely affect the outcome or interpretation of the study because this was a control group rat and sufficient data were available to evaluate this parameter. 23. Necropsy observations were not recorded for the following rat. Generation FI Dosage Group II Dosage (mg/kg/day) 1 Date 14 JUL 01 Day of Study DL 22 Sex Female. Rat Number 1362 This deviation did not adversely affect the outcome or interpretation of the study because it was a single event. 24. The pituitary was not retained for the following rat. Generation P Dosage Group I Dosage (mg/kg/day) 0 Date 07 MAR 01 Day of Study DL 22 Sex Female Rat Number 13807 This deviation did not adversely affect the outcome or interpretation of the study because this was a control group rat and sufficient data were available to evaluate this parameter. 25. The right adrenal was lost during processing and therefore not saved in neutral buffered 10% formalin for the following rat. Generation FI Dosage Group V Dosage (mg/kg/day) 30 Date 02 JUL 01 Day of Study DS 118 Sex Male Rat Number 1252 This deviation did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate this parameter. Page 753 ARGUS 418-020 26. The organ weights for brain, kidneys, spleen, ovaries, thymus, liver, adrenal glands, pituitary and uterus with oviducts and cervix were not weighed and the pituitary and adrenal glands were not retained for the following rats. Generation FI Dosage Group I II m IV V Dosage (mg/kg/day) 0 1 3 10 30 Date 08 MAR 01 08 MAR 01 09 MAR 01 26 APR 01 13 MAR 01 09 MAR 01 09 MAR 01 09 MAR 01 11 MAR 01 11 MAR 01 13 MAR 01 14 MAR 01 Day of Study DS 1 DS 1 DS 4 DS 51 DS 7 DS 3 DS 2 DS 2 DS 3 DS 3 DS 6 DS 14 Sex Female Female Female Female Female Female Female Female Female Female Female Female Rat Number 1319 1320 1365 1373 1432 1484 1562 1563 1574 1575 1559 1549 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate these parameters. 27. Reproductive organs (uterus, ovaries, oviducts, cervix and vagina) were not retained for the following rats. Generation FI Dosage Group I Dosage (mg/kg/day) 0 II 1 III 3 IV 10 V 30 a. Uterus and cervix were retained. Date 23 JUN01 06 JUL01 25 JUN 01 23 JUN 01 26 JUN 01 23 JUN 01 29 JUN 01 25 JUN 01 Day of Study DG 25 DG 25 DG 25 DG 25 DG 25 DG 25 DG 25 DG 25 Sex Female Female Female Female Female Female Female Female Rat Number 1316 1358 1378" 1458 1446s 1483 1511 1578 These deviations did not adversely affect the outcome or interpretation of the study because sufficient data were available to evaluate these parameters. All deviations are documented in the raw data. Page 754 ARGUS 418-020 APPENDIX H CERTIFICATE OF ANALYSIS Page 755 ARGUS 418-020 Centre Analytical Laboratories, Inc 3048 Research Drive State College. PA 16801 Phone: (814) 231-8032 Fax: (814) 231-1253 or (814) 231-1580 | Purity1 INTERIM CERTIFICATE OF ANALYSIS Centre Analytical Laboratories COA Reference #: 023-033 3M Product: Ammonium Perfluorooctanoate Test Control Reference #: TCR-99131-37, Lot #: 332 Purity: 95.2%_________________ Test Name Specifications i Result 95.2% Appearance Identification NMR Metals (ICP/MS) 1. Calcium 2. Magnesium 3. Sodium 4. Potassium 5. Nickel 6. Iron 7. Manganese Total % Impurity (NMR) Total % Impurity (LC/MS) Total %Impurity (GC/MS) Residual Solvents (TGA) Purity by DSC Inorganic Anions (IC) 1. Chloride 2. Fluoride 3. Bromide 4. Nitrate 5. Nitrite 6. Phosphate 7. Sulfate Organic Acids* (IC) 1. TFA 2. PFPA 3. HFBA 4. NFPA Elemental Analysis'1: 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine Ammonium AnalysisJ Ion Selective Electrode White, crystalline solid Theoretical Value = 22.3% Theoretical Value = 0.935% Theoretical Value = 3.25% Theoretical Value = 0% Theoretical Value = 66.1% Theoretical Value = 4.18% Conforms Positive 1. 0.001 wt./wt.% 2. <0.001 wt./wt.% 3. 0.005 wt./wt.% 4. <0.001 wt./wt.% 5. <0.001 wt./wt.% 6. <0.001 wt./wt.% 7. <0.001 wt./wt.% 0.34 wt7wt.% 4.49 wt^wt.% None Quantified None Detected 99.7% 1. <0.015 wt./wt.% 2. <0.005 wt./wt.% 3. <0.040 wt./wt.% 4. <0.009 wt./wt.% 5. <0.006 wt7wt.% 6. <0.006 wt7wt.% 7. <0.040 wtywt.% 1. <0.1 wt./wt.% 2. <0.1 wt./wt.% 3. <0.1 wtVwt.% 4. <0.25 wt./wt.% 1. 18.9 wt./wt.% 2. 1.31 wt./wt.% 3. 3.75 wt./wt.% 4. 4.34 wt./wt.% 5. 63.2 wt./wt.% 3.49 wt./wt. % COA023033-37.doc Page 756 Page 1of2 ARGUS 418-020 Centre Analytical Laboratories, Inc. 3048 Research Orive Phone: (814) 231-8032 State College. PA 16801 Fax: (814) 231-1253 or (814) 231-1580 INTERIM CERTIFICATE OF ANALYSIS Centre Analytical Laboratories COA Reference #: 023-033 3M Product: Ammonium Perfluorooctanoate Test Control Reference #: TCR-99131-37, Lot #: 332 Date o f Last Analysis: 12/15/00 Expiration Date: 12/15/01 Storage Conditions: < - 1 0 "C Re-assessment Date: 12/15/01 'Purity = 100% - (Total Metal impurities, 0.006% + Total NMR impurities, 0.34% + Total LC/MS impurities, 4.49%) Total impurity from all tests = 4.84% Purity 100% - 4.84% = 95.2% 2 TFA HFBA NFPA PFPA Trifluoroacetic acid Heptafluorobutyric acid Nonafluoropentanoic acid Pentafluoropropanoic acid 3Theoretical value calculations based on the empirical formula, C*FisQ2(*)NH4(+) (MW=431.1) LC/MS Purity Profile: Peak# 1 2 3 Total Retention Time (min) 12.140 13.504 14.099 - Mass(s) 269 331,319 369 - Identity e* C7 homologue/Fn PFOA - Area 167596 860991 21861700 22890287 % Area 0.73 3.76 4.49 This work was conducted under EPA Good Laboratory Practice Standards (40 CFR 160). Prepared By: Smcientist, Ce ial b o ra to rie s O i\/0l A r. Date Reviewed By: '/f/cf y /io h n . Flaherty Date Laboratory Manager, Centre Analytical Laboratories COA023033-37.doc Page 2 of 2 Page 757 ARGUS 418-020 APPENDIX I ANALYTICAL REPORT Page 758 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 - ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Analytical Report: FACT TOX-164 UMS EOO-2738 Study Title Oral (Gavage)ATmwmoo-GnieunmerPateiorfnlu(oOronoecLtaitnteorapteer(AGPeFnOer/PatFioOnA) )RienpRroadtsuctiqonyStu-dQy2o-fC' Analytical Laboratory Report Title Determination of the Presence and Concentration of PFOA Fluorochemical in Rat Sera Samples Data Requirement January 7, 2002 Author 3M Environmental Laboratory Study Completion Date At signing Performing Laboratories Sera Analyses 3M Environmental Laboratory Building 2-3E-09,935 Bush Avenue SL Paul. MN 55106 Sera Extractions Pace Analytical Services. Inc--Tier2 Facility 1700 Elm Street SE, Suite 100 Minneapolis, MN 55414 Project Identification 3M Medical Department Study: T-6889.6 Argus In-Life Study: 418-020 Analytical Report: FACT TOX-164 3M LIMS No. E00-2783 Total Number o f Pages 110 AM Fnvim nmantnl I ahnralnrv 3M Environmental Laboratory Page 759 Pane 1 Page 1 3M Medical Department Study: T-6889.6 3M Medical Department Study. T-6889.6 ; ------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-273S Analytical Report: FACT TOX-164 UMS E00-2738 This page has been reserved for specific country requirements. ni< e i 3M Environmental Laboratory Page 760 Page 2 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 Analytical ! CT TX-164 LIMS EOO-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 GLP Compliance Statement Analytical Laboratory Report Title: Determination of the Presence and Concentration of PFOA Fluorochemicai in Rat Sera Samples Study Identification Numbers: T-6889.6, FACTTOX-164, LIMS EOO-2738 This study was conducted in compliance with United States Environmental Protection Agency (EPA) Good Laboratory Practice (GLP) Standards 40 CFR Part 792, with the exceptions in the bulleted list below. Exceptions to GLP compliance: There were two study directors in this study. This study was designed as two separate studies. The in-life phase (Argus #418-020) was considered to end at the generation and shipment of specimens. The analytical study (3M FACT-TCX164) was considered to start at the receipt of these specimens for analysis. This resulted in having two separate study directors, one for each phase of the same study. However, since the technical performance of each phase was entirely separate, no effect is expected from this exception. Dose confirmation and stability samples were not analyzed according to the GLPs. The purity and stability of the surrogate THPFOS standard is not included in this report, it is not known at this time. John Butenhoff, Ph.D., Study Director David Sanders, Ph.D., Sponsor Representative JVfyt A. Cl-LflrvvjA_ _ _ _ _ _ _ _ _ _ Lisa Clemen, PrincipalAnalytical Investigator William Reagen, Ph.D., Laboratory Management Date illic it Date O i l DM I p a. Date Date 3M Environmental Laboratory 3M Environm ental Laboratory Page 761 Page 3 Page 3 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ~------ ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 Analytical Report: FACT TOX-164 LIMS E00-2738 G LP Study-- Quality Assurance Statement Analytical Laboratory Report Title: Determination of the Presence and Concentration, of PFOA Fluorochemical in Rat Sera Samples Study Identification Numbers: T-6889.6. FACT TOX-164, LIMS E00-2738 This study has been inspected by the 3M Environmental Laboratory Quality Assurance Unit (QAU) as indicated in the following table. The findings were reported to the study . director and laboratory management. Inspection Dates Phase Date Reported to Management Study Director 5/30/01 Protoool 05/30/01 05/30/01 6/27/01 Analysis 06/27/01 06/27/01 6126/01 09/25/01-09/28/01 and 10/01/01-10/02/01 11/07/01-11/08/01 Sample Dilutions Data Draft report 06/26/01 10/03/01 11/09/01 06/26/01 ! 10/03/01 11/09/01 lulled QAU Representative ih /o z - Date 3M Environmental Laboratorv 3M Environmental Laboratory Page 762 Paae4 Page 4 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 Table of Contents - --- -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Analytical Report* FACT TOX-164 LIMS EOO-2738 GLP Compliance Statement............................................................................................... 3 GLP Study - Quality Assurance Statement......................................................................... 4 List of Tables..................................................................................................................... 6 Study Personnal and Contributors..................................................................................... 7 Location of Archives....................................................................................................... ...7 Introduction and Purpose...................................................................................................8 Speciment Receipt and Maintenance................................................................................. 8 Chemical Characterization of the Reference Substance.....................................................10 Sample Preparation and Analysis...................................................................................... 11 Dose Confirmation and Stability Analyses..................................................................... 11 Sera Analyses................................................................................................................11 Method Summaries................................................................................................. 12 Preparatory Method................................................................................................ 12 Analytical Method................................................................................................... 12 Analytical Equipment.............................................................................................. 13 Deviations/Amendments............................................................................................... 14 Data Quality Objectives and Data Integrity......................................................................... 14 Data Summary, Analyses, and Results...............................................................................14 Summary of Quality Control Analyses Results............................................................... 15 Statement of Data Quality............................................................................................. 16 Summary of Sample Results......................................................................................... 16 Statistical Methods and Calculations..................................................................................17 Statement of Conclusion.................................................................................................... 17 References........................................................................................................................ 17 Appendix A: Chemical Characterization and Control Matrices............................................ 18 Appendix B: Protocol, Amendments, and Deviation(s)........................................................19 Appendix C: Extraction and Analytical Methods.................................................................. 36 ETS-8-4.1, Extraction of Perfluorooctanesulfonate or Other Fluorochemica! Compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry, (14 pages).......... 37 ETS-8-4.2, Extraction of Fluorochemical Compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry, (15 pages)...........................................................51 ETS-8-5.1, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (9 pages)..........................66 ETS-8-5.2, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (11 pages)........................ ^6 Appendix D: Dose Confirmation Analyses and Data Summary Tables................................7 Appendix E: Data Spreadsheets.........................................................................................90 3M Environmental Laboratory 3M Environmental Laboratory Page 763 Page 5 Page 5 1Department Study: T-6889.6 - - - - - - _, ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 3M Medical Department Study: T-6889-6 Analytical Report FACT TOX-164 LIMS E00-2738 Appendix F: Example Calculations.....................................................................................106 Appendix G: Interim Certificate(s) of Analysis.................................................................... 107 Appendix H: Report Signature Page...................................................................................110 List of Tables Table 1. Specimens received from Argus Research Laboratory Study (418-020) on 14 November, 2000.............................................................................................. 8 Table 2. Specimens received from Argus Research Laboratory Study (418-020) on 18 April. 2001.........................................................................................................9 Table 3. Specimens received from Argus Research Laboratory Study (418-020) on 13 July, 2001..........................................................................................................9 Table 4. Specimens received from Argus Research Laboratory Study (418-020) on 09 August. 2001.....................................................................................................9 Table 5. Characterization of the Analytical Reference Substance in Study FACT-TOX-164...................................................................................................... 10 Table 6. P Generation Rat Samples Analyzed in Study FACT-TOX-164............................ 11 Table 7. Target Ions Monitored in 3M Laboratory Analyses................................................ 13 Tabel 8. Determination of the LOQ in the Analyses of Rat Sera Extracts........................... 15 Table 9. Matrix Spike Recoveries in the Analyses of Rat Sera Extracts.............................. 16 Table 10. Characterization of the Control Matrices Used for Sera Analyses in Study FACT-TOX-164...................................................................................................... 18 Table 11. Characterization of Test Substance in Study FACT TOX-164............................ 18 Table 12. Dose Confirmation Analyses - Extracted 11/17/00, Analyzed 11/27/00............. 87 Table 13. Dose Confirmation Analyses - Extracted 11/27/00, Analyzed 11/28/00 ............ 88 Table 14. Dose Confirmation Analyses - Extracted 01/17/01, Analyzed 01/23/01............. 89 Table 15. TOX 164 Data Summary of PFOA Concentration-- Rat Serum (pg/mL).............89 Fnuim nm antal I ahnratnrv 3M Environmental Laboratory Page 764 Dono A Page 6 3M Medical Department Study: T-6889.6 3M Medical Department Study. T-6889.6 Study Personnel and Contributors ----------- A R G U S 41 8 -0 2 0 Analytical Report: FACT TOX-164 LIMS E00-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 Study Director John Butenhoff, Ph.D. 3M Corporate Toxicology 3M Medical Department Building 220-2E-02 St. Paul, MN 55144 Analytical Chem istry Laboratories Sera Analyses 3LMisaECnlveimroennm,ePnrtianlcLipaabloArantaolyrytic(3aMl InLvaebs)tigator Sponsor 3M Corporate Toxicology 3M Medical Department Building 220-2E-02 ST. Paul, MN 55144 DReapvirdesSeanntdaetivrse, Ph.D., Sponsor Sera Extractions Pace Analytical Services, Inc.-- Tier2 Facility 3M Lab Contributing Personnel Rhonda Dick* Kristen J. Hansen, Ph.D. Marlene M. Heying* Harold O. Johnson ` Contract lab protassionai service employees Kelly J. Kuehlwein* Sally A. Linda* Bob W. Wynne' Location of Archives All original raw data, protocol, and analytical report have been archived at the 3M Environmental Laboratory. The test substance and analytical reference standard reserve samples, as well as the specimens pertaining to the analytical phase of this study are archived at the 3M Environmental Laboratory. O CmW wwwmAn fe f I e h A fs M n / 3M Environmental Laboratory Page 765 Pane 7 Page 7 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 - 5 ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Analytical Report FACTTOX-164 LIMS EOO-2738 Introduction and Purpose The purpose of the study is to determine the presence and concentration of PFOA fluorochemical in rat sera samples taken from the 3M study ` Oral (Gavage) TwoGeneration (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO/PFOA) in Rats." The sera samples are the product of the in-life study completed by Argus Research Laboratories under study number 418-020 (T6889.6). Analyses of sera samples were completed by the 3M Environmental Laboratory under study number FACT-TOX-164 (EOO-2738), and the results of these analyses are presented in this report. The analytical portion of this study was initiated on 07 June, 2001. Specimen Receipt and Maintenance Tcohlele3cMtedEantvtihroenemnednotaflthLeabino-rlaifteorsyturdecye#iv4e1d8-d0o2s0aogne solution/suspension 14 November, 2000, specimens and sera specimens collected on 18 April 2001 from Argus Research Laboratories. All dosage solution/suspension specimens were received cold in good condition on ice packs while all sera/liver specimens were received frozen in good condition on dry ice. All specimens were immediately transferred to storage at -20C 10C. Specimens that were extracted at Pace Tier2 were shipped frozen on dry ice. Table 1. Specim ens received from A rgu s Research Laboratory Study (418-020) on 14 November, 2000 Specimens Dosage Soiution/Suspension Timepolnt Day 0 Stability Day 10 Stability Concentration Total# 5 5 5 3M Environmental Laboratory 3M Environmental Laboratory Page 766 Paae 8 Page 8 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ----- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-273S Analytical Report: FACT TOX-164 LIMS E00-2738 Table 2. Specim ens received from A rgu s nesoarch Laboratory Study (418-020) on 18 April, 2001 Specim ens Serum and Liver Gender Female Male Group I II III IV V I II III IV V Total 26 26 29 29 28 30 30 30 30 29 Table 3. Specim ens received from A rgu s Research Laboratory Study (418-020) on 13 July, 2001 Specim ens Dosage Sdution/Suspension Timepoirtt Concentration Total 5 Table 4. Specim ens received from A rgu s Research Laboratory Study (418-020) on 09 A u g u st 2001 S pecim ens Serum and Liver Pender Female Male G roup I II III IV V I II III IV V T otal * 28 28 27/28 28 29 30 29 30 30 29 W Pnuim nm anfal t ahnratnrv 3M Environmental Laboratory Page 767 Paoe 9 Page 9 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 --------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Analytical Report FACT TOX-164 LIMS EOO-2738 Control matrices used in sera analyses performed during FACT-TOX-164 were obtained from commercial sources and are presented in Appendix A. Samples analyzed at the 3M Environmental Laboratory will be stored and maintained at the laboratory according to GLP requirements. Chemical Characterization of the Reference Substance Am monium perfluorooetanoate CAS Number: 3825-26-1 Chemical Formula: C7F1SC 0 0`N H / Molecular Weight: 430.9 Chemical characterization information on the reference substance ammonium perfluorooetanoate used in this study is presented in tabular form below. Table 5. Characterization of the Analytical Reference Substance in Study FACT TOX-164 Location 3M Lab PFOA Substance TCR-99030-030 S our NA Expiration D M 1CV31/2006 StOTQft C ondttorts C hantfcalLot Number uP--nh-eysn-icpao-lo-n- P urity -arc itrc 332 W h powder 95.0%' NA-- NotMtobto *SoaCrnUhamatAnatymfromCantraAna^caiLaboratorinAppanttG. THPFOS (Surrogate Standard) TCR-00017- 055 SynOuast Laboratory NA atre ioc Q75-91 White powder NA 3M Fnvimnmontal Laboratory 3M Environmental Laboratory Page 768 Pace 10 Page 10 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 Sam ple Preparation and Analysis -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-273S Analytical Report: LFIAMCSTET0O0X-2-176348 D o s* Confirm ation and S ta b ility A n alyses Dose confirmation and stability analyses were performed on test substance dose samples (concentration, Day 0 Stability, and Day 10 Stability) collected on 10 November 2000 during the in-life phase of the study: the results are presented in Appendix D. Dose confirmation and stability samples were not analyzed according to the GLPs (analyses . occurred prior to study initiation). Dose confirmation and stability extractions were performed on 17 November, 2000, 27 November, 2000, and one re-extraction performed on 17 January, 2001 by diluting these samples with Milli-Q water, then extracting the samples using the ion pair procedure, ETS-8-4.1. For one dose solution concentration sample, a matrix spike was prepared (approximately 100 ng/mL) by diluting the concentraion sample then spiking the diluted solution. In all cases, samples were analyzed versus an unextracted curve using HPLC-ES/MS/MS. The instrumental parameters and analytical conditions described in ETS-8-5.1 were used for dose solution analyses. Detailed descriptions of the methods used are located in Appendix C. S era A n alyses As per the study protocol, only serum samples from the P Generation Group I, Group IV, and Group V were analyzed in this phase study (See Table 6 for more information). An equal number of male and female rat sera samples were randomly selected for analysis. Sera samples were extracted beginning on 14 June, 2001 using an ion pairing reagent and methyl-fe/l-butyl ether (MtBE). Sample extracts were analyzed using high performance liquid chromatography-electrosprayAandem mass spectrometry (HPLCESMSMS) in the multiple reaction mode versus an extracted sera curve. PFOA levels were quantitated by external calibration. Table 6. P Generation Rat Sam ples Analyzed in Study FACT-TOX-164 Dosage Group Group 1 Group IV Group V Gender Male Female Male Female Male Female Total* 3 3 10 10 10 10 TMEnvironmental Laboratory 3M Environmental Laboratory Page 769 Paoe 11 Page 11 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ---------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Analytical Report: FLAIMCSTETOOOX--2176348 Method Sum m aries Following is a brief description of the methods used during this analytical study by the 3M Environmental Laboratory. Detailed descriptions of the methods used in this study are located in Appendix C. 3M Environm enta l Laboratory Preparatory Method ETS-8-4.1, "Extraction of Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds from Serum for Analysis using HPLC-Electrospray/Mass Spectrometry" . ETS-8-4.2, "Extraction of Fluorochemical Compounds from Serum for Analysis using HPLC-Electrospray/Mass Spectrometry" Analytical samples were extracted using an ion-pairing extraction procedure. An ion pairing reagent was added to a laboratory sample and the analyte ion pair was partitioned into methyl-fert-butyl-ether (MtBE). The MtBE phase was removed and put into a nitrogen evaporator until dry. Each extracted laboratory sample was troecao0n2st.itpumtednyinlo1n.0filtmerLinotfomgelathsasnaoul taonvdiaflsilt.ered using a 3 mL plastic syringe attached Analytical Method ETS-8-5.1, "Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry" ETS-8-5.2, "Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry" Analyses were perform ed by m onitoring one or more product ions selected from a asFinonarglelyexsaipsmr,imwplaaesr,yfmriaoognlemccheuanlartear dciotfenurr4ist1hti3ec,rostfoealpeprcoatedrduticoaueslaiotrhnfelu1po6rr9iomc(aChre3yFmi7o'i)cn.aflTouhrsePinFcghOaHArPa(LCcCt7eF/rEi1s5StCi/cMOioSOn/'M) S. 169 was m onitored for quantitative analysis. 3M EnvironmenCtanluLimanbmorwaittoo lry/ a h n ro tn rv Page 770 Pane 19 Page 12 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ----------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 Analytical Report: FACTTOX-164 LIMS E00-2738 Analytical Equipment The following is representative of the settings used during the analytical phase of this study. Liquid Chromatograph: Hewlett-Packard* Series 1100 Liquid Chromatograph system Analytical column: Keystone* BetasilTM C182x50 mm (5 pm) Column temperature: 30C Mobile phase components: . Component A: 2mM ammonium acetate Component B: methanol Flow rate: 300 pL/min Injection volume: 10 pL Solvent Gradient: 8.0 minutes Time (minutes) %B 0.0 10% ' 1.0 10% 5.5 95% 7.5 95% 8.0 10% M a ss Spectrometer: Micromass* API/Mass Spectrometer Quattro ll" Triple Quadrupole system Software: Mass LynxTM 3.4 Cone Voltage: 15-60 V Collision Gas Energy. 20-50 eV Mode: Electrospray Negative Source Block Temperature: 150C 10C Electrode: Z-spray Analysis Type: Multiple Reaction Monitoring (MRM) Table 7. Target Iona M onitored In 3M Laboratory A nalyi Target Analyte Primary Ion ( a m u ) Product Ion ( a m u ) PFOA i 413.0 169.0 THPFOS ! 427.0 80.0 3M Environmental Laboratory 3M Environmental Laboratory Page 771 Page 13 Page 13 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 - ? ------ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 Devtatfons/Am endm ents There were three deviations and one amendment from the original protocol. Deviations and amendments from the original protocol and methods are included in the Appendix B. Data Quality Objectives and Data Integrity The following data quality objectives (DQOs) were indicated in the protocol for this study: Lineality: The coefficient of determination (r2) equal to or greater than 0.990 using 1/x weighting. ' Lim its of Quantitation (LOQ): The LOQ is equal to the lowest acceptable standard in the calibration curve, defined as the lowest standard that is both 2 times the matrix blank and is calculated within 30% of the expected concentration. Acceptable Accuracy: Quality control samples are required to meet 25% accuracy, provided they are quantitated within the selected calibration range. Confirmatory Methods: if a confirmatory method is used, an amendment to the protocol will be written. Demonstration o f Specificity: PFOA identification will be substantiated by chromatographic retention time (approximately 7 minutes), by the characteristic primary ion (413) and the characteristic product ion (169). Data Summary, Analyses, and Results Data quality objectives for the analytical phase of this study outlined above and in the 3M Environmental Laboratory protocol for FA C T T O X -164 (see Appendix B) were met with the exceptions noted in this report. Fnvimnmontal I ahnmtnrv 3M Environmental Laboratory Page 772 Pane 14 Page 14 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 --------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-;738 Analytical Report: FACT TOX-164 UMS EOO-2738 Sum m ary of Q u ality Control A n alyses R e su lts Linearity: The coefficient of determination (r2) of the standard curve was >0.990. Calibration Standards: Quantitation of the target analytes was based on linear regression analysis, 1/x weighted of one extracted matrix curve. High or low points on the curve may have been deactivated to provide a better linear fit over the curve range most appropriate to the data. Low curve points with peak areas less than two times that of the extraction blanks were deactivated to disqualify a data range that may have been significantly affected by background levels of the analyte. Occasionally, a single mid-range curve point that was an obvious outiier may have been deactivated. Quantitation of each analyte was based on the response of one specific product ion using the multiple response-monitoring mode of the instrument (see Appendix C, Analytical Methods). . Lim its of Quantitation (LOQ): The LOQ is equal to the lowest acceptable standard in the calibration curve (defined as a standard within 30% of the theoretical value), and is at least two times the analyte peak area detected in the extraction blanks, (see Table # 8 below). Table 8. Determinations of the LOQ in the Analyses of Rat Sera Extracts Matrix Analyte Method LOQ Sera PFOA 5.28 ng/mL Dose Solution PFOA 1 10.0 ng/mL Blanks: All blanks were below the lower limit of quantitation for the compounds of interest. Accuracy: Accuracy was determined by analysis of CCVs and was reproducible to within 25%. Matrix Spikes: Although matrix spikes were not a quality control component of this study, because the extracted matrix curves were prepared in the same matrix as the samples (rat serum); two matrix spike tests were performed. The first test was performed prior to the stari of sample extraction/analysis to determine extraction efficiency while the second test was performed after sample extraction/analysis was complete to determine extraction efficiency and recovery. The first and second tests showed that the extraction efficiency versus unextracted curves was within 35%. The second test showed that matrix spike recoveries were within 25% of the theoretical concentration versus extracted matrix curves, (see Table # 9 below). 3M Environmental Laboratory 3M Environmental Laboratory Page 773 Paae 15 Page 15 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ------------ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 Table 9. Matrix Spike Recoveries in the A nalyses of Rat Sera Extracts Concentration Recovery versus an Unextraetad Curve Recovery versus an Extracted Matrix Curve Prior to Sample Analyses After Sample Analyses 25ng/mL 500ng/mL 50ngTmL 1500ng/mL 64% 67% 96% 87% NA NA 108% 86% 50000 ng/mL 75% 89% Spike Recoveries: Spike recoveries of 25% of expected values were achieved for all continuing calibration verifications spiked in the control matrix. Surrogates: The surrogate (THPFOS) was added to all samples and standards. THPFOS was not used for quantitation, but was used to monitor for gross instrument failure. The surrogate response of each analytical run was verified to determine that it did not vary more than 50% from the mean within each analytical run. Extracts which were diluted 1:50 or 1:1000 showed surrogate deviations lower than 50%. Since these were consistently low, these outliers will not affect the outcome of this study. Statem ent o f D ata Q uality It is not possible to verify true recovery of endogenous analyte from tissues without radio labeled reference material. The only measurements of accuracy available at this time, calibration curve verification recoveries and matrix spike recoveries, indicate that these data are quantitative to 25% or greater. Summ ary of Sam ple R esults PFOA results (those obtained using lot # 332) have been corrected for purity of the analytical reference material. D o se Confirm ation and Stability A nalyses: PFO A in the Day 0, Day 10, and concentration samples were considered to be stable for at least 2 months. Initial analysis on 11/27/00 and the last analysis on 01/23/01 showed a 12% drop in recovery, which is not considered to be significant. Sam ples from Control Anim als: Low levels of PFOA were detected in the male sera of the control animals. % Sam ples from D osed Anim als: In general, PFOA levels found in female sera of the test animals increased from dose group 4 to group 5. PFOA levels found in male sera remained the same between dose group 4 and 5. Significant differences between male and female PFOA levels were observed in these data. Detailed sample data tables are presented in Appendices D and E. 3M Environmental Laboratory 3M Environmental Laboratory Page 774 Pane 1ft Page 16 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 --------- ARGUS 418-020 Analytical Report: FACT TOX-164 L1MS EOO-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 Statistical Methods and Calculations Statistical methods were limited to the calculation of means and standard deviations. See Appendix F for example calculations used to generate the serum sample data in FACT TOX-164. Statement of Conclusion Under the conditions of the present studies, the fluorochemical PFOA was observed in the sera of all rats dosed with the test substance during the in-life phase of the study. References None AM Fnuim hm antal I ahnratnru 3M Environmental Laboratory Page 775 Pano 17 Page 17 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ? ------ ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 Analytical Report: FUAMCST TEO00X--2176348 Appendix A: Chemical Characterization, and Control Matrices Table 10. Characterization of the Control Matrices Used for Sera Analyses in Study FACT-TOX-164 Control Matrix Rat Serum TN-A-4516 Source Expiration Date Storage ContStions ChemcaiLot # Physical Description Sigma-AJdnch 02/14/06 Frozen -20C 019H89291 Rat Serum Table 11. Characterization of Test Substance in Study FACT-TOX164 Test Substance Chemical Name Source Ammonium Pertluorooctanoate APFOPFOA TCR-99030-030 NA Expiration Data 1031/2006 Storage Conditions -20C10C Chem ical Lot # 332 Physical Description White powder Purity 95.0%* NAr--Not available See tne Certificate at Analysis tram d m Analytical laooratones in Acoam kt G. 3M EnvironmentalLaboratory 3M Environmental Laboratory Page 776 Page 18 Page 18 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 -'7 -- ARGUS 418-020 Analytical Report: FACT TOX- 1 6 4 LIMS EOO-ZoS Analytical Report: UFAMCSTET0O0X-2-173684 Appendix B: Protocol, Amendments, and Deviation(s) U Fnvimnmantal I ahnmtnrv 3M Environmental Laboratory Page 777 Pam 19 Page 19 3M Medical Department Study: T-6889.6 Anal-y-t-i-calARRepGonU:SFA41C8T-0T2O0X-164 Protocol FACT-TOX-L1I6M4S E00-2738 Phase Title Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO/PFOA) in Rats PHASE PROTOCOL Performing Laboratories 3M Environmental Technology & Safety Services 3M Environmental Laboratory 935 Bush Avenue St. PauLMN 55106 Pace Analytical Services. Inc. 1700 Elm Street SE, Suite 100 Minneapolis, MN 55414 Laboratory Project Identification FACT-TOX Number TOX-164 3M Toxicology Study Number T-6889.6 Argus In-life Study Number 418-020 L IM S EOO-2738 3M Environmental Laboratory 3M Environmental Laboratory Page 778 Page 1of io Page 20 3M Medical Department Study: T-6889.6 . ARGUS 418-020 Analytical Report: FACT TOX-164 ProtocolFACT-TOXL-1I6M4S EOO-2738 Study Identification Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO/PFOA) in Rats Sponsor Sponsor Representative Study Director Phase Locations PrincipalAnalytical Investigator (PA!) Analytical Testing Laboratories 3M Corporate Toxicology 3M Medical Department Building 220-2E-02 St. Paul. MN 55144 David Sanders, Ph.D. 3M Corporate Toxicology 3M Medical Department Building 220-2E-02 St. Paul. MN 55144 Telephone: (651) 733-5226 John Butenhoff, Ph.D. 3M Corporate Toxicology 3M Medical Department Building 220-2E-02 St. Paul. MN 55144 Telephone: (651) 737-1962 Lisa Clemen 3M Environmental Laboratory Building 2-3E-09 935 Bush Avenue St. Paul. MN 55106 Telephone: (651) 778-6176 Proposed Phase Timetable Analyses Start Date Analyses Termination Date Pace Analytical Services, Inc. 1700 Elm Street SE, Suite 100 Minneapolis, MN 55414 May 28.2001 November 30, 2001 3M Environmental Laboratory 3M Environmental Laboratory Page 779 Page2 of fin ,. Page 21 3M Medical Department Study: T-6889.6 Protocol FACT-TOXL-I1M64S EOO-2738 1. Study Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO/PFOA) in Rats 2. Purpose The analytical phase of this study is designed to evaluate levels of PFOA in sera specimens of FOgeneration male and female rats exposed and FI generation rat pups potentially exposed to APFO in Argus In-life Study 418-020. Sera samples will be extracted at Pace Analytical Services Inc. Tier II facility. Sera samples will be analyzed at the 3M Environmental Laboratory. Data quality objectives for this study are indicated in section 3. Regulatory Compliance This study will be conducted in accordance the United States Environmental Protection Agency Good Laboratory Practice Standards: Final Rule. 40 CFR Part 160/Pan 792. 4. Quality Assurance The 3M Environmental Laboratory Quality Assurance Unit will audit the study conduct, raw data, and final report to determine compliance with Good Laboratory Practice regulations, this protocol, and 3M Environmental Laboratory Standard Operating Procedures. .5 Reference Substance For FACT-TOX-164 Ammonium Perfluorooctanoate (APFO/PFOA), CrFisCOONH*. CAS 3825-26-1 . The target analyte is perfluorooctanoate (PFOA), CrFisCOO'. 6 Test Substance Ammonium Perfluorooctanoate (APFO/PFOA), CtFisCOO'NIL'L CAS 3825-26-1 7. Te s t S ystem Five dose groups (30/sex/group for a total of 300) of male and female rats (P Generation) were given the test substance by oral (gavage) route. After cohabitation of the P Generation, five groups of male and female rats (30/sex/group for a total of 300) will be selected from FI Generation pups for continued evaluation. FI Generation rats will be given the same dosage level of the test substance as their respective P Generation sires and dams. At scheduled sacrifice (after completion of the cohabitation period for males and day 22 postpartum for females), blood and liver samples were collected and shipped to 3M Environmental Laboratory. 3M EnvironmentalLaboratory 3M Environmental Laboratory Page 780 3M Medical Department Study: T-6889.6 7 ------ ARGUS 418-020 Analytical Repon: FACT TOX-164 Protocol FACT-TOXL-I1M64S EOO-2738 Num ber of Specim ens per D o sage group and D o sage Levels Dosage Group l n w IV V Number of Rats per Sex 30 30 30 30 30 Dosage (mg/kg/day) 0 1 3 10 30 Concentration (mg/mL.) 0 0.2 0.6 2 6 For this phase study, 40-- 100 sera samples from Group IV (10 mg/kg/day) and Group V (30 mg/kg/day) from the P Generation only will be analyzed. An equal number of male and female samples will be randomly selected from the two dose groups. Modifications to the number of samples analyzed may be implemented at the discretion of the PAI and the Study Director. 8. S pecimen Receipt Sera specimens were received from Argus Research Laboratories, Inc. at the end of the in life phase on April 18, 2001. Sera specimens were shipped by overnight courier and were received frozen on dry ice. Specimens were identified with sample numbers (lab request numbers or numbers assigned by Argus Research Laboratories, Inc.) upon receipt, registered with the 3M Environmental Laboratory and transferred to a freezer for storage. All specimens sent to the 3M Environmental Laboratory were received and tracked according to the Sample Tracking System Standard Operating Procedure. Details of specimen inspection for damage, receipt, storage, identification, chain of custody, protocols and data will be presented in the phase report. 9. Preparatory Methods ETS-8-4, "Extraction of Fluorochemical Compounds from Serum for Analysis using HPLC-Electrospray/Mass Spectrometry" Analytical samples are extracted using an ion-pairing extraction procedure. An ion-pairing reagent is added to a laboratory sample and the analyte ion pair is partitioned into methylrert-butyl-ether (MtBE). The MtBE extract is then removed and put onto a nitrogen evaporator until dry. Each extracted laboratory sample is reconstituted in 1.0 mL of methanol and filtered through a 3 cm3plastic syringe attached to a 0.2 pm nylon filter into glass autovials. 10. A nalytical Methods ETS-8-5, "Analysis of Potassium Perfluorooctanesulfonate or other Fluorochemicals in Serum Extracts using HPLC-Electrospray/Mass Spectrometry" 3M Environmental Laboratory 3M Environmental Laboratory Page 781 Page 4 of0 IQ - I . . I . Page 23 3M Medical Department Study: T-6889.6 ----------- ARGUS 418-020 Analytical Report: FACT TOX-164 Protocol FACT-TOLX-I1M64S E00-2738 Analysis is performed by monitoring one or more product ions selected from a single primary ion characteristic of a particular fluorochemical using HPLC-ESMSMS. For example, molecular ion 413, selected as the primary ion for PFOA (CtFijCOO ) analysis, is fragmented iurther to produce ion 169 (C3F7'). The characteristic ion 169 is monitored for quantitative analysis. Minor modifications to the preparatory and analytical methods may be implemented at the discretion of the PAL 11. Data Quality Objectives 11.1 Linearity The coefficient of determination (r2) of the standard curve must be equal to or greater than 0.990 using 1/x weighting. ' 11.2 Limits of Quantitation (LOQ) The LOQ will be equal to the lowest acceptable standard in the calibration curve, defined as the lowest standard that is both 2 times the matrix blank and is calculated within 30% of the expected concentration. 11.3 Acceptable Accuracy Quality control samples are required to meet 25% accuracy, provided they are quantitated within the selected calibration range. 11.4 Use o f Confirmatory Methods If a confirmatory method is used, an amendment to this protocol will be written. 11.5 Demonstration of Specificity, etc. PFOA identification will be substantiated by chromatographic retention time (approximately 7 minutes), by the characteristic primary ion (413) and the characteristic product ion (169). Minor modifications to the Data Quality Objectives may be implemented at the discretion of the PAL 12. S ub-Contracted A nalysis Pace Analytical Services, Inc. (Tier n Facility) will be performing the extraction of serum specimens for analyses. All extracted samples will be shipped to the 3M Environmental Laboratory for analysis. Pace Analytical Services, Inc. will follow all applicable 3M Environmental Laboratory Standard Operating Procedures and the following Pace Analytical Inc. Standard Operating Procedures. PSS-Admin-01 Quality System PSS-Admin-04 Laboratory Facilities PSS-Admin-06 Training Record Files Maintained by QAU PSS-ARC-02 Disposition of Archive Materials 3M Environmental Laboratory 3M Environmental Laboratory Page 782 Page 5 of STId .i Page 24 3M Medical Department Study: T-6889.6 Analytical Protocol FACT-TOXL-1I6M4S E00-2738 PSS-ARC-04 Archiving Data, Specimen and Logbooks PSS-DC-05 Lab Notebooks, Logbooks, and Phone Logs PSS-DM-03 Statistical Evaluation of Data PSS-OPS-01 Use and Maintenance of Ultra-Turrax T25 Homogenizer PSS-OPS-02 Raw Data PSS-OPS-03 Hazardous Waste Disposal PSS-OPS-04 Use and Maintenance of N-Evap Analytical Evaporator PSS-OPS-05 Use of Compressed Gases in the Laboratory PSS-OPS-06 Use and Maintenance of NANOpure II Water Purification System PSS-OPS-07 Cleaning Non-disposable Volumetric Pipettes . PSS-OPS-08 Laboratory Calculations PSS-OPS-09 Deviations from Established Procedures PSS-OPS-10 Analytical Definitions PSS-OPS-11 Use and Calibration of a Bottle-Top Dispenser . PSS-OPS-13 Use and Maintenance of Lab Refrigerators, Freezers, and Ovens PSS-OPS-14 Use and Calibration of Syringes with a Hamilton Chaney Adapter PSS-OPS-15 Glassware Cleaning PSS-OPS-16 Use and Maintenance of the Fisher Scientific Isotemp Freezer PSS-OPS-17 Use and Maintenance of Ultrasonic Water Baths (Sonicators) PSS-OPS-18 Use and Maintenance of Vortex Shakers PSS-OPS-24 Use and Maintenance of a Desiccator PSS-OPS-31 Use and Maintenance of Shakers PSS-OPS-32 Operation, Maintenance and Calibration of Laboratory PSS-OPS-37 Operation, Maintenance, and Calibration of pH Meters and pH Electrodes PSS-MC-01 Purchasing of Laboratory Supplies PSS-MC-02 Receipt of Laboratory Supplies PSS-MTR-01 Calibration of Certified Weight Set PSS-MTR-02 Calibration of Certified Thermometcrs/Thermocouples PSS-MTR-05 Calibration of Eppendorf Pipettes PSS-MTR-06 Verification of Calibration of the Eppendorf Pipettor PSS-MTR-07 New Equipment Qualification (IQ, PQ, OQ) PSS-MTR-08 Verification of Calibration and Use of Analytical Balances PSS-MTR-09 Use and Maintenance of Fisher Scientific Electronic Temperature Monitoring Devices PSS-Safety-01 General Laboratory Safety PSS-Safety-02 Use and Maintenance o f Biological Safety Cabinets PSS-Safety-04 Emergency Evacuation Procedures PSS-Safety-05 Use and Maintenance of Laboratory Fume Hoods PSS-TS-01 Training Procedures 13. S tatistical A naly sis Statistical methods will be limited to the calculation of means and standard deviations. Examples of the calculations used in the analyses will be included in the phase report. 3M EnvironmentalLaboratory 3M Environmental Laboratory Page 783 Page 6 of ? to ur . I J . Page 25 3M Medical Department Study: T-6889.6 - ------- ARGUS 418-020 Analytical Repon: FACT TOX-164 Protocol FACT-TOX-L1I6M4 S EOO-2738 14. Report A report of the analyte results will be prepared by 3M Environmental Laboratory. The report will include, but not be limited to, the following, when applicable: 14.1 Name and address of the facility performing the phase. 14.2 Dates upon which the phase was initiated and completed. 14.3 A statement of compliance by the PAI addressing any exceptions to Good Laboratory Practice Standards. 14.4 Objectives and procedures as stated in the approved phase protocol, including any amendments to the original phase protocol. 14.5 Identity, purity, stability and the solubility of the reference standard under the conditions of use. 14.6 A description of the methods used to conduct the test(s). 14.7 A description of the specimens. 14.8 A description of any circumstances that may have affected the quality or the integrity of the data. 14.9 The name of the PAI and the names of other scientists, professionals, and supervisory personnel involved in the phase. 14.10 A description of the transformations, calculations, or operations performed on the data, a summary and analysis of the analytical chemistry data, and a statement of the conclusions drawn from the analyses. 14.11 Statistical methods used to evaluate the data, if applicable. 14.12 The signed and dated reports of each of the individual scientists or other professionals involved in the phase, if applicable. 14.13 The location where raw data and the phase report are to be stored. 14.14 A statement prepared by the Quality Assurance Unit listing the dates that study inspections and audits were made and the dates of any findings reported to the Study Director and Management. 14.15 If it is necessary to make corrections or additions to a final report after it has been accepted, the changes will be made in the form of an amendment issued by the Study Director. The amendment will clearly identify the part of the final report that is being amended, the reasons for the amendment, and will be signed by the Study Director. 3M Environmental Laboratory 3M Environmental Laboratory Page 784 Page 7 of Page 26 3M Medical Department Study: T-6889.6 - 7 ------- ARGUS 418-020 Analytical Report: FACT TOX-164 ProtocolFACT-TOXL-1I6M4S E00-2738 15. Location of Ra w Data, Records, and Final Report Original data or copies thereof, will be available at 3M Environmental Laboratory to facilitate audits of the study during its progress and before acceptance of the phase report. When the phase report is completed, all original paper data, including those items listed below will be retained in the archives of 3M Environmental Laboratory. All corresponding training records, calibration records, instrument maintenance logs, standard operating procedures, equipment procedures, and methods will be retained in the archives of the 3M Environmental Laboratory. 15.1 The following raw data and records will be retained in the study folder in the archives according to 3M Environmental Laboratory Standard Operating Procedures. 15.1.1 Approved protocol and amendments 15.1.2 Study correspondence - 15.1.3 Shipping records 15.1.4 Raw data 15.1.5 Approved final report (original signed copy) 15.1.6 Electronic copies of data 15.2 The following supporting records will be retained separately from the study folder in the archives according to 3M Environmental Laboratory Standard Operating Procedures: 15.2.1 Training records 15.2.2 Calibration records 15.2.3 Instrument maintenance logs 15.2.4 Standard Operating Procedures, Equipment Procedures, and Methods 16. Data / S ample Retention All sera specimens remaining after the analytical phase is completed will be sent to and maintained by: Lisa Clemen 3M Environmental Laboratory Building 2-3E-09 935 Bush Avenue St. Paul, MN55106 3M EnvironmentalLaboratory 3M Environmental Laboratory Page 785 Page 8 of SIP Page 27 3M Medical Department Study: T-6889.6 FACT TX-164 Protocol FACT-TOXL-1IM64S EOO-2738 17. Protocol A mendments and deviations Planned changes to the protocol will be in the form of written amendments signed by the Study Director and the Sponsor's Representative. Amendments will be considered as part of the protocol and will be attached to the final protocol. All changes to the protocol will be indicated in the phase report. Any other changes will be in the form of written deviations, signed by the Study Director and filed with the raw data. 18. Attachments 18.1 Attachment A: Material Safety Data Sheets (MSDS) for Reference Standard 3M Environmental Laboratory 3M Environmental Laboratory Page 786 Page 9 of 0 to Page 28 3M Medical Department Study: T-6889.6 19. S ignatures David Sanders. Ph.D., Sponsor Representative John Butenhojf, Ph.D., Study Director -- - -- ------- ARGUS 418-020 Analytical Report: FACT TOX-164 Protocol FACT-TOXL-1IM64S EOO-2738 f/f / Date Q/ 07/ * f Date Lisa Clemen.. Principal Analytical Investigator ____________ Pk/ow /o, Date 3M EnvironmentalLaboratory 3M Environmental Laboratory Page 787 Page 10of 910^ ' Page 29 3M Medical Department Study: T-6889.6 ----------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 Study Title Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO/PFOA) in Rats PROTOCOL AMENDMENT NO. 1 Amendment Date: November 17, 2000 Performing Laboratory 3M Environmental Technology & Safety Services 3M Environmental Laboratory 935 Bush Avenue St. Paul, MN 55106 Laboratory Project Identification 3M Medical Department Study: T-6889.6 Argus In-Life Study: 418-020 Analytical Report: FACT TOX-164 3M LIMS No. E00-2738 .1/MFnvim nm tm tal Laboratory/ 3M Environmental Laboratory Page 788 Pace 1 of 3 Page 30 3M Medical Department Study: T-6889.6 Analytical Report: FACT 164 LIMS E00-2738 Protocol FACT TOX-001 Amendment No. 1 This amendment modifies the following portion(s) of the protocol: 1. Protocol reads: Dose confirmation was not discussed in the Environmental Laboratory analytical phase protocol. A mend to read: 2. The dose confirmation and stability samples were prepared and analyzed prior to the start of the analytical phase of this study. These samples were not prepared or analyzed according to the GLPs. Methods ETS-8-4.1 and ETS-8-5.1 were loosely followed. The results will be reported in the final analytical report. - Reason: From the protocol for the Primedica study: Analyses of Prepared Formulations: Concentration: Concentration of the prepared formulations will be verified during the course of this study. Duplicate samples will be taken from each concentration on the first and last days of preparation. One sample of each duplicate set will be shipped for analysis; the remaining samples will be retained as backup samples. Backup samples will be stored under the previously cited conditions and discarded at the Testing Facility upon the request of the Sponsor. Stability: Stability of the prepared formulations will be documented during this study. Two sets of duplicate samples (2 mL each) from each concentration will be taken on the first day of preparation. One sample of each duplicate set will be shipped on the day of preparation. These samples will be analyzed at the following time points: as soon after preparation as possible and ten days after the first analysis. The remaining samples will be retained at the Testing Facility as backup samples. Backup samples will be stored under the previously cited conditions and discarded at the Testing Facility upon the request of the Sponsor. Stability measurements demonstrate that the prepared test article will be stable for ten days. It is best to perform this prior to the analytical phase study initiation to ensure that prepared dosing mixtures will remain stable and thus avoid the cost and potential error of preparing doses each day. Also, no approved/validated methods were in place for dose confirmation analysis. Pnvim nm ontal I ahnratnrv 3M Environmental Laboratori' Page 789 Paoe 2 of 3 Page 31 3M Medical Department Study: T-6889.6 Amendment Approval ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Protocol FACT TOX-001 Amendment No. 1 DavidSanders, Sponsor Representative John L Butenhoff, Ph.D., Study Director Date Z Date 3M Environmental Laboratorv 3M Environmental Laboratory Page 790 Paoe 3 of 3 Page 32 3M Medical Department Study: T-6889.6 LIMS E00-2738 R e cord o f D eviation I. Identification Study/Project No. FACT-TOX-164 Argus418-020 LIMSEOO-2738 Deviation Type (Check one) QSOP X Method 0 Equipment Procedure 0 Protocol Other: Document Numbers): ETS-8-4.2, ETS-8-5.2 Date(s) of occurrence: _____________________________II_._D__e_s_cr0ip6/t1io4n/0:1,06/15/01____________________ Required Procedure/process: Method ETS-8-4.2 does not list matrix spikes as a QC parameter if the curve is prepared in the same matrix as the samples (i.e. rat serum calibration curves and rat serum samples). ' Method ETS-8-5.2 states five points, at a minimum, are to be used to generate the calibration curve and the curve r must be > 0.990. j j I ; ! Actual Procedure/process: Matrix spikes were prepared (06/14/01) prior to the start ofthe sample extraction in order to determine extraction efficiency and to determine the endogenous level of target analyte present ; in the commercially available serum. For this commercially available serum, endogenous levels were below 1.00 ppb for the target analyte. This serum was then used to prepare the extracted matrix calibration curve and continuing calibration verifications for this study. These sample extracts were analyzed on 06/15/01. For this analysis, not all stated QC criteria were followed. Only four points were used for the calibration curve instead of five points and the r2value was 0.9831 instead of 0.9900. Since these data are screening quality only and additional matrix spikes will be extracted at the end of the study these data are OK as entered. These sample extracts were not reanalyzed._______________ III. Actions Taken: (such as am endm ent issued. SO P revision, etc.) This deviation was written. Recorded By Lisa A. Clemen & ** \ IV. Impact on Study / Project No adverse impact on the outcome of this study. Date 08/10/01 OJ lobi Authorized By (StudyDirector / Project Lead) K ltfiiU u r fr 27 6T Ss<**-____ 2<5Se>/ Date tuiln D .rtilw - Tohn (kd&tn&i't puna.- RtfftJe/iMvt,. Do,,.il Abmfierr 3M E nvironm ental Laboratory Devia_tion No. _____1 Form ETS-4~8.0 (assigned by Study Director or Project Lead at the end of study or project) 3M Environmental Laboratory Page 33 3M Medical Department Study: T-6889.6 Record of Deviation 1. Identification -------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study / Project No. FACT-TOX-164 Argus 418-020 LIMS EOO-2738 Deviation Type (Check one) 1] SOP 0 Method 0 Equipment Procedure X Protocol 0 Other: Document Numbers): FACT-TOX-164 Date(s) of occurrence: II. Descr0i6p/t1io9/n0:1 Required Procedure/process: Section 7 states: An equal number o f male and female samples will be randomly selected from the two P generation dose groups (group IV - 10 mg/kg/day and group V - 30 mg/kg/day) ' Actual Procedure/process: An equal number of male and female samples were randomly selected from the two P generation dose groups (group IV -1 0 mg/kg/day and group V - 30 mg/kg/day.) In addition, 3 male and 3 female samples were randomly selected from the P generation control group (group 1 - 0 mg/kg/day) III. Actions Taken: (such as am endm ent issued, SO P revision, etc.) This deviation was written. Recorded By Date Lisa A. Clemen A Ch/tlriA. IV. Impact on Study / Project 08/10/01 _____ DS/l&io{ These samples' results will add useful information concerning endogenous levels present in the control group. No adverse impact on this study. Authorized By (Study Director / Project Lead) Date rQ Q TShZfaJ' itucU Oifictw John IWe/ih&W' jptM-OEr RlfrUMTOrWt DtW.il ScOtiu 3M Environm ental Laboratory Form E TS-4-8.0 s~ Se**- Deviation No. 1 (assigned by Study Director or Project Lead at the end o f study or project) 3M Environmental Laboratory Page 34 Page 792 3M Medical Department Study: T-6889.6 Record of Deviation I. Identification ----------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 S tu d y /P ro ject NoT FACT-TOX-164 A rg u s418-020 LIMS EOO-2738 Deviation Type (Check one) SOP X Method Equipment Procedure Protocol Other: Document N um bers): ETS-4-1, ETS-8-5.F Date(s) o f occurrence: II. Description:______________________________________________01/17/01,01/23/01______________________ Required Procedure/process: M ethods state:_A matrix spike and m atrix spike duplicate will be extracted and analyzed per forty samples, with a minimum o f 2 per batch. Actual Procedure/process: On the dose confirmation extraction performed 01/17/01 no matrix spike or matrix spike duplicate were prepared and subsequently were not analyzed on 01/23/01. III. Actions Taken: (such as amendment issued. SO P revision, etc.) This deviation was written. Recorded Bv Date Lisa A. Clemen Jj 10/05/01 IV. Impact on Study/ Project JD/ds/ di This omission will not have an adverse impact on this study, other quality control aspects o f the analysis were included (blanks, continuing calibration verifications) which met method criteria. Authorized By (Stu< tor / Project Lead) , Date A> Slu^oiitcrcT 3*hn Iporvitr RtprejeAaW Davrd 3M Environmental Laboratory Form ETS-4-8.0 Deviation No. (assigned by Study Director or Project Lead at the end of study or project) 3M Environmental Laboratory Page 35 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 A7nalytical RAeRpoGrtU: SFA4C1T8-T0O2X0-164 LIMS E00-2738 Analytical Report FACT TOX-164 LIMS E00-2738 Appendix C: Extraction and Analytical Methods This appendix includes the following methods: ETS-8-4.1, Extraction of Potassium Perfiuorooctanesulfonate or Other Fluorochemical Compounds from Serum for Analysis using HPLC-Electrospray/Mass Spectrometry, (14 pages) ETS-8-4.2, Extraction of Fluorochemical Compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry, (15 pages) ' ETS-S-5.1, Analysis of Potassium Perfiuorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (9 pages) ETS-8-5.2, Analysis of Potassium Perfiuorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (11 pages) 3M EnvironmentalLaboratory 3M Environmental Laboratory Page 794 Paae 20 Page 36 3M Medical Department Study: T-6889.6 3 M ENVIRONMENTAL LABORATORY - ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Method Extraction of Potassium Perfluorooctanesulfonate or Other Fluorochemical compounds from Serum for Analysis Using HPLC- Electrospray/Mass Spectrometry Method Number: ETS-8-4.1 Adoption Date: 03/01/99 Author Lisa Clemen, GlennLangenburg Revision Date: W/37^ Approved By: i> f i i -- Laboratory Manager (Jt--------- Group Leader Date Ht u f t 3 Date A _________________________ _____ _____________ Technical Reviewer ov/atA f Date t a t CopyofOriginal initial Data 1.0 Scope and Application_______________ ;______ ;_____________________________ 1.1 Scope: This method is for the extractionofpotassiumperfluorooctanesulfonate (PFOS) or other fluorochemical compounds fromserum. 1.2 Applicable compounds: Fluorochemical surfactants orother fluorinated compounds. 1.3 Matrices: Rabbit, rat, bovine, monkey, andhumanserum or other fluids as designated in the validation report Word 6/95 3M Environmental Laboratory ETS-8-4.1 T * TDTTACAmCm>< Page 795 Page 1 o f 14 Page 37 3M Medical Department Study: T-6889.6 ------------ ARGUS 418-020 Analytical Repon: FACT TOX-164 LIM S EOO-2738 2.0 Summary of Method_________________________________________________ __ 2.1 1 This method describes the procedure for extracting potassiumperfluorooctanesulfonate (PFOS) orother fluorochemical surfactants fromserum, orother fluids, using an ion pairing reagent andmethyl-teri-butyl ether (MtBE). In this method, seven fluorochemicals were extracted: PFOS, PFOSA, PFOSAA, EtFOSE-OH, PFOSEA MS56, and surrogate standard (see 3.0 Definitions). An ion pairing reagent is added to the sample and the analyte ion pair is partitioned into MtBE. The MtBE extract is removed andput onto a nitrogen evaporator until dry. Each extract is reconstituted in 1.0 mL of methanol, then filtered through a 3 cc plastic syringe attached to a 0.2 pm nylon filter into glass autovials. 2.2 These sample extracts are analyzed following method ETS-8-5.1 or other appropriate methods. . . 3.0 Definitions_______________________________________________.________________ 3.1 PFOS: perfluorooctanesulfonate (anion ofpotassium salt) C,F,7S03' 3.2 PFOSA: perfiuorooctane sulfonylamide CgFjTSOjNHj 33 PFOSAA: perfluorooctane sulfonylaxnido (ethyl)acetate CtF,TSOJN(CH2CHj)CHiCOI' 3.4 EtFOSE-OH: 2(N-ethylperfluorooctane sulfonamido)-ethyl alcohol CtF17S 0 2N(CHJCH3)CHICH20H 33 PFOSEA: perfluorooctane sulfonyl ethylamide C,F17SOjN(CH2CH3)H 3.6 M556: C.FpSOjNiHXCHjCOOH) 3.7 Surrogate standard: 1H-1H-2H-2Hperfluorooctane sulfonic acid 4.0 Warnings and Cautions___________________________________________________ 4.1 H ealth and safety w arnings 4.1.1 U se universal precautions, especially laboratory coats, goggles, and gloves when handling animal tissue, which may containpathogens. - 5.0 Interferences__________ ;_________________________________________________ 5.1 There are no interferences known at this time. 6.0 Equipment_______________________________________________________________ 6.1 The following equipment is used while performingthis method. Equivalent equipment is acceptable. 6.1.1 Vortex mixer, VWR, Vortex Genie 2 6 .1.2 Centrifuge, Mistral 1000 orlEC 6.13 Shaker, Eberbach orVWR 3M Environmental Laboratory ETS-8-4.1 -- --- cr Page 796 Page 2 o f14 Page 38 3M Medical Department Study: T-6889.6 --------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 6.1.4 Nitrogen evaporator, Organomation 6.1.5 Balance ( 0.100 g) 1 7.0 Supplies and Materials 7.1 Gloves 7.2 Eppendorfordisposable pipettes 13 Nalgene bottles, capable ofholding 250 mLand 1L 7.4 Volumetric flasks, glass, type A - 73 I-CHEM vials, glass, 40 mL glass 7.6 Centrifuge tubes, polypropylene, 15 mL 7.7 Labels - 7.8 Oxford Dispenser- 3.0 to 10.0 mL 7.9 Syringes, capable ofmeasuring 5 pL to 50 pL . 7.10 Graduatedpipettes 7.11 Syringes, disposableplastic, 3 cc 7.12 Syringe filters, nylon, 0 2 pm, 25 mm 7.13 Timer 7.14 Crimp cap autovials and caps 7.15 Crimpers Note: Prior to using glassware andbottles, rinse 3 times with methanol and3 times with Milli-QTMwater. Rinse syringes a minimum of9 times withmethanol, 3 rinses from 3 separate vials. 8.0 Reagents and Standards__________________________________________________ 8.1 Type 1 reagent grade water, Milli-QTM or equivalent; all water used in this method should be Milli-QTM water andmaybe providedby aMilli-Q TOCPlusTMsystem 8.2 Sodium hydroxide (NaOH), J.TBakerorequivalent - 823 Tetrabutylammoniumhydrogen sulfate(TBA), Kodak or equivalent ' 8.4 Sodium carbonate (NajCOj), J.T. Baker or equivalent 8.5 Sodium bicarbonate (NaHCOj), J.T. Bakeror equivalent 8.6 Methyl-T-Butyl Ether, Omnisolv, glass distilled orHPLC grade 8.7 Methanol, Omnisolv, glass distilled orHPLC grade 8 .8 Serum or blood, frozen from supplier 8.9 Fluorochemical standards 8.9.1 PFOS (3M Specialty Chemical Division), molecularweight = 538 8.9.2 PFOSA (3M Specialty Chemical Division), molecularweight = 499 . 3M Environmental Laboratory ETS-8-4.1 F.Ytmetinn nfP F O S frn tn S w im i Page 3 o f 14 Page 39 Page 797 3M Medical Department Study: T-6889.6 ------------ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 8.93 PFOSAA (3M Specialty Chemical Division), molecular weight = 585 8.9.4 EtFOSE*OH(3M Specialty Chemical Division), molecularweight = 570 8.9.5 PFOSEA (3M Specialty Chemical Division), molecular weight = 527 8.9.6 M556 (3M Specialty Chemical Division), molecularweight = 557 8.9.7 Surrogate standard: 4-H, perfluorooctane sulfonic acid (1-H,1-H, 2-H, 2-H C ,F13SOjH) molecular weight = 428 8.9.8 Otherfluorochemicals, as appropriate 8.10 Reagent preparation ' NOTE: Whenpreparing larger volumes thanlisted in reagent, standard, or surrogate preparation, adjust accordingly. 8.10.1 10N sodiumhydroxide (NaOH): Weigh approximately 200 g NaOH. Pour into a 1000 mLbeaker containing 500 mLMilli-QTM water, mix until all solids are dissolved. Store in a 1 LNalgene bottle. 8.10.2 1N sodium hydroxide (NaOH): Dilute 10 N NaOH 1:10. Measure 10 mL of 10 N NaOH solution into a 100 mLvolumetric flask and dilute to volume using Milli-QTMwater. Store in a 125 mLNalgene bottle. 8.10.3 0.5 Mtetrabutylammoniumhydrogen sulfate (TBA): Weigh approximately 169 g ofTBA into a 1 L volumetric containing 500 mLMilli-QTMwater. Adjust to pH 10 using approximately 44 to 54 mLof 10N NaOH (While adding the last mL of ' NaOH, add slowly because thepH changes abruptly). Dilute to volume with Milli-QTM water. Store in a 1 LNalgene bottle. 8.10-3.1 TBA requires a check prior to each use to ensure pH= 10. Adjust as needed using 1N NaOH solution. 8.10.4 0.25 M sodium carbonate/sodium bicarbonate buffer (NajCOj/NaHCOj): Weigh approximately 26.5 g of sodiumcarbonate (NajCO,) and21.0 g of sodium bicarbonate (NaHCOj) into a 1L volumetric flask andbring to volume with MilliQTMwater. Store in a 1L Nalgene bottle. 8.11 Standards preparation 8 .11.1 Prepare PFOS standards for the standard curve. 8.11.2 Prepare otherfluorochemical standards, as appropriate. Multicomponent fluorochemical standards areacceptable (for example, one working standard solution containing 1.00 ppmPFOS, 1.02 ppmPFOSA, 0.987 ppmPFOSAA, and 1.10 ppmEtFOSE-OH.) 8 .1 1 2 Weigh approximately 100 mg ofPFOS into a 100 mLvolumetric flask andrecord the actual weight 8.11.4 Bring to volume with methanol for a stock standard of approximately 1000 ppm (jig/mL). . 8.11.5 Dilute the stock solution with methanol for aworking standard 1 solution of approximately 50 ppm. 8.11.6 Dilute working standard 1with methanol for aworking standard 2 solution of approx. 5.0 ppm. . 3M Environmental Laboratory ETS-8-4.1 c,p-- ., i/orne c--. Page 4 of 14 Page 40 Page 798 3M Medical Department Study: T-6889.6 ^ ------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 8.11.7 Dilute working standard 1with methanol fora working standard3 solution of approx. 0.50 ppm. 8.12 Surrogate stock standard preparation 8.12.1 Weigh approximately 50-60 mg ofsurrogate standard 1-H.l-H, 2-H, 2-H, C,F,,SO]H into a 50 mL volumetric flask and record the actual weight. 8.12.2 Bring to volume with methanol fora surrogate stock of approximately 1000-1200 ppm. 8.12.3 Prepare a surrogate working standard. Transferapproximately 1mL of surrogate stock to a 10 mL volumetric flask andbring to volume with methanol for a working standardof 100 ppm. Recordthe actual volume transferred. 9.0 Sample Handling______________________________________'__________________ 9.1 All samples are received frozen andmustbe kept frozenuntil the extraction is performed. 9.2 Allow samples to thawto roomtemperaturepriorto extraction. 10.0 Quality Control___________________ ;___________________________________ 10.1 Solvent Blanks, Method blanks and matrix blanks 10.1.1 An aliquot of 1.0 mLmethanol is used as a solvent blank. 10.1.2 Extracttwo 1.0 mLaliquots ofMilli-QTMwater following this procedure and use as methodblanks. 10.1.3 Extract two 1.0 mLaliquots of the serumfollowing this procedure and use as matrix blanks. See 11.1.4. 10.2 Matrix spikes 10.2.1 Prepare andanalyze matrix spike andmatrix spike duplicate samples to determine the accuracy of the extraction. 10.2.2 Prepare each spike using a sample chosen by the analyst, usually the control matrixreceived with each sample set 10.2.3 Expected concentrations will fall in themid-range ofthe initial calibrationcurve. Additional spikes may be included andmay fall in the low-range of the initial calibration curve. 10.2.4 Prepare one matrix spike andmatrix spike duplicateper40 samples, with a minimum of2 matrix spikes perbatch. 10.3 Continuing calibration checks - 10.3.1 Prepare continuing calibrationcheck samples to ensure the accuracy ofthe initial calibration curve. 10.3.2 Prepare, at aminimum, one continuing checkper groupof 10 samples. For example, if a sample set = 34, fourchecks are prepared and extracted. 10.33 Prepare each continuing calibrationcheck fromthe same matrix used to prepare the initial curve. . 3M Environmental Laboratory ETS-8-4.1 * ... . . . . rw i^ A n r . n Page 799 Page 5 o f 14 Page 41 3M Medical Department Study: T-6889.6 -----------ARGUS 418-020 Analytical Repon: FACT TOX-164 L1MS EOO-2738 10.3.4 The expected concentrations will fall within the mid-range ofthe initial calibration curve. Additional spikes may be included that fall in the low-range of the initial calibration curve. This is necessary if the analyst must quantitate using only the low end of the calibration curve (for example, 5 ppb- 100 ppb, rather than 5 ppb - 1000 ppb). 11.0 Calibration Afro Standardization_________________________________________ 11.1 Prepare matrix calibration standards 11.1.1 Transfer 1mL of serumto a 15 mL centrifuge tube. ' 11.1.2 Ifmost sample volumes are less than 1.0 mL, extract standards with matrix volumes equal to the sample volumes. Do not extract less than 0.50 mL of matrix. Record each sample volume on the extraction sheet 11.1.3 While preparing a total oftwenty aliquots in 15 mLcentrifuge tubes, mix or shake between aliquots. _ 11.1.4 Two 1 mL aliquots, or other appropriate volume, serve as matrix blanks. Typically use the standard concentrations and spiking amounts listed in Table 1, at die end ofthis section, to spike, in duplicate, two standardcurves, for a total of eighteen standards, two matrix blanks, andtwo method blanks. 11.1.5 Refer to validation reportETS-8-4.0 & ETS-8-5.0-V-1, which lists the working ranges andthe Linear CalibrationRange (LCR) for calibration curves. 11.1.6 Use Attachment D as an aid in calculating the concentrations of the working standards. See Section 13.0 to calculate actual concentrations of PFOS in calibration standards. 112 To each standard, blank, or continuing check, add appropriate amount of surrogate working standard for the concentration to fall within the calibration curve range 5 ppb 1 0 0 0 ppb. 11J Extract spiked matrix standards following 12.6-12.16 of this method. Use these standards to establish each initial curve on the mass spectrometer. 3M Environmental Laboratory ETS-8-4.1 fDCACfwtm Page 6 o f 14 Page 42 3M Medical Department Study: T-6889.6 - ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Table 1 Approximate spiking amounts for standards and spikes Using 1.0 mL of matrix Working standard fiL Approx, final cone, of (approx, cone.) analyte in matrix - - Blank 0.500 ppm 10 0.005 ppm 0.500 ppm 20 0.010ppm 5.00 ppm 5 0.025 ppm 5.00 ppm 10 0.050 ppm 5.00 ppm 20 0.100ppm 50.0 ppm 5 02250 ppm 50.0 ppm 10 0.500 ppm 50.0 ppm 15 0.750 ppm 50.0 ppm 20 1.00ppm 12.0 Procedure______ ;________________________________________________________ 12.1 Obtain frozen samples and allow to thaw at room temperature or in a lukewarm waterbath. 12.2 Vortex mix for IS seconds, then transfer 1.0 mL or other appropriate volume to a IS mL polypropylene centrifuge tube. 123 Return unused samples to freezer after extraction amounts have been removed. 12.4 Record the initial volume on the extraction worksheet. 12.5 Label the tube with the study number, sample ID, date and analyst initials. See attached worksheet for documenting the remaining steps. 12.6 Spike all samples, including blanks and standards, ready for extraction with surrogate standard as described in 1122. 12.7 Spike each matrixwith the appropriate amount of standard as described in 11.1, orTable 1 in that section, for the calibration curve standards. Also preparematrix spikes and continuing calibration standards. 12.8 Vortex mix the standard curve samples, matrix spike samples, and continuing calibration samples for 15 seconds. 12.9 Check to ensure the 0.5 M TBA reagent is at pH 10. Ifnot, adjust accordingly. 12.10 To each sample, add 1 mL 0.5 MTBA and 2 mL of 0.25M sodiumcarbonate/sodium bicarbonate buffer. 12.11 Using an OxfordDispenser, add 5 mL methyl-tert-butyl ether. 12.12 Cap each sample andput on the shaker at a setting o f300 tpm, for20 minutes. 12.13 Centrifuge for 20 to 25 minutes at a setting o f3500 rpm, oruntil layers arewell separated. 3M Environmental Laboratory ETS-8-4.1 Page 7 o f 14 Page 43 Page 801 3M Medical Department Study: T-6889.6 ----------ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 12.14 Label a fresh 15 mL centrifuge tube with the same information as in 12.5. 12.15 Remove 4.0 mL ofthe organic layer to this clean 15 mL centrifuge tube. 12.16 Put each sample on the analytical nitrogen evaporator until dry, approximately 1to 2 hours. 12.17 Add 1.0 mL of methanol to each centrifuge tube using agraduatedpipette. 12.18 Vortex mix for 30 seconds. 12.19 Attach a 0.2 pmnylon mesh filter to a3 cc syringe andtransferthe sample to this syringe. Filter into a 1.5 mL glass autovial or low-volume autovial when necessary. 12.20 Label the autovial with the study number, animal number and gender, sample timepoint, matrix, final solvent, extractiondate, andanalyses) performing the extraction. 12.21 Cap and store extracts atroom temperature or at approximately 4 C until analysis. 12.22 Complete the extraction worksheet, attached to this document, and tape in the study notebook or include in studybinder, as appropriate. . 13.0 Data Analysis and Calculations________________________________________ 13.1 Calculations 13.1.1 Calculate actual concentrations ofPFOS, or other applicable fluorochemical, in calibration standards using the following equation: mLofstandardX concentration ofstandard (up /mT.l_______________ = mLof standard+ mL of surrogate standard+ initial matrix volume (mL) Final Concentration (pg/mL) ofPFOS in matrix 14.0 M ethod Performance___________________________________________________ 14.1 The method detection limit (MDL) is analyte andmatrix specific. Refer to MDL report for specific MDL and lim it o f quantitation (LOQ) values (see Attachm ents B and C). 14.2 The following quality control samples are extractedwith each batch of samples to evaluate the quality of the extraction and analysis. 14.2.1 Methodblanks andmatrix blanks. 14.2.2 Matrix spike and matrix spike duplicate samples to deteimine accuracy and precision ofthe extraction. 14.23 Continuing calibration check samples to deteimine the continued accuracy of the initial calibration curve. 143 Refer to section 14 ofETS-8-5.1 formethodperformance criteria. 15.0 P ollution Prevention and Waste Management_______________________ 15.1 Sample waste is disposed in biohazardcontainers, flammable solvent waste is disposed in high BTU containers, and used glass pipette waste is disposed in broken glass containers located in the laboratory. 3M Environmental Laboratory ETS-R-4.1 MrDur\e A, c. Page 8 of 14 Page 44 Page 802 3M Medical Department Study: T-6889.6 --------- - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 16.0 Records____________________________________________________ _ 16.1 Complete the extractionworksheet attachedto this method, andtape in the study notebook or include in the 3-ring study binder, as appropriate. 17.0 Attachments____________________________________________________ 17.1 Attachment A, Extractionworksheet 17.2 AttachmentB, MDL/LOQ values andsummary 173 Attachment C, Calibrationstandard concentration worksheet 18.0 References_________ ;___________________________________________________ 18.1 The validation report associatedwith thismethodis ETS-8-4.0 & 5.0-V-l. 18.2 FACT-M-3.1, "Analysis of Serumor OtherFluid Extracts forFluorochemicals using HPLC-ElectrosprayMass Spectrometry" 19.0 affected Documents________________________ ;___________________________ 19.1 ETS-8-5.1, "Analysis of Serumor OtherFluidExtracts forFluorochemicals using HPLC-ElectrosprayMass Spectrometry" 20.0 Rvisions___________________ ;___________________________________________ Revision Number 1 Reason ForRevision Section 12.21 Changed to include sample storage atroomtemperature. Section 12.13 Added the shaker speed. Section 12.17 Final volume is 1.0 mL; not adjusted forinitial volumes less than 1.0 mL. Revision Date 04/02/99 3M Environmental Laboratory ETS-8-4.1 F.rtractinn ofPFOS from.Serum Page9 of14 Page 45 3M Medical Department Study: T-6889.6 Extraction Worksheet ETS-8-4.1 ------ ARGUS 418-020 Analytical Repon: FACTTOX-164 LIMS EOO-2738 Study# Matrix Box# Wk/Dav DateSpiked/Analyst CCV MS MSD Surrogate Std approx, ppm actual ppm # FC-Mix approx. 0.5 pm actual ppm # FC-Mtx approx. 5 ppm actual ppm # FC-Mix approx. 50 ppm actual ppm # Comments 1 -- -- --- -- -- -- -- -- ------ -- Blank Std# amount Seram Prtr*rtUB Method : Vortex 15 sec. Pmetre Matrix Pipette 1mL of 0.5 M TBA. pH 10. pH * Volume Std. # mL Pipette 2 mL of 0J5 Na2COVDJ5M NaHCOt buffer Std.# Dispense SmL of methyl-t-butyl ether TN-A- Shake 20 min. Shaker speed: Centrifuge 20-25 min. Centrifuge speed: Remove a 4 mL aliauot of organic laver Put on Nitrogen Evaporator to drvness Temperature: Add methanol Volume mL TN-A- Filter using a 3cc B-D syringe with a 0.2um filter into a 1J mL autosample vial Cent CaLVerifications usedsamematrix as for std curve. - - - - - - - mL Date 4c Initials 3M Environmental Laboratory Page 804 n.* in h Page 46 3M Medical Department Study: T-6889.6 r ------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2'38 MDL/LOQ values for rabbit serum Compound MDL LOQ Linear Calibration Range (LCR) (PPb) (PPb) Approximate concentrations to be used for preparing the Standard Calibration Curve PFOS 1.74 5.55 5 ppb - 1000 ppb PFOSA 1.51 4.79 5 ppb - 1000 ppb PFOSAA 3.46 20.5 5 ppb - 1000 ppb EtFOSE-OH 11.4 36.2 5 ppb - 1000 ppb M556 6.03 19.2 5 ppb - 1000 ppb . PFOSEA 5.71 18.2 5 ppb - 1000 ppb MDL/LOQ values in rat, bovine, monkey, and human serum, and monkey plasma were not statistically determined. Two curves in each of these matrices were extracted and analyzed with the rabbit serum curves to determine equivalence. Responses in the rat, bovine, monkey, and human were equivalent to the rabbit responses, therefore, their MDL and LOQ will be die same values as determined in rabbit serum. . Please see LOQ Summary and MDL study in ETS-8-4.0 & 5.0-V-l for further information. Attachment B: MDL/LOQ Summary 3M Environmental Laboratory ETS-8-4.1 Page 805 Page 11 of 14 Page 47 3M Medical Department Study: T-6889.6 r* ------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 Compound: PFOS ' Prepared range Rabbit Scrum of standards (ppb) (ng/mL) Full Range Low Curve High curve 1/X 0.995 - 978 4.94 - 248 97.8 - 978 0.995 - 978 Componnd: P FOSA Prepared range Rabbit Serum of standards (ppb) (ng/mL) Full Range Low Curve High curve 1/X 0.993 - 976 4.93-97.6 24.8 - 976 0.993 - 976 Compound: PFOSAA Preparedrange Rabbit Serum of standards (ppb) (ng/mL) Full Range Low Curve High curve 1/X 0.991-974 4.92 - 247 492-974 0.991 - 974 LCRfrom curve (ppb) (ng/mL) 24.8 - 978 4.94 - 248 97.8 - 978 4.94 - 978 LCRfrom curve (ppb) (ng/mL) 4.93 - 976 4.93-97.6 24.8 - 978 4.93 - 976 LCRfrom curve (ppb) (ng/mL) 24.7 - 974 9.74 - 247 97.4 - 974 9.74 - 974 % Recovery Range 83-108 85-104 85-106 94-111 %Recovery Range 88-103 87-105 93-102 94-103 %Recovery Range 81-111 97-107 85-108 95-115 RSD Range 4.67-11.0 5.34-12.0 4.84-9.80 4.60-10.5 RSD Range 5.10-14.7 9.85-14.7 5.08-13.9 5.10-14.5 RSD Range 4.18-10.6 638-21.8 433-123 4.11-232 Attachment B: MDL/LOQ Summary 3M Environmental Laboratory ETS-8-4.1 Page 806 Page 12 of 14 Page 48 3M Medical Department Study: T-6889.6 - ------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-273S Compound: EtFOSE-OH Prepared range Rabbit Serum of standards (ppb) (ng/mL) Full Range Low Curve High curve IfX 0.993 - 976 4.93 - 97.6 49.3 - 976 0.993 - 493 Compound; PFOSE Prepared range Rabbit Serum of standards (ppb) (ng/mL) Full Range Low Curve High curve 1/X 0.993 - 976 4.93 - 248 493 - 976 0.993 - 976 Compound; M5S6 Prepared range Rabbit Serum o f standards (ppb) (ng/mL) Full Range Low Curve High curve 1/X 0.993 - 976 4.93 - 97.6 97.6 - 976 0.993-976 LCR from curve (PPb) (ng/mL) 493 - 976 9.76-97.6 97.6-976 9.76 - 976 %Recovery Range 77-110 97-107 90-109 86-111 LCR from curve (PPb) (ng/mL) 24.8 - 976 9.76-248 493 - 976 9.76 - 976 %Recovery Range 96-106 91-110 86-106 95-117 LCR from curve (ppb) (ng/mL) 24.8 - 976 9.76-97.6 97.6-976 9.76 - 976 % Recovery Range 88-106 100-105 81-111 97-110 RSD Range 1122-25.5 14.1-213 115-19.6 11.1-212 RSD Range 10.1-162 11.8-19.5 102-182 10.1-19.1 RSD Range 4.82-175 5.95-182 5.11-9.74 4.77-19.5 Attachment B: MDL/LOQ Summary 3M Environmental Laboratory ETS-M.l Page 807 Page 13 of 14 Page 49 3M Medical Department Study: T-6889.6 -A-n--a-ly--t-ic-aAl RReGpUorSt: 4F1A8C-T02T0OX-164 LIMS E00-2738 Ion Pair Standard Curves - Fluids Prep date(s): Standard number: Analyte(s): Equipment number: t Sample matrix: Final solvent andTN: Blank fluld/idenfier: Method/revision: Target analyte(s): FC mix std approx. 0.S00ppm: FCmix std approx. 5.00ppm: FCmi* std approx. 50.0ppm: Surrogate std approx. 100ppm: Actual concentrations ofstandards in the FCmix PFOS FFOSA . PFOSAA EtFOSE FFOSEA Std cone Std cone Std cone Std cone Std cone ug/mL ug/mL ug/mL ug/mL ug/mL 0.500 0.507 0.532 0.501 0221 0200 0.507 0.532 0.501 0221 5.00 5.07 522 5.01 521 5.00 5.07 522 5.01 521 5.00 5.07 5.32 5.01 521 50.0 50.1 532 50.1 52.1 50.0 50.1 532 50.1 52.1 50.0 50.1 532 50.1 52.1 50.0 50.1 532 50.1 52.1 M556 Std cone ug/mL 0.501 0201 5.01 5.01 5.01 50.1 50.1 50.1 50.1 All AU Ami Final voi spiked mL mL 0.010 ! 1.015 0.020 1.025 0.005 1.010 0.010 1 1.015 0.020 1 1.025 0.005 ! 1.010 0.010 1 1.015 0.015 1 1.020 0.020 1 1.025 C alcnlated coneentrations o f standards in th sam ple m atrix PFOS PFOSA PFOSAA EtFOSE PFOSEA M556 Surrogate Final conc Final conc Final conc Final conc Final conc Final conc Std cone ng/mL ng/mL ng/mL ng/mL ng/mL ng/mL ng/mL 4.93 5.00 524 4.94 5.01 5.13 100 9.76 9.89 10.4 9.78 9.93 102 24.8 25.1 262 24.8 25.2 25.8 S d it o t a t i 49.3 50.0 52.4 49.4 50.1 512 Final conc 97.6 98.9 104 97.8 99.3 102 ng/mL 248 251 263 248 252 258 500 493 500 524 494 501 513 735 746 782 737 749 766 976 1 989 1038 978 993 1017 AU Ami spiked mL 0.005 Validated ranges- approximate concentrations Serum PFOS PFOSA PFOSAA EtFOSE-OH PFOSEA M556 Rabbit 5.00-1000 I 5.00-1000 | 5.00-1000 | 5.00-1000 i 5.00-1000 | 5.00-1000 Bovine Estimates only. Use values for nbbit Rat Estimates only. Use values for rabbit. Monkey & Plasma Estimates only- Use values for rabbit Human Estimates only. Use values for rabbit Attachment C: Ion Pair Standard Curves 3M Environmental Laboratory ETS-8-4.1 Page 808 Page 14 o f 14 Page 50 3M Medical Department Study: T-6889.6 3M Environmental Laboratory '------ ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 M ethod Extraction of Fluorochemical compounds from Serum for Analysis Using HPLC-Electrospray/M ass Spectrometry Method Number: ETS-8-4.2 Adoption Date: 03/01/99 ECFectiveDate: L/c2. / Dl Approved By: Laboratory Manager K -t - -- Group Leader Date o ,Io j, / o i Date 1.0 S c o pe and Ap p l ic a t io n 1.1 Scope: This method is for the extraction of fluorochemical compounds from serum. 12 Applicable compounds: Fluorochemical surfactants or other fluorinated compounds. 1 2 Matrices: Rabbit, rat, bovine, monkey, andhuman serumor other fiukj the validation repon. J 2.0 S u m m a r y o f M e t h o d 2.1 This performance-based method describes the procedure for extracting perfluorooctanesulfonate (PFOS) or other fluorochemical surfactants fromserum, or other fluids, using an ion pairing reagent and methyl-reif-butyl ether (MtBE). An ion pairing reagent is added to the sample and the analyte-ion pairis partitioned into MtBE. The MtBE extract is removed and put onto a nitrogen evaporator until dry. Each extract is reconstituted in 1.0 mLof methanol, then filtered through a 0.2 pm nylon Alterusing a 3-mL plastic Word 6/95 3M Environmental Laboratory ETS-8-4.2 Extraction of Fluorochemicals from Serum Page 1 of 15 Page 51 3M Medical Department Study: T-6889.6 Analytical if8S-164 LIMS EOO-2738 i 2.2 syringe into glass autovials. (Application of this method to seven fluorochemicals was demonstrated: PFOS, PFOSA, PFOSAA, EtFOSE-OH, PFOSEA, M556, and a surrogate standard (see 3.0Definitions}). These sample extracts are analyzed following method ETS-8-5.2 or other appropriate method. 3.0 D e f in it io n s _____________________________________________________________________________ 3.1 PFOS: perfluorooctanesulfonate (anion of potassiumsalt) C1F17SO3' 3.2 PFOSA: perfluorooctane sulfonylamide C1F17SO2NH2 ' 3.3 PFOSAA: perfluorooctane sulfonylamido (ethyl)acetate C|Fi7S0 2 N(CH2CH3)CH2C0 2 ' 3.4 EtFOSE-OH: 2(N-ethylperfluorooctane sulfonamido)-ethyl alcohol CiFnSOiNfCHjCHjiCHjCHjOH 3.5 PFOSEA: perfluorooctane sulfonyl ethylamide CgFnSOjNiCHjCHj^ 3.6 M556: CiFnSOjNtHXCHjCOOH) 3.7 Surrogate standardTHPFOS: 1H-1H-2H-2H perfluorooctane sulfonic acid 4.0 W a r n in g s a n d C a u t io n s __________________________________________________________ 4.1 Health and safety warnings 4.1.1 Use universal precautions, especially laboratory coats, goggles, and gloves when handling animal tissue, which may contain pathogens. 5.0 Interferences_______________________________________________________ 5.1 There are no interferences known at this time. 6 .0 E q u i p m e n t ____________________________________________________________________________________________________ 6.1 The following equipment is used while performing this method. Equivalent equipment is acceptable. 6.1.1 Vortex mixer, VWR, Vortex Genie 2 6.1.2 Centrifuge, Mistral 1000 or IEC 6.13 Shaker, Eberbach or VWR 6.1.4 Nitrogen evaporator, Organoroation 6.13 Balance ( 0.100 g) 7.0 Su a n d M a t e r ia l s _______________________________________________________________ 7.1 Gloves 7.2 Eppendorfor disposable pipettes, plastic or glass (or equivalent) 7.3 Polypropylene bottles, capable of holding 250 mL and 1L (Nalgene or equivalent) 3M Environmental Laboratory ETS-8-4.2 t.r **. Page 810 Page 2 of 15 Page 52 3M Medical Department Study: T-6889.6 --------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 7.4 Volumetric flasks, glass, type A 7.5 40 mLglass vials (I-CHEM or equivalent) 7.6 Centrifuge tubes, polypropylene, 15 mL 7.7 Labels 7.8 Bottle-top Dispenser - 3.0 to 10.0 mL or a 5-10 mL graduated pipette, glass 7.9 Syringes, capable of measuring 5 fiL to 50 pL 7.10 Graduated pipettes 7.11 Syringes, disposable plastic, 3 mL (B&D or equivalent) 7.12 Syringe filters, nylon, 0.2 pm, 25 mm 7.13 Timer 7.14 Crimp cap glass autovials and caps 7.15 Crimpers Note: Prior to using glassware and bottles, rinse 3 times with methanol and 3 times with water. Rinse syringes a minimum of 9 times with methanol, 3 rinses from 3 separate vials. 8 .0 R e a g e n t s a n d S t a n d a r d s __________________________________________________________ 8.1 Reagent grade water, MDli-QTM, Nanopure II or equivalent 822 Sodium hydroxide (NaOH), J.T Baker or equivalent 83 Tetrabutylammonium hydrogen sulfate(TBA), Kodak or equivalent 8.4 Sodium carbonate (Na2C03), J.T. Baker or equivalent 8.5 Sodium bicarbonate (NaHCOj), J.T. Baker or equivalent 8.6 Methyl-T-Butyl Ether, Omnisolv, glass distilled or HPLC grade 8.7 Methanol, Omnisolv, glass distilled or HPLC grade 8.8 Serum or blood, frozen from supplier 8.9 Fhiorochemical standards 8.9.1 KPFOS (PFOS) (3M Specialty Chemical Division), molecular weight = 538 8.9.2 PFOSA (3M Specialty Chemical Division), molecular weight = 499 8.9.3 PFOSAA+H (PFOSAA) (3M Specialty Chemical Division), molecular weight = 585 8.9.4 EtFOSE-OH (3M Specialty Chemical Division), molecular weight = 570 8.9.5 PFOSEA (3M Specialty Chemical Division), molecular weight = 527 8.9.6 M556 (3M Specialty Chemical Division), molecular weight = 557 8.9.7 Surrogate standard: 4-H, perfhiorooctane sulfonic acid (1-H,1-H, 2-H, 2-H CiFijSOjH, [THPFOS]), molecular weight = 428 8.9.8 Other fluorochemicals, as appropriate 3M Environmental Laboratory ETS-8-4.2 Page 811 Page 3 of 15 Page 53 3M Medical Department Study: T-6889.6 - - ------ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 8.10 Reagent preparation NOTE: When preparing different volumes than listed in reagent, standard, or surrogate preparation, adjust accordingly. 8.10.1 10 N sodium hydroxide (NaOH): Weigh approximately 200 g NaOH. Pour into a 1000 mL beaker containing 500 mL water, mix until all solids are dissolved. Store in a 1L polypropylene (or equivalent) bottle. 8.10.2 1N sodium hydroxide (NaOH): Dilute 10 N NaOH 1:10. Measure 10 mL of 10 N NaOH solution into a 100 mL volumetric flask and bring to volume using water. Store in a 125 mL polypropylene (or equivalent) bottle. 8.1023 0.5 M tetrabutylammonium hydrogen sulfate (TBA): Weigh approximately 169 g of TBA into a 1L volumetric containing 500 mL water. Adjust to pH 10 using approximately 44 to 54 mL of 10 N NaOH. (Add the last 1.0 mL ofNaOH slowly, as the pH changes abruptly.) Dilute to volume with water. Store in a 1L polypropylene (or equivalent) bottle. 8.10.3.1 TBA requires a check prior to each use to ensure pH = 10. Adjust as needed using 1N NaOH solution. 8.10.4 0.25 M sodium carbonate/sodium bicarbonate buffer (NajCOi/NaHC03): Weigh approximately 26.5 g of sodium carbonate (Na2COj) and 21.0 g of sodium bicarbonate (NaHCOj) into a 1L volumetric flask and bring to volume with water. Store in a 1L polypropylene (or equivalent) bottle. 8.11 Standards preparation 8.11.1 Prepare PFOS standards for the standard curve. 8.11.2 Prepare other fluorochemical standards, as appropriate. Multicomponent fluorochemical standards are acceptable (for example, one working standard solution containing approximately 1.00 pg/mL of PFOS, PFOSA PFOSAA, PFOSEA, M556 and EtFOSE-OH). . 8.1123 Weigh approximately 100 mg of PFOS into a 100 mL volumetric flask and record .the actual weight. For standards with K* or other salts, multiply by a correction factor. For example, the molecular weight of KPFOS = 538, and the molecular weight of PFOS = 499. Calculate the correction factor by using the following equation: m olecular wt. PFO S (499 j = 0.9275 (C orrection fa c to r) m olecular wt. KPFO S ( 538) 8.11.4 Bring to volume with methanol for a stock standard of approximately 1000 pg/mL. 8.11.5 Dilute the stock solution with methanol for a working standard 1solution of approximately 50 pg/mL. ' 1000f t g / m L x 5ndA s50 fig lm L 100 m l J 8.11.6 Dilute working standard 1with methanol for a working standard 2 solution of approx. 5.0 pg/mL. 3M Environmental Laboratory ETS-8-4.2 _* . , . f T** . . * p . . r< Page 812 Page 4 o f 15 Page 54 3M Medical Department Study: T-6889.6 Analytical LIMS EOO-2-38 ' 50 pg / mL x 10m L y = 5.0 pg/mL 100 mL 8.11.7 Dilute working standard 1with methanol for a working standard 3 solution of approx. 0.50 pg/mL. 50 fig I mLxl.O mL = 0.500 flg/mL 100 mL \ 8.12 Surrogate THPFOS stock standard preparation . 8.12.1 Weigh approximately 50-60 mg of surrogate standard 1-H.l-H, 2-H, 2-H, CgFuSOjH (THPFOS) into a 50 mLvolumetric flask and record the actual weight. 8.12.2 Bring to volume with methanol for a surrogate stock of approximately 1000 1200 pg/mL. 8.123 Prepare a surrogate working standard. Transfer approximately 1 mLof surrogate stock to a 10 mLvolumetric flask andbring to volume with methanol for a working standard of 100 pg/mL. Record the actual volume transferred. 9.0 Sample Handling_________________________________________ ,______________ 9.1 All samples are received frozen and must be kept frozen until the extraction is performed. 9.2 Allow samples to thaw at roomtemperature or in lukewarmwater prior to extraction. 10.0 Quality Control_______________________________________________________ 10.1 Solvent Blanks, Method Blanks and Matrix Blanks 10.1.1 Solvent Blanks: An aliquot of 1.0 mLmethanol is used as a solvent blank. 10.1.2 Method Blanks: Following this procedure, extract two 1.0 mLaliquots of water and use as method blanks. 10.1.3 Matrix Blanks: Matrix blanks are prepared fromone of three sources: 1) a study control matrix froma study control animal received with each sample set; 2 ) a commercially obtained sample of the same species as the study animals; or 3) a surrogate matrix, also obtainedcommercially, but of a different species than the study animal (e.g. if rabbit is used to generate standardcurves and CCVs for a monkey or rat serastudy). The matrix to use depends on what matrix is used for the curve. 10.13.1 Study control matrix curve--If the study control matrix is used for the curve, prepare two (2 ) matrix blanks using the study control matrix. 10.133 Commercially obtained (same species) matrix curve--If the curve is preparedusing commercially obtained matrix in the same species as the study animal, prepare two matrix blanks using this same commercially available matrix. 3M Environmental Laboratory ETS-8-4.2 Extraction of Fluorochemicals from Serum Page 813 Page 5 of 15 Page 55 3M Medical Department Study: T-6889.6 *---------ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 10.1.3.3 Surrogate matrix curve--Ifasurrogate matrix is used for the curve and continuing calibration verification samples: a) prepare two (2 ) matrix blanks using the surrogate matrix. b) Also, prepare a matrixblank with each set of matrix spikes (a set is a matrix spike/matrix spike duplicate at one level) using a commercially available matrix of the same species as the study animals. 102 Matrix spikes . 10.2.1 Study Control Matrix Curve No matrix spikes are prepared. 10.2.2 Commercially obtained matrix curve (same species) No matrix spikes are prepared. 10.2.3 Surrogate matrix curve Matrix spikes are necessary if matrix is not available in the same species as the study animal and a surrogate matrixis used for the curve and CCV samples (e.g., rabbit sera may be used to generate standardcurves for a monkey sera study, due to measurable levels of endogenous analyte in the monkey sera). Prepare and analyze matrix spike andmatrix spike duplicate samples to verify the accuracy of the extraction for target analytes. 10.2.4 Prepare each MS and MSD at two (2) levels (usually a low and mid-range concentration) using a sample chosen by the analyst, typically sera from a control group animal received with each sample set. 10.2.4.1 If there is not sufficient sera available fromthe control group, prepare matrix spikes using commercially available matrix from the same species as the study animal - 10.2.5 Prepare one matrix spike and matrix spike duplicate at each level listed in 10.2.4 per 20 samples, with a minimumof 2 matrix spikes per level per batch. If a batch includes more than 2 0 samples, additional spikes maybe prepared at the same, low, or high range levels. 10.2.6 If more than25%of the samples are LOQ, two matrix spikes should be prepared at approximately 2-5 times the expected LOQ. 10.2.7 If the majorityof the samples are at or above the highrange of the curve, additional matrix spikes should be prepared to approximate sample concentrations. 10.3 Continuing calibration verifications (CCVs) 10.3.1 Prepare continuing calibration verification samples for instrument stability verification during analysis. Prepare and analyze CCVs for every assay run, regardless of the matrix type used to prepare the standard curve. 10.3 .2 Prepare each continuing calibration verification fromthe same matrix used to prepare the initial curve (Le., either the study control matrix, commercial matrix of same species, or surrogate matrix). 3M Environmental Laboratory ETS-8-4.2 Page 6 o f 15 Page 56 3M Medical Department Study: T-6889.6 - -------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 1023.3 The expected concentrations of the CCVs will fall within the range of the initial calibration curve; typically, the low to mid-range of the curve. 1023.4 Prepare, at a minimum, two continuing calibration verifications, each at a different concentration, per group of 10 samples. For example, if a sample set = 34, eight (8 ) checks are prepared; four (4) at a low range andfour (4) at a mid-range concentration. 10.3.5 Additional continuing calibration verifications maybe included at the same, low, mid or high-range concentration. 11.0 C a l ib r a t io n a n d S t a n d a r d iz a t io n _______________________________________________ _ 11.1 Prepare matrix calibration standards 11.1.1 Transfer 1mL of appropriate serumto a 15 mLcentrifuge tube. If commercially available sera is used, prepare two matrixblanks, using the volume of sera available formost study animals. 11.1.1.1 Depending upon study goals or if analyte-fiee commercial sera is not available, a surrogate matrix maybe used for generation of the calibration standard. For example, rabbit sera maybe used as a surrogate matrix for rat studies if quantitation of extremelylow levels of the analyte is required. 11.1.2 If most sample volumes are less than 1.0 mL, extract standards with matrix volumes equal to the sample volumes. Do not extract less than 0.50 mLof matrix. Record each sample volume on the extraction sheet. 11.13 While preparing a total of thirteen aliquots in 15-mLcentrifuge tubes, mix or shake sera between aliquots. 11.1.4 Two 1-mL aliquots, or other appropriate volume, serve as curve matrix blanks. Typically use the standardconcentrations and-spiking amounts listed inTable 1 at the end of this section to spike one standardcurve, for a total of nine standards, two matrix blanks, andtwo methodblanks. 11.13 Refer to validation report ETS-8-4.0 & ETS-8-5.0-V-1, which lists the working Tanges and the Linear Calibration Range (LCR) for calibration curves. 11.1.6 See Section 13.0 to calculate actual concentrations of PFOS in calibration standards. 11.2 To each standard, blank, continuing check, and sample add an appropriate amount of surrogate working standard to achieve aconstant concentration that falls within the calibration curve range of 2.5 ng/mL-1000 ng/mL. Usually, samples are spiked for a constant concentration in all samples at approximately 500 ng/mLor other concentration as determined by the analyst. 113 Extract spiked matrix standards following 12.6-12.16 of this method. Use these standards to establish each initial curve on the mass spectrometer. 3M Environmental Laboratory ETS-8-4.2 Page 7 o f 15 Page 57 3M Medical Department Study: T-6889.6 --------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Table 1 Approximate spiking amounts for standards and spikes Using 1.0 mL of matrix Working standard (approx, cone.) HL Approx, final cone, of analyte in matrix - - Blank 0.500 ppm 10 0.005 ppm 0.500 ppm 20 0.010ppm 5.00 ppm 5 0.025 ppm 5.00 ppm 10 0.050 ppm 5.00 ppm 20 0.100ppm 50.0 ppm 5 0.250 ppm 50.0 ppm 10 0.500 ppm 50.0 ppm 15 0.750 ppm 50.0 ppm 20 1.00ppm *ppnoti(/mL 12.0 P r o c e d u r e __________________________________________________________________________ 12.1 Obtain frozen samples and allow to thaw at roomtemperature or in lukewarmwater. 12.2 Label a 15 mLpolypropylene centrifuge tube with the studynumber, sample ID, date and analyst initials. See attached worksheet (Attachment A or similar worksheet) for documenting the remaining steps. 123 Vortex mix for 15 seconds, then transfer 1.0 mLor other appropriate volume to the 15 mLpolypropylene centrifuge tube. 12.4 Return unused samples to freezer after extraction amounts have been removed. 12.5 Record the initial volume on the extraction worksheet (Attachment A or similar worksheet). 12.6 Spike all samples, blanks andstandards, that are ready for extraction with surrogate standard as described in 11.2 . 12.7 Spike each calibration standard matrix with the appropriate amount of standard as described in 11.1, or Table 1 inthat section, for the calibration curve standards. Also prepare matrix spikes if necessary andcontinuing calibration standards. 12.8 Vortex mix the standard curve samples, matrix spike samples, and continuing calibration samples for 15 seconds. 12.9 Check to ensure the 0.5 MTBA reagent is at pH 10. If not, adjust accordingly. 12.10 To each sample, add 1mL0.5 MTBA and2 mLof 0.25M sodiumcarbonate/sodium bicarbonate buffer. 12.11 Using an bottle top dispenser or 5-10 mLgraduated glass pipette, add 5 mLmethyl-ferfbutyl ether. 12.12 Capeach sample and put on the shaker at a setting of 300 rpmfor 20 minutes. 3M Environmental Laboratory ETS-8-4.2 ci....-- U-- i. c----c. Page 816 Page 8 of 15 Page 58 3M Medical Department Study: T-6889.6 ---------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 12.13 Centrifuge for 20 to 25 minutes at asetting of 3500 rpmor until layers are well separated. 12.14 Label a fresh 15 mLcentrifuge tube with the same information as in 12.5. . 12.15 Remove 4.0 mLof the organic (top) layer to this clean 15 mLcentrifuge tube. 12.16 Put each sample on the analytical nitrogen evaporator until dry, approximately 1to 2 hours. 12.17 Add 1.0 mL of methanol to each centrifuge tube using a graduated pipette. 12.18 Vortex mix for 30 seconds, or longer if needed. 12.19 Label a 1.5 mLglass autovial (or low-volume autovial when necessary) with the study number, animal number and gender, sample timepoint, matrix, final solvent, extraction date, and analyst(s) performing the extraction. 1230 Attach a 25 mm, 0.2 pm nylon mesh filter to a 3 mLsyringe andtransfer the sample from step 12.18 to this syringe. Filter into the labeled autovial. 1231 Cap and storeextracts at roomtemperature or at approximately4 Cuntil analysis. 12.22 Complete the extraction worksheet (Attachment A or similar worksheet) and include in the study binder. 13.0 D a t a A n a l y s i s a m p C a l c u l a t i o n s ________________________________________________________ 13.1 Calculations 13.1.1 Calculate actual concentrations ofPFOS, or other applicable fiuorochemical, in calibration standards using the following equation: ________m L o f s td x concentration o f std ( f i g / m L ) _______ mL o f std + mL o f surrogate std + initial matrix volume( mL ) Final concentration (pig / mL) o f PFOS in matrix 14.0 Method Performance___________________________________________________ 14.1 The method detection limit (MDL) is analyte and matrixspecific. Refer to MDL report for specific MDL and limit of quantitation (LOQ) values (see Attachments B and C). At the discretion of the PA1, MDL maynot be defined for some studies. 14.2 The following quality control samples are extracted with each batch of samples to evaluate the quality of the extraction and analysis. 14.2.1 Method blanks and matrix blanks. 14.2.2 If surrogate matrix is used for curve and QC, matrix spike and matrix spike duplicate samples to verify extraction efficiency. 14.23 Continuing calibration check samples to determine the continued accuracy of the initial calibration curve. 14.3 Refer to section 14 of ETS-8-5.2 for method performance criteria. 3M Environmental Laboratory ETS-8-4.2 pY frartifm n f P ln n m rh p m iralt from Spnnn Page 9 of 15 Page 59 3M Medical Department Study: T-6889.6 7 ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 15.0 Pollution Prevention and Waste Management____________________ . 15.1 Dispose of sample waste, flammable solvent waste andused glass pipette waste using * proper methods and by placing each in their designated waste container. 16.0 R e c o r d s _____________________________________________________________________________________________ 16.1 Complete the extraction worksheet attached to this method (or a similar worksheet), and include in the study binder. 17.0 A t t a c h m e n t s ______________________________________________________________________________________ 17.1 Attachment A Extraction worksheet (a similar worksheet may be substituted for Attachment A) - 17.2 Attachment B, MDL/LOQ values andsummary . 17.3 Attachment C, Ion Pair Standard Curves worksheet (a similar worksheet may be substitutedfor Attachment C) 18.0 R e f e r e n c e s _______________________________________________________ 18.1 The validation report associated with this methodis ETS-8-4.0 & 5.0-V-l. 18.2 FACT-M-3.1, "Analysis of Serumor OtherFluidExtracts for Fluorochemicals using HPLC-ElectrosprayMass Spectrometry" 18.3 ETS-8-5.2, "Analysis of PotassiumPerfluorooctanesulfonate or Other Fluorochemicals m SerumExtracts Using HPLC-Electrospray/Mass Spectrometry'' 19.0 ,a f f e c t e d D o c u m e n t s ____________________________________________________________________________ 19.1 ETS-8-5.2, "Analysis of PotassiumPerfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry" 20.0 R e v i s i o n s ___________________________________________________________________________________________ Revision Number 1 2 Reason For Revision Section 12.21 Changed to include sample storage at room temperature. Section 12.13 Added the shaker speed. Section 12.17 Final volume is 1.0 mL; not adjusted for initial volumes less than 1.0 ml. Section 1.1,2.1 Eliminate `potassium* from perfluorooctanesulfonate 8.9.1 Add K to PFOS 8.9.3 Add H to PFOSAA 10.2-10.2.4, 14^2 Add information about using surrogate matrix, clarify control matrix and spiking the curve, change spikes to every 20 samples 10.3 Clarify purpose of continuing calibration checks . 1l.l Added wording about control animal sera, using and not using commercially available Revision Date 04/02/99 tissue In general, make less specific for equipment/supplies. Substitute water for Milli-Q, Nalgene or equivalent bottle may be used. 3M Environmental Laboratory ETS-8-4.2 pTtnw*finn n f P ln n ro r lw n if^ U fr/wn Q*ntvn Page 10 of 15 Page 60 3M Medical Department Study: T-6889.6 Studv# Matrix Box # Wk/Dav Date Spiked/ Analyst: Surrogate Std actual pg/mL # Extraction Worksheet ETS-8-4.2 FC-Mix approx. 0.5 FC-Mix approx. 5 FC-Mix approx. 50 pg/mL # pg/mL # pg/mL # LIMS EOO-2738 Comments Verified by: MS MSD ___________ !________ -- - .. - -- - -- - -. . - -- -- - -- . . _- -- - --- -- - -. . --. --. ,,Blank .J D J ---------------------------------------------------amount = ........... . .........mL----- 1 Seram Extraction Method ...i Date & Initials 1 _VsOE2Q2jec. ------------------------------------------------------------------------------------------------------------------------------------ 1------------------- Pipette Matrix, spike with appropriate iUITPntS onECMia. Pioctte 1 mL. of 0.5 M TBA. dH 10. dH Volume Std. # mL 1 . 1 Pipette 1 ml. of 0.25 NatCOVD.25M NaHCOi buffer Std. # Disoense/oioette 5 mL of methyl-t-butvl ether TN-A- Dispenser ID #: Shake 20 min. Shaker ID#: Shaker speed: Centrifuge 20-25 min. Centrifuge ID#:---------------------------------- Centrifuga SPttd;--------------------------- Remove a 4 mL aliouot of omniC I8VCI-------------------------------------------------------------------------------------- -Eut on Nitrogen Evaporator to d n w ---------------------------------------------------------------------------------------- Add methanol Volume mL TN-A- -.Vortex 30 sec-------------------------------------------------------------------------------------------------------------------- Filter using a 3mL B-D syringe with a 0.2um filter into a 1.5 mL autnsamnle vial__________________ ______-- ConL Cal. Verifications used same matrix as for std curve. Appendix A: Extraction Worksheet 3M Environmental Laboratory ETS-8-4.2 Page 819 Page 11 of 15 Page 61 3M Medical Department Study: T-6889.6 ----------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 MDL/LOO values for rabbit serum Compound MDL LOQ Linear Calibration Range (LCR) (ng/mL) (ng/mL) Approximate concentrations to be used for preparing the Standard Calibration Curve PFOS 1.74 5.55 5 ng/mL-1000 ng/mL PFOSA 1.51 4.79 5 ng/mL-1000 ng/mL PFOSAA 3.46 20.5 5 ng/mL-1000 ng/mL EtFOSE-OH 11.4 36.2 5 ng/mL-1000 ng/mL M556 6.03 19.2 5 ng/mL-1000 ng/mL . PFOSEA 5.71 18.2 5 ng/mL-1000 ng/mL MDL/LOQ values in rat, bovine, monkey, and human serum, and monkey plasma were not statistically determined. Two curves in each of these matrices were extracted and analyzed with the rabbit serum curves to determine equivalence. Responses in the rat, bovine, monkey, and human were equivalent to the rabbit responses, therefore, their MDL and LOQ will be the same values as determined in rabbit serum. Please see LOQ Summary and MDL study in ETS-8-4.0 & 5.0-V-l for further information. AppendixB: MDL/LOQValuesandSummary ETS-8-4.2 F.xtmrtinn n f Fhinmrh^mtral from Serum 3M Environmental Laboratory Page 820 Page 12 of 15 Page 62 3M Medical Department Study: T-6889.6 ? ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Compound: PFOS Preparedrange Rabbit Serum of standards (ng/mL) Full Range 0.995 - 978 LowCurve 4.94 - 248 High curve 97.8 - 978 1/X 0.995-978 LCRfrom curve (ng/mL) 24.8 - 978 4.94 248 97.8-978 4.94 - 978 % Recovery Range 83-108 85-104 85-106 94-111 RSD Range 4.67-11.0 5.34- IZ0 4.84-9.80 4.60-10.5 Compound: PFOSA Prepared range Rabbit Serum of standards (ng/mL) Full Range 0.993 - 976 Low Curve * 4.93 - 97.6 High curve 24.8 - 976 1/X 0.993 - 976 LCR from curve (ng/mL) 4.93 - 976 4.93 - 97.6 24.8 - 978 4.93 - 976 %Recovery Range 88-103 87-105 93-102 94-103 RSD Range 5.10-14.7 9.85-14.7 5.08-13.9 5.10-14.5 Compound: PFOSAA Preparedrange RabbitSerum of standards (ng/mL) Full Range 0.991 -974 LowCurve 4.92 - 247 High curve 49.2-974 1/X 0.991 - 974 LCRfrom curve (ng/mL) 24.7 - 974 9.74 - 247 97.4-974 9.74 - 974 % Recovery Range 81-111 97-107 85-108 95-115 RSD Range 4.18-10.6 6.38-21.8 4.33-12.5 4.11-23.2 Appendix B: MDL/LOQValues and Summary ETS-8-4.2 Extraction ofFluorochemicals from Serum 3M Environmental Laboratory Page 821 Page 13 of 15 Page 63 3M Medical Department Study: T-6889.6 Analytical! (-164 LIMS E00-2738 Compound: EtFOSEOH Prepared range Rabbit Serum of standards (ng/mL) Full Range 0.993 - 976 Low Curve 4.93-97.6 High curve 49.3 - 976 1/X 0.993 - 493 LCRfrom curve (ng/niL) 493 - 976 9.76 - 97.6 97.6 - 976 9.76-976 %Recovery Range 77-110 97-107 90-109 86-111 Compound: P FOSEA Prepared range Rabbit Serum of standards (ng/mL) Full Range 0.993 - 976 Low Curve 4.93 - 248 High curve 49.3 - 976 1/X 0.993 - 976 LCRfrom curve (ng/mL) 24.8-976 9.76 - 248 493 - 976 9.76 - 976 % Recovery Range 96-106 91-110 86-106 95-117 Compound: MSS6 Prepared range Rabbit Serum of standards (ng/mL) Full Range 0.993 - 976 Low Curve 4.93 - 97.6 High curve 97.6 - 976 1/X 0.993 - 976 LCRfrom curve (ng/mL) 24.8 - 976 9 .7 6 -9 7 .6 97.6 - 976 9.76-976 %Recovery Range 88-106 100-105 81-111 97-110 RSD Range 11.2-25.5 14.1-21.3 11.5-19.6 11.1-21.2 RSD Range 10.1-16.2 11.8-19.5 10.2-18.2 10.1-19.1 RSD Range 4.82-17.9 5 .9 5 -1 8 .2 5.11-9.74 4.77-193 AppendixB:MDL/LOQValuesandSummary ETS-8-4.2 3M Environmental Laboratory Page 822 Page 14 of 15 Page 64 3M Medical Department Study: T-6889.6 ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 E xam ple Ion P air Standard Curves - Fluids Analyses) Study number: : Prepdate(s): Final solvent andTN: Analyte(s): Blankfluid/identifier: 'RecorJmaimused<pr: are curve-, <c.g., `Rabbit.'ID Study Animal Matrix: #XXX)I * Method/revision: Target anaiyte(s): FCmix std approx. 0.500 ppm: FCmixstd approx. 5.00 ppm: FCmixstd approx. 50.0 ppm: f Record the standards used to prepare the extracted c a n e s .} Surrogate std approx. 100ppm: Actual concentrations ofstandards in the FCmixin methanol PFOS PFOSA PFOSAA EtFOSE PFOSEA M556 AU Std cone Std cone Std cone Std cone Std cone Std cone Ain't Ug/mL ug/mL ug/mL ug/mL ug/mL ug/mL spiked mL 0.500 0.507 0.532 0.501 0-521 0.501 0.010 0.500 0.507 0.532 0.501 0.521 0.501 0.020 5.00 5.07 5.32 5.01 5.21 5.01 0.005 5.00 W S7 532 5.00 jj__S07''C - r 5*2% - w mu5.01 5.21 ^ 5.01 0.010 1 _ 0.020 50.0 i 50.1 5 50.0 s d t / ILdLJ1L is2 j p a r 0.005 0.010 50.0 50.1 53.2 50.1 1 52.1 50.1 0.015 50.0 50.1 53.2 50.1 52.1 50.1 0.020 AU Final vol mL 1.015 1.025 1.010 1.015 1.025 1.010 1.015 1.020 1.025 Calculated concentrations of standards in the sera matrix: Rabbit PFOS PFOSA PFOSAA EtFOSE PFOSEA M556 Surrogate Final cone Final cone Final cone Final cone Final cone Final cone Std cone ng/mL ng/mL ng/mL ng/mL ng/mL ng/mL ng/mL AU Amt spiked mL Validated ranges - approximateconcentrations Serum PFOS PFOSA PFOSAA Rabbit 5.00-1000 5.00-1000 5.00-1000 ng/mL ng/mL ng/mL Bovine Estimates only. Use values for rabbit. Rat Estimates only. Use values for rabbit Monkev & Plasma Estimates only. Use values for rabbit. Human Estimates only. Use values for rabbit EtFOSE-OH 5.00-1000 ng/mL PFOSEA 5.00-1000 ng/mL MS56 5.00-1000 ng/mL Attachment C:IonPairStandardCurves ETS-8-4.2 Extraction ofFluorochemicals from Serum 3M Environmental Laboratory Page 823 Page 15 of 15 Page 65 3M Medical Department Study: T-6889.6 3M Environmental Laboratory -------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Method Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry Method Number: ETS-8-5.1 Author: Lisa Clemen, Robert Wynne Approved By: Q-i I ' i -- Laboratory Manager Adoption Date: 03/01/99 Revision Date: ^ V ^/ Date Group Leader Date dxin. A Technical Reviewer oh/ u / m Date BactOopyofOrigM X it/o / tomai (tata 1.0 Scope and Application 1.1 Scope: This method describes the analysis ofserum extracts for fluorochemical surfactants using HPLC-electrospray/mass spectrometry. 1.2 Applicable Compounds: Fluorochemical surfactants or other fluorinated compounds, or otherionizable compounds. 1.3 Matrices: Rabbit, rat, bovine, monkey, andhumanserum, or other fluids as designated in the validationreport Word 6/95 3M Environmental Laboratory ETS-8-5.1 Analysis ofSerumExtractUsing ES/MS Page 1of9 Page 66 Page 824 3M Medical Department Study: T-6889.6 --7 ------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 2.0 Summary of Method_________________________________________________________ 2.1 This method describes the analysis of fluorochemical surfactants extracted from serum or other fluids, using HPLC-electrospray/mass spectrometry, orsimilar system as appropriate. The analysis is performedby monitoring a single ion characteristic of a particular fluorochemical, such as the perfluorooctanesulfonate (PFOS) anion, m/z= 499. Additionally, samples may be analyzed using a tandemmass spectrometer to further verify the identity of a compoundby detecting daughter ions ofthe parent ion. 3.0 Definitions_______________________________________________ '_________ 3.1 Atmospheric Pressure Ionization (API): The Micromass Quattro II triple quadrupole systems allow for various methods ofionization by utilizing various sources, probes, and interfaces. These include but are not limited to: Electrospray Ionization (ESI), Atmospheric Pressure chemical Ionization (APcI), Thermospray, etc. The ionization process in these techniques occurs at atmosphericpressure (i.e., not underavacuum). 3.2 Electrospray Ionization (ES, ESI): amethod of ionization performed at atmospheric pressure, whereby ions in solution are transferredto the gas phase via tiny charged droplets. These charged droplets areproducedby the application of astrong electrical field. 3.3 Mass Spectrometry, Mass Spectrometer (MS), TandemMass Spectrometer (MS/MS): The API Quattro II triple quadrupole systems are equippedwith quadrupole mass selective detectors. Ions are selectively discriminatedby mass to chargeratio (m/z) and subsequently detected. A single MS maybe employed forion detection or aseries (MS/MS) formore specific fragmentationinformation. 3.4 Conventional vs. Z-spray probe interface: The latest models ofMicromass Quattro II triple quadrupole systems (post 1998) utilize a "Z-spray" conformation. The spray emitted froma probe is orthogonal to the cone aperture. In the conventional conformation it is aimed directly at the cone aperture, afterpassing throughatortuous pathwayin the counter electrode. Though the configuration is different, the methods of operation, cleaning, and maintenance are the same. However, Z-spray components andconventional components are not compatible with one another, but only with similar systems (i.e., Z-spray components are compatible with some other Z-spray systems, etc.) 3.5 Mass Lynx Software: System software designed forthe specific operation ofthese Quattro II triple quadrupole systems. CurrentlyMassLynx has Windows 95 andWindowsNT 4.0 versions. All versions are similar. Formore details see the manual specific to the instrument (Micromass Quattro II triple quadrupoleMassLynx orMassLynxNT User's Guide). 4.0 W arnings and Cautions_________________________________________________ __ 4.1 Health and Safety Warnings: 4.1.1 Use caution with the voltage cables forthe probe. When engaged, the probe employs a voltage ofapproximately 5000 Volts. 4.1.2 Whenhandling samples or solvents wear appropriateprotective gloves, eyewear, and clothing. 3M Environmental Laboratory ETS-8-5.1 Page 825 Page 2 o f9 Page 67 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACTTOX-164 LIMS EOO-2738 4.2 Cautions: 4.2.1 Do not operate solvent pumps above capacity of400 bar (5800 psi) back pressure. If the backpressure exceeds 400 bar, the HP1100 will initiate automate shutdown. 4.2.2 Do not runsolvent pumps to dryness. 5.0 I nterferences__________________________________;____________________________ 5.1 To minimize interferences when analyzing samples, teflon should not be used for sample storage or anypart ofinstrumentationthat comes in contact with the sample or extract. 6.0 Equipment__________________________________________________________________ 6.1 Equipment listed below maybemodifiedin order to optimize the system. Document any modifications in therawdataasmethod deviations. 6.1.1 Micromass QuattroII triple quadrupoleMass Spectrometer equipped with an electrosprayionization source 6 .1.2 HP1100 lowpulse solventpumping system, solvent degasser, column compartment, andautosampler 7.0 Supplies and Materials________________ ;_____________________________________ 7.1 Supplies 7.1.1 Highpuritygradenitrogengas regulated to approximately 100 psi (House air system) 7.1.2 HPLCanalytical column, specifics to be determinedby the analyst and documented in therawdata. 7.13 Cappedautovials or capped 15 mLcentrifuge tubes 8.0 Reagents and Standards________________________________ ;___________________ 8.1 Reagents 8.1.1 Methanol,HPLCgradeor equivalent 8.13 Milli-QTMwater, all waterused in this method should be Milli-QTM water or equivalent, andmaybe providedby aMilli-Q TOCPlus system or othervendor 8.13 Ammoniumacetate, reagent grade or equivalent 83 Standards 8.2.1 Typically two methodblanks, twomatrixblanks, andeighteen matrix standards are preparedduring the extractionprocedure. Sec ETS-8-4.1. 9.0 Sample Handling__________________________________________________________ _ 9.1 Freshmatrix standards arepreparedwith each analysis. Extracted standards and samples are storedin capped autovials or capped 15 mL centrifuge tubes until analysis. 3 M E n viro n m e n ta l L a b o ra to ry-- . ETS-8-5.1 AnalysisofSerumExtractUsing ES/MS . -- - , T-. _ Page 826 Page 3 of9 Page 68 3M Medical Department Study: T-6889.6 ------------ARGUS 418-020 Analytical Report: FACT TOX-164 LIM S E00-2738 92 If analysis will be delayed, extracted standards andsamples can be refrigerated at approximately 4 C, or at room temperature, until analysis can be performed. . 10.0 Q uality Control__________________________________________ _____________ 10.1 Solvent Blanks, Method Blanks and Matrix Blanks 10.1.1 Solvent blanks, methodblanks andmatrixblanks areprepared and analyzed with each batch to determine contamination orcarryover. 10.1.2 Analyze amethodblankand amatrixblankpriorto each calibration curve. 10.2 Matrix Spikes . 10.2.1 Matrix spikes arepreparedand analyzed to determinethe matrix effect onthe recovery efficiency. 1023. Matrix spike duplicates arepreparedand analyzedto measure the precision and the recovery foreach analyte. 10.2.3 Analyze amatrix spike andmatrix spike duplicateperforty samples, with a minimumof2 spikes perbatch. 10.2.4 Matrix spike andmatrixspike duplicate concentrations will fall in the mid-range of the initial calibrationcurve. Additional spike concentrations may fall in the lowrange ofthe initial calibration curve. 10.3 Continuing Calibration Verifications 10.3.1 Continuing calibrationverifications areanalyzedto verify the continued accuracy ofthe calibration curve. 10.3.2 Analyze amid-range calibrationstandardafterevery tenthsample, with a minimum of one perbatch. 11.0 C a l i b r a t i o n a n d S t a n d a r d i z a t i o n _______________________________________________ 11.1 Analyze the extractedmatrix standardspriorto andfollowing each set of extracts. The average oftwo standardcurves will be plottedby linearregression (y=my + b), weighted 1/x, not forced throughzero, using MassLynx orother suitable software. - 11.2 Ifthe curve does notmeet requirements,performroutine maintenance orreextract the standard curve (ifnecessary) andreanalyze. 113 Forpurposes of accuracy when quantitating low levels of analyte, it maybe necessaryto use the low end ofthe calibrationcurveratherthanthe full range ofthe standardcurve. Example: when attempting to quantitate approximately 10 ppb ofanalyte, generate a calibration curve consisting ofdie standards from5 ppbto 100 ppbratherthanthe full range of the curve (5 ppb to 1000 ppb). This will reduce inaccuracy attributedto linear regressionweighting of high concentrationstandards. . 3M Environmental Laboratory-- j ETS-8-5.1 A m ilv tit rtf S im m P.Ytnirt Ttino P S/M S ---- _ Page 827 Page 4 of9 Page 69 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIM S EOO-2738 12.0 Procedures__________________________________________________ __________ 12.1 Acquisition Set up 12.1.1 Click on start button in the Acquisition Control Panel. Set up a sample list. Assign a filename usingMO-DAY-last digit of year-sample number, assign a method (MS) for acquiring, andtype in sample descriptions. 12.1.2 To create amethod click on scanbuttonin the Acquisition control panel and select SIR (Single IonRecording) orMRM. Set Ionization Mode as appropriate andmass to 499 or other appropriatemasses. A full scan is usually collected alongwith the SIRs. Save acquisitionmethod. IfMS/MS instruments areemployed, additional product ion fragmentation informationmay be collected. See Micromass MassLynx GUIDETODATAACQUISITION for additional information and MRM (Multiple ReactionMonitoring). 12.1.3 Typically the analytical batchrunsequence begins with aset of extractedmatrix standards and ends with a set ofextractedmatrix standards. 12.1.4 Samples are analyzed with a continuing calibration check injected after everytenth sample. Solvent blanks shouldbe analyzedperiodicallyto monitorpossible analyte carryoverand are not considered samples but maybe included as such. 122 Using the Autosampler 12.2.1 Set up sample tray according to the sample list prepared in Section 12.1.1. 122.2 Set-up the HP1100/autosampler atdie following conditions or at conditions the analyst considers appropriate for optimal response. Record actual conditions in the instrument logbook: 12.2.2.1 Sample size = 10 pL injection 12.2.2.2 Inject/sample = 1 12.2.2.3 Cycle time *=13.5 minutes 12.2.2.4 Solvent ramp - Time 0.00min. 8.50 min. 11.0min. 12.0min. MeOH 40% 90% 90% 40% 2.0 mM Ammonium acetate 60% 10% 10% 60% 12.2.2.5 Press the "Start"button. 123 Instrument Set-np 123.1 Refer to ETS-9-24.0 formore details. 123 2 Check the solvent level in reservoirs andrefill ifnecessary. 3M Environmental Laboratory-- _ ETS-8-5.1 A n a lv m n f Jsffimi F.xtrairt I f*ino KS/MS ------- . Page 828 PageS of 9 Page 70 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 1233 Check the stainless steel capillary at the end ofthe probe. Use an eyepiece to check the tip. The tip should be flat with nojagged edges. Ifthe tip is found to be unsatisfactory, disassemble die probe andreplace the stainless steel capillary. 123.4 Set HPLCpump to "On". Set die flow to 10 - 500 uL/min or as appropriate. Observe droplets coming out ofthe dp ofthe probe. Allow to equilibrate for approximately 10 minutes. 123.5 Turn on thenitrogen. A fine mist shouldbe expelled with no nitrogen leaking around the dp of theprobe. Readjust the dp ofthe probe if no mist is observed. 123.6 The instrument uses theseparameters atthe following settings. These settings may change in orderto optimize the response: 123.6.1 Drying gas 250-400 liters/hour 123.63 ESI nebulizing gas 10-15 liters/hour ' 123.63 HPLC constant flow mode, flowrate 10- 500 pL/min 123.6.4 Pressure<400 bar(This parameteris not set, it is aguide to ensure the HPLCis operating correcdy.) 123.7 Carefully guide the probe into the opening. Insertprobe until it will not go any further. Connect the voltage cables to the probe. 123.8 Printthe tune page, withits parameters, andstore it in the studyhinderwith a copy tapedinto the instrument log. 123.9 Using die cross-flow counterelectrode in the ES/MS source is recommended for the analysis ofbiological matrices. 123.10Click on startbuttonin die Acquisition Control Panel (this may vary among MassLynx versions, see appropriateMassLynxUSER'S GUIDE). Press die start button. Ensure start and endsample numberincludes all samples to be analyzed. 13.0 Data Analysis and Calculations_________________________________________ 13.1 Calculations: 13.1.4 Calculate matrix spike percentrecoveries using the following equation: %Recovery* ObservedResult - BackgroundResult x 100 Expected Result 13.13 Calculate percent difference using the following equation: %Difference * Expected Cone. - Calculated Cone, x 100 Expected Cone. 13.1.6 Calculate actual concentrationofPFOS, orother fluorochemical, in matrix (ligfooL): fag ofPFOS calc, from std. Curvex Dilution Factor) x 1 ug /Initial Volume ofmatrix (mLI + mLof Surrogate Standard) 1000 ng Final Volume (mL) ETS-S-5.1 . Anilvsi* ofSerumExtractLisins ES/MS 3M Environmental Laboratory--^ +- *------- . Page 829 Page 6 o f9 Page 71 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 14.0 M e t h o d P e r f o r m a n c e _____________________________________________ _ 14.1 Method Detection Limit (MDL) andLimit ofQuantitation(LOQ) aremethod, analyte, and matrix specific. Please see ETS-8-4.1, Attachment B, for a listing of current validated MDL andLOQvalues. 14.2 Solvent Blanks, Method Blanks, and MatrixBlanks 14.2.1 Solvent blanks, methodblanks, andmatrixblanksvalues are mustbe below the lowest standardin the calibrationcurve 143 Calibration Curves 14.3.1 The r3 value for the calibration curvemust be 0.980 orbetter. 14.4 Matrix Spikes . 14.4.1 Matrix spikepercent recoveries aremustbe within 30%ofthe spiked concentration. 14.5 Continuing Calibration Verifications 14.5.1 Continuing calibrationverificationpercentrecoveries must be 30%ofthe spiked concentration. 14.6 If criterialisted in thismethodperformance section isn't met, maintenancemaybe ' performed on the system andsamples reanalyzed orotheractions as determinedby the analyst Document all actions in the appropriate logbook. 14.7 Ifdataare to be reportedwhenperformancecriteriahave not been met, the datamust be footnoted ontables anddiscussed inthetext ofthereport 15.0 Pollution Prevention and Waste Management____________________________ 15.1 Sample extractwaste and flammable solvent is disposed inhighBTU containers, and glass pipette waste is disposedinbrokenglass containerslocated inthe laboratory. 16.0 R e c o r d s ____________________________________________________________________________________________ 16.1 Eachpage generatedfor astudymusthavethefollowing informationincluded eitherin the header orhandwritten on the page: studyorprojectnumber, acquisitionmethod, integrationmethod, sample name, extraction date, dilutionfactor (ifapplicable), and analyst 16.2 Print the tunepage, sample list andacquisitionmethod fromMassLynx to include in the appropriate study folder. Copy thesepages andtape into the instrument runlog. 163 Plot the calibration curveby linearregression,weighted 1/x, thenprint these graphs and store in the studyfolder. 16.4 Print dataintegration summary, integrationmethod, andchromatograms, fromMassLynx, and store in the studyfolder. 3M Environm ental Laboratory ETS-8-5.1 Analysis ofSerumExtractUsingES/MS Page 830 Page 7 o f9 Page 72 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 16.5 Summarize datausing suitable software (Excel 5.0) and store in the study folder, see Attachment A for an example ofa summaryspreadsheet 16.6 Back up electronic datato appropriatemedium. Record in study notebook the file name and location ofbackup electronic data. 17.0 T ables. Diagrams. Flowcharts, and Validation Data_______________________ 17.1 Attachment A: ETS-8-5.1 Datasummary spreadsheet 18.0 References_____________________________________________________ _______ 18.1 FACT-M-4.1, "ExtractionofPotassiumPerfiuorooctanesulfonate or OtherFluorochemical compounds fromSerumforAnalysis UsingHPLC-Electrospray/Mass Spectrometry 18.2 ETS-9-24.0, "Operation andMaintenance ofthe Micromass Atmospheric Pressure lonization/Mass SpectrometerQuattro n triple quadrupole Systems" 1&3 The validation report associatedwiththis methodis ETS-8-4.0 &5 .0-V-l. 19.0 a f f e c t e d D o c u m e n t s ____________________________________________________________________________ 19.1 ETS-8-4.1, "Extraction ofPotassiumPerfiuorooctanesulfonate or OtherFluorochemical Compounds fromSerumfor AnalysisUsingHPLC-Electrospray/Mass Spectrometry" 20.0 R e v i s i o n s _______________________________________________________________________________________ Revision Number. 1 Reason For Revision Section 6.1.2 Clarification ofHP1100 systemcomponents. Section 11.1 Average oftwo curves, not standardvalues, areused for plotting linearregression and added die 1/x weighting ofthe curve. Section 12.2.2.4 Clarification of solvent ramp. Section 17.1 Changed from attachmentB to A. Revision Date 04/02/99 3M Environm ental Laboratory ETS-8-5.1 Analysis ofSerumExtractUsingES/MS Page 831 Page 8 o f9 Page 73 3M Medical Department Study: T-6889.6 --------- ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 L aboratory Study # ` Study: Test Material: Matrix/Final Solvent Method/Revision: Analytical Equipment SystemNumber Instrument Software/Version: Filename: R-SquaredValue: Slope: YIntercept Date ofExtraction/Analyst Date ofAnalysis/Analyst Group Sample# Concentration Dose . ug/mL Initial VoL mL Dilution Factor Final Cone. ug/mL Slope: Takenfromlinearregressionequation. - Group/Dose: Taken fromthe study folder. Sample#: Takenfromdie studyfolder. Concentration (ug/mL): Taken fromthe MassLynxintegrationsummary. Initial Volume (mL): Takenfromthe studyfolder. DilutionFactor. Takenfromthe studyfolder. Final Cone. (ug/mL): by dividingdieinitialvolume fromdie concentration AttachmentA*Summary Spreadsheet ETS-8-5.1 . Analysis ofSerumExtractUsingES/MS 3M Environm ental Laborato ry , _ Page 832 Page 9 of9 Page 74 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Method Modification M ethods: Section modified: ETS-8-7.0, ETS-8-5.1, ETS-8-97.0 add section 14.3.2 Method reads: NA Modify method toread: 14.3.2 The second(bracketing)calibrationcurve mtybe deactivatedif instrumental drift affects the data. The first curveandacceptablecalibration hall bracketusabledata. Effective date ofmodification ETS-8-7.0: 7/22/99 Effective date ofmodification ETS-8-5.1: 4/26/99 Effective date ofmodification ETS-8-97.0: 7/28/99 Signature ofPAI anddate Exsct Copy of Original 3M Environm ental Laborato ry Page 833 Page 75 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 3M Environmental Laboratory t Method Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry Method Number. ETS-8-5.2 Adoption Date: 03/01/99 Author: Lisa Clemen, Kris Hansen Revision Date: i) l l Of Approved By: - f r ur*.---- ------------------------Laboratory Manager Date U Group Leader ?2-/c i f c f Date 'o f Technical Reviewer B ori Copyof Origini - t - d J .Zfo/e/ tatti M i 1.0 Scope and Application____________________________________________________ 1.1 Scope: This method describes the analysis of serumextracts for fluorochemical surfactants using HPLC-electrospray/mass spectrometry. 1.2 Applicable Compounds: Fluorochemical surfactants or other fhiorinatedcompounds, or other ionizable compounds. 1.3 Matrices: Rabbit, rat, bovine, monkey, and human serum, or other fluids as designated in the validation report. Word 6/95 3M Environm ental Laboratory-- ___ -- ETS-8-5.2 T W CCA4C Page 834 Page 1of 11. Page 76 3M Medical Department Study: T-6889.6 - --------- - ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 2.0 S u m m a r y o f M e t h o d ______________________________________________________________________________ _ 2.1 Although supported by a validation for most commonlyused matrices, this is a \ performance-basedmethod. Careful attentionshould be paid to method QC as there is great variability in sera. This method describes the analysis of fluorochemical surfactants extracted fromserumor other fluids, using HPLC-electrospray/mass spectrometry, or similar system as appropriate. The analysis is performed bymonitoring asingle ion characteristic of aparticular fluorochemical, such as the perfluorooctanesulfonate (PFOS) anion, m/z= 499. Additionally, samples may be analyzedusing a tandemmass spectrometer to further verify the identity of acompound by detecting daughter ions of the parent ion. 3.0 D e f i n i t i o n s ___________________________________________________________________________________________ 3.1 Atmospheric Pressure Ionization (API): The Micromass Quattro II andUltima triple quadrupole systems allow for various methods of ionization by utilizing various sources, probes, and interfaces. These include but are not limited to: Electrospray Ionization (ESI), Atmospheric Pressure chemical Ionization (APcI), Thermospray, etc. The ionization process in these techniques occurs at atmospheric pressure (Le.t not under a vacuum). 3.2 Electrospray Ionization (ES, ESI): a method of ionization performed at atmospheric pressure, wherebyions in solution are transferred to the gas phase via tiny charged droplets. These charged droplets are produced by the application of astrong electrical field. 3.3 Mass Spectrometry, Mass Spectrometer (MS), Tandem Mass Spectrometer (MS/MS): The API Quattro II andUltimatriple quadrupole systems are equipped with quadrupole mass selective detectors. Ions are selectively discriminated by mass to charge ratio (m/z) and subsequently detected. A single MS maybe employed for ion detection or a series (MS/MS) for more specific fragmentation information. 3.4 Conventional vs. Z-spray probe interface: The latest models of Micromass triple quadrupole systems (post 1998) utilize a "Z-spray" conformation. The sprayemitted from a probe is orthogonal to the cone aperture. In the conventional conformation it is aimed directly at the cone aperture, after passing through a tortuous pathway in the counter electrode. Though the configuration is different, the methods of operation, cleaning, and maintenance are the same. H ow ever. Z-spray com ponents and conventional com ponents are not compatible with one another, but only with similar systems (i.e., Z-spray components are compatible with some otherZ-spray systems, etc.) 3.5 Mass Lynx Software: System software designed for the specific operation of these Quattro II triple quadrupole systems. CurrentlyMassLynx has 'Windows 95 andWindowsNT 4.0 versions. All versions are similar. For more details see the manual specific to the instrument (Micromass Quattro II or Ultimatriple quadrupole MassLynx or MassLynx NT User's Guide). 4.0 W a r n i n g s a n d C a u t i o n s _______________________________________________ 4.1 Health and Safety Warnings: 4.1.1 Use caution with the voltage cables for the probe. When engaged, the probe employs a voltage of approximately 5000 Volts. Word 6/95 3M Environm ental Isihnm tary ETS-8-5.2 Analysis of Serum Extract Usine ES/MS ... ------ __ Page 835 Page 2 of 11 Page 77 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 4.1.2 When handling samples or solvents wear appropriate protective gloves, eyewear, and clothing. 4.2 Cautions: 4.2.1 Do not operate solvent pumps above capacity of 400 bar (5800 psi) back pressure. If the back pressure exceeds 400 bar, the HPLCwill initiate automatic shutdown. 4.2.2 Do not run solvent pumps to dryness. 5.0 I n t e r f e r e n c e s ___________ ______________________________________________________________ 5.1 To minimize interferences when analyzing samples. Teflon should not be used for sample storage or anypart of instrumentation that comes incontact with the sample or extract. 6.0 E q u i p m e n t __________________________________________________________________;__________ 6.1 Equipment listed below maybe modified in orderto optimize the system. Document any modifications in the raw data as method deviations. 6.1.1 Micromass Qualtro II orUltimatriple quadrupole Mass Spectrometer equipped with anelectrospray ionization source 6.1.2 HP1100 or Agilent low pulse solvent pumping system, solvent degasser, column compartment, and autosampler 7.0 Supplies and Materials_________________________________________________ 7.1 Supplies 7.1.1 High purity grade nitrogen gas regulated to approximately 100 psi (House air or nitrogen system) 7 .1 .2 HPLC analytical column, specifics to be determinedbythe analyst and documented in the rawdata. 7.1.3 Capped autovials and capped 15 mLcentrifuge tubes 8.0 Reagents and Standards________________________________________________ 8.1 Reagents 8.1.1 Methanol. HPLC grade or equivalent 8 .1 .2 Milli-QTMwater, all water used in this method should be Milli-QTM water or equivalent, and may be providedby aMilli-QTOCPlus systemor other vendor 8.1.3 Ammoniumacetate, reagent grade or equivalent 8.2 Standards 8.2.1 Typically two method blanks, two matrixblanks, andeighteen matrix standards are prepared during the extractionprocedure. See ETS-8-4.2. . 3M Environmental Laboratory A w lw tit ____ _ ETS-8-5.2 lle iw e P C /M C Page 836 Page 3 of 11 Page 78 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 9.0 S a m p l e Handling_______________________________________________ _________ _ 9.1 Fresh matrix standards are prepared with each analysis. Extracted standards and samples are stored in capped autovials or capped IS mLcentrifuge tubes until analysis. 1 93 If analysis will be delayed, extracted standards and samples can be refrigerated at approximately4 C, or at roomtemperature, until analysis can be performed. 10.0 Quality Control 10.1 Solvent Blanks, Method Blanks and Matrix Blanks ________ 10.1.1 Solvent blanks, method blanks andmatrix blanks are prepared and analyzed at least once during the course of the studyto determine if contamination occurred during sample prep. 10.1.2 Analyze at least one solvent blankpriorto each calibration curve. 10.1.3 Matrix blanks should be analyzed with each sample list that includes undiluted extracts. 10.2 Matrix Spikes 10.2.1 If curves andmethod QCare preparedina surrogate matrix (e.g. curves in rabbit sera, samples are monkey sera), matrix spikes andmatrix spike duplicates are prepared in blank sample matrix (e.g., monkeysera) and analyzed to verify extraction efficiency. 10.2 .2 If curves andmethod QCare prepared inthe samematrix as samples, no additional matrix spikes are required. 103 Continuing Calibration Verifications (CCVs) 103.1 Continuing calibration verifications are analyzed to verify the continued accuracy of . the calibrationcurve. 1033 Analyze two calibrationstandards (one at each of 2 levels) after every one to ten samples, with a minimumof two per batch and always finishing an injection sequence with at least two calibration standards. 11.0 Calibration and Standardization________________________________________ 11.1 Analyze the extractedmatrixcalibration standards prior to each set of extracts. The curve will be plotted by linear regression, weighted 1/x, not forced through zero, using MassLynx or other suitable software. 113 Ifthe curve does not meet requirements, performroutine maintenance, reextract samples, or reanalyze the standardcurve. 113 For purposes of accuracywhen quantitating levels of analyte at the limits of the curve range, it maybe necessary to use eitherthe low end or the high end of the calibration curve rather than the full range of the standardcurve. Example: when attempting to quantitate approximately 10 ppbof analyte, it maybe beneficial to generate a calibration curve consisting of the standards from5 ppb to 100 ppb rather thanthe full range of the curve (5 ppb to 1000 ppb). This will reduce inaccuracy attributed to linear regression weighting of ETS-8-5.2 Analysis o f Serum Extract Usine ES/MS 3MEnvironmental Jnhnmtmy ^ ____-- Page 837 Page 4 of 11 Page 79 3M Medical Department Study: T-6889.6 -----------ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 high concentration standards. It is also acceptable to breakthe linear range into a low curve and a high curve. Ifthis is done, no more than one point should be used in common between the curves. For example, the low curve may include the following points: 1,5, 25, 100,250 ppb and the high curve may include the points: 250,500,750,1000,1250 ppb. 12.0 Pr o c e d u r e s ____________________________________________________ ____ 12.1 Acquisition Set np 12.1.1 On the MassLynx mainpage, set upa sample list name. Save the list as instrument designator letter, last 2 digits of test year-mo-day, and a letter that will increase through the alphabet with each additional list for that day. Example Sample List: IYYMMDDa or D010712a . I=instrument name (D for "Davey") YY=year of test (01) MM=month of test (07) DD=day of test (12) a=first sample list (run) of the day (the next sample list will end with `b,' the next `c' and so on.) 12.1.2 Assign a filename using the instrument designator letter, the last 2 digits of year-moday, anda 3-digit sequential file number that starts with 1andincreases by one for each filename. Example File Name: IYYMMDD### or D010712001 I=instrument name (D for "Davey") YY=year of test (01) MM=month of test (07) DD=day of test (12) ###=3-digit sequential file number starting with 1 through 999 (001) Also, as part of the sample list, assign amethod (MS) for acquiring, an inlet file, a bottle number, an injection volume and sample descriptions. 12.123 To create a method, click on Method Editor button in the MS Status Pane and select SIR (Single Ion Recording) or MRM(Multiple Reaction Monitoring). Set Ionization Mode as appropriate andmass to 499 or other appropriate masses. Also set the acquisition start andstop times. Save acquisition method If MS/MS instruments are employed, additional product ion fragmentation information may be collected See Micromass MassLynx GUIDE TO DATAACQUISITION for additional information andMRM. 12.1.4 Typically the analytical batch runsequence begins with solvent blanks and a set of extracted matrix standards. . 12.1.5 Sample extracts are analyzedwith two CCVs injected every one to ten samples. Solvent blanks should be analyzed periodically to monitor possible analyte carryover and are not considered sample extracts but may be included as such. 3M Environmental la b o ratory E T S -8 -5 .2 Analvais ofSonno F.rtract Usino FS/MS Page 838 Page 5 of 11 Page 80 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 122 Using the HPLC 12*2.1 Set up sample tray according to the sample list prepared in Section 12.1.1. 1222 Set-up the HPLCto the following conditions or at conditions the analyst considers appropriate for optimal response. Record actual conditions in the instrument logbook: 1222.1 Sample size = 10 pL injection 12222 Inject/sample = 1 12222 Cycle time = 10.0 minutes 12224 How rate = 300 pL/nrin 12225 Mobile Phase (program) . Time 0 .0 0 min. 1 .0 0 nrin. 5.50 min. 7.50 min. 8 .0 0 min. MeOH 10% 10% 95% 95% 10% 20 mMAmmonium acetate (in H20) 90% 90% 5% 5% 90% 1223 Instrument Set-up 123.1 Refer to ETS-9-24 for more details. 1232 Check the solvent level inreservoirs andrefill if necessary. 1233 Check the stainless steel capillary at the end of the probe. Use an eyepiece to check the tip. The tip should be flat with nojagged edges. If the tip is found to be unsatisfactory, disassemble the probe and replace the stainless steel capillary. The probe should be checked weekly. 123.4 Set HPLCpump to "On". Set the flow to 10 - 500 pL/min or as appropriate. Observe droplets coming out of the tip of the probe. 1235 Turn on the nitrogen. A fine mist should be expelled with no nitrogen leaking around the tip of the probe. Readjust the tip of the probe if no mist is observed. 123.6 The instrument uses these parameters at the following settings. These settings may change inorder to optimize the response: 123.6.1 Drying gas 250-400 liters/bour 123.62 ESI nebulizing gas 10-15 liters/hour 122.63 HPLCconstant flow mode, flow rate 10- 500 pL/min 123.6.4 Pressure <400 bar (This parameter is not set, it is a guide to ensure the HPLCis operating correctly.) 123.7 Carefully guide the probe into the opening. Insert probe until it will not go any further. Connect the voltage cables to the probe. 3M Environm ental Laboratory-- ETS-8-5.2 Analysis of Serum Extract Using ES/MS ------^,7-..- -- Page 839 Page 6 of 11 Page 81 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 12.3.8 Print the tune page, MS file, HPLCparameters, sample list and the Microsoft Word summary page and store in the study binder with a copy taped into the instrument log. 12 3 .9 Click on start button in the MassLynx mainpage (this may vary among MassLynx versions, see appropriate MassLynxUSER'S GUIDE). Ensure start andend sample number includes all samples to be analyzed. 13.0 D a t a A n a l y s i s a n d C a l c u l a t i o n s _____________________________________________________________ 13.1 Calculations: 13.1.1 Calculate matrix spike percent recoveries using the following equation: _ ,, Observed R esult - M atrixBlank R esult 9h R ecovery = ----------------------------------------------------------- x 100 Spuung Level 13.1.2 Calculate percent difference using the following equation: _% D ifference = Expected Cone. - Calculated Cone. -- ---------- ------------------------------------- x 100 Expected C one 13.1.4 Calculate actual concentration of PFOS, or other fluorochemical, inmatrix (pg/mL): T( Cone, o f PFOS Calc, from Std. Curve ( n g / mL) x Dilution F actor) ( Initial Volume o f M atrix (mL) + m L c f Surrogate Standard) Final Volum e( m L ) J 1 fig 1000 ng 14.0 Method Performance_____________________________________________________ 14.1 Method Detection Limit (MDL) andLimit of Quantitation (LOQ) are method, analyte, and matrix specific. Please see ETS-8-4.2, Attachment B, for a listing of current validated MDL andLOQ values. 14.2 Solvent Blanks, Method Blanks, and M atrix Blanks 14.2.1 Solvent blanks, method blanks, and matrix blanks values must be below the lowest active standard in the calibrationcurve. 143 Calibration Curves 143.1 The coefficient of determination value for the calibration curve must be 0.990 or better. . 3M Environmental Laboratory-- . E T S -8 -5 .2 -------A--n-nlvci n_fS m im F.*rrart Thine FS/MS Page 840 Page 7 of 11 Page 82 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 143.2 All active calibration curve points must be within 25% of the theoretical value with the exception of the LOQ point, which may deviate up to 30%. 14.3.3 Calibration standards with peak areas less than two times the curve matrix blank must be deactivated to disqualify a data range that may be affected by background levels of the analyte. 143.4 Low or high curve points may be deactivated to optimize a linear range appropriate to the data. 1 4 3 3 Not including low or high points dropped to optimize the linear range, curve points may be deactivated if they deviate more than 25% from the theoretical value when the curve is evaluated over a linear range appropriate to the dara 143.6 One point below the LOQ may remain active even if it deviates more than 30% or has a peak area less than two times the matrix blank; however, the LOQ will be defined at the lowest point with acceptable deviation. 143.7 A valid calibration curve must contain at least 5 active points above and including the LOQ. 14.4 Matrix Spikes 14.4.1 The average matrix spike percent recoveries should be within 30% of the spiked concentration. Recoveries outside of this range should be discussed in the report. 143 Continuing Calibration Verifications (CCVs) . 143.1 Continuing calibration samples within the linear range of the run must show a percent recovery within 25% of the spiked concentration. If a CCV is outside of this recovery, subsequent data should not be accepted. Acceptable data must be bracketed by the curve and passing CCVs. 14.6 If criteria listed in this method performance section isn't met, maintenance may be performed on the system and samples reanalyzed or other actions as determined by the analyst. Document all actions in the appropriate logbook. 14.7 If data are to be reported when performance criteria have not been met, the data must be footnoted on tables and discussed in the text o f the report. 15.0 Pollution Prevention and Waste Management___________________________ 15.1 Sample extract waste and flammable solvent is disposed in high BTU containers, and glass pipette waste is disposed in broken glass containers located in the laboratory. 16.0 Records_______________________________________________________________ 16.1 The first page of each data packet generated for a study must have the following information included either in the header, in the footer or hand written on the page: study or project number, instrument, sample matrix and time point, date, and analyst. 163 A data packet includes the following; data review summary form, MassLynx quantify compound summary report for each target analyte, quantify calibration report for each target analyte (curve), method report, Word document listing set-up parameters, tune 3M Environmental Jjihnrntm y ETS-8-5.2 Analysis of Serum Extract Using ES/MS . ____ _ __ Page 841 Page 8 of 11 Page 83 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 method report, MassLynx scanning method report, HPLC method report, sample list, and quantity sample report (chromatogram). 163 For each analysis, after printing the tune method report. Word document listing, set-up parameters, MassLynx scanning method report, and sample list, copy and tape into the instrument runlog. The original is maintained in the data packet. 16.4 On each page of the quantify compound report, quantify calibration report (curve), and quantify sample report (chromatogram), the following information must be included either in the header, the footer, or hand written on the page: study or project number, instrument, method, calibration (the method and calibration are usually assigned the same name), analyst, and date. 163 The analyst must date and initial the first page in a packet as long as their initials and daty are electronically included on each page. If initials and date are not electronically included, they must date and initial each page. 16.6 Summarize data using suitable software (e.g., Excel) for inclusion in the final report. See Attachment A for an example of a summary spreadsheet. 16.7 Back up electronic data to appropriate medium. Record the file name and location of backup electronic data in instrument log book. 17.0 Tables. Diagrams. Flowcharts, anp Validation Data______________________ 17.1 Attachment A: Data summary spreadsheet. 18.0 REFERENCES___________________________________________________________________ 18.1 FACT-M-4.1, "Extraction o f Potassium Perfiuorooctanesulfonate or Other Fluorochemical compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry 18.2 ETS-9-24.0, "Operation and Maintenance o f the Micromass Atmospheric Pressure lonization/Mass Spectrometer Quattro II triple quadrupole Systems" 1 8 3 T h e validation re p o rt associated w ith this m ethod is ETS-8-4.0 & 5.0-V -l. ' 19.0 Affected Documents______________________________________________________ 19.1 ETS-8-4.2, "Extraction of Potassium Perfiuorooctanesulfonate or Other Fluorochemical Compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry" . 3M Environmental Laboratory ETS-8-53 Analysis of Serum Extract Usine ES/MS . ___ _ _ Page 842 Page 9 of 11 Page 84 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 20.0 Revisions_____________________________________________________________________ Revision ; Number. Reason For Revision 1 1 Section 6.1.2 Clarification of HP1100 system components. Section 11.1 Average of two curves, not standard values, are used for plotting linear regression and added the 1/x weighting of the curve. Section 12.2.2.4 Clarification of solvent ramp. Section 17.1 Changed from attachment B to A. Revision Date 04/02/99 2 10.1 Clarified when blanks arerun. 10.2 Added instructions for when surrogate matrix is used. 103 Specify requirements for CCVs. 11.1 Requires onlya calibration curve before thesamples. . 113 Clarify what to do if curvedoes not meet requirements. 113 Allow to truncate the curve. 12.1.1 Clarifysample list ID. 12.1.3 Clarify typical run. 123 Changes to mobile phase gradientand specify flowrate. 143 Change acceptable limits. Add specifics for acceptance of calibration curve. 14.33 When to deactivatecalibration standards based on blank response. 1433 When to deactivate calibration standards within the linear range. 14.4 Modifies evaluation and use ofmatrix spikes. 143 Describes evaluation and use of CCVs. 143.1 Evaluation ofCCVs. 16.0 Add requirements for records and documentation. Attachment A: SummarySpreadsheet ETS-8-5.2 Analysis ofSerum Extract Using ES/MS 3M Environm entalLaboraiaqu~- i --- ------ _ Page 843 Page 10 of 11 Page 85 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 Laboratory Study # k Study: Test Material: Matrix/Fmal Solvent: Metfaod/Revision: Analytical Equipment SystemNumber Instrument Software/Version: Filename: R-Squared Value: Slope: Y Intercept: Date of Extraction/Analyst Date of Analysis/Analyst Group Sample# Concentration Dose np/tnL Initial VoL mL Dilution Factor Final Cone. ue/mL SIodc: Taken from linearregression eouation. Groun/Dose: Taken from the study folder. Sample#: Takenfromthe study folder. Concentration lue/mL): Taken from the MassLvnx integration summary. Initial Volume (mL): Taken fromthe study folder. Dilution Factor: Taken fromthestudy folder. Final Cone. (ue/mLl: Calculated by dividing the initial volume from the concentration Attachment A: Summary Spreadsheet ETS-8-5.2 Analysis of Serum Extract Using ES/MS 3M Environmental Laboratory Page 844 Page 11 of 11 Page 86 3M Medical Department Study: T-6889.6 3 M M e d ical D epartm en t Study: T -6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 UMS EOO-2738 A n alytical R e p o r t F A C T T O X -1 64 U M S EO O-2738 Appendix D: Dose Confirmation Analyses and Data Sum m ary Tables Table 12. D ose Confirm ation A nalyses - Extracted 11/17/00, Analyzed 11/27/00 Group Dose Sam ple Concentration of PFOA ug/m Lor % R e c t Expected Cone of PFOAugAnL* % Recovery Method Bik OC 111700-WBik-1 111700-WB#t-2 111700-WBik-3 B-418-020-A-C-100ppt>-MS B-418-020-A-C-100oOt>-MSO <LOQ (10 ng/mL) <LOQ (10 ng/mL) <LOQ (10 no/mL) 0.0822 0.0855 NA NA NA 0.0979 0.0979 j1 NA 1 64% 87% B-416-C20-A-C-0.5 mL Stability Dey 0 11/10/00 B-41B-020-A-A-0.5 mi. <LOQ (10 ng/mL) <LOQ (10 ng/mL) NA NA NA B-418-020-A-D10-0.5 mL <LOQ (10 no/mU NA B-418-020-A-A-1 <LOQ (10 ng/mL) NA NA B-418-020-A-A-2 <LOO (10 no/mU NA B-41B-020-B-A-1 191 200 95% Stability Day 0 ll/ioroo B-41B-020-B-A-2 B-418-020-C-A-1 B-418-020-C-A-2 B-416-020-D4-1 B-41B-020-D-A-2 189 485 438 1809 1893 200 95% 600 81% 600 73% 2000 90% 2000 95% B-418-020-E-A-1 5579 6000 93% B-41B-020-E-A-2 6350 6000 106% B-418-020-A-010-1 <LOQ (10 ng/mL) NA NA B-418-Q20-A-D10-2 LOQ (10 no/mL) NA B-416-020-B-D10-1 B -*18-020-B-D10-2 177 175 200 88% 200 68% Stab1il1i/t1y0D/0a0y 10 B-41S-020-C-D10-1 6 4 1 8-020-C-D10-2 B-41B-020-D-O10-1 B-418-020-D-D10-2 481 451 1732 1685 600 77% 600 75% 2000 87% 2000 85% B-418-020-E-D10-1 5825 6000 97% B-41B-020-E-D10-2 5614 6000 94% B-418-020-A-C-1 <LOQ (10 ng/mL) NA B-418-020-A-C-2 <LOQ (10 no/mL) NA NA B-418-020-B-C-1 j 179 200 90% B-418-020-B-C-2 ! 170 200 85% Con11c/e1n0t/r0a0tion B-418-020-C-01 B-418-020-C-C-2 494 478 600 82% 600 80% B-418-020-D-C-1 1820 2000 91% B-418-020-0-C-2 1800 2000 90% B-418-020-E-C-1 6140 6000 102% B-418-020-E-C-2 6026 6000 100% * Information was obtained from chain of custody forms accompanying samples. PFOA j PFOA Mean ' RPD NA . ii NA 1 86% 4% NA NA NA NA 95% 1% 77% 10% 93% 5% 99% 13% NA NA 88% 1% 7% 2* 86% 2% 95% 4% NA NA 87% 5% 81% 3% 90% 1% 101% 2% tU F nuim nm antal I ahnratnrv 3 M E n viro n m en ta l L a h n ra tm y ... . Page 845 Paoe21 Page 87 3M Medical Department Study: T-6889.6 3 M M e d ical D epartm en t Study: T -6889.6 ------------ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 A n alytical Report: F A C T T O X -1 6 4 L IM S E 00-2738 Table 13. D o se Confirm ation Analyse - Extracted 11/27/00, Analyzed 11/28/00 Group Dose Sam ple# I I Concentration of PFOA Expected Cone of PFOA PFOA uq/mL or % Roe PFOAug/mL* ! % Recovery Meen i RPD 112700-WBHt-l i <LOQ (10 ng/mL) NA : Method Bik 112700-WBIk-2 1 <LOQ (10 ng/mL) NA NA NA 112700-WB*k-3 ! <LOQriOna/mLl NA i 1 QC I B-418-020-A-C-100ppb-MS J B-418-020-A-C-100oob-MSD 0.0864 0.0856 0.0679 0.0979 88% 87% 88% 1% Stability Day 0 j 11/10/00 B-418-020-A-C-0.5 mL B-418-020-A-A-0.5 mL <LOQ (10 ng/mL) <LOQ (10 ng/mL) NA NA NA NA NA ' B-41B-020-A.D104.5 mL LOO MOna/mLl NA I B-41ILC20-A-A-1 B-*18-02(Wt-A-2 cLOQ (10 niymL) <LOO (10 na/mLl NA NA NA NA NA B-418-020-B-A-1 B-418-C20-B-A-2 155 147 200 200 76% 73% 76% 6% Stability Dey 0 11/10/00 B-418-020-C-A-1 B-418-020-C-A-2 489 468 600 600 82% 78% 80% 4% B-418-020-D-A-1 B-41S-020-D-A-2 1788 1793 2000 2000 89% 90% 90% 0% B-41W20-E-A-1* B-41S-020-E-A-2* 11183 11256 6000 186%A 187%* 1% 6000 168%* B-418-020-A-010-1 B-416-020-A-D10-2 LOQ (10 ng/mL) LOO (10 na/mLl NA NA NA NA NA B-418-020-B-010-1 B-418-020-B-D10-2 138 157 200 200 69% 78% 74% 13% Stability Oey 10 B-41S-020-C-D10-1 11/10/00 B-418-020-C-D10-2 464 496 600 77% 80% 7% 600 83% B-41B-020-0-010-1 B-41B-020-D-010-2 1560 1756 2000 2000 78% 88% 83% 12% B-41S-020-E-D10-1 B-41B-020-E-010-2 5553 5657 6000 6000 93% 99% 96% 7% B-418-Q20-A-C-1 B-41ILC20-A-C-2 LOQ (10 ng/mL) <LOQ HO na/mLl NA NA NA NA NA I B-418-020-B-C-1 1 B-418-02O-B-C-2 158 165 200 200 79% 62% 81% 4% Con11c/e1n0t/r0a0tion B-418-020-C-C-1 B-41S-020-C-C-2 452 443 600 600 75% 74% 75% 2% B-416-C20-O-C-1 B-41S-020-0-C-2 1741 1883 2000 2000 87% 94% 91% 8% B-41B-020-E-C-1 B-418-020-E-C-2 5376 5441 6000 90% 90% 1% 6000 91% 1 * a Sam ple re-extracted o n 01/23/01 to confirm recovery. Recovery w as not confirmed, considered an outlier. * Information w as obtained from chain o f custody form s accom panying sam ples. 3M FnvimnmtmtalLaboratory 3M Environmental Ijihnrntary . .. . . Page 846 Paoe22 Page 88 3M Medical Department Study: T-6889.6 3 M M e d ica l D epartm en t Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 A n alytical R e p o r t F A C T T O X -1 6 4 L IM S EO O-2738 Table 14. D ose Confirm ation A nalyses - Extracted 01/17/01, Analyzed 01/23/01 Group Dose 1 ! Sam ple* Concentration of PFOA Expected Cone of u sfrn L o r% R e c PFOAug/mL* % Recovery Method Blk i 011701-WBUc-l-l <LOQ (10 ngftnL) NA NA 011701-WBIk-1-2 <LOQ (10 rxVmu NA Sta1b1il/i1ty0/D00ay 0 !1 B-418-020-E-A-1 B-418-02O-E-A-2 5466 5014 6000 91% 6000 84% * Information was obtained from chain of custody forms accompanying samples. PFOA Mean NA 87% PFOA RPO NA 9% Table 15. T O X 164 Data Sum m ary of PFO A Concentration-- Rat Serum (pg/mL) Gender/ H m epolnt PFOA Cone. Average S D Group 1 (X0 mg/kg/day Group* lOmg/kg/day Group 5 30 mg/kg/dey Female Lactation Day 22 Male End of cohabitation Female Lactation Day 22 Male End of cohabitation Female Lactation Day 22 Male End of cohabitation <LOQ (0.00528 ug/mL) r*3 0.0344 0.0148 n*3 OSTO 0.0805 n>10 51.1 9.30 rw10 1.02 0.425 n>10 45.3 12.6 rt>10 3 M EnvironmentalLaboratory 3MEnvironmental Tsihnr n ta iy .... Page 847 Paoe 23 Page 89 3M Medical Department Study: T-6889.6 3 M M e d ical D epartm en t Study: T -6889.6 Appendix E: Data Spreadsheets ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 A n alytical Report: F A C T T O X -1 6 4 L IM S E00-2738 3MEnvironm3eMntEanlvLiarbonomreanttoarlyLaborat.o.r. y______ Page 848 Paae24 Page 90 3M Medical Department Study: T-6889.6 FACT-TOX-144 A rfo * 418420 imtr Pa* n Na*(TNHm m ctt fACT-TOX-tM. A i a 4 t* a O a U G ^ ta e lT i i Cm ff A Cmrm- -- 3-- ta rvS*4.l4C T M S.I D--y 07079* i n a t a n f -- ; X APPO a t i ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Omm tUm ta r f lta U M N 'A iii post VERIFICATION SAMPLES O-- One s" * " ' M atad Ilk OC ta x a i Day 11/10*3000 SitailHy Pay 0 11/100000 S utatayleyio 11/10/3000 lll?00WBIk-l IH T O O .W II-2 IMTOO-WBfc.J B-4i*420A-C-l<n--XMS B ^ ft-030-A-C-100--1 MSP B -4 l* -0 2 0 > A ^4 .)aL M IM lt<A <A 4SM .4 I9 4 2 0 .A -D I0 4 J mL B-41W20-A-A-I B4IIO20>A-A'2 BA IM U O ^-A -I B-41-O JM -A -: B ^IM 20-C *A -l |4 lt-0 2 0 -C * A > 2 B-4I K O-O-A-l B-4l-020-D-A-: B-41-020--A-I B-41M30-E-A-2 0-4l*-O2<NADiO.I B -ilt- U O -B -D tO -t B-4I-CQOC-OIO.I B-411420-D-DlO' l fr4l4B0E-DJ<Ni B-4l*02Q-A-C-i B-411-020-A-C-2 B -4 l* ^ 2 0 .B - C - i B-4lt-OJO-B-C-2 B-4l*02OC-C-l B -4t43aC C -2 B aiM U O ^X -l b-* i *-02o-d-c .: *4I*020>E<-1 II/I7A 0 RWW 11/2700 MMH 11/2*00 MMH Im -- VflL mL j1 I1 !! ii 11 i 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 talO pM NA NA na NA Na Na NA NA , na NA NA NA NA NA NA NA NA NA NA na NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA na NA mu Hi 103 103 IOS 105 105 105 IOS I.J 105 IOS 105 IOS 105 IOS 105 IOS 105 >03 105 IOS 105 IOS 1 U i" 103 US 105 IOS IOS IOS IOS 105 to s IOS IOS IOS IOS IOS 105 -I 1 1 1 1 1 2 2 2 2001 2001 2001 2001 S00I 9001 30001 20001 SQ00I 50001 2001 2001 2001 2001 saoi 5001 20001 50001 50001 2001 3001 2001 2001 5001 SODI 20001 20001 50001 50001 Moa CMC. ftatL aoo 0.00 000 *5.75 4*40 aoo 040 aoo 040 aoo 7424 7S.72 77M 70.01 72J5 73.77 H J7 101*0 aoo aoo 747* H .H 75 50 72.15 *9.27 *7 7* M J0 1f9tf.l1f5l aoo 71.72 *7.04 79.10 7*41 71*0 71 M *424 9*42 FHm m 0001127015 000112701* OOOI127017 00011270*5 DODI 1270*4 0001127015 D00I12701* 0001127022 D00II27025 000112702 0001127055 j 000112705* 0001127045 00011270*4 00011270)1 0001127052 D001I270S9 00011370*0 C--W6I--II-- f PFOA *m L *t H Itat LOO(lO**>nL; <LOQ(IOtaraL] LOQdOwmM 0.0*22 0 045) L0Q( 10 >**! L O Q IlO ng/at; <L0Q HO > LOQlt06*/%i <LOOUOm w iL| 1*1 ft s 4)1 1109 lt SST9 ISO D 0 0 I127050 00011270)7 D 0 0 I1270)1 0001127015 D00II27O4* 000112705) 00011270*1 00011270*4 L O O d O --'n iU 177 175 4*1 4SI 17)2 1**S 5*25 5*14 D00II27024 00011270)1 OOOI 127052 00011270)9 0001137040 0001127050 0001127057 D00I177031 <LO O (IO M m U 179 ITO 4*4 471 tu o 1*00 *140 *02 T a ifa Case. rrtO A ra t NA NA NA 00479 0 0*74 NA NA NA NA KA 200 TOC *00 *00 2000 2000 *000 000 NA NA 200 200 00 *00 2000 2000 *000 ODO NA NA 200 200 0 0 2000 2000 % turn a i m V. T w v * Cm c . na MS IH . NA NA *)* 5% 1% 7Mt W. *5% 9)*.. 106** IX t% 77% 7J% 17% *5% *7% NA *% "" s% . . _______ S S ----------- *0% M-- ** M% NA NA 5% 77% *7% 9% 7% 0% 000 100% ITO NA 4% NA 1% 10% 7)1 4% 5% 1% 2% D aC anM y O atV atta*B y 01/15*1 LAC 01/1401 k/h CD-a2*m*aLt 3M Environmental laboratory Page 849 Page 91 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-14 AfyMMIS-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 SMy P m m Ntn Saw) bMUSttnWOM hWMK RSa-- IVate: sta r V-Uwpt D m *fEaoima/Aaaty. D m afA M ym A M yic SenpteData DOSE VERIFICATIONSAMPLES Grasp Dm lim a a Mofead BU OC iiafcUicy Day 1I/MM0 SufeUlfy DayO 11/1*00 Mafetfery Day 10 11/1*00 - ------- 11/1*00 PrOA/rQAA f t 111700-WBlk-l 1IIT0O -W U -: IUT00-WBB-3 d^ i*02*a< . iwq^ ir IKOO-AC-lOnpafe MSP *4IM 20>A<<aSad. B ^IM SO U N M Jok B -4 l*4S*A 4>IO JiaL IM IU IkA -A -l B*4I*020AWL2 fe^lMTftl A 1 B-4U-020.B A 2 B-llM2tNC-A-l B4IB4BDCA-2 D*IB4B*D*A.| esiM U 4 M ii-eae*A.i V4IM BW AO M H WADIMB-aiMBO-A-DIO-l 4 BVB-4-4atIMiMMnl3W**BCO44>tI)OOl*>ll2 V4lt-flB*-OI0>2 *4IM B ftO -O lO >i B 4IM 10M >ia2 41142*4*01*1 1*41140040104 V41M20-A-C- B*4ieOIA*C2 B-4IW 2M-C-1 *D44I1S*-(4Q2*0C0*C0 2'I *4iw a*c-c-2 B-4IM 20OC-I B-4IM30-IVC-2 B4I14BOVC-1 A 1M 2 * VC-2 D aiam M y Dm VwtimBy: 0011//1IM*01I kLjkAC CmMu MSMi9ACT-TQX-I04. A i m 4l*0B a C M (G a*e> T r-- ETS-M I A rTV-5 l D m y 0707*1 m l m u k M y a# A H O m ftaa 1i1t1/1z/01nMneoDee tww MmMmHh mu Cm * M -L aeo aeo aoo U a .4 aeo aeo aeo aoo aeo 102 TJ.7 7J.S iao 724 15.7 i *j 102 aeo aeo mi 70.0 Tj.a 721 *9.3 art MJ nt aeo aeo 71.7 7 7..1 704 721 720 H2 9*4 Cm o w n m em u s*nL .r% *ac <L O Q (!O apaD < L O Q (IO o*oL ) <LOOUOaaraL) a 22 aotss U JQ (IO ^ mL) <L O Q <IO ^aL ) <LOO(IOa*ad.) <LOQOOfe*aU l o o m o m u leaeesj 1I9J047 4M.7219 4J74500 10020404 1991-M47 Si79.417 *150.127 <L O Q (l0aenak) <L O O nom L) 174.90*5 I7S 037S 4*1.9423 4sa9or 1731.19*6 s19m94.u11t4s7 se ia a v n <LOQ<lOa*wL) <UX>M 0mL) 179.9097 109.9949 9*4.4799 477*5*0 1000910 1799.3900 0140)221 BOJIOS 02 co* D -2 Tare Case. enoA fraO. KA NA NA 00974 00979 NA NA NA NA NA 200 200 000 000 2000 2000 M00 0000 NA NA 200 200 000 000 2000 2000 0000 0000 NA NA 200 200 000 000 2000 2000 0000 0000 f lo a n n ar % Tare C ase PFOA fetaaa PFOA uro NA NA NA 14% 7% 14% 4*. NA NA M* 95% IIV. 7J% 90% S% ir. (04% NA >*% 11% 77% 71% 17% IS% 97% 94% NA 90% IS% 12% 0% 91% 90% 102% lOPN NA NA 1 95% 1 T7->. as*. (` 99*/. - NA ' tl% : 74% . 4% 1 95% NA ! ITT. ; l i s !i "* 1 (01% NA NA 10% <*. 11% NA (% 29. 29. 4% NA 5% 1% I9t 29i 3M Environmental l-ahnratary Page 850 Page 92 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-IM Arfa*4IS-02S f ACTTQXt*t. A lp a w o a O lM G 1^11 PMA CawMipla m-t4.iAETS4.si Pl i WWW 4Bm Analytical Report: FACT TOX-164 LIMS EOO-2738 M M ytf AFFO m M l Valar m e f A M t7e*A aahfet Oh i T O M I lIlI/OTMHDO RMWUWH 11/79*0 MMH CMP Ont M H rtIU t. QC tH H lH y P ty O ii/iooooo SHHwyOeye S iH k * IJTOOaWil.t uaw vw ift.a I13700.WBIL1 *a4i*O2O-A-C-l0(fc*6-MS 84lM 2^A <C 4>aL 4 1 4 * 2 0 .A-A*.} HL 0-4l*2A.A .I SuM m yPiylB tl/fCVM00 a4IUB0-DA'2 tM 1MQO-A-010-1 P4it*010-C>010>l t4|02O 4>l(M 41**204.0-2 FFOA/fOAA M k H M H i A S m H hhw m h H i0l/I7t lim a VL HL t l I 1 *1 1 1 1 l 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 l 1 1 1 1 t 1 1 1 1 irn-- m VHtfM NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA ; MA MA NA NA us 115 us US US US US US US US US US US US US US US US US US US US US US U5 US US US US US US US US US US US US *M<vy aw tm m m mmmSm. mu 1 1 1 2 2 2 2001 2001 2001 2001 MOI 0001 20001 20001 SCODI SOOOI 2001 2001 2001 2001 MOI MOI 20001 20001 SOOOI 90001 2001 MB! 2001 2001 MOI MOI 20001 20001 9000) SOOOI Dm Em h M t Daat V e n ta i By 01/1*01 LAC Ol'tWOlkjk CMC. MML *00 *00 000 00.19 MW *00 *00 *00 *00 *00 02.10 9*71 1U I 94.00 ?IJ] 71.73 17**2 10*10 *00 0.00 9*03 02.41 74JS 7*J7 0*41 7032 0*05 su i 0.00 *00 0*23 45*0 7U3 7*00 M il 75.91 0*01 *7*3 FM POQI12MI5 D00112M1* d o oiu m p D 0 0 I120005 DOS!120004 D001120011 DOOl120014 D 0 0 I12007* 0001120033 0001120034 000112*043 DODI12*044 000112*051 DO0II290S2 0001120054 O00I1200M 0001120031 0001120043 0001120044 0001120053 D001120054 DODI 120041 0001120004 DOOM20024 000112*037 000112*0)9 D 0 0 )120047 DOOM2M57 000112*051 C w in iiH rrrO A tM torT * LO0 ( 10 M/" lk 1 < L O 0 (1 0 n 'w ii L O O ilO M xnU 0*444 0.0*94 <LOO(lOn4'ntL) <LOOIIOBna*> <LOOflOn9'iiiL' LOQllNpnU.; <LOOnOn*MLl 195 147 404 4M ITM 174J 111*3 1129* LOQOOM'HLJ cLOMOh AoLI 131 157 4*4 44* 19*0 >751 5553 9457 <LOO MOMxnL) ISt 145 432 M3 1741 III) 5)74 5441 c --^ a * h '"L B0.]HpnL 0 * * 4 ***. P-an^pxrHn.t Tory* CMC HFFOA 4M L NA NA NA 0 0479 OWM NA NA NA NA 200 200 *00 400 2000 X 4000 NA 200 200 400 2000 2000 4000 NA NA 200 200 MO 400 2000 M00 % M l i t Q #r % T w f tt C**C NA PTOA r r o A -- KFD NA NA na 71% 73% *2% 71% t**V t**% NA NA 4% 0% 4% A A HA **% 93% 40% 19% 17% 3M Environmental Laboratory Page 851 Page 93 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-1M Ar(iM*4U-020 Analytical Report: FACT TOX-164 LIMS E00-2738 mMFACT-TOX-Mt. A>gM4l*42aCH((m ^t)TiCmmmm In il n 11 mOyafAPfOiifcm rrvM-Arrv4-ji IlffMB KWW 114MB MMH 11/2*40IAIH DOSE VERIFICATION SAMPLES CfMp Dom IMO PfOA Cm . 1- rfrnu WoLir%te MIM Stk 11270O-WBO-1 U27Q04Wft-2 II2700-WM-) ooo loqoombmu aoo LOQ(IOm M-) 080 <LOOIIOm m L) oc MIM2C.101ID1 IIS M.l aoo** B-iuoo.A<-iaope*-MSD 04 aoo** llHIfciyT 11/10*00 fi-4l*-Q20-A^<5^. MISOA^AA *, B4IM20^-DIMS nt 040 <UX)(IOaWD MO <OQ(I*AO aoo <00(10w*mL) SttMivDa0 11/10*00 B-4H-C2Q-A-A-1 B^IMOD-A-A-2 MIIOOI A 1 B-4H030B A2 aoo <L0Q(10bmL) aoo <0000aM) *2.1 IS* in 147 i-4IB2DC^-l B^IU0-C-A-2 7U TA 0 4M DMIMHB-P-A-I D4IS-CBMNA-2 7U 71.7 nt im 411MOI * 1 B411020A 2 17 100 IIIU 112*4 MaMBfyDay10 B^IUBO-A-PIM aoo <OQ(IOaML) aoo <00(10aaaaLl B-4H OJOBDKH B-M420010-2 B-41M2OC-O10-1 SS.I 2* 74J IM J7 4*4 *41*48*0-010.2 1*4 4M B4IS4204VDIO1 2.4 1*40 B4l*48OIO-2 TOJ 1751 D4IOOIO&OIO>I D4I041M-OI0-2 00* 09J *552 S0J7 CiminMi 4U-020-A-C-1 041*4804-02 aoo <OQ(IOafMU aoo LOOllOaMU B4I042OO-C! tu 1*1 041*420*^-2 **. MS 84I04BOCOI 712 452 04IB420C-C-2 041*48004-1 70* 4*4 44) 1141 041*480*4-2 TU 1003 041*48004-1 **.0 UH 041*48004-2 *?.t Mt PFOA/POaA -PvHaammaaB -Timi.. . i~ aMAnakiffeMWy. MmmymaaMaMfeaMAamaNm TariciCm c 4fPOCA waL NA NA NA 0.0*1* ao*i* NA NA NA NA NA 200 200 MO 00 00 2000 MOO N* NA 0 200 MO MO m 2000 000 4000 NA NA 200 200 *00 00 2000 2000 MOO MOO Rim rMiCli Om vMi By Ot/IVDl LAC OWIMI k* Hirnwyr % Im Cmc PfOA rroA Mtu KPD NA NA 1*% *1% -* NA NA NA NA n% UH 74% % 2% n% 10% 4% m. *0% 40% 0*. ll*>. A IIRV. A 1*7% NA **% 7TN 12% 77*.. I)% so*.. 7*% IIX *2% 12% *)% **% NA . . . 12% *1% 4% 75% 74% 75% 2% 7% 4% 1% % 1% 0% 1% KaterLcacr A-0**iL B-a2nB/aiL C *O.i^ptnC 0*2 tafinl. 3M Environmental Inhnratnry Page 852 Page 94 3M Medical Department Study: T-6889.6 fA C T -T O X -M . P fO A CMMk^lR Dwi)UWW teHw M/tlADI tWW 0I/ZM 1 MMH OISMQI M M H FACT-TOX-IM AlIM041S-O2O i r im i ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 M A P fO u ifa IM h w d ti D w V v iW Iy IO*OVOI LAC -UaML ' C D 0 2 MjrmL B*paL iA/Environmental inhnmtnry. L... -----__ Page 853 Page 95 ARGUS 418-020 3M Medical Department Study: T-6889.6 f a c t -t o x -i m Alfa 41*420 Analytical Report: FACT TOX-164 LIMS E00-2738 S-- r t, iAftOmlmPACT-TOX-IM . A ip 4 IM 1 0 .O a H G -- b>Tm Cb w h i I m i m i T i mu rrvMi*nv4-s.] Om*i IT W I P w f A m l|M >AAiyt Dm o TDm iatmmx A m iy r Suaptf Dm i DOSE VERIFICATION SAMPLES C tw f Om iM p t* M M IIk fO A A O liT O i-W U -l-l PO AA0M 70I-W U-I-2 PFOA/POAA * B*4St400B>A2 Dm E ftw d A y Dm V n 6 M Br IM S I LAC 0 oi/tmi ftw OLOVOI M U H D IA M I MMH P fO A CMC. WML fl oo OOO r ao tfP T O A W c L v H Ic U JQ IIO ia .) LO O IIBm M .1 M44 M I4 rfm u M L MA NA 000 000 Cm Uh A>0a^wiL C*<UNymL D3 wymL % B o x i l i % Tarm i Cm r- NA *1% PFOA Mm PFOA BPD j NA ! NA 1 |1 \ 1 n 3M Environmental 1shnrntnry Page 854 Page 96 3M M edical Department Study: T-6889.6 FACT-TOX-164 Argus 418-010 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study: P r o t e i NuntbctfTest Substance) M ani: M e ta odfflcviaiao: A a a ly o a l iq u ip m a l System Number iM m u m t Softwin/Vcnton: FACT-TOX-164. A n u s 4IS-020. O n l (C avate) T wo-Generauon Reamxtucnon Study o f AFFO in Rats FFOA Cou udano o f Co-- aun Sam pkt H TS4-4.I AETS-a-5.1 Davey 070799 Masatynx 3 4 Sample D iu DOSE VERIFICATION SAMPLES Graap Dm Sam ple* E xtracte 11/17/00. Aaalyaed 11O T00 % R vavcryar % T if f Coac. Maas RTD Exw ctad 11/27/OQ. Analyzed 11/28/00 % PFOA PFOA R ttw tfy ar Mean RPD % Target Caac. Metbod Blk QC WBlk-l WBlk-2 WBlk-3 B - 4 1 S - 0 2 0 -A - C - 100ppb-M S NA 84% 87% NA 86% NA 4% NA 88% 87% NA 88*,; NA 1% Stability Day 0 B-4l-020-A -C -0.i mL 11/10/00 B-41 *-020-A-A-0 5 mL . n a NA NA NA NA NA Stability D ay 0 11/10/00 B-4 )8-020-A-A- 1 B-418-020-A-A-2 B-4I8-020-B-A-1 B-418-020-B-A-2 B-418-020-C-A-1 B-418-020-C-A-2 B-418-020-D-A-1 B-4I8-020-D-A-2 NA 95% 93% 11% 73% 90% 93% NA 95% 77% 93% NA 1% 10% 5% NA 78% 73% 82% 78% 89% 90% NA 76*/; 80% 90% NA 6*/; 4% o*/; B-418-020-E-A-1 93% 106% 99% 13% 116V / H V / II7V / i% SubUlty Day 10 11/10/00 B-4I6O20-A-DI0-1 B-4IS-020-A-D10-2 B-41-020-B-DI0-I B-4IS-020-B-D10-2 B-4U-020-C-D10-1 B-4IB-020-C-D10-2 B-41&-O20-D-DIO-1 B-4IS-020-D-D10-2 B-4I8-020-E-D10-I NA 88% 88% 77% 73% 87% 85% 97% 94% NA 88% 76% 86% 93% NA 1% 2% 2% 4% NA 69% 78% 77% 83% 78% 88% 93% 99% NA 74% so*/; 83% 96% NA 13% 7% 12% 7% C a v e a traboa 11/10/00 B-418-020-A-C-1 B - 4 1 8-02 O-A-C-2 B-4I8-020-B-C-1 B -4 18-020-B-C-2 B-4I8-020-C-C-1 B-418-020-C-C-2 B-418-020-D-C-l B-418-020-D-C-: B-4I8-020-E-C-1 B-418-020-E-C-2 NA 90% 83% 82% 80% 91% 90% . 102% 100% NA 87% 81% 90% 101% NA 3% 3% 1% 2% NA 79% 82% 75V. 74% 87% 94% 90% 9t% NA 81% 75% 91% 90% NA 4% 2% 8% 1% A- S e n t e re-cetncted on 01 /17/01 to confim i h u h recovery Recovery w as not confirmed. ctmaufcred an outlier. E atnctadQ I.'IW I. Altaivied 01/22/01 II % PFOA Recovery ar RPD % Target Cane. NA NA NA NA NA NA NA NA NA NA NA 91% 84% NA NA NA ' NA NA NA NA NA NA NA NA NA NA NA NA 87% NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 9% NA NA NA NA NA NA NA NA NA NA 3M Environmental Tnhnrntnry Page 855 Page 97 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-164 ArfU#41M20 Analytical Repon: FACTTOX-164 LIMS E00-2738 Sody: FACT-TOX-144. EOO-27JI Produrr NnmbeffTest Suhwancr ) M am M etbad /R rrom tSoftwaro/Vamoo n S p i r i Voe: Slope: Y-lmerccpt D am o f Exvaam v Analyst Dans o f Analysa/Analyst: Dale o f Data RcducnowAnalyst: Sample Data O n) (Govofe)Ta n fi---- no (Owe L n r pm Ganninno) Reproducooe Smy o f PFOA m Rots T-609X R Sra E T S4-4J * ETS-t-SJ a n s an a m e n d m m curve A nfe06249l Moariyan3.4 So*/ S o t/ S o t/ 06/1*01 RWW 06/21*1. 0607/01.07/17/01 MMH 0602/01.060*01.07/11/01 MMH Box: 01-029 RAT SERUM Group Dote Sample a Method Blk M anu Blk Group 1 0.0 m/ktd*y Groups 10 mg/kg/day CrM pS 30mg/kg/day RTS062101-H2O Blk-1 RTS06210I-K2O BUt-2 RTS062I01-Sen Blk-1 RTS062I01-Sm Blk-2 PI3tOiF.Grpl.OMJCD.LD22 PI3l02F.Gfpl.0MKD.LD22 P1386F.Gfp 1.0MKD.LD22 P1360IM.GipI.0MKD. PD106 P13607M.&P 1.0MKD. PD 107 P13613M.Gfpl.0MKD. PDlOt P 13891F.Gip4.10MKD.LD22 P l3892F.G ip 4.I0M KD XD 22 P 1393F.Grp4.10MKDXD22 P 13894F.Gfp4.10MKD.LD22 MJI95F.GfT4.10MKD.LD22 i PlM tF .G fP . I0MKD.LD12 : F 13l97F.Gfp4. I0MKDXO22 ! PI3l9tF.Gfp4.l0MKD.LD22 F13S99F.Gfp4.10MKD.LD22 PI390IF.Gip4.IOMKD.LD22 P 13691M.Gfp4.lOMJCD. PD106 P13692M.Gfp4.10MKD. PD 106 PI397M.Gip4.IOMKD. PDI07 PI369IM.Gfp4.IOMKD. PD107 P13703M.Gtp4.10MKD. PDlOt P13704M.Grp4.10MKD. PDlOt* P13709M.Grpd.)0MKD. PD109 Pl37lOM.Grp4.10.MKD. PD 109 P137ISM.Grp4.10MKD. PD110 P137 l6M.Grp4.10MKD. PD I10 P 13921 F.Grpi JOMKDXD22 PI 3922F.GrpSJOMKDXD22 P 13923F.GfpS.30MKD.LD22 P 13924F.GfpSJOMKD.LD22 P 13925F.GtpSJOMKD.LD22 P 13926F.GfpS.30MKDXD22 P 13927F.GfpS.30MJCD.LD22 PI 392IF.Gfp3JOMKDXD22 P 13930F.GrpS.30M KDl.D22 P13931 F.GipSJ0MKD.LD22 ! P13721 M.Grp5JOMKD. PD 106 P13722M.Grp5JOMKD. PDI06 P13727M.GipSJ0MKD. PDI07 PI372tM.GrpSJOMKD. PDI07 PI3733M.GrpS.30MKD. PDlOt P13734M.GrpSJOMKD. PDlOt 1 m 7H M .G fpSJ0M K D .rO in P13740M.GrpSJOMKD. PD 109 PI3746M.GrpSJOMKD. PDI 10 PFOA Den Eamed/Br. 07/ltt'OI.Ot/Od'Ol LAC Dale Verified/ By: 08/13/01 nm * Intti) VaL mL 1 1 1 1 1 1 1 1 1 l I 1 1 1 1 1 1 l 1 l 1 1 1 1 l 1 1 1 i 1 ! 1 l t 1 1 1 ! 1 1 1 l 1 1 1 1 1 Surroga* VM M 2nd Analysis OK 2nd Analysis OK NA 2nd Aaalvsu OK NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Confirmed Law C onfined Low NA Caulvmtd Low Confirmed Low Confirmed Lou NA Confirmed Low NA NA NA Catf-- i Low NA NA NA NA NA NA Confirmed lew Confirmad Low C onfinad Low NA Confirmed Low Cinfirmi i Low NA Confirmed Low C on fined Low NA C onfined Low PFOA Dflnttra Factor l l 1 l 1 i 1 1 5 5 S 5 5 25 5 5 25 5 1000 1000 1000 1000 1000 1000 1000 1000 1000 1000 SO so SO so so 10 10 10 10 50 1000 1000 1000 1000 1000 1000 1000 1000 1000 1000 PFOA Crac. ot/mL 1.63 1.29 1.77 141 2.M 1.1! 3 24 S0.I4 20J l 32.17 65.14 79.13 41.13 I5.4S 90.13 16.73 50.11 77.67 11.94 66.15 36.12 56.73 61.41 SO. II 54 44 39 46 59.00 51.7* 48.04 46.29 22.01 16.96 27.60 37X3 18J l 57.45 90.11 9X70 39.07 26.43 50.92 29.94 39.57 61.12 33.44 4X17 S6XJ 27.42 50.07 61.55 Filename C racen in tira o f PFOA wf/mL er % Ree A010627016 LOQ (0.00528 ug/niL) A010627017 LOO (0.00528 uu niL: AOIO627018 <LOQ (0.00528 ug/mL) AOI0627019 LOO (0.00521 titi/mL) A 010627020 LOQ (0.00528 ug/mL) A01062702! LOO (0.00528 utf/niL) A 010627022 <LOOfO 00528 ut/rnll A010627023 A0I0627024 0.0501 0.0208 AOI0627025 0 0322 A010627Q29 0.326 A 010627030 A010627031 AOI0627032 0.396 0.241 0.427 AOIO627033 M0107I7023 A010627035 AOI0627036 M 0 10717024 0.451 0418 0J51 0.388 0.474 AOIO627038 M0107I7031 0.331 36.8 M0I07I7032 56.7 MO10717036 M010717037 61.4 50.2 M0107I7038 544 M0107I7039 MOI0717040 M0I07I704I 39.5 59.0 51.8 M0I0717042 M0I07I7O43 MO10717025 MOI07I7026 48.0 46.3 1 10 0*48 M0I07I7027 MO10717028 IJ8 1.18 M0I0717029 AO10627060 0.910 0.574 A 010627061 AOIO627062 A0I0627063 MOI07I7030I MO107170*4 M0I0717O45 0.90! 0.927 0.391 1.32 50.9 29.9 MOI07I7049 39.6 MOI07I7O5O M0107I70S1 MOI0717052 MOI07I70S3 MOI07170541 61 1 33.4 4X2 56.4 274 M0107I70S5 MO10717056 50.1 61.6 Mean PFOA a|/m L i LOO RSO SM. Of MS/MSD RTD NA ^LOO 1 1 < 1 .0 0 NA NA NA 0 0344 430 0.0148 0.370 21.7 0.0803 ISJ 51.1 9.30 41 5 1.02 0.425 27.9 4SJ 12.6 3M Environmental Laboratory . Page 856 Page 98 3M Medical Department Study: T-6889.6 SM y: FACT-TOX-1M. EOO-2TU Product K u n b cfffo t ffnh-- r r ): Mattu MMbudflUvoioo: F lir t arar R-Sduucd Value: Slope: V-h ecccpc: D uet o f EsPpeuop^AMhPC Palet o f Aualyua/Aaalyet: Due o f Dot Reducbo^Analyst: Sim ple Data FACT-TOX-1M Arxns# 418-420 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 O n lf f n --D T i il fin in -- (Oue LmcrparGcMranen) Ripm du n inn Sudy o f PFOA m Roo T-U94 Rat &mn ET V 44.2 A ET5-ft-3-2 orna m u n c M rat m uni a ove H u t ) 3.4 0 6 1 9 * 1 RWW 0 6 2 1 * 1 .0 6 2 7 * 1 , 07/17/01 MMH 0 6 2 2 * 1 .0 6 2 1 * 1 .0 7 /1 1 * 1 MMH RAT SERUM Croup D ot S a u p te f Mcibod B it Mame Bk Group 1 0.0 mg/kg/day Croup 4 I0mg/kg/day Croup $ 30 mp/kg/day PFOA PcrfluoraecouQue RTS062101-H2O B k-I RTS6210I-H2O BIk-2 RTS062101Su> B k-I R T S 0 6 2 t0 l-S ffiB fc-2 PUOtF.Gfpl.OMKDXD22 PIM02F.Git 1.0MKD.LD22 PIMOF.GiI.OMKD.LD22 FI3MIM.GlFl.0MKD. PD106 PI3607M.GfTl.064U>. PDI07 PI3613M.GfTl.0MKD. PDI00 P l # 9 1FXrp*. 10MKDXD22 P13l92FjGfr4.10MKDXD22 P1393F.Grp4.l0MKDXD22 PI3S94FXkp.IOMKDXD22 PI30*SFfT4.l064XDXDU P13M6F.Gtr4.l0MKD.LD22 P13fl97FjGtr4.IOMKD.L022 P13 flO flF 0 tr4 .I O M K D J 0 2 2 P I3 IW Ap4.10M KD1D22 PI300IFDf*4.10MXDXD22 PI369IM.Grpd.lOMKD. PD1M PIJ692ACGrp4.10MKD. PDI0* P13607M.Grr4.l0MKD. PD 107 P136M640fT4.IO.MKD. PDI07 P13703M.Grp4.10MKD. PDIM PI3704M.Gfr4.10MKD. PDIM P13709M.Grp4,10MKD. PDI0 P13710M.Gfp4.IOMKD. PD100 P1371S34.Gfr4.10MKD. PD1I0 PI37l66LGn>4.1064KD. PD I10 P I3 ea iF .G ip S J O M K D .U U 2 PI3O22F0fT3JO64KDXDn PI3923F.GepSJ0MKDJJ322 P I3924F.Grp5.30MICD.LD22 TIM25F.Gtr5J0MKD.LD22 P 13926F.GrpSJ0MKD.LD22 PIM27F.Gfr5JOMKD.LD22 PI592fF.GtT5JOMKO.LD22 TIMMF.Gfr5JOMKD.LD22 P1393 IF.GfpSJOMJCDXD22 PI3721M.GipSJOMKD. PDI06 PI3722M fp5J0M KD. PDI0 PI37776LGfTiJOMKD. PD107 P1372*M0fr5JOMKD. PDI07 PI37316LGfT>J0M KD. PDIM PU73464GfT>J06KD. PDIM PI373T6ATM 06IXD. PDIO0 PI37406iGfT3J0MKD. PD100 P1376M.Gfr3J064KD. PDI 10 PI374764.GfrU0MKD. PDI 10 PFOA Cooc n tm L 143 1J9 1.77 1.4 246 1JI 3J4 50.1 20J 312 65.1 79.1 4S.1 5.4 90.1 16.7 sai 77.7 IL9 662 36J 56.7 614 502 S4.4 39.5 99.0 51J 41.0 46.3 22.1 17.0 276 374 12 574 90.1 92.7 39.1 26.4 50.9 29.9 39.6 61.1 33.4 4L2 564 27.4 90.1 61.6 Cauceurmrao o f PFOA a a L u r % Rae <LOQ (0.0052ft apaiL) <LOQ (0.00521 w n i U <LOQ <000523 u^mL) <LOO(&OOS2f uataiL) <LOQ <000521 ugrinL) <LOQ (0.00S2S ug/mL) <LOO (0.0052ft ug/mL) 0.0301 0420 0.0322 0.326 0J96 0.241 0.427 0.451 0411 (L25I 0JU 0.474 0.331 36.1 56.7 61.4 502 544 39.5 59.0 SI.I 41.0 46.3 1.10 0.ft4l IJft IAS 0.910 0.374 0.901 0.927 0.391 U2 50.9 29.9 394 61.1 33.4 *22 564 274 30.1 614 Mean PFOA upoiL NA NA <LOQ 0.0344 0.370 511 1.02 453 RSD Std. Dev. MS/MSD RPD KA NA KA NA 43.0 0 0148 21.7 o.otos 18.2 9.30 41.5 0.423 27.9 12.6 Due Euerad/By: Due Verified/ By*. 0 7 /1 0 * 1 .0 1 * 6 0 1 LAC 0613*1 uud 3M Environmental Ijihnratnry Page 857 Page 99 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-164 Arfas 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 Study FACT-TOX-164. EOO-2731 Prodan >iumtow<Tct Snhnancr) M on: McBod/RfriuOfi: AiBlyncdE^watSymn Sentar: BSffvncat Softwmo/Verwon Filmarne: R-SmandValae: Slope: Y-iniencpt Dotes o f Exmcuon/Analyst: Dobs o f Analysts/Analyst Date o f Data ReductionAnalyte Sample Data On] (G rape) Twn G r a n ir (One U ser pm Qmmmteu) Reprodaetmo Study o f PFOA Rau T 4N 94 ET S-M JA ET S4-12 SoapO20IP9 06/14/01 RWW ' O VlVO i MMH 06/11/01 MMH Boa: 01-021 RATSERUM Crnnp Dooe Sampie * Method Blank RTS06I401-H2O Bik-1 RTS06I40I-H20 Blk-2 M ora Blank R T S 06l401-S osB lk -l RTS06l40l-Son Blk-2 o c RTS06I4QI-MS-2S ppb RTS06I40I-MSD-25 ppb RTS06140t-MS`500 ppb RTS061401-MSD-500 ppb PFOa - Perfluaraoaaaoate Initial VoL L l t 1 t 1 l 1 I R itm e m a DMatinn Factor 1.25 1.25 IJS t.25 1.25 1.25 1.25 US S arm ew c Verified OatHtpii Out Hath OotH*b Oat Hink 0H i(k Oat High NA NA PFOA Dilation Factor 1 1 1 1 1 i PFOa Cane. mpmL 0.00 000 0.00 000 12.67 I4J6 287J0 276.16 Filename SOI06I50II SOI061SOIO S0I0615020 S0I06IS02I SO10615022 S010615023 SOI0015024 S 0 I 0 6 15025 Concentration O f PFOA i p m l o r V* lire <LOQ (0.00107 ap/iuLl <LOQ(0.00l07 gjt'mLl <LOQ (0.00107 upmL) <LOO(0 00107 wpmL) 601. 61V. 68'.. 65',. Mean PFOA offm L <LOQ <LO 64V. 67% RSD Std. Drv MS/MSD RPD NA NA 13V. 4% Dote Emered/Byr 06/22/01 LAC Dole Verified/By; 01/13/01 north 3M Environmental I-ahnratory Page 858 Page 100 3M Medical Department Study: T-6889.6 S u l ,: FACT-TOX-164. 600-2731 Product NumbertTe Suhstmct) Matru MethadAevtMoe: ta n u n e a i Softwm'VfDOB: Filename: R SpoiledValut Slope Y 4 a is c (p : Dans o f Enaction/Analys: f l u of A ulyiivA M lyit Date o f D an Reduction/Analyst Sample D au FACT-TOX-164 Arcat 418-020 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 O ni (Gavas) To-Gananuoa (Ok Lncr per Generalioni Reproduction Study o f PFOa in Rais T-6M9.6 Rai Sem a E T S-44J A ETS-S-5J a s a au unesvuned curve SaupTOOlf Maaalyua 3.4 06/1441 RWW 06/1 S l MMH O6/IS/0I MMH RAT SERUM Group Dom Method S U s i Mama Blank QC PFOa Periluoroocnnour S tm k t RTS06I40I-H20 Blk-1 KTS06I401-H2O Blk-2 RTS061401-Sun Blk-I RTS06I401-Sun Blk-2 RTS06I40I-MS-25 ppb RTS06140NMSD-25 ppb RTS06I401-MS-500 ppo RTS06L40lMSIV$00ppb PFOA of/nL 0.00 0.00 0.00 0.00 12.7 14.4 2*7 276 Caaeeatratioa o f PFOA o a /n L e r % Ree <LOQ (0.00107 *TML> <LOQ (0.00107 ugfmL) <LOQ (0.00107 upfeaL) LOO (0.00107 60% 61% 61% 65% Mean PFOA u f/m L <LOO <LO0 64% 67% KSD Sid. Dev MS/MSD RPD NA NA 13% 4% Date Entered/By Date Verified/ By: 0602/01 LAC 0t/l3OI neu6 3M Environmental Laboratory Page 859 Page 101 3M Medical Department Study: T-6889.6 FACT-TOX-164 Argus 418-020 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Study: FACT-TOX.IM. EOO-27 Product NambafTeu Subitanee) Mania: Mctbod/Rcviuon: Analytical E geprant Synem Kumt l a w n e at Softww /Vcmon R-SpwedVak: Siepe : V Ihmreap; Dam of EaeaeuraAnalyst. Date of Aanlysts/Analyst: D m o f Dan Redncbon/Analyst Sample Data Olii (Gavage) Tao i n c w (One Laar per Gwcnooo) Repmdunmei Study o f PFOA m Rau T-6SSM RnSeran ETS-S4J A ETS4-12 w r a s MKMd m w e m rav e Soup020l99 Mratyn34 OS/I3/OI RWW M/IVOI MMH 02D I MMH B o a t: 01-031 RATSERUM Group Dose Simpt Method Blank RTSM130I-H20 Blk-l Mama Bleak RTS0SI30I-H2O Blk-2 RTS0S 1301-Sen Blk-l RTS0S1301-Seva B&-2 o c RISOS 130 l-MS-50 ppb rsosi30i-MSD-soppb RSOSI 301-MS-1500 ppb RISOS 1301-MSD-1500 ppb RTS0S1301-MS-50000 ppb RISOS 301-MSD-50000 ppb PFOA Perfluoroocunoaie A Peak was not euegrated. not above B e tbmbbold Imit- initial Vel bL 1 1 1 l 1 1 1 1 1 Sample Verified NA NA NA ConfinadHifh NA NA NA NA NA NA PFOA Marten Factor 1 1 1 1 t 1 50 50 1000 1000 PFOA Cene g/mL Filename Concentrane* e f PFOA eg/m i. o r */ Ree Meaa PFOA eg/m L 0.00 MOIOS15Q30 <LOQ (0.00536 ug/mL) 0.00 M0I0S1503I <LOO (0.00536 up'inL) <LOQ 0.00 MOIOS15032 <LOQ (0.0053d ufi/rnL) A 0.00 MOIOSI5033 LOO (0.00536 ug'mLi <LOO S5.Il MOIOS15034 5SJ4 M0I0815035 106% 110% 108% 2144 M0IOBI5036 92% 24.SS M010S1503 7 SO*/. S6% 46.89 M0I0S15038 4 3 4 0 M0I0S15039 92% 16% 9% Daae Emcied/By: t/29/OI LAC Den Verified' B r W4/0I wnb RSD Sid Dv% MS/MSD RPD NA NA 4% 13% t% 3M Environmental Laboratory--^ Page 860 Page 102 3M Medical Department Study: T-6889.6 Study: FACT-TOX-164.EOO-273S ProductNumberfTestSubitanee) Manx Method/Revaion Anaiyual EquipmentSystemNamber lammest SoAware/Vcmoa: Filmarne: R-SquaredValue Slope Y-lniereept OatesofExtracttvAnalyst: DatesofAnaivsis/Analyst. DateofDau Reduction'Analyst: Simple D au ARGUS 418-020 FACT-TOX-164 Artus 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Oui (Gavaft)Two-Gcnereuoo(One LinerperGeneration>ReproductionStudyofPFOA inRau T4 SS9.6 RalSown ETS I O Sl ETS4 -S.2 versosanesnaeo m sennncurve Soop020199 Mnaalyu 3.4 SaeAnacfamesu SeeAambmcso 0I/IJ/01 R W W 0S/IV01 M M H 0S/20ftl M M H RAT SERUM Group Dose Sample a Metbod Blau* RTS0I130I-H2O Blk*i MatrixBlank RTS0S130I-H2O Blk-2 RTS0S130l-Scrs Blk-1 RTSM1301 Sen Blk-2 OC RTS081301-MS-50 ppb RTSO8t301-MSD-S0mb RTS011301-MS-1500 ppb RISOS 1301-MSD-1500 ppb RTS0S1301-MS-50000 ppb RTSOS1301 -MSD-50000 ppb PFOa - Pernuoraocuooate A - Peakwasnoiimegrated,notabovethetbreahboidlnut DateEntered-Bv DareVerified/By: 01/29/01 LAC 9/4/01 nanfa PFOA CMC. nf/m L 0.00 0.00 0.00 0.00 554 5SJ 2S.4 24.9 46.9 43.4 Concentrai ofPFOA apnL or % Ree Mean PFOA ug'ntl. <LOQ (0.00536 u-mL) <LOQ (0.00536 urmL) <LOO <LOQ (0.00536 up*raL) A <LOQ (0.00536 up`mL) <LO0 106% 110% 10S% 92% 80% 86*/. 9126%% 89"/. RSI) Sid.Dev MS-'MSO RPD SA NA 4*. 13% 8% 3M Environmental Laboratory--=. Page 861 Page 103 3M Medical Department Study: T-6889.6 FACT-TOX-164 Artus 418-020 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 Study FACT-TOX-164.E00-2738 fm lm i NmnhrrfTfff l idm u rrl M eta o d rtte vu oe AnaJyoraJ Egyganrnt Synem Number t a m n o t Software/Vouon: Fikamac R-S+andVatoe: Staat: Y-lamcept: D a n e f Euacuon/Analyst Data* o f Aaalystt/AaaJys:: Duce o f Dan Radyenoa/Aailys: Sam ple Data Oral(Gavage)Tan f i r f i u n n (O aaU ser perGeneras ) Reproducan Stody o f PFOA m Kau T-6889.6 ETS<M2 A ETS4-12 v man o tto n a adcave MadelmeMlOM MaaalyaaXd See Beta oa/ivoi Rww 08/27/Dl MMH Ot/29/Ol MMH B o s t: 01*031 RATSERUM Groap Da Sample Method B lau RTS08I30I-H20 81k-1 RTS081301-H 20 Blk-2 M anu Blank RTS08l30J-5craBik-l RTSM1301-Sera Blk-2 o c RTSOS130I-MS-SG ppb RTS081301-M5D-S0 ppb RTS08130l-MS-lJ00ppb RTS011301-MSD-1500 ppb RTS0S130l-MS-S0000ppb RTSM I301-MSD-50000 ppb PFOA Perflueroocunoau Jaidai VaL mL l 1 ) l l l l 1 1 ) b tn ctM DBadaa Factor 1J5 1.25 1.25 1.25 US US US \2 S US 12$ Sarragaia VertOad Canfinaad High Caafirniad High Confirmad Higb Coafamed High C n fn ad H ip Confa-- d Hieb na NA na NA PFOa Ditattan Factor 1 SO SO 1000 1000 PFOA Conc. o |/m L 0.00 0.00 0.00 0.00 4 I 39 47 20.83 22.47 32.71 28 4P Filename ; C en tn iF iiiO u 1 of PFOA ug/mL or % Ree M tt* PFOA ug/mL MUI0827017 1 <LQ (C.00268 ug/inLl jM01M270I! 1 <LO0 10 00268 ug'mL) M0I08270I9 <LOQ (0.00268 up/niL) MO10127020 1 <LOQ (0.00268 upmL) ` LOO <LOQ M01M2702I i M010827022 ! iM010R27023 M010827024 98% 93V. -. 90% ,j 96% 1 87% 1 M010827025 ! MOI0827026 1 817. 70% 75% 1 RSD Scd. De* MS/MSO RPD NA NA 5% 85. 14% Date Eaertd/By: 09/04/01 LAC Dale Verified' By: OU/DJ mota 3M Environmental Lahnratnry Page 862 Page 104 3M Medical Department Study: T-6889.6 Study FACT-TOX-164. EOO-273I Product NumbefTTew Subetauce > M iau Mctbod/Revisioe. Analytical Equipment Synan Number immunem Software/Vcnme: Filename: R-Squired Value: Slope: Y-intereept Daces of EzoicuocvAnalyst: Daces of Analvsi*Analyst: Date of Data Reducuan/Analyst: Sam ple D ata FACT-TOX-l 64 Arfus 418-020 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS E00-2738 Osai (Cavage) Two-Gcaoauao (One Luter per Generaiion Reproduction Study of PFOA Rats T-6U9.6 Rai Scran E T S 4 4 J A ETS-^-i-2 vcnua aa unexoacied curve MarirbnKHI098 Mamiynx 3.4 01/13/01 RWW 08/27/01 MMH 01/3*01 MMH RAT SERUM Group Dose Method Blank Matrix Blank : I I ( QC . 1 1 : PFOA * Perfluoroooaooate Sample RTS0S1301-H2OBlk-l RTS011301*H20 Blk*2 RTSOI1301<Scn Blk-I RT$08I301-Scra Blk-2 RTSOd1301-MS>50 ppb RTS0SI30l-MSD-50p*fe RISOS 1301-MS*1500 ppb RTS08130|.MSD>l500ppb RTS011301-MS-50000 ppb RTS0I1301-MSD-S0000 ppb PFOA Co k agad. 0.00 0.00 0.00 0.00 4U 39.5 20J 22.5 32.7 28.5 Cuncentranon f PFOA ug/mL or % Ree <LOQ <0-00261 ug/mLi <LOO (0.00268 uiymLl <LOQ (04)0264 ug/mL) <LOQ (0.00268 ug/mL) 98% 93% 84% 90% 81% 70% Mean PFOA u rin L <LOQ <LOO 96% 7T. 75% KSU Sid. De>. M S 'M S D R P U SA NA 5% 8% 14% Date Eatered/By: Date Verified/ By 09/04/01 LAC *4/01 mmfa 3M Environmental Laboratory . Page 863 Page 105 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Analytical Report FACTTOX-164 UMS E00-2738 Appendix F: Example Calculations Formula Used for Sera A nalyses in Study FACT TOX-164 AR (ng/mL) XDF XFV (mL) x 1.0 pg = Reported Concentration (pg/mL) EV (mL) 1000 ng Calculation U sed for G roup 4, LD22, Anim al ID P13B91F 65.14 ng/mL x 5 x 1mL x 1.0 pg = 0.326 pg/mL 1mL 1006 ng AR-- Analytical result from MassLynx summary DF--Dilution factor FV--Final extract volume (1.0 mL unless otherwise noted) EV--Volume of sera extracted P n v im n m a n ta l I o H n r a tr w 3M Environmental Inhnmtnry Page 864 Paha 25 Page 106 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 3 M M e d ical D epartm en t Study: T -6889.6 A n alytical R eport: F A C T T O X -1 6 4 L IM S EO O-2738 Appendix G: Interim Certificate(s) of Analysis IW Pnvimnmantal /ahnratnn/ 3M Environmental Inhnratary . Page 865 P an a 2fi Page 107 3M Medical Department Study: T-6889.6 ' ARGUS 418-020 Analytical Report: FACT TOX-164 IlMS E00-2738 Centre Analytical Laboratories, Ine. 3048 Research Drive State College. RA 16801 www.centrelab.com (814) 231-8032 Fax: (814) 231-1253 or (814) 231-1580 INTERIM CERTIFICATE OFANALYSIS Revision 2 (10/17/01) Centre Analytical Laboratories COA Reference #: 023-034 3M Product: PFOA, Primary Standard Test Control Reference #: TCR-99030-30 _____________________________ Parity; 95.0%_____________________ 1 Ted Name Specifications Result Purity1 95.0% Appearance Identification NMR Metals (ICP/MS) 1. Calcium 2. Magnesium 3. Sodium 4. Potassium 5. Nickel 6. Iron 7. Manganese Total %Impurity (NMR) Total %Impurity (LC/Mi>) Total %Impurity (GC/MS) Residual Solvents (TGA) Punty by DSC Inorganic Anions (IC) 1. Chloride 2. Fluoride 3. Bromide 4. Nitrate 5. Nitrite 6. Phosphate 7. Sulfate 1Organic Acids' (IC) : 1. TFA i 2. PFPA 3. HFBA i 4. NFPA Elemental Analysis': 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine Ammonium Analysis' Ian Selective Electrode White, crystalline solid 1. Theoretical Value - 22.3% 2. Theoretical Value " 0.935% 3. Theoretical Value - 3.25% 4. Theoretical Value = 0% 5. Theoretical Value * 66.1% Theoretical Value " 4.18% Conforms Positive 1. 0.001 wt/wt.% 2. <0.001 wt/wt.% 3. 0.001 wt/wt.% 4. <0.001 wt./wt% 5. <0.001 wt./wt% 6. <0.001 wt/wt.% 7. <0.001 wt/wt.% 0.36 wt/wt% 4.68wt/wt% None Quantified.% None Detected 99.8% 1. <0.015 wt/wt% 2. <0.005 wt/wt.% 3. <0.040 wt/wt.% 4. <0.009 wt/wt% 5. <0.006 wt/wt% 6. <0.006 wtArt.% 7. <0.040 wtArt.% 1. <0.1 wt/wt.% 2. <0.1 wt/wt.% 3. <0.1 wt/wt% 4. <0.25 wt7wt% I. 18.9wt/wt% 2. 1.27 wt/wt% 3. 3.76 wt/wt% 4. 4.38 wt/wt% 5. 62.1 wt/wt.% 2.94 wt/wt. % COA023034 REVISION Zdoc 3M Environmental Inhnrnimy Page 866 Page I of2 Page 108 3M Medical Department Study: T-6889.6 ARGUS 418-020 -A--n-a--ly--t-ic--a-l--R--e-p-o--n-:- FEATMCTSETOOUX--J1/J6g4 Centre Analytical Laboratories, inc 3048 Research Drive State College, PA16801 www.c8ntreiaD.com ^ ^ F f ^ ^ J Q ^ P h o n e : (814)231-8032 Fax: (814) 231-1253 or (814) 231-1580 INTERIM CERTIFICATE OFANALYSIS Revision 2 (10/17/01) Centre Analytical Laboratories COA Reference #: 023*034 3M Product: PFOA, Primary Standard Test Control Reference #: TCR-99030-30 Date o f Last Analysis: 10/31/00 Expiration Date: 10/31/06 Storage Conditions: < -10 C Re-assessment Date: 10/31/06 'Purity *=100% - (total metal impurities, 0.002% + Total NMR impurities, 0.36 + Total LC/MS impurities, 4.68 %) Total impurity from all tests * 5.042% Purity = 100%- 5.042% = 95.0% 2 TFA HFBA NFPA PFPA Trifluoroacetic acid Heptafluorobutyric add Nonafluoropentanoic add Pentafluoropropanoic add 3T heoredcal value calculations based on the empirical formula, C|Fi (MW=431.1) This work was conducted under EPA Good Laboratory Practice Standards (40 CFR 160). LC/MS Purity Profile: Peak# 1 2 Total Retention Time (min) 12.144 0 3 3 14.238 - Mam(a) 29.0 331,319 369 - Identity Area C6 205859 F ,,/C 7 " 903329 PFA 22630600 - 23739788 /.A rea 0.87 3.81 4.68 Prepared By: Charles ak/sL. mc Scientist, ical Laboratories Reviewed By: risL 0 ^JhnFlaherty Date Laboratory Manager, Centre Analytical Laboratories COA023034 REVISION 2doc 3M Environmental Laboratory Page 867 Page 2 o f2 Page 109 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 Appendix H: Report Signature Page ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Analytical Report FACTTOX-164 UMS E00-2738 Study DirectorJ o h n Bu te n hoff, P h .D ., D ate D a v id S a n d e rs, P h .D ., Sponsor Representative D ate (y L isa A C le m en, Principal Analytical Investigator o i I o h I z D ate W illia m R e a g e n , P h .D ., Labor_a__t_o__r_y__M__a__n__a_g__e__m__e__n_t_____ D ate S U Fm sim n m o n ta IS m hnm tnrv 3M Environmental Laboratory _ ^ . Page 868 Pane 27 Page 110 ARGUS 418-020 APPENDIX J ENVIRONMENTAL AND HUSBANDRY REPORTS Page 869 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 05 Protocol Number: 418-020 Range of Dates: 07-Nov-2000 14:11 to 13-Nov-2000 08:59 Target Range: Species: Rat Total Number o f Days: Total Number o f Hours: Total Number o f Data Points: Temperature 64F to 79F 7 138.5 139 Relative Humidity 30% to 70% 7 138.5 139 Mean ( SD): Maximum: Median: Minimum: Number o f Points in Range (%): Number o f Points High (%): Number o f Points Low (%): 68.5 (1.4) 51.9 (4.0) 71.1 63.9 68.0 50.8 66.6 44.1 139 (100.0) 139 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Report Generated: 18-Jul-2001 at 11:07 COMMENTS: REVIEWED BY: ' a _ DATE: 7 7VDI ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 17 Protocol Number: 418-020 Range of Dates: 13-Nov-2000 08:00 to 21-Mar-2001 16:59 Target Range: Species: Rat Total Number of Days: Total Number o f Hours: Total Number of Data Points: Temperature 64F to 79F 129 3080.75 3078 Relative Humidity 30% to 70% 129 3080.75 3078 Mean ( SD): Maximum: Median: Minimum: Number of Points in Range (%): Number of Points High (%): Number of Points Low (%): 67.4 70.1 67.3 65.9 3078 0 0 ( 0.6) (100.0) (0.0) (0.0) 45.8 62.4 46.7 30.8 3078 0 0 ( 6.2) (100.0) (0.0) (0.0) Report Generated: 18-Jul-2001 at 14:06 COMMENTS: REVIEWED BY: - .& n tr^K DATE: 7 Page 871 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 16 Protocol Number: 418-020 Range of Dates: 09-Feb-2001 14:30 to 02-Mar-2001 12:59 Target Range: Species: Rat Total Number o f Days: Total Number of Hours: Total Number o f Data Points: Temperature 64F to 79F 22 502.25 501 Relative Humidity 30% to 70% 22 502.25 501 Mean ( SD): Maximum: Median: Minimum: Number o f Points in Range (%): Number of Points High (%): Number o f Points Low (%): 70.3 ( 0.8) 46.5 72.1 63.1 70.2 45.8 68.3 27.7 501 (100.0) 498 0 (0.0) 0 0 (0.0) 3 < 5.6) (99.4) (0.0) (0.6) Report Generated: 18-Jul-2001 at 14:11 COMMENTS: REVIEWED BY: _ /V ) A ^ DATE: *7- pi Page 872 ARGUS 418-020 ARGUS Relative Humidity Deviations Report Location: Room 16 Protocol Number: 418-020 Range of Dates: 09-Feb-2001 14:30 to 02-Mar-2001 12:59 Humidity Target Range: Species: Rat Date 25-Feb-2001 25-Feb-2001 25-Feb-2001 Time 06:00 07:00 08:00 R.H. 29.0 L 27.7 L 28.5 L 30% to 70% Date Time R.H, H = Value out of range - High L = Value out of range - Low R.H. = Relative H um idity (% ) Report Generated: 18-Jul-2001 at 14:16 L^These deviations did not adversely affect the outcome or interpretation of the study. The following deviation(s) impacted on the outcome of the study as described: Page 873 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 01 Protocol Number: 418*020 Range of Dates: 05-Mar*2001 11:30 to 21-Mar*2001 16:59 Target Range: Species: Rat Total Number o f Days: Total Number of Hours: Total Number o f Data Points: Temperature 64F to 79F 17 389.25 390 Relative Humidity 30% to 70% 17 389.25 390 1+ o cn Mean ( SD): Maximum: Median: Minimum: Number o f Points in Range (%): Number of Points High (%): Number of Points Low (%): 70.0 55.2 ( 2.0) 70.9 63.2 70.1 55.3 67.1 39.3 390 (100.0) 390 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Report Generated: 18-Ju!-2001 at 11:13 COMMENTS: R E V IE W E D B Y : 0 & r-7 D A T E : 7 2H-J Page 874 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 40 Protocol Number: 418*020 Range of Dates: 21*Mar2001 16:00 to 24-Mar-2001 08:59 Target Range: Species: Rat Total Number o f Days: Total Number o f Hours: Total Number o f Data Points: Mean ( SD): Maximum: Median: Minimum: Number of Points in Range (%): Number o f Points High (%): Number o f Points Low (%): Temperature 64F to 79F 4 64.75 65 70.5 ( 3.3) 74.1 72.2 64.6 65 (100.0) 0 (0.0) 0 (0.0) Relative Humidity 30% to 70% 4 64.75 65 51.4 ( 6.7) 67.9 48.9 43.0 65 (100.0) 0 (0.0) 0 (0.0) Report Generated: 18-Jul-2001 at 14:01 COMMENTS: R EV IEW ED BY: /"- DATE: 7 Page 875 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 41 Protocol Number: 418*020 Range of Dates: 21-Mar-2001 16:00 to 24-Mar-2001 08:59 Target Range: Species: Rat Total Number o f Days: Total Number o f Hours: Total Number o f Data Points: Temperature 64'F to 79F 4 64.75 65 Relative Humidity 30% to 70% 4 64.75 65 Mean ( SD): Maximum: Median: Minimum: Number o f Points in Range (%): Number of Points High (%): Number o f Points Low (%): 72.0 (1.7) 57.8 ( 2.8) 74.2 63.4 72.6 57.8 68.6 50.5 65 (100.0) 65 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Report Generated: 18-Jul-2001 at 11:32 COMMENTS: REVIEWED BY: > m t^ K - DATE: 7 7> Page 876 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 01 Protocol Number: 418-020 Range of Dates: 24-Mar-2001 08:30 to 25-Mar-2001 15:59 TSapregceiet sR:aRnagte: Total Number o f Days: Total Number o f Hours: Total Number o f Data Points: Mean ( SD): Maximum: Median: Minimum: Number o f Points in Range (%): Number of Points High (%): Number o f Points Low (%): Report Generated: 18-Jul-2001 at 14:08 T6e4mFpteora7t9urFe 3132.225 70.7 ( 0.4) 677910...928 3002 (1((0000..00.0)) ) Rel3a0ti%vetoH7u0m%idity 3132.225 52.0 (1.7) 455815...878 3002 (1((000..000.))0) COMMENTS: REVIEWED BY: / ) ' Vn DATE: 7 2 v b i Page 877 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 04 Protocol Number: 418-020 Range of Dates: 24-Mar-2001 08:30 to 25-Mar-2001 15:59 TSapregceiet sR:aRnagte: Total Number o f Days: Total Number of Hours: Total Number o f Data Points: Mean ( SD): Maximum: Median: Minimum: Number o f Points in Range (%): Number o f Points High (%): Number o f Points Low (%): Report Generated: 18-Jul-2001 at 14:09 T6e4mFpteora7t9uerFe 3132.225 69.7 (0.5) 676809...856 3002 (1((000.0.00.))0) Rel3a0ti%vetoH7u0m%idity 3132.225 42.1 (1-6) 443519...327 3002 (1((000..000.))0) COMMENTS: REVIEWED BY: Z7 fi D A T E : 7 7 *--&( Page 878 ARGUS ARGUS 418-020 Temperature and Relative Humidity Report Location: Room 40 Protocol Number: 418-020 Range of Dates: 25-Mar-2001 15:35 to 15-Apr-2001 15:59 TSapregceiet sR:aRnagte: Total Number o f Days: Total Number o f Hours: Total Number o f Data Points: Mean ( SD): Maximum: Median: Minimum: Number o f Points in Range (%): Number o f Points High (%): Number o f Points Low (%): Report Generated: 15-Aug-2001 at 09:30 T6e4*mFpteora7t9urFe 55020424.0 72.6 (1.0) 75.4 7702..17 50004 (1((0000..00.))0) Rel3a0ti%vetoH7u0m%idity 55020424.0 50.5 ( 5.0) 753013...553 50013 (((9009..02.8))) COMMENTS: REVIEWED BY: -C j jH DATE: f - /S' / ARGUS 418-020 ARGUS Relative Humidity Deviations Report Location: Room 40 Protocol Number: 418-020 Range of Dates: 25-Mar-2001 15:35 to 15-Apr-2001 15:59 Humidity Target Range: Species: Rat Date Time 06-Apr-2001 06:00 R.H. 71.5 H 3 0 % to 70% Date Time R.H. H - Value out o f range - High L = Value out of range - Low R.H. = Relative Hum idity (%) Report Generated: 15-Aug-2001 at 09:34 / These deviations did not adversely affect the outcome or interpretation of the study. _____ The following deviation(s) impacted on the outcome of the study as described: Page 880 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 41 Protocol Number: 418-020 Range of Dates: 25-Mar-2001 15:35 to 15-Apr-2001 15:59 TSapregceiet sR:aRnagte: Total Number o f Days: Total Number o f Hours: Total Number o f Data Points: Mean ( SD): Maximum: Median: Minimum: Number o f Points in Range (%): Number of Points High (%): Number o f Points Low (%): Report Generated: 18-Jul-2001 at 11:15 T6e4mFpteora7t9urFe 5052402.401 73.2 ( 0.9) 777035...438 504 (100.0) 00 ((00..00)) Rel3a0ti%vetoH7u0m%idity 5052402.401 59.3 (4.8) 457936...100 49095 (98.2) ((10--80)) COMMENTS: R E V IE W E D BY: 0 kr, D A T E : ~7 l ^ j ARGUS 418-020 ARGUS Relative Humidity Deviations Report Location: Room 41 Protocol Number: 418-020 Range of Dates: 25-Mar-2001 15:35 to 15-Apr-2001 15:59 Humidity Target Range: Species: Rat Date 00011112979222-------AAAAAAAppppppprrrrrrr-------2222222000000000000001111111 1133--AApprr--22000011 Time 06:00 06:00 001781:::000000 0190::0000 0161::0000 R.H. 77771222....6338 HHHH 72.2 H 7760..07 HH 7710..86 HH 3 0 % to 70% Date Time H = Value out o f range - High L = Value out of range - Low R.H. = Relative Hum idity (%) Report Generated: 18-Jul-2001 at 11:29 These deviations did not adversely affect the outcome or interpretation of the study. The following deviation(s) impacted on the outcome of the study as described: Page 882 ARGUS 418-020 PM1 N U T R IT IO N INTEtNATIONAL Page 1 o f2 Sample No.: L0022289-3 Received: 08/03/00 Reported: 08/16/00 Site: RHI Locator. 5002 Project: CERT. CERTIFIED RODENT DIET MEAL LOT NUMBER AUG 01 00 2C Assav / Analvte Protein, Kjeldahl (N x 6.25) Protein Fat Fat Fiber, crude Fiber, Crude Arsenic Arsenic Cadmium Cadmium Calcium Calcium Lead Lead Mercury Mercury Phosphorus Phosphorus Selenium Selenium PRKR FTEE/FTAH FIBR ASF CDF CAF PB HGSP PF SE Result 20.9 6.01 4.25 <0.200 0.056 0.788 0.187 <0.025 0.560 0 .3 6 2 Units % % % ppm ppm % ppm ppm % DDm For additional information, please contact (1) For assay methodology - Customer Services, 314-982-1310 (2) For Nutritional Interpretation - Dr. Dorrance Haught, 314-768-4362 (3) All other questions - Richmond, IN Manufacturing Plant, 765-962-9561. The term "Less Than' is used to signify the lower limit o f quantitation o f the procedure under the conditions employed. The use of the term "Less Than" does not imply that traces o f Analyte were present Samples submitted to Ralston Analytical Laboratories for routine analysis will be retained for a minimum o f thirty (30) days after the report o f analysis is issued. Extended storage requirements must be brought to the attention o f Ralston Analytical Laboratories prior to or at the tim e o f sample submission. OHL, A wA,m G,a________________IPfgfr/ffl--------- REVIEWED BY: DATE 1401 S. Hanley Road S t Louis, MO 63144 Phone: 314-768-4100 fax: 314-768-4765 ARGUS 418-020 PMI N U T R IT IO N :soc CERT INTERNATIONAL CERTIFIED RODENT DIET MEAL LOT NUMBER AUG 01 00 2C Assav / Analvte Result Organophosphate pesticides Diazinon Disulfoton Ethion Malathion Methyl Parathion Parathion Thimet Thiodan Trithion Organochlorine pest&PCB's Heptachlor Epoxide Heptachlor DDE Lindane Endrin Mirex Alpha-BHC Delta-BHC Aldrin Dieldrin DDT Chlordane Methoxychlor Beta-BHC HCB PCB Aflatoxin screen Aflatoxins ORGP RSPB AFTC <0.0200 <0.0200 <0.0200 0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <0.150 <5.00 Units ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm PPb For additional information, please contact: (1) For assay methodology - Customer Services, 314-982-1310 (2) For Nutritional Interpretation - Dr. Dorrance Haught, 314-768-4362 (3) All other questions - Richmond, IN Manufacturing Plant, 765-962-9561. The term "Less Than" is used to signify the lower limit o f quantitation o f the procedure under the conditions employed. The use of the term "Less Than" does not imply that traces o f Analyte were present Samples submitted to Ralston Analytical Laboratories for routine analysis will be retained for a minimum o f thirty (30) days after the report o f analysis is issued. Extended storage requirem ents musts be brought to the attention o f Ralston Analytical Laboratories prior to or at the time o f sam ple submission. nn\>AAOi/[ REVIEWED BY: lolrf-.lnn DATE 1401 5. Hanley Road Sc. Louis. M O 63144 Phone: 314-768-4100 Fax: 314-768-4765 Page 884 EXACT COP v J& fr 7M M ; tMdMO________ _________ REVIEWED BY: DATE certine Papers Keinevai LabDietl'.M NUTRITION Return to Certified Analysis Retrieval ARGUS 418-020 Product Code: Product Desc: Lab Number: Lot Code: Entered: 5002M CERTIFIED RODENT DIET MEAL L0025623-1 OCT 03 00 3A 10/5/00 Assay PROTEIN FAT (ACID HYDRO.) FIBER (CRUDE) ARSENIC CADMIUM CALCIUM LEAD MERCURY PHOSPHORUS SELENIUM Analysis Units 21.5 % 5.64 % 5% LESS THAN 0.2 PPM 0.083 PPM 1.07 % 0.147 PPM LESS THAN 0.025 PPM 0.748 % 0.361 PPM ORGANOPHOSPHATES PPM Diazinon LESS THAN 0.02 Ethion LESS THAN 0.02 Methyl Parathion LESS THAN 0.02 Thimet LESS THAN 0.02 Trithion 0L.E0S2S THAN ORGANOPHOSPHATES PPM Disulfoton LESS THAN 0.02 Malathion LESS THAN 0.02 Parathion LESS THAN 0.02 Thiodan 0L.E0S2S THAN PESTICIDES AND PCB Aldrin Beta-BHC DDE Delta-BHC Endrin Heptachlor Lindane Mirex PPM LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 PESTICIDES AND PCB Alpha-BHC Chlordane DDT Dieldrin HCB Heptachlor Epoxide Methoxychlor PCB PPM LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.02 LESS THAN 0.15 http ://www. Iabdiet.com/certified/pwa_spc002.asp Page 885 exact CO,-; 12/ 20/2000 ARGUS 418-020 Aflatoxin Aflatoxins LESS THAN 5 PPB No notes. For additional information, please contact: 1) Michael J. Murphy at (314) 982-2383 - for assay methodology 2) Dr. Dorrance Haught at (314) 768-4362 - for nutritional interpretation 3) Richmond, IN Manufacturing Plant at (765) 962-9561 - all other questions The term "Less Than" is used to signify the lower limit of quantitation of the procedure under the conditions employed. The use of the term "Less Than" does not imply that traces of analyte were present. u v \1 ia a Q a REVIEWED BY: la/a/w DATE Page 886 sEXACT CO.- \/M H 7/ft/o *2? ' ; ARGUS 418-020 Paga 1 o f2 Sample No.: L0028475-2 Received: 11/30/00 Reported: 12/14/00 Sto: RHI Locator: 3002 Project CERT. CERTIFIED RODENT DIET MEAL LOT NUMBER DEC 01 00 IB Protein, Kjehlah) (N x 6^5) Protein Fat Fat Fiber, crade Fiber, Crude A m ale Aneoic Cadminia Cadauna Calcium Calcium Load Lead M ercury Mercury Phosphor Phosphorus Salaaiam Selenium PRXR FTEE/FTAH FDR ASF CDF CAF PB HGSP PF SE Result 20.8 3.92 3.99 <0.200 0.033 0.977 0.139 <0.023 0.659 0.159 Unit H % % ppm ppm K ppm ppm H ppm For additional information, pleate contect (1) For u ie y methodology -Customer Services, 314*982-1310 (2) ForNutritional Interpretation - Dr. Donanoe Huight, 314-764-4362 (3) An otherquestions Richmond, INMmnfscturtngPint, 765-902-9361. The m b TamThaT a BMdto apiay the towerBait efquwtlMrioacfdie procedine nadir the ceadMcm employed. Theiaoof the tarn *LmtThee* do tux boptytba n e ofAnaiytt we pew s. Suspl uterine! lo Rilrtoo Aaityticii laboretoriet fbr Extended tenge reqwranMttiBut be tenetelo the andon ofR itasi Anaiyticil U fcm ori prior oer a t te tine ofunpte lubmiaton. 1 REVIEWED BY: DATE EXACT CC . > n > tf 7 li9 lM _ Page 887 CERTIFIEDRODENT DIET MEAL LOTNUMBER DEC0100 IB T / hr*___________________ OrgoophMpfeatepMttddM DUMB Mmlsthion MethylPnthioo Panthion Thimet Thiodan Trilhiac Organocfaloriae pwtfcPCB'i HeptachluEpoxide Heptachlor DDE T Jw4 m Eadrto Minx Atpbe-BHC DahaBHC Aldrin Dieldrin DDT Chiudane Methoxycfalu Beta-BHC HCB PCB Aflatoxtai K fm Aflatndm ORGP RSPB AFTC Locator 3002 Project CERT. ARGUS 418-020 Remit 0 .0 2 0 0 0.0200 0.0200 0 .0 2 0 0 <0 .0 2 0 0 0 .0 2 0 0 0.0200 0 .0 2 0 0 0 .0 2 0 0 0 .0 2 0 0 0 .0 2 0 0 0 .0 2 0 0 0.0200 0.0200 0.0200 0.0200 0.0200 0 .0 2 0 0 0 .0 2 0 0 0 .0 2 0 0 0 .0 2 0 0 0 .0 2 0 0 0 .0 2 0 0 0.0200 0.150 <5.00 Unto ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm PP*> Foradditional information,platee contact (1) Forueay methodology-CudomerServirne, 3U-9S2-1310 (2) ForNutritional Interpretation- Dr. Durance Haqgbt, 314-763-4332 (3) All other queetknu - Richmond, IN Memi&ctsring Plant, 765-962-9561. T betra le w Th" baw d Unritqfg u a ta r! ofthe proomiur anda Cm conditi employed. Tla urn of d a t a m i Thee*dMMCknpIyt h a n ofAnlyfcwereperno. Snptaw bnlttad toRatonAaalytied L etam a fcr TMd tayeii win be natoedtor ed* ofthirty (30)deyi*tkrthe portof My Ubooed. BxKnded s o a p nqmiiuihim a te traaglXtoita m fcm efRaton AmtytktaUbontori priorto or ta te time ofnrnpie wbmiuien. m l i h d rx oh* REVIEWED BY: exact c" " Page 888 DATE ARGUS 418-020 LancasterLaboratories Where qualityis ascience. Lancaster Laboratories Sample No. WW 3634413 Collected:06/2C/2001 10:J0 by EA Account Number: 02423 Submitted: 06/20/2001 16:30 Primedica Argus Reported: 06/23/2001 at 14:25 57 Union Street Discard: 0"7/29/20Cl Worcester MA 01606 Point #2 Formulation Lab 905 Sheehv Dr Bldg F Grab Water S a m d e Page 1of2 CAT No. 00224 00226 00225 C036B 01504 C15 0 6 01505 A nalysis Naas C hloride O rtho-Phosphate as S ulfate N itra te N itrogen F luoride N itrite n itrogen Brom ide P 00178 P e s tic id e s /P C E ' s m w ater 00453 00454 00455 00469 00477 00475 00638 019C2 01903 01904 01905 01506 01907 C1908 01509 01910 C1 9 1 1 01512 01913 01914 01915 01916 0191" 01918 01919 Gamma BHC - L i n d a n e H eptachlor A ldrm D ield n n E n d rm DDT E ndrm A ldehyde A l p h a BHC B e t a BHC D e l t a BHC H ep tach lo r Epoxide DDE ODD C hlordane Toxapnene E ndosulfan 1 Endosulfan II E ndosulfan S u lfa te PCB-1016 PCB-1221 P C S -1232 PCB-1242 P C 5-124S PCB-1254 FCB-126C H e rS ic is e s :r, W ater CAS N u a b a r 16687-00-6 14265-44-2 14808-79-0 14797-55-8 16984-48-8 14757-65-0 n .a . As R ocaivod R asult < 2.0 < 0.020 < 5.0 < 0.50 < 0.50 < 0.50 < 2.5 As R acaiv ad L iait of Q uan titatio n 2.0 0.020 5.0 0.50 C.5C 0.50 2.5 U nits m g/i mg / I mg/ I m g/1 mg / I m g/1 m g/1 D ilu tio n F actor e. 1 5 & 5 5 5 50_QC,_i " 6-44-8 309-00-2 60-57-1 72-20-8 50-25-3 7421-53-4 219-84-6 319-05-7 315-86-8 1024-57-3 72-55-5 "2-54-6 57-74-9 9001-35-2 959-98-3 33213-65-9 1031-OT-6 12674-11-2 11104-28-2 11141-16-5 53465-21-5 12672-29-6 11097-65-1 11096-82-5 < 0.0094 < 0.0054 < 0.0094 < 0.0094 < C. 0094 < 0.0094 < 0.094 < 0.0094 < 0.0094 < 0.0094 < 0.0094 < 0.0094 < 0.0094 < C.25 < 3.8 < 0.0094 < 0.0094 < 0.029 < 0.94 < 0.94 < 0.94 < 0.94 < 0.94 < 0.94 < 0.54 C. 0094 C. 0094 0.0094 0.0094 C.0094 0.0094 0.094 0.0094 0.0094 0.0094 0.0094 0.0094 C.0094 0.28 3.8 0.0094 0.0094 .02S 0.94 0.94 0.94 0.94 0.94 0.94 0.54 u g /i ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 MEMBER Lancaster Laooratones. Inc 2^25 New Holland Pise PO Box 12425 Lancaster. PA 175C5-2425 717-5o-2300 Fax: 717-65-2SB1 mEXACT C 7 /17/qI Page 889 2216 Rev. 9/11/00 # LancasterLaboratories Where qualityis ascience. ARGUS 418-020 rs\ Lancaster Laboratories Sample No. WW 3634413 Dollected:06/20/2001 10:40 by EA Account Number: 024:3 Submitted: 06/20/2001 16:30 P n m e d i C 2 Arcus Reported: 06/28/2001 at 14:26 5- Union Street Discard: 07/29/2001 Worcester MA 01603 Point #2 Formulation Lab 905 Sheeny Dr 31dc F Grab Water Sample Page 2 of: A 0 1) fR o o o CAT NO. A nalysis Naas 01857 01858 05296 052B7 05288 05289 05290 05291 052 52 C5252 03103 2 , 4-D 2 , 4 , 5-TP Da l a p o n D inoseb Dicamba MCPP MCPA 2,4-D P (D aciilorprop) 2 . 4 -DB P entachlorophenol CAS N u m b e r As R eceiv ed R esult 54-75-7 93-72-1 53-76-5 75-95-0 99-65-7 1916-00-9 93-65-2 94-74-6 120-36-5 . 54-32-6 S7-S6-5 < 0.49 < 0.045 < 0.049 < 1.2 < 0.30 < 200. < 200. < 0.4? < 0.4? < 0.05 Commonwealth o f P e n n s y lv a n ia Lab C e r t i f i c a t i o n No. 3 6 -0 3 " As R eceived L ia it of Q uanti ta tio n C.49 0.049 0 .0 4 ? 1.2 C.25 :.3 o 200. :o c. 0 .4 5 0.4? 0.05 U nits u a /1 U3/1 ua/1 ug/1 ua/1 ua/1 ug/1 ua/1 ua/1 u o /'l D ilu tio n F actor : ; : : i : : 2 1 : CAT No. 00224 00226 00226 00363 1504 01506 01505 00178 01856 00816 00317 Analysis Naae C hloride O rtho-Phosphate as P S ulfate N itra te N itrogen F luoride N itrite N itrogen B rom ide P e s t i c i d e s / P C B *s m W a t e r H e rb ic id e s m W ater W ater Sam ple H e rb ic id e E xtract W ater Sam ple P e s t. E x tractio n Laboratorv Chronicle Analysis Method EPA 3 0 0 . 0 T r i a i t D a t e a n d 'r i s a 1 06/21/2001 14:25 EPA 3 6 5 .3 1 0 6 /2 1 /2 0 0 1 21 : 00 EPA 3 0 0 . 0 : 06/21/2001 14:25 EPA 3 0 0 . 0 i 06/21/2001 14:25 EPA 3 0 0 . 0 EPA 3 0 0 . 0 06/21/2001 14:25 0 6 / 2 1 / 2 0 0 1 14 :2 5 EPA 3 0 0 . 0 EPA 608 i 06/21/2001 14:25 i 06/21/2001 19:45 SW-84 81S1A SW-646 8151A i 06/25/2001 16:12 1 06/22/2001 EPA 09 06/21/2001 05:45 Analys t Mark A. B u c k w a lte r D aniel S. Sm ith M ark A. B u c k w a l t e r M ark A. B u c k w a l t e r M ark A. B u c k w a l t e r M ark A. B u c k w a l t e r M ark A. B u c k w a l t e r A n i t a M. D a l e T i f f a n y A. Leyda D e b o r a h M. Z i m m e r m a n Dilution Factor 5 1 5 5 5 5 5 1 1 1 Amanda E . Wade 1 M EM BER Lancaster Laboratories, ine. 412S New Holland Pike PO Boa 1242S Lancaster, PA 17605-2425 717-656-2300 Faa: 717-656-2681 EXACT J t Page 890 'A A - ' I 2216 Rev- 9/11/00 e LancasterLaboratories Where qualityisascience. ARGUS 418-020 alysis R e p o rt Lancaster Laboratories Sample No. WW 3634414 Collected:06/20/2001 10:30 by A Account Number: 02423 Submitted: 06/20/2001 16:30 Reported: 06/28/2001 at 1-5:26 Discard: 07/25/2001 Point #3 Analytical lab 505 Sheehv Dr Bldg 5 Grab Water Samcie Pnmedica Argus 57 Union Street Worcester MA 01608 Page 1 o f 2 CAT No. 00224 00226 00229 00358 01504 01506 01505 A n a l y s i s Name C hloride O rtho-Phosphate as S ulfate N itra te N itrogen F luoride N itrite N itrogen Brom ide P 00176 P e s tic id e s /P C B 's in W ater 00453 00454 00455 00469 00477 00476 0063c 01902 01903 01904 01905 01506 01907 01908 01909 01910 01911 01912 01913 01914 01915 01916 C1917 C1919 01915 Gamma BHC - L i n d a n e H eptachlor A larm D ield n n C ndrin DDT E n d n n A ldehyde A l p h a BHC B e t a BHC D e l t a BHC H eptachlor E p o x id e DDE ODD C hlordane Toxaphene E ndosulfan I Endosulfan II E ndosulfan S u lfa te PCB-1016 PCB-1221 PCB-1232 P C S -1242 PCB-1248 P C S -1254 PCB-1260 01556 H e rb ic id e s m W ater CAS N u a b e r 16867-00-6 14265-44-2 14808-75-3 14797-55-8 16984-46-8 14797-65-0 n .a . AiR R e c e i v e d R esult < 2.0 < 0.020 < 5.0 < C. 50 < 0.50 < C.50 < 2.5 As R eceiv ed L ia it of Q u an titatio n 2.0 0.020 5.0 .50 0 .5 0 0.50 2.5 U nits mg / 1 mg/ I mg ,'l mg / I mg / I m g /1 m g/1 D ilu tio n F acto r 5 1 5 5 5 5 5 56-85-9 76-44-8 309-00-2 60-57-1 72-20-0 50-25-3 7421-53-4 3 1 5-B 4-6 315-85-7 319-86-B 1024-57-3 72-55-9 72-54-8 57-74-9 8001-35-2 959-98-8 33213-65-9 1031-07-6 12674-11-2 11104-28-2 11141-16-5 5 3 4 6 5 -2 1 -5 12672-29-6 11097-69-1 11096-62-5 < 0.0095 < C.0095 < 0.0095 < 0.0095 < 0.0095 < 0.0095 <0.095 <0.0095 <0.0095 <0.0095 <0.0095 <0.0095 <0.0095 <0.29 <3.8 <0.0095 <0.0095 <0.029 < 1 .0 < 1 .0 < 1 .0 < 1 .0 < 1 .0 < 1 .0 < 1.0 0.0095 0.0095 0.0095 0.0095 0.0095 0.0095 0.095 0.0095 0.0095 0.0095 0.0095 0 .0 0 9 5 0.0095 0 .2 9 3.8 0.0095 0.0095 0.029 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ug/1 u g /i ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 U3/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 1 2 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Lancaster Laboratories, Inc. PMfEjMW_BiiEJ1MR9m m 2425 New Holland Pike p o b o x i242s Lancaster. PA 17S0S-242S 717-656-2300 Fax: 717-656-2681 . (EXACT C O , - . U tJ la M - Page 891 2216. Rev. 9/11/00 ARGUS 418-020 Z i LancasterLaboratories Where qualitys ascience. Lancaster Laboratories Sample No. W W 3634414 Collecte :06/20/1:Cl 10:3C by EA .-icccur.t Number: O^li..- Submitted: G6/2G/2Q01 16:30 Reported: 06/2S/2001 at l-i:2S Discard: 07/29/2001 Point #3 Anaivtical Lac 905 Sheeny Dr Eldg 3 Grab Water Sample Primedica Argus 5~ Onion Street Worcester MA 0160c Pace : o f : CAT NO. Analysis Nano 01857 01958 05296 05287 0528B 05289 05290 05291 05292 05293 08103 4-D 4 , 5-T D alap o n D inoseo Dicamoa MCP? MCPA Z , 4-DP (D ic h io r p ro p i 2 . 4-DB P e n tac h lo rc p n e n o l CAS Nuabor 94-">5-7 93-72-1 93-76-5 75-55-0 86-95-7 1910-00-9 93-65-2 94-74-6 120-36-5 94-82-6 57-86-5 As Roeaivod Rosult < 0.48 < 0.048 < 0.046 < 1.2 < 0.24 < 0.29 < 190. < 190. < G. 48 < 0.48 < 0.05 Com monwealth o f F e n n s y lv a n l a Lab C e r t i f i c a t i o n No. 36-037 As Roeoivod Liait of Quantitation 0.48 0.046 0.048 1.2 0.24 0 .2 5 190. 190. 0.46 0.45 0.05 Units u g .'l U Q /i U3/1 uc. 1 ug/1 ug/1 u g /I ug/1 uo/1 ua/1 ug/1 Dilution Factor : :1 7 1 1 1 CXT No. 00224 00226 0022? 30365 01504 01506 01505 0017S 01356 00816 0061" Analysis Na m C hlcnde Jrthc-P hcsphate as P S ulfate N itra te N itrogen F luoride N itrite N itrogen Brom ide P esticid es/P C B 's m w ater H e rb ic id e s in W ater W ater Sam ple H e rb ic id e E xtract W ater Sam ple P e s t. E x tractio n Laboratory Chronicle EPA EPA EPA EPA EPA EPA EPA EPA >d 300.0 365.3 300.0 300.0 300.0 3 0 0 .0 3 0 0 .0 606 Trial# 1 1 1 1 1 1 1 1 Analysis Data and Tims 06/21/2001 14:39 06/21/2001 21:00 06/21/2001 14:39 06/21/2001 14:39 06/21/2001 14:39 06/21/2001 14:39 06/21/2001 14:39 06/21/2001 20:05 SW-B46 8151A 1 06/25/2001 16:49 SW-846 8151A 1 06/22/2001 09:00 EPA 608 1 06/21/2001 09:45 (Hark A. B u c k w a l t e r D an iel S . Sm ith M ark A. B u c k w a l t e r M ark A. B u c k w a lte r M ark A. B u c k w a lte r M ark A. B u c k w a lte r M ark A. B u c k w a l t e r A n i t a M. D ale T iff a n y A. Leyda D e b o r a h M. Z i m m e r m a n Dilution F a c to r 5 1 5 5 5 5 5 1 1 1 Amanda E. wade 1 MEMBER Lancaster Laboratories. In;. 2425 'le w Hciianc Pike PO Box 12425 Lar.caste- rA 175C5-2425 717-SS5-23CC j *. ?17 5*25S: 2>- 7A Page 892 EXACT COPY JMJ/lJ ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. BOX 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8197-00A Date sampled : 11/28/00 Time sampled : 1400 Date received: 11/28/00 Sampled by : EM Sanple source: Formal ation I-- tborY'S-erij (D . 1t>S r iSKc^7v^r,vc- >^7/oo ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DBP drinking water standards for this parameter. Pararne!er MCL Sesuit Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 2~ >. '-yLi y / # # All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks {**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Marynn E. Fedock/ President Page 893 E X A C T ;l 7 /u /o i ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Or., Building A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8197-00B Date sampled : 11/28/00 Time sampled : 1400 Date received: 11/28/00 Sampled by : EM Sanqple source: Rm. 39 4S &he.ck >nvc- 1 f-a/j7/00 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the SPA and DEP drinking water standards for this parameter. Parameter ML Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <l <1 0.1 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 -3 3 2 Maryafm E. Fedock/ President Page 894 e x a c t c Z~~'- .TZlsfaj ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8197-00C Date sampled : 11/28/00 Time sampled : 1400 Date received: 11/28/00 Sampled by : EM Sample source: Rm. 15 1^ 7/O lirivc. ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of saiqpling, meets the EPA and DSP drinking water standards for this parameter. Parameter Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 MCL <1 RU!_L <1 <1 < 0.1 ~2) 00 All results which are outside the "Maximum Contaminant Level" (MCL) establishec under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less them TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 -3 3 2 Maryafin E. Fedock/ President Page 895 ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8197-00D Date sampled : 11/28/00 Time sampled : 1400 Date received: 11/28/00 Sampled by : EM Sample source: Analytical l-- *herh>ry `OS. e> 'Sc.cAyb nvc~ ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the BPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 2) y /U 7 / 0 # All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less them TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 -3 3 2 Maryann E. Fedock/ President Page 896 e x a c t : , '" ' -7/k A , ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 ARGUS 418-020 SAMPLE ANALYSIS REPORT C u s to m e r: Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : 215-443-858 Sample number: 8331-00A Date sampled : 12/18/00 Time sampled : 1315 Date received: 12/18/00 Sampled by : EM Sample source : Analytical y'or V '-i /v ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Earamster MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 ~- /a/ All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count {> 200) mg/1 - milligram/liter PA DEP # 0 9 -3 3 2 Maryanj^TE. Fedock/ President Page 897 EXcfcr.'-:D/ ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8331-00B Date sampled : 12/18/00 Time sampled : 1315 Date received: 12/18/00 Sampled by : EM Sample source: Chem. Lab ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <l <l < 0.1 "V /-* / i All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP #09-332 Maryan^. Fedock/ President Page 898 ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT C u s to m e r : Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX # : 215-443-858 Sample number: 8331-00C Date sampled : 12/18/00 Time sampled : 1315 Date received: 12/18/00 Sampled by : EM Sample source: Rm. 38 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 -3 3 2 Maryann^. Fedock/ President Page 899 [ex AC tL?/ '1/C ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT C u s to m e r: Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : 215-443-858 Sample number: 8331-00D Date sampled : 12/18/00 Time sampled : 1315 Date received: 12/18/00 Sampled by : EM Sample source: Rm. 20 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Eararceter MCL RssilLl Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 0.4 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 -3 3 2 Maryan^E. Fedock/ President Page 900 ARGUS 418-020 Analysis Report -V. \ Lancaster Laboratori* Sample Ho. HH 3542350 Collected:03/26/2001 08:50 by EA Submitted: 01/26/2001 16:00 Reported: 02/06/01 at 05:22 AM Discard: 3/9/01 90S Analytical Lab Point #1 Grab Water Sample Semi-Annual Account Number: 02423 Pnmedica Argus 57 Union Street Worcester MA 01608 Page 1of2 90 SAP CAT No. 00224 0022 003 01*04 01506 07322 01505 Analytn NtM Chloride Sulfate Nitrate Nitrogen Fluoride Nitrite Nitrogen O r t h o -phosphate Bromide 00178 Pesticides/PCB's in water 00453 00454 00455 00469 00477 00475 00638 01902 01903 019C4 01905 02906 C19C7 01908 01909 01910 01911 01922 01913 01914 01915 01916 02927 Cl?19 01919 Gemme BHC - Lindane Heptecfilor Aldnn Dieldnn Cndrin DDT E n d n n Aldehyde Alpha BKC Beta BKC Delta BKC Heptachlor Epoxide ODE ODD Chlordane Toxaphene Endosulfan I Endosulfan 11 Endosulfan Sulfate PCB-1016 PCB-1221 PCB-1232 PCS-1242 PCa-1248 PCS-1254 ?CB-2260 CAS Number 16187-00-6 14808-79-0 14797-55-8 16994-48-8 14797-65-0 14265-44-2 n.a. Rnault c 2.0 < 5.0 < 0.5C < 0.50 < Q.50 <5.0 <2.5 58-89-9 76-44-8 309-00-2 60-57-1 72-20-8 50-29-3 7421-93-4 319-84-6 319-8S-7 319-86-8 1024-57-3 72-55-9 72-54-8 57-74-9 8001-35-2 959-98-8 33213-65-9 1031-07-9 22674-11-2 11104-28-2 11141-16-5 53469-21-9 12672-29-6 11097-69-1 21096-52-5 < 3.0099 < 0.0096 < 0.0098 < 0 0098 < 0.0098 < 3.0096 < C.09B < 0.0096 < 0.0098 < 0.0098 < 0.0098 < 0.009B < 0.0098 < C .29 <3.9 < 0.0098 < 0.0098 < 0.029 <1.0 <1.0 < 1.0 < i .0 < 1.0 < 2.2 < 2.2 As Received Limit of Quantisation 2-0 5.0 0.50 0.50 0.50 5.0 2.5 units mg/1 mg/1 mg/1 mg/1 mg/1 mg/1 mg/1 Dilucin Factor 5 5 5 5 5 5 5 0.0098 0.0098 0.0098 0.0098 0.0098 0.0098 0.098 0.0098 0.0098 0.0098 0.0098 0.0098 0.0098 0.29 3.9 0.0098 0.0098 0.029 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ug/1 ug/l ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 1 1 1 1 1 1 1 1 l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 MEMBER ----- A G IL la n ca tte r la n o ra te ric t. in t 2i2i N*w Me"*"* Plk* Bai 1242S Lancaster. P> 17MS-242S 717 656-2300 Fa 717434-26(1 EXACT COPY Onrerlirlo i Page 901 2216 Rav. /11/00 ARGUS 418-020 Analysis R eport LancasterLaboratories r Wherequalityisa science. Lancaster Laboratories Sample No. WW 3542350 Collected:01/26/2001 08:50 by EA Submitted: 01/26/2001 16:00 Reported: 02/06/01 at 05:22 AM Discard: 3/9/01 905 Analytical Lab Point #1 Grab Hater Sample Semi-Annual Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 Page2of2 CAT No. 0X854 A u l y t i s Mima Herbicidas in Water 01857 0X858 05286 05287 05288 05289 05290 0529X 05292 05293 08X03 2,4-D 2*4,5-TP 2.4,5-T Dalapon Dinoseb Dicaaba MCPP MCPA 2,4-DP (OichXorprop) 2,4-DB Pentachlorophanol . CAS H a b e r A# i M b i r a d Aoault 94-75-7 93-72-1 93-76-S 75-99-0 88-85-7 19X8-00-9 93-45-2 94-74-6 120-36-5 94-82-6 87-86-5 < 0.48 < 0.048 < 0.048 < 1.2 <0.24 < 0.29 < 190. < 190. < 0.48 < 0.48 <0.05 Commonwealth o Pennsylvania Lab Certification No. 36-037 Ae Aacaived Liait of Quantitation Unica 0.48 0.048 0.046 1-2 0.24 0-29 190. 190. 0.46 0.48 0.05 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 Dilution Factor 1 1 1 1 1 1 1 1 1 1 1 MEMBER A C IL Lancaster Laboratories, me. 2425 Now HoMentf M o PO ftox 12425 Lancaster. M 17405-2425 717-454*2300 fa 717-455-2481 Page 902 I JI EXACT COPY I s)mr8hs'h i 2214 ftev. 9/11/00 ARGUS 418-020 Analysis R ep o rt taneiitir Laberateriti Sample Mo. NW 3542351 Collected:01/26/2001 08:40 by EA Submitted: 01/26/2001 16:00 Reported: 02/06/01 at 05:22 AM Discard: 3/9/01 905 Formulation Lab Point #2 Grab Water Sample Semi-Annual Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 Page 1of! 905-2 CAT No. 00224 00226 00366 01504 01506 07322 01505 Afttlyiii N u t Chloride Sulfate Nitrate Nitrogen Fluoride Nitrite Nitrogen Crtho-phosphate Bromide 00178 Festitides/PCB's in water 00453 00454 00455 0046? 0047^ 00476 00638 01902 01903 01904 01905 01905 01907 31909 31909 31910 31911 31912 01913 31914 31915 31916 01917 31913 31913 Gamma BHC - Lindane Heptachlor Al dr in Oieldrin Endrm C3T Endrin Aldehyde Alpha BHC Beta BHC Celta BHC Heptachlor Epoxide 22 ODD Chlordane Tdxaphene Sndosulfan I Sndosulfan XI Endosulfan Sulfate PCB-1016 FCB-1221 7C3-1232 ?C3-1242 PC3-1246 FCa-1254 7CS-1253 CAS Number 16867-00-6 14808-79-8 14797-55-B 16984-48-6 14797-65-0 14265-44-2 n.a. As Received Beeult c 2.0 < 5.0 < 0.50 < 0.50 c 0.53 < 5.0 < 2.5 As Received Limit of Quantitatioo 2.0 5.0 o.so 0 .SO 0.50 5 .0 2.5 Unit mg/1 mg/1 mg/1 mg/1 mg/1 mg/1 mg/1 Dilution Factor 5 5 5 5 5 5 5 58-89-9 75-44-8 309-00-2 60-57-1 72-20-8 50-29-3 7421-93-4 319-84-6 319-85-7 319-86-8 1024-57-3 72-55-9 72-54-8 57-74-9 8001-35-2 959-91-8 33213-65-9 1031-07-8 12674-11-2 11104-28-2 11141*16-5 53469-21-9 12572-29-6 11097-69-1 11096-82-5 < C .0096 < C .0096 < 0.0096 < Z .0096 < 0.0096 < 3.0096 < C.096 < 0.0395 0.0096 < 0.0096 < 0.0096 < 0.0096 < 0.0096 < 0.29 < 3.6 < 0.0096 < 3.0096 0.029 < 1.0 < 1.3 <1.2 < 1.0 1.0 < 2.2 < 1.2 0.0096 0.0096 0.0096 0.0096 0.0096 0.0096 0.096 0.0096 0.0096 0 .0096 0.0096 0.0096 0.0096 0.29 3.6 0.0096 0.0096 0.029 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 MEMB ER a c ii: Lancaster la o o raton e s. me. 2425 N ew H olland he PO to a 12425 Lancaster, M 17605*2425 717*656*2300 Faa: 717*656*2661 EXACT COPY w y //5 -/o / Page 903 1 > LJlr-v-- ->//u/0 2114 . 9/11/00 ARGUS 418-020 Analysis R e p o rt Lancaster Laboratories Sample Ho. WN 3542351 Collected:01/26/2001 08:40 by EA Submitted: 01/26/2001 16:00 Reported: 02/06/01 at 05:22 AM Discard: 3/9/01 905 Formulation Lab Point #2 Grab Water Sample Semi-Annual Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 905-2 CAT NO. 01856 Analysis Naas Herbicides uv water 01157 01858 05286 05287 05288 05289 05290 05291 05292 05293 08103 2.4-D 2,4.5-TP 2.4.5-7 Oalapon Dinoseb Dieambe MCPP MCPA 2.4-OP (Dichlorprop) 2 ,4-DB Per.tachlorophenol CAS Nimber As Meceived Raoulc 94-75-7 93-72-1 93-76-5 75-99-0 88-85-7 1918-00-9 93-65-2 94-74-6 120-36-5 94-82-6 87-86-5 m + o V < 0.048 < 0.048 < 1.2 < 0.24 < 0.29 < 190 . < 190 . < 0.48 0.48 < 0.05 Commonwealth of Pennsylvania Lab Certificacin No. 16-03'' As fteesived Limit of Quantitation aits 0.48 0.048 0.048 1.2 0.24 0.29 190. 190 . 0.48 0.48 0.05 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 Page2of2 Dilution Factor 1 1 1 1 1 1 1 1 1 1 1 AOL meLancaster Laooratone*. 242S N ew H eiland Pike PO to a 12425 Lancaster. Pa 17605-2425 717456-2300 Fas: 717-656-2601 Page 904 EXACT COPY 'faPrhs-loi z/ j l / c i 2216 Mew. t/11/00 ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. BOX 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: 2018-01A Date sampled : 01/03/01 Time sampled : 1430 Date received: 01/03/01 Sampled by : EM Sample source: Chem-Lab Vf/*! nu-- / ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result. Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <l <l < 0.1 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 M a r y E . Fedock/ President Page 905 Im iI eC Ax*a( ,c t c . 2M&L. ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: Sample number: 2018-01B Date sampled : 01/03/01 Time sampled : 1430 Date received: 01/03/01 Sampled by : EM Sample source: Rm. 38 `J r / o ) 9OS S h o ' b n sjc. / ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <l <1 <1 1.1 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP #09-332 Maryajfii E . Fedock/ President Page 906 / EXACT c Z: ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: Sample number: 2018-01C Date sampled : 01/03/01 Time sampled : 1430 Date received: 01/03/01 Sampled by : EM Sample source : Analytical L.aboraitor if- 9&S& Shc-ehy ri ve. !/A>' ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the BPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 '/r /a l All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 /y -- Marnn E. Fedock/ President ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. BOX 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn : 215-443-8710 FAX # : Sample number: 2018-01D Date sampled : 01/03/01 Time sampled : 1430 Date received: 01/03/01 Sampled by : EM Sample source: Rm. 14 ^ ? 0<5 'S h c . c J ^ y & n v c . ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Threfore, the water supply, at the time of sampling, meets the EPA and DBP drinking water standards for this parameter. Parameter Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 MCL <1 Result <1 <1 0.6 Z /-r-oi All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Marnn E. Fedock/ President Page 908 i e x a c t c ~ ~ ;` ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX # : Sample number: 2337-01A Date sampled : 02/14/01 Time sampled : 1515 Date received: 02/14/01 Sampled by : EM Sample source: Chem. Lab *7& h ^SA C.C.Ay c. ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 -- 7r~ 2/o /f All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Maryann E. Fedock/ President Page 909 !D A M O ! ' ` \ / H > K 7li2Mi ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: Sample number: 2337-01B Date sampled : 02/14/01 Time sampled : 1515 Date received: 02/14/01 Sampled by : EM Sample source: Rm. T-2 f a ) ^ 7 ^ 5 'SAe.e.A,/bn VC. ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 0.5 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Maryann E. Fedock/ President Page 910 EXACT CCW* ANALYTICAL LABORATORIES, INC. P.O. BOX 319 CHALFONT, PA 18914 (215) 723-6466 ARGUS 418-020 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: Sample number: 2337-01C Date sampled : 02/14/01 Time sampled : 1515 Date received: 02/14/01 Sampled by : EM Sample source: Rm. 5 "*/<*>/* -S/ c . c j ) V C - ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the BPA and DEP drinking water standards for this parameter. EaramaLar MCL Rasult Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <l <i 0.1 ~2>- - All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Maryann E. Fedock/ President ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: 2337-01D Date sampled : 02/14/01 Time sampled : 1515 Date received: 02/14/01 Sampled by : EM Sample source: Analytical i)/"/ve. O ' */**/*/ ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 2) A _ All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Maryann E. Fedock/ President Page 912 ANALYTICAL LABORATORIES, INC. F.O. Box 319 CHALPONT, PA 18914 (215) 723-6466 ARGUS 418-020 SAMPLE ANALYSIS-REPORT v Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 Sample number: 4135-01A Date sampled : 03/07/01 Time sampled : 1430 Date received: 03/08/01 Sampled by : FO FAX # : Sample source: Room #39 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 0.6 ^ J O A r - g -- All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP #09-332 ,/ M a r y a i ^ E . Fedock/ President Page 913 EXACT COPY ' f t 't>( ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX # : Sample number: 4135-01B Date sampled : 03/07/01 Time sampled : 1430 Date received: 03/08/01 Sampled by : FO Sample source : Chem. La* ^ 5 F She-t.hj br>v ,, / ^ V 0' ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the BPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <l <1 <1 < 0.1 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count {> 200) mg/1 - milligram/liter PA DEP #09-332 Maryaim E. Fedock/ President Page 914 ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: 4135-01C Date sampled : 03/07/01 Time sampled : 1430 Date received: 03/08/01 Sampled by : FO Sample source: Analytical U c J ^ o r c J - c r ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 MCL <1 Result <1 <1 < 0.1 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 ______ ____ _ Maryann E. Fedock/ President Page 915 ! tX A C T COi-V r !A & H - 7 / i w t I i ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : Sample number: 4135-01D Date sampled : 03/07/01 Time sampled : 1430 Date received: 03/08/01 Sampled by : FO Sample source: Room #5 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the BPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 Q Jr, - 'P.r r >o>-r-i >r< -Z/u/l > J P P -/T Z . . /L lJ iJ a l <1 <1 <1 1.5 2> All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks ( * * ) . Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP #09-332 Maryann E. Fedock/ President Page 916 ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. BOX 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE A N A LY S I S REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : Sample number: 4266-01A Date sampled : 04/02/01 Time sampled : 1400 Date received: 04/02/01 Sampled by : FO Sample source : Analytical ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <l <l < 0.1 ~2 L J -- 9 - 9 -o/ All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Maryann E. Fedock/ President fibbj E X A C T 'C O . ` 1 7//7/0I Page 917 ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: Sample number: 4266-01B Date sampled : 04/02/01 Time sampled : 1400 Date received: 04/02/01 Sampled by : FO Sample source: Rm. 16 Rack 027 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <l <l <1 0.6 ~2>. 9-9-4/ All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Maryann E . Fedock/ President Page 918 EXACi COr Y : 7 lnfo\ ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Bax 319 CHALPONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX # : Sample number: 4266-01C Date sampled : 04/02/01 Time sampled : 1400 Date received: 04/02/01 Sampled by : FO Sample source: Rm. 39 Rack 121 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <i <i <1 0.3 - 9-#t All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Marynn E. Fedock/ President Page 919 * C.A * 'v-' w' \M'A Ihllzll ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Pena Lebo Attn: 215-443-8710 FAX #: Sample number: 4266-01D Date sampled : 04/02/01 Time sampled : 1400 Date received: 04/02/01 Sampled by : FO Sample source: Formulations ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <l < 0.1 )-L -r y - ? - 7 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP # 0 9 - 3 3 2 Maryann E . Fedock/ President Page 920 e x a c t ex' ~ I > 7 //7 /a ( ARGUS 418-020 #LancasterLaboratories Where qualityb a science. Lancaster Laboratories Sample No. SS Collected:01/26/2001 09:50 by EA Submitted: 01/26/2001 16:00 Reported: 02/06/01 at 05:22 AM Discard: 3/9/01 Bedding: Lot S MJ1600 Sample 3542353 Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 Page I ofZ CAT No. 00159 01546 01649 01651 01655 01666 06935 06936 Asulyii Naat Mercury Barium Cadmium Chromium Lead Silver Arsenic 7R Selenium TR 01224 Pesticides/PCBs in Solids CAS Number 7439-97-6 7440-39-3 7440-43-9 7440-47-3 7439-92-1 7440-22-4 7440-38-2 7782-49-2 Aa Received Xeeult < 0.096 < 9.9 < 2.0 <4.0 < 9.9 < 2.0 <0.99 1.20 As Received Limit of Quantitation 0.096 9.9 2.0 4.0 9.9 2.0 0.99 0.99 Doits mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg tng/itg mg/kg Dilution Factor 1 1 1 1 1 1 1 - 01218 01219 01220 01221 01222 01223 01359 01981 01982 01983 01984 01985 01986 01987 01986 31989 01990 01991 01992 01993 01994 01995 01996 01997 C1998 Gamma 9HC - Lindane Heptachlor Aldrin DDT Dieldrm Sndrin Methoxvchlor Alpha BHC Beta BHC Delta 3HC Heptachlor Epoxide DDE DDD Chlordane Toxaphene Endosuifan I Endosuifan II Endosuifan Sulfate Sndrin Aldehyde PCB-101S ?CB-1221 PC3-1232 PCB-1242 PC3-1246 PCB-1254 58-89-9 76-44-8 309-00-2 50-29-3 60-57-1 72-20-8 72-43-5 319-84-6 319-85-7 319-86-9 1024-57-3 72-55-9 72-54-0 57-74-9 8001-35-2 959-98-8 33213-65-9 1031-07-8 7421-93-4 12674-11-2 11104-28-2 11141-16-5 53469-21-9 12672-29-6 11097-69-1 < 0.33 < 0.33 < 0.33 < 0.67 < 0.67 < 0.67 < 3.3 < 0.33 < 0.33 < 0.33 < 0.33 <0.67 < 0.67 < 17. < 33. < 0.33 < 0.67 <0.67 < 0.67 < 17. < 17. < 17. < 17. < 17. < 1?. 0.33 0.33 0.33 0.67 0.67 0.67 3.3 0.33 0.33 0.33 0.33 0.67 0.67 17. 33 . 0.33 0.67 0.67 0.67 17. 17. 17 . 17. 17. 17. ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg ug/kg 1 1 1 1 1 1 1 1 1 1 l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 & kc. C.-> ! V i^ v iT -tv n .-ie y iT - y --Ae. u . rS .u /r u \ju >nw<>l .;ncjsicr Ljoon::nes. :nc M :M 3 3 I42S Mew mollano Pike * ?c soa :242s Lancaster. ? 7005-2425 77-i5*23C0 ?!7*556*2S* /ln /if EXACT COPY ,j, a- pr. n.vT`:! 'c.j'j/tJ'exL. e r SC "3 j. jljLt - a3^ u / d 2215 lev.O'11/OO **h n P ? /n r\o i Page 921 ARGUS 418-020 alysis Report LancasterLaboratories # r Where qualityisascience. Lancaster Laboratories Sample Ho. S5 3542353 Collected:01/26/2001 09:50 by EA Submitted: 01/26/2001 16:00 Reported: 02/06/01 at 05:22 AM Discard: 3/9/01 Bedding: Lot # MJ1600 Sample Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 Page 2 of CAT No. 01999 Aaalyiia Naao PCB-1260 CAS Humber 11096-82-5 01863 Appendix IX Herbicides in Soil 04174 2 , 4 - D 04176 2,4,5-TP 94-75-7 93-72-1 As Received Aesult 17. < 17. < 1.7 A* Received Limit of Quantitation 17. talea ug/kg 17 . 1.7 ug/kg ug/kg Dilution Factor 1 1 1 2" ). A/ EXACT COPY s h s -jo / MEMBER /C IL Lancestor laboratories. Inc 2425 Mew Holland Pike PO Boa 1242S Lancaster. PA 17605-2425 7T7-4S6-2300 fS K 7T7-454-26It Page 922 2215 R*v. 9/11/00 ARGUS 418-020 Explanation of Sym bols and Abbreviations The following defines common symbols and abbreviations used in reporting technical data. N.D. TNTC IU nhos/cm C Cal meq 9 Ufl ml m3 none detected Too Numerous To Count International Units micromhos/cm degrees Celsius (diet) calories miliiequivalents gram(s) microgram(s) milliliters) cubic meter(s) BMQL MPN CP Units NTU F lb. kg mg 1 ul fib >5 um/ml Below Minimum Quantitation Level Most Probable Number cobalt-chloroplatinate units nephelometric turbidity units degrees Fahrenheit pound(s) kilogram(s) milligram(s) liter(s) microliter(s) fibers greater than 5 microns in length per ml < > ppm ppb Dry weight basis less than - The number following the sign is the limit of quantitation, the smallest amount of analyte which can be reliably determined using this specific test greater than parts per million - One ppm is equivalent to one milligram per kilogram (mg/kg), or one gram per million grams. For aqueous liquids, ppm is usually taken to be equivalent to milligrams per liter (mg/l). because one liter of water has a weight very close to a kilogram. For gases or vapors, one ppm is equivalent to one microliter of gas per liter of gas. parts per billion Results pnnted under this heading have been adjusted for moisture content. This increases the analyte weight concentration to approximate the value present in a similar sample without moisture. U.S. EPA data qualifiers: Organic Qualifiers A B C D E J N P U X.Y.Z TIC is a possible aidoLcondensation product Analyte was also detected in the blank Pesticide result confirmed by GC/MS Compound quantitated on a diluted sample Concentration exceeds the calibration range of the instrument Estimated value Presumptive evidence of a compound (TICs only) Concentration difference between primary confirmation columns >25% Compound was not detected Defined in case narrative Inorganic Qualifiers B Value is <CRDL, but >IDL E Estimated due to interference M Duplicate injection precision not met N Spike sample not within control limits S Method of standard additions (MSA) used for calculation U Compound was not detected w Post digestion spike out of control limits Duplicate analysis not within control limits + Correlation coefficient for MSA <0.995 Tests results relate only to the sample tested. Clients should be aware that a critical step in a chemical or microbiological analysis is the collection of the sample. Unless the sample analyzed is truly representative of the bulk of material involved, the test results will be meaningless. If you have questions regarding the proper techniques of collecting samples, please contact us. We cannot be held responsible for sample integrity, however, unless sampling has been performed by a member of our staff. This report shall not be reproduced except in full, without the written approval of the laboratory. W ARRAN TY A N D L IM IT S O F L IA B ILIT Y in accepting analytical work, wa warrant the accuracy of test results for the sample as submitted. THE FO R EG O IN G E X P R E S S W A RRA N TY IS E X C L U SIV E A N D IS G IV EN IN LIEU OF ALL O TH ER W A RRA N TIES. E X P R E S S E D O R IM PLIED. W E D ISC LA IM A N Y O TH ER W A RR A N T IES. E X P R E S S E D O R IM PLIED. IN CLU D IN G A W ARRANTY OF F IT N ESS FOR PA RTICU LA R P U R P O SE AN D W ARRA N TY OF M ERCH ANTABILITY. IN NO EV EN T SH A LL LA N C A ST ER LA BO RA TO RIES BE LIABLE FO R IN DIRECT. SPEC IA L. C O N SE Q U E N T IA L O R IN CID EN TA L D A M A G ES INCLUDING . BUT NOT " `T E D TO. D A M A G ES FO R L O S S OF PR O FIT O R G O O DW ILL R E G A R D L E S S OF (A) THE N EG L IG EN C E (EIT H ER SO L E O R C U RREN T) OF LA N C A ST ER LA B O R A T O R IES AN D (B) W H ETH ER LA N C A ST E R LA BO RA T O RIES H A S BEEN IN FO R M ED OF THE PO SSIB ILIT Y OF SU C H D A M A G ES. W e accept no legal responsibility for the purposes for which the client uses the test results. No purchase order or other order for work shall be accepted by Lancaster Laboratories which includes any conditions that vary from the Standard Terms and Conditions of Lancaster Laboratories and we hereby object to any conflicting terms contained in any acceptance or order submitted by diem. Page 923 ARGUS 418-020 APPENDIX K HISTOPATHOLOGY REPORT Page 924 ARGUS 418-020 RESEARCH PATHOLOGY SERVICES, INC. 438 East Butler Avenue, New Britain, PA 18901 Phone: 215-345-7070 Fax: 215-345-4326 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: 7-6889.6 HISTOPATHOLOGY REPORT SU B M IT T E D TO: Raym ond G. York, Ph.D., D.A.B.T. Argus Research 905 Sheehy Drive Horsham, P A 19044 SU B M IT T E D BY: u ~, Z 0~tA x y . 1 ,2 - i> 2 -- W. Ray Brown, D.V.M., Ph.D. Veterinary Pathologist March 25, 2002 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERA T IO N ) R EPR O D U C T IO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTO PATH O LO G Y R EPO R T TABLE OF CONTENTS Page REPORT M e th o d ........................................................................................................ 1 R e su lts............................................................................................ 3 Sum m ary..................................................................................................... 6 Quality A ssurance Unit Statem ent................................................................... 8 TABLES 1. Incidence and Degree of Severity of Histomorphologic Observations P G eneration.......................................................................................9 2. Incidence and Degree of Severity of Histomorphologic Observations P Generation Reduced Fertility A n im als................................................. 13 3. Incidence and Degree of Severity of Histomorphologic Observations F1 Generation.................................................................................... 16 4. Incidence and Degree of Severity of Histomorphologic Observations F1 Generation Reduced Fertility A n im a ls............................................... 22 A PPEN D ICES I. Histomorphologic Observations - P Generation................................. 1-1 to 1-18 Key to Histomorphologic O bservations....................................................... 1-1 Tables 1-1. I-2. I-3. I-4. I-5. I-6. I-7. I-8. I-9. 1-10. Histomorphologic Observations - Group I Male R a t s ............................I-2 Histomorphologic Observations - Group II Male R a t s ...........................I-4 Histomorphologic Observations - Group III Male R a t s ..........................I-6 Histomorphologic Observations - Group IV Male R a ts..........................I-8 Histomorphologic Observations - Group V Male R a ts .........................1-10 Histomorphologic Observations - Group I Female R a t s ...................... 1-12 Histomorphologic Observations - Group II Female R a t s ..................... 1-14 Histomorphologic Observations - Group III Female R a t s .................... 1-15 Histomorphologic Observations - Group IV Female R a t s ....................1-16 Histomorphologic Observations - Group V Female R a t s ................. ...1-17 Page 926 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (O NE LITTER P E R G EN ERA TIO N ) REPR O D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTOPATHOLOGY R EPO RT TABLE OF CONTENTS (Continued) Page II. Histomorphologic Observations-F1 Generation................................ 11-1 to II-20 Key to Histomorphologic O bservations..................................................... 11-1 Tables 11-1. II-2. II-3. II-4. II-5. II-6. II-7. II-8. II-9. 11-10. Histomorphologic Observations - Group I Male R a t s .......................... II-2 Histomorphologic Observations - Group II Male R a t s ......................... II-4 Histomorphologic Observations - Group III Male R a t s ........................ II-6 Histomorphologic Observations - Group IV Male R a ts........................ II-8 Histomorphologic Observations - Group V Male R a ts....................... 11-11 Histomorphologic Observations - Group I Female R a ts ..................... 11-14 Histomorphologic Observations - Group II Female R a t s .................... 11-16 Histomorphologic Observations - Group III Female R a t s ................... 11-17 Histomorphologic Observations - Group IV Female R a t s .................. 11-18 Histomorphologic Observations - Group V Female R a t s ................... 11-19 III. Individual Animal G ro ss and Histomorphology Data P G eneration...................................................................... 111-1 to 111-106 IV. Individual Animal G ro ss and Histomorphology Data F1 Generation......................................................................IV-1 to IV-130 V. Individual Animal G ro ss and Histomorphology Data G ro ss Lesions - F1and F2 P u p s .......................................................... V-1 Page 927 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERATIO N ) R EPRO D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTOPATHOLOGY REPO R T METHOD: Microscopic examination w as made of the specified tissues from male and female C rl:C D (SD )IG S B R VAF/Plus rats of the P and F1 generations divided into five groups used in a two-generation reproduction study of ammonium perfluorooctanoate (AFPO). A brief outline of the study design is shown below. Group Number of Rats per Sex per Generation Dosage (mg/kg/day) Concentration (mg/mL) Dosage Volume (mL/kg) I 30 0 0 5 II 30 1 0.2 5 III 30 3 0.6 5 IV 30 10 2 5 V 30 30 6 5 The test substance was considered 100% pure for the purpose of dosage calculations. - The P generation male and female rats were given the test substance once daily, beginning at approximately six weeks of age (at least 70 days before cohabitation) and continuing until the day before sacrifice. The F1 generation adult rats were given the sam e d o sa ge levels of the test substances a s their respective P generation sires and dam s (once daily, beginning at weaning [approximately 70 days before cohabitation] and continuing until the day before sacrifice). F1 and F2 pups have been exposed to the test substance in utero during maternal gestation and via maternal milk during the lactation period. The in-life portion of the study, necropsies, and recording of the gro ss necropsy observations were performed by the staff of Argus Research. The preserved tissues were then submitted to Research Pathology Services, Inc. for tissue processing, microscopic slide preparation and histopathologic evaluation. The protocol-specified tissues were routinely processed, embedded in paraffin, sectioned, and stained with hematoxylin and eosin for microscopic evaluation with Research Pathology Services, Inc. -1 Page 928 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERATIO N ) R EPR O D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTO PATH O LO G Y R E P O R T the exception of the testes sections which were stained with the periodic acid-Schiff technique. The tissues specified for microscopic evaluation from the P and F1 generation adult rats of Groups I and V included adrenal glands, pituitary and testis, epididymis, prostate, seminal vesicles and coagulating gland (male rats) or ovaries, oviducts, uterus, cervix and vagina (female rats). In addition, the reproductive tissues were examined from male and female rats of the P generation and male rats of the F1 generation suspected of reduced fertility. G ro ss lesions were examined from all P and F1 generation rats and F1 and F2 pups of all groups. Upon completion of the project, all raw data (remaining wet tissue, paraffin blocks, microscopic slides and histology records) will be returned to A rgus R e search for archiving. Research Pathology Services, Inc. Page 929 -2 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERATIO N ) REPR O D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTOPATHOLOGY REPO RT RESULTS: The type, incidence, and degree of severity of all histomorphologic observa tions in the P and F1 generation adult rats are summarized in Tables 1 and 3, re spectively. Tables 2 and 4 summarize the histomorphologic observations in the rats suspected of reduced fertility in the P and F1 generations, respectively. Individual microscopic findings from the P and F1 generation adult rats are presented in tabular form in Appendices I and II, respectively. A key to the individ ual microscopic observations precedes Table 1-1 and Table 11-1. The gro ss necropsy observations, microscopic findings, and a correlation of the gro ss and microscopic changes, when applicable, are included in Appendices III and IV for the P and F1 generation parental adult rats, respectively. M acroscopic observations and corresponding microscopic findings in the tissues with grossly observed changes for the F1 and F2 pups are listed in Appendix V. P Generation Adult R ats (Tables 1 and 2.1-1 to 1-10. Appendix III): No treatment-related microscopic changes were observed in the reproductive organs of any of the 10 male and 10 female rats P generation rats selected for histopathologic evaluation that had been given 30 mg/kg/day of the test substance. A treatment-related microscopic change w as observed in the adrenal glands of 2/10 and 7/10 male rats of Groups IV and V, respectively, designated for examination (Table 1). The change in the adrenal glands consisted of increased thickness and prominence of the zona glomerulosa due to cytoplasmic hypertrophy and vacuolation of the cells of this zone of the adrenal cortex. A similar adrenal effect w as not observed in the male rats of G roups II and III or in any of the Group V female rats. Male and female rats described a s showing "reduced fertility"were those male rats which failed to sire healthy offspring or for which sperm or spermatid number, sperm motility or morphology were affected or female rats that failed to mate, conceive or deliver healthy offspring. The rats characterized a s "reduced fertility" of the P generation are identified in the individual tables of microscopic findings in Research Pathology Services, Inc. -3 Page 930 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERATIO N ) REPR O D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTOPATHOLOGY REPO RT Appendix I a s "S S R F ". The type, incidence and degree of severity of these findings are summarized in Table 2. There were a few changes observed in these "reduced fertility" rats, but these changes occurred sporadically and are of the type that occur spontaneously in male and female rats of this age and strain (Table 2) and were not compound-related. All other microscopic changes observed in the male and female rats designated for microscopic evaluation were considered to have occurred spontaneously and to be unrelated to treatment. The type, incidence, or severity of these spontaneously occurring changes w as not influenced by administration of the test substance. In general, these changes occurred at single, low, or similar frequencies am ong the control and compound-treatment groups. These changes are listed and summarized in the attached histomorphology tables. F1 Generation Adult Rats (Tables 3 and 4. 11-1 to 11-10. Appendix IV): No treatment-related microscopic changes were observed in the reproductive organs of any of the 10 male and 10 female F1 generation rats selected for histopathologic examination that had been given 30 mg/kg/day of the test substance. Microscopic examination of the adrenal glands revealed a treatment-related effect similar to that seen in the P generation male rats, consisting of an increased thickness and prominence of the zona glomerulosa due to cytoplasmic hypertrophy and vacuolation of cells of this zone of the adrenal cortex in 7/10 high dose male rats of the F1 generation (Table 3). This adrenal gland change w as not observed in the F1 generation male rats of G roups II, III and IV or in any of the F1 generation Group V female rats. Treatment-related microscopic ch an ge s also were observed in the liver of male rats of G roups III, IV and V. These livers were grossly observed to be enlarged or to have tan areas in the liver lobes. Microscopically, these gro ss changes were due to diffuse hypertrophy of hepatocytes (Table 3). Hepatocytes in all areas (diffuse) of the hepatic lobules were enlarged due to an increased dense, Research Pathology Services, Inc. -4 Page 931 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (O N E LITTER P E R G EN ERATIO N ) R EPR O D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTOPATH OLOGY R EP O R T eosinophilic cytoplasm. A very low incidence of single-cell or focal/multifocal necrosis of hepatocytes also w as observed in a few rats of these groups. Hepatic tissue w as available for microscopic examination only from rats with gro ss observations in the liver. There were no compound-related microscopic changes observed in any of the male rats identified a s having "reduced fertility" (Table 4). The few changes in the male reproductive tissues were typical of those that occur spontaneously and their type, incidence or severity w as not affected by administration of the test substance. None of the changes that were observed in these male rats were of sufficient degree to have resulted in reproductive insufficiency. These rats are identified in the individual tables of microscopic findings a s "S S R F ". All other microscopic changes observed in the various organs and tissues were considered to have occurred spontaneously and to be unrelated to treatment. These changes were typical of those of which occur in male and female rats used in multigeneration reproduction studies. The type, incidence or severity of these changes were not influenced by A P F O administration. These changes are listed and summarized in the attached histomorphology tables. Research Pathology Services, Inc. Page 932 -5 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERATIO N) REPR O D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B ER : T-6889.6 H ISTO PATH O LO G Y R EP O R T SUMMARY: Microscopic examination w as made of the specified tissues from selected parental male and female rats of the P and F1 generations and F1 and F2 generation pups of an oral (gavage) two-generation (one litter per generation) reproduction study of ammonium perfluorooctanoate (APFO). The concentrations used in the study were 0 (vehicle control), 1, 3, 10, or 30 mg/kg/day of the test substance. No treatment-related microscopic changes were observed in the reproductive organs of any of the male or female rats of the P and F1 generations designated for microscopic examination that were given any of the d o sa ge levels of A PFO . A treatment-related microscopic change w as observed in the adrenal glands of the P generation male rats of the 10 and 30 mg/kg/day APFO-treatment groups and F1 generation male rats exposed to 30 mg/kg/day of A P F O . This change w as characterized by hypertrophy and vacuolation of cells of the zona glomerulosa of the adrenal cortex. A similar effect in the adrenal glands w as not observed in male rats of the lower d o sage groups or in female rats of the 30 mg/kg/day d o sage group of either generation. Microscopic examination of liver sections of F1 generation male rats which were observed grossly to be enlarged or have tan areas in the liver lobes showed up to marked diffuse hepatocellular hypertrophy. Single or lower incidences of hepatocellular necrosis also were observed in the male rats rats of these groups. There were a few male and female rats in each of the P and F1 generations that were classified a s demonstrating "reduced fertility". Microscopic examination of the reproductive organs of the male and female rats of the P generation and male rats of the F1 generation designated a s "reduced fertility" animals showed no consistent microscopic ch an ge s and the changes that were seen were not considered to be treatment-related. Research Pathology Services, Inc. Page 933 -6 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERATIO N ) R EPRO D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTOPATHOLOGY REPO RT All other microscopic ch an ge s observed in the various organs and tissues of the P and F1 generation adult male and female rats and F1 and F2 generation pups were considered to have occurred spontaneously and to be incidental and unrelated to treatment with A P F O . Research Pathology Services, Inc. Page 934 -7 ARGUS 418-020 ORAL (GAVAGE) TW O -GENERATIO N (O NE LITTER P E R G EN ERA T IO N ) R E PR O D U C T IO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTOPATH OLOGY REPO R T QUALITY A S S U R A N C E UNIT ST A TEM EN T All aspects of the tissue processing, microscopic slide preparation, histopathologic evaluation and report preparation for the study listed above have been performed according to the Standard Operating Procedures of Research Pathology Services, Inc. and were audited in accordance with the procedures established by the Quality Assurance Unit of Research Pathology Services, Inc. in compliance with the Good Laboratory Practice regulations specified in the protocol. Quality Assurance inspections were performed as shown below. There were no deviations from the protocol, Standard Operating Procedures and/or appropriate Good Laboratory Practice regulations noted during the conduct of the study that had any impact on study integrity. A summary report of Q A inspections was submitted to the Study Director on March 25,2002. Dates of Inspection Study Phase 10/25/01,01/15/02 11/07/01,01/18/02 11/17/01,12/27/01,01/22/02 Trimming Embedding Microtomy 11/19/01,12/28/01,01/23/02 Staining 01/02/02 01/03/02 01/24/02 01/24/02 01/28/02 01/31/02 02/01/02 03/25/02 Histopathology Data Entry Data Verification Data Processing Report Preparation Pre-Submission Audit Draft Report Final Report Date Reported to Management 10/31/01,01/31/02 11/30/01,01/31/02 11/30/01,12/31/01, 01/31/02 11/30/01,12/31/01, 01/31/02 01/31/02 01/31/02 01/31/02 01/31/02 01/31/02 01/31/02 02/01/02 03/25/02 Date Reported to Study Director 09/14/01,02/01/02 02/01/02 02/01/02 02/01/02 02/01/02 02/01/02 02/01/02 11/01/01,02/01/02 11/02/01,02/01/02 02/01/02 02/01/02 03/25/02 Research Pathology Services, Inc. Karen W. Harkins, BS Quality Assurance Unit Date -8 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1 Incidence and Degree of Severity of Histomorphologic Observations P Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 13 15 13 13 15 I II III IV V FFFFF 13 4 3 4 13 ADRENAL GLANDS: NO. EXAMINED NO. NORMAL -degeneration, cystic, cortex minimal 10 10 10 10 10 78 6 72 [0] [0] [0] [0] [0] 00000 10 0 80 [1] [0] 10 o 0 00 [0] [0] 00 10 9 [1] 1 -hypertrophy/vacuolation, zona glomerulosa minimal mild moderate [0] [0] [0] [2] [7] 00021 00002 00004 [1] [0] [0] [0] [0] 10000 00000 00000 -vacuolation, cortex minimal mild moderate PITUITARY: NO. EXAMINED NO. NORMAL [3] [2] [4] [1] t3] 12213 20 100 00100 10 0 0 0 10 10 0 0 0 10 [0] [0] [0] [0] [0] 00000 00000 00000 10 0 0 0 10 9 0 0 0 10 -cyst(s), pars intermedia 00000 10000 TESTIS: NO. EXAMINED NO. NORMAL 13 4 2 2 15 12 3 2 1 13 -atrophy/degeneration, multifocal moderate marked [1] [0] [0] [0] [2] 10 0 0 1 00001 -dilatation, rete testis 01011 -hypoplasia, diffuse marked [0] [1] to ] [1] [0] 01010 EPIDIDYMIS: NO. EXAMINED NO. NORMAL 13 4 2 2 14 10 0 1 1 10 -atrophy minimal mild moderate [0] [1] [0] [1] [1] 0 1000 0 00 10 00001 -exfoliated spermatogenic cells minimal mild moderate [0] [1 ] [1 ] [0] [2] 00001 01000 00 10 1 [ ] = Total incidence of specified lesion, all grades. Page 936 -9 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1 (Continued) Incidence and Degree o f Se v e rity o f Histom orphologic O bservations P Generation Dose Group: Sex: Number o f Animals/GrouD: EPIDIDYMIS (Continued): I II MM 13 __15- I I I IV MM 13 . 13 V M 15 I II FF 13 4 I I I IV FF 34 -hypospermia m ild marked [0] [1] [1] t l ] [2] 00 10 0 01012 - i n f i l t r a t i o n , m ononuclear-cell, focal [3] [3] [0] t l ] t2] minimal 3 2 0 12 m ild 01000 PROSTATE: NO. EXAMINED NO. NORMAL 13 3 2 1 14 4 12 06 -atrophy, focal minimal m ild [3] to] to] to] [2] 2 000 1 10001 -d ila ta tio n , minimal m ild moderate glandular, focal [2] [0] to] [0] t2] 00001 10001 10000 -inflanm ation, chronic minimal m ild [5] [2] to] [1] t4] 31002 2 1012 -inflanm ation, suppurative, focal minimal m ild [2] [0] to] [0] t l ] 10 00 1 10 000 SEMINAL VESICLES: NO. EXAMINED NO. NORMAL 13 3 2 1 14 13 3 2 1 14 COAGULATING GLAND: NO. EXAMINED NO. NORMAL 13 3 2 1 14 13 3 2 1 14 OVARIES: NO. EXAMINED NO. NORMAL 11 2 1 0 82 10 -c y st(s), intraovarian 2000 -c y stic bursa(e) 1000 OVipUCT(S): NO. EXAMINED NO. NORMAL 10 2 1 0 10 2 1 0 UTERUS: NO. EXAMINED NO. NORMAL 11 2 1 0 1110 [ ] = Total incidence of sp ecified lesion , all grades. Page 937 V F 13 11 10 1 0 11 11 11 0 -10 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) ' REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1 (Continued) Incidence and Degree o f S e v e rity o f Histom orphologic O bservations P Generation Dose Group: Sex: Number o f Animals/GrouD: UTERUS (C ontinu ed): I II MM 13 __15-- III M 13 IV M 13 V M 15 I II FF 13 4 I I I IV FF 34 V F 13 -d iste n tio n , minimal m ild moderate marked lumen [1] [1] [0] [0] [3] 00001 10 00 1 00001 01000 -gla n d (s), endometrial, c y stic 0000 1 -macrophages, pigmented minimal m ild moderate marked CERVIX: NO. EXAMINED NO. NORMAL -d ila ta tio n moderate VAGINA: NO. EXAMINED NO. NORMAL -m ucification m ild moderate (10] [0] [0] [0] [10] 20001 10002 70006 00001 11 2 10 10 11 2 1 0 9 [0] [0] [0] [0] [1] 00001 10 2 1 0 10 8 2 1 0 10 [2] [0] [0] [0] [0] 10000 10000 OVARIAN FOLLICLES/CORPORA LUTEA: -absence o f corpora lutea -presence of corpora lutea -presence of growing/antral f o llic le s EAR( S ): NO. EXAMINED NO. NORMAL 020 10 00000 00001 11 2 1 0 10 11 2 1 0 11 2 1 13 2 00000 -chondropathy, au ricu la r m ild moderate marked [0] [2] [0] [1] [0] 00000 02010 00000 [2] [1] [1] [3] [2] 000 10 10011 11111 EXTREMITIES: NO. EXAMINED NO. NORMAL 00000 00000 0 1000 00000 -fracture 00000 01000 [ ] = Total incidence of specified lesion, all grades. Page 938 -11 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUM8ER: T-6889.6 TABLE 1 (Continued) Incidence and Degree o f Se ve rity o f Histomorphologic Observations P Generation Dose Group: Sex: Number o f Animals/GrouD: EYES: NO. EXAMINED NO. NORMAL -cataract I I I I I I IV V MMMMM 13 15 -1 3 - 13 15 00000 00000 00000 I II FF 13 4 I I I IV FF 34 V F 13 0 0 1 0 0 00000 0 0 10 0 -k e r a titis , chronic moderate [0] [0] [0] [0] to] 00000 [0] [0] tl] .[0] [0] 00100 KIDNEYS: NO. EXAMINED NO. NORMAL -d ila ta tio n , minimal m ild moderate p e lv is 0 1212 00001 to] [1] [2] 11] t l] 01110 00001 00100 00000 00000 [0] [0] [0] [0] to] 00000 00000 00000 -hyperplasia, p e lvic/p ap illary epithelium, focal m ild [0] [0] [0] tl] to] 00 0 10 LUNG: NO. EXAMINED NO. NORMAL 10 00 0 00000 -hemorrhage, m u ltifocal moderate [1] [0] [0] [0] to] 10000 -inflan m ation , i n t e r s t i t i a l , m u ltifo ca l [1] [0] [0] to] to] moderate 10000 to] to] to] to] [0] 00000 00000 00000 to] to] [0] [0] to] 00000 [0] to] [0] to] to] 00000 PALATE: NO. EXAMINED NO. NORMAL 00000 00000 10000 00000 -fracture -hemorrhage marked 00000 [0] [0] to] to] [0] 00000 10000 tl] [0] [0] to] [0] 10000 t ] = Total incidence of specified lesion, a ll grades. Page 939 -12 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 2 Incidence and Degree o f S e v e rity o f Histom orphologic Observations - Reduced F e r t i l i t y Animals P Generation Dose Group: Sex: Number o f Animals/GrouD: ADRENAL GLANDS: NO. EXAMINED NO. NORMAL I I I I I I IV V MMMMM 332 4 00 10 0 00100 I I I I I I IV V FFFFF 12 1 1 1 0 0 o 0 0 00000 TESTIS: NO. EXAMINED NO. NORMAL 332 14 232 13 -atrophy/degeneration, m ultifocal moderate [1] [0] [0] [0] [1] 100 0 1 -d ila tatio n , rete te stis EPIDIDYMIS: NO. EXAMINED NO. NORMAL -atrophy moderate 00001 33214 30112 [0] [0] [0] [0] [1] 00001 -e xfoliate d spermatogenic c e lls minimal m ild moderate [0] [1] CU [0] [2] 00001 0 10 00 00101 -hypospermi a m ild marked [0] [0] [1] [0] [2] 00100 00002 - i n f i l t r a t i o n , m ononuclear-cell, focal [0] [2] [0] [0] [0] minimal 01000 m ild 0 1000 PROSTATE: NO. EXAMINED NO. NORMAL 33 2 14 0 1203 -atrophy, focal minimal m ild [3] [0] [0] [0] [1] 20001 10000 -inflammation, chronic minimal m ild [1] [2] [0] [1] [0] 11000 01010 SEMINAL VESICLES: NO. EXAMINED NO. NORMAL 332 14 33 2 14 COAGULATING GLAND: NO. EXAMINED NO. NORMAL 332 14 332 14 [ ] = Total incidence of specified lesion , a ll grades. -13 Page 940 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 2 (Continued) Incidence and Degree o f Se v e rity o f Histom orphologic O bservations - Reduced F e r t i li t y Animals P Generation Dose Group: Sex: Number o f Animals/GrouD: I I I I I I IV V MMMMM 3? ? 14 I I I I I I IV V FFFFF 12111 OVARIES: NO. EXAMINED NO. NORMAL 1 2 1 0 1 0 2 100 -c y st(s), intraovarian 10001 OVIDUCTfS): NO. EXAMINED NO. NORMAL UTERUS: NO. EXAMINED NO. NORMAL -d is te n tio n , lumen moderate marked 12 10 1 12 10 1 12 10 1 1 1 10 0 [0] [1] [0] [0] [1] 00001 0 1000 CERVIX: NO. EXAMINED NO. NORMAL VAGINA: NO. EXAMINED NO. NORMAL 12 10 1 12101 12 10 1 02 10 1 -mucifi cation m^ld [1] [0] [0] [0] to] 10000 OVARIAN FOLLICLES/CORPORA LUTEA: -absence of corpora lutea -presence o f corpora 1utea -presence o f growing/antral f o llic le s 00001 12 100 1 2 101 EAR(S): NO. EXAMINED NO. NORMAL 01000 00000 00100 00000 -chondropathy, au ricu lar moderate marked [0] [1] [0] [0] [0] 01 0 00 00 000 [0] [0] [1] [0] [0] 00000 00100 KIDNEYS: NO. EXAMINED NO. NORMAL 0 10 02 0000 1 00000 00000 [ ] = Total incidence of specified lesion, a ll grades. Page 941 -14 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 2 (Continued) Incidence and Degree o f S e v e rity o f Histom orphologic Observations - Reduced F e r t i l i t y Animals P Generation Dose Group: Sex: Number o f Animals/GrouD: I I I I I I IV V MMMMH 33 214 I I I I I I IV V FFFFF 12 1 11 KIDNEYS (C o n tln u e d l: dilatation, pelvis minimal m ild [0] [1] [0] [0] [1] 0 10 00 00001 [0] [0] [0] [0] [0] 00000 00000 [ ] = Total incidence of sp ecified lesion , all grades. Page 942 -15 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 3 Incidence and Degree o f S e v e rity o f Histcm orphologic O bservations FI Generation Dose Group: Sex: Number o f Animals/GrouD: ADRENAL GLANDS: NO. EXAMINED NO. NORMAL I I I I I I IV V MMMMM )7 1? 1? ?6 25 10 10 10 10 9 66982 I II FF 12 5 I I I IV FF 11 V F 11 10 0 10 0 0 0 00 10 9 -hyperplasia, co rtica l, focal minimal [0] [0] [0] [0] [0] 00000 [0] [0] [0] [0] [1] 00001 -hypertrophy/vacuolation, zona glomerulosa minimal m ild [0] [0] [0] [0] [7] 00003 00004 [0] [0] [0] [0] [0] 00000 00000 -v a c u o la tion, cortex minimal [4] [4] [1] [2] [2] 44 122 [0] [0] [0] [0] [0] 00000 LIVER: NO. EXAMINED NO. NORMAL 0 0 6 9 10 00000 0 1000 00000 -hematopoiesis, extramedullary, m ultifocal minimal [0] [0] [1] [13 [1] 00111 [0] [0] [0] [0] [0] 00000 -hypertrophy, h e p ato ce llu lar, d iffu s e [0] [0] [6] [9] [10] m ild 00233 moderate 00466 marked 00001 [0] [0] [0] [0] [0] 00000 00000 00000 -in fa rc t, liv e r lobe 00000 01000 -inflam m ation, chronic, fo c a l/m u ltifo c a l [0] to] [2] [2] [1] minimal 00111 m ild 00 110 [0] [0] [0] [0] [0] 00000 00000 -necrosis, focal/m ultifocal minimal m ild [0] [0] [1] [3] [2] 00010 0 0 12 2 [0] [0] [0] [0] [0] 00000 00000 -necrosis, sin gle -ce ll minimal [0] [0] [0] [1] [0] 00010 [0] [0] [0] [0] [0] 00000 TESTIS: NO. EXAMINED NO. NORMAL 12 3 2 2 10 11 3 2 2 10 -atrophy/degeneraiion, m ultifocal minimal [1] [0] [0] [0] [0] 10000 EPIDIDYMIS: NO. EXAMINED NO. NORMAL 12 3 2 2 10 10 3 2 2 7 [ ] Total incidence of specified lesion , a ll grades. -16 Page 943 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) * REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 3 (Continued) Incidence and Degree o f S e v e rity o f Hlstotnorphologic O bservations FI Generation Dose Group: Sex: Number o f Animals/GrouD: EPIDIDYMIS (Continued): I I I I I I IV V I II MMMH H FF ______ LZ_ 13 IS . 26 _ 2 5 ____ 12 5 I I I IV FF 11 V F 11 - i n f i l t r a t i o n , m o nonuclear-cell, focal [2] [0] [0] [0] [3] minimal 20003 PROSTATA NO. EXAMINED NO. NORMAL 12 3 2 2 10 10 2 1 1 7 -atrophy, focal minimal m ild [0] [0] [0] [1] [1] 00010 00001 -d ila tatio n , glandular, focal m ild [1] [0] [0] [0] [0] 10000 - inflammation, chronic minimal m ild [2] [1] [1] [0] tl] 1 10 0 1 10100 -inflam nation, suppurative minimal [0] [0] [0] [0] tl] 00001 SEMINAL VESICLES: NO. EXAMINED NO. NORMAL 12 3 2 2 10 12 3 2 2 10 COAGULATING GLAND: NO. EXAMINED NO. NORMAL 12 3 2 2 10 12 3 2 2 10 OVARIES: NO. EXAMINED NO. NORMAL 10 0 0 0 10 10 0 0 0 9 -c y st(s), intraovarian 00001 UTERUS: NO. EXAMINED NO. NORMAL 10 0 0 0 10 20000 -d iste n tio n , minimal m ild moderate lumen [2] [0] [0] [0] [2] 10000 10000 00002 [ J * Total incidence of specified lesion , a ll grades. Page 944 -17 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 3 (Continued) Incidence and Degree o f Se ve rity o f Histomorphologic Observations FI Generation Dose Group: Sex: Number o f Animals/GrouD: UTERUS (C ontinued): I I I I I I IV V MMMMM )7 1? 19 26 25 I II FF 12 5 I I I IV FF 11 V F 11 -macrophages, pigmented minimal m ild moderate marked CfRVIX: NO. EXAMINED NO. NORMAL VAGINA: NO. EXAMINED NO. NORMAL -inflammation, chronic, focal minimal -mucifi cation minimal m ild moderate [7] [0] [0] [0] [10] 00001 10001 40007 20001 10 0 0 0 10 10 0 0 0 10 10 0 0 0 10 60007 [1] [0] (0] [0] [0] 10000 [4] [0] [0] [0] [3] 20000 10001 10002 OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence o f growing/antral f o llic le s PITUITARY: NO. EXAMINED NO. NORMAL -c y st(s), pars d istal is 10 0 0 0 8 10 0 0 0 6 00001 10 0 0 0 10 10 0 0 0 10 10 0 0 0 10 10 0 0 0 9 00001 -c y s t (s ), pars intermedia CECUM: NO. EXAMINEO NO. NORMAL 00001 000 10 00000 00000 00000 00000 -distention marked [0] [0] [0] [1] [0] 00010 [0] [0] (0] [0] [0] 00000 -edem a/inflaim ation, submucosa m ild [0] [0] [0] [1] [0] 000 10 [0] [0] [0] [0] [0] 00000 COLON: NO. EXAMINED NO. NORMAL 000 10 00000 00000 00000 [ ] = Total Incidence of specified lesion , a ll grades. -18 Page 945 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 3 (Continued) Incidence and Degree o f S e v e rity o f Histom orphologic O bservations FI Generation Dose Group: Sex: Number o f Animals/GrouD: COLON (Continued): I I I I I I IV V MMMMM 17 1? 19 ? 25 I II FF 12 5 I I I IV FF 11 V F 11 -distention marked [0] [0] to] t l ] to] 00010 [0] to] to] to] to] 00000 EAR(S): NO. EXAMINED NO. NORMAL 00010 00000 30001 00000 -chondropathy, au ricu lar moderate marked EYfS: NO. EXAMINED NO. NORMAL -abscess, periocular [0] [0] [0] t l] to] 00000 000 10 40002 10002 00000 t3] to] to] [0] t l] 10000 2 0001 0 00 10 00000 00010 -atrophy, i r i s / c i l i a r y body marked [1] [0] [0] to] to] 10 00 0 to] [0] to] [0] to] 00000 -atrophy, retinal, focal m ild [1] [0] [0] to] to] 10000 -inflantnation, chronic, ir is moderate [2] [0] to] to] to] 20000 -neuropathy, optic nerve(s) moderate [2] [0] to] to] [0] 20000 ILEUM: NO. EXAMINED 0 0 0 10 NO. NORMAL 00000 -Advanced a u t o ly s is precludes evalu atio n 0 0 0 1 0 [0] to] to] to] [0] 0 0000 [0] to] to] to] to] 00000 to] to] [0] to] to] 00000 01000 00000 00000 -distention marked [0] [0] to] to] to] 00000 [0] t l ] [0] to] [0] 01000 KIDNEYS: NO. EXAMINED NO. NORMAL 00030 00000 00101 00000 -dilatation, pelvis m ild moderate [0] [0] [0] [3] [0] 00020 000 10 [0] [0] t l ] to] [1] 00100 00001 -hyperplasia, p e lvic/pap illary urothelium minimal [0] [0] to] t l] to] 000 10 to] [0] to] to] to] 00000 [ ] * Total incidence of specified lesion, a ll grades. -19 Page 946 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 3 (Continued) Incidence and Degree o f S e v e rity o f Histom orphologic O bservations FI Generation Dose Group: Sex: Number o f Animals /Gtoud: KIDNEYS (Continued): I I I I I I IV V MMMMM 17 l ? 19 ?6 25 I II FF 12 5 I I I IV FF 11 V F 11 -m ineralization, pelvis minimal [0] [0] [0] [1] [0] 0 0 0 10 [0] [0] [0] [0] [0] 00000 -pyelonephritis moderate [0] [0] [0] [0] [0] 00000 [0] [0] [0] [0] [1] 0 0 0 .0 1 SKIN (GROSS LESION): NO. EXAMINED NO. NORMAL 10 10 0 00000 00000 00000 -derm atitis, chronic moderate [0] [0] [1] [0] [0] 00100 [0] [0] [0] [0] [0] 00000 -derm atitis, ulcerative moderate [1] [0] [1] [0] [0] 10 100 [0] [0] [0] [0] [0] 00000 SPLEEN: NO. EXAMINED NO. NORMAL -atrophy marked 00011 00000 [0] [0] [0] [0] [1] 00001 10000 00000 [1] [0] [0] [0] [0] 10000 -necrosis marked STOMACH: NO. EXAMINED NO. NORMAL [0] [0] [0] [1] [0] 0 0 0 10 00010 00000 [0] [0] [0] [0] [0] 00000 01000 00000 -e r o s io n (s ), glan d u la r mucosa minimal m ild [0] [0] [O] [1] [0] 000 10 00000 (0) (1] [O] [O] [O] 00000 0 1000 -p e rito n itis, focal minimal [0] [0] [0] [1] [0] 00010 [0] [0] [0] [0] [0] 00000 -u lc e r(s), glandular area moderate [0] [0] [0] [1] [0] 000 10 [0] [0] [0] [0] [0] 00000 TAIL: NO. EXAMINED NO. NORMAL 000 13 00002 03001 0 1000 -abscess 00010 00000 -con striction , focal 00001 00000 [ ] = Total incidence of specified lesion, a ll grades. Page 947 -20 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 3 (Continued) Incidence and Degree o f Se v e rity o f Histom orphologic O bservations FI Generation Dose Group: Sex: Number o f Animals/GrouD: TAIL (Continued): I I I I I I IV MMMM 17 - . 13-- - 1 9 . 26 V M 25 I II FF 12 5 I I I IV FF 11 V F 11 -hyperplasia/hyperkeratosis moderate [0] [0] [0] [1] [0] 000 10 [0] [0] to] to] to] 00000 -inflam nation, chronic minimal m ild [0] [0] [0] [0] [0] 00000 00000 [0] [1] [0] to] tl] 01000 0 0 0 0 1 -necrosis, focal m ild [0] [0] [0] [0] [0] 00000 [0] [1] to] [0] [1] 01001 THYMUS: NO. EXAMINED NO. NORMAL 00010 00000 00000 00000 -atrophy marked [0] [0] [0] [1] [0] 00 0 10 [0] [0] [0] to] to] 00000 URETER: NO. EXAMINED NO. NORMAL 00000 00000 00001 00000 -distention marked [0] [0] [0] [0] [0] 00000 [0] [0] to] to] tl] 00001 -h yp e rp lasia, mucosa moderate [0] [0] [0] [0] [0] 00000 [0] [0] to] to] tl] 0000 1 -inflanm ation, chronic m ild [0] [0] [0] [0] [0] 00000 [0] to] [0] to] [1] 0000 1 URINARY BLADDER: NO. EXAMINED NO. NORMAL 00000 00000 00001 00000 -c y stitis , hyperplastic marked [0] [0] [0] [0] [0] 00000 [0] to] to] [0] [1] 00001 [ ] Total incidence of sp ecified lesion , all grades. Page 948 -21 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 4 Incidence and Degree of Severity of Histomorphologic Observations - Reduced Fertility Animals FI Generation Dose Group: Sex: Number of Animals/GrouD: I 11 III IV V MMMMM 23221 ADRENAL GLANDS: NO. EXAMINED NO. NORMAL 0 0 0 '1 0 00010 TESTIS: NO. EXAMINED NO. NORMAL EPIDIDYMIS: NO. EXAMINED NO. NORMAL -infiltration, mononuclear-cell, focal minimal PROSTATE: NO. EXAMINED NO. NORMAL -atrophy, focal minimal -inflammation, chronic minimal mild SEMINAL VESICLES: NO. EXAMINED NO. NORMAL COAGULATING GLAND: NO. EXAMINED NO. NORMAL 23221 2 3 2 .2 1 23221 23220 [0] [0] [0] [0] [1] 00001 23 2 2 1 22111 [0] [0] [0] [1] [0] 000 10 [0] [1] [1] [0] [0] 01000 0 0 100 23221 23 2 2 1 23221 23 22 1 [ ] = Total incidence of specified lesion , a ll grades. Page 949 -22 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERATIO N ) REPRODUCTION) ST U D Y OF AM M O N IU M PERFLU O RO O CTA N O A TE (AFPO) IN R A T S P R O T O C O L 418-020 H ISTO PATH O LO G Y R EPO R T APPEN DIX I H ISTO M O RPH O LO G IC O B SER VA T IO N S P G EN ERATIO N Page 950 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (O N E LITTER P E R G EN ERATIO N ) REPR O D U C TIO N ST U D Y OF AM M O N IU M PERFLU O RO O CTA N O A TE (AFPO) IN R A T S P R O T O C O L 418-020 H ISTOPATHOLOGY R EPO RT KEY TO H ISTO M O RPH O LO G IC O BSER VA T IO N S -= *= <> = <-> = () = A= No change (not remarkable, within normal histologic limits or indicated change not present). Tissue not available (specified tissue missing, insufficient tissue in plane of section, artifact precludes evaluation, or specified tissue not present in section). Microscopic finding(s) in tissue(s) with gro ss observation(s). Within normal limits [no microscopic change(s) to correlate with the gross observation(s)]. Only one of a pair of organs available for processing/evaluation. Advanced autolysis precludes evaluation. P = Indicated change or lesion present. 1 = Minimal degree or amount of indicated change or lesion. 2 = Mild degree or amount of indicated change or lesion. 3 = Moderate degree or amount of indicated change or lesion. 4 = Marked degree or amount of indicated change or lesion. SS SD SM SSRF = Sacrifice-Scheduled = Spontaneous Death = Sacrifice-Moribund = Scheduled (Reduced Fertility) 1-1 Page 951 ARGUS 418-020 ORAL (GAVASE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-1 Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: I 13602 M SS I 13609 M SSRF I 13610 M SSRF I 13611 M SSRF I 13612 M SS I 13614 M SS I 13615 M SS ADRENAL GLANDS: -vacuolation, cortex *-2 PITUITARY: - --- TESTIS: -atrophy/degeneration, multifocal EPIDJpYMf; -infiltration, mononuclear-cell, focal PROSTATE: -atrophy, focal -dilatation, glandular, focal -inflammation, chronic -inflammation, suppurative, focal SEMINAL VESICLES: COAGULATING GLAND: 3----- 1------ - 211- - 3- - - - - 1_ 1_ 2--- - 1 --- -- - - ---- - -- LUNG: -hemorrhage, multifocal -inflammation, interstitial, multifocal <3> <3> Page 952 1-2 ARGUS 418-020 ORAL (GAVAGE) TW-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-1 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: I 13616 M SS I 13621 M SS I 13622 M SS I 13624 M SS I 13625 M SS I 13626 M SS ADRENAL GLANDS: -vacuolation, cortex PITUITARY: TESTIS: EPIDIDYMIS: -infiltration, mononuclear-cell, focal PROSTATE: -dilatation, glandular, focal -inflanmation, chronic -inflaimiation, suppurative, focal SEMINAL VESICLES: COAGULATING GLAND: ___ 1 2 -------- - -- - - - 1- 1 .2 - 21- . -- -2- ------ --- - - - EARfS): Page 953 1-3 ARGUS 418-020 ORAL (6AVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-2 Histomorphologlc Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: II II II II 13632 13636 13638 13639 MMMMM SS SS SSRF SSRF II 13642 M SS II 13644 M SS II 13645 M SS II 13646 SS ADRENAL GLANDS: -vacuolatlon, cortex . ---1 TESTIS: -dilatation, rete testis -hypoplasia, diffuse <P> <4> - - EPIDIDYMIS: -atrophy -exfoliated spermatogenlc cells -hyposperml a -Infiltration, mononuclear-cell, focal <i> -2 <4> <1> - . 1 PROSTATE: -inflamnation, chronic -2 SEMINAL VESICLES: COAGULATING GLAND: EARiS): -chondropathy, auricular <3> KIDNEYS: -dilatation, pelvis <i> Page 954 1-4 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF AMMONIUN PERFLUOROOCTANOATE (APFO) IN RATS PROTXOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 TABLE 1-2 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: ADRENAL GLANDS: -vacuolation, cortex II 13650 M SSRF II 13651 M SS II 13652 M SS II 13653 M SS II 13654 M SS II 13655 M SS II 13656 M SS 1 TESTIS: EPIDIDYMIS: -in filt ra tio n , mononuclear-cel 1, focal 2 PROSTATE: -inflamnation. chronic SEMJNA1. V E S I C A : 1 . COAGULATING GLAND: - EAR(S): -chondropathy, auricular <3> Page 955 1-5 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) . REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-3 Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: III 13661 M SS III 13662 M SSRF Ill 13668 M SS III 13670 M SS in 13671 M SS III 13672 M SS III 13673 M SS ADRENAL GLANDS: -vacuolation, cortex 1 __ _ _ TESTIS: - EPIDIDYMIS: - PROSTATE: - SEMINAL VESICLES: - COAGULATING GLAND: - KIDNEYS: -dilatation, pelvis <3> <1> Page 956 1-6 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-3 (Continued) Histcmorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: III 13674 M SSRF III 13675 M SS III 13676 M SS III 13682 M SS III 13683 M SS III 13684 M SS ADRENAL GLANDS: -vacuolation, cortex 2 13 TESTIS: EPIDIDYMIS: -exfoliated spermatogenic cells -hypospermi a - 3 2 PROSTATE: - SEMINAL VESICLES: - COAGULATING GLAND: - Page 957 1-7 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-4 Histomorphologlc Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: IV 13693 M SS IV 13695 M SS IV 13699 M SS IV 13700 M SSRF IV 13703 M SS IV 13704 M SS IV 13706 M SS ADRENAL GLANDS: -vacuolation, cortex 1 TESTIS: -dilatation, rete testis -hypoplasia, diffuse - <P> - <4> EPIDIDYMIS: -atrophy -hypospermia -infiltration, mononuclear-cell, focal - <2> - <4> - <1> PROSTATE: -inflanmation, chronic 2 SEMINAL VESICLES: - COAGULATING GLAND: - Page 958 1-8 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-4 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: IV 13708 M SS IV 13710 M SS IV 13711 M SS IV 13716 M SS IV 13717 M SS IV 13719 M SS ADRENAL GLANDS: -hypertrophy/vacuolation, zona glomerulosa EAR(S): -chondropathy, auricular 1 ,1 <3> KIDNEYS: -dilatation, pelvis -hyperplasia, pelvic/papillary epithelium, focal <1> <2> Page 959 1-9 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 TABLE 1-5 H1stornorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: V 13721 M SS V 13722 M SS V 13728 M SS V 13729 M SSRF V 13731 M SS V 13732 H SM V 13733 M SSRF V 13734 M SS ADRENAL GLANDS: -hypertrophy/vacuolation, zona glomerulosa -vacuolation, cortex PITUITARY: 133 - "1 --- 2 - - 1 - TESTIS: -atrophy/degeneration, multifocal - - - - - <4> - - EPIDIDYMIS: -atrophy -exfoliated spermatogenic cells -hypospermi a -infiltration, mononuclear-cell, focal PROSTATE: -dilatation, glandular, focal -inflammation, chronic -inflammation, suppurative, focal SEMINAL VESICLES: ----- ---- - ---- - 11 -- - 2- - 1 2- - - 2 --- - - ----- <3> <i> 4 - - --- -1 -- COAGULATING GLAND: ----- -- KIDNEYS: -dilatation, pelvis <-> <2> Page 960 1-10 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 TABLE 1-5 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: V 13735 M SS V 13736 M SS V 13741 M SSRF V 13742 M SS V 13743 M SS V 13744 M SS V 13750 M SSRF ADRENAL GLANDS: -hypertrophy/vacuolation, zona glom erulosa -v a c u o la tion, cortex -3 -- 23 - 1- - PITUITARY: -- --- TIJSTJS: -atrophy/degenerati on, multi focal -d ila tatio n , rete te stis EPIDJpYMJJ; -e xfoliate d spermatogenic c e lls -hypospermi a PROSTATE: -atrophy, focal -inflammation, chronic - - <3> - - <P> - - - <3> - - <4> - 2- -- - 1- - - - <-> - - <-> -- -- -1- - - 1 - SEMINAL VESICLES: COAGULATING GLAND: ------- - -- - -- Page 961 1-11 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-6 Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: I 13802 F SS I 13804 F SM I 13809 F SS I 13811 F SSRF I 13812 F SS I 13814 F SS I 13815 F SS ADRENAL GLANDS: - - - - PITUITARY: -c y st(s ), pars intermedia P- - - OVARIES: -c y st(s), intraovarian 0VIDUCTIS1: UTERUS: -d is te n tio n , lumen -macrophages, pigmented CERVIX: P- - - - --* - 2 3 3- 3 3 - --- - VAGINA: -muci fic a tio n 3 - 2- - OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence of growing/antral f o llic le s P PPP P P PPP P EAR(Sl: -chondropathy, au ricu lar <3> PALATE: -fracture -hemorrhage <P> <4> Page 962 1-12 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-6 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: I 13816 F SS I 13821 F SS I 13822 F SM I 13824 F SS I 13825 F SS I 13826 F SS ADRENAL GLANDS: -degeneration, cy stic, cortex -hypertrophy/vacuolation, zona glom erulosa PITUITARY: OVARIES: -cy st(s), intraovarian -c y stic bursa(e) OVIDUCTfSl: UTERUS: -macrophages, pigmented CERVIX: VAQJNA: OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence o f growing/antral f o llic le s EARfS); -chondropathy, a u ricu lar 1 1- --- P --* - -- 123 ----- PPP PPP --- -* -- 33 --- PP PP <4> P - 1 * P P Page 963 1-13 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 TABLE 1-7 Hlstcmorphologlc Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: II 13836 F SM II 13840 F SSRF II 13851 F SSRF II 13856 F SS OVARIES: - .- OVIDUCTfSl: -- UTERUS: -d is te n tio n , lumen -4 CERVIX: -- VAGINA: -- OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence o f growing/antral f o llic le s PP PP EAR(S): -chondropathy, au ricu lar <4> EXTREMITIES: -fracture <P> Page 964 1-14 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-8 Hlstomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: III 13862 F SSRF in 13869 F SS hi 13885 F SS OVARIES: - OVIDUCTiS): - UTERUS: - CERVIX: - VAGINA: - OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence o f growing/antral fo llic le s P P EAR(S): -chondropathy, au ricu lar <4> EYES: -cataract -k e r a titis, chronic <P> <3> KIDNEYS: Page 965 1-15 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-9 Histomorphologlc Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: OVARIES: OVIDUCT fS : UTERUS: CERVIX: VAGINA: OVARIAN FOLLICLES/CORPORA LUTEA: IV 13898 F SS IV 13900 F SSRF IV 13901 F SS IV 13908 F SS * * * *. * EAR(S): -chondropathy, au ricu lar <4> <3> <2> Page 966 1-16 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 TABLE 1-10 Hlstomorphologlc Observations P Generation Dose Group: Animal Number: Sex: Death Type:__________________________ V 13921 F SS V 13922 F SS V 13927 F SS V 13928 F SS V 13929 F SSRF V 13933 F SS V 13934 F SS ADRENAL GLANDS: -degeneration, c y stic, cortex 1 PITUITARY: OVARIES: -c y st(s), intraovarian P OVIDUCT(ST: UTERUS: -d is te n tio n , lumen -gla n d (s), endometrial, c y stic -macrophages, pigmented CERVIX: VAGINA: 23 2 * * P 2 OVARIAN FOLLICLES/CORPORA LUTEA: -absence of corpora lutea -presence of corpora lutea -presence o f growing/antral f o llic le s PP PP P P PP PPPP EARfS): -chondropathy, au ricu lar <4> Page 967 1-17 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-10 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: V 13935 F SS V 13936 F SS V 13942 F SS V 13943 F SS V 13944 F SS V 13946 F SS ADRENAL GLANDS: - -- - - PITUITARY: ----- OVARIES: - -- - - OVIDUCTfS): ----- UTERUS: -d is te n tio n , lumen -macrophages, pigmented CERVIX: -d ila ta tio n VAGINA: 1 1433 3 - 3- - ----- OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence o f growing/antral f o llic le s EAR(S): -chondropathy, au ricu lar PPP P P PPPPP <3> Page 968 1-18 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 HISTOPATHOLOGY REPORT APPENDIX II HISTOMORPHOLOGIC OBSERVATIONS F1 GENERATION Page 969 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 HISTOPATHOLOGY REPORT KEY TO HISTOMORPHOLOGIC OBSERVATIONS -= *= <> = <-> = () = A= No change (not remarkable, within normal histologic limits or indicated change not present). Tissue not available (specified tissue missing, insufficient tissue in plane of section, artifact precludes evaluation, or specified tissue not present in section). Microscopic finding(s) in tissue(s) with gross observation(s). Within normal limits [no microscopic change(s) to correlate with the gross observation(s)). Only one of a pair of organs available for processing/evaluation. Advanced autolysis precludes evaluation. P = Indicated change or lesion present. 1 = Minimal degree or amount of indicated change or lesion. 2 = Mild degree or amount of indicated change or lesion. 3 = Moderate degree or amount of indicated change or lesion. 4 = Marked degree or amount of indicated change or lesion. SS = Sacrifice-Scheduled SD = Spontaneous Death SM = Sacrifice-Moribund SSRF = Scheduled (Reduced Fertility) 11-1 Page 970 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I I - l Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: I 1003 M SS I 1012 M SSRF I 1017 M SS I 1018 M SM I 1019 M SM I 1020 M SM I 1022 M SS I 1024 M SD I 1026 M SS ADRENAL GLANDS: -vacuolation, cortex 1 1 TESTIS: --- - EPIDIDYMIS: - in f ilt r a t io n , mononuclear-cell, focal 1 - - - PROSTATE --- - SEMINAL VESICLES: --- - COAGULATING GLAND: --- - PITUITARY: -- - EYES: -atrophy, i r i s / c i l i a r y body -atrophy, re tin al, focal -inflaim ation, chronic, ir is -neuropathy, optic nerve(s) <-> - - <-> <3> <3> <-> <3> <3> <-> <4> <2> - - SKIN (GROSS LESION): -derm atitis, ulcerative <3> Page 971 II-2 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I I - l (Continued) Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: I 1034 M SS I 1035 M SS I 1040 M SSRF I 1047 M SS I 1048 H SS I 1051 M SS I 1052 M SS I 1054 M SS ADRENAL GLANDS: -vacuolation, cortex _ __1 1 TESTIS: -atrophy/degenerat ion, multi focal 1- - - - - -- EPIDIDYMIS: - in filt r a t io n , mononuclear-cell, focal - - - 1- - - - PROSTATE: -d ilatatio n , glandular, focal -inflammation, chronic 2 - - - 2* - - 1 SEMINAL VESICLES: COAGULATING GLAND: PJTVITARY: --------------- -- --- -- Page 972 11-3 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I1-2 Hlstomorphologlc Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: TESTIS: II 1063 M SS II 1066 M SSRF - II 1077 M SSRF - II 1078 M SS II 1082 M SSRF II 1096 M SS <-> EPIDIDYMIS: -- <-> PROSTATE: -Inflanmation, chronic -1 - SEMINAL VESICLES: -- - COAGULATING GLAND: -- - ADRENAL GLANDS: -vacuo!ation. cortex 1 II 1098 M SS Page 973 11-4 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) ' REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I1--2 (Continued) Hlstomorphologlc Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: II 1100 M SS II 1106 M SS II 1107 M SS II 1116 M SS II 1118 M SS ADRENAL GLANDS: -vacuolatlon, cortex 11 II 1120 M SS 1 Page 974 11-5 ARGUS 418-020 ORAL (GAVAGE) TV0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE II-3 Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: III 1123 M SS III 1124 M SS III 1125 M SS III 1126 M SS III 1128 M SS III 1129 M SS III 1134 M SS III 1136 M SS III 1142 M SSRF III 1149 M SS TESTIS: - EPIDIDYMIS: - PROSTATE: -inflammation, chronic 2 SEMINAL VESICLES: - COAGULATING GLAND: - ADRENAL GLANDS: --- LIVER: -hematopoiesis, extramedullary. multifocal -hypertrophy, hepatocellular. di ffuse -Inflammation, chronic, focal/multi focal -necrosis, focal/multifocal <1> - -- <3> <3> <2> <3> - <2> <1> < 2> - - - - SKIN (GROSS LESION): -dermatitis, chronic -dermatitis, ulcerative <3> <3> Page 975 11-6 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I1-3 (Continued) Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: III 1154 M SS III 1156 M SS III 1159 M SS III 1164 M SS III 1165 M SS III 1167 M SSRF III 1175 M SS III 1177 M SS TESTIS: EPIDIDYMIS: - PROSTATE: - SEMINAL VESICLES: - COAGULATING GLAND: - ADRENAL GLANDS: -vacuolation, cortex - -- -1 LIVER: -hypertrophy, hepatocellular, diffuse <2> <3> III 1180 M SS Page 976 11-7 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I1-4 Histomorphologlc Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: IV 1182 M SS IV 1189 M SS IV 1190 M SS IV 1191 M SS IV 1192 M SSRF IV 1193 M SS IV 1194 M SS IV 1197 M SS TESTIS: EPIDIDYMIS: PROSTATE: -atrophy, focal SEMINAL VESICLES: COAGULATING GLAND: ADRENAL GLANDS: LIVER: -hypertrophy, hepatocellular, diffuse -inflamnation, chronic, focal/multi focal -necrosis, single-cell <3> < 1> < 1> <3> - - <3> - - TAIL: -abscess -hyperplasi a/hyperkeratosi s <P> <3> IV 1198 M SS Page 977 II-8 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I1-4 (Continued) Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: IV 1200 M SM IV 1205 M SS IV IV 1206 1207 MMM SS SSRF IV 1211 M SS IV 1212 M SS IV 1217 M SS IV 1218 M SS IV 1223 SS TESTIS; EPIDIDYMIS: PROSTATE: SEMINAL VESICLES: COAGULATING GLAND: ADRENAL GLANDS: -vacuolation, cortex CECUM: -distention -edema/inflanmation, submucosa <4> <2> --1 COLON: -distention <4> ILEUM: <A> LIVER: -hematopoiesis, extramedullary, multifocal -hypertrophy, hepatocellular, diffuse -necrosis, focal/multifocal -<3> <2 <2> - <i <2> <2> <1> - STOMACH: -erosion(s), glandular mucosa -peritonitis, focal -ulcer(s), glandular area THYMUS: -atrophy <1> <1> <3> <4> Page 978 11-9 ARGUS 418-020 ORAL (GAVAGE) TV0-6ENERATI0N (OHE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE II--4 (Continued) Histomorphologic Observations Fl Generation Dose Group: Animal Number: Sex: Death T v D e : ADRENAL GLANDS: -vacuolation, cortex IV IV 1224 1225 MM SS _ss__ IV 1229 M ss___ IV 1232 M SS IV 1234 M SS IV 1235 M SS IV 1236 M SS IV 1240 M SS 1 EAR fS1: -chondropathy, auricular <4> KIDNEYS: -dilatation, pelvis <3> -hyperplasia, pelvlc/papillary urothellim - -mineralization, pelvis - LIVER: -hypertrophy, hepatocellular, diffuse -inflaiimation, chronic, focal /multi focal -necrosis, focal/multifocal SPLEEN: -necrosis <2> - <3> < 2> < 2> <3> - <4> <2> <1> < 1> ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS ' PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I1-5 H1stamorpholog1c Observations FI Generation Dose Group: Animal Number: Sex: Death TvDe: V 1241 M SS V 1243 H SS V 1244 M SS V 1250 M SS V 1251 M SS V 1254 M SS V 1256 M SS V 1262 M SS V 1263 M SD TESTIS: -- - EPIDIDYMIS: -- - PROSTATE: -inflanmation, chronic SEMINAL VESICLES: -- __ 1 _ COAGULATING GLAND: -- - ADRENAL GLANDS: -hypertrophy/vacuolation. zona glomerulosa 21 -vacuolation, cortex -1 2 - PITUITARY: -cyst(s), pars distal is EYES: -P - <-> LIVER: -hypertrophy, hepatocellular, diffuse <3> <2> <3> TAIL: -constriction, focal <-> <p> Page 980 11-11 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE II--5 (Continued) Histornorphologlc Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: VV 1264 1266 MM SD _ss___ V 1268 M SS V 1269 M SS V 1270 M SS V 1271 M SS V 1273 M SS TESTIS: - EPIDIDYMIS: -Infiltration, mononuclear-cell, focal - 1 PROSTATE: -atrophy, focal -Inflammation, suppurative 1 2 SEMINAL VESICLES: - COAGULATING GLAND: - ADRENAL GLANDS: -hypertrophy/vacuolation, zona glomerulosa -vacuolation, cortex 2 - 1 1 PITUITARY: -cyst(s), pars intermedia P <-> V 1275 M SM V 1276 M SS -hypertrophy, hepatocellular, diffuse -inflaimiation, chronic, focal/multi focal -necrosis, focal/multifocal SPLEEN: -atrophy TAIL: <4> - <2> <-> <2> <3> - <1> <2> - <4> Page 981 11-12 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I1-5 (Continued) H1stomorpholog1c Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: V 1278 M SSRF V 1279 M SS V 1283 M SS V 1287 M SS V 1288 M SS V 1293 M SS V 1295 M SS TESTIS: -- EPIDIDYMIS: -infiltration, mononuclear-cell, focal 1 1- PROSTATE: - -- SEMINAL VESICLES: COAGULATING GLAND: ADRENAL GLANDS: -hypertrophy/vacuolation. zona glomerulosa PITUITARY: - --- 12 -- LIVER: -hematopoiesis, extramedullary. multifocal -hypertrophy, hepatocellular, diffuse - <1> <3> <2> -. <3> <3> Page 982 11-13 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFRO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE II-6 Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death TvDe: I 1312 F SS I 1321 F SS I 1328 F SS I 1335 F SS i 1340 F SS I 1341 F SS OVARIES: - - - '- UTERUS: -distention, lumen -macrophages, pigmented 1 -33 33 CERVIX: VAGINA: -muci fication - - - - '- - 2- 3 OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles PPPPP PP P PP ADRENAL GLANDS: --- -- PITUITARY: --- -- EARiSl: -chondropathy, auricular <4> <3> Page 983 11-14 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE II-6 (Continued) Histomorphologi c Observt ions FI Generation Dose Group: Animal Number: Sex: Death Tvoe: I 1342 F SS I 1345 F SS I 1353 F SS I 1355 F SS I 1359 F SS I 19780 F SS OVARIES: - - - ' - UTERUS: -distention, lumen -macrophages, pigmented 2 -*442 CERVIX: VAGINA: -inflamnation, chronic, focal -mucifi cation OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles ADRENAL GLANDS: PITUITARY: ---- 1 -1*-1 PPPPP PPPPP ----- -- -- - EAR(S) : -chondropathy, auricular <4> SPLEEN: -atrophy <4> Page 984 11-15 ARGUS 418-020 ORAL (GAVA6E) TW0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE II-7 Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: II 1365 F SD II 1373 F SD II 1374 F SS II 1407 F SS II 1415 F SS ILEUM: -distention <4> LIVER: -infarct, liver lobe <?> STOMACH: -erosion(s), glandular mucosa TAIL: -inflamnation, chronic -necrosis, focal <2> <-> <1> <2> <-> - Page 985 11-16 ARGUS 418-020 ORAL (GAVAGE) IVO-GENERATION (ONE LITTER PER GENERATION) ' REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE I1--8 Hl Stornorphologic Observations Fl Generation Dose Group: Animal Number: Sex: Death Tvoe: ` KIDNEYS: -dilatation, pelvis ' III 1428 F SS <2> Page 986 11-17 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE II-9 Histomorphologic Observations FI Generation Dose Group: IV Animal Number: 1495 Sex: F Death Type:________________________________________________________________________________________ SS EYES: -abscess, periocular <P> Page 987 11-18 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 11-10 Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: V 1544 F SS V 1546 F SS V 1548 F SS V 1551 F SS V 1552 F SS V 1557 F SS OVARIES: --- -- UTERUS: -distention, lumen -macrophages, pigmented CERVIX: VAGINA: -muci fication 3 343 --- __ - 3 32 '- - -3 OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles PPP PPP PP PP ADRENAL GLANDS: -hyperplasia, cortical, focal PITUITARY: -cyst(s), pars distal is 1P - . -__ EAR(S ): -chondropathy, auricular <4> TAIL: -inf1armati on, chronic -necrosis, focal < 2> <2> Page 988 11-19 ARGUS 418-020 ORAL (6AVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 11-10 (Continued) Histamorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: V 1573 F SS V 1579 F SS V 1589 F SS V 1593 F SS V 1598 F SS OVARIES: -cyst(s), intraovarian __ P UTERUS: -macrophages, pigmented 3 1333 CERVIX: VAGINA: -muc1fication ---- 32- - OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles PPP PP PPPPP ADRENAL GLANDS: ----- PITUITARY: --- -- KIDNEYS: -dilatation, pelvis -pyelonephritis <<33>> <<33>> URETER: -distention -hyperplasia, mucosa -inflammation, chronic , *" <4> <3> <Z> URINARY BLADDER: -cystitis, hyperplastic <4> Page 989 11-20 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (O NE LITTER P E R G EN ERATIO N ) R EPR O D U C TIO N ST U D Y OF AM M O N IU M PERFLU O RO O CTA N O A TE (AFPO) IN R A T S P R O T O C O L 418-020 H ISTOPATHOLOGY R EPO RT A P P E N D IX III INDIVIDUAL ANIM AL G R O S S A N D H IST O M O R PH O LO G Y DATA P Generation KEY TO CO RRELATIO N OF H ISTO M O RPH O LO G IC O BSER V A T IO N S Not applicable = Microscopic evaluation/correlation not appropriate or not required by protocol. Page 990 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13602 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATIONfS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (minimal) inflaimation, chronic (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COAGULATING GLAND PITUITARY End of Record- 13602 SEMINAL VESICLES Page 991 III-l ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13609 SEX: M n sssssssssssssssssssssssssssssssssss GROSS OBSERVATION(S): GENERAL: No aross chanaes. DOSE GROUP: DEATH TYPE: I Scheduled (Reduced Fertility) HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: TESTIS: atrophy, focal (mild) atrophy/degeneration, multifocal (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 13609 Page 992 III-2 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13610 SEX: M GROSS OBSERVATION(S): GENERAL: No oross chanaes. DOSE GROUP: DEATH TYPE: I Scheduled (Reduced Fertility) lfaSSSaaB*tBS*eSSSaB>SBtB3tCSBeSSS3SXe3SSBBS3SSSSS3EB=:=3S=SBS: HISTOMORPHOLOGIC OBSERVATION(S): . Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: atrophy, focal (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 13610 TESTIS Page 993 111-3 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13611 SEX: M DOSE GROUP: DEATH TYPE: I Scheduled (Reduced Fertility) m *C B f*M nas*B issm nsi8S M taiIBB8HBHBMMaHtBmeBStlUia*nSSaS8SS8SnSI8SMSS8t8SSSSSfSt GROSS OBSERVATION(S1: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: inflamnation, chronic (minimal) atrophy, focal (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS COAGULATING GLAND EPIDIDYMIS End of Record- 13611 SEMINAL VESICLES TESTIS Page 994 111-4 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13612 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 13612 ' PITUITARY Page 995 III-5 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13614 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATIONS) : .UNG: All lobes- dark red areas too numerous to count ranging in size from pinpoint to 0.2cm in di ameter. HISTOMORPHOLOGIC OBSERVATION?SI : hemorrhage, multifocal inflanmation, interstitial, multifocal HISTOMORPHOLOGIC OBSERVATIONS: LUNG: PROSTATE: hemorrhage, multifocal (moderate) inflanmation, interstitial, multifocal (moderate) inflanmation, chronic (mild) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 13614 PITUITARY Page 996 111-6 ARGUS 418-020 ORAL (6AVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13615 SEX: M SSSSSSSSS2SS3SSSSaSSS88SSSS8SSS: GROSS OBSERVATION(S): GENERAL: No aross chanaes. DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled HISTOMORPHOLOGIC OBSERVATIONfSl: ' Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: vacuolati on, cortex (mild) inflanmation, suppurative, focal (minimal) dilatation, glandular, focal (moderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13615 SEMINAL VESICLES Page 997 111-7 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-5889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13616 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): EAR(S): Swollen, both. HISTOMORPHOLOGIC OBSERVATION(S): Tissue not available THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY TISSUEfS) NOT AVAILABLE FOR EVALUATION: EAR(S) End of Record- 13616 Page 998 I I I -8 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13621 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled Btm iaBiHiam M iiuiHnm aivniaaim m NiaianitBiaHSM itunM acniissssntsnsicssssisssssBss GROSS OBSERVATION!SI: HISTOMORPHOLOGIC OBSERVATIONfS): GENERAL: No gross changes. Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLANO SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 13621 PITUITARY Page 999 111-9 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13622 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: inflammation, chronic (mild) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 13622 PITUITARY Page 1000 III-10 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13624 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled c i n t n s t t s a i m a i t s s s n a a t n B s a i B a a B a a a a a a a a a a B B B a a a a a a a a a a a a a B S a a a a a a a a a a a a a a ia a a s a a a a a a a a a a a a a a sa ia i GROSS OBSERVATION(SI: HISTOMORPHOLOGIC OBSERVATIONS): GENERAL: No aross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (minimal) inflamnation, chronic (minimal) dilatation, glandular, focal (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COAGULATING GLAND PITUITARY End of Record- 13624 SEMINAL VESICLES Page 1001 III-ll ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTIOI. STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 ' SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Ind-vidual Animal Gross and Histanirphology Data P Generation ANIMAL NUMBER: 13625 SEX: M DOSE .ROUP: DEATH TYPE: I Sacrifice-Scheduled StBSCBSSSSSBSSSCSSSSSHtBSSBItS ?2SBISBBSISSBBnBIBSIBtBnSBSr :SBSSSBSZSSBSS8S8BSSSSSSBSSSS8SSSSSSSSBSS: GROSS OBSERVATION(S): GENERAL: No aross chanaes. HIST'HORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: vacuolation, cortex (minimal) inflammation, suppurative, focal (mild) . THE FOLLOWING TISSUEfSl WERE VIITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPID'DYMIS PITUITARY End of Record- 13625 SEMINAL VESICLES Page 1002 111-12 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13626 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONfS): ' Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: EPIDIDYMIS: vacuolation, cortex (mild) infiltration, mononuclear-cell, focal (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS COAGULATING GLAND TESTIS PITUITARY End of Record- 13626 PROSTATE SEMINAL VESICLES Page 1003 I I 1-13 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13632 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION!SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13632 Page 1004 III-14 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13636 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled *SMSmSie8SS8Se8SaSS3SenS3S8SS8S8CSStSIBSMSUnM8l8S8fltS8ISSS8SS3S8SS8SSSBSSC8SSSSSS:SSSSSSSSSSS GROSS OBSERVATION(S): HIST0M0RPH0L06IC OBSERVATION(S): EPIDIDYMIDES: Right- small and flaccid. TESTES: Right- small and flaccid. atrophy, EPIDIDYMIS hypospermia, EPIDIDYMIS infiltration, mononuclear-cell, focal, EPIDIDYMIS hypoplasia, diffuse, TESTIS dilatation, rete testis, TESTIS HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: TESTIS: End of Record- 13636 atrophy (minimal) hypospermia (marked) infiltration, mononuclear-cell, focal (minimal) hypoplasia, diffuse (marked) dilatation, rete testis Page 1005 111-15 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13638 DOSE GROUP: II SEX: M OEATH TYPE: Scheduled (Reduced Fertility) M iiM H n M M iM tn r a s n m s s M is M a s n tiM ia a M n a g n iM e m m is B n n s B s iB R ts s s s B x flS B s is s u s s s s s s s GROSS OBSERVATION(S): EAR!SI: Swollen, right. HISTOMORPHOLOGIC OBSERVATIONS): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): EPIDIDYMIS: chondropathy, auricular (moderate) exfoliated spermatogenic cells (mild) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PROSTATE SEMINAL VESICLES End of Record- 13638 TESTIS Page 1006 I I 1-16 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13639 SEX: M DOSE GROUP: DEATH TYPE: II Scheduled (Reduced Fertility) GROSS OBSERVATION(S): KIDNEYS: Right- pelvis, slight dilation. HISTOMORPHOLOGIC OBSERVATION(S): dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS: PROSTATE: Infiltration, mononuclear-cell, focal (minimal) dilatation, pelvis (minimal) inflammation, chronic (mild) THE FOLLOWING TISSUEISl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES TESTIS End of Record- 13639 Page 1007 '111-17 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) ' REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13642 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13642 Page 1008 III-18 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13644 SEX: M DOSE GROUP: DEATH TYPE: II Sacri fice-Schedul ed GROSS OBSERVATION(S): GENERAL: No gross changes. THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13644 HISTOMORPHOLOGIC OBSERVATION(S): Not applicable Page 1009 111-19 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13645 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S1: Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13645 Page 1010 I I 1-20 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 Appendix III Individuai Animai Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13646 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS) : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANOS: End of Record- 13646 vacuolati on, cortex (minimal) Page 1011 I I 1-21 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and HIstomorphology Data P Generation ANIMAL NUMBER: 13650 SEX: M DOSE GROUP: DEATH TYPE: II Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (mild) inflanmation, chronic (minimal) THE FOLLOWING TISSUE!ST WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES TESTIS End of Record- 13650 Page 1012 II1-22 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 136S1 SEX: M DOSE GROUP: DEATH TYPE: II Sacri fice-Schedul ed GROSS OBSERVATION(S): GENERAL: No gross changes. HIST0M0RPH0L06IC OBSERVATION(S): Not applicable HIST0M0RPH0L06IC OBSERVATIONS: ADRENAL 6LANDS: End of Record- 13651 vacuo!ation, cortex (minimal) Page 1013 I I 1-23 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13652 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATIONS!: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfSi: Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13652 Page 1014 1I 1-24 ARGUS 418-020 ORAL (GAVAGE) IVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13653 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION(S): EARiSl: Swollen, riaht. HISTOMORPHOLOGIC OBSERVATIONS!: ' chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13653 chondropathy, auricular (moderate) Page 1015 III-25 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13654 SEX: M nsssssssssssssssssssssssi GROSS OBSERVATION(S): GENERAL: No gross changes. DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled HISTOMORPHOLOGIC OBSERVATIONS! : Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13654 Page 1016 - I I I -26 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histamorphology Data P Generation ANIMAL NUMBER: 13655 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOHORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13655 Page 1017 I11-27 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13656 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION(SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: AORENAL GLANDS End of Record- 13656 Page 1018 I I 1-28 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Oata P Generation ANIMAL NUMBER: 13661 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATIONS) : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13661 vacuolation, cortex (minimal) Page 1019 II1-29 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTXOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13662 SEX: M DOSE GROUP: DEATH TYPE: III Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No gross changes. HIST0M0RPH0L06IC OBSERVATIONS): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 13662 PROSTATE Page 1020 I11-30 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-3889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13668 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATIONS): GENERAL : No gross changes. THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIHITS: ADRENAL GLANDS End of Record- 13668 HISTOMORPHOLOGIC OBSERVATION!Si : Not applicable Page 1021 I I I -31 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13670 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATIONS!: KIDNEYS: Right- pelvis, moderate dilation. HISTOMORPHOLOGIC OBSERVATION! S): dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 13670 dilatation, pelvis (moderate) Page 1022 I I 1--32 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13671 SEX: H GROSS OBSERVATION(S): GENERAL: No gross changes. DOSE GROUP: III DEATH TYPE: Sacrifice-Scheduled [iszsnsa=ssx=x3r=s=s=s=sscss=sz=8:===3z;rx=s=== HIST0M0RPH0L06IC OBSERVATIONS!: Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13671 Page 1023 III-33 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13672 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): KIDNEYS: Right- pelvis, slight dilation. HISTOMORPHOLOGIC OBSERVATION(S): dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 13672 dilatation, pelvis (minimal) Page 1024 I11-34 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13673 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION!S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13673 Page 1025 II1-35 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) * REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13674 SEX: M DOSE GROUP: DEATH TYPE: III Scheduled (Reduced Fertility) GROSS OBSERVATIONfS): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONfS): . Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: hypospennia (mild) exfoliated spermatogenic cells (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PROSTATE SEMINAL VESICLES End of Record- 13674 TESTIS Page 1026 III-36 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13675 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATIONS) : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13675 vacuolation, cortex (mild) Page 1027 I I 1-37 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13676 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13676 HISTOMORPHOLOGIC OBSERVATION!Si : . Not applicable Page 1028 I I 1-38 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13682 SEX: M DOSE GROUP: OEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13682 HISTOMORPHOLOGIC OBSERVATION?S): Not applicable vacuolation, cortex (minimal) Page 1029 . 111-39 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTXOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13683 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13683 vacuolation, cortex (moderate) Page 1030 III-40 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13684 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No qross chanqes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13684 Page 1031 III--41 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) ' REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13693 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATIONS): GENERAL: No qross changes. HISTOMORPHOLOGIC OBSERVATION(S): ' Not appl icabl e THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13693 Page 1032 III-42 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13695 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATIONfS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS): Not applicable ' THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13695 Page 1033 II1-43 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13699 SEX: M DOSE GROUP: DEATH TYPE: IV Sacri fi ce-Schedul ed GROSS OBSERVATION(Si: GENERAL: No gross changes. HIST0M0RPH0L06IC OBSERVATION^!: Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13699 Page 1034 I I 1-44 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13700 SEX: M DOSE GROUP: DEATH TYPE: IV Scheduled (Reduced Fertility) GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): ` Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: inflanmation, chronic (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 13700 TESTIS Page 1035 I I 1-45 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13703 SEX: M GROSS OBSERVATION(S): GENERAL: No gross changes. DOSE GROUP: IV DEATH TYPE: Sacrifice-Scheduled tminMusannuiBCttUBSsaisesssssBeiesasssssss HIST0M0RPH0L06IC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANOS End of Record- 13703 Page 1036 111-46 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13704 SEX: M S S IIS S B IB S S S S S S S S S S S B S S X S S GROSS OBSERVATION!S): GENERAL: No gross changes. DOSE GROUP: IV DEATH TYPE: Sacrifice-Scheduled tesssssmssBssssssssssssssssBSStssi HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUE(S) MERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13704 Page 1037 III--47 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) * REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and HIstomorphology Data P Generation ANIMAL NUMBER: 13706 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): EPIDIDYMIDES: Right- small and flaccid. TESTES: Right- small and flaccid. HISTOMORPHOLOGIC OBSERVATION(S): atrophy, EPIDIDYMIS hypospermia, EPIDIDYMIS infiltration, mononuclear-cell, focal, EPIDIDYMIS hypoplasia, diffuse, TESTIS ' dilatation, rete testis, TESTIS HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: EPIDIDYMIS: TESTIS: End of Record- 13706 vacuolation, cortex (minimal) atrophy (mild) hypospermia (marked) infiltration, mononuclear-cell, hypoplasia, diffuse (marked) dilatation, rete testis focal (minimal) Page 1038 II1-48 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (OHE LITTER PER GEHERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13708 SEX: M OOSE GROUP: DEATH TYPE: IV Sacri fi ce-Scheduled GROSS OBSERVATION?S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS) : Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANOS End of Record- 13708 Page 1039 I I 1-49 ARGUS 418-020 ORAL (6AVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13710 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): EARfS): Swollen, right. HISTOMORPHOLOGIC OBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13710 chondropathy, auricular (moderate) Page 1040 I I 1-50 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13711 SEX: M GROSS OBSERVATION!S): GENERAL: No aross chanaes. DOSE GROUP: IV DEATH TYPE: Sacrifice-Scheduled m s n n u f n n ta u in tn a n n M itn iim is iH iB iM iB B a B C iB a s s B B K M i HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13711 hypertrophy/vacuolation, zona glomerulosa (minimal) Page 1041 III-51 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13716 DOSE GROUP: IV SEX: M DEATH TYPE: Sacrifice-Scheduled SBcssnsenssssscnssascBsstssssssSB88SStSSSSBS8BBSBSSBB8BSSSBB8SSSBBB8SB8SSS8SS83S8SSBS8BS8SSSS88BSSS: GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No aross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13716 hypertrophy/vacuolation, zona glomerulosa (minimal) Page 1042 111-52 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13717 DOSE GROUP: IV SEX: M DEATH TYPE: Sacrifice-Scheduled n*tSSS*UC&SSSS8SSSSSSSm8*SSBSSSURnSSmnn*n>BansBtSSBtBSSS83BS8SSSSSSSS8SSB8S8SSBS8SSS8SSSSSS GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION?S): KIDNEYS: Right- pelvis, slight dilation. dilatation, pelvis hyperplasia, pelvic/papillary epithelium, focal HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 13717 ' dilatation, pelvis (minimal) hyperplasia, pelvic/papillary epithelium, focal (mild) Page 1043 I I 1-53 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13719 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATIONfSl: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13719 Page 1044 I I 1-54 ARGUS 418-020 ORAL (GAVASE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13721 SEX: M GROSS OBSERVATION(S): GENERAL: No oross chanaes. DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled lltlllW ilW W lW M illtll8 W t l l 8 1 tS M 1 8 aig ll8 8 S C T 8 S S S 8 g a8 HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: EPIDIDYMIS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (minimal) infiltration, mononjclear-cel1, focal (minimal) inflanmation, chronic (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PITUITARY SEMINAL VESICLES End of Record- 13721 TESTIS Page 1045 III-55 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13722 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATIONS) : GENERAL: No gross changes. HISTOHORPHOLOGIC OBSERVATIONS) : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: EPIDIDYMIS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (moderate) infiltration, mononuclear-cell, focal (minimal) dilatation, glandular, focal (mild) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PITUITARY SEMINAL VESICLES End of Record- 13722 TESTIS Page 1046 I I 1-56 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-S889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13728 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled 3SICsn8SSSSBS8*SSSlSSKIBISiasniBaB3MS88WBlMgmMH88Sg88BagaS8g8a8BBBS88gBagBBSS3SSSS8S8 GROSS OBSERVATIONS!: HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No oross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolation. zona glomerulosa (moderate) vacuolation. cortex (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End of Record- 13728 PROSTATE Page 1047 II1-57 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13729 SEX: M DOSE GROUP: DEATH TYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATION!S): KIDNEYS: Right- pelvis, slight dilation. HISTOMORPHOLOGIC OBSERVATION(S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: No microscopic change to correlate THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS KIDNEYS End of Record- 13729 PROSTATE Page 1048 I I 1-58 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13731 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (mild) inflaimation, chronic (mild) dilatation, glandular, focal (minimal ) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13731 SEMINAL VESICLES Page 1049 111-59 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13732 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Moribund SnSB8BSSSSS&SKaSSSSSSSSS888S8SSSSasSS8aUnnSKSaSSSI8S8SSSSrSS8SBS&S8SSSSSSSSSeSS8SSSSSSS8SSSS8SSSS GROSS OBSERVATIONS): HISTOMORPHOLOGIC OBSERVATION(S) : . LIVER: All lobes pale, tan in color. TESTES: Bilateral- red. necrosis, centrilobular atrophy/degeneraiion, multifocal, TESTIS HISTOMORPHOLOGIC OBSERVATIONS: LIVER: TESTIS: End of Record- 13732 necrosis, centrilobular (moderate) atrophy/degeneration, multifocal (marked) Page 1050 I I 1-60 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and HIstomorphology Data P Generation ANIMAL NUMBER: 13733 SEX: M DOSE GROUP: DEATH TYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATION(S): EPIDIDYMIDES: Left- small and flaccid. KIDNEYS: Right- pelvis, slight dilation. HISTOMORPHOLOGIC OBSERVATION?S): exfoliated spermatogenic cells, EPIDIDYMIS atrophy, EPIDIDYMIS dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS: , exfoliated spermatogenic cells (minimal ) atrophy (moderate) hypospermia (marked) dilatation, pelvis (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PROSTATE SEMINAL VESICLES End of Record- 13733 TESTIS Page 1051 ITI-61 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13734 SEX: M DOSE 6R0UP: V DEATH TYPE: Sacrifice-Scheduled GROSS OBSERVATION^!: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: vacuolation, cortex (minimal) inflammation, suppurative, focal (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13734 SEMINAL VESICLES Page 1052 III-62 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13735 SEX: M DOSE GROUP: DEATH TYPE: V Sacri fice-Schedul ed GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: atrophy, focal (mild) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 13735 PITUITARY Page 1053 II1-63 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTXOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13736 SEX: M GROSS OBSERVATION(S): GENERAL: No aross chanaes. DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled is s s s ts c tn tin n u iiM n B iis iis s B tB S S S S C tc u n s m s s s & s s s iz B is s s s s s s : HISTOMORPHOLOGIC OBSERVATIONfS): ' Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (moderate) inflaimtation, chronic (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13736 SEMINAL VESICLES Page 1054 II1-64 ARGUS 418-020 ORAL (GAVAGE) TV0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Oata P Generation ANIMAL NUMBER: 13741 SEX: M DOSE GROUP: DEATH TYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATIONfS): EPIDIDYMIDES: Bilateral- soft and flaccid. TESTES: Bilateral- soft and flaccid. HISTOMORPHOLOGIC OBSERVATIONfS): hypospermia, EPIDIDYMIS exfoliated spermatogenic cells, EPIDIDYMIS atrophy/degeneration, multifocal, TESTIS dilatation, rete testis, TESTIS HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: TESTIS: hypospermia (marked) exfoliated spermatogenic cells (moderate) dilatation, rete testis atrophy/degeneration, multifocal (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PROSTATE SEMINAL VESICLES End of Record- 13741 Page 1055 III-65 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13742 SEX: M DOSE GROUP: OEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolation, zona glomerulosa (mild) vacuolation, cortex (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 13742 PITUITARY PROSTATE Page 1056 II1--66 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13743 SEX: M GROSS OBSERVATIONS): GENERAL: No aross chanaes. DOSE GROUP: V DEATH TYPE: Sacrifice-Scheduled ranmaiiiiiintucnutnMtauMsssBSBSSSSBiBisBssMsssssssss HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: hypertrophy/vacuolatlon, zona glomerulosa (moderate) inflamnation, chronic (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS ' PITUITARY End of Record- 13743 SEMINAL VESICLES Page 1057 II1--67 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and H1stomorphology Data P Generation ANIMAL NUMBER: 13744 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION!SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 13744 PITUITARY Page 1058 II1-68 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13750 DOSE GROUP: V SEX: M DEATH TYPE: Scheduled (Reduced Fertility) B i s t n i a M S K s e s i B M B i i i t t a M s s s H m u i IBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBS8BBaBBBB8BBBBBBBBBaBBBBg=BS8S8: GROSS OBSERVATIONS): HISTOMORPHOLOGIC OBSERVATION(S): TESTES: Left- larae. No microscopic change to correlate, TESTIS HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: TESTIS: atrophy, focal (minimal) No microscopic change to correlate THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 13750 TESTIS Page 1059 II1-69 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13802 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No cross chances. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: PITUITARY: UTERUS: VAGINA: presence of corpora lutea presence of growing/antral follicles cyst(s), pars intermedia macrophages, pigmented (moderate) distention, lumen (mild) mucification (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS CERVIX OVARIES End of Record- 13802 OVIDUCT(S) Page 1060 III-70 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13804 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Moribund GROSS OBSERVATIONS): HEAD: Broken palate. HISTOMORPHOLOGIC OBSERVATION(S): fracture, PALATE hemorrhage, PALATE HISTOMORPHOLOGIC OBSERVATIONS: PALATE: End of Record- 13804 fracture hemorrhage (marked) Page 1061 I I 1-71 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13809 DOSE GROUP: I SEX: F DEATH TYPE: Sacrifice-Scheduled sangiiat*s>M tii*m nM tt**ia*iMssramsauuaRnRiMsausBsisnuMBSSSBssassssas GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growlng/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13809 OVIDUCT(S) Page 1062 I11-72 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13811 SEX: F GROSS OBSERVATION(S): GENERAL: No aross chanaes. DOSE GROUP: 1 3DEATH TYPE: Scheduled (Reduced Fertility) i M B B s n e m M a > e tSK>estSBsasasssssssBsse===s==esas:sseEiscE HISTOMORPHOLOGIC OBSERVATION!S): . Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: OVARIES: VAGINA: presence of corpora lutea presence of growing/antral follicles cyst(s), intraovarian mucification (mild) THE FOLLOWING TISSUEIS) WERE WITHIN NORMAL LIMITS CERVIX OVIDUCT(S) End of Record- 13811 UTERUS Page 1063 I11-73 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13812 SEX: F aaB anaisncuM rauttu GROSS OBSERVATION!SI: GENERAL: No gross changes. DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled HISTOMORPHOLOGIC OBSERVATION!Si : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS VAGINA CERVIX OVARIES PITUITARY TISSUEfSl NOT AVAILABLE FOR EVALUATION: OVIDUCT(S) End of Record- 13812 Page 1064 III-74 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOT NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13814 DOSE GROUP: I SEX: F DEATH TYPE: Sacrifice-Scheduled assnsMsssssBsssssinssscs&xssst BSBBIIlSttnBtStMnSUSBSSnBSBKSSBSSBSaBSSBSSSSBnSMBSSSSSSMSBSSS: GROSS OBSERVATION(S): EARISl: Swollen, riaht. HISTOMORPHOLOGIC OBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13814 chondropathy, auricular (moderate) Page 1065 111-75 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13815 DOSE GROUP: I SEX: F DEATH TYPE: Sacrifice-Scheduled SBSSiniB K SSSB lSISSB lSSSSSSrSSX IEBBBBBBBXBSBSBBBBBBBKBBBBBBBBBBSeSXZZB8BBBBBr=BZ=XCB3ESS=S=====BBSC==: GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13815 OVIDUCT(S) Page 1066 III-76 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROXTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13816 SEX: F GROSS OBSERVATIONS) : GENERAL: No aross chanoes. DOSE 6R0UP: I DEATH TYPE: Sacrifice-Scheduled ZSS8SS8S8ISraaU U B SB U SB SU H SS**SSSSSSK SIS>9SSSSSSSSSSSSS8SX SSSS: HISTOMORPHOLOGIC OBSERVATIONS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: degeneration, cystic, cortex (minimal) presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS CERVIX VAGINA OVARIES End of Record- 13816 OVIDUCT(S) PITUITARY Page 1067 111-77 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13821 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!SI: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: OVARIAN FOLLICLES/CORPORA LUTEA: OVARIES: UTERUS: hypertrophy/vacuolation, zona glomerulosa (minimal) presence of corpora lutea presence of growing/antral follicles cyst(s), intraovarian macrophages, pigmented (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIHITS: CERVIX OVIDUCT(S) PITUITARY End of Record- 13821 VAGINA Page 1068 I I 1-78 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-3889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13822 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Moribund GROSS OBSERVATIONfS): GENERAL: No gross changes. H ISTOMORPHOLOGIC OBSERVATIONfS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13822 OVIDUCT(S) Page 1069 I I 1-79 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13824 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled BSatSIBSBSSSiaSBSSBISCtCSSSSBSIlIBBBBBBBBBBBBBBBBBBBBBBBBSBBBBEBBSBBSBBBBBBBSaBBBBSCSSSSBBBSBZSSBBBBB: GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13824 OVIDUCT(S) Page 1070 II1-80 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13825 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATIONfSl: EAR(S): Swollen, both. HISTOHORPHOIOGIC OBSERVATIONS!: chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S ): OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: chondropathy, auricular (marked) presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13825 OVIDUCT(S) Page 1071 III--81 ARGUS 418-020 ORAL (GAVAGE) TV0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13826 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATIONiS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION?SI : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: OVARIES: UTERUS: presence of corpora lutea presence of growing/antral follicles cystic bursa(e) macrophages, pigmented (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS CERVIX OVIDUCT(S) PITUITARY TISSUE!SI NOT AVAILABLE FOR EVALUATION: VAGINA End of Record- 13826 Page 1072 I I 1-82 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13836 SEX: F DOSE GROUP: DEATH TYPE: II Sacrifice-Moribund GROSS OBSERVATIONfS): EXTREMITIES: Swollen limbs, left front leg, left front paw. HISTOMORPHOLOGIC OBSERVATION(S): fracture HISTOMORPHOLOGIC OBSERVATIONS: EXTREMITIES: End of Record- 13836 fracture Page 1073 III-83 ARGUS 418-020 ORAL (GAVAGE) TWO-GEHERATIOH (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13840 DOSE GROUP: II SEX: F DEATH TYPE: Scheduled (Reduced Fertility) SN SssnsszssssssssssssHBsusnss KISMBIBSSStSSmiSSUtSSUnBSISSasSSSSSSSSSBBSSSSSSSSSSSSSSSSSSSSBS: GROSS OBSERVATIONS!: HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No aross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: presence of corpora lutea presence of growing/antral follicles THE FOLLOWING TISSUEfSl WERE UITHIN NORMAL LIMITS: CERVIX VAGINA OVARIES OVIDUCT(S) End of Record- 13840 UTERUS Page 1074 II1-84 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and H1stcmorphology Data P Generation ANIMAL NUMBER: 13851 DOSE GROUP: II SEX: F DEATH TYPE: Scheduled (Reduced Fertility) 3 33t i i i K M a K B i z s i a s B s m B s i s c a x x B s s i S B > m i i H i i i K S s e i B S z B s t e a s & S B C xz=xEssrxzs=azasBsssEe= GROSS OBSERVATIONfSl: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles distention, lumen (marked) THE FOLLOWING TISSUE!ST WERE WITHIN NORMAL LIMITS: CERVIX End of Record- 13851 OVARIES OVIDUCT(S) VAGINA Page 1075 I I 1--85 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-8889.6 Appendix III Individual Animal Gross and Hlstomorphology Data P Generation ANIMAL NUMBER: 13856 DOSE GROUP: II SEX: F DEATH TYPE: Sacrifice-Scheduled ucssssassssxsssssussssssas:sBBSSBssaistscessissssssscssBHssieBisssaescisaEicssscccccsscscscr::: GROSS OBSERVATION!S): EAR(S): Swollen, rloht. HISTOMORPHOLOGIC OBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13856 chondropathy, auricular (marked) Page 1076 I I 1-86 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13862 SEX: F OOSE GROUP: DEATH TYPE: III Scheduled (Reduced Fertility) S*im8SS3SSSS8SSSSSS3SSSSSSBMS38SBS8SaS83n8UCSSt88SIBSSBKS88S388S3S88S3333S338S83SSS38333SS3S3SS GROSS OBSERVATIONS): EARfS): Swollen, both. HISTOMORPHOLOGIC OBSERVATIONS): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): OVARIAN FOLLICLES/CORPORA LUTEA: chondropathy, auricular (marked) presence of corpora lutea presence of growing/antral follicles THE FOLLOWING TISSUES) WERE WITHIN NORMAL LIMITS: CERVIX VAGINA OVARIES OVIDUCT(S) End of Record- 13862 UTERUS Page 1077 II1-87 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13869 SEX: F DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATIONfS): EYES: Traumatized cornea. HISTOMORPHOLOGIC OBSERVATIONfS): keratitis, chronic cataract HISTOMORPHOLOGIC OBSERVATIONS: EYES: End of Record- 13869 keratitis, chronic (moderate) cataract Page 1078 111-88 ARGUS 418-020 ORAL (6AVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13885 SEX: F DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): KJDNEYS: Left- pelvis, marked dilation. HISTOMORPHOLOGIC OBSERVATION(S): Tissue not available TISSUE(S) NOT AVAILABLE FOR EVALUATION: KIDNEYS End of Record- 13885 Page 1079 I I 1-89 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and HIstomorphology Data P Generation ANIMAL NUMBER: 13898 DOSE GROUP: IV SEX: F = iicsssias3BS3SS3s m a s s 3SSSSszs::a* M * nicss* s n B m s DEATH scsssi TYPE: Sacrifice-Scheduled * si* 8zsssasss3Sssissss8 sssssssss=ssssssi GROSS OBSERVATION!SI: EARfS): Swollen, riaht. HISTOMORPHOLOGIC OBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13898 chondropathy, auricular (marked) Page 1080 I I 1-90 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13900 SEX: F GROSS OBSERVATIONS: GENERAL: No aross chanaes. DOSE GROUP: DEATH TYPE: IV Scheduled (Reduced Fertility) mMtSMBItnSltltSSMSt8tKSBS8SSSSSSS8SSS3SSSSSSSSSS33SSSSS: HISTOMORPHOLOGIC OBSERVATION(S): Not applicable TISSUE(S) NOT AVAILABLE FOR EVALUATION: CERVIX OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCTfS) UTERUS VAGINA End of Record- 13900 Page 1081 I I 1-91 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTICt STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13901 DOSE GROUP: IV SEX: F DEAT:i TYPE: Sacrifice-Scheduled SSS*SBtB0BteeSMIB3BSS*Mliri EBBSBZB38SBS1BIBBB3BB8BBSB8BBB:BBBISSI3IB(B3BSBISBBSS3:S3Sr:=SCS:SS33SS= GROSS OBSERVATION(S): EAR(S): Swollen, right. HISTf)'0RPH0L0GIC OBSERVATION(S) : chond opathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13901 chondropathy, auricular (moderate) Page 1082 1 1 1-92 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13908 SEX: F DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): EAR(S): Swollen, right. HIST0M0RPH0L06IC OBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13908 chondropathy, auricular (mild) Page 1083 I I 1-93 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal 6ross and Histomorphology Data P Generation ANIMAL NUMBER: 13921 SEX: F GROSS OBSERVATIONS!: GENERAL: No aross chanaes. DOSE GROUP: V DEATH TYPE: Sacrifice-Scheduled iis n s s s a s u M u m a s M n n m B iiis iia iim iB B a x N iN n s s c s s s B S B iS s s s : HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEiS! WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13921 OVIDUCT(S) Page 1084 II1-94 ARGUS 418-020 ORAL (GAVAGE) TV0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13922 SEX: F DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13922 OVIDUCT(S) Page 1085 I I 1-95 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) . REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13927 SEX: F DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled BnsissaaBisssessMsnsHsssassss BZBBBBBBBtMSBSaBBnBIBBSBSSBBBBSBSBBBSBSSSBBSBBSBSBSSSBSBSBSSSBSBSSS; GROSS OBSERVATION(S): EAR(S): Swollen, riaht. HISTOMORPHOLOGIC OBSERVATION(S1: chondropathy, auricular . HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13927 chondropathy, auricular (marked) Page 1086 I I 1-96 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomarphology Data P Generation ANIMAL NUMBER: 13928 DOSE GROUP: V SEX: F DEATH TYPE: Sacrifice-Scheduled S8nS3B6SSBS3SSSSSSSBSSSSSSSSSSSSS88SISSlSt83aisn3CBBttZ83SS*3SStSSB8ESS8E3S383SS88Si:3S3SSS8S88SSS3: GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (mild) distention, lumen (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS ADRENAL GLANDS OVARIES OVIDUCT(S) PITUITARY TISSUE!S) NOT AVAILABLE FOR EVALUATION: CERVIX VAGINA End of Record- 13928 Page 1087 I 11-97 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13929 DOSE GROUP: V SEX: F DEATH TYPE: Scheduled (Reduced Fertility) SSSlSMIBlSBCBSSSSSXISSISIICIlCISSeSl BBBBBBBBSBBBBBBSBBSBBBSBBBBBBBBSBBBBBBBBBBtBBBBSSSBXECSSSBBBSSSEC: GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: OVARIES: UTERUS: absence of corpora lutea presence of growing/antral follicles cyst(s ), intraovari an distention, lumen (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS CERVIX OVIDUCT(S) End of Record- 13929 VAGINA Page 1088 I I 1-98 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13933 DOSE GROUP: V SEX: F DEATH TYPE: Sacrifice-Scheduled BBBBBaaaaBSSBSBSBBaBasBBBaaBsaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaai GROSS OBSERVATIONS): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: degeneration, cystic, cortex (minimal) presence of corpora lutea presence of growlng/antral follicles gland(s), endometrial, cystic macrophages, pigmented (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS CERVIX VAGINA OVARIES End of Record- 13933 OVIDUCT(S) PITUITARY Page 1089 I I 1-99 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13934 SEX: F DOSE GROUP: DEATH T m : V Sacrifice-Scheduled SS8UMIIBS*SSSSmeS88BK8SSSS8:SSSS3BSSKSSSSSBBBSBBBBSSSBSBSSXSBSSSSSSSSSSSS38SSSSSSSSSSBSSSSSSSSSSS GROSS OBSERVATION!S): HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No cross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS ADRENAL GLANDS PITUITARY CERVIX VAGINA End of Record- 13934 OVARIES OVIDUCT(S) Page 1090 III-100 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13935 SEX: F GROSS OBSERVATION!S): GENERAL: No cross chanaes. DOSE GROUP: DEATH TYni: V Sacrifice-Scheduled iiamiraasnnmmnaBaBtssicHinissssssBssnssssssissssssssassss: HISTOMORPHOLOGIC OBSERVATION!S): ` Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13935 OVIDUCT(S) Page 1091 III- 1 0 1 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13936 SEX: F GROSS OBSERVATIONS) : GENERAL: No aross chanaes. DOSE GROUP: V B itB tsn n u u tm siissnDsEsAtTBH MTfftlu::sn ssiSsascnriBfgicses-sSscshseaduslsesdsssssssB sss: HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: CERVIX: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: dilatation (moderate) presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (marked) THE FOLLOWING TISSUEiS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS VAGINA OVARIES OVIDUCT(S) End of Record- 13936 PITUITARY Page 1092 II1-102 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13942 SEX: F asessissssssssssssssssssBS GROSS OBSERVATION(S): GENERAL: No gross changes. DOSE GROUP: DEATH T H E: V Sacrifice-Scheduled tmtlSIBSHSISSaSSISSIBSMBSSSSSSBl HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13942 OVIDUCT(S) Page 1093 111-103 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13943 SEX: F DOSE GROUP: DEATH TY8E: V Sacrifice-Scheduled GROSS OBSERVATION!SI: GENERAL: No gross changes. HISTOHORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13943 OVIDUCT(S) Page 1094 MI-104 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) - REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13944 SEX: F DOSE GROUP: DEATH TY8E: V Sacrifice-Scheduled s n s n t a n s s s s s s s s a i s i n u c i s s B s i i iBIUIUS8HSamsantCXSIBC8SSUBSSSSSSSSSSSSSSSSSSSS3S8SSSSSBS8SS: GROSS OBSERVATION^!: HISTOMORPHOLOGIC OBSERVATION!S): . GENERAL: No aross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) distention, lumen (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13944 0VIDUCT(S) Page 1095 MI-105 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13946 SEX: F DOSE GROUP: DEATH TN t : V Sacrifice-Scheduled GROSS OBSERVATIONS): EAR(S): Swollen. HISTOMORPHOLOGIC OBSERVATION(S): ' chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13946 chondropathy, auricular (moderate) Page 1096 I I I - 106 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (O N E LITTER P E R G EN ERATIO N ) REPR O D U C TIO N ST U D Y OF AM M O N IU M PERFLU O RO O CTA N O A TE (AFPO) IN R A T S P R O T O C O L 418-020 H ISTO PATH O LO G Y R EP O R T Q A P P E N D IX IV INDIVIDUAL ANIM AL G R O S S A N D H IST O M O R PH O LO G Y DATA F1 Generation KEY TO CO RRELATIO N OF H ISTO M O RPH O LO G IC O B SER V A T IO N S Not applicable = Microscopic evaluation/correlation not appropriate or not required by protocol. Page 1097 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1003 SEX: M DOSE GROUP: DEATH TTPE: I Sacrifice-Scheduled nnSSIUSSBBesSSICBS3MS88UlUI*Cim>ailSMmnmBn8SIS8SSSaS8SSSSSSIB8SS8SSSSS8SSSSSSSSSSSSS GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOHORPHOLOGIC OBSERVATION?S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: infiltration, mononuclear-cell, focal (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS PITUITARY End of Record- 1003 PROSTATE Page 1098 IV-1 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1012 SEX: M DOSE GRUP: DEATH TYfE: I Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS1: Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIHITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 1012 . SEMINAL VESICLES Page 1099 IV-2 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1017 SEX: M DOSE GROUP: DEATH TffE: I Sacrifice-Scheduled GROSS OBSERVATION fS I: GENERAL: No gross changes. HISTOHORPHOLOGIC OBSERVATIONfS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: vacuolation. cortex (minimal) THE FOLLOWING TISSUEfS) MERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End of Record- 1017 PROSTATE Page 1100 IV--3 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) * REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1018 SEX: M DOSE GROUP: DEATH TW E: I Sacrifice-Moribund GROSS OBSERVATIONfS): EYES: Corneal opacity, both eyes. HISTOMORPHOLOGIC OBSERVATIONfS): inflammation, chronic, iris neuropathy, optic nerve(s) HISTOMORPHOLOGIC OBSERVATIONS: EYES: End of Record- 1018 inflamnation, chronic, iris (moderate) neuropathy, optic nerve(s) (moderate) Page 1101 IV-4 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and Histomorphology Data FI Generation ANIMAL NUMBER: 1019 SEX: M DOSE GROUP: DEATH TTfE: I Sacrifice-Moribund GROSS OBSERVATIONS): EYES: Corneal opacity, both eyes. HISTOMORPHOLOGIC OBSERVATION(S): inflanmation, chronic, iris neuropathy, optic nerve(s) HISTOMORPHOLOGIC OBSERVATIONS: EYES: End of Record- 1019 inflanmation, chronic, iris (moderate) neuropathy, optic nerve(s) (moderate) Page 1102 IV-5 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1020 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Moribund GROSS OBSERVATION(S): EYES: Corneal opacity, both eyes. HISTOMORPHOLOGIC OBSERVATION(S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: EYES: No microscopic change to correlate THE FOLLOWING TISSUEIS) WERE WITHIN NORMAL LIMITS EYES End of Record- 1020 Page 1103 IV--6 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1022 SEX: M DOSE GROUP: DEATH TTfE: I Sacri fi ce-Scheduled GROSS OBSERVATIONS): HEAD: Lesion, left side, 1.0cm in diameter. HISTOMORPHOLOGIC OBSERVATION? S ): ` dermatitis, ulcerative. SKIN (GROSS LESION) HISTOMORPHOLOGIC OBSERVATIONS: SKIN (GROSS LESION): End of Record- 1022 dermatitis, ulcerative (moderate) Page 1104 IV-7 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H lstom orphology D ata FI G eneration ANIMAL NUMBER: 1024 SEX: M DOSE GRQUP: DEATH T1TE: I Spontaneous Death GROSS OBSERVATION(S): LUNG: M o ttle d d a rk r e d , a l l lo b e s . HISTOMORPHOLOGIC OBSERVATION(S): hemorrhage, m u ltifo cal HISTOMORPHOLOGIC OBSERVATIONS: LUNG: End o f R e c o rd - 1024 hem orrhage, m u ltifo cal (m ild) Page 1105 IV-8 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ro ss and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1026 SEX: M GROSS OBSERVATION(S): EYES: R ig h t e y e e n la r g e d . HISTOMORPHOLOGIC OBSERVATION(S): atrophy, re tin a l, focal atrophy, i r i s / c i l i a r y body HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: EYES: v a c u o la tio n , c o rte x (m inim al) atro p h y , r e tin a l, fo cal (m ild) atro p h y , i r i s / c i l i a r y body (marked) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End o f R eco rd - 1026 PROSTATE Page 1106 IV-9 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1034 SEX: M DOSE GROUP: DEATH T m ; : I S acrifice-S cheduled GROSS OBSERVATIONS!: GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATIONS!: Not a p p lic a b le THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End o f R ecord- 1034 PITUITARY Page 1107 IV -10 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ro ss and H lstom orphology D ata FI G eneration ANIMAL NUMBER: 1035 SEX: M DOSE GROUP: DEATH TW E: I S acrifice-S cheduled GROSS OBSERVATIONS): GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End o f R eco rd - 1035 PITUITARY Page 1108 IV-11 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OP AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology Data FI G eneration ANIMAL NUMBER: 1040 SEX: M GROSS OBSERVATIONfS): GENERAL: No g r o s s c h a n g e s . DOSE GROUP: DEATH TVK.: I Scheduled (Reduced F e r t il it y ) ISS*BSBsnilBtS>S88SBBSSSSSS8BS8BBSS88&SSSS HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End o f R ecord- 1040 SEMINAL VESICLES Page 1109 IV-12 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal 6 ro s s and H lsta n o rp h o lo g y D ata FI G eneration ANIMAL NUMBER: 1047 SEX: M DOSE GROUP: DEATH J m .: I Sacri fi ce-Scheduled GROSS OBSERVATION(S): GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: i n f il tr a t io n , m o n o n u clear-cell, fo cal (m inim al) Inflam m ation, chronic (m ild) d ila ta tio n , g la n d u la r, focal (m ild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COAGULATING GLAND PITUITARY End o f R ecord- 1047 SEMINAL VESICLES Page 1110 IV--13 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1048 SEX: M DOSE GROUP: DEATH T i f t : I S acrifice-S cheduled GROSS OBSERVATIONfS): GENERAL: No g r o s s c h a n g e s . HISTOHORPHOLOGIC OBSERVATIONfS): Not a p p lic a b le THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE End o f R ecord- 1048 COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY Page 1111 IV--14 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1051 DOSE GROUP: I SEX: M DEATH TYPE: S a c r i f ic e - S c h e d u le d SSSBBSSM ISSSSSSSSSSSBBStSSSSSSI*:BB8B8BBBBSBBBBSBBBBBSSSBBSS88BBSBBB&SBSSSSBSSSSSSS8SBSSSSSSSSSS8SBSBBS GROSS OBSERVATIONS!: GENERAL: No o r o s s c h a n a e s . HISTOMORPHOLOGIC OBSERVATIONS) : ' Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: TESTIS: v a c u o la tio n , c o rte x (m inim al) a trc p h y /d e g e n e ra tio n , m u ltifo c a l (m inim al) THE FOLLOWING T IS S U E S ) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS PITUITARY End o f R ecord- 1051 PROSTATE Page 1112 IV -15 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUN PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1052 SEX: M DOSE GROUP: DEATH T rfE : I S acrifice-S cheduled GROSS OBSERVATIONS) : GENERAL: No g r o s s c h a n g e s . HISTOMORPHOL06IC OBSERVATION!S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: v a c u o la tlo n , c o rte x (m inim al) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End o f R e c o rd - 1052 PROSTATE Page 1113 IV--16 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istcm orphology D ata FI G eneration ANIMAL NUMBER: 1054 SEX: M DOSE GROUP: DEATH T lE : I S acrifice-S cheduled GROSS OBSERVATION!SI: GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: in f l .in n a tion, chronic (m inim al) THE FOLLOWING TISSUEISl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS End o f R ecord- 1054 PITUITARY Page 1114 IV--17 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -5 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1063 SEX: M DOSE GROUP: DEATH T W : II Sacri f i ce-Schedul ed GROSS OBSERVATION(S): GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATIONS) : Not a p p lic a b le THE FOLLOWING TISSUEiSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End o f R ecord- 1063 Page 1115 IV-18 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istcxnorphology D ata FI G eneration ANIMAL NUMBER: 1066 SEX: M DOSE GROUP: DEATH T : II Scheduled (Reduced F e r t il it y ) GROSS OBSERVATION(S): GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End o f R ecord- 1066 SEMINAL VESICLES Page 1116 IV-19 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1077 SEX: M aunnsBUScssssuscsscss GROSS OBSERVATIONfSl: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: DOSE GROUP: DEATH TTTC: II Scheduled (Reduced Fertility) IBSe88SSSBS8SBBSSSBSSSSS8SSZSS8SSSS8SSSSSS8S HISTOMORPHOLOGIC OBSERVATION(S): Not applicable inflammation, chronic (minimal) THE FOLLOWING TISSUEfS! WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 1077 TESTIS Page 1117 IV--20 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1078 DOSE GROUP: II SEX: M DEATH Tift: Sacrifice-Scheduled ssiBCsassBBssBssssetnsssmsHSSSSBSSSBBBBBBSaMBBBasBSBBBSBBBBBBBaBBISSBBBBBSSSSSSBBBBSBBBSBSSBSBSBSi GROSS OBSERVATIONS! : HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No aross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 1078 vacuolation, cortex (minimal) Page 1118 IV-Z1 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 A ppendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1082 SEX: M DOSE GROUP: DEATH TY*ft: II Scheduled (Reduced Fertility) GROSS OBSERVATION!SI: EPIDIDYMIDES: Left- small. TESTES: Left- small, flaccid. HISTOMORPHOLOGIC OBSERVATIONS!: No microscopic change to correlate, EPIDIDYMIS No microscopic change to correlate, TESTIS HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: TESTIS: No microscopic change to correlate No microscopic change to correlate THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 1082 SEMINAL VESICLES Page 1119 IV--22 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphclogy Data FI Generation ANIMAL NUMBER: 1096 SEX: M DOSE GROUP: DEATH T f t : II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1096 Page 1120 IV-23 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and Histomorphology Data FI Generation ANIMAL NUMBER: 1098 SEX: M DOSE GROUP: DEATH Tift: II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1098 Page 1121 IV-24 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorpho!ogy Data FI Generation ANIMAL NUMBER: 1100 DOSE GROUP: II SEX: M DEATH TY*ft:: Sacrifice-Scheduled SB isim ascsstiiB iiseB iisttiiscse!isuunBnBMVsnnnimistBiusiisKssBBCBtsznKsss&Bsssssssessssss: GROSS OBSERVATION!SI: HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No aross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 1100 vacuolation, cortex (minimal) Page 1122 IV-25 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphoiogy Data FI Generation ANIMAL NUMBER: 1106 SEX: M DOSE GROUP: DEATH TYft: II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOHORPHOLOGIC OBSERVATIONfS): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1106 Page 1123 IV--26 ARGUS 418-020 ORAL (6AVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1107 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfST : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 1107 vacuolation, cortex (minimal) Page 1124 IV--27 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.B Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1116 SEX: M DOSE GROUP: DEATH TYTC: II Sacrifice-Scheduled GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOHORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1116 Page 1125 IV-28 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and Histomorphology Data Fl Generation ANIMAL NUMBER: 1118 SEX: M DOSE GROUP: DEATH TW E : II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfS) MERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1118 Page 1126 IV-29 ARGUS 418-020 ORAL (GAVA6E) TW0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histamorphology Data FI Generation ANIMAL NUMBER: 1120 DOSE GROUP: II SEX: M DEATH T1E: Sacrifice-Scheduled u n s tm M S c n iis B m K a s s s s a M iW88SnUtlMIBIM*SnBll8SSS3tB88SS8SSMSSM3SBSSB88SSSSSSSS3SSSES: GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONS): . Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 1120 vacuolation, cortex (minimal) Page 1127 IV-30 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1123 SEX: M DOSE GROUP: DEATH rWE: III Sacri fi ce-Scheduled GROSS OBSERVATIONfS): Swollen snout. HISTOMORPHOLOGIC OBSERVATIONfS): fracture with callus formation deviation, nasal septum HISTOMORPHOLOGIC OBSERVATIONS: HEAD: End of Record- 1123 fracture with callus formation deviation, nasal septum Page 1128 IV--31 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal 6 ro s s and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1124 SEX: M DOSE GROUP: DEATH TV^E: III S acrifice-S cheduled GROSS OBSERVATIONS): LIVER: L e f t l a t e r a l lo b e - ta n a r e a s to o num erous to co u n t, ran g in g from p in p o in t to 0.3cm. HISTOMORPBOLOGIC OBSERVATION(S) : hypertrophy, h e p a to c e llu la r, d iffu se n ecrosis, focal/m ultifocal hem atopoiesis, extram edullary, m ultifocal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R e c o rd - 1124 hypertrophy, h e p a to c e llu la r, d iffu s e (m oderate) n e c ro sis, fo c a l/m u ltifo c a l (m ild) h em atopoiesis, ex tram ed u llary , m u ltifo c a l (m inim al) Page 1129 IV-32 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 Appendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1125 DOSE GROUP: I I I SEX: M DEATH T # E : S a c r i f ic e - S c h e d u le d i sN asi* saB siB n > iB i S B * iM n im t H raK im n tim M M sn B ssn > n s i* sn isu asiB S siafB M e GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): LIVER: L e ft l a t e r a l lo b e - t a n a r e a s (4 ) ra n g e d in s iz e from p in p o in t to 0.1cm . hypertrophy, h e p a to c e llu la r, d iffu se inflam m ation, c h ro n ic, fo c a l/m u ltifo c a l HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R ecord- 1125 inflam m ation, ch ro n ic, fo c a l/m u ltifo c a l (m ild) hypertrophy, h e p a to c e llu la r, d iffu s e (m oderate) Page 1130 IV--33 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) * REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H lstom orphology D ata FI G eneration ANIMAL NUMBER: 1126 SEX: M DOSE GROUP: DEATH TYPE: III S acrifice-S cheduled GROSS OBSERVATIONS): HEAD: L e s io n , n e c k , r i g h t s i d e , 2 .0 x 0.5cm ; le s io n , head, to p , 0.2cm in d ia m e te r; le s io n , head, r ig h t s id e , 0.2cm In d ia m e te r; le s io n , head, l e f t s id e , 0.2cm in d ia m e te r. LIVER: L e ft l a t e r a l lo b e - ta n a r e a s r a n g in g from a p in p o in t to 0.2cm in s iz e , to o numerous to c o u n t. HISTOMORPHOLOGIC OBSERVATION(S): d e r m a t i t i s , c h r o n i c , SKIN (GROSS LESION) d e r m a t i t i s , u l c e r a t i v e , SKIN (GROSS LESION) hypertrophy, h e p a to c e llu la r, d iffu se inflam m ation, c h ro n ic, fo c a l/m u ltifo c a l HISTOMORPHOLOGIC OBSERVATIONS: LIVER: SKIN (GROSS LESION): End o f R eco rd - 1126 inflam m ation, ch ro n ic , fo c a l/m u ltifo c a l (m inim al) hypertrophy, h e p a to c e llu la r, d iffu s e (m ild) d e rm a titis , chronic (m oderate) d e rm a titis , u lc e ra tiv e (m oderate) Page 1131 IV-34 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1128 DOSE GROUP: I I I SEX: M DEATH T1TE: S a c r i f i c e - S c h e d u l e d a a e e e 3 iic s B ie s s s s s B a is s s s is iB n m e m x s > e ta B B ie u e is s e s 3 s 8 s s ia t 8 B S S 8 S 3 s s s B B iB ts s s z s > B is s s = s s :E E = GROSS OBSERVATION!SI: LIVER: L e ft l a t e r a l l o b e - ta n a r e a , 0 .4 x 0.2cm . HISTOHORPHOLOGIC OBSERVATION(S): hypertrophy, h e p a to c e llu la r, d iffu se HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R ecord- 1128 hypertrophy, h e p a to c e llu la r, d iffu s e (m oderate) Page 1132 IV-35 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H Istom orphology D ata FI G eneration ANIMAL NUMBER: 1129 SEX: M DOSE GROUP: DEATH TYPE: III S acrifice-S cheduled GROSS OBSERVATION(S): GENERAL : No g r o s s c h a n g e s . THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End o f R eco rd - 1129 HISTOMORPHOLOGIC OBSERVATIONiS): Not a p p lic a b le Page 1133 IV-36 ARGUS 418-020 ORAL (GAVAGE) TVO-6ENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H Istom orphology D ata FI G eneration ANIMAL NUMBER: 1134 SEX: M DOSE GRQUP: DEATH TYPE: III S acrifice-S cheduled GROSS OBSERVATION(S): GENERAL: No g r o s s c h a n g e s . THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End o f R ecord- 1134 HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le Page 1134 IV-37 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1136 SEX: M B M U s s n iB C s s s a m u is s s s s s s u s s n GROSS OBSERVATION!Si: HEAD: S w o llen s n o u t. DOSE GROUP: DEATH T i f t : III S acrifice-S cheduled HISTOMORPHOLOGIC OBSERVATIONS! : fra c tu re w ith c a llu s form ation n ecro sis, tooth r h in itis , suppurative HISTOMORPHOLOGIC OBSERVATIONS: HEAD: fra c tu re w ith c a llu s form ation n ecro sis, tooth r h i n it is , su p p u rativ e (m ild) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End o f R ecord- 1136 Page 1135 IV -3 8 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1142 SEX: M DOSE GROUP: DEATH TV : III Scheduled (Reduced F e r t i l i t y ) GROSS OBSERVATION(S): GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOSIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOSIC OBSERVATIONS: PROSTATE: in f l aninati on, ch ro n ic (m ild) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End o f R ecord- 1142 TESTIS Page 1136 IV--39 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1149 SEX: M DOSE GROUP: DEATH TYPE: III Sacri fice-S chedul ed GROSS OBSERVATION(S): GENERAL: No g r o s s c h a n g e s . HISTOHORPHOLOGIC OBSERVATION(S): Not a p p lic a b le THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End o f R ecord- 1149 Page 1137 IV-40 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1154 SEX: M DOSE GROUP: DEATH TYPE. III S acrifice-S cheduled GROSS OBSERVATION!SI: GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End o f R ecord- 1154 Page 1138 IV--41 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1156 DOSE GROUP: I I I SEX: M DEATH TYPE: S a c r i f i c e - S c h e d u l e d n m is n s n s s M s s s a s is s a B s s B S B s s s B B S M u n M a s n tn n a n n u s s s s iB S S s s s x s is s B s s s a B s s s s s s s s s s s & s s s s s s s GROSS OBSERVATION(S): LIVER: L e f t l a t e r a l lo b e - 6 t a n a r e a s , p i n p o i n t to 0.3cm. HISTOMORPHOLOGIC OBSERVATIONS): ' hypertrophy, h e p a to c e llu la r, d iffu se HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R eco rd - 1156 hypertrophy, h e p a to c e llu la r, d iffu s e (m ild) Page 1139 IV-42 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology Data FI G eneration ANIMAL NUMBER: 1159 SEX: M GROSS OBSERVATIONS!: GENERAL: No g r o s s c h a n g e s . DOSE GROUP: I I I DEATH TYPE: S a c r i f ic e - S c h e d u le d innnSSS8SSt&SSSSaSSS8S38SSaSS8SSSSSZS8SBSBSS8SSS HIST0M0RPH0L06IC OBSERVATION(S): Not a p p lic a b le THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End o f R ecord- 1159 Page 1140 IV-43 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Hlstomorphology Data FI Generation ANIMAL NUMBER: 1164 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled SSSSS33BSZSS3SSSSS33CSSIZ8SSSSSSSSSSSSSSSSSSCSMaiMBMSSSSSSSCSS&CSSSSSSSSSSSSSSSSSSSSaSSSSSSSSSSSSSS: GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONS): ' Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1164 . Page 1141 IV-44 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Hi stornorphoiogy Data FI Generation ANIMAL NUMBER: 1165 SEX: M DOSE GROUP: DEATH T^ E : III Sacrifice-Scheduled GROSS OBSERVATIONS): LIVER: Left lateral lobe- tan areas too numerous to count, ranging in size from pinpoint to 0.2cm. HISTOHORPHOLOGIC OBSERVATION(S): hypertrophy, hepatocellular, diffuse HIST0M0RPH0L06IC OBSERVATIONS: LIVER: End of Record- 1165 hypertrophy, hepatocellular, diffuse (moderate) Page 1142 IV-45 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data Fl Generation ANIMAL NUMBER: 1167 SEX: M DOSE GROUP: DEATH TYifc: III Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL : No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE!S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 1167 SEMINAL VESICLES Page 1143 IV-46 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1175 SEX: M DOSE GROUP: III DEATH TYPE: Sacrifice-Scheduled i m n n u i i a t a n M MasaiuatiasstsiKasaisiMssssniBSUSSseBsssissBsass: GROSS OBSERVATION(S): GENERAL: No aross changes. HISTOMORPHOLOGIC OBSERVATION(S): ' Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1175 . Page 1144 IV-47 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and Histcmorphology Data FI Generation ANIMAL NUMBER: 1177 SEX: M DOSE GROUP: DEATH TTPE: III Sacri fi ce-Scheduled GROSS OBSERVATIONfSI: GENERAL: No gross changes. HISTOHORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 1177 vacuolation, cortex (minimal) Page 1145 IV-48 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1180 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1180 Page 1146 IV-49 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1182 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION!S): GENERAL: No gross changes. HIST0M0RPH0L06IC OBSERVATION!S): Not applicable THE FOLLOWING TISSUFfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1182 Page 1147 IV-50 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Hlstomorphology Data FI Generation ANIMAL NUMBER: 1189 SEX: M DOSE GROUP: DEATH TY^E: IV Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1189 Page 1148 IV--51 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and H1stomorphology Data FI Generation ANIMAL NUMBER: 1190 SEX: M DOSE GROUP: DEATH TIE: IV Sacrifice-Scheduled GROSS OBSERVATIONS): LIVER: Left lateral lobe, median lobe- tan areas ranging from a pinpoint to 0.2cm in size, too numerous to count. HISTOMORPHOLOGIC OBSERVATIONS): hypertrophy, hepatocellular, diffuse inflammation, chronic, focal/multifocal necrosis, single-cell HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1190 inflammation, chronic, focal /multi focal (minimal) necrosis, single-cell (minimal) hypertrophy, hepatocellular, diffuse (moderate) Page 1149 IV-52 ARGUS 418-020 ORAL (GAVAGE) TW0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data Fl Generation ANIMAL NUMBER: 1191 SEX: M DOSE 6R0UP: DEATH T : IV Sacrifice-Scheduled GROSS OBSERVATION^!: LIVER: Lateral lobe- tan areas too numerous to count ranging in size from pinpoint to 0.1cm. HISTOMORPHOLOGIC OBSERVATIONfS): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1191 hypertrophy, hepatocellular, diffuse (moderate) Page 1150 IV-53 ARGUS 418-020 ORAL (6AVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.G Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1192 SEX: M 6R0SS OBSERVATIONS): GENERAL : No gross changes. HISTOHORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: atrophy, focal (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COAGULATING GLAND EPIDIDYMIS End of Record- 1192 SEMINAL VESICLES Page 1151 IV - 54 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphclogy Data Fl Generation ANIMAL NUMBER: 1193 SEX: M DOSE GROUP: DEATH TTfE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Left lateral lobe- four tan areas, pinpoint to 0.2cm. HISTOMORPHOLOGIC OBSERVATION(S): ' hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1193 hypertrophy, hepatocellular, diffuse (moderate) Page 1152 IV-55 ARGUS 418-020 ORAL (6AVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Hlstomorphology Data FI Generation ANIMAL NUMBER: 1194 SEX: M DOSE GROUP: DEATH TTPE: IV Sacrifice-Scheduled GROSS O B S E R V AT IO NS : GENERAL: No oross changes. THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1194 HISTOMORPHOLOGIC OBSERVATION(S): Not applicable Page 1153 IV-56 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1197 SEX: M DOSE 6R0UP: DEATH Tffe: IV Sacrifice-Scheduled GROSS OBSERVATION(S): TAIL: Tip missing 5.0cm from base. HISTOMORPHOLOGIC OBSERVATIONiS): hyperplasia/hyperkeratosis abscess HISTOMORPHOLOGIC OBSERVATIONS: TAIL: End of Record- 1197 hyperplas ia/hyperkeratos is (moderate) abscess Page 1154 IV-57 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histamorphology Data FI Generation ANIMAL NUMBER: 1198 SEX: M DOSE GROUP: DEATH Tffc: IV Sacrifice-Scheduled GROSS OBSERVATION!S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1198 Page 1155 IV-58 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individuel Animal Gross and HIstomorphology Data FI Generation ANIMAL NUMBER: 1200 SEX: M DOSE GROUP: OEATH TYfc: IV Sacrifice-Moribund GROSS OBSERVATION(S): GASTROINTESTINAL TRACT: Intestines- distended with gas; stomach, cardiac region- ulcerations one region too numerous to count, range in size from pinpoint to 0.1cm in diameter, second region five ulcerations pinpoint size in diameter. THYMUS: Small. HISTOMORPHOLOGIC OBSERVATIONS) : . ulcer(s). olandular area. STOMACH erosion(s). glandular mucosa, STOMACH peritonitis, focal, STOMACH Advanced autolysis precludes evaluation, distention, COLON - distention, CECUM edema/inflammation, submucosa, CECUM atronhv ILEUM HIST0M0RPH0L0GIC OBSERVATIONS: CECUM: COLON: ILEUM: STOMACH: THYMUS: distention (marked) edema/inflamnation, submucosa (mild) distention (marked) Advanced autolysis precludes evaluation ulcer(s), glandular area (moderate) erosion(s)r glandular mucosa (minimal) peritonitis, focal (minimal) atrophy (marked) AUTOLYSIS PRECLUDES EVALUATION: ILEUM End of Record- 1200 Page 1156 IV-59 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Hlstomorphology Data FI Generation ANIMAL NUMBER: 1205 SEX: M GROSS OBSERVATION(S): LIVER: Left lateral lobe- tan areas ranging In size from pinpoint to 0.5cm, too numerous to count. DOSE GROUP: IV DEATH TYTt: Sacrifice-Scheduled imsssMissfmtsmsM Misestactssisntssssns HISTOMORPHOLOGIC OBSERVATIONfS): ' hypertrophy, hepatocellular, diffuse necrosis, focal/multifocal HIST0H0RPH0L06IC OBSERVATIONS: LIVER: End of Record- 1205 necrosis, focal/multifocal (mild) hypertrophy, hepatocellular, diffuse (moderate) Page 1157 IV-60 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and HIstomorphology Data FI Generation ANIMAL NUMBER: 1206 SEX: M DOSE GROUP: IV DEATH TYPE: Sacrifice-Scheduled i u s s B s s im s s s s s > s c 8 S B s s s a s s P 8 C S 8 s s s s s s s s s s 8 s s s n s B e : GROSS OBSERVATIONS): LIVER: Left lateral lobe- tan ares, too numerous to count, ranging in size from pinpoint to 0.5 x 0.1cm. HISTOHORPHOLOGIC OBSERVATION(S): hypertrophy, hepatocellular, diffuse HISTOHORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1206 hypertrophy, hepatocellular, diffuse (mild) Page 1158 IV--61 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1207 SEX: M DOSE GROUP: DEATH TYPE: IV Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONS): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 1207 SEMINAL VESICLES Page 1159 IV-62 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1211 SEX: M DOSE GROUP: DEATH rfi^E: IV Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1211 Page 1160 IV-63 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1212 SEX: M nSSBSSSSNSSSISSMHSSBSS GROSS OBSERVATION(S): GENERAL: No gross changes. DOSE GROUP: DEATH Tf>E: IV Sacrifice-Scheduled HISTOMORPHOLOSIC OBSERVATION(S): . Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1212 Page 1161 IV-64 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and H1stomorphology Data FI Generation ANIMAL NUMBER: 1217 SEX: M GROSS OBSERVATION(S): GENERAL: No aross chanaes. DOSE GROUP: IV DEATH Tlife: Sacrifice-Scheduled iBmBBasBBBBBSBBBSBSSBBBBBSBSBSSBBSBSssBBSBBBBBBSssssBBSBS&ssBBSSBSsBBs: HISTOMORPHOLOGIC OBSERVATION(S): . Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 1217 vacuolation, cortex (minimal) Page 1162 IV-65 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histcmorphology Data FI Generation ANIMAL NUMBER: 1218 SEX: M OOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATIONfS): LIVER: Left lateral lobe- one tan and black area, 0.2 x 0.2cm; caudate lobe- one tan area, 0.4cm. HISTOMORPHOLOGIC OBSERVATION!SI : ' hypertrophy, hepatocellular, diffuse necrosis, focal/multifocal hematopoiesis, extramedullary, multifocal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1218 necrosis, focal/multifocal (minimal) hematopoiesis, extramedullary, multifocal (minimal) hypertrophy, hepatocellular, diffuse (mild) Page 1163 IV-66 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1223 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATIONS 1: LIVER: Left lateral lobe- tan area, too numerous to count, ranging in size from pinpoint to 0.2cm in diameter. HISTOMORPHOLOGIC OBSERVATION!S): hypertrophy, hepatocellular, diffuse HISTOHORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1223 hypertrophy, hepatocellular, diffuse (mild) Page 1164 IV--67 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1224 SEX: M DOSE 6RQUP: DEATH TYPE: IV S acrifice-S cheduled GROSS OBSERVATION!Si : KIDNEYS: R ia h t - Del v i e d i l a t i o n , s l i a h t . HISTOMORPHOLOGIC OBSERVATION!S): ' d ila ta tio n , pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End o f R ecord- 1224 d ila ta tio n , p e lv is (m oderate) Page 1165 IV-68 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal 6ro s s and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1225 SEX: M DOSE GROUP: DEATH TYPE: IV S acrifice-S cheduled GROSS OBSERVATION(S): GENERAL: No g r o s s c h a n g e s . HISTOHORPHOLOGIC OBSERVATIONtSI : ' Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End o f R eco rd - 1225 v a c u o la tio n , c o rte x (m inim al) Page 1166 IV--69 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1229 SEX: M DOSE GROUP: DEATH T Y rt: IV S acrifice-S cheduled GROSS OBSERVATIONfS): EAR(S): S w ollen, b o th . SPLEEN: Tan a r e a , 2 .0 x 1.5cm , e x te n d s i n t o t h e parenchym a. HISTOMORPHOLOGIC OBSERVATIONfS): chondropathy, a u ric u la r n e c ro s is HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): SPLEEN: End o f R ecord- 1229 chondropathy, a u ric u la r (marked) n e c ro s is (marked) Page 1167 IV-70 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal 6ro s s and H lstom orphology Data FI G eneration ANIMAL NUMBER: 1232 SEX: M DOSE GROUP: DEATH TYPfe: IV S acrifice-S cheduled GROSS OBSERVATION(S): KIDNEYS: R ig h t- p e l v i c d i l a t i o n , s l i g h t . HISTOMORPHOLOGIC OBSERVATIONS) : d ila ta tio n , pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End o f R ecord- 1232 d ila ta tio n , p e lv is (m ild) Page 1168 IV-71 ARGUS 418-020 ORAL (GA'fAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -088S .6 A ppendix IV In d iv id u a l Animal G ross and HistCM irp h o lo g y D ata FI G eneration ANIMAL NUMBER: 1234 SEX: M GROSS OBSERVATION(S): LIVER: Tan a r e a s , m edian lo b e o i e t a n a r e a 0.2cm , l e f t la te r a l lobe to o numerous to co u n t, rang in g from p in p o in t to 0.7cm. DOSE liROUP: DEATH T ^ ff: IV S acrifice-S cheduled tm m m m -t iiiBUBiMaaiisBsttt*BSBietBausinssssB HISTOMORPHOLOGIC OBSERVATIONS): hypertrophy, h e p a to c e llu la r, d iffu se necrosis, focal/m ultifocal inflam m ation, c h ro n ic, fo c a l/m u ltifo c a l HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R ecord- 1234 n e c ro sis, fo c a l/m u ltifo c a l (m ild) inflam m ation, ch ro n ic, fo c a l/m u ltifo c a l (m ild) hypertrophy, h e p a to c e llu la r, d iffu s e (m oderate) Page 1169 IV-72 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1235 SEX: M DOSE GROUP: DEATH TYPE: IV S acrifice-S cheduled 6R0SS OBSERVATIONS!: LIVER: Tan a r e a s , m edian lo b e to o num erous t o count ran g in g in s iz e from p in p o in t to 0.3cm, l e f t l a t e r a l lo b e 4 -5 tarn a re a s ra n g in g from p in p o in t to 0.1cm. HISTOMORPHOLOGIC OBSERVATIONS!: hypertrophy, h e p a to c e llu la r, d iffu se HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R eco rd - 1235 hypertrophy, h e p a to c e llu la r, d iffu se (m oderate) Page 1170 IV-73 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1236 SEX: M DOSE GROUP: DEATH TYt E: IV Sacri fi ce-Scheduled GROSS OBSERVATIONfSl: GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION!S): Not a p p lic a b le THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End o f R ecord- 1236 Page 1171 IV -74 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.G A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1240 SEX: M GROSS OBSERVATIONS): KIDNEYS: R ig h t - p e l v i c d i l a t i o n , s l i g h t . HISTOMORPHOLOGIC OBSERVATIONS) : d ila ta tio n , pelvis m ineralization, pelvis hy p erp lasia, p e lv ic /p a p illa ry urothelium HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End o f R ecord- 1240 d ila ta tio n , p e lv is (m ild) m in e ra liz a tio n , p e lv is (m inim al) h y p e rp la sia , p e lv ic /p a p illa ry urothelium (m inim al) Page 1172 IV--75 ARGUS 418-020 ORAL (GAVAGE) TVO-6ENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata Fl G eneration ANIMAL NUMBER: 1241 SEX: M SSBIBSSItSSSBSaiSI: GROSS OBSERVATIONfS): GENERAL: No g r o s s c h a n g e s . DOSE GROUP: OEATH T Y ?t: V S acrifice-S cheduled HISTOMORPHOLOGIC OBSERVATION(S) : Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: h y p ertro p h y /v acu o latio n , zona glom erulosa (m ild) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End o f R ecord- 1241 PROSTATE Page 1173 IV-76 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-0Z 0 SPONSOR'S STUOY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1243 SEX M GROSS OBSERVATIONfSI: HEAD: L e s io n , 0.2cm in d ia m e te r . HISTOMORPHOLOGIC OBSERVATION!S): d e rm a titis, chronic HISTOMORPHOLOGIC OBSERVATIONS: HEAD: End o f R e c o rd - 1243 d e rm a titis , chronic (m oderate) Page 1174 IV-77 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1244 SEX: M V Sacri fi ce-Scheduled GROSS OBSERVATIONS): GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PITUITARY: h y p ertro p h y /v a cu o latio n , zona glom erulosa (m inim al) v a c u o la tio n , c o rte x (m inim al) c y st(s), pars d ista l is THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End o f R e c o rd - 1244 SEMINAL VESICLES Page 1175 IV-78 ARGUS 418-020 ORAL (GA/AGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1250 DOSE GRQUP: V SEX: M DEATH TYPE: S a c r i f i c e - S c h e d u l e d aBBSSBIISSSSBSISCISilSZSSSSlSSSaiWHllMWMtBMWl1 8 ia a i M lia 8 gISS8 8 a8 la8 1 8 8 8 8 8 gSSBgggBSSSSi GROSS OBSERVATION(S): TAIL: A nnular c o n s t r i c t i o n . HISTOMORPHOLOGIC OBSERVATION(S): ` No m ic ro s c o p ic c h a n g e t o c o r r e l a t e HISTOMORPHOLOGIC OBSERVATIONS: TAIL: No m ic ro s c o p ic c h an g e t o c o r r e l a t e THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: TAIL End o f R ecord- 1250 Page 1176 IV-79 ARGUS 418-020 ORAL (6AVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1251 SEX: M GROSS OBSERVATION(S): LIVER: Left lateral lobe and median lobe- tan areas, too numerous to count, ranging in size from pinpoint to 0.3cm in diameter. DOSE GROUP: DEATH TY^C: V Sacrifice-Scheduled ISUSSSS8IIIK8*SIU8U3nsnnSS8SS88eSSS8SS8SSSS HISTOMORPHOLOGIC OBSERVATION?S): . hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1251 hypertrophy, hepatocellular, diffuse (moderate) Page 1177 IV-80 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1254 SEX: M DOSE GROfiP: DEATH TYPE: Sacri fi ce-Scheduled GROSS OBSERVATION^!: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (mild) inflanmation, chronic (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 1254 SEMINAL VESICLES Page 1178 IV--81 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data Fl Generation ANIMAL NUMBER: 1256 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S) : LIVER: Left lateral lobe- tan area, 0.8cm. HISTOMORPHOLOGIC OBSERVATIONS) : ' hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1256 hypertrophy, hepatocellular, diffuse (mild) Page 1179 IV-82 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and HIstomorphology Data FI Generation ANIMAL NUMBER: 1262 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATIONS!: LIVER: Tan areas, median lobe five tan areas pinpoint to 0.3cm; left lateral lobe tan six tan areas pinpoint to 0.1cm. TAIL: Annular constrictions of tail. HISTOMORPHOLOGIC OBSERVATION(S): . hypertrophy, hepatocellular, diffuse constriction, focal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: TAIL: End of Record- 1262 hypertrophy, hepatocellular, diffuse (moderate) constriction, focal Page 1180 IV-83 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and Histomorphology Data FI Generation ANIMAL NUMBER: 1263 SEX: M DOSE GROUP: DEATH TYPE: V Spontaneous Death GROSS OBSERVATION!SI : IVES: Corneal opacity, both eyes. HISTOMORPHOLOGIC OBSERVATION!S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: EYES: No microscopic change to correlate THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: EYES End of Record- 1263 Page 1181 IV-84 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOT NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data , FI Generation ANIMAL NUMBER: 1264 SEX: M GROSS OBSERVATION(S): EYES: Corneal opacity, both eyes. DOSE GROUP: DEATH TYPE: V Spontaneous Death IMII88BUnBaSSS8SSI8SS8SSSSKnSS88S8SB: HISTOMORPHOLOGIC OBSERVATION(S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: EYES: No microscopic change to correlate THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: EYES End of Record- 1264 Page 1182 IV-85 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and H1stomorphology Data FI Generation ANIMAL NUMBER: 1266 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled M M n i a i n M s s s s s M e a i s s m i B i u : B aaaaaaaaaaaaaaaaataaaaasaaaaaaaaaiattaaaaaaaaaaaaaaaaaaaaaaB M aaaaaB i GROSS OBSERVATION!S): HISTOMORPHOLOGIC OBSERVATIONS) : GENERAL: No aross chanaes. Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PITUITARY: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (mild) cyst(s), pars intermedia inflaninatlon, suppurative (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 1266 TESTIS Page 1183 IV-86 ARGUS 418-020 ORAL (GAVA6E) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1268 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Tan area, median lobe too numerous to count ranging in size from pinpoint to 0.4 x 0.2cm. HISTOMORPHOLOGIC OBSERVATION(S): ' hypertrophy, hepatocellular, diffuse necrosis, focal/multifocal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1268 necrosis, focal/multifocal (mild) hypertrophy, hepatocellular, diffuse (marked) Page 1184 IV-87 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1269 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS) : Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 1269 PITUITARY Page 1185 IV-88 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROXTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1270 DOSE GROUP: V SEX: M DEATH TYPE: Sacrifice-Scheduled 3BZBS33MSS3BEEZSSSSSOSSSSSXZSS3SBXS==333X=UBBBBBBIBXSSS8E3=BBS33BBS3SXS=BESS3SB3=ZZSZBZ33=33=33B=33: GROSS OBSERVATION(S): TAIL: Annular constriction. HISTOMORPHOLOGIC OBSERVATION(S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: TAIL: No microscopic change to correlate THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: TAIL End of Record- 1270 Page 1186 IV-89 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and HIstomorphology Data FI Generation ANIMAL NUMBER: 1271 SEX: M aasBSSBBeBfsstsaasssssBSsa GROSS OBSERVATIONS): GENERAL: No gross changes. DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (minimal) atrophy, focal (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COAGULATING GLAND PITUITARY End of Record- 1271 SEMINAL VESICLES Page 1187 IV-90 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphoiogy Data FI Generation ANIMAL NUMBER: 1273 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled l*ISSSBSneSSSBIINBmiS8UItISUtSIIIIBmBniSSaU*SSSI*8SS88SSSSSS3CSSSSSS8B8SSSSCKSS&SSS GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): . Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolation, zona glomerulosa (minimal) vacuolation, cortex (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE SEMINAL VESICLES COMMENTS: PITUITARY The pituitary was damaged at necropsy and the section that could be obtained was not adequate for evaluation. TISSUEfS) NOT AVAILABLE FOR EVALUATION: PITUITARY End of Record- 1273 Page 1188 IV-91 ARGUS 418-020 ORAL (6AVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1275 OOSE GROUP: V SEX: M DEATH TYPE: S a c r if ic e - M o r ib u n d S2BUBIBZZCSBtSSSXXS3S3SCSS>SSCIXSMSIBSaSS>lSB>8*eBS3BXES:SSCSSSSSS3SSSE18ESBS3C:C33CS3==E=S== GROSS OBSERVATION!SI: LIVER: M edian lo b e - t a n a r e a s to o num erous t o count ran g in g in s iz e from p in p o in t to 0.1cm . SPLEEN: Sm al1 . HISTOMORPHOLOGIC OBSERVATION!S): hypertrophy, h e p a to c e llu la r, d iffu se n ecro sis, focal/m ultifocal a tro p h y HISTOMORPHOLOGIC OBSERVATIONS: LIVER: SPLEEN: End o f R ecord- 1275 n e c ro s is, fo c a l/m u ltifo c a l (m ild) hypertrophy, h e p a to c e llu la r, d iffu s e (m ild) a tro p h y (marked) Page 1189 IV--92 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROXTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1276 DOSE GROUP: V SEX: M DEATH T r f t : S acrifice-S cheduled SISSaaESIBSCESISXSSBSIZXaSBSSSaSSBBBBBBBBBBBBBSSBBBSBSXBBBBBSXBBBBBXEBBBBBKBSBBSBBBtBBSXSBESBXXXXSXZEBI GROSS OBSERVATIONS): LIVER: L a ra e . HISTOMORPHOLOGIC OBSERVATION(S): hypertrophy, h e p a to c e llu la r, d iffu se inflam nation, chronic, fo cal/m u lti focal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R ecord- 1276 in D am nation, ch ro n ic , fo c a l/m u lti fo cal (m inim al) hypertrophy, h e p a to c e llu la r, d iffu se (m oderate) Page 1190 IV-93 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1278 DOSE GRQUP: V SEX: M DEATH T Y ft: S c h e d u le d (R educed F e r t i l i t y ) ZlttM H SSSS38SSSC*StSSSniS8S:isssssisscBBnstnssnM cssscssm Bnszssscssnssssscssssssssssnssssss: GROSS OBSERVATIONS!: GENERAL: No a r o s s c h a n a e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: i n f il tr a t io n , m o n o n u clear-cell, fo cal (m inim al) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PROSTATE SEMINAL VESICLES End o f R ecord- 1278 TESTIS Page 1191 IV -94 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1279 SEX: M DOSE GROUP: DEATH TYffe: V S acrifice-S cheduled GROSS OBSERVATION(S): LIVER: L e ft l a t e r a l l o b e - ta n a r e a s to o num erous to count. HISTOMORPHOLOGIC OBSERVATIONS): hypertrophy, h e p a to c e llu la r, d iffu se HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R eco rd - 1279 hypertrophy, h e p a to c e llu la r, d iffu s e (m oderate) Page 1192 IV-95 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal 6 ro s s and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1283 SEX: M DOSE GROUP: DEATH TrPfc: V S acrifice-S cheduled GROSS OBSERVATION!S): LIVER: L e ft l a t e r a l a n d m edian l o b e s - t a n a r e a s to o numerous to count ranging in s iz e from p in p o in t to 0 .3 x 0.1cm. HISTOMORPHOLOGIC OBSERVATION(S): . hypertrophy, h e p a to c e llu la r, d iffu se hem atopoiesis, extram edullary, m u ltifo cal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R ecord- 1283 h em atopoiesis, ex tram ed u llary , m u ltifo c a l (m inim al) hypertrophy, h e p a to c e llu la r, d iffu s e (m ild) Page 1193 IV-96 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal 6 ro s s and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1287 SEX: M DOSE GROUP: DEATH T r f t : V S acrifice-S cheduled GROSS OBSERVATION!S): GENERAL: No a r o s s c h a n a e s . HISTOMORPHOLOGIC OBSERVATIONfS): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: EPIDIDYMIS: h y p ertro p h y /v a cu o latio n , zona glom erulosa (m inim al) in f i l t r a t i o n , m o n o n u clear-cell, fo cal (m inim al) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS PITUITARY PROSTATE End o f R eco rd - 1287 SEMINAL VESICLES Page 1194 IV-97 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1288 SEX: M DOSE GRQUP: DEATH T l # : V S acri f i ce-Schedul ed GROSS OBSERVATIONfS): GENERAL: No g r o s s c h a n g e s . HISTOHORPHOLOGIC OBSERVATIONfS): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: h y p ertro p h y /v acu o latio n , zona glom erulosa (m ild) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End o f R e c o rd - 1288 PROSTATE Page 1195 IV-98 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1293 SEX: M GROSS OBSERVATION!Si: LIVER: L e ft l a t e r a l lo b e to o num erous t o c o u n t ta n a re a s ranging in s iz e from p in p o in t to 0.5cm . DOSE GRQUP: DEATH T Y ft: V Sacri fi ce-Scheduled I888SSSBSSSSBZSSSS38SSS3SSSSSSNB HISTOMORPHOLOGIC OBSERVATION(S): hypertrophy, h e p a to c e llu la r, d iffu se HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R e c o rd - 1293 hypertrophy, h e p a to c e llu la r, d iffu se (m oderate) Page 1196 IV--99 ARGUS 418-020 ORAL (GAVAGE) TV0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1295 SEX: M GROSS OBSERVATION(S): LIVER: L e ft l a t e r a l lo b e f o u r ta n and w h ite a r e a s ran g in g in s iz e from p in p o in t to 0.3cm. DOSE GRQUP: V DEATH TYTt: S a c r i f ic e - S c h e d u le d samssBSSSSSSzsscssssBSSBBBrBsss: HISTOHORPHOLOGIC OBSERVATION(S): ` hypertrophy,, h e p a to c e llu la r, d iffu s e HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R ecord- 1295 hypertrophy, h e p a to c e llu la r, d iffu s e (m oderate) Page 1197 IV-100 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istcm orphology D ata FI G eneration ANIMAL NUMBER: 1312 SEX: F DOSE 6HQUP: DEATH TYfE: I S acrifice-S cheduled GROSS OBSERVATIONS): GENERAL: No a r o s s c h a n a e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: presence of corpora lu tea presence o f grow ing/antral f o llic le s THE FOLLOWING TISSUE!ST WERE WITHIN NORMAL LIMITS ADRENAL GLANDS PITUITARY CERVIX UTERUS OVARIES VAGINA End o f R e c o rd - 1312 OVIDUCT(S) Page 1198 IV-101 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6889.E A ppendix IV In d iv id u a l Animal G ross and H istcm orphology D ata FI G eneration ANIMAL NUMBER: 1321 DOSE GROUP: I SEX: F DEATH T w E : S a c r i f i c e - S c h e d u l e d SSSSS8UBSSSSSSSSSSSSSS8SSIS8SSS88SStSSUHSICnasSMCKI8SBS8<SB*3SSS8SSSSSSCSSS8SBn&SSSSSSSSas GROSS OBSERVATION(SI: GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION!S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence o f corpora lu tea presence o f grow ing/antral f o llic le s m acrophages, pigm ented (m oderate) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End o f R ecord- 1321 OVIDUCT(S) Page 1199 IV-102 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal 6 ro s s and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1328 SEX: F GROSS OBSERVATION(S): GENERAL: No g r o s s c h a n g e s . IS C X U S ] DOSE GROUP: DEATH T O E : I S acri fi ce-Scheduled HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence of corpora lu tea presence o f grow ing/antral f o llic le s m acrophages, pigm ented (m oderate) m u cificatio n (m ild) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End o f R ecord- 1328 OVIDUCT(S) Page 1200 TV-103 ARGUS 418-020 ORAL (GAVAGE) TW0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Oata FI Generation ANIMAL NUMBER: 1335 SEX: F DOSE GROUP: OEATH Tw E: I Sacrifice-Scheduled GROSS OBSERVATION!SI: EAR(S): Swollen, both. HISTOMORPHOLOGIC OBSERVATIONS): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: chondropathy, auricular (marked) presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1335 OVIDUCT(S) Page 1201 IV--104 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and Histomorphology Data FI Generation ANIMAL NUMBER: 1340 SEX: F DOSE GtyJUP: DEATH PWE: I Sacri fi ce-Schedul ed GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: HISTOMORPHOLOGIC OBSERVATION(S): Not applicable presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) distention, lumen (minimal) mucification (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 1340 OVIDUCT(S) Page 1202 IV-105 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1341 SEX: F DOSE GROUP: DEATH T # E : I Sacrifice-Scheduled GROSS OBSERVATIONS): EAR(S): Swollen, both. HISTOMORPHOLOGIC OBSERVATION(S): ' chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 1341 chondropathy, auricular (moderate) Page 1203 IV-106 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1342 SEX: F DOSE GROUP: DEATH TtrE: I Sacrifice-Scheduled GROSS OBSERVATION IS): EARfS1: Swollen, both. HISTOMORPHOLOGIC OBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: chondropathy, auricular (marked) presence of corpora lutea presence of growing/antral follicles distention, lumen (mild) THE FOLLOWING TISSUE!Si WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1342 OVIDUCT(S) Page 1204 IV-107 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1345 OOSE GRQUP: I SEX: F DEATH TYPE: Sacrifice-Scheduled s u s s s c n s s s s s s s s c & B S S ts s e is s s ts c s s B s a s u M n s u n n s w a n s s ttu s B s n s is B s s s B s s s s & s B s s s s s a a i GROSS OBSERVATION(SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: VAGINA: presence of corpora lutea presence of growing/antral follicles inflamnation, chronic, focal (minimal) muc1fication (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX UTERUS OVARIES End of Record- 1345 OVIDUCT(S) Page 1205 TV-108 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) * REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and Hi stornorphoiogy Data FI Generation ANIMAL NUMBER: 1353 SEX: F GROSS OBSERVATIONfS): GENERAL: No gross changes. DOSE GROUP: I DEATH TWE: Sacrifice-Scheduled l*WmSSnn*IMSS*S*8SB8UBIB8SSStS8Sas8SBN83BS HISTOHORPHOLOGIC OBSERVATIONfS): Not appiicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (marked) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1353 OVIDUCT(S) Page 1206 IV-109 ARGUS 418-020 ORAL (GAVAGE) TV0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889,6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1355 SEX: F GROSS OBSERVATIONS): GENERAL: No aross chanaes. DOSE GROUP: I DEATH TYPE: Sacrifice-Scheduled ISSSSSSS-- MtWT"YWSISSStSSSSaBSSSlSSBlSSSS3SSSSSSSlS HISTOMORPHOLOGIC OBSERVATIONS!: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (marked) THE FOLLOWING TISSUES) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1355 OVIDUCT(S) Page 1207 IV-110 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Hlstomorphology Data FI Generation ANIMAL NUMBER: 1359 SEX: F DOSE GRQUP: DEATH TYPE: I Sacri fice-Scheduled GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence of corpora lutea presence of growlng/antral follicles macrophages, pigmented (mild) mucificatlon (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 1359 OVIDUCT(S) Page 1208 IV-111 ARGUS 418-020 ORAL (GAVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 19780 DOSE GROUP: I SEX: F DEATH TfPE: Sacrifice-Scheduled sassssiisiscsssssssssssBm Bsnsss:ssssa>samBsnsna*aBSSBssBC*sessnBBSssssss8sssssss3SsssssssBSESs: GROSS OBSERVATIONI SI: HISTOMORPHOLOGIC OBSERVATION(S): SPLEEN: Small. atrophy HISTOMORPHOLOGIC OBSERVATIONS: SPLEEN: End of Record- 19780 atrophy (marked) Page 1209 IV--112 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1365 SEX: F s n ss sa ssa sssssssstsssssssc sa u ss GROSS OBSERVATION(S): TAIL: Tlo missina. DOSE GltyUP: DEATH TYfE: II Spontaneous Death HISTOMORPHOLOGIC OBSERVATION!S): necrosis, focal HISTOMORPHOLOGIC OBSERVATIONS: TAIL: End of Record- 1365 necrosis, focal (mild) Page 1210 IV-113 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 . SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal 6ross and Histomorphology Data FI Generation ANIMAL NUMBER: 1373 SEX: F DOSE GROUP: DEATH Tr#E: II Spontaneous Death GROSS OBSERVATIONS!: GASTROINTESTINAL TRACT: Stomach and intestinesdistention. LUNG: Dorsal surface, right apical lobe, depressed white area, 0.3cm in diameter. HISTOMORPHOLOGIC OBSERVATION(S): erosion(s), glandular mucosa, STOMACH distention, ILEUM necrosis, focal macrophages, alveoli, focal HISTOMORPHOLOGIC OBSERVATIONS: ILEUM: LUNG: STOMACH: End of Record- 1373 distention (marked) necrosis, focal (mild) macrophages, alveoli, focal (mild) erosion(s), glandular mucosa (mild) Page 1211 IV--114 ARGUS 418-020 ORAL (GAVAGE) TW0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and HIstomorphology Data FI Generation ANIMAL NUMBER: 1374 SEX: F DOSE GROUP: DEATH T# t : II Sacrifice-Scheduled GROSS OBSERVATION!S): TAIL: Annular constrictions of the tail. HISTOMORPHOLOGIC OBSERVATION(S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: TAIL: No microscopic change to correlate THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: TAIL End of Record- 1374 Page 1212 IV-115 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .S A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1407 SEX: F DOSE GROUP: DEATH TYW: II S acrifice-S cheduled GROSS OBSERVATIONfSl: TAIL: T ip m is s in g . HISTOMORPHOLOGIC OBSERVATIONfSl: ' inflam m ation, chronic HISTOMORPHOLOGIC OBSERVATIONS: TAIL: End o f R ecord- 1407 in flam n atio n , ch ro n ic (m inim al) Page 1213 IV-116 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1415 SEX: F DOSE GROUP: DEATH TTfE: II S acrifice-S cheduled 88Ma888aiSSS8SStaglSlSSlS888aa18K81lM W M t g81aM8181888S8SS1888SSS888SSSSg88S38S GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION!SI: LIVER: L e ft l a t e r a l lo b e - m ass a d h e re d t o l e f t la te r a l lo b e , 2 .0 x 1.2 x 0.4cm, firm . in f a rc t, liv e r lobe HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End o f R ecord- 1415 in f a r c t, liv e r lobe Page 1214 IV-117 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata Fl G eneration ANIMAL NUMBER: 1428 SEX: F DOSE GROUP: DEATH T # E : III Sacri f i ce-Schedul ed GROSS OBSERVATIONS): KIDNEYS: P e lv i c d i l a t i o n , s l i g h t , b i l a t e r a l . HISTOMORPHOLOGIC OBSERVATIONS!: d ila ta tio n , pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End o f R e c o rd - 1428 d ila ta tio n , p e lv is (m ild) Page 1215 IV-118 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .5 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1495 SEX: F DOSE GROUP: DEATH TYPE: IV S acrifice-S cheduled GROSS OBSERVATION(S): EYES: S o ft t i s s u e s u r r o u n d in g e y e s w o lle n . HISTOMORPHOLOGIC OBSERVATION(S): abscess, periocular HISTOMORPHOLOGIC OBSERVATIONS: EYES: End o f R eco rd - 1495 abscess, p eriocular Page 1216 IV-119 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal 6 ro s s and H lstcm orphology D ata FI G eneration ANIMAL NUMBER: 1544 SEX: F DOSE GRQUP: DEATH TYfE: V S acrifice-S cheduled GROSS OBSERVATIONS): 6ENERAL: No a r o s s c h a n a e s . HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: OVARIAN FOLLICLES/CORPORA LUTEA: PITUITARY: UTERUS: HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le h y p e rp la sia , c o r tic a l, fo cal (m inim al) presence of corpora lu tea presence o f grow ing/antral f o llic le s c y st(s), pars d ista l is m acrophages, pigm ented (m oderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: CERVIX OVARIES OVIDUCT(S) End o f R eco rd - 1544 VAGINA Page 1217 IV-120 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY NUMBER: T-6889.15 A ppendix IV In d iv id u a l Animal G ross and H 1stam orphology D ata FI G eneration ANIMAL NUMBER: 1546 SEX: F DOSE GRftUP: DEATH T % : Sacri f i ce-Scheduled GROSS OBSERVATIONS): GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lu tea presence o f grow ing/antral f o llic le s m acrophages, pigm ented (marked) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End o f R ecord- 1546 OVIDUCT(S) Page 1218 IV-121 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1548 SEX: F GROSS OBSERVATIONS): EARfS): S w ollen, r i o h t . DOSE GR0UP: V DEATH T #EI: S a c r i f i c e - S c h e d u l e d aasessaasaasasssaggsgSKSScssssssscss! HISTOMORPHOLOGIC OBSERVATION(S): ` chondropathy, a u ric u la r HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: chondropathy, a u ric u la r (marked) presence of corpora lu tea presence o f grow ing/antral f o llic le s m acrophages, pigm ented (m oderate) d i s t e n t i o n , lumen (m o d erate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End o f R eco rd - 1548 OVIDUCT(S) Page 1219 IV-122 ARGUS 418-020 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 Appendix IV In d iv id u a l Animal G ross and H istom orphology D ata Fl G eneration ANIMAL NUMBER: 1551 SEX: F DOSE GRflJJP: DEATH TYfE: V S acrifice-S cheduled GROSS OBSERVATION(S): TAIL: T ip m is s in g 11 cm from t h e b a s e . HISTOMORPHOLOGIC OBSERVATION(S): inflam nation, chronic n ecro sis, focal HISTOMORPHOLOGIC OBSERVATIONS: TAIL: End o f R ecord- 1551 in flam n atio n , ch ro n ic (m ild) n e c ro sis, focal (m ild) Page 1220 IV-123 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orpbology D ata FI G eneration ANIMAL NUMBER: 1552 DOSE GROUP:: V SEX: F DEATH T ^ E : S acrifice-S cheduled BsssxcssssizsisssssxssanssscBssaiSBSSSsaBBsuaeeBSBisssssss8SBi:ssBSssisisssBissssesBiasssEscas3i GROSS OBSERVATIONfS): HISTOMORPHOLOGIC OBSERVATION!S): GENERAL: No a r o s s c h a n a e s . Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lu tea presence o f growing/antml f o l li c le s m acrophages, pigm ented (m oderate) d is te n tio n , lumen (m oderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End o f R eco rd - 1552 OVIDUCT(S) Page 1221 IV--124 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .S A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1557 SEX: F GROSS OBSERVATIONS): GENERAL: No g r o s s c h a n g e s . DOSE GROUP: DEATH T Y : Sacri ff ce-Scheduled BCKESESa HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence o f corpora lu tea presence o f grow ing/antral f o llic le s m acrophages, pigm ented (iniId) m u cificatio n (m oderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End o f R eco rd - 1557 OVIDUCT(S) Page 1222 IV-125 ARGUS 418-020 ORAL (SAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 41 8 -0 2 0 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ro ss and H istom orpho'logy D ata FI G eneration ANIMAL NUMBER: 1573 SEX: F DOSE GROUP: DEATH 1W E : V S acrifice-S cheduled GROSS OBSERVATION!SI: GENERAL: No g r o s s c h a n g e s . HISTOHORPHOLOGIC OBSERVATION!Si : Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence o f corpora lu tea presence o f grow ing/antral f o llic le s m acrophages, pigm ented (m oderate) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End o f R e c o rd - 1573 OVIDUCT(S) Page 1223 IV--126 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) * REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology Data FI G eneration ANIMAL NUMBER: 1579 SEX: F GROSS OBSERVATIONS): GENERAL: No g r o s s c h a n g e s . DOSE GROUP: V DEATH T#E: S a c r i f ic e - S c h e d u le d IUiaStt8SSSBSCSSSSS8SS8SCSSSSSBSSSSSSSSSSS8SS HISTOMORPHOLOGIC OBSERVATIONS!: Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence o f corpora lu tea presence of grow ing/antral f o llic le s m acrophages, pigm ented (m inim al) m u cificatio n (m oderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End o f R ecord- 1579 OVIDUCT(S) Page 1224 IV--127 ARGUS 418-020 ORAL (GAVAGE) TV0-6ENERATI0N (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1589 DOSE GtyJjJP: V SEX: F DEATH TTPE: S a c r i f ic e - S c h e d u le d ItSSSStSSSBSISSSSSBSSUSBSStSl(BBSBSBeBBBStBBeeeeBBBBBBSBBBBSBBlBSBBSSBBIBBSBBBIBBSBBBBSSSSXESaSESSE GROSS OBSERVATIONS): GENERAL: No c r o s s c h a n a e s . HISTOMORPHOLOGIC OBSERVATION(S): Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence o f corpora lu tea presence o f grow ing/antral f o llic le s m acrophages, pigm ented (m oderate) m u cificatio n (m ild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End o f R ecord- 1589 OVIDUCT( S) Page 1225 IV-128 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ro ss and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1593 SEX: F DOSE GRUP: DEATH TYPE: V S acrifice-S cheduled GROSS OBSERVATION(SI: KIDNEYS: R ig h t- p e l v i s m o d e ra te d i l a t i o n . URETER: C a l c u l i , 1 .0 x 0.5xm , one l o c a t e d a t t h e caudal end o f each u re te r. URINARY BLADDER: W a lls th i c k e n e d . HISTOMORPHOLOGIC OBSERVATIONfSl: d ila ta tio n , pelvis p y e lo n e p h ritis disten tio n h y p e rp la sia , mucosa in flaim atio n , chronic c y s titis , hyperplastic HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: OVARIAN FOLLICLES/CORPORA LUTEA: OVARIES: URETER: URINARY BLADDER: UTERUS: d ila ta tio n , p e lv is (m oderate) p y e lo n e p h ritis (m oderate) presence o f corpora lutea presence o f grow ing/antral fo llic le s c y st(s), intraovarian d is te n tio n (marked) h y p e rp la sia , mucosa (m oderate) in flan m atio n , chronic (m ild) c y s t i t i s , h y p e rp la s tic (marked) m acrophages, pigm ented (m oderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS VAGINA CERVIX OVIDUCT(S) End o f R eco rd - 1593 PITUITARY Page 1226 IV-129 ARGUS 418-020 ORAL (6AVA6E) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T -6 8 8 9 .6 A ppendix IV In d iv id u a l Animal G ross and H istom orphology D ata FI G eneration ANIMAL NUMBER: 1598 SEX: F DOSE GROUP: DEATH T^?E: V S acrifice-S cheduled GROSS OBSERVATIONS): GENERAL: No g r o s s c h a n g e s . HISTOMORPHOLOGIC OBSERVATION(S) : Not a p p lic a b le HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence o f corpora lu tea presence o f grow ing/antral f o llic le s m acrophages, pigm ented (m oderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End o f R ecord- 1598 OVIDUCT(S) Page 1227 IV-130 ARGUS 418-020 O RAL (GAVAGE) TW O -GENERATIO N (ONE LITTER P E R G EN ERATIO N ) R EPR O D U C TIO N S T U D Y O F A M M O N IU M P E R F L U O R O O C T A N O A T E (AFPO ) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 H ISTO PATH O LO G Y R EPO R T APPEN DIX V INDIVIDUAL ANIMAL G R O S S AND HISTOMORPHOLOGY DATA G R O S S L E S IO N S - F1 and F2 Pups Page 1228 ARGUS 418-020 O RAL (GAVAGE) TW O -G ENERATIO N (ONE U TTER P E R G EN ERATIO N) R EPR O D U C T IO N ST U D Y OF AM M O N IU M PERFLU O RO O CTA N O A TE (APFO) IN R A T S P R O T O C O L 418-020 S P O N S O R 'S S T U D Y N U M B E R : T-6889.6 APPEN DIX V 9 Individual Animal G ro ss and Histomorphology Data G ro ss Lesions - F1 and F2 Pups Dam #. GrouD #. Pud # 13921, Group V, Pup #1 13946, Group I, Pup #10 1304, Group I, Pup #1 1383, Group II, Pup #6 1459, Group III, Pup #14 1476, Group III, Pup #3 1523, Group IV, Pup #11 1523, Group IV, Pup #3 Gross Observation^) Histom oroholoaic O bservations Mouth- mass #3, 0.2 x 0.3 x 0.1cm Tissue not available Kidney- right, pelvis, dilated, moderate Tissue not available Kidney- pelvis, dilated, slight Dilatation, pelvis, moderate Kidney- right, dilation, pelvis, moderate Dilatation, pelvis, moderate Kidney- bilateral, dilation, pelvis, moderate Dilatation, pelvis, mild Kidney- right, pelvis, dilated, slight Dilatation, pelvis, mild Tail- bent Tissue not available Domed head; brain- dilated third and lateral ventricles, marked Eye- right not present Dilatation, ventricular, marked Confirmed microscopically V-1 Page 1229 ARGUS 418-020 APPENDIX L HISTORICAL CONTROL DATA Page 1230 ARGUS 418-020 FEMALE FERTILITY HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus [Crl:CD(SD)IGS BR VAF/Plus] RATS SUMMARY 1995-2002 1891 TOTAL LITTERS AVERAGE MINIMUM MAXIMUM # STUDIES INCL. IN ANALYSIS DELIVERED UTTERS N 4 33 93 IMPLANTATION SITES PER DELIVERED LITTER N MEAN 15.3 63 13.4 519 17.7 93 93 PUPS FOUND DEAD OR PRESUMED CANNIBALIZED DAY 1 N N % 0.4% DAYS 1-4 DAYS 15-21 N N % 2.2% N N % 0.3% VIABILITY INDEX (Day 4) % 97.8% N N VIABILITY INDEX (Day 7) % N N 1.0 LACTATION INDEX % 98.8% N N SURVIVING PUPS/LITTER Day 1 MEAN 14.2 0.0% 2.7% 0.0% 9.0% 0.0% 91.0% 3.8% 100.0% 91.5% 100.0% 94.4% 100.0% 12.0 16.1 Page 1231 72 88 68 84 10 77 92 ARGUS 418-020 FEMALE FERTILITY HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus [Crl:CD(SD)IGS BR VAF/Plus] RATS SUMMARY 1995-2002 1891 TOTAL LITTERS AVERAGE MINIMUM MAXIMUM # STUDIES INCL. IN ANALYSIS DELIVERED LITTERS N 4 33 93 Day 4 (Preculling) MEAN 13.9 11.4 15.8 89 Day 4 (Postculling) MEAN 8.7 7.6 10.0 27 Day 21 MEAN 11.8 6.0 15.5 67 PUP WEIGHT/LITTER (GRAMS) Day 7 MEAN 13.0 10.6 17.6 62 Day 14 MEAN 26.0 21.2 34.8 48 Day 21 MEAN 40.9 31.1 60.4 67 Page 1232 ARGUS 418-020 DURATION OF GESTATION HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus [Crl:CD(SD)IGS BR VAF/Plus] RATS 1997-2002 SUM M ARY 1428 T O T A L L IT T E R S # S T U D IE S IN C L . IN A V E R A G E M IN IM U M M A X IM U M A N A L Y S IS DELIVERED LITTERS N DURATION OF GESTATION IN DAYS MEAN 22.6 8 21.7 33 23.2 59 59 Page 1233 ARGUS 418-020 SEXUAL MATURATION HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus (Crl:CD(SD)IGS BR VAF/Plus) RATS CODE: DRAFT FINAL REPORT MAIL DATE TYPE OF STUDY: 1995 - 2000 SUMMARY 42 STUDIES INCLUDED IN ANALYSIS SEXUAL MATURATION MALE RATS Preputial Separation (Avg. day postpartum obs.) N MEAN FEMALE RATS Vagina Patent (Avg. day postpartum obs.) N MEAN AVERAGE MINIMUM MAXIMUM 4 6 .1 43 .9 47 .7 3 2 .1 3 0 .1 34 .0 Page 1234 ARGUS 418-020 SEXUAL MATURATION HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus (Crl:CD(SD)IGS BR VAF/Plus) RATS CODE: DRAFT FINAL REPORT MAIL DATE: TYPE OF STUDY: 142 03/21/95 Seg. Ill 148 151 06/13/95 07/20/95 Harmonized Harmonized Seg. Il/lll Seg. m il 187 07/23/96 Seg. Il/lll 188 08/05/96 Repro, and Postnatal 192 08/30/96 Seg. Il/lll 199 10/09/96 Seg. Il/lll SEXUAL MATURATION MALE RATS Preputial Separation (Avg. day postpartum obs.) N MEAN 25 46.7 FEMALE RATS Vagina Patent (Avg. day postpartum obs.) N MEAN 24 32.4 25 46.7 25 32.1 25 44.7 25 31.9 25 46.1 25 32.2 25 45.9 25 31.6 25 . 25 44.5 47.6 25 31.8 25 31.4 Page 1235 ARGUS 418-020 SEXUAL MATURATION HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus (Crl:CD(SD)IGS BR VAF/Plus) RATS ' CODE: DRAFT FINAL REPORT MAIL DATE: TYPE OF STUDY: 208 10/25/96 EmbryoFetal Dev. 222 01/14/97 Seg. Il/Ill 228 01/23/97 Preand Postnatal Dev. 234 03/05/97 Seg. Il/Ill SEXUAL MATURATION MALE RATS Preputial Separation (Avg. day postpartum obs.) N MEAN 66 45.3 FEMALE RATS Vagina Patent (Avg. day postpartum obs.) N MEAN 80 32.9 25 45.9 25 31.7 24 45.8 25 31.7 25 46.2 24 31.8 Page 1236 ARGUS 418-020 SEXUAL MATURATION HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus (Crl:CD(SD)IGS BR VAF/Plus) RATS CODE: DRAFT FINAL REPORT MAIL DATE: TYPE OF STUDY: 242 04/09/97 Seg. Il/lll 251 06/02/97 Pre and Post Natal 255 06/11/97 Seg. Il/lll 258 07/18/97 Seg. Il/lll 266 09/30/97 Seg. Il/lll 282 02/03/98 Pre and Post Natal 290 03/10/98 Dev. Neurotox. SEXUAL MATURATION MALE RATS Prputial Sparation (Avg. day postpartum obs.) N MEAN 25 46.6 FEMALE RATS Vagina Patent (Avg. day postpartum obs.) N MEAN 25 32.0 136 45.3 34 33.7 25 45.7 25 30.1 25 43.9 25 30.3 25 46.8 25 32.0 24 . 20 45.7 44.2 24 20 32.6 32.4 Page 1237 ARGUS 418-020 SEXUAL MATURATION HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus (Crl:CD(SD)IGS BR VAF/Plus) RATS CODE: DRAFT FINAL REPORT MAIL DATE. TYPE OF STUDY: 294 305 310 345 04/30/98 06/23/98 08/03/98 01/28/99 Neurobehav. Comb. Pil.+ Oral (Gavage) Dev. Neurotox. Dev. Full Dev. + 6-wk. toxicity Peri/Post Repro. and toxicokin. 353 03/05/99 Multi-Gen. 359 04/21/99 Dev. Neurotox. SEXUAL MATURATION MALE RATS Preputial Separation (Avg. day postpartum obs.) N MEAN 60 45.2 FEMALE RATS Vagina Patent (Avg. day postpartum obs.) N MEAN 60 31.6 25 46.7 25 32.1 14 60 30 . 57 45.1 45.4 46.1 47.2 15 60 30 51 32.2 31.6 32.5 32.0 Page 1238 ARGUS 418-020 FEMALE FERTILITY HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus [Crl:CD(SD)IGS BR VAF/Plus] RATS 1992 - 2002 SUMMARY 3343 TOTAL RATS AVERAGE MINIMUM MAXIMUM # STUDIES INCLUDED ESTROUS CYCLING OBSERVATIONS RATS EVALUATED N 8 48 131 PREDOSAGE ESTROUS CYCLING ESTROUS STAGES/7 DAYS MEAN 2.0 2.0 2.0 2 ESTROUS STAGES/14 DAYS MEAN 3.4 2.4 3.9 79 ESTROUS STAGES/15 DAYS MEAN 3.6 3.6 3.6 1 ESTROUS STAGES/16 DAYS MEAN 3.9 3.9 3.9 1 MEAN NUMBER OF COMPLETE ESTROUS CYCLES/GROUP MEAN 3.7 3.5 3.8 3 RATS WITH 6 OR MORE CONSEC. DAYS OF DIESTRUS N 0 2 85 RATS WITH 6 OR MORE CONSEC. DAYS OF ESTRUS N 0 0 85 MEAN ESTROUS CYCLE LENGTH/GROUP MEAN 4.1 4.1 4.1 3 PRECOHABITATION ESTROUS CYCLING MEAN NUMBER OF COMPLETE ESTROUS CYCLES/GROUP MEAN 3.2 3.2 3.2 4 ESTROUS STAGES/14 DAYS MEAN 3.4 2.5 7.0 117 ESTROUS STAGES/20 DAYS MEAN ESTROUS STAGES/21 DAYS MEAN 5.0 4.8 5.2 7 ESTROUS STAGES/28 DAYS MEAN 6.5 6.5 6.5 1 RATS WITH 6 OR MORE CONSEC. DAYS OF DIESTRUS N 0 7 126 RATS WITH 6 OR MORE CONSEC. DAYS OF ESTRUS N 0 3 126 MEAN ESTROUS CYCLE LENGTH/GROUP MEAN 4.1 4.0 4.2 3 Page 1239 ARGUS 418-020 FEMALE FERTILITY HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus [Crl:CD(SD)IGS BR VAF/Plus] RATS 1992 - 2002 SUMMARY 3343 TOTAL RATS AVERAGE MINIMUM MAXIMUM # STUDIES INCLUDED RECOVERY PER. ESTROUS CYCLING ESTROUS STAGES/28 DAYS MEAN 5.0 5.0 5.0 RATS WITH 6 OR MORE CONSEC. DAYS OF DIESTRUS N 00 RATS WITH 6 OR MORE CONSEC. DAYS OF ESTRUS N 00 1 1 1 Page 1240 ARGUS 418-020 FEMALE FERTILITY HISTORICAL CONTROL DATA Cr1:CDBR VAF/Plus [Crt:CD(SD)IGS BR VAF/Plus] RATS 1992 - 2002 SUMMARY 3343 TOTAL RATS * STUDIES AVERAGE MINIMUM MAXIMUM INCLUDED RATS IN COHABITATION DAYS IN COHABITATION RATS THAT MATED RATS WITH CONFIRMED MATING DATES RATS MATING DAYS 1-4 DAYS 5-7 RATS MATED BY FIRST MALE DAYS 1-7 DAYS 8-14 DAYS 15-21 RATS MATED BY SECOND MALE DAYS 8-14 DAYS 15-21 FERTILITY INDEX COPULATION INDEX PREGNANCY RATE RATS PREGNANT/RATS IN COHABITATION N MEAN 2.8 N % 99.3% N 7 1.6 87.5% 7 40 5.2 100.0% 39 N % 96.0% N % 4.0% 96.0% 4.0% 96.0% 4.0%, N % 97.0% N % 2.1% N % 2.0% 84.0% 0.0% 0.0% 100.0% 16.0% 4.0% N % 2.6% N % 2.0% N N % 93.8% N N % 98.5% N N % 96.7% 0.0% 0.0% 64.0% 93.3% 92.0% 12.5% 8.0% 100.0% 100.014 100.0% N N % 93.1% 64.0% 100.0% Page 1241 117 116 111 115 1 1 113 97 2 13 54 111 7 4 107 ARGUS 418-020 APPENDIX M QUALITY ASSURANCE STATEMENT Page 1242 ARGUS 418-020 90S Sheehy Drive, Bldg. A Horsham, PA 19044 Telephone; (215) 443-8710 Telefax: (215) 443-3587 ARGUS RESEARCH Charles River Laboratories Discovery and Development Services QUALITY ASSURANCE STATEMENT Argus Protocol: 418-020 Sponsor's Study Number: T-6889.6 Study Director: Raymond G. York, Ph.D., DABT The protocol, critical phases, raw data and final report were inspected by the Quality Assurance Unit (QAU), to assure conformance with: U.S. Environmental Protection Agency. Federal Insecticide, Fungicide and Rodenticide Act/Toxic Substances Control Act (FIFRA/TSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160/Part 792. POrrignacnipisleastioonf GfooroEdcLoanboomraictoCryo-Porpaecrtaicteiosn [aCn(d9D7)e1v8e6lo/FpimnaelJn.t (1998). The Revised OECD The undersigned indicate that the interim report is an accurate representation of the raw data. Data provided by the Sponsor or a subcontractor were not audited by the Argus Research Quality Assurance Unit. Page 1243 ARGUS 418-020 The QAU inspection and report audit dates are listed below: Inspection Phase Date(s) Findings Date(s) Findings Submitted to Study Submitted to Inspection Datis) Director Management Protocol TS Preparation TS Administration Natural Delivery/ LBiltoteodr OCboslleercvtaiotionns Male Sacrifice/ Sperm Evaluations Dam/Litter Sacrifice Vaginal Patency Preputial Separation FI Natural Delivery/ FLiIttBerloOodbsCerovlaleticotniosn FI Male Sacrifice/ Sperm Evaluations FI Dam/Litter Sacrifice In-Life Data Formulations Data Necropsy Data 0166-N07ONVO0V0 00 17 NOV 00 07 NOV 00 20 NOV 00 20 NOV 00 15 FEB 01 02 MAR 01 26 FEB 01 12 MAR 01 02 MAR 01 0183 MMAARR 0011 23 MAR 01 111322 MMMAAARRR 000111 30 MAR 01 21 JUN01 03 JUL 01 27 JUN 01 03 JUL 01 03 JUL 01 13 JUL 01 16-24 M AY 01 19-20 JUL 01 and 23-26 JUL 01 19-21 NOV 01, 26-30 NOV 01 and 0110,-0137-D04EDCE0C1 01 06 AUG 01 17 DEC 01 04-07 DEC 01 17-18 DEC 01 05 JUL 01 23 JUL 01 24 MAY 01 27 JUL 01 0147 DDEECC 0011 06 AUG 01 17 DEC 01 07 DEC 01 18 DEC 01 07 NOV 00 20 NOV 00 20 NV 00 26 FEB 01 12 MAR 01 12 MAR 01 1132 MMAARR 0011 30 MAR 01 27 JUN 01 03 JUL 01 05 JUL 01 23 JUL 01 24 MAY 01 27 JUL 01 04 D E C 01 17 DEC 01 06 AUG 01 17 DEC 01 07 DEC 01 18 DEC 01 Page 1244 ARGUS 418-020 Inspection Phase Report Tables Report Text Revised Report Date(s) Findings Submitted to Study Inspection Dateis) Director 30 JUL01 and 03 AUG 01 03 AUG 01 30 JUL 01 to 05 AUG 01 17-21 DEC 01 06 AUG 01 21 DEC 01 06-09 AUG 01 09 AUG 01 13-14 AUG 01 14 AUG 01 2167-,2270,2D1E,2C60D1EC 01 26 DEC 01 27 DEC 01 27 DEC 01 27 DEC 01 25 MAR 02 25 MAR 02 Date(s) Findings Submitted to Management 03 AUG 01 06 AUG 01 21 DEC 01 09 AUG 01 14 AUG 01 26 DEC 01 27 DEC 01 2257 DMEACR0012 cs(p P lyA \ Matthew J. Vaneman, B.S. Date Manager of Regulatory Compliance ^ -- Z G /x ^V " o J - LCQeyuanadtlheitiryaaAMnsd.sPuKrreainlnsccciephaAlsAsoucdiaittoer/TeamDate Page 1245